Pharmacotherapy of infectious disease:

5. Skin and Skin Structure Infections

Mengist Awoke (MSc, Assistant Professor)

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Lesson objectives
1. Discuss skin structure and function responsible for preventing infection.

2. Describe the epidemiology, etiology, pathogenesis, and clinical

manifestations associated with acute bacterial skin and skin structure
infections (ABSSSIs).

3. Identify goals of therapy associated with clinical response in patients

with ABSSSI.

4. Recommend effective Non-pharmacological, and empiric and definitive

antimicrobial regimens

5. Monitor chosen antimicrobial therapy for safety and efficacy.

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Introduction

 The largest organ of the body  Barrier against toxins,

 It has three layers pathogens and dehydration

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Introduction….
Intact skin generally is resistant to infection.
 Mechanical barrier,
 Its relative dryness,
 Slightly acidic pH,
 Colonizing bacteria,
 Frequent desquamation, and
 Production of various antimicrobial defense chemicals,
including sweat(which contains IgG and IgA), prevent
invasion by various microorganisms.
 SSTIs involving any or all layers of the skin (epidermis, dermis,
subcutaneous fat), fascia, and muscle.
 most common infections seen in community and hospital settings.

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Introduction….
Normal flora of the skin
 Staphylococcus epidermidis
 Staphylococcus aureus (can be
pathogen)
 Streptococcus sp.
 Micrococcus species
 Peptostreptococcus species
 Neisseriae species
 Propionibacterium species
 Diphtheroids
 Candida species (can be
pathogenic)
 Acinetobacter species (can be
pathogenic)
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Risk factors of SSI

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 Pathophysiology of SSTIs
(a) high concentrations of bacteria (more
Any risk factors,
than 105 microorganisms),
 Skin puncture, abrasion,
 underlying diseases (eg, (b) excessive moisture of the skin,
diabetes), PAD, SAM, (c) inadequate blood supply,
 Recent antibiotic Rx, and (d) availability of bacterial nutrients, and
young/old age (e) damage to the corneal layer allowing
for bacterial penetration

Impairs skin protection

against microbes

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Common SSTIs

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Common SSTIs…
Primary Infections
 Caused by a single pathogen, usually affect normal skin.
 Impetigo, folliculitis, and boils are common types.
 The most common primary skin pathogens are S aureus, B-
hemolytic streptococci, and coryneform bacteria.
 Organisms usually enter through a break in the skin.
Secondary Infections
 Secondary infections occur in skin that is already diseased.
 Because of the underlying disease, the clinical picture and
course of these infections vary.

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Common SSTIs…

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1. Impetigo
It’s a common skin infection that can occur in any age-group
but most frequently affects children between 2 and 5 years.
Starts as a red, itchy sore.
As it heals, a crusty, yellow or “honey-colored” scab forms over the sore

Pathogens
β-Hemolytic streptococci (Streptococcus pyogenes or Group A Streptococcus
[GAS]) and S. aureus
Transmitted easily within the body and to other persons

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Treatment
Goals :
Preventing infection spread within the patient and
to others,
Symptom relief (eg, itching)
Infection resolution
Preventing recurrence
Improving cosmetic appearance
Prevention of the rare but serious complications

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 Non-pharmacological Rx
Increased hygiene along with soaking and cleansing lesions
with soap and water.
Use skin emollients to dry skin areas….reduce spread and
urge to scratch itchy lesions.
Natural remedies ? tea tree oil and Manuka honey may
provide some anecdotal benefit

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Pharmacological Rx
Antibiotic therapy is recommended to prevent spread of
infection and complications.

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Pharmacological Rx…

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Pharmacological Rx…
The following steps outline the proper administration topical
preparations:
1. Applicants wash hands thoroughly with warm water and
antibacterial soap.
2. Using a clean washcloth soaked in warm soapy water,
gently rub the crusty lesions to loosen the debris, thus
allowing for adequate antibiotic penetration.
 In order to prevent further infection…take care to avoid scrubbing the
lesions.
3. Apply a thin layer of the prescribed ointment to each sore,
including the surrounding area.
4. When finished, wash hands well and, if necessary, apply a
piece of gauze to the infected area.

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Complications and preventions
 A rare complication of impetigo is poststreptococcal
glomerulonephritis (PSGN)…2 weeks after infection
Prevention ?
Proper hygiene
Washing hands vigorously with antibacterial soap and water
and taking regular baths
Instructed to use clean washcloths and towels every time
Avoid sharing any personal care products such as clothing
and towels
Not attend school or playgroups until 48 hours after
starting treatment or until the sores have blistered and
dried up.
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2. Folliculitis, Furuncles, and Carbuncles

 Folliculitis is inflammation of the hair follicle and is caused by

physical injury, chemical irritation, or infection.
 Infection occurring at the base of the eyelid is referred to as
a stye.

 While folliculitis is a superficial infection with pus present only

in the epidermis,
 furuncles and carbuncles occur when a follicular infection extends from
around the hair shaft to involve deeper areas (subcutaneous tissue) of
the skin
 The lesions are called carbuncles when adjacent furuncles coalesce to
form a single inflamed area

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Folliculitis, Furuncles, and Carbuncles

S. aureus and CA-MRSA

Klebsiella, Enterobacter, and Proteus species.. facial skin, nasal mucous membranes,
and neighbouring areas

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Folliculitis, Furuncles, and Carbuncles…Clinical
Presentation

Folliculitis
 Clustering, pruritic papules localized to hair follicles.
 Generally develop in areas subject to friction and perspiration.
 Papules are generally 5 mm or less in diameter and erythematous.
 Papules evolve into pustules that generally spontaneously rupture in
several days.
 Systemic signs (fever, malaise) are uncommon.

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Folliculitis, Furuncles, and Carbuncles…Clinical
Presentation

Furuncles
 Inflammatory, draining nodule involving a hair follicle.
 Generally develop in areas subject to friction and perspiration.
 Lesions are discrete, whether occurring as singular or multiple nodules.
 Lesion starts as a firm, tender, red nodule that becomes painful and
fluctuant.
 Lesions often drain spontaneously.
 Lesions caused by CA-MRSA often have necrotic centers
 Systemic signs are uncommon.

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Folliculitis, Furuncles, and Carbuncles…Clinical
Presentation

Carbuncles
Formed when adjacent furuncles coalesce to form a single inflamed
area.
Form broad, swollen, erythematous, deep, and painful follicular
masses.
Commonly develop on the back of the neck
Commonly associated with systemic signs (fever, chills, malaise).
Bacteremia with secondary spread to other tissues is common.

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Rx of Folliculitis, Furuncles, and Carbuncles
Desired Outcomes
 Relieving discomfort,
 Preventing further spread of the infection, and
 Preventing recurrence
 Non-pharmacological Rx
 Local application of moist heat (38°C to 40°C applied for 15 to 20
minutes),
 Daily chlorhexidine washes and daily washing of personal items such
as towels, bedding, and clothes
 Drainage of the lesion,
 Phototherapy,

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Pharmacological Rx
Topical antibiotics….number of lesions is limited
 Fusidic acid 2% cream twice daily
 Clindamycin 2% gel twice daily
 Mupirocin 2% ointment applied two to three times daily
 Applied for 7 days.
• S/E dermatitis, dryness, or pruritus over the applied area
 Topical antiseptic agents alone or in combination with
antibiotics…. especially in recurrent furunculosis
 Benzoyl peroxide 2% to 10% twice daily gel, cream, soap, or Solution
 Hypochlorite 3% to 5% solution
 Systemic antibiotics…systemic symptoms such as fever,
lymphadenitis, or cellulitis appear

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Pharmacological Rx..
 First‐line oral antibiotics
 Dicloxacillin (250 mg four times daily) and
 Cephalosporins (such as cefadroxil 500 mg twice daily)
 Antibiotic‐resistant [Link]
 Clindamycin, tetracyclines, trimethoprim‐sulphamethoxazole, linezolid,
or glycopeptide (vancomycin) may be used
 For gram‐negative folliculitis (antipseudomonal activity)
• Oral or parenteral ciprofloxacin 400 to 500 mg twice daily
 Duration of Rx varied across the etiologies
• 5 to 10 days…gram +ve bacteria
• 7 to 14 days…. gram –ve bacteria and MRSA

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 Pharmacological Rx..
Drug Regimen

Cefadroxil Adult: 1 g orally daily in a single dose or in divided doses twice a day
Pediatric: 30 mg/kg orally once daily or in equally divided doses every 12 hours
Ciprofloxacin Adult: 500 mg orally every 12 hours for 7 to 14 days; 400 mg IV every 12 hours for 7
to 14 days
Clindamycin Adult: 150 to 300 mg orally every 6 hours, 600 to 1200 mg/d IV or IM divided every 6
to 12 hours
Pediatric: 8 to 16 mg/kg/d ORALLY divided every 6 to 8 hours; 15 to 20 mg/kg/d IV or
IM divided every 6 to 8 hours
Tetracyclines Adult: 500 mg orally twice daily or 250 mg orally 4 times per day
Pediatric: (older than 8 years) 25 to 50 mg/kg orally in 4 equally divided doses
Trimethoprim‐sulphamethoxazo Adult: sulfamethoxazole 800 mg/trimethoprim 160 mg to sulfamethoxazole 1600
le mg/trimethoprim 320 mg orally twice daily
Pediatric: (older than 1 month) based on trimethoprim component: 8 to 12 mg/kg/d
orally in 2 divided doses
Linezolid Adult: 400 to 600 mg ORALLY every 12 hours for 10 to 14 days
Pediatric: (birth through 11 years) 10 mg/kg IV or ORALLY every 12 hours
vancomycin) Adult: 30 mg/kg/d IV in 2 divided doses or 40 mg/kg/d IV in 4 divided doses
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Evaluation of Therapeutic Outcomes
 Many follicular infections resolve spontaneously without
medical or surgical intervention.
 Lesions should be incised if they do not respond to a few days
of moist heat and nonprescription topical agents.
 Following drainage, most lesions begin to heal within several days
without antimicrobial therapy.
 Any patient who is unresponsive to several days of systemic
antibiotic therapy or suffers recurrent infection should have a
culture and sensitivity test performed to guide continued
antibiotic selection.

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3. Erysipelas
 It’s distinct form of cellulitis involving the more superficial
layers of the skin and cutaneous lymphatics
 It is characterized by an area of erythema that is well
demarcated, raised, and burning pain
 Often affects the lower extremities, with the face being the
second most commonly affected site.

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3. Erysipelas…Risk factor/Etiology
Risk Factors
 Excising the saphenous vein for bypass
 Lymphatic edema (major risk factor)
 Lymphatic obstruction
 Arteriovenous fistula
 Status post-surgery (eg mastectomy)
 Nephrotic syndrome
 Immunocompromised state
 Insect bites, stasis ulceration, surgical incisions, and venous insufficiency
 obesity, lymphedema, athlete’s foot, leg ulcers, eczema, intravenous drug
abuse, poorly controlled diabetes, and liver disease
 Almost always caused by β-hemolytic streptococci
 Group A streptococci ([Link])
 Occurs in areas of preexisting lymphatic obstruction or edema

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3. Erysipelas…Treatment
 Goals
 Rapid eradication of the infection,
 Providing relief of symptoms (pain, tenderness, fever)
 Preventing recurrent infection
 Mild-to-moderate cases
 IM procaine penicillin G or penicillin VK for 7 to 10 days
 Penicillin-allergic patients
 treated with clindamycin

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3. Erysipelas…Treatment
Inpatient vs outpatient Rx
 Children younger than 3 months,
 Critically ill appearing patient
 Local complications,
 Debilitated patient (chronic conditions, the elderly) or
 If there is a risk of non-compliance with or failure of outpatient
treatment.
 Treat other patients as outpatients.

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3. Erysipelas…Treatment
Outpatient Rx (7 to 10 days)
Cefalexin
PO for Children 1 month to under 12 years: 25 mg/kg 2 times daily
Children 12 years and over and adults: 1 g 2 times daily or
Amoxicillin/clavulanic acid (co-amoxiclav) in the ratio of 8:1
or 7:1
Children < 40 kg: 25 mg/kg 2 times daily
Children ≥ 40 kg and adults2 times daily
For penicillin-allergic patients, clindamycin
Children: 10 mg/kg 3 times daily;
Adults: 600 mg 3 times daily.
In the event of worsening clinical signs after 48 hours of
antibiotic treatment, consider IV route.
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3. Erysipelas…Treatment
Inpatient Rx
First line therapy]
 Cloxacillin IV infusion over 60 minutes
 Children 1 month to under 12 years: 12.5 to 25 mg/kg every 6 hours
 Children 12 years and over and adults: 1 g every 6 hours or
 Amoxicillin/clavulanic acid (co-amoxiclav) by slow IV injection (3
minutes) or IV infusion (30 minutes).
 Children under 3 months: 30 mg/kg every 12 hours
 Children 3 months and over: 20 to 30 mg/kg every 8 hours (max. 3 g
daily)
 Adults: 1 g every 8 hours
 If pencillin allergy: clindamycin IV infusion over 30 minutes
 If there is clinical improvement after 48 hours switch PO at the
doses indicated above to complete 7 to 10 days of treatment.

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3. Erysipelas…Treatment
 If there is no clinical improvement after 48 hours, consider
MRSA:
 Clindamycin IV infusion over 30 minutes (If resistance rate is
low (e.g., <10%).
 Children 1 month and over: 10 mg/kg every 8 hours
 Adults: 600 mg every 8 hours
 After 48 hours, change to clindamycin PO at the doses
indicated above to complete 7 to 10 days of treatment.
 If resistance is High, Rx?

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4. Cellulitis

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4. Cellulitis
 It is an infection of epidermis, dermis and may spread
subsequently within the superficial fascia.
 It’s a common and potentially serious infection caused by
bacteria.
 It usually affects the arms and legs

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4. Cellulitis
 Injection drug users….. S. aureus, including MRSA and
Clostridium species
 Diabetics……mixed aerobic and anaerobic pathogens
 Complications of cellulitis
oLocal abscess,
oMyositis,
oOsteomyelitis,
oSeptic arthritis,
oBacteremia,
oEndocarditis, and
oSepsis.

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4. Cellulitis….Clinical presentation
 Signs and symptoms
 fever, chills, or malaise and complain that the affected area feels hot
and painful.
 Erythema and edema of the skin.
 Lesions are nonelevated and have poorly defined margins.
 Affected areas generally are warm to touch
 Purulent drainage, exudates, and/or abscesses
 Tender lymphadenopathy associated with lymphatic involvement
 Systemic findings such as hypotension, dehydration, and
altered mental status are common.
 Lab Tests: Cultures, Gram stain, CBC

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4. Cellulitis…Treatment
Goals
 Rapid eradication of the infection
 Prevention of further complications
 Avoidance of unnecessary antimicrobials that contribute to increased
resistance, and
 Minimizing toxicities and cost of therapy
 Non-pharmacological Rx
 Elevation and immobilization of the involved area to decrease swelling
 Cool sterile saline dressings may decrease pain and can be followed
later with moist heat to aid in localization of the cellulitis
 Surgical intervention (incision and drainage)

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4. Cellulitis…Treatment

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Evaluation of Therapeutic Outcomes
 If treated promptly with appropriate antibiotics, the majority
of patients with cellulitis are cured rapidly.
 Culture and sensitivity results should be evaluated carefully
for both the adequacy of culture material and the presence
of resistant organisms.
 Additional high-quality samples for culture may be needed
for microbiologic analysis.
 Failure to respond to therapy also may be indicative of an
underlying local or systemic problem or a misdiagnosis.

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5. Necrotizing Soft-tissue Infections

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5. Necrotizing Soft-tissue Infections

NF is a rapidly progressive, life-threatening infection causing necrosis of

subcutaneous tissue and fascia.
Due to GAS infection, its associated mortality rate approaches 25%
Most frequently involve the abdomen, perineum, and lower extremities.
NF can affect any age-group.
The major clinical entities of necrotizing infections are necrotizing fasciitis
and clostridial myonecrosis (gas gangrene)

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5. Necrotizing Soft-tissue Infections

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5. Necrotizing Soft-tissue Infections…RFs
 Diabetes
 Chronic disease
 Immunosuppressive drugs (eg, prednisolone)
 Malnutrition
 Age > 60 years
 Intravenous drug misuse
 Peripheral vascular disease
 Renal failure
 Underlying malignancy
 Obesity
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5. Necrotizing Soft-tissue
Infections…etiology and classification
 Caused by aerobic and/or anaerobic bacteria and
 Results in progressive destruction of the superficial fascia and
subcutaneous fat

80%

flesh-eating bacteria Eg. S. pyogenes

5% Gas production and muscle necrosis…gas

gangrene

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5. Necrotizing Soft-tissue
Infections…etiology and classification

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5. Necrotizing Soft-Tissue Infections…Clinical
presentation

• Rapid diagnosis is critical due to the aggressive nature and

high associated mortality (20%-50%).
Symptoms
• Fever, chills, and leukocytosis and
• Shock and organ failure…type II infections.
• Pain in the affected area and systemic toxicity are
characteristically more pronounced than with cellulitis.

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5. Necrotizing Soft-Tissue
Infections…Clinical presentation
Signs
 Affected area…hot, swollen, and erythematous without sharply
demarcated margins.
 Affected area… shiny, exquisitely tender, and very painful.
 Diffuse swelling of the area is followed by the appearance of bullae
filled with clear fluid.
 Rapidly progressive infection with the frequent development of a
maroon or violaceous color of the skin after several days.
 Infection may rapidly evolve into a cutaneous gangrene, sometimes
with myonecrosis.
 Investigations: Tissue samples (culture and susceptibility
testing), MRI/CT, CBC, chemistry, C-reactive protein…..

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5. Necrotizing Soft-Tissue
Infections…Treatment
Goals
Rapid eradication of the infection,
Prevention of further complications, and
Reduction in mortality
Avoidance of unnecessary antimicrobials that contribute to increased
resistance, and
Minimizing toxicities and cost of therapy
Non-pharmacological Rx
 Immediate and aggressive surgical debridement of all necrotic tissues
 Hyperbaric oxygen therapy
 Occlusive conventional dressings using humid or vaseline gauze
dressings

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 5. Necrotizing Soft-Tissue
Infections…pharmacological Rx

The mean
11/17/2023 duration of antibiotic therapy for NF
BY MAis 4–6 weeks. 51
Evaluation of Therapeutic Outcomes
 Vital signs and laboratory tests should be monitored carefully
for signs of resolution of the infection.
 Change in antimicrobial therapy or additional surgical
debridement may be needed in patients who do not show
signs of improvement.

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6. Diabetic Foot Infections

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6. Diabetic Foot Infections….Introduction
Diabetic foot infections range in severity from superficial
paronychia to deep infection involving bone.
Major types of foot infections are seen in diabetic patients:
deep abscesses, cellulitis of the dorsum, and mal perforans
ulcers
The lifetime risk of developing at least one foot ulcer in
persons with diabetes is estimated at 30%.
DFIs are the main risk factor for limb amputation, and in
addition to significant morbidity and impact on quality of life,
the healthcare costs
71,000 lower-extremity amputations/year
20% of them will undergo additional surgery or amputation of a second
limb within 12 months of the initial amputation

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DFI…RFs/Etiology
Risk factors Etiology of DFIs

30%

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 Pathophysiology
1. Neuropathy
 Affect the motor nerve supply of small intrinsic muscles of the foot, resulting in
muscular imbalance, abnormal stresses on tissues and bone, and repetitive injuries
 Diminished sensory perception
 Absence of pain and unawareness of minor injuries and ulceration
2. Sympathetic nerve supply may be damaged,
 Resulting in an absence of sweating that may lead to dry cracked skin and secondary
infection
3. Atherosclerosis (micro/macro angiopathy)
 Ischemia and PAD, ultimately leading to skin breakdown, infection, and impaired
wound healing.
4. Impaired phagocytosis and intracellular microbicidal function
 Defects in cell-mediated immunity make patients with diabetes more susceptible to certain types of
infection and impair the patients’ ability to heal wounds adequately

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DFI...Clinical presentation and Dx

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DFI...Clinical presentation and Dx

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DFI...Clinical presentation and Dx
DFI are classified into four categories based on clinical
presentation using the PEDIS scale (perfusion, extent/ size,
depth/tissue loss, infection, sensation)

PEDIS 1

PEDIS 2

PEDIS 3

PEDIS 4

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Treatment
Goals
 Successfully treat infected wounds by using effective nondrug
and antibiotic therapy;
 Prevent additional infectious complications;
 Preserve as much normal limb function as possible;
 Avoid unnecessary use of antimicrobials that contribute to
increased resistance; and
 Minimize toxicities and cost while increasing patient quality of
life.

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Non-pharmacological Rx
 Debridement of necrotic or nonviable tissue,
 Wound dressings,
 Vascular or orthopedic surgery, and
 Off-loading pressure from the wound
 Prevention
Periodic foot examinations with monofilament testing and patient
education regarding proper foot care,
Optimal glycemic control, and
Smoking cessation are key preventative strategies

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Pharmacological Rx
Selection of empiric antimicrobial therapy guided by
 Severity of a patient’s infection and Based on the PEDIS scale,

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Pharmacological Rx

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Evaluation of Therapeutic Outcomes

 Therapy should be reevaluated carefully after 48 to 72 hours

to assess favorable response.
 Change in therapy (or route of administration, if oral) should
be considered if clinical improvement is not observed at this
time.
 For optimal results, drug therapy should be appropriately
modified according to information's from deep-tissue culture
and the clinical condition of the patient.
 Infections in diabetic patients often require extended courses
of therapy because of impaired host immunity and poor
wound healing.

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