Urinary Tract Infections Urinary Tract Infections Keri A. Mattes, Pharm.D., BCPS September 15, 2003 7 million episodes of acute cystitis and 250,000 episodes of pyelonephritis annually in the U.S. Epidemiology Women z z 1 in 3 infected before age 24 50% have at least one during their lifetime Epidemiology 7 million office visits 1 million ER visits 100,000 hospitalization in 1997 Men z Incidence is very low prior to age 50 Epidemiology Cathether-associated UTI Most common nosocomial infection z >1 million cases in hospitals and NHs z Implications Financial z z Community acquired UTI = $1.6 billion Nosocomial UTI = >$400 million Elderly z z 2nd most common form of infection 25% of all infections 1 Implications Assess the Patient Medical Classify by: Bacteremia z Symptoms z Pregnancy Location Complications z Organisms z Pathophysiology z z z z z Pyelonephritis, premature delivery, fetal complications and mortality, PIH z Pediatrics z Host defense mechanisms, virulence factors Risk Factors z Clinical Presentation z Impaired renal function, renal scarring, ESRD * * Classification of UTIs Complicating Factors Lower Tract z z z z Male Sex Elderly Indwelling urinary catheter or recent instrumentation Obstruction/Stone Prostatic Hypertrophy Pregnancy Urethritis Cystitis Prostatitis Epididymitis Upper Tract z z Pyelonephritis Intrarenal/perinephric abscess Etiology Uncomplicated Infections E. coli 80% Staph. Saprophyticus 10-15% Klebsiella less common pneumoniae,Proteus sp., Enterobacter and Enterococcus sp. * Diabetes Immunosuppression Neurologic Deficit Childhood UTI Recent antibiotic use Symptoms for > 7 days Hospital-acquired infection Presents at an urban ER Etiology – Complicated Infections E. coli Enterococcus fecalis Proteus sp. K. pneumoniae Serratia marcescens Enterobacter sp. P. aeruginosa Staph aureus Enterococci Candida sp. <50% 2 Etiology - Pediatrics Etiology - Elderly E. coli Proteus sp. Klebsiella sp. Serratia marcescens E. coli Polymicrobial Etiology – Spinal Cord Injury or Catheterized Etiology - Diabetes Klebsiella sp. Enterococcus E. coli Candida sp. E. coli Pseudomonas aeruginosa Proteus mirabilis Staph. aureus Enterococci Candida sp. * Etiology-HIV/AIDS Enterococcus sp. Pathophysiology Ascending Hematogenous Lymphatic 3 * * Defense Mechanisms Low pH Stimulation of bladder emptying/diuresis Extremes in osmolality High urea concentration Antiadherence z z High Organic Acid Conc. Glycosaminoglycan layer Tamm-Horsfall protein Immunoglobulins z Virulence Ability to adhere to epithelial cells z Bacterial fimbrae Hemolysin Bacterial Glycocalyx Urease Production IgG and IgA Prostatic secretions * Risk Factors Female Extremes of age Obstruction Diabetes Immunosuppression Pregnancy History of UTI Instrumentation Neurologic dysfunction Renal disease Sexual intercourse Diaphragm or spermicide use Antimicrobial use Short Urethra Proximity of urethra to perirectal area Use of spermicides and diaphragms Lack of prostatic fluid Clinical Presentation Lower Tract Why women > men? Upper Tract Clinical Presentation Elderly z Dysuria z Lower tract symptoms z Typical symptoms may be absent z Urgency z Frequency Flank pain/CVA tenderness z z Altered mental status, change in eating habits, gi symptoms z Nocturia z Suprapubic heaviness z +/- gross hematuria z Abdominal pain z Fever N/V Malaise Increased WBC z z z 4 Recurrent UTI Re-infection vs. Relapse Re-infection UTI that occurs more than 2 weeks after treatment of the first UTI z Risk Factors: Sexual intercourse Diaphragm/spermicide use z History of recurrent UTIs z First UTI at < 15 yo z Mother with a history of UTIs z Reduced levels of estrogen z z Re-infection No proven association with: Pre and post-coital voiding patterns z Frequency of urination z Delayed voiding habits z Wiping patterns z Douching z Use of hot tubs z Frequent use of pantyhose or tights z BMI z Relapsing UTI Within 2 weeks after treatment Resistance Nonadherence Inappropriate choice of antibiotic Complicating factors Symptomatic Abacteriuria Urethritis z C. trachomatis, N. gonorrhoeae, herpes simplex virus z Clinical Presentation: z Gradual onset, mild symptoms, vaginal discharge or bleeding, lower abdominal pain, new sexual partner, cervicitis, vulvovaginal herpetic lesions on exam Symptomatic Abacteriuria Vaginitis z Candida sp., Trichomonas vaginalis z Clinical Presentation z Vaginal discharge or odor, pruritus, external dysuria, no increased frequency or urgency, vulvovaginitis on exam 5 * Diagnosis Clinical presentation and: z z history alone, if no risk factors dipstick urinalysis Urinalysis pH RBC Leukocyte Esterase WBC Casts Nitrite Other: glucose, ketones, epithelial cells, color/ appearance Protein Urinalysis pH leuk. est. Nitrite Protein RBC WBC Casts 5.5 trace negative 30 mg negative 2/hpf negative Urinalysis pH leuk. est. Nitrite Protein RBC WBC Casts Urinalysis pH leuk. est. Nitrite Protein RBC WBC Casts 6.5 large positive >300 mg 2/hpf 14/hpf negative 7.0 large positive > 300 mg 5/hpf 18/hpf positive Urine Culture Acute uncomplicated cystitis in women z No culture needed Symptomatic patients z > 105 organisms/ml Asymptomatic women z > 105 organisms/ml Men z > 103 organisms/ml 6 Resistance Resistance Risk Factors z z z z z z z z Recent or current antibiotic use Age Diabetes Recent hospitalization History of UTI Cancer Chronic neurologic or urologic disorder Long term care facility Resistance Goals of Therapy Very low for fluoroquinolones and nitrofurantoin Prevent or treat systemic consequences of infection Increasing for TMP-SMX Eradicate the invading organism >28% for beta-lactams Prevent recurrence of infection Appropriate Therapy Well tolerated Safe Well absorbed Achieve high urinary concentrations Cover suspected pathogen Acute Uncomplicated Cystitis Single dose 3 day 7 Acute Uncomplicated Cystitis Acute Uncomplicated Cystitis Single dose therapy z 3-day therapy 65-100% cure rates Superior to single-dose Equal efficacy to 7-day therapy z Increase adherence, decrease cost and ADRs compared to 7-day z TMP/SMX DS #2 z Gatifloxacin 400mg z Fosfomycin 3g z z * 3-day Therapy TMP/SMX DS po bid TMP 200mg po bid Acute Uncomplicated Cystitis Short-course therapy inappropriate for: Complicated UTIs Patients with comorbidities z History of infections caused by resistant bacteria z z If E. coli resistance > 10-20% z Fluoroquinolones Case #1 CC: “burning when I pee” HPI: 27 yo WF comes into clinic stating that the pain started last night (12 hr ago) and has gotten worse today. Also has increased frequency. PMH: pregnant, exerciseinduced asthma FH: non-contributory Case #1 SH: - EtOH, - Tob, works as a fashion designer ALL: PCN Meds: Albuterol inhaler prn PE: negative Need a UA?? 8 Trimethoprim/ Sulfamethoxazole Case #1 U/A: Lg leuk. est., nitrite +, 20 wbc/hpf,protein -, 3+ bacteria 1 DS po BID x 3 days z The “standard therapy” for acute uncomplicated cystitis 7-10 day therapy for complicated cystitis Safe in 1st and 2nd trimester of pregnancy Fluoroquinolones Uncomplicated and Complicated Cystitis z 3-10 day therapy FQ-Drug Interactions Al, Mg, Ca, Fe Warfarin Theophylline, cyclosporine 1st line if TMP/SMX resistance is >10-20% Contraindicated in pregnancy Trimethoprim Uncomplicated and Complicated Cystitis 7 day therapy with TMP equal efficacy to 7 days of TMP/SMX Nitrofurantoin Uncomplicated and Complicated Cystitis Not recommended for 3 day therapy Useful if TMP/SMX resistant organism Safe in pregnancy Avoid use if Cr Cl < 50 ml/min 9 Beta-lactams Uncomplicated and Complicated Cystitis Urinary Analgesia Phenazopyridine Not recommended for short-course therapy z 100-200mg po TID x 2-3 days Less effective in eradication of bacteriuria and prevention of recurrence z Discolors urine z Not useful if Cr Cl < 50 ml/min Safe in pregnancy Treatment – Case #1 Complicated Cystitis Treatment for 7-10 days Monitor Resolution of symptoms in 24-48 hours F/U urine culture for identification and sensitivity of organism Repeat UA and culture only if symptoms not resolving Adverse effects of individual drug therapy Acute Pyelonephritis Upper UTI z Flank pain, CVA tenderness, abdominal pain, fever, N/V and malaise Hospitalization/IV antibiotics indicated: N/V Dehydration z Pregnancy z z 10 Uncomplicated vs. Complicated FQ x 14 days z * IV Therapy FQ FQ x 14 days Cipro x 7 days AG +/- ampicillin TMP/SMX DS x 14 days z 3rd z z or 4th generation cephalosporin z Ampicillin or Amox/Clav Gent/Tobra peak 6-10, trough < 2 µg/mL Cefotaxime, Ceftriaxone, Ceftazidime, Cefepime ß-lactam/ ß-lactamase inhibitor +/- AG x 14 days Gram + cocci z Gent/Tobra peak 3-6, trough < 2 µg/mL IV Æ PO Monitor Afebrile x 24 hours Symptoms should resolve in 48-72 hours F/U urine culture in 2 weeks to ensure eradication Renal function for antibiotic dosing and renal impairment Adverse effects of drug therapy Expect symptoms to resolve after 48-72 hours of therapy * Prostatitis Acute vs. Chronic Sudden onset Relapsing UTI Inflammation of the prostate gland Fever Difficulty urinating Rare if < 30 y.o. Tenderness Lower back pain Urinary symptoms Suprapubic tenderness 11 Risk Factors Sexual intercourse Indwelling catheters Urethral instrumentation Transurethral prostatectomy Prostatitis Pathogens E. coli K. pneumoniae P. mirabilis P. aeuriginosa Serratia marcescens 75% Altered prostate secretory function BPH Case #2 CC: fever, chills and frequent urination HPI: 57 yo white male with onset of symptoms 6 hours ago, but increasing in severity. PMH: Multiple UTIs, hyperlipidemia, BPH Case #2 SH: EtOH 4 beer/day and Tob 2ppd/60pyh ALL: NKDA Meds: Bactrim SS bid, Lipitor 10 QHS, Hytrin 5 QHs FH: non-contributory Case #2 PE: Tm 1028, very tender prostate upon rectal exam U/A: pH 8, Lg leuk est, 20 wbc/hpf, nitrite+, 1-2 rbc/hpf, trace protein, no casts Prostatitis Therapy Acute x 4 weeks Chronic x 4-6 weeks FQ z TMP/SMX z 12 Asymptomatic Bacteriuria Treatment – Case #2 Cipro 500 mg po BID z Urine culture > 105 of the same organism x 2 x 4 weeks Occurs in 4-10% of pregnant women * ASB Treatment of Asymptomatic Bacteriuria Risk Factors Pregnancy z Elderly z Female patients with diabetes z History of UTI z Lower education z Treat Do not treat Children Elderly Pregnancy (Catheterized) Diabetes UTIs in Catherized and Spinal Cord Injury Patients Most common nosocomial infection Acquisition rate is 5% per day >30 days, 78-95% incidence of bacteriuria 40% of SCI patients die of renal-related problems Treatment of ASB (Catheter & SCI) Remove catheter and monitor for symptoms 13 Symptomatic UTICatheterized/SCI Culture Remove/Change catheter Treat as complicated z * 7-14 days * UTI Prevention or eliminate use of spermicides and/or diaphragms Cranberry Juice Estrogen in postmenopausal women Antimicrobial prophylaxis IF: > 2 symptomatic UTIs over a 6 month period z > 3 over 12 months z Antimicrobial Prophylaxis Continuous Antimicrobial Prophylaxis Post-coital TMP/SMX SS TMP 100mg z Nitrofurantoin 50-100mg z Cephalexin 250mg z Norfloxacin 200-400mg z Ciprofloxacin 250mg Nitrofurantoin 50mg po QD z Trimethoprim 100mg po QD z TMP/SMX SS tab po QD or 3x/week z Norfloxacin 200 mg po 3x/week z z z Self-treatment Funguria Candida albicans z 40-65% C. tropicalis, C. krusei, C. glabrata Funguria Lower tract z Ascending route Upper tract z Hematogenous route 14 Funguria - Risk Factors Reversible z z z z Antibacterial therapy Indwelling urinary catheter Anatomical abnormalities Urinary tract manipulation/instrumentation Funguria Treatment Spontaneous Resolution z 23% Non-pharmacological z Reverse any reversible risk factors Irreversible z z z Female Diabetes Immunosuppressive therapy Funguria - Treatment Fluconazole z 200 mg x 1, then 100 mg/day x 4 days Fluconazole & Ampho B Advantages z High levels in urine z Good bioavailability z Sustained fungicidal effect z Ease of administration Amphotericin B Continuous low concentration z Intermittent high concentration z Disadvantages z Doesn’t clear funguria as rapidly z Optimum dosage and duration unknown Urinary Tract Infections Keri A. Mattes, Pharm.D., BCPS September 15, 2003 15