Urinary tract infection ประส ทธ อ พาพรรณ สาขาว ชาโรคต ดเช อ ภาคว ชาอาย รศาสตร คณะแพทยศาสตร มหาว ทยาล ยศ รนคร นทรว โรฒ

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1 Urinary tract infection ประส ทธ อ พาพรรณ สาขาว ชาโรคต ดเช อ ภาคว ชาอาย รศาสตร คณะแพทยศาสตร มหาว ทยาล ยศ รนคร นทรว โรฒ

2 Introduction Urinary tract infections (UTIs) are extremely common. Most frequent in infants, young women, and the elderly. UTIs are around twice as common in women as in men (except age < 1 yr ; vesicoureteral reflux and age > 50 yr ; BPH, calculi). 50 % of women having had an episode of UTI in their lifetime. -Am J Med 2002;113(1A):5S 13S. -Abhay Rané RD. Urinary Tract Infection: New York Dordrecht; Foxman B, UTI; self-reported incidence and associated costs. Ann Epidemiol 2000;10: Hooton TM, A prospective study of risk factors for symptomatic UTI in young women. N Engl J Med 1996;335:

3 Epidemiology Risk Factors for Urinary-tract Infections by Age Group Age in yrs. Females (% prevalence) Males (% prevalence) <1 Anatomic or functional urologic abn. (1%) Anatomic or functional urologic abn. (1%) 1-5 Congenital abn. ; vesicoureteral reflux (4.5%) Congenital abn., uncircumcised penis (0.5%) 6-15 Vesicoureteral reflux (4.4%) Vesicoureteral reflux (0.5%) Sexual intercourse, diaphragm use, spermicidal jelly, previous urinary tract infection (20%) Anatomic urologic abnormality. Insertive rectal intercourse. (0.5%) Gynecologic surgery, bladder prolapse (35%) Prostate hypertrophy, obstruction (20%) >65 Estrogen deficiency (40%) All of the above, incontinence, long term catherization, condom catheters (35%) Magdalena E. Sobieszczyk, Urinary Tract Infections (MID11)

4 Common definitions Bacteriuria Pyuria Significant bacteriuria Bacteria in urine, demonstrated by microscopy or quantitative culture UA ; WBC > 5 cells/hpf in unspin urine If pyuria but not found the bacteriuria = sterile pyuria - Specified quantitative count of bacteria (> 10 5 CFU/ml) CFU/ml (with symptoms and signs/ Male) Clin Infect Dis 2005;40(5): Abhay Rané RD. Urinary Tract Infection: New York ; 2013.

5 Common definitions Symptomatic bacteriuria Asymptomatic bacteriuria Urosepsis Bacteria in urine in the context of typical symptoms of UTI Bacteria in urine in the absence of symptoms of UTI -Women: 2 consecutive voided urine specimens (isolation of the same bacterial strain in quantitative counts > 10 5 cfu/ml) - Men: A single, clean-catch voided urine specimen (1 bacterial species isolated in a quantitative count > 10 5 cfu/ml) UTI with accompanying sepsis syndrome Clin Infect Dis 2005;40(5): Abhay Rané RD. Urinary Tract Infection: New York ; 2013.

6 Classifications Upper urinary tract infection (pyelonephritis) - Classically presenting (Fever, N/V, CVA tenderness) - Lower UTI symptoms may or may not be present. - Frequently cause urosepsis, and complications. - Most cases ; admission and IV ATB Drekonja DM, Johnson JR. Urinary tract infections. Prim Care Lower urinary tract infection (cystitis/urethritis) - Rare; Systemic manifestations (fever) And long-term sequelae. - Usually treated with oral antibiotics (high levels in the urine, but not necessarily achieving high systemic or tissue levels)

7 Classifications Uncomplicated UTIs -Lower UTI, pyelonephritis (no complicate) -Young women with healthy -Treat; narrower spectrum, oral antibiotics for short courses. Complicated UTIs - Children and men (considered) - Structural and functional abnormalities, metabolic disorders, or impaired immunity. - Protracted courses of broader spectrum ATB. - Multi-resistant organisms : more common. Recurrent UTIs ; > 25% of women (UTI) will experience a recurrence. - Relapses ; recur on cessation of treatment (same organism) - Reinfection ; a new causative organism. *Important to explore non-pharmacological methods to reduce recurrences*

8 Etiology Virus ; Adenovirus type 11 (hemorrhagic cystitis, transplant pt.) and type 21 Flores-Mireles AL, Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol 2015;13:

9 Most common route: 95% Enterobacteriaceae: E. Coli Entry of pathogen - Instruments -Sexual intercourse - Vesicoureteral reflux Pathogenesis Uncommon ; Staphylococcus aureus and Candida *Originate from oral sources in immunosuppressed patients. Rare ; - Bacteria from adjacent organs. - Conditions ; retroperitoneal abscesses and severe bowel infections. Brenner & Rector s The kidney, 8 th edition Niall F. Davis and Hugh D., The Pathogenesis of Urinary Tract Infections, september 2011.

10 Pathogenesis Biofilm formation -Protect their members from neutrophils, antibiotics and other stresses. - A physical barrier to antibiotic entry Flores-Mireles AL, Urinary tract infections. Nat Rev Microbiol 2015;13:

11 Pathogenesis Flores-Mireles AL, Urinary tract infections. Nat Rev Microbiol 2015;13: Symptoms of cystitis

12 Pathogenesis Colonization of the kidneys Host tissue damage by bacterial toxins ; Symptoms Bacteraemia ; Urosepsis Flores-Mireles AL, Urinary tract infections.nat Rev Microbiol 2015;13:

13 Microbial factors Host factors Environmental factors Risk factors Bacterial virulence factor ;adhesins (type 1 fimbriae, P fimbriae) Biofilm formation K antigen ; avoid phagocytosis Endotoxin (lipid A, core oligosaccharide, O-polysaccharide) Female sex: short urethra DM (increase risk) Smoking : associated with lower UTI in male. Presence of a catheter : disrupt glycosaminoglycan (bladder) Blockages in the urinary tract Urinary stone or BPH Pregnancy Uterus compress the ureter High progesterone level (decrease muscle tone of ureter and bladder induced vesicoureteral reflux ) Increase vaginal ph (decrease acidity) or change of normal floras sexual activity (increase E. coli colonization) cervical diaphragms or spermicides (toxic to normal flora) Menopause : estrogen deficiency (decrease vaginal acidity) (Lactobacilli ลดลง และ E. coli มาแทนท ) Gupta K, and Barbara W. Trautner. Harrison's Principles of Internal Medicine. 19 ed. New York: McGraw-Hill; ส เมธพ มลช ย ว. Journal of the Nephrology การต ดเช อทางเด นป สสาวะในผ ใหญ : THE NEPHROLOGY SOCIETY OF THAILAND; 2554.

14 Clinical manifestations letbehealthy.com website

15 Pyuria : high sensitivity, low specificity Laboratory findings Urinalysis (UA); simple, Good specimen (collection and transportation) Specimen collection Bacteriuria (microscopic exam or urine strip test) - Gram stain Suprapubic of uncentrifuged aspiration: urine gold standard 1 cell/oil but field invasive : low sensitivity : infant (< 10 5 cfu/ml) A single catheter - Nitrate Clean-catch test: poor sensitivity, midstream high technique specificity Enterobacteriaceae: limit to others organism Specimen transportation nitrate-reductase enzyme Nitrates nitrite (need time 4 hr) Plated within 2 h after collection - Leukocyte Refrigerated esterase test in 4 : C, high < 48 sensitivity hr and specificity Detect leukocyte esterase enzyme : the host s PMN leukocytes in the urine (cell intact or lysed) Clin Infect Dis 2004;38(8) // Clinical practice, acute uncomplicated UTI in women, 2012 S.guido, Asystematic review, The diagnosis of urinary tract infection, Dtsch Arztebl int 2010.

16 Diagnosis Clinical syndrome and significant bacteriuria Urine culture : gold standard : Results not available until hr. Dipstick method -cheaper, faster - more convenient. - most accurate Clin Infect Dis 2004;38(8)1150-8

17 Radiologic and urologic evaluation Men and women with persistent hematuria, recurrences pyelonephritis (same strain), persistent fever after proper Tx, complications or anatomy abnormality. Plain KUB: Urinary calcium stone, screen for abnormal anatomy. Ultrasound KUB : kidneys (hydronephrosis), bladder, and prostate (Operator dependent) Intravenous pyelogram (IVP) : Obstructions : cautions for GFR < 30, pregnancy CT scan : Stone (non-contrast), High sensitivity compare to ultrasound. Voiding cystourethrography (VCU) : detect vesicoureteral reflux Cystoscope : Stricture of urethra or hemorrhagic cystitis. Kawashima A, LeRoy AJ. Radiologic evaluation of patients with renal infections. Infect Dis Clin North Am 2003;17:433-56

18 Management Acute UTI symptoms -Dysuria -Frequency -Urgency Healthy women Not pregnant, clear history Woman with risk factors for STD Male with perineal Pelvic or prostatic pain Indwelling urinary catheter All other patients Consider uncomplicated cystitis -No U/C Consider uncomplicated UTI or STD -Dipstick, -UA and culture -STD evaluation, -pelvic exam Consider acute prostatitis -UA and culture -Urologic evaluation Consider CAUTI -Exchange or -remove catheter -UA and culture -H/C if fever present Consider complicated UTI -UA and culture -Modifiable anatomic -or functional abn. Gupta K, and Barbara W. Trautner. Harrison's Principles of Internal Medicine. 19 ed. New York: McGraw-Hill; 2015.

19 Management Acute onset of -Back pain -N/V -Fever -Possible cystitis symptoms Otherwise healthy woman who is not pregnant All other patients Consider uncomplicated pyelonephritis -Urine culture -Consider outpatient management Consider pyelonephritis -Urine culture -Blood culture Gupta K, and Barbara W. Trautner. Harrison's Principles of Internal Medicine. 19 ed. New York: McGraw-Hill; 2015.

20 Acute uncomplicated cystitis and pyelonephritis Complicated UTI Avoid unnecessary ATB use to prevent resistance and S/E collateral damage Treatment Appropriate empirical ATB initiation in serious infections Drug effectiveness Choice of regimen : antimicrobial resistance (uropathogenic strains of E. coli)

21 Acute uncomplicated cystitis: empirical treatment Goal ; rapid resolution of symptoms Not recommended if resistant > 20% Not recommended if resistant > 10% Clinical practice, acute uncomplicated UTI in women, 2012

22 National Antimicrobial Resistance Surveillance Center : 2015 Susceptibility report of UA specimen, Thailand Organism Total specimen AMPICILLIN CEFTRIAXONE MEROPENEM CIPROFLOXACIN LEVOFLOXACIN OFLOXACIN AMIKACIN GENTAMICIN Fosfomycin NITROFURANTOIN CO-TRIMOXAZOLE E. coli 1 7, (12641) 52.8 (11200) 99.2 (12336) 37.6 (12320) 38.8 (4874) 39.4 (2917) 97.1 (14821) 63.1 (16055) 98.3 (2592) 94.3 (1227) 39.3 (14568) NARST report website, 2015

23 Main pharmacokinetic parameters of quinolones (mean values) Lower UTI : OK // Upper UTI ; sense to this drug, Low MIC T. Mazzei et al. International Journal of Antimicrobial Agents 28S (2006) S35 S41

24 Acute uncomplicated pyelonephritis : empirical treatment Not recommended if resistant > 10% Not recommended if resistant > 20% Clinical efficacy Ciprofloxacin 7 days; 96% Outpatients - Not complicated infection Levofloxacin 5 days; 86% - No signs of systemic toxicity - Take oral medications, closely followed -Initial treatment :1 g of ceftriaxone or 24-hr dose of an aminoglycoside is recommended Clinical (Thailand). efficacy Admit 83% initial dose of iv ceftriaxone - Severe cases 92% if pathogen was susceptible - Treated with a parenteral antimicrobials 35% if pathogen not susceptible - Improvement 24-48h changed to an oral antimicrobials N Engl J Med 2003;349: and International CPG for treatment of acute uncomplicated cystitis and pyelonephritis in women, CID, 2011

25 Complicated UTI treatment Idividualized patient care; previous urine culture. Minimize the effects of obstruction / anatomic abnormality Aggressive use of antibiotics Appropriate use and dosages of broad-spectrum drugs (the antibiogram) Adjust antibiotics after the cultures and sensitivities have returned Clinical not improved, urologic evaluation Urol Clin North Am 2008;35(1):13-22

26 NARST report website, 2015

27 Prevention Behavioral counseling Reduction in frequency of intercourse Spermicide (condoms),diaphragm contraceptive recommend changing to another method Recommend urinate soon after intercourse drink fluids liberally not routinely delay urination wipe front to back after defecation avoid tight-fitting underwear avoid douching -The strongest risk factor -Strong risk factor -In case control studies *None of these : shown to be associated with a reduced risk of recurrent UTIs **Suggest; low risk and might be effective Clinical practice, acute uncomplicated UTI in women, 2012

28 Prevention Biologic mediators Cranberry juice, capsules or tablets Topical estrogen Adhesion blockers (D-mannose) -Inhibition of uropathogen adherence. -Cochrane review 2008: significantly reduced the incidence of UTIs at 12 months (RR 0.65, 95%CI ) -Cranberry juice fails to prevent recurrent UTI (RCT, Clin Infect Dis 2011) -Postmenopausal women: topical estrogen normalizes the vaginal flora and reduces the risk of recurrent UTIs. -Oral estrogens are not effective -Mannosides ; block adhesion; -D-mannose has not been evaluated in clinical trials Clinical practice, acute uncomplicated UTI in women, 2012

29 Management : Recurrent Acute Uncomplicated Cystitis - Not a preventive strategy. - U/C ; periodically before treatment to confirm presence of UTI and drug susceptibilities Quality of life Drug resistance Fluoroquinolones; Pregnancy category C - If UTIs are temporally related to coitus Clinical practice, acute uncomplicated UTI in women, First ; confirmed U/C negative 1-2 wk - Recommend ; 6-month trial - Discontinue ; 50% recurrences of cystitis.

30 UTI in pregnancy Asymptomatic bacteriuria : occur in 2-10%. If untreated mothers : 30% acute cystitis, 50% acute pyelonephritis (low birthweight and preterm birth). Dipstick testing: not sufficiently. (U/C should be the investigation of choice) ATB treatment is effective : 7 days course Ampicillin, and the cephalosporins : relatively safe. Avoid : Sulfonamides 1 st trimester (possible teratogenic effect) and near term (kernicterus), Fluoroquinolones (cartilage development) A national clinical guideline, Management of suspected bacterial urinary tract infection in adults, july 2012.

31 UTI in special conditions Post-coital UTI Pregnancy Men Catheter-associated UTI Infected stone Cystic kidney Renal tuberculosis Candiduria Xanthogranulomatous pyelonephritis Transplant kidney Vaccines ATB prophylaxis for UTI after removal of urinary catheter: meta-analysis,2013

32 Conclusions Urinary tract infections (UTIs) ; common diseases. Frequently affect ; women (due to a shorter urethra) Diagnosis ; clinical symptoms + significant bacteriuria (urine culture). Antibiotics are often effective therapy, antibiotic resistance is increasing. Pyuria, Bacteriuria Antibiotic use Colonization Gupta K, and Barbara W. Trautner. Harrison's Principles of Internal Medicine. 19 ed. New York: McGraw-Hill; 2015.

33 THANK YOU

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35 Susceptibility report : UA specimen, Thailand, 2015 NARST report website, 2015