INFECTIOUS DISEASES SELF-ASSESSMENT PROGRAM

2025
SERIES EDITORS

Elizabeth S. Dodds Ashley, Pharm.D., MHS, BCIDP

Alan E. Gross, Pharm.D., FCCP, BCPS, BCIDP

ACCP collaborates with ASHP on

Infectious Diseases Pharmacy activities.
 INFECTIOUS DISEASES SELF-ASSESSMENT PROGRAM

IDSAP Series Editors

Elizabeth S. Dodds Ashley, Pharm.D., MHS, BCPS, Associate Professor of Medicine,
Division of Infectious Diseases Duke, University School of Medicine, Director of
Operations, Duke Antimicrobial Stewardship Outreach Network (DASON) Durham, North
Carolina

Alan E. Gross, Pharm.D., FCCP, BCPS, BCIDP, Clinical Associate Professor, Department
of Pharmacy Practice, University of Illinois at Chicago Retzky College of Pharmacy,
Infectious Diseases Pharmacist, Hospital Pharmacy Services, University of Illinois Hospital
and Health Sciences System, Chicago, Illinois

The IDSAP Series Editors design each year’s release by drawing from the domains, tasks, and knowledge statements in the BPS
Pharmacotherapy Specialist Certification Content Outline/Classification System. Working with a Faculty Panel Chair (guest editor),
the Series Editors refine the list of chapters and features so that only the most relevant topics are updated in each release. In
addition to current therapeutic topics, each release will address stewardship and current clinical controversies. Members of the
faculty panel collaborate on the content outline for each chapter and feature, ensuring a complete review of published evidence
on that clinical topic. Generalist BCIDP reviewers join the editorial process to enhance the material’s appropriateness for the
recertifying audience. The result is an evidence-based update that can be used to self-assess clinical skills and improve patient
outcomes.

New for 2025!

• Second-Chance Posttest Option
Visit the ACCP Store at
• Complete single chapters/features for credit
• 12-month recertification posttest window [Link]/store

IDSAP Release Release Date Recertification Deadline ACPE Deadline Minimum Hours

IDSAP 2025 May 15, 2025 May 15, 2026 May 15, 2028 15.0

IDSAP 2026 May 15, 2026 May 14, 2027 May 15, 2029 15.0

IDSAP 2027 May 17, 2027 May 17, 2028 May 17, 2030 15.0

ACCP’s Self-Assessment Programs are home study series that provide clinical
pharmacists with pertinent therapeutic updates to enhance their practice skills
and improve patient outcomes.
The American College of Clinical Pharmacy and American Society of Health-System
Pharmacists are approved by BPS as a provider for the recertification of BCIDP. ®
IMPORTANT INFORMATION ON THE RELEASE
OF IDSAP 2025

Book Formats and Content

Online book: All purchasers of this IDSAP release have access to the online book (interactive PDFs). To access, go to [Link]
and sign into your My Account page using your e-mail address and password (technical assistance is available). Scroll down to
find your book and the required posttests under My Products. The online book can be saved to the desktop or printed. The latest
version of Adobe Acrobat Reader (available free) offers functionality such as highlighting or adding “sticky notes” to the text.

E-Media Format: All purchasers of this IDSAP book also have access to the e-media version. Follow these instructions to load the
text and self-assessment questions in this book onto your e-reader, tablet, or Android phone.

Electronic annotation: The online format of this book can be saved to the desktop or printed. The latest version of Adobe Reader
(available free) offers functionality such as highlighting and adding “sticky notes” to the text.

Hyperlinks: To facilitate further learning and research, this publication incorporates live hyperlinks to websites administered by
other organizations. The URLs provided are those of third parties not affiliated in any way with ACCP. ACCP assumes no liability
for material downloaded from or accessed on these websites. It is the responsibility of the reader to examine the copyright and
licensing restrictions of linked pages and to secure all necessary permissions.

Abbreviations, Laboratory Values, and Hyperlinks: The first page of each chapter and feature includes two links: (1) a link to a
table of common abbreviations; and (2) a link to a table of reference values for laboratory tests commonly used in ambulatory
care. These tables can be used as a resource in completing the self-assessment questions. This book contains both internal and
external hypertext links (visible as underlined blue text). These links are active in the Online and e-Media versions of the book.

NOTE: The editors and publisher of IDSAP recognize that the development of this volume of material offers many opportunities for
error. Despite our best efforts, some errors may persist into publication. Drug dosage schedules are, we believe, accurate and in
accordance with current standards. Readers are advised, however, to check package inserts for the recommended dosages and
contraindications. This is especially important for new, infrequently used, and highly toxic drugs.
Director, Professional Development and Marketing: Joanna Gillette, B.A.
Consultant, ACCP Publications: Keri A. Sims, Pharm.D., BCPS
Senior Managing Editor: Edward Alderman, B.S., B.A.
Managing Editor: Peter Burns, B.A.
Senior Medical Editor: Kimma Sheldon-Old, Ph.D.
Director, Information Technology: Brent Paloutzian, A.A.S.

For ordering information or questions, e-mail: accp@[Link]

IDSAP 2025
ISBN 13: 978-1-964074-20-7

To cite this IDSAP book:

Authors. Learning activity name. In: Dodds Ashley E, Gross A, eds. Infectious Diseases Self-Assessment Program, 2025.
Lenexa, KS: American College of Clinical Pharmacy, 2025:page range.

IDSAP™ is a registered trademark of the American College of Clinical Pharmacy.

Infectious Diseases
Self-Assessment
Program

Copyright ©2025 by the American College of Clinical Pharmacy and the American Society of Health-System Pharmacists. All
rights reserved. This book is protected by copyright. No part of this publication may be reproduced, stored in a retrieval system,
or transmitted, in any form or by any means, electronic or mechanical, including photocopy, without prior written permission of
the American College of Clinical Pharmacy and the American Society of Health-System Pharmacists. NOTE: Purchasers of this
ACCP product may have one copy of the PDF printed for their personal educational use.
Continuing Pharmacy Education and
Recertification Instructions
TESTING

Book Release Date: May 15, 2025

BCIDP test deadline: 11:59 p.m. (Central) on May 15, 2026
ACPE test deadline: 11:59 p.m. (Central) on May 15, 2028

Before submitting a posttest: Check the online errata for any changes or updates to this Infectious Diseases Self-Assessment
Program release. You may complete one or all available learning activity for credit. Submitting the required posttest for BCIDP
recertification attests that you have completed the test as an individual effort and not in collaboration with any other individual or
group. Failure to complete this test as an individual effort may jeopardize your ability to use IDSAP for BCIDP recertification.

IDSAP Target Audience: The target audience for BCIDP 2025 is pharmacotherapy specialists and advanced-level clinical
pharmacists whose responsibilities may include providing care for individuals with or at risk for infectious diseases.

Available CPE credits: Purchasers who successfully complete all posttests for BCIDP 2025 can earn 23.0 contact hours of CPE credit.
The universal activity numbers are as follows:

Learning Activity Learning Objectives ACPE Activity Number CPE Hrs

Chapter: Acinetobacter 1. Classify the global epidemiology of Acinetobacter, 0217-9999-25-078-H01-P 3.0

baumannii highlighting its resistance patterns, regional
variations in susceptibility rates, and the evolution and
dissemination of clonal lineages.
2. Assess the biological and ecological features of
Acinetobacter, its increasing virulence, and the
challenges it poses in clinical settings because of drug
resistance and its role in nosocomial infections.
3. Analyze the various exogenous and endogenous
resistance mechanisms employed by Acinetobacter
isolates and their impact on therapeutic efficacy.
4. Evaluate current and emerging antimicrobial therapies
for Acinetobacter infections.

Chapter: Pseudomonas 1. Classify the microbiology, epidemiology, pathogenesis, 0217-9999-25-079-H01-P 2.5

aeruginosa and mechanisms of resistance of infections caused by
Pseudomonas aeruginosa.
2. Distinguish differences in patient characteristics or
risk factors that increase the likelihood for an infection
caused by P. aeruginosa including multidrug resistant
strains.
3. Design a therapeutic regimen for a patient with
suspected or confirmed P. aeruginosa infection.
4. Justify the pharmacist’s role with antimicrobial and
diagnostic stewardship in the management of patients
with P. aeruginosa infections.

(continued)
Learning Activity Learning Objectives ACPE Activity Number CPE Hrs

Chapter: Enterobacterales 1. Distinguish the changing epidemiology and taxonomic 0217-9999-25-080-H01-P 2.0
updates associated with Enterobacterales.
2. Assess likely mechanisms of resistance in
Enterobacterales given a susceptibility report.
3. Interpret and apply updated susceptibility test
interpretative criteria (ie, breakpoints) and reporting
strategies on the basis of genotypic and phenotypic
results.
4. Evaluate the clinical relevance and spectrum of activity
for recently approved and late-stage pipeline agents.
5. Devise an appropriate treatment regimen for an
Enterobacterales infection considering relevant
phenotypes, genetic information, clinical factors, and
best practice recommendations.

Chapter: Hepatitis C and 1. Evaluate a patient for hepatitis B virus (HBV) infection 0217-9999-25-081-H01-P 2.0
Hepatitis B Viruses using serology and laboratory findings.
2. Distinguish among therapeutic options for various
patient populations with HBV infection.
3. Evaluate a patient’s risk of HBV infection and need for
vaccination or revaccination.
4. Evaluate a patient for hepatitis C virus (HCV) infection
before, during, and after HCV therapy.
5. Distinguish the use of the specific therapies in various
patient populations with HCV infection.

Chapter: Community 1. Distinguish differences between CLIA-waived and other 0217-9999-25-082-H01-P 1.5
Pharmacy Point-of-Care POCTs.
Test and Treat Programs 2. Using clinical guidelines, evaluate patients for
for Respiratory Tract potential community pharmacy POCT and treatment of
Infections respiratory tract infections.
3. Compose a plan for implementing a POCT and treat
program in a community pharmacy.
4. Apply the appropriate statistical method for the best
diagnostic accuracy of respiratory pathogen CLIA-
waived POCTs.
5. Determine effectiveness of community pharmacy POCT
and treat programs based on published studies.
6. Develop a plan for addressing barriers to
implementation of community pharmacy POCT and
treat programs.

Chapter: Herpesviruses 1. Evaluate epidemiologic and patient risk factors 0217-9999-25-083-H01-P 3.0
in Immunocompromised associated with herpesvirus infections.
Patients 2. Develop prophylactic therapy plans against
herpesviruses for the immunocompromised host
(hematopoietic stem cell transplant and solid organ
transplant).
3. Design therapeutic treatment plans for patients with
herpes simplex viruses, varicella zoster virus/herpes
zoster, and cytomegalovirus.
4. Develop a plan to detect and manage drug-resistant
herpesvirus infections.

(continued)
Learning Activity Learning Objectives ACPE Activity Number CPE Hrs

Chapter: Application of 1. Demonstrate knowledge of the National Healthcare 0217-9999-25-084-H01-P 2.5

NHSN Antimicrobial Use Safety Network (NHSN) reporting requirements for
and Resistance Data antimicrobial use and resistance (AUR).
2. Develop an institutional or health-system specific plan
for submitting AUR data to NHSN
3. Construct reports for AUR data to include the required
data elements.
4. Perform an analysis of AUR data using available data
analysis and reporting tools available through NHSN.
5. Apply NHSN data to identify potential antimicrobial
stewardship targets and assess the impact of
stewardship intervention.

Case Series: TJC/CMS 1. Account for the history and importance of antimicrobial 0217-9999-25-085-H01-P 3.0
Regulatory Updates stewardship.
2. Distinguish updates to the CDC and CMMS antimicrobial
stewardship elements and how they relate to
accreditation bodies, including the Joint Commission
3. Evaluate appropriate resources; relevant accreditation,
legal, regulatory and safety requirements; and quality
metrics as they relate to antimicrobial stewardship.
4. Assess the effectiveness of antimicrobial stewardship
strategies.
5. Assess institutional readiness for upcoming
accreditation survey.

Chapter: β-Lactam 1. Apply fundamental pharmacokinetic and 0217-9999-25-086-H01-P 3.5

Therapeutic Drug pharmacodynamic principles of β-lactams in disease
Monitoring management.
2. Distinguish patient populations at risk for alterations in
β-lactam pharmacokinetics/pharmacodynamics that
may benefit from β-lactam therapeutic drug monitoring
(TDM) for dose optimization.
3. Apply current evidence regarding the impact of β-lactam
TDM on patient outcomes, including clinical outcomes
such as mortality and microbiologic outcomes.
4. Evaluate a patient’s β-lactam dosing regimen and
provide recommendations for dose adjustment using
appropriately obtained concentrations.
5. Justify the pharmacist’s role in implementation of a
successful β-lactam TDM program.
TO EARN CPE CREDITS FROM THIS IDSAP
BOOK
Posttest access: Go to [Link] and sign in with your e-mail address and password. Technical support is available from 8 a.m.
to 5 p.m. (Central) weekdays by calling (913) 492-3311. IDSAP products are listed under My Products on your My Account page.

BCIDP Recertification Credit: To receive BCIDP recertification CPE credit, an IDSAP posttest must be submitted within
the 12-month period after the book’s release (see above). Only completed posttests are eligible for credit; no partial or
incomplete tests will be processed. You may complete one or all available learning activities for credit.

The passing point to earn BCIDP recertification credit is based on an expert analysis of the assessment items in each posttest module.
Any posttest submitted before the BCIDP test deadline that meets this passing point will earn BCIDP recertification credits. These
credits will be assigned as of the date of test submission and reported within 48 hours to BPS. For statements of recertification
credit, visit [Link].

Remediation: In accordance with BPS guidelines concerning remediation for products launched in 2024 and after, posttests that do
not reach the passing point for recertification credit will generate a second-chance test option. This test will automatically appear
in the learner’s My Account page and will have assessment items presented in a different order. To qualify for recertification credit,
the second-chance test must be submitted before the deadline stated above.

BCIDP Recertification: The ACCP Recertification Dashboard is a free online tool that can track recertification credits as they are
earned through ACCP and schedule new opportunities for credits from upcoming ACCP professional development programs.
Questions regarding the number of hours required for BCIDP recertification should be directed to BPS at (202) 429-7591 or
[Link].

ACPE CPE Credit: To receive ACPE CPE credit for an IDSAP module, a posttest must be submitted within 3 years after the book’s
release (see above). Any posttest submitted before the ACPE deadline that scores 50% or greater will be awarded the appropriate
CPE. These credits will be assigned as of the date of test submission and reported within 48 hours. For statements of CPE credit,
visit [Link].

Posttest answers: The explained answers – with rationale and supporting references – will be posted 2 weeks after the BCIDP
test deadline and will be available on the My Account page to anyone who has either (1) submitted a posttest or (2) waived the
right to receive credit from a posttest. Go to [Link] and sign in with your e-mail address and password. To waive credit
and access the explained answers, click on the waiver link for that module; the explained answers will appear starting 2 weeks
after the BCIDP test deadline. By completing the waiver form, you waive the opportunity to receive CPE credit for that module.

Continuing Pharmacy Education Credit: The American College of Clinical Pharmacy is accredited by the Accreditation
Council for Pharmacy Education as a provider of continuing pharmacy education.

The American Society of Health-System Pharmacist is accredited by the Accreditation Council for Pharmacy Education as
a provider of continuing pharmacy education with Commendation.

The American College of Clinical Pharmacy and the American Society of Health Systems Pharmacists
are approved by the Board of Pharmacy Specialties (BPS) as providers for BCIDP recertification.

BPS is an autonomous division of the American Pharmacists Association. To maintain its strict,
independent standards for certification, BPS does NOT endorse or provide review information,
preparatory courses, or study guides for board certification examinations. BPS, through its specialty
councils, is responsible for specialty examination content, administration, scoring, and all other
aspects of its certification programs. BPS is totally separate and distinct from ACCP. For information
about BPS specialty recertification or the BPS recertification process, go to: [Link]
IDSAP 2025 Faculty Panel
Series Editors: Faculty Panel Chair:
Elizabeth S. Dodds Ashley, Pharm.D., MHS, BCIDP Navaneeth Narayanan, Pharm.D., MPH, BCIDP
Professor in Medicine Clinical Associate Professor
Division of Infectious Diseases Rutgers Health
Duke University School of Medicine Ernest Mario School of Pharmacy
Director of Operations Infectious Diseases Pharmacist
Duke Antimicrobial Stewardship Outreach Network (DASON) Robert Wood Johnson University Hospital
Durham, North Carolina RWJ Barnabas Health
Alan E. Gross, Pharm.D., FCCP, BCPS, BCIDP New Brunswick, New Jersey

Clinical Associate Professor

Disclosures: ACCP Staff/Series Leaders
Department of Pharmacy Practice
University of Illinois at Chicago Retzky College of Pharmacy Consultancies: Elizabeth Dodds-Ashley (HealthTrackRX);
Infectious Diseases Pharmacist Navaneeth Narayanan (Beckman-Coulter)
Hospital Pharmacy Services Grants: Alan Gross (AHRQ); Navaneeth
University of Illinois Hospital and Health Sciences System Narayanan (Merck, Shionigi)
Chicago, Illinois Royalties: Elizabeth Dodds-Ashley (UpToDate)
Honoraria: Alan Gross (APhA; PROCE); Navaneeth Narayanan
(Astellas, Beckman-Coulter, Paratek, T2 Biosystems)
Nothing to disclose: Ed Alderman, Peter Burns, Joanna
Gillette, Brent Paloutzian, Kimma Sheldon-Old, Keri Sims

Note: All relevant financial relationships listed for these individuals have been mitigated.

Note: Any views, thoughts, or opinions expressed by authors and reviewers in this publication do not necessarily reflect the
faculty member’s employer, organization, committee, or other group or individual.

Learning Activity Authors Reviewers Disclosures

Chapter: Acinetobacter Ashlan J. Kunz Coyne, Amanda Binkley, Pharm.D., BCIDP, AAHIVP Amanda Binkley:
baumannii Pharm.D., MPH Clinical Pharmacy Specialist Infectious Diseases Consultancies
Assistant Professor RPD PGY2 ID Pharmacy Residency Program (Shionogi)
Pharmacy Practice and Department of Pharmacy Ashlan Kunz Coyne:
Science Penn Presbyterian Medical Center Consultancies
University of Kentucky Philadelphia, Pennsylvania (Abbvie);
Lexington, Kentucky Grants (PhRMA
Rupal Jaffa, Pharm.D., MBA, BCPS, BCIDP
Clinical Pharmacist Foundation,
Antimicrobial Support Network Society of
Atrium Health Infectious Diseases
Charlotte, North Carolina Pharmacists)

Sarah B. Green, Pharm.D., BCIDP, AAHIVP Sarah B. Green:

Clinical Pharmacy Specialist, Infectious Diseases Nothing to disclose
Emory University Hospital Rupal Jaffa: Nothing
Adjunct Assistant Professor to disclose
Department of Infectious Diseases
Emory University School of Medicine
Atlanta, Georgia

(continued)
Learning Activity Authors Reviewers Disclosures

Chapter: Pseudomonas Dana R. Bowers, Pharm.D., Catherine H. Vu, Pharm.D., BCIDP Dana Bowers: Grants
aeruginosa BCPS, BCIDP Clinical Pharmacy Specialist, Infectious Diseases (Merck Sharp &
Associate Professor Saint Peters University Hospital Dohme Corp.)
Department of New Brunswick, New Jersey Lynn Chan: Nothing
Pharmacotherapy Kelli A. Kronsberg, Pharm.D., BCPS, BCIDP to disclose
Washington State University Instructor Kelli Kronsberg:
College of Pharmacy and Department of Pharmacy Practice and Science Nothing to disclose
Pharmaceutical Sciences University of Arizona R. Ken Coit College of
Yakima, Washington Catherine H. Vu:
Pharmacy
Nothing to disclose
Phoenix, Arizona
Lynn Chan, Pharm.D., BCIDP
Infectious Diseases/OPAT Clinical Pharmacist
Ronald Reagan UCLA Medical Center
Los Angeles, California

Chapter: Brandon K. Hawkins, Heather L. Cox, Pharm.D., BCIDP Heather Cox:

Enterobacterales Pharm.D., BCIDP, AAHIVP Lead Pharmacist, Infectious Diseases Nothing to disclose
Assistant Professor Associate Director, Antimicrobial Stewardship Lindsay Donohue:
Department of Clinical Director, PGY2 Infectious Diseases Pharmacy Consultancies
Pharmacy and Translational Residency (Fingerpaint
Science Department of Pharmacy Services Marketing);
University of Tennessee UVA Health University Medical Center
Brandon Hawkins:
Health Science Center Charlottesville, Virginia
Consultancies
College of Pharmacy
Lindsay E. Donohue, Pharm.D., BCIDP (ASHP, APhA,
Clinical Pharmacy Specialist
Clinical Pharmacist, Infectious Diseases Belmont University)
– Infectious Diseases and
Assistant Director,
Antimicrobial Stewardship
PGY2 Infectious Diseases Pharmacy Residency
Department of Pharmacy
Department of Pharmacy Services
University of Tennessee
UVA Health University Medical Center
Medical Center
Charlottesville, Virginia
Knoxville, Tennessee

Chapter: Hepatitis Paulina Deming, Pharm.D. HaYoung Ryu, Pharm.D., BCIDP, AAHIVP Jessica Cottreau:
C and Hepatitis B Associate Professor Hepatitis C/HIV Pharmacist Nothing to disclose
Viruses Pharmacy Practice and Department of Pharmacy Services Paulina Deming:
Administrative Sciences Oregon Health & Science University Hospital Nothing to disclose
College of Pharmacy Portland, Oregon HaYoung Ryu:
Associate Director Jessica Cottreau, Pharm.D, BCPS, BCIDP Nothing to disclose
Viral Hepatitis Programs Chair, Department of Pharmacy Practice Esther Fasanmi:
Project ECHO Rosalind Franklin University College of Pharmacy Consultancies
University of New Mexico Chicago, Illinois (Merck)
Health Sciences Center
Albuquerque, New Mexico Esther O. Fasanmi, Pharm.D., BCPS, BCIDP, AAHIVP
Clinical Pharmacist – Ambulatory (HIV/Hepatitis C)
Pharmacy Clinical Services, Outpatient
JPS Health Network
Fort Worth, Texas

(continued)
Learning Activity Authors Reviewers Disclosures

Chapter: Community Renee R. Koski, Pharm.D., Michael Postelnick, BSPharm, BCPS-AQ ID Julie Akers:
Pharmacy Point- FMPA, CACP System Program Director, Antibiotic Stewardship Consultancies
of-Care Test and Professor Department of Pharmacy (AstraZeneca,
Treat Programs for Department of Pharmacy Northwestern Medicine Genentech)
Respiratory Tract Practice Chicago, Illinois Michael E. Klepser:
Infections Ferris State University Nothing to disclose
Julie Akers, Pharm.D., FWSPA
College of Pharmacy Renee R. Koski:
Executive Associate Dean
Big Rapids, Michigan Nothing to disclose
Department of Pharmacotherapy
Michael Postelnick:
Michael E. Klepser, Pharm.D., Washington State University College of
Nothing to disclose
FCCP, FIDP Pharmacy and Pharmaceutical Sciences
Ron Welch: Nothing
Senior Director, CAPE Spokane, Washington
to disclose
Professor
Ron Welch, Pharm.D., BCPS, BCIDP
Ferris State University
Clinical Lead Specialist
College of Pharmacy
Baptist Memorial Hospital – Golden Triangle
Big Rapids, Michigan
Columbus, Mississippi

Chapter: Nancy N. Vuong, Pharm.D., Caleb E. Rux, Pharm.D., BCIDP Dipti Patel: Nothing
Herpesviruses in MBIOT, BCPS, BCIDP Clinical Pharmacist – Transplant to disclose
Immunocompromised Clinical Pharmacy Specialist Infectious Diseases Caleb E. Rux:
Patients – Infectious Diseases Department of Pharmacy Nothing to disclose
Department of Pharmacy Loyola University Medical Center
Jennifer Sparks:
UT MD Anderson Cancer Maywood, Illinois
Grants (WV DHHR)
Center
Jennifer Sparks, Pharm.D., BCPS, BCIDP Nancy N. Vuong:
Houston, Texas
Clinical Pharmacy Assistant Professor Nothing to disclose
Department of Pharmaceutical Practice
Administration and Research
Marshall University School of Pharmacy
Huntington, West Virginia

Dipti Patel, Pharm.D., BCPS, BCIDP, BCCCP

Clinical Pharmacist, Critical Care
Department of Pharmacy
Southern Regional Medical Center
Riverdale, Georgia

(continued)
Learning Activity Authors Reviewers Disclosures

Chapter: Application of Natasha N. Pettit, Pharm.D., Julie Akers, Pharm.D., FWSPA Julie Akers:
NHSN Antimicrobial FIDSA, BCIDP Executive Associate Dean Consultancies
Use and Resistance Clinical Pharmacist, Department of Pharmacotherapy (AstraZeneca,
Data Infectious Diseases Washington State University College of Genentech)
Department of Pharmacy Pharmacy and Pharmaceutical Sciences Michael Postelnick:
University of Chicago Spokane, Washington Nothing to disclose
Medicine
Michael Postelnick, BSPharm, BCPS-AQ ID Natasha Pettit:
Chicago, Illinois
System Program Director, Antibiotic Stewardship Honoraria (SIDP,
Department of Pharmacy ASHP
Northwestern Medicine Hunter Rondeau:
Chicago, Illinois Consultancies
Hunter O. Rondeau, Pharm.D., BCIDP (Cosmas Health)
Antimicrobial Stewardship Coordinator Samira Zantout:
Department of Pharmacy Nothing to disclose
SSM Health
St. Louis, Missouri

Samira Zantout, Pharm.D.,

BCPS, BCIDP, AAHIVP
Clinical Pharmacist
Departments of Infectious Diseases and
Pharmacy
Avera McKennan Hospital & University Health
Center
Sioux Falls, South Dakota

Case Series: TJC/CMS Arsheena Yassin, Pharm.D., Dominic Chan, Pharm.D., BCIDP Dominic Karr Chan:
Regulatory Updates BCIDP, AAHIVP Director of Pharmacy Nothing to disclose
Infectious Diseases Clinical Department of Pharmacy Kari A. McCracken:
Pharmacist Legacy Health Nothing to disclose
Department of Pharmacy Portland, Oregon
Jessica Leri: Nothing
Robert Wood Johnson
Kari A. McCracken, Pharm.D., MBA, BCPS, to disclose
University Hospital
BCIDP Arsheena Yassin:
New Brunswick, New Jersey
Market Clinical Pharmacy Manager Nothing to disclose
Department of Pharmacy
Ascension St John Health System
Tulsa, Oklahoma

Jessica Leri, Pharm.D., BCIDP

Lead Clinical Pharmacist
ChristianaCare
Newark, Delaware

(continued)
Learning Activity Authors Reviewers Disclosures

Chapter: β-Lactam Barbara A. Santevecchi, Nathaniel J. Rhodes, Pharm.D., MSc, BCPS Veena Venugopalan:
Therapeutic Drug Pharm.D., BCIDP Associate professor of Pharmacy Practice Grants (Merck
Monitoring Clinical Assistant Professor Department of Pharmacy Practice Pharmaceuticals)
Department of Pharmacy Midwestern University Barbara A.
Education and Practice Downers Grove, Illinois Santevecchi: Grants
University of Florida College (Shionogi, Inc.,
Yehya El Khawly, Pharm.D., BCIDP
of Pharmacy AbbVie, Inc.)
Clinical Pharmacist
Clinical Pharmacy Specialist,
Department of Pharmacy Nathaniel J. Rhodes:
Infectious Diseases
Hamad Medical Corporation – Al Wakra Hospital Consultancies
Department of Pharmacy
Doha, Qatar (Third Pole
University of Florida Health
Therapeutics,
Shands Hospital
Apothecademy, LLC,
Gainesville, Florida
NIH and CDMRP);
Veena Venugopalan, Grants (NIH [two
Pharm.D., BCIDP grants], FDA)
Clinical Associate Professor Yehya El Khawly:
Department of Nothing to disclose
Pharmacotherapy and
Translational Research
University of Florida, College
of Pharmacy
Gainesville, Florida
TABLE OF CONTENTS
Chapter: Acinetobacter baumannii Risks of HBV Reactivation ����������������������������������������������������������������96
By Ashlan J. Kunz Coyne, Pharm.D., MPH Prevention of HBV ������������������������������������������������������������������������������97

Introduction ������������������������������������������������������������������������������������������1 HCV Infections ��������������������������������������������������������������������������������� 100

Epidemiology ����������������������������������������������������������������������������������������2 Pharmacotherapy ����������������������������������������������������������������������������101

Biological and Ecological Features ����������������������������������������������������3 Special Populations ������������������������������������������������������������������������107

Resistance Mechanisms ��������������������������������������������������������������������4 Conclusion ����������������������������������������������������������������������������������������111

Therapeutic Approaches ��������������������������������������������������������������������6 References ����������������������������������������������������������������������������������������111

Conclusion�������������������������������������������������������������������������������������������18 Self-Assessment Questions������������������������������������������������������������114

References ������������������������������������������������������������������������������������������18
Self-Assessment Questions��������������������������������������������������������������26 Chapter: Community Pharmacy Point-of-
Care Test-and-Treat Programs for
Chapter: Pseudomonas aeruginosa Respiratory Tract Infections
By Dana R. Bowers, Pharm.D., BCPS, BCIDP By Renee R. Koski, Pharm.D., FMPA, CACP;
Michael E. Klepser, Pharm.D., FCCP, FIDP
Introduction ����������������������������������������������������������������������������������������31
Microbial Characteristics ������������������������������������������������������������������31 Introduction����������������������������������������������������������������������������������������117

Clinical Impact of P. aeruginosa Infections ������������������������������������32 Clinical Guidelines for Relevant Respiratory
Infectious Pathogens������������������������������������������������������������������������119
Antimicrobial Resistance Mechanisms ������������������������������������������35
POCT and Treat Implementation����������������������������������������������������125
Antimicrobial Treatment Options for Suspected
or Confirmed P. aeruginosa Infection ����������������������������������������������37 Point-of-Care Tests ��������������������������������������������������������������������������126

Role of Antimicrobial Stewardship ������������������������������������������������� 43 Diagnostic Accuracy ������������������������������������������������������������������������128

Conclusion ������������������������������������������������������������������������������������������45 Community Pharmacy Test-and-Treat Program Studies ������������129

References ������������������������������������������������������������������������������������������45 Implementation Barriers������������������������������������������������������������������131

Self-Assessment Questions��������������������������������������������������������������51 Conclusion�����������������������������������������������������������������������������������������131

References ����������������������������������������������������������������������������������������132

Chapter: Enterobacterales Self-Assessment Questions������������������������������������������������������������136

By Brandon K. Hawkins, Pharm.D., BCIDP, AAHIVP

Enterobacterales ��������������������������������������������������������������������������������57 Chapter: Herpesviruses in

Mechanisms of Resistance in Enterobacterales ���������������������������59 Immunocompromised Patients
Antibiotic Susceptibility Testing and Reporting Updates ������������59 By Nancy N. Vuong, Pharm.D., MBIOT, BCPS, BCIDP

New Data, Recently Approved, and Late-Stage Pipeline Introduction����������������������������������������������������������������������������������������141

Agents Active Against Enterobacterales ����������������������������������������65
Herpes Simplex Virus ����������������������������������������������������������������������141
Treating Commonly Encountered Enterobacterales
VZV and HZ��������������������������������������������������������������������������������������� 145
Phenotypes ����������������������������������������������������������������������������������������69
Prophylaxis and Prevention ������������������������������������������������������������147
Conclusion ������������������������������������������������������������������������������������������76
Treatment of HSV������������������������������������������������������������������������������151
References ������������������������������������������������������������������������������������������76
Treatment of VZV and HZ����������������������������������������������������������������158
Self-Assessment Questions��������������������������������������������������������������83
Management of Drug-Resistant Herpesviruses����������������������������158

Chapter: Hepatitis C and Hepatitis B Viruses Cytomegalovirus ����������������������������������������������������������������������������� 160

Antiviral Agents for Treatment or Prophylaxis
By Paulina Deming, Pharm.D.
of HSV, VZV/HZ, and CMV���������������������������������������������������������������165
Introduction to Viral Hepatitis Infections ����������������������������������������89 Conclusion���������������������������������������������������������������������������������������� 168
HBV Infections ������������������������������������������������������������������������������������89 References ��������������������������������������������������������������������������������������� 168
Treatment of HBV ������������������������������������������������������������������������������93 Self-Assessment Questions������������������������������������������������������������178
Treatment of HBV in Special Populations ��������������������������������������94

IDSAP 2025 xii Table of Contents

Chapter: Application of NHSN Antimicrobial Chapter: ß -Lactam Therapeutic Drug
Use and Resistance Data Monitoring
By Natasha N. Pettit, Pharm.D., FIDSA, BCIDP By Barbara A. Santevecchi, Pharm.D., BCIDP;
and Veena Venugopalan, Pharm.D., BCIDP
Introduction��������������������������������������������������������������������������������������� 183
AUR Data Submission Requirements ������������������������������������������� 184 Introduction��������������������������������������������������������������������������������������� 247

Data Reporting ����������������������������������������������������������������������������������186 ß-Lactam PK/PD������������������������������������������������������������������������������� 249

NHSN AUR and Reporting Tools����������������������������������������������������� 188 Patient Populations Experiencing PK/PD Variability ����������������� 250

Using NHSN Data to Identify Antimicrobial Stewardship Indications for ß-Lactam TDM������������������������������������������������������� 255
Targets and Evaluate the Impact of Stewardship ß-Lactam PK/PD Targets ��������������������������������������������������������������� 256
Interventions��������������������������������������������������������������������������������������199
Impact of ß-Lactam TDM in Clinical Practice������������������������������ 260
Conclusion���������������������������������������������������������������������������������������� 203
Focus on Guideline and Consensus Recommendations
References ��������������������������������������������������������������������������������������� 203 for ß-Lactam TDM ��������������������������������������������������������������������������� 263
Self-Assessment Questions����������������������������������������������������������� 205 Logistic Considerations for ß-Lactam
TDM Implementation����������������������������������������������������������������������� 263

Case Series: TJC/CMS Regulatory Updates Implementation Strategies for Success��������������������������������������� 267

By Arsheena Yassin, Pharm.D., BCIDP, AAHIVP Barriers and Limitations ����������������������������������������������������������������� 269
Future Directions ����������������������������������������������������������������������������� 269
Introduction����������������������������������������������������������������������������������������212
Conclusion���������������������������������������������������������������������������������������� 270
AMS Regulatory and Accreditation Requirements ����������������������217
References ��������������������������������������������������������������������������������������� 270
Hospital AMS Accreditation Elements ������������������������������������������219
Self-Assessment Questions����������������������������������������������������������� 276
Internal Coordination����������������������������������������������������������������������� 226
Monitor Antibiotic Use��������������������������������������������������������������������� 229
Ambulatory Health Care AMS Accreditation Elements��������������� 234
Preparing for Survey ����������������������������������������������������������������������� 238
Conclusion���������������������������������������������������������������������������������������� 239
References ��������������������������������������������������������������������������������������� 239
Self-Assessment Questions����������������������������������������������������������� 242

IDSAP 2025 xiii Table of Contents

Chapter: Acinetobacter baumannii
By Ashlan J. Kunz Coyne, Pharm.D., MPH

Reviewed by Amanda Binkley, Pharm.D., BCIDP, AAHIVP; Rupal Jaffa, Pharm.D., BCIDP; and Sarah B. Green, Pharm.D., BCIDP, AAHIVP

LEARNING OBJECTIVES

1. Classify the global epidemiology of Acinetobacter, highlighting its resistance patterns, regional variations in susceptibility
rates, and the evolution and dissemination of clonal lineages.
2. Assess the biological and ecological features of Acinetobacter, its increasing virulence, and the challenges it poses in
clinical settings because of drug resistance and its role in nosocomial infections.
3. Analyze the various exogenous and endogenous resistance mechanisms employed by Acinetobacter isolates and their
impact on therapeutic efficacy.
4. Evaluate current and emerging antimicrobial therapies for Acinetobacter infections.

INTRODUCTION
ABBREVIATIONS IN THIS CHAPTER
Epidemiology
ABC Acinetobacter baumannii-­
calcoaceticus complex Acinetobacter spp are catalase-positive, oxidase-negative, nonmo-
BSI Bloodstream infection tile, and nonfermenting gram-negative pathogens commonly found
CLSI Clinical and Laboratory Standards in the environment, with a strong ability to survive on surfaces, mak-
Institute ing them prominent colonizers in health care settings (Howard 2012;
COPD Chronic obstructive pulmonary Beavers 2009). Recognized as Acinetobacter since 1971, the genus
disease
includes clinically significant species like A. baumannii, which, along-
CRAB Carbapenem-resistant A. baumannii
side Acinetobacter calcoaceticus and related genomic species, forms
HAI Health care–associated infection the A. baumannii-calcoaceticus complex (ABC) (Sarshar 2021). A. bau-
ID- Iron-depleted cation-adjusted mannii, especially in its carbapenem-resistant form (CRAB), poses a
CAMHB Mueller Hinton broth major threat because of multidrug resistance, prompting the WHO
MBL Metallo-β-lactamase to classify CRAB as a high-priority health care–associated infection
MDR Multidrug-resistant (HAI) pathogen (Jiang 2022; WHO 2014). In the United States, 28% to
OMP Outer membrane protein 45% of HAIs caused by Acinetobacter show carbapenem resistance,
OXA Oxacillinase and the CDC reported 8500 CRAB cases in hospitalized patients in
PBP Penicillin-binding protein 2017, with mortality rates of up to 73% in severe infections (CDC 2023,
PK/PD Pharmacokinetic/pharmacodynamic 2022). High carbapenem resistance rates of 36% to 45% in the United
RND Resistance-nodulation-cell division States and up to 86% in Asia and Latin America contribute to the global
VAP Ventilator-associated pneumonia antimicrobial resistance burden of Acinetobacter, potentially resulting
XDR Extensively drug-resistant in 1.91 million antimicrobial resistance–attributable and 8.22 million
antimicrobial resistance–associated deaths by 2050 if left unchecked
Table of other common abbreviations. (Naghavi 2024; Wang 2024; Ma 2021).

Resistance Mechanisms
The extraordinary ability of A. baumannii to acquire resistance to mul-
tiple classes of antibiotics is a key factor in its clinical significance.
Resistance mechanisms include the production of β-lactamases (eg,
oxacillinase [OXA]-23, OXA-24/40), efflux pumps, alterations in outer
membrane proteins (OMPs), and target site modifications (Kyriakidis

IDSAP 2025 1 Chapter: Acinetobacter baumannii

2021; Evans 2014). The CRAB isolates often produce addi- Therapeutic Approaches
tional serine β-lactamases, such as A. baumannii–derived Managing CRAB infections is particularly challenging because
cephalosporinases (ADCs), further limiting the effectiveness of several factors. Once A. baumannii exhibits carbapenem
of common β-lactam agents (McLeod 2018; Penwell 2015). resistance, it usually acquires resistance to most other anti-
Sulbactam resistance arises from β-lactamases and muta- biotics effective against wild-type A. baumannii, leaving few
tions targeting penicillin-binding proteins (PBPs) (PBP 1a, therapeutic options (Mancuso 2023). Colistin, tigecycline,
1b, 3). Aminoglycoside resistance is because of modifying and minocycline are often used as last-resort treatments for
enzymes or 16S ribosomal RNA (rRNA) methyltransferases, multidrug-resistant (MDR) strains. Recently, sulbactam-durlo-
whereas fluoroquinolone resistance is mediated by mutations bactam and cefiderocol have shown promising activity in vitro
in chromosomal quinolone resistance–determining regions against CRAB, offering potential options for therapy; however,
(Bonomo 2006). Efflux pumps like AdeABC and AdeIJK are the available health outcomes literature remains limited, and
critical in expelling a wide range of antibiotics from the bac- further clinical evidence is needed to confirm their real-world
terial cell, further complicating treatment efforts (Abdi 2020). effectiveness.
Furthermore, A. baumannii can form biofilms on both biotic Although sulbactam-durlobactam and cefiderocol both
and abiotic surfaces, enhancing its survival and resistance to show activity, they may not necessarily be considered equally
antimicrobial agents. Biofilm formation and quorum-sensing effective options. In the CREDIBLE-CR trial, cefiderocol treat-
mechanisms significantly contribute to its pathogenicity and ment was associated with a higher mortality rate (49%) than
persistence in clinical environments (Gedefie 2021). alternative therapies (18%) in patients with CRAB infections,
possibly because of imbalances such as ICU admission rates
and ongoing septic shock at randomization (Bassetti 2021).
In contrast, sulbactam-durlobactam, specifically designed to
BASELINE KNOWLEDGE STATEMENTS
target A. baumannii, has shown more targeted activity and
Readers of this chapter are presumed to be familiar favorable outcomes in recent trials, though published clin-
with the following: ical data remain limited. In addition, in the APEKS-NP trial,
• General knowledge of nosocomial infections, cefiderocol was noninferior to meropenem for nosocomial
particularly those caused by multidrug-resistant pneumonia, and 28-day mortality rates did not differ signifi-
(MDR) organisms cantly for patients with CRAB infection (Wunderink 2021).
• Fundamental understanding of antimicrobial These results suggest that although cefiderocol remains a
resistance mechanisms, including β-lactamases, viable option, its performance in CRAB infections requires
efflux pumps, and outer membrane protein cautious interpretation.
alterations
Combination therapies, such as colistin with meropenem,
• Drug knowledge of the oral and parenteral agents have been investigated to enhance efficacy and prevent the
used to treat MDR gram-negative pathogens,
development of resistance. The continuous evolution of resis-
including carbapenems, polymyxins, and novel
agents like cefiderocol and sulbactam-durlobactam tance mechanisms necessitates ongoing surveillance and
the development of novel antimicrobial agents to combat
• Awareness of the global epidemiology of
this formidable pathogen. A standardized antibiotic regimen
Acinetobacter baumannii, especially its role in
health care–associated infections and its for CRAB infections is lacking, and robust comparative effec-
resistance patterns tiveness studies between commonly used agents are limited.
Data supporting the prioritization of specific agents or the
Table of common laboratory reference values additive benefits of combination regimens for CRAB infections
remain incomplete, necessitating ongoing research and clini-
ADDITIONAL READINGS cal vigilance.

The following free resources have additional back-

ground information on this topic: EPIDEMIOLOGY
• Tamma PD, Heil EL, Justo JA, et al. Infectious Health Care Infection Emergence
Diseases Society of America guidance on the
treatment of antimicrobial-resistant gram-negative A. baumannii has emerged as a significant health care–associ-
infections. Clin Infect Dis. 2024;Aug 7:ciae403. ated pathogen, particularly noted for its ability to cause a wide
• Shields RK, Paterson DL, Tamma PD. Navigating range of infections, including ventilator-associated pneumo-
available treatment options for carbapenem-­ nia (VAP), bloodstream infection (BSI), wound infections, and
resistant Acinetobacter baumannii-calcoaceticus UTIs (Wong 2016). Ubiquitous in the environment, these organ-
complex infections. Clin Infect Dis. 2023;76(suppl 2): isms can survive on surfaces for extended periods, making
S179-S193.
them formidable colonizers, particularly in health care settings
(Beavers 2009). This environmental persistence facilitates the

IDSAP 2025 2 Chapter: Acinetobacter baumannii

pathogen’s role in outbreaks in health care settings globally, Resistance Rates
especially in ICUs (Diao 2024). Acinetobacter spp are notorious Resistance rates in A. baumannii are notably high across vari-
for causing HAIs, particularly in the patients who are most vul- ous antibiotics, presenting a serious challenge for treatment.
nerable to illness (Jiang 2022). The WHO has classified CRAB as Carbapenem resistance in A. baumannii is especially of con-
a critical threat, on par with Pseudomonas aeruginosa and car- cern, with imipenem and meropenem resistance rates greater
bapenem-resistant Enterobacterales, underscoring the urgent than 36% (Diekema 2019; Gales 2019). Susceptibility rates for
need for effective prevention and control measures (WHO other antibiotics are similarly low: amikacin (45.7%), ampicil-
2014). Of all hospital-acquired bacteria, Acinetobacter spp had lin-sulbactam (36.5%), cefepime (35.5%), and ciprofloxacin
the highest rates of carbapenem and multidrug resistance at (32.4%). The prevalence of pandrug-resistant isolates high-
56% and 54%, respectively (Appaneal 2021). These resistance lights the critical difficulty in treating infections caused by A.
rates are particularly high in catheter-associated UTIs. In the baumannii. Colistin remains a last-resort agent, with 96.9% sus-
pediatric population, Acinetobacter spp rank as the 15th most ceptibility, but reliance on this antibiotic underscores limited
common cause of HAIs and the 9th leading cause of VAP. options for MDR cases (Diekema 2019). Furthermore, exten-
Between 2018 and 2021, the National Healthcare Safety sively drug-resistant (XDR) A. baumannii strains are especially
Network reported that of all the HAIs in the United States prevalent in Europe, where 66.4% of isolates are XDR, followed
caused by Acinetobacter spp (n = 1951), 28% to 45% of these by Latin America, Asia-Pacific, and North America (Gales
isolates showed intermediate or resistant susceptibility to car- 2019).
bapenem antibiotics (CDC 2023, 2022). According to the CDC Regional molecular variations have been observed, with
antibiotic resistance threats report, there were 8500 CRAB different clonal complexes and sequence types dominating
cases in hospitalized patients in 2017 (CDC 2022). Mortality in various areas. Globally, three main clonal lineages (CC1,
for severe A. baumannii infection ranges from 14% to 73%, CC2, and CC3) correspond to Pasteur sequence types ST1,
underscoring the significant clinical challenge posed by this ST2, and ST3 (Abdul-Mutakabbir 2021). In the United States,
pathogen (Alrahmany 2022). CC2 is predominant, accounting for over 75% of CRAB infec-
tions, with sequence types such as ST122, ST208, ST281,
Surveillance Data and ST349 associated with particular resistance genes
The SENTRY Antimicrobial Surveillance Program has exten- (Adams 2019). For example, ST208, ST281, and ST349 often
sively monitored resistance trends of A. baumannii across harbor the plasmid-acquired blaOXA-23, whereas ST499 is
North America, Europe, Asia-Pacific, and Latin America (Gales linked to blaOXA-24 (Wallace 2016). Resistance profiles vary
2019). Over 2 decades (1997-2016), a marked increase in MDR by sequence type, with notable nonsusceptibility to colis-
A. baumannii has been documented, with MDR rates exceeding tin increasing to 22% in recent isolates, especially in ST281
70% in some regions, particularly in Europe and Latin America strains (Queenan 2012). This resistance variability across
(Sader 2019). A. baumannii ranks among the top 10 pathogens regions and strains emphasizes the need for region-specific
causing BSIs, with higher prevalence in Latin America and treatment approaches and highlights the complex nature of
the Asia-Pacific than in North America and Europe (Diekema combating CRAB infections.
2019). In addition, the Study Network of Acinetobacter as a
carbapenem-resistant Pathogen (SNAP) study, conducted
BIOLOGICAL AND ECOLOGICAL
in 2017-2019 across 5 global regions, reported significant
FEATURES
regional differences in CRAB infection outcomes (Wang 2024).
Of 842 hospitalized patients, 24% died within 30 days, with Patient Populations at High Risk
mortality rates varying from 6% in Australia-Singapore to 49% A. baumannii poses a significant threat in health care settings,
in South-Central America. The highest mortality rate (42%) particularly among patient populations at high risk. Patients in
was observed in patients with BSIs. Key mortality risk fac- the ICU are especially vulnerable because of factors such as
tors included BSIs, higher age-adjusted Charlson Comorbidity prolonged hospital stays, mechanical ventilation, invasive pro-
Index, and monomicrobial infections. cedures, and underlying severe health conditions (Uwingabiye
The SNAP study also found regional differences in infec- 2017; Maragakis 2008). These patients often have VAP, BSI,
tion sites and clonal distribution. Respiratory tract infections wound infections, and UTI caused by A. baumannii. The
were most common in China, whereas BSIs predominated in increase in MDR strains of A. baumannii exacerbates the
South-Central America. Clonal group 2 (CG2) strains, which threat to patients at high risk. Resistant A. baumannii strains
are often associated with carbapenem resistance, were domi- are particularly prevalent in the ICU, where use of broad-spec-
nant in most regions except for South-Central America, where trum antibiotics is common, further selecting for resistant
non-CG2 strains were more common. These findings under- strains (Gharaibeh 2024).
score the need for region-specific strategies to address the Immunocompromised patients represent a particularly vul-
varying challenges of CRAB, emphasizing the importance of nerable subset within the populations at high risk affected
global surveillance and tailored interventions. by Acinetobacter infections. Patients with cancer, especially

IDSAP 2025 3 Chapter: Acinetobacter baumannii

those undergoing intensive chemotherapy for acute myeloid RESISTANCE MECHANISMS
leukemia, are at elevated risk of colonization and subsequent β -Lactamases
infection with MDR organisms, including A. baumannii (Ballo
β-Lactamase enzymes are crucial resistance mechanisms
2019). One study found that in patients with cancer, delayed
against β-lactam antibiotics in gram-negative bacilli, includ-
treatment of XDR A. baumannii BSIs was more strongly
ing Acinetobacter spp. These enzymes are classified into
associated with mortality than the degree of neutropenia,
four molecular classes (A, B, C, and D) according to con-
emphasizing the critical importance of early detection and
served amino acid motifs (Hussain 2021). Class A, C, and D
appropriate management (Freire 2016). The challenge is fur-
enzymes have an active site serine, whereas class B metal-
ther compounded by the emergence of CRAB strains, which
loenzymes use zinc ions at their active site (Tooke 2019).
significantly limit treatment options for these already vulnera-
Acinetobacter spp harbor intrinsic β-lactamase genes such as
ble patients (Papadopoulou 2024; Jiang 2022).
ADC and OXAs from class C and class D, respectively (Hussain
2021; Evans 2014). A. baumannii–derived cephalosporinase
Antimicrobial Susceptibility Testing
enzymes hydrolyze penicillins and cephalosporins, whereas
Antimicrobial susceptibility testing is crucial for manag-
OXA enzymes hydrolyze carbapenems (Smartsheet 2024;
ing A. baumannii infections, especially given the organism’s
Bonomo 2017; Turton 2006).
rapid acquisition of resistance to multiple antibiotics. Various
Several studies have shown the prevalence and variety of
methods are used to assess the susceptibility of A. bauman-
acquired β-lactamase genes in Acinetobacter spp, highlight-
nii, including broth microdilution (BMD), disk diffusion (DD),
ing the bacteria’s ability to acquire foreign DNA and facilitate
and automated antimicrobial susceptibility testing systems
horizontal gene transfer (Cooper 2017). The SENTRY database
like VITEK 2 and MicroScan. The Clinical and Laboratory
revealed the dominance of blaOXA-23-like and blaOXA-24-like
Standards Institute (CLSI) provides guidelines for these
genes among CRAB isolates (Gales 2019). Table 1 outlines
methods to ensure standardized and reliable results. It also
common antibiotic resistance mechanisms identified in A.
regularly reviews new pharmacokinetic/pharmacodynamic
baumannii, including β-lactamase enzymes.
(PK/PD) and clinical data to incorporate emerging findings and
resistance patterns (Prinzi 2023). However, turnaround time in
Efflux Overexpression
incorporating these updated breakpoints into clinical microbi-
ology laboratories can be prolonged, especially in automated Efflux pumps, also known as multidrug transporters, play a
antimicrobial susceptibility testing panels, which may delay significant role in conferring A. baumannii resistance. These
application of the most current resistance information in clin- systems actively extrude a variety of antimicrobial agents and
ical settings. This lag can affect timely decision-making for other toxic substances from the bacterial cell, contributing to
effective antimicrobial therapy. its MDR phenotype. Efflux systems in Acinetobacter can be
An in-depth study was conducted to establish new suscep- classified into several families, including the major facilitator
tibility test interpretive criteria (STIC) for four antimicrobial superfamily, the small multidrug resistance protein family, the
agents—amikacin, ceftazidime, ciprofloxacin, and minocy- multidrug and toxic compound extrusion family, and the resis-
cline—against A. baumannii. This comprehensive approach tance-nodulation-cell division (RND) family, with RND-type
integrated in vitro surveillance data, preclinical murine infec- efflux pumps being the most prevalent among gram-negative
tion models, population PK, simulations, and PK/PD target organisms (Zack 2024; Abdi 2020).
attainment analyses. In vitro data were collected from 1647 Several specific efflux systems have been identified in A.
clinical A. baumannii isolates from 109 centers in the United baumannii (Table 2). These include AdeABC, AdeIJK, and
States and Europe (Lepak 2023). These isolates were used to AdeFGH from the RND superfamily; AbeM from the multidrug
select specific strains for evaluation in murine infection mod- and toxic compound extrusion superfamily; and AbaF, AmvA,
els. Pharmacokinetics and dose-ranging studies conducted in CraA, Tet(A), Tet(B), and Tet(X) from the major facilitator super-
neutropenic murine thigh and lung infection models provided family (Castanheira 2023; Kornelsen 2021). Overexpression of
PK/PD targets associated with bacterial stasis and reduction, these systems can significantly elevate MICs for various anti-
which were crucial for determining the STIC. The recom- biotics, though modestly in the absence of other resistance
mended susceptibility breakpoints for the 4 agents against mechanisms.
A. baumannii were amikacin 8 mg/L or less for pneumonia
(ceftazidime 32 mg/L or less [or 8 mg/L or less for pneumo- Outer Membrane Proteins
nia]), ciprofloxacin 1 mg/L or less, and minocycline 0.5 mg/L Alterations in OMPs are another significant resistance mech-
or less (or 1 mg/L or less for high dosing regimens) (Lepak anism in A. baumannii. These proteins form channels through
2023). These breakpoints were derived from the highest MIC which molecules, including antibiotics, enter the bacte-
at which the probabilities of achieving PK/PD targets associ- rial cell. Mutations or downregulation of these OMPs can
ated with a 1-log10 CFU reduction from baseline approached or reduce antibiotic uptake, thereby conferring resistance. Loss
exceeded 90%. or modification of OMPs such as CarO, OmpA, and OprD-like

IDSAP 2025 4 Chapter: Acinetobacter baumannii

 Table 1. A. baumannii Resistance Mechanisms and Antibiotic Affected

Resistance gene Mechanism of resistance Antibiotics affected

Ambler class A β-lactamase Hydrolyze β-lactam antibiotics by cleaving the β-lactam ring Penicillin
CTX-M, KPC, SHV, TEM Cephalosporins
Carbapenems

Ambler class B (metallo) Use a zinc ion at their active site to hydrolyze carbapenems Penicillin
β-lactamase and other β-lactams Cephalosporins
IMP, NDM, VIM Carbapenems
β-Lactam/β-lactamase
inhibitor combinations

Ambler class C β-lactamase Hydrolyze cephalosporins and monobactams, conferring Cephalosporins

ADC resistance while being unaffected by β-lactamase inhibitors (except cefepime)

Ambler class D β-lactamase Hydrolyze carbapenems and oxacillin, leading to resistance to Penicillins
OXA-23/24/40/50/51/58 carbapenems and extended-spectrum β-lactams Carbapenems

Aminoglycoside-modifying Enzymatically modify aminoglycosides through acetylation, Aminoglycosides

enzymes adenylation, or phosphorylation, preventing the antibiotic from
AAC(6’)-Ib, AAC(6’)Ih binding to its target
AAC(3)-Ia, ANT(200)Ia
APH(3’)-Ia

DNA gyrase amino acid Mutations in DNA gyrase and topoisomerase IV reduce Fluoroquinolones
substitution fluoroquinolone binding, disrupting antibiotic action and
gyrA and parC genes conferring resistance

Efflux pumps Efflux pumps actively transport antibiotics out of the bacterial Tetracyclines
TetA, TetB cell, reducing their intracellular concentration

PBP reduced expression Reduce the binding affinity for β-lactam antibiotics Sulbactam
PBP2/3 Cefiderocol

Porin channel mutations Decrease antibiotic influx, limiting drug entry and reducing Cephalosporins
OmpA susceptibility Carbapenems

Siderophore-receptor gene Impairs the transport of siderophore-antibiotic complexes into Cefiderocol

reduced expression the bacterial cell, limiting drug uptake
PiuA

Abbreviations: ADC, A. baumannii–derived cephalosporinases; OXA, oxacillinase; PBP, penicillin-binding protein.

proteins has been linked to increased β-lactam resistance in (Moussa 2023; Penwell 2015). These mutations lead to amino
A. baumannii (Han 2022; Kyriakidis 2021). Modifications in the acid substitutions that compromise the binding affinity of sul-
expression of these OMPs often accompany other resistance bactam, resulting in a considerable increase in resistance
mechanisms, such as the production of β-lactamases and levels. Of note, although the frequency of sulbactam resis-
efflux pump overexpression, contributing to the overall MDR tance is low, with rates estimated at 4 × 10 -9, specific pbp3
phenotype of A. baumannii. mutations, such as serine-to-threonine and serine-to-phenyl-
alanine substitutions, significantly affect the effectiveness of
Target Site Alteration sulbactam. Although these mutations can confer resistance,
Target site alteration is a crucial mechanism by which they often come with a fitness penalty, indicating that resis-
Acinetobacter acquires resistance to various antibiotics, par- tant strains may survive antibiotic pressure but may be less
ticularly sulbactam (Penwell 2015). The antibacterial effect competitive in the absence of the drug (Penwell 2015).
of sulbactam is primarily mediated through the inhibition of
PBPs, specifically PBP1 and PBP3, though it does not signifi- Virulence Factors
cantly affect PBP2 (Penwell 2015). The high-level resistance Virulence factors enhance the pathogenicity and resistance
to sulbactam has been linked to mutations in the pbp3 gene of A. baumannii. These factors include enzymes, toxins, and

IDSAP 2025 5 Chapter: Acinetobacter baumannii

 Pharmacokinetic/pharmacodynamic evaluations in a
Table 2. Efflux Systems in A. baumannii and Affected murine pneumonia model assessed optimal dosing for ampi-
Antibiotics cillin-sulbactam against A. baumannii (Abouelhassan 2024a).
Using 21 clinical isolates, including carbapenem-resistant
Efflux
pump Family Antibiotics affected strains, the study showed sulbactam’s time-dependent activ-
ity, with fractionated dosing (every 6 hours and every 3 hours)
AdeABC Aminoglycosides, β-lactams,
enhancing bacterial kill rates. The key efficacy measure, %fT
fluoroquinolones, chloramphenicol
> MIC, varied significantly with resistance levels. Simulation
AdeIJK β-Lactams, fluoroquinolones, results showed that the standard dose of 1 g every 6 hours
RND
tetracyclines achieves over 90% probability of target attainment (PTA) for
AdeFGH Chloramphenicol, fluoroquinolones, isolates with an MIC of 4 μg/mL or less. For those with inter-
trimethoprim mediate susceptibility (MIC 8 μg/mL), a high-dose regimen
of 3 g every 8 hours, delivered by a 4-hour infusion, is neces-
AbeM MATE Fluoroquinolones, aminoglycosides
sary to maintain over 90% PTA. However, for isolates with an
AbaF Carbapenems MIC of 16 μg/mL or greater, even increased dosing regimens
AmyA Chloramphenicol, erythromycin reached only 57% PTA, indicating that monotherapy is likely
ineffective. The study also differentiated PK/PD targets for
CraA Chloramphenicol
MFS carbapenem-susceptible versus resistant phenotypes, finding
Tet(A) Tetracyclines that sulbactam- and meropenem-resistant isolates needed up
Tet(B) Tetracyclines to 60.37% fT > MIC for a 1-log bacterial kill. Thus, the authors
concluded that standard dosing suffices for MICs of 4 μg/mL
Tet(X) Tetracyclines
or less, high-dose extended infusion is advisable for MICs of
8 μg/mL, and combination therapy is recommended for MICs
Abbreviations: MATE, multidrug and toxic compound extru- of 16 μg/mL or greater to effectively address resistant A. bau-
sion; MFS, major facilitator superfamily; RND, resistance-
nodulation-cell division. mannii infections.
Another study evaluated the efficacy of two sulbactam dos-
ing regimens against A. baumannii pneumonia using a murine
structural components that aid in disease causation and model, with a specific focus on the impact of the blaOXA-23
immune evasion. One of the most critical virulence factors is resistance gene (Abouelhassan 2024b). Thirty-two A. bau-
the ability to form biofilms on medical devices and surfaces mannii clinical isolates were assessed, with 10 classified as
within health care settings. Biofilms provide a protective envi- sulbactam susceptible (MIC, 4 mg/L or less), 6 as intermediate
ronment against antibiotics and immune responses, making (MIC, 8 mg/L), and 16 as resistant (MIC, 16 mg/L or greater).
infections challenging to eradicate. A. baumannii also pro- Of note, 11 of these isolates carried the blaOXA-23 gene, which
duces various enzymes and toxins that contribute to its was closely associated with sulbactam resistance (resistant
virulence (Upmanyu 2022). Enzymes such as phospholipases n = 10, intermediate n = 1). In dose-fractionation studies, both
and proteases degrade host tissues, facilitating bacterial inva- sulbactam regimens (1 g every 6 hours as a ½-hour infusion
sion and infection (Yao 2023). In addition, secretion of outer and 3 g every 8 hours as a 4-hour infusion) achieved over a
membrane vesicles enables the direct delivery of virulence 1-log kill against sulbactam-susceptible isolates. However,
factors to host cells, enhancing the bacterium’s ability to the presence of blaOXA-23 significantly reduced the efficacy
cause disease (Weng 2023). of both regimens, with neither achieving effective bacterial kill
against blaOXA-23-positive resistant isolates. The high-dose,
prolonged-infusion regimen (3 g every 8 hours) showed some
THERAPEUTIC APPROACHES improved efficacy against isolates with intermediate suscep-
tibility, killing 6 of 6 isolates in vivo, but was largely ineffective
β -Lactams
against most of the blaOXA-23-positive isolates. In contrast,
Ampicillin-Sulbactam the 1-g every-6-hours regimen did not show efficacy against
Ampicillin-sulbactam, a fixed-dose combination in a 2:1 ratio any blaOXA-23-positive isolates. Genotypic analysis using
of ampicillin to sulbactam, is effective against A. baumannii whole genome sequencing showed that the presence of the
because of sulbactam’s unique antibacterial activity (Penwell blaOXA-23 gene correlated with higher MICs for sulbactam.
2015). Unlike traditional β-lactamase inhibitors, sulbactam Among the resistant isolates, those lacking blaOXA-23 showed
independently targets A. baumannii by binding to and satu- better in vivo efficacy, suggesting that other resistance mech-
rating specific PBPs (PBP1a, PBP1b, and PBP3), inhibiting anisms allow for successful sulbactam treatment in the
cell wall synthesis and contributing to its antibacterial effects absence of blaOXA-23. The study highlights that although
(Papp-Wallace 2012). both sulbactam regimens are effective against susceptible

IDSAP 2025 6 Chapter: Acinetobacter baumannii

isolates, the presence of blaOXA-23 is a critical factor in pre- Sulbactam-durlobactam, a dual β-lactamase inhibi-
dicting treatment failure in resistant strains. These findings tor combination designed for adults (18 years and older), is
underscore the importance of improving blaOXA-23 detection indicated for treating hospital-acquired bacterial pneumo-
in clinical settings to guide more effective treatment strate- nia and ventilator-associated bacterial pneumonia (VABP)
gies for A. baumannii infections, particularly in cases involving caused by susceptible strains of the ABC (El-Ghali 2023). This
multidrug resistance. novel therapeutic was FDA approved in May 2023 to address
High-dose sulbactam, particularly in combination with other MDR Acinetobacter infections. Durlobactam is the only β-
agents, has shown promising results in treating MDR and XDR lactamase inhibitor that reliably inhibits OXA carbapenemases,
A. baumannii infections, especially in critically ill patients with which are prevalent in MDR Acinetobacter strains (Shapiro
VAP. In a clinical trial comparing colistin monotherapy with a 2021). Durlobactam also inhibits class A and C β-lactamases,
combination of colistin and high-dose ampicillin-sulbactam, enhancing its range of activity against resistant Acinetobacter
patients receiving the combination therapy had a significantly strains. In June 2023, CLSI approved sulbactam-durlobactam
higher early cure rate (70%) than those receiving colistin alone breakpoints for Acinetobacter spp, establishing both MIC and
(15.8%) (Makris 2018). Although the 28-day mortality rates DD breakpoints to guide clinical use (McLeod 2024).
between the two groups did not show a statistically signifi- The recommended dosing regimen for sulbactam-durlo-
cant difference, early treatment response was closely linked to bactam involves administering 1 g of sulbactam and 1 g of
improved survival, underscoring the potential benefit of com- durlobactam (2 g total) every 6 hours, delivered by a 3-hour
bining colistin with high-dose sulbactam for more favorable intravenous infusion to optimize drug exposure (O’Donnell
clinical outcomes in VAP caused by CRAB. 2023). Sulbactam-durlobactam is shown to achieve
A comprehensive 2017 Bayesian network meta-analysis, PK/PD goals for over 90% of A. baumannii isolates with MICs
including 23 studies and 2118 patients, further supported of 4/4 μg/mL or less, thereby aligning with both FDA and CLSI
sulbactam’s efficacy in this context (Jung 2017). This breakpoints and maximizing efficacy against this pathogen
meta-analysis ranked sulbactam monotherapy highest for (Abouelhassan 2022; Jaruratanasirikul 2019). The detailed
reducing all-cause mortality among 15 regimens, with a PK/PD assessment highlights the effectiveness of sulbac-
mortality rate as low as 18%. Compared with intravenous tam-durlobactam in managing A. baumannii pneumonia,
colistin monotherapy, sulbactam showed superiority in both particularly in the context of HAIs, as supported by current
survival and microbiological clearance, suggesting that dosing recommendations.
sulbactam-based regimens offer safer, more effective alterna- In a global collection of Acinetobacter spp clinical isolates
tives than colistin alone in managing resistant A. baumannii (n = 5032) collected in 2016-2021, the MIC90 was 64 μg/mL
infections. to sulbactam alone, whereas the MIC90 against the sulbac-
A more recent meta-analysis from 2021, involving 18 stud- tam-durlobactam combination was 2/4 μg/mL (Karlowsky
ies and 1835 patients, compared high-dose sulbactam (6 2022). The antimicrobial activity of sulbactam-durlobactam
g/d or more) with colistin-based therapies for MDR and XDR was consistent across individual Acinetobacter spp, resistance
A. baumannii infections (Liu 2021). This analysis identified phenotypes, and geographic regions. The MIC breakpoint of
high-dose sulbactam, particularly in combination with agents 4 μg/mL aligns with the epidemiologic cutoff value, which
like levofloxacin or tigecycline, as similar or even superior to includes 98.1% of clinical isolates from combined clinical trials
colistin with respect to clinical improvement and cure rates. and surveillance studies data sets.
In addition, high-dose sulbactam was associated with lower The efficacy of sulbactam-durlobactam was shown in the
nephrotoxicity than colistin. Although colistin remains a ATTACK trial, a phase 3 multinational, randomized, active-
potent option, these findings highlight high-dose sulbactam controlled, noninferiority clinical trial involving patients with
as a safer, effective alternative or adjunctive therapy, particu- pneumonia or BSI caused by A. baumannii (Kaye 2023). In
larly when nephrotoxicity is a concern. this study, 181 patients (125 with CRAB) were randomized to
receive either sulbactam-durlobactam or colistin, both in com-
Sulbactam-Durlobactam bination with imipenem-cilastatin. The primary outcome of
Sulbactam has activity against Acinetobacter but has seen 28-day mortality showed that sulbactam-durlobactam was
increasing resistance. The addition of durlobactam, a non–β- noninferior to colistin, with mortality rates of 19% in the sul-
lactam diazabicyclooctane and potent inhibitor of class A (eg, bactam-durlobactam group compared with 32% in the colistin
TEM-1), class C (eg, ADC), and class D β-lactamases (eg, OXA- group. Furthermore, sulbactam-durlobactam showed higher
24/40, OXA-23), restores sulbactam activity against resistant clinical cure and microbiologic response rates and lower neph-
Acinetobacter strains by facilitating sulbactam to reach its PBP rotoxicity rates than colistin.
targets (El-Ghali 2023). Although durlobactam does reduce Concomitant administration of imipenem-cilastatin (tar-
the likelihood of sulbactam hydrolysis by carbapenemases, gets PBP2) to sulbactam-durlobactam (targets PBP1, PBP3)
allowing sulbactam to successfully reach its PBP targets, it has shown multi-fold decreases in sulbactam-durlobactam
does not inhibit class B metallo-β-lactamases (MBLs). MIC, likely because of expanded saturation of target PBPs and

IDSAP 2025 7 Chapter: Acinetobacter baumannii

imipenem serving as a substrate of OXA carbapenemases, higher mortality rate than those who received alternative
protecting sulbactam-durlobactam activity (Tamma 2024). regimens. Specifically, of the 56 patients with CRAB infec-
However, clinical data on the efficacy of sulbactam-durlobac- tion, mortality among patients treated with cefiderocol was
tam without imipenem-cilastatin are currently unavailable, and 49% compared with 18% in the alternative-therapy arm at the
adjunctive therapy with a carbapenem is recommended on the end-of-study visit. Patients in the cefiderocol arm were more
basis of in vitro findings. In the ATTACK trial, which compared likely to be in the ICU at randomization and have ongoing sep-
sulbactam-durlobactam with colistin, imipenem-cilastatin tic shock, which may partly explain the imbalanced mortality
was used as background therapy in both arms, underscoring proportions. The APEKS-NP study, a subsequent randomized
the current reliance on combination therapy in clinical practice phase 3 trial of patients with nosocomial pneumonia, showed
because of the lack of monotherapy data. that cefiderocol was noninferior to dose-optimized mero-
In a reported case, a critically ill patient with XDR A. bau- penem among 292 patients (Wunderink 2021). For those with
mannii necrotizing pneumonia complicated by empyema was CRAB infection, 28-day mortality rates did not differ signifi-
treated with sulbactam-durlobactam and meropenem after cantly between cefiderocol and meropenem treatment groups.
standard antibiotics failed (Holger 2022). Laboratory tests Several observational studies have provided mixed results
showed synergistic killing between sulbactam-durlobactam regarding cefiderocol’s effectiveness in real-world settings. A
and meropenem, reducing meropenem’s MIC 4-fold and sul- study from a single center in Italy compared cefiderocol-based
bactam-durlobactam’s MIC 2-fold. This synergy, indicated by regimens with colistin-based regimens for treating CRAB
a fractional inhibitory concentration index of 0.375 and con- infections (Falcone 2022). The study found that treatment
firmed by time-kill analysis with a greater than 2-log reduction with cefiderocol was associated with a lower risk of 30-day
in bacterial count, contributed to infection resolution after mortality in an adjusted analysis, but microbiologic failures
13 days of therapy. Furthermore, cefepime has shown in vitro were higher in the cefiderocol group than in the colistin group.
synergy with sulbactam-durlobactam, particularly against A. Moreover, treatment-emergent resistance to cefiderocol has
baumannii isolates with high MICs (Fouad 2023). This combi- been reported, highlighting the potential for resistance devel-
nation may be a viable alternative to carbapenems in cases of opment during therapy. Use of combination therapy, involving
polymicrobial infections or high MICs. cefiderocol with other agents like ampicillin-sulbactam or
ceftazidime-avibactam, has shown promise in preventing
Cefiderocol resistance emergence and enhancing bacterial killing in vitro
Cefiderocol is a novel siderophore cephalosporin designed to and in animal models (Gill 2023).
treat infections caused by carbapenem-resistant gram-nega- Cefiderocol’s PK/PD properties present a promising profile,
tive bacteria, including A. baumannii. Cefiderocol overcomes showing exposures in the epithelial lining fluid of ventilated
key A. baumannii resistance mechanisms, including OXA-type patients similar to other cephalosporins (Kawaguchi 2022;
carbapenemases, efflux pumps, porin loss, and broad-spec- Katsube 2021, 2019). However, treating infections caused by
trum β-lactamases, by using the bacterial iron transport CRAB poses significant challenges. One of the primary diffi-
system to penetrate the outer membrane and inhibit PBPs, culties in accurately testing susceptibility to cefiderocol arises
specifically PBP3 (Huang 2024). This unique siderophore-me- from the inconsistent breakpoints established by different
diated entry also stabilizes cefiderocol against MBLs. regulatory agencies. These varying criteria can lead to con-
This allows cefiderocol to overcome resistance mech- fusion in clinical decision-making, emphasizing the need for
anisms that typically render other β-lactams ineffective, caution when interpreting susceptibility results (CLSI 2024;
including OXA-type carbapenemases, broad-spectrum Flamm 2016).
β-lactamases, efflux pumps, and porin loss, by using the bac- Interpreting cefiderocol antimicrobial susceptibility testing
terial iron transport system for entry and maintaining stability results for Acinetobacter presents unique challenges, partic-
against MBLs (Karakonstantis 2022). Surveillance studies ularly because of the issue of trailing MICs and the critical
have shown universally high rates of susceptibility against role of iron concentrations in the testing media. To accurately
CRAB when defined by the CLSI breakpoint of 4 mg/L or less, determine cefiderocol susceptibility, it is crucial to consider
including against isolates with varying molecular mechanisms iron concentrations in the testing media. The standard cat-
of resistance (Seifert 2023). However, the in vitro activity of ion-adjusted Mueller Hinton broth (CAMHB) requires iron
cefiderocol has not consistently translated into superior clini- depletion to provide reproducible MICs that predict in vivo
cal efficacy against CRAB infections. activity (Simner 2020). CLSI has recommended a method for
In CREDIBLE-CR, an open-label phase 3 trial, patients were preparing iron-depleted CAMHB (ID-CAMHB) that involves
randomly assigned to receive cefiderocol or an alternative chelating cations from the broth to ensure iron concentrations
therapy for the treatment of infections caused by carbap- remain at or below 0.03 μg/mL (CLSI 2024). This iron-depleted
enem-resistant gram-negative pathogens (Bassetti 2021). environment is essential because cefiderocol relies on active
Among the 118 patients in the microbiologic intent-to-treat iron transport for entry into the bacterial periplasm, where it
population, those treated with cefiderocol had a numerically can inhibit cell wall synthesis through binding to PBPs (Holbein

IDSAP 2025 8 Chapter: Acinetobacter baumannii

2021). Studies have shown that MICs for cefiderocol are sig- When effective, carbapenems are preferred for their broad
nificantly influenced by the presence of iron; higher MICs were efficacy and favorable tolerability compared with non–β-lac-
observed when cefiderocol was tested with standard CAMHB tam antibiotics. A multicenter study of Acinetobacter BSIs over
compared with iron-depleted media (Seifert 2023; Nakamura 5 years evaluated the clinical impact of carbapenem MICs on
2019; Yamano 2019). outcomes, including 224 patients treated with either mero-
Given the critical role of iron-depleted environments in opti- penem or imipenem (Yang 2017). A. baumannii was the most
mizing cefiderocol susceptibility testing, it is equally important commonly isolated pathogen (54%), and no significant differ-
to explore the various methods used to assess its efficacy ences in 30-day mortality were observed between patients
against resistant Acinetobacter strains. A study investigated receiving meropenem compared with imipenem. However,
the effectiveness of various antimicrobial susceptibility mortality rates increased notably with higher carbapenem
testing methods (eg, DD, E-test, and BMD) for assessing cefid- MICs: mortality was 23.5% for MICs of 4 mg/L or less but
erocol’s activity against Acinetobacter; the research compared increased to 42.9% at an MIC of 8 mg/L, indicating poorer out-
2 commercial BMD kits (ComASP and UMIC) and evaluated DD comes as resistance levels increased.
and E-test methods using standard MH agar and iron-depleted Use of continuous or prolonged carbapenem infusions is
(ID-MH) agar (Kolesnik-Goldmann 2023). The results indicate suggested to optimize PK and improve infection-related out-
that testing on ID-MH agar significantly improves diagnostic comes. In an assessment of 30 patients with A. baumannii
performance, with DD on ID-MH achieving a categorical agree- VAP, those treated with extended infusions of meropenem had
ment of 95.1% with the reference BMD method, compared with lower relapse rates than those treated with conventional 1-hour
lower categorical agreements with standard MH agar. The infusions, though clinical success rates were similar (Wang
E-test on ID-MH also showed a higher essential agreement of 2009). Additional studies of severe infections like VAP have
75%. The findings suggest that both DD and E-test methods further supported the benefits of extended-infusion β-lactams
on ID-MH agar are better than commercial BMD methods for for pathogens with elevated MICs (Hong 2023; Chastre 2008).
detecting high-level resistance. Although extended-infusion carbapenems have shown
This expanded understanding of the effect of iron on benefits for non-CRAB, wild-type A. baumannii isolates with
cefiderocol testing highlights the complexity of interpreting moderately elevated MICs, the emergence of CRAB has
antimicrobial susceptibility testing results, especially in the necessitated the use of combination therapies to overcome
presence of trailing MICs, which are particularly common in the higher levels of resistance seen in these strains. Use of
Acinetobacter spp (Stracquadanio 2024). Trailing, where par- meropenem in combination therapy, especially with colistin,
tial or delayed bacterial growth leads to ambiguous MIC end has been widely studied because of the high rates of in vitro
points, must be carefully managed. When trailing occurs, the synergy observed (Ju 2022; Gunalan 2021). Colistin enhances
MIC should be read as the first well where there is a significant carbapenem activity by depolarizing the outer cell membrane,
reduction in growth compared with the control, ignoring the which allows carbapenems better access to target sites within
trailing effects (CLSI 2024). the periplasmic space (Pogue 2021). Despite this promising
In addition, the dynamic nature of resistance in A. bauman- mechanism, two large randomized clinical trials concluded
nii can lead to the emergence of resistance during treatment, that combining colistin with meropenem offered no added
a phenomenon that may not be detected by initial suscepti- benefit over colistin monotherapy in treating invasive CRAB
bility testing (Huang 2024). This issue is compounded by infections (Kaye 2022; Paul 2018).
cefiderocol heteroresistance, where studies have shown that Given these findings, alternative regimens with high-dose
around 59% of CRAB isolates harbor a resistant subpopula- ampicillin-sulbactam have been investigated. One study exam-
tion despite appearing susceptible in standard testing (Choby ined the effectiveness of high-dose ampicillin-sulbactam in
2021). Such heteroresistance can lead to treatment failures if combination with carbapenems, highlighting that carbap-
only conventional methods are used to assess susceptibility. enems, limited by widespread resistance, serve primarily
as adjuncts within these regimens. Although carbapenems
Carbapenems alone show limited efficacy against CRAB, their combination
Meropenem, a broad-spectrum carbapenem antibiotic, with high-dose ampicillin-sulbactam—which effectively sat-
is widely used to treat severe bacterial infections, includ- urates PBPs—has shown potential for enhancing bacterial
ing those caused by A. baumannii. Meropenem functions clearance. The study suggested that combining high-dose
by inhibiting bacterial cell wall synthesis through PBP bind- ampicillin-sulbactam with carbapenems and other agents,
ing. However, the increasing prevalence of CRAB has such as tigecycline or polymyxins, would improve clinical
limited its effectiveness. Resistance to meropenem in A. outcomes where carbapenem efficacy alone is insufficient
baumannii is primarily mediated by the production of carbapenem- (Bartal 2022).
hydrolyzing β-lactamases, such as OXA-type enzymes, and Another study tested a three-drug regimen of high-dose
changes in membrane permeability because of modifications ampicillin-sulbactam (administered as 9 g every 8 hours),
in OMPs (Kyriakidis 2021; Wong 2019; Poirel 2006). meropenem, and polymyxin B in critically ill patients with

IDSAP 2025 9 Chapter: Acinetobacter baumannii

COVID-19 with CRAB infections (Heil 2023). In this cohort, the widespread resistance mechanisms, including the production
addition of meropenem did not significantly increase clinical of β-lactamases such as AmpC and carbapenemases. Studies
success beyond the combination of sulbactam and polymyxin show that the susceptibility of A. baumannii to ceftriaxone is
alone. Only 50% of patients achieved clinical resolution, and minimal, with most clinical isolates showing high resistance
the 30-day mortality rate was 22%, indicating that even high- rates. For instance, in a cohort of MDR A. baumannii, ceftriax-
dose meropenem offers limited benefit in this combination. one resistance was prevalent across various anatomical sites,
Of importance, there was no observed emergence of new with blood and respiratory isolates being particularly resistant.
carbapenem resistance among isolates collected before and Furthermore, resistance was inversely correlated with bacterial
after treatment, suggesting that although carbapenems play a motility and biofilm production, suggesting that strain-specific
supportive role, they are insufficient as primary agents against phenotypic factors influence susceptibility (Boone 2021).
CRAB without high-dose sulbactam. Ceftriaxone use has also been identified as an independent
Imipenem-cilastatin may retain activity against some mero- risk factor for the emergence of MDR A. baumannii in hospi-
penem-resistant isolates because imipenem’s hydroxyethyl tal settings, particularly among ICU patients with prolonged
side chain differs from the methyl group on meropenem, hospital stays or prior exposure to immunomodulatory thera-
affecting how these drugs interact with bacterial carbapen- pies such as tocilizumab (Mihalov 2023). In ICU patients with
emase enzymes and PBPs (Jones 2006). These structural COVID-19, prior ceftriaxone exposure significantly increased
differences make imipenem less susceptible to hydrolysis the odds of developing MDR A. baumannii infections (OR 4.1;
by certain resistance mechanisms, allowing it to be effective 95% CI, 1.4-11.9), underscoring its role in promoting resistance
where meropenem is not. However, the MICs of both agents under high antimicrobial pressure (Mihalov 2023). Given these
against CRAB isolates are almost always significantly higher findings, ceftriaxone is not recommended for the treatment of
than 8 μg/mL (Jones 2006). A. baumannii infections and should be avoided unless suscep-
tibility testing confirms efficacy.
Other β-Lactams
Cefepime Piperacillin-Tazobactam
Cefepime, a fourth-generation cephalosporin, shows limited Piperacillin-tazobactam shows limited efficacy against A.
efficacy against A. baumannii infections because of wide- baumannii infections, particularly in MDR and carbapen-
spread resistance mechanisms. Studies indicate that cefepime em-resistant strains. Susceptibility studies have shown that
resistance in A. baumannii is driven by intrinsic AmpC cephalo- the efficacy of piperacillin-tazobactam against A. baumannii
sporinases, including ADC-56, which enhances the hydrolysis of isolates is generally low, often below 20% (Alrahmany 2021;
cefepime and contributes to resistance (Tian 2011). In addition, Higgins 2004). Furthermore, variations in testing methods
frequent hospital use of cefepime has been shown to correlate complicate susceptibility determination. For instance, when
positively with the emergence of resistant A. baumannii strains, tested at fixed concentrations, trailing effects during suscepti-
with resistance often becoming detectable within 1 month of bility testing can lead to ambiguous MIC results and potentially
increased cefepime use (Kousovista 2021). Resistance rates overestimated activity (Brauers 2005; Higgins 2004). In clin-
in clinical isolates have exceeded 50% in some regions, further ical studies, prior use of piperacillin-tazobactam has been
limiting cefepime’s usefulness as a monotherapy for A. bau- associated with increased odds of A. baumannii infections,
mannii infections (Kousovista 2021). particularly carbapenem-resistant strains, with an odds ratio
Recent data suggest potential benefits of cefepime when of 2.5 (Chen 2014). These findings collectively render pipera-
used in combination therapies. The combination of cefepime cillin-tazobactam unsuitable as monotherapy for serious A.
with sulbactam-durlobactam has shown in vitro synergy baumannii infections, especially MDR strains.
against certain MDR A. baumannii isolates, particularly those Despite these limitations, piperacillin-tazobactam may play
with elevated MICs to sulbactam-durlobactam alone (Fouad a role in combination therapies, though this application remains
2023). However, this combination showed no antagonism, and inadequately validated. Some studies have reported limited in
its clinical efficacy requires further validation (Fouad 2023). vitro synergy when piperacillin-tazobactam is combined with
Given the high resistance rates, cefepime is not recommended agents such as sulbactam or colistin (Brauers 2005; Higgins
for empiric monotherapy against A. baumannii infections. 2004). However, clinical outcomes with these combinations
Instead, cefepime use should be restricted to combination remain inconsistent, and adverse events have been noted
regimens guided by susceptibility testing and in scenarios when piperacillin-tazobactam is used in MDR A. baumannii
involving polymicrobial infections where other gram-negative infections (Alrahmany 2021). Moreover, retrospective analyses
pathogens are targeted (Fouad 2023; Tian 2011). suggest that prior use of piperacillin-tazobactam contributes
to resistance selection (Chen 2014). Overall, the usefulness of
Ceftriaxone piperacillin-tazobactam is limited to use in empiric therapy for
Ceftriaxone, a third-generation cephalosporin, has limited polymicrobial infections involving nonresistant gram-negative
efficacy against A. baumannii because of the pathogen’s

IDSAP 2025 10 Chapter: Acinetobacter baumannii

 Table 3. Colistin and Polymyxin B Considerations for Acinetobacter spp

Parameter Colistin Polymyxin B

PK/PD Prodrug (colistimethate sodium) converted to active colistin; Active drug administered directly; faster onset
slower onset of action; concentration-dependent killing of action; concentration-dependent killing

Tissue Poor tissue penetration; low in lungs and CSF; accumulates Better tissue penetration than colistin; higher
concentrations in kidneys concentrations in lungs and blood

Elimination Renally eliminated (prodrug); risk of accumulation in renal Nonrenal elimination (biliary/fecal); safer in
impairment renal impairment

Dosing Dose adjustment required for renal function; typically 2.5-5 No dose adjustment for renal function; fixed
mg/kg/d of CBA in divided doses dosing: 1.5-3 mg/kg/d in divided doses

Abbreviations: CBA, colistin base activity; PK/PD, pharmacokinetic/pharmacodynamic.

pathogens, with susceptibility testing being crucial for appro- Cai 2016). In the context of combination therapy, studies sug-
priate use (Brauers 2005; Higgins 2004). gest limited benefits of combining colistin with meropenem.
The OVERCOME (Colistin Monotherapy versus Combination
Polymyxins Therapy) trial, a double-blind, placebo-controlled trial, com-
Polymyxins, including colistin and polymyxin B, are often pared colistin monotherapy with colistin plus meropenem (1 g
considered essential for treating CRAB infections because every 8 hours as a 30-minute infusion) for BSI or pneumonia,
of their reliable in vitro activity (Bartal 2022). Of note, poly- and a subsequent meta-analysis found no significant improve-
myxin B is usually preferred to colistin in non-UTIs because ments in mortality or clinical outcomes when meropenem was
of its PK advantages, such as less interpatient variability in added to colistin for treating MDR A. baumannii (Huang 2022;
drug exposure, more predictable steady-state concentrations, Kaye 2022). These findings underscore the limited usefulness
and improved safety with respect to reduced nephrotoxicity of colistin-carbapenem combinations in CRAB management
(Garcia 2023; Gupta 2009). Unlike colistin, which requires con- and further support the preference for polymyxin B when a
version to its active form in the urinary tract, making it more polymyxin agent is required, given its faster and more reliable
suitable for CRAB-related UTIs, polymyxin B achieves active achievement of steady-state concentrations and less variability
concentrations more consistently in the bloodstream, which in drug exposures.
may benefit patients with systemic CRAB infections (Aslan An alternative, promising approach is a three-drug reg-
2022). Table 3 shows considerations for the use of colistin and imen involving polymyxin B, ampicillin-sulbactam, and a
polymyxin B in patients with A. baumannii infections. carbapenem. Mechanistic studies suggest that polymyxins
A significant limitation in the clinical use of polymyxins for enhance the activity of ampicillin-sulbactam and carbapen-
CRAB is the absence of a CLSI susceptibility breakpoint for ems by increasing bacterial membrane permeability, allowing
A. baumannii, raising concerns about their applicability, par- each agent to target complementary PBPs effectively (Pogue
ticularly given that efficacy diminishes when MICs exceed 2021). Time-kill studies have shown that this triple combina-
2 μg/mL (Pogue 2020). This issue is further compounded by tion achieves more rapid and extensive bacterial killing than
the variability in serum concentrations achieved with stan- two-drug regimens, especially against colistin-resistant CRAB
dard dosing, which often fail to reach bactericidal levels. When strains (Cai 2016). In a single-center observational study, a
MICs are above 2 μg/mL, the risk of treatment failure increases 30-day mortality rate of 0% was reported for patients treated
because higher doses required for efficacy coincide with the with the three-drug regimen, in contrast to a 60% mortality rate
threshold for nephrotoxicity (Wu 2022; Nation 2019; Cai 2016). among those receiving other treatments, indicating potential
In addition, intravenous polymyxins show poor penetration clinical benefits in severe cases (Qureshi 2015).
into pulmonary epithelial lining fluid, limiting their effective- A separate study conducted during a COVID-19 outbreak
ness in treating CRAB-related pneumonia (Almangour 2021). evaluated a dose-optimized regimen of ampicillin-sulbactam,
The ability of polymyxin B to achieve consistent steady- polymyxin B, and meropenem to treat CRAB pneumonia; it
state concentrations across patients, including those with identified a relatively low 30-day mortality rate of 23% (3 of
renal impairment, further supports its preference over colis- 13) and suppression of further resistance development (Heil
tin (Wu 2022; Nation 2019). However, polymyxin monotherapy 2023). This finding suggests that a three-drug regimen incor-
is usually discouraged because of high rates of clinical fail- porating high-dose ampicillin-sulbactam, polymyxin B, and
ure and the potential for resistance development (Yang 2024; extended-infusion meropenem is effective for invasive or

IDSAP 2025 11 Chapter: Acinetobacter baumannii

resistant CRAB infections that have not responded to other the usefulness of tetracyclines as monotherapy for BSIs where
treatments. However, the cumulative toxicity risks associated sustained systemic concentrations are crucial.
with dual β-lactams and polymyxin B necessitate close moni- Despite their potential, tetracycline-based treatments for
toring, especially in critically ill patients. CRAB lack the rigorous evaluation seen with polymyxin- and
sulbactam-based regimens. To date, no randomized clinical
Tetracyclines trials have directly compared tetracycline-based regimens
Tetracycline derivatives (eg, minocycline, tigecycline, eravacy- with other CRAB therapies, leaving a gap in high-quality
cline) have shown effectiveness against CRAB in laboratory evidence. Observational studies offer some insights but
settings, but significant limitations affect their clinical use. are often limited by small sample sizes, varied infection
Resistance to these agents in CRAB primarily arises through types, and inconsistent dosing regimens. These studies
efflux pumps, particularly the RND-type transporters, which also often combine tetracyclines with other agents or eval-
actively expel tetracyclines from bacterial cells, reducing their uate them in monotherapy, complicating the interpretation
efficacy (Castanheira 2023). Another major drawback is the of their efficacy. Given these factors, tetracyclines are typ-
PK profile of tetracyclines; these drugs rapidly distribute into ically considered as part of combination therapy for CRAB,
tissues after administration, resulting in low concentrations in with their role as monotherapy limited by PK challenges and
the serum and urine (Musher 1975). Consequently, this limits resistance mechanisms. Of note, tetracyclines have a lower

Table 4. Tetracycline Considerations for Acinetobacter spp

Parameter Minocycline Tigecycline Eravacycline Omadacycline

Activity against Significant in vitro activity; Active against MDR Potent in vitro activity Moderate activity; inhibits
CRAB effective against ~60%- and XDR CRAB; limited with lower MICs ~68% of CRAB isolates
80% of CRAB isolates; efficacy in BSIs and than minocycline or at ≤ 4 mg/L; synergy in
retains activity against pneumonia tigecycline; lacks clinical combination therapies
TetB efflux pump breakpoints for CRAB

PK/PD High tissue penetration Rapid tissue distribution Limited PK/PD data; high Limited systemic efficacy
challenges but lower systemic with low serum fAUC targets needed as monotherapy;
levels; achieves concentrations; PK for efficacy; tissue significant bactericidal
therapeutic targets at targets not achieved penetration similar to activity in combinations
MICs ≤ 1 mg/L for MIC > 1 mg/L tigecycline

Resistance Resistant to TetB efflux RND-type efflux pumps; Limited resistance data; Resistance through efflux
mechanisms pump; limited at higher reduced activity at active against some tige- pumps; retains activity
MIC values (> 1 mg/L) higher MICs cycline-resistant strains against some minocycline-
resistant strains

Clinical data High clinical success Inferior outcomes as Real-world studies show Limited clinical data; small
(~78%) in respiratory, monotherapy; better 30-d mortality ~24% in case series suggest ~67%
bloodstream, and skin efficacy in combination CRAB; poorer outcomes success in bone/joint and
infections; well studied therapy; high-dose regi- in bacteremia or CRAB infections
in combination therapy mens recommended coinfections

Dosing IV: 200 mg q12h; High dose: 200 mg IV: 1 mg/kg q12h; well IV/oral: 100 mg q12h; good
considerations no renal/hepatic loading, then 100 mg tolerated; limited tolerability; potential for
adjustments; oral/IV q12h; PK variability in nephrotoxicity combination regimens
switchable critically ill patients

Combination Effective in combination Improved outcomes Potential role in Synergy in combinations

therapy with colistin, sulbactam, when combined with combination therapy; with sulbactam and
potential or aminoglycosides; colistin or sulbactam; synergy observed polymyxin B; triple
clinical success ~80% in avoids nephrotoxicity with sulbactam and regimens improve
severe infections polymyxin B bactericidal effects

Information from: Dingle 2019; Khanna 2018; Tariq 2017.

Abbreviations: BSI, bloodstream infection; CRAB, carbapenem-resistant A. baumannii; IV, intravenous(ly); MDR, multidrug-resistant;
PK/PD, pharmacokinetic/pharmacodynamic; q, every; RND, resistance-nodulation-cell division; XDR, extensively drug-resistant.

IDSAP 2025 12 Chapter: Acinetobacter baumannii

Clostridioides difficile risk than other antibiotic classes, which In combination therapy, minocycline was used with
may offer a benefit in some patient populations at high risk antibiotics such as colistin, ampicillin-sulbactam, and ami-
(Dingle 2019; Khanna 2018; Tariq 2017). Table 4 summarizes noglycosides in 94 cases, achieving clinical success rates
considerations for the use of tetracyclines for A. baumannii as high as 78%, particularly in severe infections (Ning 2014;
infections. Pogue 2014). A recent prospective observational study evalu-
ated minocycline in combination therapy for VABP caused by
Minocycline
XDR or pandrug-resistant A. baumannii (Athanassa 2024). In
Minocycline is the only tetracycline that shows significant in 20 ICU patients with VABP treated with minocycline plus colis-
vitro effectiveness against MDR A. baumannii, often showing tin and meropenem, clinical success was observed in 80%
greater activity than other tetracyclines; this agent is available of cases, with a 72% microbiological success rate. However,
in both oral and intravenous forms (Lashinsky 2017; Jankowski 50% of the patients died within 28 days, though most of these
2012). Unlike other tetracyclines, minocycline’s structure deaths were unrelated to VAP.
allows it to overcome certain resistance mechanisms, such as
the TetB efflux pump, which limits the effectiveness of other Tigecycline
tetracyclines in A. baumannii. Minocycline has high tissue pen- Tigecycline, a glycylcycline antibiotic, has emerged as a treat-
etration and does not require dose adjustments for patients ment for infections caused by MDR and XDR A. baumannii.
with renal or hepatic impairment, making it convenient in However, tigecycline’s clinical efficacy is variable, particularly
clinical settings (Agwuh 2006). The ability of minocycline to in severe infections such as pneumonia and BSI, where mono-
change between intravenous and oral formulations without therapy has been associated with higher all-cause mortality
significant changes in efficacy further enhances its usabil- rates (Jung 2017; Liou 2015). Because of the lack of clinical
ity. International surveillance data suggest that minocycline breakpoints specifically for A. baumannii, clinicians often rely
retains activity against around 60% to 80% of CRAB isolates on the FDA breakpoint for Enterobacterales (2 mg/L or less),
using the CLSI breakpoint of 4 mg/L or less (CLSI 2024; Flamm though this may not be entirely appropriate for treating this
2016). However, these surveillance data may be overestimated pathogen (Research, 2023). Consequently, tigecycline’s role in
based on available PK/PD data. the management of A. baumannii infections remains a topic of
A phase 4, open-label study evaluated the PK/PD of a sin- ongoing investigation and debate.
gle 200-mg intravenous dose of minocycline in 55 critically ill Studies indicate that tigecycline monotherapy can lead
ICU patients with MDR A. baumannii infections over a 48-hour to poorer outcomes than combination regimens, especially
period on the basis of an animal lung model (Lodise 2021). when treating infections with higher mortality risks, such as
Results indicated that a standard dosing regimen of 200 mg BSI (Cai 2016; Cheng 2015). Combination therapy, commonly
every 12 hours achieved desired therapeutic targets, with 90% with agents like colistin and sulbactam, has shown improved
or greater probability of reaching the free AUC (fAUC) target of clinical cure rates compared with tigecycline alone, though no
12 in plasma for bacterial stasis in simulated patients with A. standardized combination protocols have been established
baumannii isolates at MIC values of up to 1 mg/L and a 90% or (Kengkla 2018). When used as part of a combination, tigecy-
greater probability of reaching the fAUC target of 18 for a 1-log cline may contribute to the therapeutic efficacy by targeting
bacterial reduction in patients with MIC values of up to 0.5 resistant strains and enhancing bacterial eradication, particu-
mg/L. The authors noted that percent susceptibility of CRAB larly when the MIC is 2 mg/L or less.
isolates for minocycline would decrease substantially to 40% Pharmacokinetic/pharmacodynamic data highlight signifi-
at an MIC of 1 mg/L or less. cant challenges in achieving effective tigecycline concentra-
Retrospective studies of minocycline for the treatment of tions in critically ill patients. Standard doses of tigecycline
A. baumannii have shown high clinical success across various often fail to meet the necessary fAUC targets for bacterial sta-
infection types, including respiratory tract, bloodstream, bone, sis and reduction when MICs exceed 1 mg/L, given that these
and skin and soft tissue infections (Lashinsky 2017). Around targets are crucial for ensuring bactericidal activity (Xie 2017).
78% of cases showed clinical improvement with minocycline In critically ill patients, where the PK profile of tigecycline is
alone or combined with other antimicrobials, with microbi- altered, studies show that standard dosing achieves therapeu-
ological cure rates ranging from 50% to 89%. In five studies tic concentrations reliably only when MICs are as low as 0.5
focused on monotherapy, 23 patients with primarily respira- mg/L. To address this, high-dose regimens, such as an initial
tory (73%), skin and soft tissue (18%), and bone infections (9%) loading dose of 200 mg followed by 100 mg every 12 hours,
received minocycline or doxycycline, usually at an intravenous have been recommended to improve outcomes, especially in
dose of 100 mg twice daily (Goff 2014; Chan 2010; Bishburg combination therapy settings (De Pascale 2014).
2009; Griffith 2008; Wood 2003). These studies reported a Despite these adjustments, tigecycline’s effectiveness is
clinical success rate of 81.8% for monotherapy, though a few still limited by factors such as nonlinear plasma protein binding
cases involved doxycycline. and suboptimal penetration into the epithelial lining fluid of the
respiratory tract, where A. baumannii often causes infections

IDSAP 2025 13 Chapter: Acinetobacter baumannii

(De Pascale 2020; Xie 2017). Studies underscore the variability microbiological cure rates of only 17% compared with 59% in
in target attainment within both the serum and epithelial lining patients treated with best available therapy. The study also
fluid, suggesting that even high-dose tigecycline regimens can noted that patients treated with eravacycline had higher rates
fall short in severe cases of respiratory tract infections. This of concurrent COVID-19 (22% vs 2%) and CRAB BSI (15% vs 3%),
limitation is particularly relevant in patients with pneumonia, factors that likely influenced the clinical outcomes negatively.
where adequate drug penetration into the infection site is cru- A post hoc analysis indicated that both BSI and COVID-19 pos-
cial for therapeutic success. itivity were significantly associated with worse outcomes,
A systematic review and network meta-analysis encom- given that patients with bacteremia had higher mortality rates.
passing 29 studies with a total of 2529 patients found that When excluding patients with bacteremia, the 30-day mortality
tigecycline-based therapies are generally associated with lower rates were similar between eravacycline and other treatments
nephrotoxicity than colistin monotherapy but that they offer (22% vs 16%; P = .506), and when further excluding those with
limited efficacy in achieving microbiological cure, especially in both bacteremia and SARS-CoV-2, there were no significant
BSIs (Abushanab 2022). The analysis concluded that although differences in primary or secondary outcomes. Despite these
tigecycline may be beneficial in less severe infections or as part findings, eravacycline may still hold potential in specific cases
of a combination therapy, it should be avoided as monotherapy of CRAB pneumonia, particularly in patients without bacte-
in severe MDR and XDR A. baumannii infections like bacteremia, remia or coinfections with SARS-CoV-2. Study limitations
where alternatives like colistin in combination with sulbactam include its retrospective nature and small sample size, which
or other agents have shown superior microbiological outcomes. limit the generalizability of results. Moreover, the inability to
confirm bacterial pneumonia versus colonization adds a level
Eravacycline of complexity to interpreting outcomes. Still, the study under-
Eravacycline, a synthetic fluorocycline, has shown lower MICs scores the need for further research to delineate the role of
than minocycline or tigecycline in surveillance studies, indi- eravacycline, particularly in severe infections, where its per-
cating potentially enhanced-potency CRAB (Morrissey 2020; formance compared with other agents remains questionable.
Livermore 2016). However, like tigecycline, eravacycline lacks
specific clinical breakpoints for A. baumannii, leading clinicians Omadacycline
to rely on breakpoints for Enterobacterales, which can intro- Omadacycline, a novel tetracycline derivative available in both
duce uncertainty when interpreting susceptibility test results. intravenous and oral formulations, has shown mixed efficacy
According to PK/PD studies in a murine model, eravacycline’s against CRAB in preclinical studies (Noel 2021). A recent in
mean fAUC targets for bacteriostasis and a 1-log reduction vitro study evaluated omadacycline’s activity alone and in com-
against Escherichia coli were higher than similar targets for bination against 41 carbapenem-nonsusceptible A. baumannii
minocycline and tigecycline, suggesting that eravacycline isolates (Abbey 2022). This study found an MIC50/MIC90 of 4/8
requires careful dose optimization to achieve effective concen- mg/L, effectively inhibiting 68.3% of isolates at concentrations
trations, particularly in CRAB where PK/PD data remain limited. of 4 mg/L or less, with 74.2% of minocycline-resistant isolates
A multicenter, real-world study involving 46 patients with also inhibited at this level. Although omadacycline alone did not
A. baumannii infections, of which 69.5% were CRAB, provides show bactericidal activity in time-kill assays, combination thera-
some insight into the potential clinical role of eravacycline pies showed promise. The combination with sulbactam achieved
(Alosaimy 2022). In this study, most patients (84.4%) received synergy in 80% of isolates and was bactericidal in 8 of 10 strains,
eravacycline as part of a combination therapy, resulting in a including both minocycline-susceptible and nonsusceptible iso-
30-day mortality rate of 23.9% overall and 21.9% among the lates. When combined with polymyxin B, omadacycline showed
CRAB subgroup, indicating that eravacycline could be a viable synergy in 30% of cases and eradicated 60% of the isolates. A
option in certain scenarios. In addition, eravacycline was gen- triple-drug regimen of omadacycline, sulbactam, and polymyxin
erally well tolerated, with only 1 patient reporting mild GI side B further accelerated bacterial clearance, reducing the time to
effects, highlighting its potential safety profile compared with a 99.9% bacterial load reduction by over 6 hours compared with
other antibiotics commonly used for CRAB. the omadacycline-sulbactam combination alone.
Another study conducted a retrospective comparison of Clinical data on omadacycline remain limited, with a small,
eravacycline-based therapy for CRAB pneumonia versus alter- uncontrolled case series exploring its use in MDR and XDR
native therapies across six hospitals in Nevada (Scott 2022). gram-negative bacterial infections across multiple US centers
Of the 93 patients included, the in-hospital 30-day mortality (Morrisette 2022). This pilot study included 9 cases, primar-
rate for those receiving eravacycline was 33% compared with ily involving CRAB infections, and reported a 66.7% overall
15% for patients receiving other regimens. Patients treated clinical success rate, with an 80% success rate in bone/joint
with eravacycline also had longer durations of mechanical infections and those caused by CRAB. These findings are
ventilation, with a median of 10.5 days compared with 6.5 encouraging, given the limited treatment options, but highlight
days for patients receiving alternative therapies. The clinical the need for larger studies to fully assess omadacycline’s effi-
cure rate was lower for patients treated with eravacycline, with cacy for CRAB infections.

IDSAP 2025 14 Chapter: Acinetobacter baumannii

 Patient Care Scenario
M.R., a 72-year-old man, is admitted to the medical ICU Antimicrobial MIC (mg/L) Interpretation
after developing a fever, tachypnea, and hypoxia. His
Meropenem ≥8 R
medical history includes chronic obstructive pulmonary
disease (COPD), and he was hospitalized 3 weeks ago for Minocycline 2 S
a COPD exacerbation, during which he required mechan-
Tobramycin 4 I
ical ventilation. M.R.’s current symptoms began a few
days ago, with increasing shortness of breath, productive Trimethoprim- ≥ 80 R
cough, and fever. On examination, he is febrile (tempera- sulfamethoxazole
ture 38.7°C), tachycardic (pulse rate 120 beats/min),
hypotensive (blood pressure 95/55 mm Hg), and hypoxic
(Spo2 88% on a non-rebreather mask). Chest radiogra- Despite initial empiric therapy with meropenem, the
phy reveals bilateral infiltrates, and his WBC is elevated at patient’s condition has worsened, requiring increas-
15.2 × 103/μL. Cultures obtained from his blood and endo- ing doses of vasopressors and higher oxygen support.
tracheal aspirate grow A. baumannii with the following Given his worsening clinical status and the antimicrobial
susceptibility profile: susceptibilities, which one of the following is best to rec-
ommend as combination therapy for M.R.?
Antimicrobial MIC (mg/L) Interpretation
A. Colistin
Ampicillin-sulbactam 32-16 I B. Tobramycin
Ciprofloxacin ≥4 R C. Minocycline
D. Sulbactam-durlobactam
Colistin 0.5 I

ANSWER
Management of infections caused by CRAB can be ampicillin-sulbactam (total daily dose of 9 g of the sulbac-
challenging because of the limited number of effec- tam component) in combination with at least one other
tive therapies. Once A. baumannii exhibits carbapenem agent, such as polymyxin B, minocycline, tigecycline, or
resistance, it typically acquires resistance to most other cefiderocol, may be considered.
antibiotics active against wild-type strains, significantly In M.R.’s case, despite initial empiric therapy with
narrowing therapeutic choices. Resistance in CRAB is meropenem, his worsening condition necessitates recon-
often mediated by the production of OXA carbapene- sidering the treatment strategy. Colistin could be added
mases (eg, OXA-23, OXA-24/40), which confer resistance for combination therapy; however, its nephrotoxicity and
to β-lactams, including carbapenems and sulbactam. the need for alternative, more effective combinations
In addition, CRAB isolates may produce other serine β- should be weighed carefully. Tobramycin and minocycline
lactamases, such as ADCs, which further limit the efficacy could also be added, but their intermediate susceptibility
of common β-lactam agents. Aminoglycoside-modifying and limited data supporting their efficacy as monotherapy
enzymes or 16S rRNA methyltransferases generally pre- in CRAB infections limit their usefulness. Minocycline,
clude aminoglycosides as viable treatment options. though potentially effective in combination therapy,
Mutations in chromosomally encoded quinolone resis- should not be used alone because of its PK profile and
tance–determining regions usually mediate resistance to potential for suboptimal plasma concentrations in severe
fluoroquinolones. infections.
Given these complexities and the absence of a clear Given these factors, the most suitable option for this
standard of care, the suggested approach is to use a patient would be to add sulbactam-durlobactam for com-
combination therapy regimen, ideally including a sul- bination therapy (Answer D is correct). This regimen
bactam-containing agent. Sulbactam-durlobactam in aligns with the suggested approach for treating CRAB
combination with a carbapenem (imipenem-cilastatin or infections, targeting the pathogen effectively and poten-
meropenem) is the preferred regimen for treating CRAB tially improving clinical outcomes. Close monitoring of
infections. Sulbactam-durlobactam has shown signifi- the patient’s response to therapy and adjustment on the
cant in vitro and clinical efficacy against CRAB because basis of clinical improvement and susceptibility data are
it combines sulbactam’s ability to inhibit PBPs with durlo- essential for optimizing treatment outcomes (Tamma
bactam’s potent inhibition of several β-lactamases. 2024; Shields 2023).
If sulbactam-durlobactam is unavailable, high-dose

Despite its limited standalone efficacy, omadacycline’s regimens enhance antibacterial activity and provide a viable
role in combination therapies, especially with sulbactam alternative in CRAB treatment, though additional studies are
and/or polymyxin B, underscores its potential in treating CRAB necessary to validate these combinations clinically.
infections. These findings suggest that omadacycline-based

IDSAP 2025 15 Chapter: Acinetobacter baumannii

Aminoglycosides common sources of infection included respiratory tract infec-
Many MDR ABC isolates are resistant to aminoglycosides; tions, followed by BSIs. Baseline characteristics were similar,
hence, clinical experience with these agents is limited. When with differences in ICU mortality (21.9% vs 34.4%) and micro-
susceptible, the usefulness of aminoglycosides is hindered bial eradication (55% vs 50%). In addition, no differences in
because of low volume of distribution and resistance emer- nephrotoxicity occurred, showing that either agent may be
gence. The most-used aminoglycoside is tobramycin (Akers useful, especially as a concomitant antimicrobial. Plazomicin,
2010). Aminoglycosides are primarily used in combination the newest aminoglycoside, has no advantage over other ami-
for MDR organisms (either intravenously or inhaled for respi- noglycosides for the treatment of ABC infections (Clark 2020).
ratory tract infections), including A. baumannii (Arnold 2012). There are currently no established susceptibility breakpoints
Intravenous tobramycin and colistin for A. baumannii infec- for plazomicin, and therapeutic drug monitoring in the clinical
tions were compared in 64 patients (Gounden 2009). The most setting is challenging.

Table 5. Antibiotic Resistance Mechanisms, Efficacy, and Dosing Considerations for A. baumannii Infections

Resistance Dosing
Drug mechanisms Summary of available data Standout items considerations

β-Lactams

Ampicillin- blaOXA-23 gene, Effective for MIC ≤ 4 μg/mL. High-dose regimens 1 g q6h standard; 3 g
sulbactam carbapenem High-dose infusion (3 g q8h) critical; combination q8h by 4-h infusion for
resistance, PBP needed for MIC = 8 μg/mL. therapy essential for resistant isolates
modifications Monotherapy fails for MIC ≥ resistant strains
16 μg/mL

Sulbactam- Class A, C (ADC), and D FDA approved for MDR Unique inhibition 1 g sulbactam + 1 g
durlobactam β-lactamases; excludes Acinetobacter. Noninferior to of ADC and OXA durlobactam q6h (3-h
MBLs colistin in the ATTACK trial; carbapenemases; infusion)
safer nephrotoxicity profile breakthrough approval
for HABP/VABP

Cefiderocol OXA carbapenemases, High in vitro susceptibility Iron depletion critical for 2 g q8h over 3-h
efflux pumps, porin but inconsistent clinical susceptibility testing. infusion; testing
loss; heteroresistance outcomes. Requires Combination therapy requires iron-depleted
and iron dependency iron depletion in AST for avoids resistance media
accurate MICs emergence

Meropenem Carbapenemase Extended infusion improves Combination therapies 3 g q8h by 3-h infusion;
enzymes (eg, OXA- outcomes for isolates with are vital; extended combination therapy
type), membrane elevated MICs. Combination infusion critical for improves efficacy
permeability changes therapy (polymyxins/sulbac- elevated MICs
tam) improves efficacy

Imipenem- Retains activity against Effective where meropenem Retains some activity Dose depends on
cilastatin meropenem-resistant fails; synergistic with where meropenem susceptibility;
isolates; structural sulbactam and colistin. Role fails. Synergy with prolonged infusion
differences inhibit as adjunctive therapy noted sulbactam enhances for synergy with
some carbapenemases outcomes sulbactam

Cefepime AmpC-type Limited efficacy as Combination with 2 g q8h (3-h infusion);

cephalosporinases monotherapy because of sulbactam-durlobactam avoid monotherapy
(eg, ADC-56), high resistance rates (> 50%). shows promise but for MDR infections
carbapenemases (eg, Synergy observed with requires further clinical
OXA-23); efflux pumps sulbactam-durlobactam in validation
MDR isolates

Ceftriaxone AmpC-type High resistance rates across Significant resistance 1-2 g q12-24h; avoid
cephalosporinases, A. baumannii isolates. Rarely limits usefulness; monotherapy for A.
carbapenemases (OXA used because of limited monotherapy baumannii infections
family), efflux pumps activity. May be part of is ineffective.
combinations Combination regimens
unproven (continued)

IDSAP 2025 16 Chapter: Acinetobacter baumannii

 Table 5. Antibiotic Resistance Mechanisms, Efficacy, and Dosing Considerations for A. baumannii Infections (continued)

Resistance Dosing
Drug mechanisms Summary of available data Standout items considerations

Piperacillin- β-Lactamases (eg, OXA- Resistance common in MDR Effective only in 4.5 g q6-8h (prolonged
tazobactam type), AmpC variants, and XDR A. baumannii. combination therapy; infusion); combination
porin loss Limited in vitro synergy with monotherapy therapy critical for
sulbactam or colistin. Poor associated with poor MDR infections
monotherapy outcomes outcomes

Polymyxins

Polymyxins Resistance emerges Polymyxin B achieves steady Polymyxin B preferred Polymyxin B: 1.5-3
(colistin, at MIC > 2 μg/mL; state faster than colistin; because of PK mg/kg/d; no renal
polymyxin B) nephrotoxicity and triple regimens (sulbactam/ advantages; triple adjustment required
heteroresistance limit carbapenem) show promise therapy reduces
use mortality in severe
CRAB infections

Tetracyclines

Minocycline Efflux pumps (eg, TetB); 78% success in severe Minocycline effective Minocycline: 200
retains activity in lower infections; effective in against TetB efflux; mg q12h IV; oral/IV
MIC ranges; tissue combination therapies. clinical success ~78% interchangeable
penetration concerns Achieves high tissue in combination therapy
concentrations

Tigecycline RND-type efflux pumps; Combination therapy Combination therapy High dose: 200 mg
suboptimal systemic improves outcomes for (eg, sulbactam, loading, 100 mg
concentrations; PK/PD pneumonia. High-dose colistin) critical; avoids q12h; optimized for
challenges for MIC > 1 regimens needed; avoid nephrotoxicity combination therapy
mg/L monotherapy for BSI

Eravacycline Low MICs; limited Real-world studies show Lower MICs improve IV: 1 mg/kg
resistance data but 24% mortality; effective in activity; effective as q12h; careful PK
promising in vitro combinations. Lower MICs part of combination optimization required
potency; lacks clinical than tigecycline therapy for CRAB
breakpoints pneumonia

Omadacycline Moderate activity; Limited data; synergistic Synergy with sulbactam 100 mg q12h IV/oral;
retains synergy combinations with and polymyxins effective in synergistic
in combinations; sulbactam/polymyxins accelerates bacterial combinations
resistance mediated by enhance efficacy clearance in resistant
efflux pumps strains

Aminoglycosides

Aminoglycosides Limited because of Tobramycin shows Tobramycin used with Tobramycin IV;
resistance emergence; results similar to colistin; colistin; plazomicin dosing guided
tobramycin most used; plazomicin lacks established offers no advantage. by susceptibility;
plazomicin offers no breakpoints. Limited Limited real-world data therapeutic drug
clear advantage efficacy as monotherapy monitoring critical

Abbreviations: ADC, A. baumannii–derived cephalosporinase; AST, antimicrobial susceptibility testing; BSI, bloodstream infection;
CRAB, carbapenem-resistant A. baumannii; HABP, hospital-acquired bacterial pneumonia; IV, intravenous(ly); MBL, metallo-β-­
lactamase; MDR, multidrug-resistant; OXA, oxacillinase; PBP, penicillin-binding protein; PK/PD, pharmacokinetic/pharmacodynamic;
q, every; RND, resistance-nodulation-cell division; VABP, ventilator-associated bacterial pneumonia; XDR, extensively drug-resistant.

IDSAP 2025 17 Chapter: Acinetobacter baumannii

 therapies often playing a crucial role in improving outcomes.
Practice Points
The ongoing evolution of resistance mechanisms and critical
• Understanding the Epidemiology and Resistance need for accurate susceptibility testing highlight the impor-
Patterns: Acinetobacter baumannii is a significant noso-
tance of combination therapies and the continuous search
comial pathogen, particularly in ICU settings. A. baumannii
has high rates of drug resistance globally, with carbapen-
for new therapeutic strategies. Addressing the challenges
em-resistant A. baumannii (CRAB) posing a considerable posed by A. baumannii requires a comprehensive approach
threat because of limited treatment options. Understanding that includes robust infection control measures, antimicro-
the local epidemiology and resistance patterns is crucial bial stewardship, and ongoing research to stay ahead of this
for effective management. ever-adapting pathogen.
• Recognizing Resistance Mechanisms: A. bauman-
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Self-Assessment Questions
1. A 65-year-old man with a history of chronic obstructive of the following is the best education point to share with
pulmonary disease (COPD) is admitted to the ICU with this patient’s team regarding the use of minocycline for
severe pneumonia. He was recently discharged after treat- treating CRAB infections, particularly with respect to
ment for a UTI. On admission, the patient is intubated and its pharmacokinetic (PK) properties and susceptibility
mechanically ventilated. His vital signs are of concern, breakpoints?
with temperature 38.5°C, blood pressure 90/60 mm Hg,
A. Minocycline is consistently effective against all
pulse rate 110 beats/min, respiratory rate 24 breaths/min,
strains of A. baumannii because of its low MIC
and Sao2 92% on 60% fraction of inspired oxygen. Labora-
breakpoints.
tory tests show WBC 18 × 103/μL, SCr 1.8 mg/dL (baseline
B. A single 200-mg dose of minocycline is sufficient
1.0 mg/dL), BUN 40 mg/dL, ALT 45 U/L, and AST 48 U/L.
for achieving optimal pharmacokinetic/
Blood and sputum cultures return positive for carbapen-
pharmacodynamic (PK/PD) profiles in all patients.
em-resistant Acinetobacter baumannii (CRAB). Given his
C. Minocycline may have compromised efficacy against
clinical status and the identification of CRAB, which one
CRAB isolates with MICs between 2 and 4 μg/mL
of the following is best to recommend for this patient?
because of suboptimal antibiotic concentrations at
A. Monotherapy with colistin alone infection sites.
B. Combination of sulbactam-durlobactam with D. International surveillance data confirm that
meropenem minocycline is ineffective against most CRAB
C. Cefiderocol monotherapy isolates.
D. Tigecycline combined with an aminoglycoside
4. Your hospital laboratory has recently acquired new testing
2. A 72-year-old woman with a history of chronic kidney capabilities for evaluating cefiderocol activity against A.
disease and diabetes is admitted to the ICU with septic baumannii, specifically focusing on resistant strains. The
shock secondary to health care–associated pneumo- laboratory is assessing different methods to determine
nia. She was previously treated with multiple courses of which provides the most reliable results. The laboratory
antibiotics for recurrent UTIs. Blood and respiratory cul- technicians compared several methods, including disk
tures identify Acinetobacter baumannii with resistance diffusion (DD) and E-test on standard Mueller Hinton
to multiple classes of antibiotics, including carbapen- (MH) agar, as well as DD and broth microdilution (BMD)
ems. The clinical microbiology laboratory confirms that using iron-depleted MH agar (ID-MH). Preliminary data
the isolate harbors a specific gene responsible for high- show that one method has a 95% categorical agreement
level resistance to carbapenems. The patient’s condition with the reference BMD method when using iron-de-
is worsening despite initial broad-spectrum antimicrobial pleted conditions. As the clinical pharmacist reviewing
therapy. Which one of the following best assesses the pri- the laboratory’s findings, which one of the following best
mary genetic determinant responsible for the high-level explains the method that showed the highest categorical
resistance to carbapenems in A. baumannii in this patient, agreement with the reference BMD under iron-depleted
and what is its mechanism of action? conditions?
A. blaNDM-1 gene encoding a metallo-β-lactamase A. DD on standard MH agar is sufficient for reliable
(MBL) that hydrolyzes carbapenems cefiderocol testing against A. baumannii.
B. blaOXA-23 gene producing a class D β-lactamase B. E-test on standard MH agar may not be the most
that confers resistance to carbapenems reliable method for cefiderocol testing.
C. blaOXA-24/40 gene encoding a class D β-lactamase C. DD on ID-MH is the most reliable method for
found in carbapenem-resistant A. baumannii assessing cefiderocol activity against A. baumannii
D. ADC β-lactamase gene encoding a class C under iron-depleted conditions.
cephalosporinase associated with β-lactam D. BMD using commercial kits provides the most
resistance accurate results regardless of the iron content in the
medium.
3. A 58-year-old man with a history of COPD has developed a
health care–associated pneumonia caused by CRAB. His 5. A 78-year-old woman with end-stage renal disease receiv-
care team is considering the use of minocycline on the ing hemodialysis and COPD presents with sepsis after
basis of susceptibility testing. You are asked to provide treatment for a multidrug-resistant Acinetobacter bau-
education to the health care team regarding the implica- mannii UTI. She had been receiving cefiderocol but has
tions of using minocycline for this infection. Which one experienced no clinical improvement. The microbiology

IDSAP 2025 26 Chapter: Acinetobacter baumannii

 lab reports MIC testing using both cation-adjusted Muel- 8. A 68-year-old man comes to the ED with fever, chills, and
ler Hinton broth (CAMHB) and iron-depleted CAMHB difficulty breathing. He has thick, foul-smelling secretions
(ID-CAMHB). Given her ongoing deterioration and the from his tracheostomy site. The patient was discharged
known implications of iron content on cefiderocol sus- 4 weeks ago after a prolonged surgical ICU stay due to
ceptibility testing, which one of the following is best to trauma. During that stay, a tracheal aspirate cultured
recommend for this patient? Acinetobacter baumannii susceptible to minocycline,
ampicillin-sulbactam, colistin, meropenem, and tobramy-
A. Continue cefiderocol and add polymyxin B based on
cin. He had no signs of infection at that time. Today his
CAMHB MICs
WBC is 16.8 × 10³/μL, pulse 110 beats/minute, BP 101/60
B. Increase cefiderocol dosage guided by MICs from
mm Hg, RR 24 breaths/minute, and chest radiography
ID-CAMHB
shows bilateral infiltrates. Cultures from the tracheos-
C. Discontinue cefiderocol and initiate sulbactam-
tomy and blood finalize as A. baumannii with the following
durlobactam due to treatment failure
MICs:
D. Switch to colistin therapy guided by local resistance
data Antimicrobial MIC (mg/L) Interpretation

6. Which one of the following patients with multidrug-re- Ampicillin-sulbactam 16/8 I

sistant Acinetobacter baumannii is most likely to benefit Ciprofloxacin ≥4 R
from sulbactam-durlobactam therapy?
Colistin 1 -
A. 64-year-old man with a bloodstream infection; the
Meropenem 4 I
isolate carries the TEM-1 gene (class A β-lactamase)
B. 72-year-old woman with ventilator-associated Minocycline 4 S
pneumonia; the isolate harbors the NDM-1 gene Tobramycin 2 S
(class B metallo-β-lactamase)
Trimethoprim- ≥ 80 R
C. 58-year-old man with a complicated urinary tract
sulfamethoxazole
infection; the isolate carries a PER-1 gene (class A
extended-spectrum β-lactamase) Given his worsening clinical status and the culture results,
D. 69-year-old woman with a wound infection; which one of the following is best to recommend for this
the isolate carries the IMP gene (class B patient?
metallo-β-lactamase) A. Add colistin for combination therapy.
7. A 69-year-old man with a history of multiple hospital- B. Add sulbactam-durlobactam for combination therapy.
izations for recurrent pneumonia is admitted to the ICU C. Initiate minocycline monotherapy.
with sepsis. Cultures show A. baumannii resistant to D. Add minocycline for combination therapy.
multiple classes of antibiotics, including carbapenems,
aminoglycosides, and fluoroquinolones. The microbi- The next three questions pertain to the following
ology report identifies the presence of the blaOXA-23 case.
and blaNDM-1 genes. Which one of the following resis- L.T., a 70-year-old man with a medical history that includes
tance mechanisms is most likely responsible for the diabetes and COPD, is admitted to the ICU with severe pneu-
high level of MDR observed in this patient’s A. bauman- monia. He was previously hospitalized for a UTI and was
nii isolate? treated with broad-spectrum antibiotics. Despite initial treat-
A. Production of oxacillinase (OXA)-type ment, L.T.’s condition worsens, and blood and sputum cultures
carbapenemases and NDM-1 MBLs, which degrade return positive for CRAB. The patient’s current antimicrobial
β-lactam antibiotics and contribute to resistance therapy includes meropenem and tobramycin, but there has
against carbapenems. been no clinical improvement.
B. Overexpression of the Tet(A) efflux pump, which 9. Which one of the following is best to recommend to
actively expels antibiotics from the bacterial cell, optimize L.T.’s treatment regimen?
reducing intracellular drug concentration.
A. Discontinue current therapy and initiate monotherapy
C. Alteration of outer membrane proteins (OMPs),
with colistin.
reducing permeability and preventing antibiotics
B. Add high-dose ampicillin-sulbactam to the existing
from entering the bacterial cell.
regimen.
D. Formation of biofilms on biotic and abiotic surfaces,
C. Replace meropenem with cefiderocol and continue
which protects the bacteria from antimicrobial
tobramycin.
agents and contributes to persistent infections.

IDSAP 2025 27 Chapter: Acinetobacter baumannii

 D. Discontinue tobramycin and initiate sulbactam- 13. W.M. is initiated on a combination of cefiderocol and
durlobactam. high-dose tigecycline. After a few days, she shows some
clinical improvement; however, repeat cultures still show
10. L.T.’s microbiology report identifies the presence of bla-
the presence of CRAB. Given the persistent infection, the
OXA-23 and A. baumannii–derived cephalosporinase
health care team is considering adding a third agent to
(ADC) genes in the A. baumannii isolate, which are known
the regimen. Which one of the following is best to recom-
to confer resistance to carbapenems and cephalosporins,
mend adding to W.M.’s regimen?
respectively. The patient’s renal function also begins to
decline, and his CrCl decreases to 30 mL/min. Given the A. Polymyxin B
resistance mechanisms (blaOXA-23 and ADC genes) and B. Eravacycline
his declining renal function (CrCl 30 mL/min), which one C. Rifampin
of the following is best to recommend for L.T.’s treatment D. Fosfomycin
adjustment?
A. Reduce the dose of sulbactam-durlobactam and The next two questions pertain to the following case.

continue the current regimen. S.V., a 66-year-old woman with a medical history that includes
B. Change to cefiderocol and polymyxin B to cover the hypertension and diabetes, is admitted to the ICU with septic
resistance profile. shock secondary to a CRAB BSI. Blood cultures show that the
C. Continue sulbactam-durlobactam and add CRAB isolate harbors the blaOXA-23 gene. Initial susceptibility
minocycline for enhanced coverage. testing shows the following MIC data:
D. Discontinue all β-lactams and initiate high-dose
Meropenem ≥ 16 μg/mL (resistant)
tigecycline.
Cefiderocol 2 μg/mL (susceptible)
11. After 1 week on the adjusted regimen, L.T. shows par-
tial clinical improvement, but the latest blood culture still Ampicillin-sulbactam 16-8 μg/mL (intermediate)
shows persistent CRAB bacteremia. The team considers Polymyxin B 1 μg/mL (susceptible)
further modifications to the treatment regimen. Which
one of the following is best to recommend to manage 14. Which one of the following is best to recommend for S.V.?
L.T.’s infection?
A. Monotherapy with cefiderocol
A. Add high-dose tigecycline to the regimen for B. Combination therapy with cefiderocol and polymyxin B
enhanced bactericidal activity. C. High-dose ampicillin-sulbactam monotherapy
B. Change to high-dose polymyxin B and discontinue D. Combination therapy with tigecycline and ampicillin-
other agents. ­sulbactam
C. Continue current therapy and add rifampin for
15. After 48 hours of the chosen initial therapy, S.V. shows
synergistic effect.
minimal clinical improvement, and repeat blood cul-
D. Add cefiderocol to the current regimen for enhanced
tures still show the presence of CRAB. The health care
activity against CRAB.
team decides to perform additional susceptibility testing,
which provides the following updated MIC data:
The next two questions pertain to the following case.

W.M., a 68-year-old woman with a medical history of hyperten- Cefiderocol 4 μg/mL (intermediate)
sion and end-stage renal disease while receiving hemodialysis, Polymyxin B 2 μg/mL (intermediate)
is admitted to the ICU with sepsis. She develops pneumonia
Sulbactam-durlobactam 2/4 μg/mL (susceptible)
secondary to mechanical ventilation, and blood cultures reveal
CRAB harboring blaNDM-1 and blaOXA-23 genes. Initial treat-
Considering the new MIC data and her lack of clinical improve-
ment with cefiderocol is started, but W.M.’s condition remains
ment, which one of the following is best to recommend for
unchanged after 72 hours.
S.V.?
12. Which one of the following is best to recommend to opti- A. Change to high-dose sulbactam-durlobactam
mize W.M.’s antimicrobial regimen? monotherapy.
A. Change to high-dose colistin monotherapy. B. Continue the current therapy and monitor closely.
B. Add high-dose tigecycline to the cefiderocol regimen. C. Add sulbactam-durlobactam to the current regimen
C. Continue cefiderocol and add high-dose for combination therapy.
ampicillin-sulbactam. D. Discontinue all current antibiotics and initiate high-
D. Change to sulbactam-durlobactam and discontinue dose tigecycline.
cefiderocol.

IDSAP 2025 28 Chapter: Acinetobacter baumannii