Urinary Tract Infections (UTIs) Anatomy © The urinary tract consists of the kidneys, ureters, bladder and urethra. — Adrenal gland fe Left upper {Kane kidney urinary tract | Ureters, Lower urinary Urethra Male prostate Female cervix Terms & Abbreviations - Urinary Tract Diseases * Urinary tract infection (UTD - A spectrum of diseases caused by microbial invasion of the genito-urinary tract that extends from the renal cortex of the kidney to the urethral meatus. © Bacteriuria - Bacteria in urine, as demonstrated by microscopy or quantitative culture. + Asymptomatic Bacteriuria - In a patient without signs and symptoms of urinary origin, the presence of bacteria in a non-contaminated urine specimen is defined as asymptomatic bacteriuria. © Urethritis - inflammation of the urethra © Ureteritis © Cystitis - inflammation of the bladder ¢ Pyelonephritis - inflammation of both the lining of the pelvis and the parenchyma of the kidney © Pyuria — presence of white blood cells in urine © Hematuria - Blood in the urine, either visible to the naked eye (macroscopic) or invisible to the naked eye (microscopic) © Urosepsis - UTI with accompanying sepsis syndrome inflammation of the ureters Dept. of Medical Microbiology, SME. aUTIs Classification I. UTIs can be classified according to anatomical localization a) Lower urinary tract © Urethritis (urethra) © Cystitis (bladder) © prostatitis in males (prostate) b) Upper urinary tract and systemic © Pyelonephritis (renal parenchyma) * ureteritis (ureters) Il. UTI - Clinical Classification 1. Single versus Recurrent episode, and 2. Complicated versus Uncomplicated episode. * Single episode UTI - A single-episode UTI occurs once and does not recur. + Recurrent/Chronic episode UTI - Patients with chronic or recurrent UTIs have repeated episodes of bacteriuria, with or without clinical manifestations. © Recurren/Chronic UTI - 2 types: a) Relapse - involves the same organism and implies a focus of infection in the renal or prostatic parenchyma b) Reinfection - involves a different organism and is usually limited to the bladder. © Uncomplicated UTI © Uncomplicated infections occur primarily in otherwise healthy females and ‘occasionally in male infants and adolescent and adult males. Most uncomplicated infections respond readily to antibiotic agents to which the etiologic agent is susceptible. © Complicated UTI © Complicated infections occur in both sexes. In general, individuals who develop complicated infections often have certain risk factors. In general, complicated infections are more difficult to treat and have greater morbidity (e.g., kidney damage, bacteremia) and mortality compared with uncomplicated infections © Urinary tract infections identified in pregnant women, men, children, and hospitalized patients or patients in other healthcare-associated settings (e.g., cancer outpatient clinics) may be considered complicated infections. + Risk Factors - Complicated UTI © Underlying diseases that predispose the kidney to infection. (e.g., diabetes, sickle cell anemia) © Kidney stones Structural or functional abnormalities of the urinary tract (e.g., a tipped bladder) © Indwelling urinary catheters ° Dept. of Medical Microbiology, SME. aMost Common Symptoms of UTI Dysuria, urgency, frequency, and suprapubic tenderness for the lower urinary tract Fever and abdominal or flank pain, usually accompanied by flank tendemess, and nausea as signs of a febrile upper UTI or pyelonephritis Chills and shivering as signs of bacteraemia Circulatory instability and eventually organ failure as signs of sepsis Prevalence of bacteriuria in female & male Infections in early childhood can ase asa ‘Changes in the prostate can alter bladder result of structural abnormalities, 2, ‘emptying allowing bacteria to enter the posterior urethral valves bladder. Asymptomatic baterula can occu 5 | Taandsoare often drectly UTicanarise as aresutofnormal | | related to sexual activty.NB_ | | Changes inthe pelvic anatomy after the [physiological or structural changes) | ASYMPTOMATIC BACTEAIURIA | | menopause enable bacteria to enter the inthe rena tract and pelvis IN PREGNANCY. bladder Asymptomatic bacteria ean occur 1 | Infections between the ages of ‘of population yoo ot ° 10 20 20 4 50 @ 70 ey Years Fig - General prevalence of bacteriuria at various ages in the female and male - The prevalence of bacteriuria, in percent, in males (blue text/line) and females (pink text/line) in the stages of life, Note that asymptomatic bacteriuria is a common finding in the patient over (60 years, and there is no benefit in diagnosing and treating this. Possible pathogens causing UTI More than 95% of uncomplicated UTIs are caused by a single bacterial species. Escherichia coli is the most frequent infecting organism in initial infections. In the presence of complicated UTI, itis not uncommon to isolate multiple organisms from the urine. Because instrumentation and repeated courses of antimicrobial therapy are common in complicated UTI patients, antibiotic-resistant isolates might be expected. Anaerobic organisms are rarely pathogens in the urinary tract. Adenoviruses (particularly type 11) have been strongly implicated as causative agents in haemorrhagic cystitis in paediatric patients (especially boys) and in allogeneic hematopoiet stem cell transplant recipients, and in UTI in renal transplant recipients. Dept. of Medical Microbiology, SME. BHUropathogens by Type of UTIs Uncomplicated UTI Complicated UTI © [Link] © Similar to uncomplicated UTI * 8. saprophyticus * Antibiotic-resistant £. coli © Enterococcus spp. © P. aeruginosa *K. pneumoniae * Acinetobacter baumannii © P. mirabilis © Enterococcus spp. © Staphylococcus spp. Uropathogens by Type of UTIs CA-UTI Recurrent UTI © P. mirabilis * P. mirabilis © Morganella morganii * K. pneumoniae © Providencia stuartii © Enterobacter spp. © [Link] * Antibiotic-resistant £. coli © Candida spp. © Enterococcus spp. © Staphylococcus spp. Laboratory Diagnosis * Screening Procedures (Rapid Nonculture Methods) - test for the presence or absence of bacteriuria provides physicians important same-day information. © Manual Urine Screening Methods * Microscopy - for detection of bacteria and pyuria * Chemical Methods (Indirect Indices) - detects presence of bacterial enzymes or PMN enzymes Microscopy - Gram Stain * Uncentrifuged urine samples may be used for a © Presence of one or more bacterial cells per oil immersion field in at least five fields in a smear of uncentrifuged urine correlates with more than 10° CFU/ml. © If the uncentrifuged preparation tests negative, the centrifuged (5 minutes at 2000 rpm) preparation should be stained. * Bacterial cells seen in this preparation indicate a density of fewer than 10° organisms per milliliter and, in the presence of clinical findings of acute pyelonephritis, may suggest urinary obstruction or perinephric abscess. * The presence of gram-positive or gram-negative bacteria or fungi assists in the selection of an appropriate antibiotic therapy. ined smear. Dept. of Medical Microbiology, SME. aroscopy ~ Pyuria Pyuria often indicates urethritis, cystitis, or pyelonephritis. Pyuria (10 leukocytes/mm*, using a hematocytomer from a clean catch midstream specimen) is the hallmark of inflammation, and the presence of polymorphonuclear neutrophils (PMNs) can be detected and enumerated in uncentrifuged specimens. Chemical Methods 1 Nitrate Reductase (Greiss) Test (Dipstick) © Gram-negative bacteria reduce nitrates to nit Leukocyte Esterase Test (Dipstick) © Measures presence of WBC enzyme Catalase (Tube) © Measures catalase present in bacteria and somatic cells Sterile Pyuria The finding of WBC (5 to 8 WBC per HPF) in a urinalysis in the absence of bacteria in concurrent routine urine culture is referred to as “sterile pyuria,” Sterile Pyuria - Treatment/non-infective causes © Recent antibiotic therapy co Recent surgery ©. Foreign bodies in the genito-urinary tract, including catheters © Tumors of the genito-urinary tract Sterile Pyuria - Infective causes © Tuberculosis © Uncommon infection with fastidious organism such as Haemophilus or rarely anaerobes © Uncommon infection with fastidious organism such as mycoplasma; consider empirical clarithromycin if other options excluded © Patient on recent trimethoprim or co-trimoxazole. Consider nutritionally deficient, thymidine-dependent ‘coliforms’, Selection of Media It is generally accepted that urine cultures should be processed on Blood agar and a gram-negative selective medium (MacConkey agar [MA] or eosin-methylene blue [EMB] agar). BA can be substituted Columbia colistin-nalidixic acid agar (CNA) or phenylethyl alcohol agar to facilitate detection of gram-positive organisms when overgrowth of gram-negative organisms is anticipated. MA can be substituted by cystine-lactose electrolyte-deficient (CLED) agar. CLED agar does not contain sodium chloride, inhibiting the characteristic swarming of Proteus spp., but still supports adequate growth of most common urinary pathogens. Dept. of Medical Microbiology, SME. aA variety of chromogenic media are available for the identification and differentiation of urine pathogens. e.g., CHROMagar, CPS ID3, Spectra UTI, etc. ‘Specimen Inoculation and Incubation Calibrated loops of 0.001 mL (1 il) to 0.01 mL (10 4) should be used. For voided urine specimens and those from indwelling catheters, culture at least 1 yl For other urine specimens collected by sterile techniques, culture at least 10 yl Use of 0.01 mL can detect as few as 10° CFUs. ‘These loops, made of platinum, plastic, or other material, can be obtained from laboratory, Before inoculation, urine is mixed thoroughly, and the top of the container is then removed. The calibrated loop is inserted vertically into the urine in a cup, as a more horizontal position may increase the volume beyond calibration. It should also be observed visually for bubbles that would decrease the volume. Dept. of Medical Microbiology, SME. oInoculation methods for colony count (choose one method) a) Method of streaking urine with 111 loop Using the loop, make a straight line down the canter of the plate and streak the urine by making a series of passes at 90" angles through the inoculum (method for I tl only). b) Method of streaking urine with Ip! or 10yL loop Deliver the loopful onto one quadrant of plate by making a straight line or a V-shaped line. Streak urine onto the first quadrant, and proceed by streaking onto all four quadrants, ) Spreader method of streaking urine after inoculation with either a 10u or 1yt1 Use a sterile spreader or bent rod (L-spreader) to spread the loopful of urine over the surface of the entire plate in three directions Dept. of Medical Microbiology, SME.d) Method of streaking 10 111 of urine using drip method for count & quadrant streaking for isolation Pipette inoculation methods - With a sterile pipette tip and calibrated pipettor, aspirate 10 tl of well-mixed urine onto one side of plate and allow to drip down plate. Streak urine in quadrants on rest of plate with sterile loop Specimen Inoculation and Incubation © Plates should be incubated for at least 16 hours, but preferably for 24 hours at 35° to 37°C. * Ifconvenient, incubate BA and CNA in 5% CO; to enhance growth of Gram-positive organisms. Interpretation of Urine Cultures For positive cultures, examine culture media for the quantity and morphological type of ‘organisms’ present. a 1pl loop, one colony equals 1,000 CFU/ml. 2. With a 10p1 loop, one colony equals 100 CFU/ml, Interpretation of Urine Cultures * Determine the colony count of each morphotype in the culture separately by examining BA. * Using following criteria determine the extent of workup of each organism. Table - Interpretation of Counts Counts (CFU/ml) | Interpretation <1000 Insignificant bacteriuria; UT-unlikely 1000 - 100,000 | Probably Sig icant bacteriuria; UTI Probable > 100,000 Significant bacteriuria; UTI certain Dept. of Medical Microbiology, SME. aTable - Workup of voided urine speci No. of isolates Colony Count (CFU/ml) Definitive Identification 1 >10* Yes, if possible uropathogen <10" No (descriptive ID only) Both >10* Yes, if possible uropathogen Both <10° ‘No (descriptive ID only) 12104 ans 1<10* Yes, only for 1>10* if PU 33 110° Yes, if possible uropathogen Any other combination No (descriptive ID only) Table - Workup of urine specimens collected by invasive* methods No. of isolates Colony Count (CFU/ml) Definitive Identification 1 21000 (10°) Yes, if possible uropathogen <10° No (descriptive ID only) 2 Both >10° Yes, if possible uropathogen Both <10° No (descriptive ID only) 1210° ans 1<10° Yes, only for 1=10° if PU 23 110° Yes, if possible uropathogen Any other combination No (descriptive ID only) * Indwelling and non-indwelling catheters, suprapubic bladder aspirate, cystoscopy and nephrostomy Interpretation of Counts — Notes * Streptococcus agalactiae should be reported from women in childbe: regardless of the count. © Pure culture of S. aureus is considered to be significant regardless of the number of CFUs © Count of 10° CFU/ml or more for Salmonella, can be considered significant, ig years, Identification of Isolat * Identify significant uropathogens * Do not identify normal urogenital microbiota to the genus or species level. Dept. of Medical Microbiology, SME. aReporting Results a) Report Gram stain results for bacteria and cells. b) Negative results 1. If no growth is observed on all media, report “Urine culture negative” or “No growth of uropathogens.” 2. IF Apt was cultured, report “No growth of uropathogens at 10°/ml.” ) Positive cultures should be reported with the colony count and either minimal morphologic or definitive identification of each potential pathogen isolated. Antimicrobial Susceptibility Testing * Antibiotic susceptit patients with bacteriuria and colony counts that are cli ty testing should be performed on isolates from symptomatic ically significant. Asymptomatic Bacteriuria (ASB) ‘+ ASB is the presence of 1 or more species of bacteria growing in the urine at specified quantitative counts (10° CFU/mL or >10° CFU/L), irrespective of the presence of pyutia, in the absence of signs or symptoms attributable to UTI. * For women, 2 consecutive specimens should be obtained, preferably within 2 weeks, to confirm the persistence of bacteriuria. © For men, a single urine specimen meeting these quantitative criteria is sufficient for diagnosis. Dept. of Medical Microbiology, SME.