UTIs

Question 1

epidemiology

Answer 1

UTIs are the most common bacterial infections; ≈ 60% of females will develop a UTI during their lifetime and recurrence will occur in ≈ 25% within 1 year
Prevalence varies with age and gender
UTIs in men occur less frequently until 65 years of age; similar prevalence to females

Question 2

classifications of UTIs

Answer 2

Lower urinary tract – involving the bladder (cystitis), urethra (urethritis), and prostate (prostatitis)
Upper urinary tract – involving the kidneys (pyelonephritis)
Uncomplicated – infections in otherwise healthy, premenopausal women who lack structural or functional abnormalities that interfere with normal urine flow or voiding mechanisms
Complicated – infections resulting from a predisposing lesion of urinary tract (congenital abnormality, stone, indwelling catheter, prostatic hypertrophy, obstruction, neurologic deficit)
Recurrent – characterized by multiple symptomatic episodes with asymptomatic periods occurring between episodes ( 2+ UTIs in 6 months or 3+ UTIs in 1 year)
-Re-infection – occurs over 2 weeks after the previous UTI; different organism; treated as a new UTI
-Relapse – occurs within 2 weeks of the original infection (unsuccessful treatment, resistant organism, anatomical abnormality); same organism
Asymptomatic bacteriuria
-Common, especially in patients 65+ years of age
-Significant bacteriuria (over 10^5 bacteria/ml) in the absence of symptoms
Symptomatic abacteriuria (acute urethral syndrome)
-Symptoms of frequency and dysuria in the absence of significant bacteriuria
-Commonly associated with chlamydial infections (sexually transmitted disease)

Question 3

criteria for defining significant bacteriuria

Answer 3

≥ 10^2 CFU coliforms/ml or ≥ 10*5 noncoliforms/ml in a symptomatic female
≥ 10^4 CFU bacteria/ml in a symptomatic male
≥ 10^5 CFU bacteria/ml in asymptomatic individuals on two consecutive specimens
Any growth of bacteria on suprapubic catheterization in a symptomatic patient
≥ 10^2-5 CFU bacteria/ml in a catheterized patient

Question 4

etiology

Answer 4

acute uncomplicated cystitis - E. coli* 80-90%
acute uncomplicated pyelonephritis - E coli* 89%
complicated UTI - many causative organisms
catheter- associated UTI (CA-UTI) - many causative organisms
with many causative organisms - have to culture to know how to treat

Question 5

pathogenesis - ascending pathway

Answer 5

Entry of colonic bacteria colonizing the anterior urethra and/or vagina into the bladder
Short length of female urethra and proximity to perirectal area → colonization
Other factors promoting urethral colonization: diaphragm/spermicide use, antibiotics

Question 6

pathogenesis - hematogenous spread (uncommon)

Answer 6

Spread of pathogens from distant sites of infection

Most common with S. aureus → renal abscesses

Question 7

pathogenesis - host defense mechanisms

Answer 7

Urine – capable of inhibiting and killing organisms
-Low pH, extremes in osmolality, high urea and organic acid concentrations
-Flushing and diluting effects of urine; voiding
-Introduction of bacteria into the bladder stimulates micturition → increased diuresis and emptying of the bladder
-Men – prostatic secretions further inhibits bacterial growth
Antiadherence factors in bladder (urinary mucus, IgG, IgA)

Question 8

clinical manifestations in young children

Answer 8

non-specific (fever, poor feeding, vomiting)

Question 9

clinical manifestations in adults

Answer 9

abrupt onset of symptoms
Acute uncomplicated cystitis: Fever and systemic symptoms are absent, Dysuria, urgency, frequency, Nocturia, Suprapubic heaviness, Urine may be foul smelling or turbid (white cells), Hematuria in 20-30% of cases
Acute pyelonephritis: Systemic symptoms are more common, Fever ± chills, Nausea, vomiting, abdominal pain, Flank pain, costovertebral tenderness, Wide spectrum of illness – mild infection to gram-negative sepsis
Complicated UTIs: Presentation is often atypical and non-specific, Resistant bacteria more common, Response to therapy may be delayed or absent, Complications and recurrences are more common
Elderly: Often asymptomatic, May present with altered mental status, change in eating habits, or GI
symptoms
Patients with indwelling catheters or neurologic disorders: Lower tract symptoms usually absent, Flank pain and fever are common in upper tract infections

Question 10

Diagnosis overview

Answer 10

Requires documentation of significant numbers of organisms in an appropriate urine specimen

Question 11

preferred methods for collecting urine for testing

Answer 11

Midstream clean-catch – preferred method for routine collection (after cleaning the urethral opening in men and women)
Catheterization –use aseptic technique to avoid introduction of bacteria in bladder - In patient with indwelling catheter, obtain sample for culture from specimen collection port on the catheter
Suprapubic bladder aspiration – preferred in newborns, infants, paraplegics, seriously ill patients, when other methods provide confusing or equivocal results

Question 12

urinalysis

Answer 12

Description of color, specific gravity, pH of the urine, glucose, protein, ketones, blood, and bilirubin
Microscopic examination
-Bacteriuria – best assessed using gram stain of uncentrifuged urine
—Presence of at least one organism/oil-immersion field correlates with ≥ 105 bacteria/ml of urine
—Not readily detected with lower colony counts (102 to 104 CFU/ml) – centrifuged specimen is more sensitive
-Leukocytes
—Count leukocytes in uncentrifuged specimen using a hemocytometer chamber – more accurate and reproducible than assessing centrifuged urine sediment (used in most labs)
—Pyuria – WBC > 10 cells/mm3 of urine; nonspecific – signifies presence of inflammation, not necessarily infection
-Hematuria
—Present in 40-60% of patients with acute cystitis
—Absent in other dysuric syndromes
Biochemical test for screening urine
-Urine dipstick to detect presence of nitrite in urine (bacteria reduce nitrate normally present in urine)
-Leukocyte esterase test – detects LE enzyme, which is present in neutrophil granules; indicates presence of WBCs

Question 13

Quantitative urine culture and identification of organism - most reliable for diagnosis

Answer 13

most reliable for diagnosis
Differentiate contamination from infection (specimen must be properly collected)
Contamination – low bacterial counts, usually nonpathogenic species, multiple species present
Infection – higher bacterial counts, typical uropathogens only
>105 bacteria/ml has been shown to differentiate contamination from infection
In acutely symptomatic women, significant bacteriuria ≥ 102 CFU/ml of a known uropathogen

Question 14

Susceptibility testing

Answer 14

Susceptibility breakpoints usually based on achievable serum concentrations
Therapy may be completed before culture and susceptibilities are known
Must known resistance trends to select appropriate therapy
When is susceptibility testing essential**
-Suspected upper tract infection
-Presence of complicating factors
-All male patients

Question 15

goals of UTI therapy

Answer 15

Eradicate the causative pathogen
Prevent or treat systemic manifestations of infection
Prevent recurrence of infection
Prevent emergence of bacterial resistance

Question 16

general treatment principles for UTI

Answer 16

Initial antibiotic selection is based on severity of presenting sign and symptoms, site of infection, and whether infection is uncomplicated or complicated.
Other considerations: ability of agent to achieve adequate concentrations in the urine, antibiotic susceptibility, side effect profile, cost
Factors affecting rate and extent of drug excretion into urine: patient’s GFR, molecular weight, protein binding, active tubular secretion

Question 17

treatment of acute uncomplicated cystitis - single dose therapy

Answer 17

not first line
Highest cure rates with TMP/SMZ (2 DS tablets) and fluoroquinolones
Effective in women with acute cystitis (cure rates 82-100%); recurrence more frequent than 3-day therapies
Advantages: less expensive; better compliance; few side effects; less potential for development of resistance(?)
Patients which single dose therapy should not be recommended
-Pregnant women
-Symptoms of upper tract infection
-Patients with diabetes, immunosuppression, or urinary tract abnormalities
-Patients with symptoms > 7 days before starting therapy
-Males

Question 18

acute uncomplicated cystitis - recommended empiric treatment

Answer 18

Nitrofurantoin monohydrate/macrocrystals (Macrobid®) 100 mg PO BID x 5 days**
-Each 100 mg capsule contains 75% monohydrate and 25% macrocrystals (slower dissolution and absorption than monohydrate)
-Monohydrate forms a gel matrix when exposed to gastric and intestinal fluids, which releases nitrofurantoin over time
-Plasma concentration are very low (less than 1 µg/ml) - use only for uncomplicated cystitis
-Bioavailability increased to ≈ 40% with food
-20-25% excreted into urine as unchanged drug
-Bactericidal in urine at therapeutic doses
-Not active against** Proteus sp, Serratia marcescens, or P. aeruginosa
-Contraindicated** in patients with creatinine clearance under 60 ml/min, pregnant women at term (38-42 weeks), neonates under 1 month of age
-Adverse events: pulmonary toxicity (diffuse interstitial pneumonitis, pulmonary fibrosis), hepatotoxicity, peripheral neuropathy, hemolytic anemia
-Drug interaction: antacids (decrease rate and extent of absorption)
-Pregnancy category B**
TMP/SMZ 160/800 mg [1 DS] BID x 3 days** – if local resistance rates for uropathogens under 20% or if pathogen is known to be susceptible
Fosfomycin trometamol (Monurol®) 3 grams as a single dose
-Available as a sachet – contents must be dissolved in water**
-Bioavailability – 37% fasting, 30% with food
-around 38% of dose recovered in the urine (mean urine concentrations ≈ 700 µg/ml within 2-4 hours after oral dosing under fasting conditions)
-Mean half-life 5.7 ± 2.8 hours (prolonged in renal insufficiency)
-Bactericidal – inactivation of enolpyruvyl transferase (one of first steps in cell wall synthesis)
-Active against E. coli, K. pneumoniae (including ESBL- and carbapenemase-producing strains), Enterobacter sp., Proteus sp., S. marcescens, P. aeruginosa, enterococci (including VRE)
-Pregnancy category B
Fluoroquinolone (ciprofloxacin 250 mg q12h, levofloxacin 250 mg q24h) x 3 days – high propensity for collateral damage; do not consider first-line**
β-lactams (amoxicillin/clavulanate, cefdinir, cefaclor, cefpodoxime) x 3-7 days – only when other agents cannot be used
Consider 7-10 day regimen if complicated, diabetes, symptoms over 7 days, recent UTI, use of diaphragm, age > 65yr (levofloxacin 750 q24h x 5 days)
Pregnancy –7-day regimen
-Amoxicillin/clavulanate 500 mg q8h or 875 mg q12h
-Nitrofurantoin 100 mg qid or Macrobid® capsule q12h (avoid at term)
-Cefpodoxime proxetil 100 mg q12h
-TMP/SMZ 160/800 mg q12h (avoid in last trimester)
Follow-up urine culture – recommended if patient fails to respond or symptoms return within 2 weeks

Question 19

treatment of UTIs in males

Answer 19

Obtain urine culture before treatment
Should be considered a complicated infection – treat for 10-14 days
TMP/SMZ
Fluoroquinolone – ciprofloxacin or levofloxacin
Follow-up cultures 2 weeks after therapy – important
If culture positive 2 weeks after therapy, recurrent infections (? prostate source) – treat for 6 weeks

Question 20

treatment of asymptomatic bacteriuria

Answer 20

Majority of patients are elderly, female, and pregnancy women
Management depends on age of patient and whether they are pregnant
-Children – greater risk of developing renal scarring and long-term renal damage → treat
-Pregnancy – increased risk of developing pyelonephritis; increased incidence of prematurity and low birth weight
-Non-pregnant females, elderly – no treatment recommended

Question 21

acute pyelonephritis treatment

Answer 21

Organisms in bladder can ascend the ureters to the kidneys
Can be subdivided into:
-Mild disease – manage in outpatient setting
-Patients sufficiently ill to require hospitalization for parenteral therapy
-Complicated infection occurring in the setting of catheterization, hospitalization, urologic surgery, or known urological abnormalities
Urine culture and susceptibility testing should always be performed
Outpatient* therapy (mildly-to-moderately symptomatic)
-Ciprofloxacin* 500 PO q12h x 7-10 days – if prevalence of resistance does not exceed 10%
-Ciprofloxacin extended release 1000 mg once daily x 7 days
-Levofloxacin* 750 mg once daily x 5 days
-TMP/SMZ* 1 DS twice daily for 14 days – if pathogen known to be susceptible
Parenteral therapy (seriously ill; signs of nausea, vomiting, dehydration)
-TMP/SMZ 160/800 mg IV q12h x 14 days if uncomplicated
-Fluoroquinolone (ciprofloxacin 400 mg IV q12h, levofloxacin 500-750 mg IV q24h)
-3rd or 4th generation cephalosporin
-Ampicillin/sulbactam + gentamicin (effective vs. enterococci)
-When afebrile for ≥ 24 hours and can take PO, complete 7-14 days with oral therapy (TMP/SMZ, fluoroquinolone)
-Follow-up urine culture 2 weeks after completion of therapy to ensure response and detect possible relapse
-Consider Pseudomonas and enterococci if patient has been hospitalized in past 6 months, has a urinary catheter, or is in a nursing home
—Ceftazidime, cefepime, piperacillin/tazobactam, aztreonam, imipenem, or meropenem in combination with aminoglycoside
—If patient responds, may stop aminoglycoside after 3 days

Question 22

treatment of reccurrent UTI infections

Answer 22

Management strategies depend on predisposing factors, number of episodes per year, and patient preference
If less than 3 infections/year, treat each episode as new infection (3-day regimen)*
Therapeutic options for reinfection (account for 80% of recurrences)
-Self-administered therapy (reserve for women with 1-2 infections/yr)
-Post-coital therapy (single dose TMP/SMZ) - most 3/day
-Continuous low dose prophylaxis for 6 to 12 months – in patients with frequent symptomatic infections (≥ 3 infections/yr)
—TMP/SMZ 40/200 mg daily
—Trimethoprim 100 mg daily
—Nitrofurantoin 50-100 mg daily
Post-menopausal women – topical (vaginal) estrogen cream may reduce incidence of infection
Relapses** account for 20% of recurrences
-Usually indicates renal involvement, structural abnormalitiy of urinary tract, or chronic bacterial prostatitis
-In women, if relapse occurs after short course therapy, treat for 2 weeks
-If relapse after 2 weeks, continue therapy for additional 2-4 weeks
-If relapse occurs after 6 weeks of therapy, urologic evaluation should be performed.
In randomized placebo-controlled study in 319 college women, recurrence rate with cranberry juice not significantly different than placebo (20% vs. 14%)

Question 23

treatment of CA-UTI

Answer 23

Catheter-associated bacteriuria is the most common source of gram-negative bacteremia in hospitalized patients
Defined by presence of signs and symptoms of UTI with ≥ 103 CFU/ml of ≥ 1 bacterial species in the urine from a patient whose catheter has been removed within the previous 48 hours
Entrance of bacteria into catheterized bladder
-Introduced at the time of catheterization
-Enter on the external surface of the catheter (most common, esp. in women)
-Enter the draining system by contamination of the collecting bag or disconnection of the junction between the catheter and the collecting tube, then ascend through the lumen of the catheter
Risk of infection increases with the length of time the catheter is in place
-about 50% become bacteriuric if catheterized for 2 weeks (rate 5%/day)
-All patients with permanent indwelling catheters eventually become infected
Sterile closed collecting systems – can prevent bacteriuria for 10 days in majority of patients; after 30 days, 78-95% incidence of bacteriuria
Signs and symptoms – new onset fever, chills, altered mental status, malaise, lethargy, flank pain, acute hematuria, pelvic discomfort
Treatment only in patients with symptomatic infection***
-Remove the catheter, culture the urine, start appropriate therapy, reintroduce new catheter and draining system (if still required)
-Treat for 7 days in patients with prompt resolution of symptoms; 10-14 days if delayed response
-If fever and flank pain, start parenteral therapy

Question 24

pathogenesis/etiology of prostatitis

Answer 24

Routes of infection (not well understood)
-Reflux of infected urine into prostatic ducts (direct inoculation) – primary pathogenic mechanism
-Invasion by rectal bacteria through direct extension or lymphatic spread
-Ascending infection of the urethra (during sexual intercourse)
-Risk factors – urinary tract instrumentation, urethral stricture, urethritis (usually due to sexually transmitted pathogen)
Etiology** – gram-negative enteric organisms
-E. coli accounts for 75% of cases
-Enterobacteriaceae (K. pneumoniae, Proteus species) – 10-30% of cases
-Enterococcus species – 5-10% of cases
-P. aeruginosa - less than 5% of cases

Question 25

clinical presentation of prostatitis

Answer 25

Acute bacterial prostatitis – abrupt onset
-High fever, chills, malaise, myalgias, localized pain (perineal, rectal, sacrococcygeal)
-Other urinary tract symptoms (frequency, urgency, dysuria, nocturia, retention)
-Digital palpation may reveal a swollen, tender, warm, or indurated prostate
-Bacteremia may result from digital prostate palpation – safe if performed gently
-Massage of prostate will produce purulent discharge; pathogen recovered
-Diagnosis on basis of clinical presentation and presence of significant bacteriuria
Chronic bacterial prostatitis
-Develops in ≈ 5% of men with acute bacterial prostatitis
14
-Characterized by relapsing UTIs with the same pathogen
-Presenting symptoms: vague complaints of voiding difficulties, low back pain, perineal and suprapubic discomfort
-May be asymptomatic
-Physical exam of prostate may be normal

Question 26

treatment of acute uncomplicated UTI caused by E. coli

Answer 26

primary: ciprofloxacin 400 mg IV or 500 mg PO BID or levofloxacin 500-750 mg IV/PO QD
alternative agents: SMX/TMP DS BID