12/6/19 Updates in miss Diagnosis & Treatment of UTIs EE.gg Brian S. Schwartz, MD Professor of Medicine m a UCSF, Division of Infectious Diseases 1 Lecture outline • Upper and lower tract infections • Asymptomatic bacteriuria • Recurrent UTIs EE.gg m a 2 1
12/6/19 Lecture outline • Upper and lower tract infections • Asymptomatic bacteriuria • Recurrent UTIs EE.gg m a 3 Case • 27 y/o female presents to your clinic with 4 days of dysuria and frequency . Denies vaginal discharge or pelvic pain • First episode of symptoms. Lives in SF. • Urinalysis: 3+ Leukocyte esterase 4 2
12/6/19 Do you obtain a urine culture? A.Yes B.No 5 Empiric antibiotic? A. Nitrofurantoin x 5 days B. TMP-SMX x 5 days C. Ciprofloxacin x 3 days D. Cefazolin x 7 days 6 3
12/6/19 When to get a urine culture for uncomplicated cystitis? • Most cases susceptible E coli, culture not needed • But culture if… – Complicated UTIs (pyelonephritis) – Recurrent UTIs – Recent antibiotic exposure – Healthcare exposure – High local rates of resistance Hooton TM. NEJM. 2012 7 UCSF E. coli urine isolates treatment. Drug Percent susceptible Amoxicillin/clavulanate (when used for lower urinary tract 68% infections) Cephalexin (when used for lower urinary tract infections) 90% TMP/SMX 69% Ciprofloxacin 73% Nitrofurantoin* 97% 8 4
12/6/19 IDSA guidelines for cystitis • Nitrofurantoin : 100 mg PO BID x 5 days • TMP-SMX DS : 1 tab PO BID x 3 days – avoid if resistance >20%, recent usage • Fosfomycin: 3 gm PO x 1 Gupta K. CID 2011 9 Nitrofurantoin Effective in Elderly? • Study pop: women mean age 79, GFR 38 • Evaluated for (FQ/TMP-SMX) vs. nitrofurantoin Treatment failure Low GFR High GFR Nitrofurantoin 516/3,739 (13.8%) 7,759/70,758 (11%) TMP-SMX 184/1463 (12.6%) 3,683/37,665 (9.8%) FQ (cipro/nor) 264/4021 (6.5%) 4447/74211 (6.0%) Singh N. CMAJ. 2015 10 5
12/6/19 Nitrofurantoin safe in elderly? • Age > 65 years with Dx cystitis • N=13,421 (2007-12) • Evaluated for nitrofurantoin use ≈ lung injury • Nitrofurantoin exposure ≠ lung injury • Chronic use ≈ lung injury (aRR 1.53 [1.04-2.24]) Santos JM. JAGS. 2016 11 Take home on nitrofurantoin • Less efficacious than FQs • Unlikely dangerous for Rx • Danger increase for chronic suppression 12 6
12/6/19 1-dose Fosfomycin a good choice? • Study: RCT (513 patients enrolled) • Patients: Women > 18 w/ symptoms + UA • Nitrofurantoin x 5 days vs. Fosfomycin x 1 day Cure Nitrofurantoin Fosfomycin Clinical (28d) 171/244 (70%) 139/241 (58%) p=0.004 Micro 129/175 (74%) 103/163 (63%) p=0.04 Huttner A. JAMA. 2018 13 Case continued… • Started empiric TMP-SMX (low resistance area) • Culture returns next day: • >50% of GBS resistant to TMP-SMX • What do you do next? 14 7
12/6/19 Utility of the midstream void culture? • > 200 pre-menopausal women w/ dysuria • Midstream void and catheter specimen • Cultures positive – 99% midstream – 74% catheter specimens Hooton TM. NEJM. 2013 15 Utility of the midstream void culture? • E. coli, Klebsiella, S. saprophyticus – Strong correlation (10 2 ) with catheter specimen • >1 organism in 86% midstream specimens – When E. coli in midstream, often in catheter specimen • Enterococcus and Group B strep (10% cultures) – Nearly never found in catheter specimens – 61% had E. coli grew from catheter cultures • Midstream cultures going to change treatment? Hooton TM. NEJM. 2013 16 8
12/6/19 Case continued… • Started empiric TMP-SMX (low resistance area) • Culture returns next day: • >50% of GBS resistant to TMP-SMX • What do you do next? No change 17 Case E. coli > 1x10 6 CFU/mL •77 y/o female presents Amoxicillin – R with 4 days of dysuria and TMP-SMX – R Nitrofurantoin – R frequency. Cephalexin – R •No fever, no flank pain. Ceftriaxone – R Gentamicin - S •Multiple UTIs in past 4 mos Ertapenem - S – UA micro: > 50 WBC/hpf Meropenem - S 18 9
12/6/19 E. coli > 1x10 6 CFU/mL Next steps? Amoxicillin – R TMP-SMX – R A. IV Cefepime Nitrofurantoin – R Cephalexin – R B. IV Ertapenem Ceftriaxone – R Gentamicin - S C. PO Augmentin Ertapenem - S Meropenem - S D. PO Fosfomycin E. Intravesicular gentamicin 19 ESBL producing GNR infections in hospitalized patients in US CDC 20 10
12/6/19 High-Risk for Resistant Bacteria (ESBL)? • Prior resistant bacteria • Recent hospitalization • Recent FQ/B-lactam • Recent travel to Asia/Middle East/Africa 21 Oral antibiotics active against ESBLs 100 % isolates susceptible n=46 80 60 40 20 0 Fosfomycin Nitrofurantoin Doxycycline Cipro Amox-clav Prakash V. AAC 2009 22 11
12/6/19 Fosfomycin (Monurol) • Activity against Gram pos and neg • FDA approved for Rx of uncomplicated UTI • Treatment for complicated infections : – 3 gm (mixed in 4 oz H 2 O) Q2 days for 7-14 d 23 Case A. Ceftriaxone IV 32 y/o women presents with B. Moxifloxacin PO fever, flank pain, C. Nitrofurantoin PO and positive D. Cefpodoxime PO UA? 24 12
12/6/19 Empiric treatment of pyelonephritis • Recommended – Cipro 500 mg PO/IV q12 ( Levo ok, not Moxi ) – Ceftriaxone 1 gm IV q24 • Not recommended – TMP-SMX – Nitrofurantoin – Cefpodoxime • Health-care associated: – Ertapenem (Meropenem if critical ill or h/o pseudomonas) 25 Lecture outline • Upper and lower tract infections • Asymptomatic bacteriuria • Recurrent UTIs EE.gg m a 26 13
12/6/19 Case • 65 y/o female w/ DM presents to clinic for routine evaluation. She has been feeling well. A urinalysis is sent to look for proteinuria and the lab processes for culture because bacteria are seen • UA: WBC-0, RBC-0, Protein-300 • The next day you are called because the urine culture has >100,000 Klebsiella pneumoniae 27 What do you recommend? A. No antibiotics indicated B. Ciprofloxacin and await susceptibilities C. Repeat culture in 1 week and if bacteria still present then treat 28 14
12/6/19 Case • 65 y/o female w/ DM presents to clinic for routine evaluation. She has been feeling well. A UA is sent to look for proteinuria and when the leukocyte esterase is +++, the lab sends culture • UA: WBC->50 , RBC-0, Protein-300 • The next day you are called because the urine culture has >100,000 Klebsiella pneumoniae 29 What do you recommend? A. No antibiotics indicated B. Ciprofloxacin and await susceptibilities C. Repeat culture in 1 week and if bacteria still present then treat 30 15
12/6/19 Asymptomatic bacteriuria • Bacteriuria without symptoms • Pyuria present > 50% of patients 31 Asymptomatic bacteriuria is common Pre-menopausal women 1-5% Pregnant women 2-10% Post-menopausal women, 50-70 yrs 3-9% Diabetics 9-27% Elderly in LTC facilities (women; men) 15-50% Pts with spinal cord injuries 23-89% Pts undergoing HD 28% Pts with indwelling catheters 25-100% Nicolle. CID. 2005 32 16
12/6/19 Which patient(s) should be treated for asymptomatic bacteriuria? A. Patients with T2 paralysis B. Patients > 75 years of age C. Patient 1 year post renal transplant D. Patient undergoing TURP 33 Which patient(s) should be treated for asymptomatic bacteriuria? • Clear benefit – Pregnant women – Patients undergoing traumatic urologic interventions with mucosal bleeding (TURP) • Possible benefit – Neutropenic Nicolle. CID. 2005 34 17
12/6/19 Who does not benefit from Rx of asymptomatic bacteriuria? • Premenopausal (non-pregnant) women • Postmenopausal women • Institutionalized men and women • Patients with spinal cord injuries • Patients with urinary catheters • Diabetics Asscher AW. BMJ. • Renal transplant recipients 1969; Abrutyn E. J Am Soc Ger. 1996; 35 Treatment of asymptomatic bacteriuria in diabetic women • Placebo controlled, RCT (N=105) • Diabetic women w/ asymptomatic bacteriuria • Intervention: Antimicrobial vs. placebo x 14d • 1 ° endpoint: Time to 1 st symptomatic UTI • 42% Rx vs. 40% placebo , p=0.42 Harding GKM. NEJM 2003; Cai T. Clin Infect Dis. 2015 36 18
12/6/19 Asymptomatic bacteriuria post renal transplant • > 2 mo post transplant + ASB, N=112 • RCT: Antibiotics vs. placebo • Primary outcome: Pyelonephritis – 7.5% vs. 8.4% (OR 0.88, 95% CI 0.22-3.47) • No significance difference: C diff, rejection Origuen J. AJT. 2016 37 Bacteriuria with some concern for infection (fever, leukocytosis, altered MS, etc…) 1. No pyuria -- not an infection 2. Could it be blood, lungs, meds, etc. 3. Candiduria – usually not cause of infection 4. Consider UTI as a diagnosis of exclusion 38 19
12/6/19 Lecture outline • Upper and lower tract infections • Asymptomatic bacteriuria • Recurrent UTIs EE.gg m a 39 Case 65 y/o woman has had 3 UTIs in the last 6 months. What would be your next step to prevent recurrent UTIs? A. Daily suppressive nitrofurantoin B. Intra-vaginal estrogen C. Cranberry tablets D. Urology consult 40 20
12/6/19 Recurrent UTIs in women • 20-30% will have a recurrent UTI in 6 mo • Risk factors: – Frequent sex, spermicide, new partner – Genetic: Age of 1 st UTI ≤ 15 yrs; Mother h/o UTIs – Urinary incontinence Scholes D. JID. 2000; Raz R. CID 2000. 41 Pathogenesis of UTI in women Prevent vaginal colonization w/ uropathogens Prevent growth of uropathogens in bladder Correct anatomic/neurologic problems 42 21
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