Microbiology 63 [5-11

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Microbiology 63: Urinary Tract Infections

Most common bacterial infection in humans

UTI -> can occur at any site in urinary tract (usually bladder, kindey, prostate)

Urethritis caused by Neisseria gonorrhea and Chlamydia pneumoniae

Acute uncomplicated UTI = acute cystitis in healthy women

Acute nonobstructive pyelonephritis = kidney infection in healthy women

Complicated UTI = underlying structural or functional abnormality

Asymptomatic bacteriuria = bacteria in urine without symptoms

Bacterial prostatitis = bacterial infection of prostate

Acute bacterial prostatitis = severe infection, acute onset

Chronic bacterial prostatitis = persistence of bacteria in prostate

Renal abscess = can occur with severe pyelonephritis or bacterial spread

Recurrent infection = reinfection or relapse

Pathogenesis

Infecting organisms -> from normal gut flora ascending up the urinary tract, turbulent flow in men with prostate hypertrophy, or bloodstream from other site (multiple cortical abscesses) o S. aureus and Candida common with hematogenous spread

Most important uropathogen = Escherichia coli

Acute Uncomplicated UTI = E. coli with mannose-sensitive fimbria (FimH) -> adherence to urothelial cells o Staphylococcus saprophyticus (Gram +) in 5-15% of -> temporal variation (autumn) o E. coli in 90% of acute nonobstructive pyelonephritis from P fimbriae (adhesion) bind to

glycosphingolipid Gal(α1-4) Galβ disaccharide

Aerobactin (iron scavenger) and hemolysin (lyse host cells) -> virulence factors on pathogenicity islands on E. coli chromosome

Complicated UTI = E. coli most common pathogen, lower virulence factors than above (host principal determinant of infection) o Enterobacteriacease family (Klebsiella, Enterobacter, Citrobacter), nonfermenting Gram neg. organisms (Pseudomonas aeruginosa), urease-producers (Proteus mirabilis,

Morganella morganii and Provendencia -> metabolize urea to ammonia for further damage) o Enterococcus species and coag neg staph are most common Gram + o Candida alibans, C. tropicalis, C. glabrate, C. parapsilosis (occasionally) o Many have indwelling urologic devices (catheter, stent, or nephrostomy tube)

 Biofilm has microorganisms

Asymptomatic Bacteriuria = E. coli in healthy women, low virulence factors

Bacterial Prostatitis = S. aureus or E. coli, prevalence of virulence factors, prostate stones source of bacteria

Host Factors

Uncomplicated UTI = normal voiding, genetic predisposition through nonsecretor of ABH blood

group antigens (bind to bacteria preventing attachment) or behavioral risk with sexual

intercourse and spermicide use for birth control, or estrogen deficiency o Lactobacillus flora in vagina maintains acidity but spermicide kills normal flora o New sexual partner, diaphragm use, and antimicrobial therapy also increase risk

Complicated UTI = structural or functional abnormalities (reflux, stones, pregnancy or catheters)

Host response

Acute cystitis = inflammatory response with local cytokine production (IL6, IL8, IL10), IgA and

IgG antibody response o Local immunity from acute cystitis does not protect from subsequent episodes

Acute uncomplicated pyelonephritis = pyuria, cytokine production, fever, leukocytosis, elevated

CRP, IgM (first infection) and IgG (subsequent infection)

Spontaneous resolution less frequent in complicated UTI

Gram + (Enterococcus) and coag neg staph less often accompanied by pyuria

Clinical presentation

Uncomplicated cystitis or pyelonephritis = dysuria, frequency, urgency, suprapubic or low-back discomfort, some hematuria o Physical exam normal in acute cystitis by CVA pain and tenderness in pyelonephritis

(fever, nausea, vomiting)

Complicated UTI = symptoms of acute cystitis/pyelonephritis

Bacterial Prostatitis = high fever, pelvic pain, urinary retention, swollen tender prostate (digital exam not recommended), if chronic-> recurrent episodes of acute cystitis

Urine Culture

Contamination from periurethral area or vagina -> false positive o Clean-catch specimen mid-void is adequate

Colony counts of contaminants in voided specimens are low, while infecting organisms

achieve high concentrations o Prompt forward to lab o Most have 1 organism but complicated UTI may have more

Biofilm-coated devices -> greater number and higher count of organizms o Use new catheter for urine collection to avoid biofilm organisms

Any quantitative count of potential uropathogen is consistent with UTI for women with acute

uncomplicated UTI o In pyelonephritis or complicated UTI -> at least 10 5 CFU/mL of pathogen o Asymptomatic bacteriuria IDed with 2 consecutive urine specimens w/ > 10 5 count

H. influenzae and Ureaplasma urealyticum infrequently cuase and not isolated with lab methods

Other Lab Tests

Pyuria -> dipstick leukocyte esterase test (not specific for UTI)

Systemic manifestations require blood culture obtained

Treatment

Antimicrobials excreted in urine preferred (achieve high urinary levels)

Acute uncomplicated cystitis = treat empirically, antimicrobial short-course (3-day) therapy o Trimethoprim/sulfamethoxazole (TMP/SMX) or trimethoprim = first choice drugs o Second choice = fluoroquinolone (3 days) or nitrofurantoin (7 days) o If pregnant, use cephalosporins o Fosfomycin trometamol (single does) not as effective

Acute uncomplicated pyelonephritis = urine culture pretherapy, leukocyte count and blood/urine cultures o Oral therapy = TMP/SMX, TMP, or fluoroquinolone o Parenteral therapy = extended spectrum cephalosporin, aminoglycoside, or fluroquiniolone (10-14 days)

Complicated UTI = urine culture pretherapy, if sever may need hospitalization and initial parenteral therapy

Asymptomatic bacteriuria = common in nursing homes, mostly don’t treat (unless pregnant or need procedure with potential trauma) o If in pregnancy, may risk pyelonephritis later (end of 2 nd or early 3 rd trimester)

Recurrent UTI = management of pt instead of treat individual episode (prolonged antimicrobial therapy)

Acute Uncomplicated UTI = if 2 episodes every 6 months or 3 every year, prophylactic therapy

(long-term low-dose therapy) o TMP-SMX, TMP, and fluoroquinolones reduce Gram – flora o Nirtofurantoin effective but no impact on flora (intermittent urine sterilization)

Complicated UTI = suppressive therapy with recurrent infection and urologic abnormalities

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