Urinary Tract Infections. Keri A. Mattes, Pharm.D., BCPS September 15, 2003

Transcription

1 Urinary Tract Infections Keri A. Mattes, Pharm.D., BCPS September 15, 2003

2 Urinary Tract Infections 7 million episodes of acute cystitis and 250,000 episodes of pyelonephritis annually in the U.S.

3 Epidemiology Women 1 in 3 infected before age 24 50% have at least one during their lifetime Men Incidence is very low prior to age 50

4 Epidemiology 7 million office visits 1 million ER visits 100,000 hospitalization in 1997

5 Epidemiology Cathether-associated UTI Most common nosocomial infection >1 million cases in hospitals and NHs Elderly 2 nd most common form of infection 25% of all infections

6 Implications Financial Community acquired UTI = $1.6 billion Nosocomial UTI = >$400 million

7 Implications Medical Bacteremia Symptoms Pregnancy Pyelonephritis, premature delivery, fetal complications and mortality, PIH Pediatrics Impaired renal function, renal scarring, ESRD

8 Assess the Patient Classify by: Location Complications Organisms Pathophysiology Host defense mechanisms, virulence factors Risk Factors Clinical Presentation

9 * Classification of UTIs Lower Tract Urethritis Cystitis Prostatitis Epididymitis Upper Tract Pyelonephritis Intrarenal/perinephric abscess

10 * Complicating Factors Male Sex Elderly Indwelling urinary catheter or recent instrumentation Obstruction/Stone Prostatic Hypertrophy Pregnancy Diabetes Immunosuppression Neurologic Deficit Childhood UTI Recent antibiotic use Symptoms for > 7 days Hospital-acquired infection Presents at an urban ER

11 Etiology - Uncomplicated Infections E. coli 80% Staph. Saprophyticus 10-15% Klebsiella less common pneumoniae,proteus sp., Enterobacter and Enterococcus sp.

12 * Etiology Complicated Infections E. coli <50% Enterococcus fecalis Proteus sp. K. pneumoniae Serratia marcescens Enterobacter sp. P. aeruginosa Staph aureus Enterococci Candida sp.

13 Etiology - Pediatrics E. coli Proteus sp. Klebsiella sp. Serratia marcescens

14 Etiology - Elderly E. coli Polymicrobial

15 Etiology - Diabetes Klebsiella sp. Enterococcus E. coli Candida sp.

16 Etiology Spinal Cord Injury or Catheterized E. coli Pseudomonas aeruginosa Proteus mirabilis Staph. aureus Enterococci Candida sp.

17 Etiology-HIV/AIDS Enterococcus sp.

18 * Pathophysiology Ascending Hematogenous Lymphatic

19 * Defense Mechanisms Low ph Extremes in osmolality High urea concentration High Organic Acid Conc. Prostatic secretions Stimulation of bladder emptying/diuresis Antiadherence Glycosaminoglycan layer Tamm-Horsfall protein Immunoglobulins IgG and IgA

20 * Virulence Ability to adhere to epithelial cells Bacterial fimbrae Hemolysin Bacterial Glycocalyx Urease Production

21 * 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

22 Why women > men? Short Urethra Proximity of urethra to perirectal area Use of spermicides and diaphragms Lack of prostatic fluid

23 Clinical Presentation Lower Tract Dysuria Urgency Frequency Nocturia Suprapubic heaviness +/- gross hematuria Upper Tract Lower tract symptoms Flank pain/cva tenderness Abdominal pain Fever N/V Malaise Increased WBC

24 Clinical Presentation Elderly Typical symptoms may be absent Altered mental status, change in eating habits, gi symptoms

25 Recurrent UTI Re-infection vs. Relapse

26 Re-infection UTI that occurs more than 2 weeks after treatment of the first UTI Risk Factors: Sexual intercourse Diaphragm/spermicide use History of recurrent UTIs First UTI at < 15 yo Mother with a history of UTIs Reduced levels of estrogen

27 Re-infection No proven association with: Pre and post-coital voiding patterns Frequency of urination Delayed voiding habits Wiping patterns Douching Use of hot tubs Frequent use of pantyhose or tights BMI

28 Relapsing UTI Within 2 weeks after treatment Resistance Nonadherence Inappropriate choice of antibiotic Complicating factors

29 Urethritis Symptomatic Abacteriuria C. trachomatis, N. gonorrhoeae, herpes simplex virus Clinical Presentation: Gradual onset, mild symptoms, vaginal discharge or bleeding, lower abdominal pain, new sexual partner, cervicitis, vulvovaginal herpetic lesions on exam

30 Vaginitis Symptomatic Abacteriuria Candida sp., Trichomonas vaginalis Clinical Presentation Vaginal discharge or odor, pruritus, external dysuria, no increased frequency or urgency, vulvovaginitis on exam

31 Diagnosis Clinical presentation and: history alone, if no risk factors dipstick urinalysis

32 * Urinalysis ph Leukocyte Esterase Nitrite Protein RBC WBC Casts Other: glucose, ketones, epithelial cells, color/ appearance

33 Urinalysis ph 5.5 leuk. est. trace Nitrite negative Protein 30 mg RBC negative WBC 2/hpf Casts negative

34 Urinalysis ph 7.0 leuk. est. large Nitrite positive Protein > 300 mg RBC 5/hpf WBC 18/hpf Casts positive

35 Urinalysis ph 6.5 leuk. est. large Nitrite positive Protein >300 mg RBC 2/hpf WBC 14/hpf Casts negative

36 Urine Culture Acute uncomplicated cystitis in women No culture needed Symptomatic patients > 10 5 organisms/ml Asymptomatic women > 10 5 organisms/ml Men > 10 3 organisms/ml

37 Resistance Risk Factors Recent or current antibiotic use Age Diabetes Recent hospitalization History of UTI Cancer Chronic neurologic or urologic disorder Long term care facility

38 Resistance

39 Resistance Very low for fluoroquinolones and nitrofurantoin Increasing for TMP-SMX >28% for beta-lactams

40 Goals of Therapy Prevent or treat systemic consequences of infection Eradicate the invading organism Prevent recurrence of infection

41 Appropriate Therapy Well tolerated Safe Well absorbed Achieve high urinary concentrations Cover suspected pathogen

42 Acute Uncomplicated Single dose Cystitis 3 day

43 Acute Uncomplicated Cystitis Single dose therapy % cure rates TMP/SMX DS #2 Gatifloxacin 400mg Fosfomycin 3g

44 Acute Uncomplicated 3-day therapy Cystitis Superior to single-dose Equal efficacy to 7-day therapy Increase adherence, decrease cost and ADRs compared to 7-day

45 3-day Therapy TMP/SMX DS po bid TMP 200mg po bid If E. coli resistance > 10-20% Fluoroquinolones

46 * Acute Uncomplicated Cystitis Short-course therapy inappropriate for: Complicated UTIs Patients with comorbidities History of infections caused by resistant bacteria

47 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

48 Case #1 SH: - EtOH, - Tob, works as a fashion designer ALL: PCN Meds: Albuterol inhaler prn PE: negative Need a UA??

49 U/A: Lg leuk. est., nitrite +, 20 wbc/hpf,protein -, 3+ bacteria Case #1

50 Trimethoprim/ Sulfamethoxazole 1 DS po BID x 3 days The standard therapy for acute uncomplicated cystitis 7-10 day therapy for complicated cystitis Safe in 1 st and 2 nd trimester of pregnancy

51 Fluoroquinolones Uncomplicated and Complicated Cystitis 3-10 day therapy 1 st line if TMP/SMX resistance is >10-20% Contraindicated in pregnancy

52 FQ-Drug Interactions Al, Mg, Ca, Fe Warfarin Theophylline, cyclosporine

53 Trimethoprim Uncomplicated and Complicated Cystitis 7 day therapy with TMP equal efficacy to 7 days of TMP/SMX

54 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

55 Beta-lactams Uncomplicated and Complicated Cystitis Not recommended for short-course therapy Less effective in eradication of bacteriuria and prevention of recurrence Safe in pregnancy

56 Urinary Analgesia Phenazopyridine mg po TID x 2-3 days Discolors urine Not useful if Cr Cl < 50 ml/min

57 Treatment Case #1

58 Complicated Cystitis Treatment for 7-10 days

59 Monitor Resolution of symptoms in 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

60 Acute Pyelonephritis Upper UTI Flank pain, CVA tenderness, abdominal pain, fever, N/V and malaise Hospitalization/IV antibiotics indicated: N/V Dehydration Pregnancy

61 Uncomplicated vs. Complicated FQ x 14 days Cipro x 7 days FQ x 14 days TMP/SMX DS x 14 days Ampicillin or Amox/Clav x 14 days Gram + cocci

62 * IV Therapy FQ AG +/- ampicillin Gent/Tobra peak 6-10, trough < 2 µg/ml 3 rd or 4 th generation cephalosporin Cefotaxime, Ceftriaxone, Ceftazidime, Cefepime ß-lactam/ ß-lactamase inhibitor +/- AG Gent/Tobra peak 3-6, trough < 2 µg/ml

63 IV PO Afebrile x 24 hours Expect symptoms to resolve after hours of therapy

64 Monitor Symptoms should resolve in hours F/U urine culture in 2 weeks to ensure eradication Renal function for antibiotic dosing and renal impairment Adverse effects of drug therapy

65 Prostatitis Inflammation of the prostate gland Rare if < 30 y.o.

66 * Acute vs. Chronic Sudden onset Fever Tenderness Urinary symptoms Relapsing UTI Difficulty urinating Lower back pain Suprapubic tenderness

67 Risk Factors Sexual intercourse Indwelling catheters Urethral instrumentation Transurethral prostatectomy Altered prostate secretory function BPH

68 Prostatitis Pathogens E. coli 75% K. pneumoniae P. mirabilis P. aeuriginosa Serratia marcescens

69 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 FH: non-contributory

70 Case #2 SH: EtOH 4 beer/day and Tob 2ppd/60pyh ALL: NKDA Meds: Bactrim SS bid, Lipitor 10 QHS, Hytrin 5 QHs

71 Case #2 PE: Tm 102 8, 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

72 Prostatitis Therapy Acute x 4 weeks Chronic x 4-6 weeks FQ TMP/SMX

73 Treatment Case #2 Cipro 500 mg po BID x 4 weeks

74 Asymptomatic Bacteriuria Urine culture > 10 5 of the same organism x 2 Occurs in 4-10% of pregnant women

75 ASB Risk Factors Pregnancy Elderly Female patients with diabetes History of UTI Lower education

76 * Treatment of Asymptomatic Bacteriuria Treat Children Do not treat Elderly Pregnancy (Catheterized) Diabetes

77 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

78 Treatment of ASB (Catheter & SCI) Remove catheter and monitor for symptoms

79 Symptomatic UTI- Culture Catheterized/SCI Remove/Change catheter Treat as complicated 7-14 days

80 * 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 > 3 over 12 months

81 * Antimicrobial Continuous Prophylaxis Nitrofurantoin 50mg po QD Trimethoprim 100mg po QD TMP/SMX SS tab po QD or 3x/week Norfloxacin 200 mg po 3x/week

82 Post-coital Antimicrobial Prophylaxis TMP/SMX SS TMP 100mg Nitrofurantoin mg Cephalexin 250mg Norfloxacin mg Ciprofloxacin 250mg Self-treatment

83 Funguria Candida albicans 40-65% C. tropicalis, C. krusei, C. glabrata

84 Funguria Lower tract Ascending route Upper tract Hematogenous route

85 Funguria - Risk Factors Reversible Antibacterial therapy Indwelling urinary catheter Anatomical abnormalities Urinary tract manipulation/instrumentation Irreversible Female Diabetes Immunosuppressive therapy

86 Funguria - Treatment Spontaneous Resolution 23% Non-pharmacological Reverse any reversible risk factors

87 Funguria - Treatment Fluconazole 200 mg x 1, then 100 mg/day x 4 days Amphotericin B Continuous low concentration Intermittent high concentration

88 Fluconazole & Ampho B Advantages High levels in urine Good bioavailability Sustained fungicidal effect Disadvantages Doesn t clear funguria as rapidly Optimum dosage and duration unknown Ease of administration

89 Urinary Tract Infections Keri A. Mattes, Pharm.D., BCPS September 15, 2003