Presentation on theme: "UTI 101: Antimicrobial agents, duration and prophylaxis April 30, 2012"— Presentation transcript:
1UTI 101: Antimicrobial agents, duration and prophylaxis April 30, 2012 Jennifer J. Schimmel, MDBaystate Medical CenterDivision of Infectious Diseases and Antimicrobial StewardshipFocus on older patients, especially in a facility
2ObjectivesDescribe the agents used for treating bacterial urinary tract infections (UTI’s) and understand how to choose the most appropriate agentUnderstand the appropriate duration of therapy and monitoringUnderstand the options for prophylaxis of recurrent UTIFocus on the elderly in long term care
3BackgroundUTI is one of the most common infections in the elderly in the community and in long-term careTwo problems: overdiagnosis and overtreatmentSubsequent issues:C. difficileAntibiotic resistanceWhat’s important?Proper diagnosisAppropriate antibiotic choice and duration
4Defining the Problems Lower UTI: infection in bladder and/or urethra Uncomplicated UTI: lower UTI ANDNot pregnantNo urinary tract abnormalitiesNo indwelling urinary deviceComplicated UTI:Upper UTI (systemic symptoms, extension beyond urethra/bladder)Functional or structural urinary tract abnormalityUTI in menUrinary catheter (CA-UTI)Older female patientsMany have functional or structural abnormalitiesBacter: usu 10 to the 5..unlikely to be contaminated, but still doesn’t mean clinically significant. May be asymptomatic and not need rx % of women and 15-40% of men without catheters in NH have asymptomatic bacteriuria Furthermore, lower levels may be significant.Pyuria: doesn’t represent disease, can be seen with or w/o bacteria. Associated with urinary catheter, stone, tumor, infection.Lower UTI: not associated with signs of systemic infectionUncomplicated UTI: this is where 3 day short course recs are applicable, SO NOT MALES, NOT CA-UTI and not systemic symptomsCA-UTI: greatest risk for infection with catheter is the duration of catheterization. Indwelling ur cath almost universally leads to bacteriuria within 3-4 days due to formation of biofilm between catheter and urethral mucosa.Rates of infection are high in postmenopausal women because of bladder or uterine prolapse causing incomplete bladder emptying; loss of estrogen with attendant changes in vaginal flora (notably, loss of lactobacilli), which allows periurethral colonization with gram-negative aerobes, such as E coli; and higher likelihood of concomitant medical illness, such as diabetes.
5Most Common Organisms E.coli Other gram-negatives Klebsiella pneumoniaeProteus mirabilisStaphylococcus saprophyticusEnterococcus faecalisIn the elderly: EcoliE coli causes 70-95% of both upper and lower UTIs. Various organisms are responsible for the remainder of infections, including S saprophyticus, Proteus species, Klebsiella species, Enterococcus faecalis, other Enterobacteriaceae, and yeastWhere do bacteria come from that cause urinary tract infections?GI tractPerineumManipulation (catheter/procedure)
6Microbiology in Nursing Homes New Haven, CT5 Nursing Homes May551 patients, presumed UTIDas ICHE Nov 2009Das R et al. ICHE 2009;30(11):
7Case 175 year old woman s/p recent vertebral fracture, in NH for past 2 weeks, no prior UTI’sNow several days of urinary frequency, urgency, burningNo fevers or back painU/a with significant pyuriaStarted empirically on ciprofloxacin
8What to use empirically? Take into account most likely uropathogensPatient FactorsOther medications/interactionsAllergiesOther past infectionsOther medical problems (renal insufficiency, C.diff, etc)Threshold for failureLocal epidemiologyCostEmpirically: define
9Antibiogram Helps to determine best choices for empiric therapy Helps with empiric choices, but still need to take into account the clinical pictureMostly concerned about Gram-negative bacteriaFor example for Bactrim for acute cystitis (TRIM-SULFA), if local resistance rates of uropathogens causing UTI do not exceed 20% (or if sensitivity of organism know). Threshold of 20% is based on expert opinion derived from clinical, in vitro and mathematical modeling studies.BUT for pyelonephritis, threshold is lower, if 10% resistance to cipro, expert opinion recommends additional or alternative agent
10Antimicrobial Susceptibilities from Nursing Home Residents in New Haven, CT Das R et al. ICHE 2009;30(11):
11Case 1: Culture Data What can you do now? Collect date: 04/15/12 08:35Result Status: Auth (Verified)Result Date: 04/17/12 09:33SPECIMEN DESCRIPTION : URINE CLEAN CATCH/MIDSTREAMSPECIAL REQUESTS : NONECULTURE : >100,000 COL/ML ESCHERICHIA COLITEST PERFORMED AT BAYSTATE MEDICAL CENTER, SPRINGFIELD, MAREPORT STATUS : FINAL 04/17/2012ORGANISM >100,000 COL/ML ESCHERICHIA COLIMETHOD MIN. INHIB. CONC. (MCG/ML)AMPICILLIN RESISTANTAMPICILLIN/SULBACTAM INTERMEDIATEAMOXICILLIN/CLAVULAN SUSCEPTIBLECEFAZOLIN SUSCEPTIBLECEFEPIME SUSCEPTIBLECEFTRIAXONE SUSCEPTIBLECIPROFLOXACIN SUSCEPTIBLEERTAPENEM SUSCEPTIBLEGENTAMICIN SUSCEPTIBLELEVOFLOXACIN SUSCEPTIBLEMEROPENEM SUSCEPTIBLENITROFURANTOIN SUSCEPTIBLEPIPERACILLIN/TAZOBAC SUSCEPTIBLETRIMETH/SULFAMETHOX SUSCEPTIBLETETRACYCLINE SUSCEPTIBLEHelp with narrowing/finalizing therapy
12Seeking the perfect antibiotic… Needs to get into urinary tractAnd sometimes the prostateTreat specific organismNarrowest spectrum possibleMinimize adverse effectsAvoid drug interactionsNo allergyComplianceCostOral option?
13Case 275 year old woman with well-controlled Crohn’s disease on mesalamine, admitted with syncopal eventFound to have conduction abnormalityAllergy to penicillin (unknown)Has pacemaker placed (perioperative Clindamycin)2 days after procedure still has unexplained leukocytosis with WBC 13no obvious source of infection, no urinary symptoms, no diarrhea, CXR unremarkable, u/a with 1 wbc
14Case 2 Urine culture pending at the time of discharge to rehab What would be the next best step?A) Discharge on 5 days of Levofloxacin for possible UTIB) Follow off antibioticsC) Keep her in the hospital and repeat u/a tomorrowD) Treat with Ceftriaxone 1g IV and additional antibiotics base on culture dataE) Treat with Tobramycin 5mg/kg and additional antibiotics based on culture dataB is best option…but what really happened is A. Culture negative, unclear if result followed up at NH. Then readmitted within 2 weeks for Cdiff (and I just saw this week with her probably 3rd recurrence…
15C. diff-o-genicity High risk Medium risk Low risk Carbapenems 2nd – 4th generation cephalosporinsFluoroquinolonesClindamycinMedium riskPenicillins1st generation cephalosporinsMacrolidesAztreonamLow riskAminoglycosidesVancomycinDaptomycinNitrofurantoinLinezolidTrimethoprim/sulfamethoxazoleTetracyclinesRifampinColistinFosfomycinMullane et al. Clin Infect Dis. 2011;53:
16Recommendations from the Guidelines In this case, there was no UTI to treat, but what if there is a UTI to treat?Unfortunately, no specific guidelines for post-menopausal, NH population.
18Uncomplicated UTI: Lower Tract Brings up several issues in the elderly and LTC:Are elderly/postmenopausal women uncomplicated?What about if diabetes without urologic issues? No clear answers from the guidelines, so probably depends on clinical factors/illness/host, etc…Take home: trying to avoid so much FQ use..March NEJMAuthor also of IDSA guidelinesProvides simple clearly uncomplicated caseAddresses that “complicated UTI” is a heterogeneous group: risks of infection and treatment failure vary. Current classification schemes are overly simplistic.Suggests that Short course regimens are likely to be effective for mild-mod cystitis in healthy, ambulatory, compliant women who are elderly, have CA-UTI, pregnant or mild DMNF and fosfomycin: minimal resistance (possibly because of limited effects on fecal flora), minimal collateral damage “ecological effects”: such as the selection of drug-resistant organism and colonization or infection with multidrug resistant organisms.Collateral damage is important to consider esp with uUTI: minimal risk of progression to tissue invasion or sepsis (25-50% will get better if not treated or if treated with drug that doesn’t have in vitro activity vs pathogen)NF: and Fosfomycin avoid if early pyelonephritis.Pivmecillinam: beta lactam with specificity for urinary tract, minimal resistance and collateral damage, not available in US or CanadaGupta K et al. Clinical Infectious Diseases 2011;52(5):e
19Nitrofurantoin (Macrobid, Macrodantin) Minimal “collateral” damageDRUG INTERACTIONSMinimalConcomitant administration of a magnesium trisilicate antacid may decrease the absorption of nitrofurantoinNitrofurantoin may reduce the effect of quinolone antibioticsFluconazole: increased risk of pulmonary and hepatic toxicityAvoid if creatinine clearance less than 60Due to potentiation of adverse effectsCommon side effects: nausea, headacheOther serious adverse effects:Peripheral neuropathyPulmonary hypersensitivityHepatoxicityDecreased renal functionHemolytic anemiaPulm hypersens: maybe more in elderly, esp 1st week and with chronic rx (>6mos)Example of cr cl <60 pretty much any women over age 70 even with nl cr (1).
20Fosfomycin Issues: Minimal resistance Minimal collateral damage High urinary levelsProlonged bactericidal effectMinimal drug interactionsNot always availableSusceptibility data not routinely availableRole for treatment of resistant organisms such as ESBL’s, VRE, MRSAMaybe less effective than other short-course regimensDrug interaction: Metoclopramide (Reglan) increases FF excretion
21Trimethoprim/Sulfamethoxazole TMP/SMX (Bactrim) DRUG INTERACTIONSWarfarinMethotrexateFluconazole (incr QT)TCA, antipsychotics, antiarrhythmicsAntihyperglycemicsCommon side effects: nausea, vomiting, rashOther serious adverse effects:Bone marrow suppressionHepatic necrosisSevere rashHyperkalemiaHypoglycemia (esp with renal and liver disease)Increased creatinine…may be falsely elevatedIn contrast to NF and Fosfo, more effect on fecal flora and more issues with antimicrobial resistance with TMP/SMX, quinolones (and amp).Other issues: resistance right around 20%.....but local resistance rates reported in hospital antibiogram may be skewed by cultures of samples from inpts/those with complicated infection and may not predict susceptibilities in women with uncomplicated comm acq UTI in whom resistance rates tend to be lower And it remins very effective (with est clinical cure 85% even in regions with 30% resistance)And some evidence that if used in the preceding 3-6 mos, that is an independent RF for TMP/SMX resistance
22Quinolones: Ciprofloxacin and Levofloxacin Highly efficacious in a 3-day regimenNumerous issues with collateral damage: C.difficile and resistanceSave for other usesBlack Box Warning: tendonitis/tendon rupture esp. over age 60, steroids, transplantInteractions:calcium, aluminum, magnesium, iron, and zinc (antacids, nutritional supplements, multivitamin and mineral supplements), sucralfateWarfarinAntihyperglycemicsOther issues:QT prolongation esp. in elderlyDecreased seizure thresholdAlso Moxifloxacin: Many uses, but doesn’t get in to urinary tractFQ: linked to infection with MRSA, increasing R to FQ in GNB such as Pseudomonas.
24Alternatives Amoxicillin-clavulanate Cefdinir (Omnicef) Cefpodoxime-proxetil (Vantin)Cefaclor (Ceclor)Not for empiric therapy due to poor efficacy and resistance: amoxicillin and ampicillinCefdinir: 3rd gen cephCefaclor: 2nd gen cephCefpodoxime: 3rd, but some properties that are more like 2ndDown side: collateral damage:Ceph linked to subsequent VRE, ESBL K pneumo, Betalactam resistant acinetobacter, Cdiff
25Upper Tract Infection: Acute Pyelonephritis Not requiring hospitalization (and resistance less than 10%):Ciprofloxacin 500mg PO BID for 7 daysCiprofloxacin 1000mg ER for 7 daysLevofloxacin 750mg for 5 daysBactrim DS BID for 14 days (if pathogen susceptible)Alternative initial IV antibiotic: Ceftriaxone 1g IV or AminoglycosideAlternative: Oral b-lactam (initial IV dose Ceftriaxone) and daysHospitalized:IV regimen:FluoroquinoloneAminoglycoside +/- ampicillin2nd or 3rd generation cephalosporin +/- aminoglycosideExtended spectrum penicillin +/- aminoglycosideCarbapenemNRH: initial IV dose (Cipro)Also 1 dose IV CTX then oral cefixime (3rd gen ceph)(Suprax) 400mg BID for 2 days and then 7 more days oral abx based on susceptibilities was comp to CTX 1g for 3 daysGupta K et al. Clinical Infectious Diseases 2011;52(5):e
26Catheter-Associated UTI (CA-UTI) Most common health care-associated infection worldwide40% of hospital-acquired infections5-10% of LTCF residents with long-term indwelling cathetersAlmost all have bacteriuriaSingle organism in short-term catheterMultiple organisms in long-term catheterizationHooton TM et al. Clinical Infectious Diseases 2010;50:
27CA-UTIE.coli (30%), Klebsiella species, Serratia species, Citrobacter species, Enterobacter species, Pseudomonas aeruginosa, coagulase-negative staphylococci, Enterococcus speciesLong-term catheters: the organisms above and: Proteus mirabilis, Morganella morganii, Providencia stuartiiChoice of abx will depend on local epi, prior infections, how ill……May choose a broader agent empirically and then narrow once culture data
28CA-UTI Duration: Other issues Prompt resolution of symptoms: 7 days Delayed response: daysNot severely ill: 5 day Levofloxacin may be consideredWomen aged 65 or under with CA-UTI and no upper tract symptoms, with removal of catheter: consider 3 days of therapyOther issuesDe-escalation/narrowing of therapy as soon as possibleIf catheter in place for >2 weeks and is still needed, catheter should be replacedMore rapid resolution of symptomsDecrease risk of subsequent CA-bacteriuria and CA-UTIUrine culture specimens should ideally be obtained from freshly placed catheter if in place for 2 weeks and still neededChoice of drug more complicated, depends on prior hx, cultures.Hooton TM et al. Clinical Infectious Diseases 2010;50:
29Case 368 yo woman with poorly-controlled diabetes, dysuria, fever and chillsPrior history of UTI’s with resistant KlebsiellaNo allergiesWBC 18KCr 2.6U/a with >182 wbc, 2 rbc, 1 sq epith cellGuideline Wish ListComplicated UTIUTI Management for Patients in Long-Term CarePost-menopausal UTI
30Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO. COLONY COUNT >100,000 CFU/ml RESULT COMMENT: ** DRUG RESISTANT ORGANISM ** Drug Resistant Organism KLEBSIELLA PNEUMO. SSP PNEUMO. MULTIPLE DRUG RESISTANCE TRIMETHOPRIM/SULFAMETHOXAZOLE R >=320 AMPICILLIN R >=32 AMPICILLIN/SULBACTAM R >=32 CEFAZOLIN R >=64 CEFOXITIN R >=64 CEFTAZIDIME R >=64 CEFTRIAXONE R >=64 CEFEPIME R >=64 CIPROFLOXACIN R >=4 GENTAMICIN R >=16 LEVOFLOXACIN R >=8 IMIPENEM R >=16 NITROFURANTOIN R >=512 TOBRAMYCIN R >=16 AMIKACIN R >=64 PIPERACILLIN/TAZOBACTAM R >=128What are the antibiotic options in this case?NoneColistinGatifloxacinErtapenemOther ideas?
31New FDA Antibiotic Approvals Increasing Resistant Organisms14 new classes of antibiotics between 1935 and 2003Since 1998, only 11 new antibiotics approved\Decreasing antimicrobial drug developmentSignificant lag time between discovery of molecules and introduction into clinical useIncreasing multi-drug resistant organismsBoucher HW et al. Clinical Infect Diseases 2009;48:1-12.
32Answers Colistin Tigecycline Fosfomycin Reasonable to have ID consultant involved
33Case 3, Part 2Patient is treated with colistin, has resolution of her symptoms, leukocytosis and eventually improved renal function.Which of the following should be done?A) Repeat u/a 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat u/a and culture are not indicated
34Test of Cure Not routinely recommended Except in pregnant women, certain cases for urologic intervention
35Case 470 year old woman with 4 E.coli UTI’s in the past 6 months, urologist notes a mild cystocele and atrophic vaginal mucosa on examWhat do you recommended?A) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weeklyDepends: but topical estrogen is probably the most reasonable to start with. Also, little down side to cranberry juice.
36Recurrent UTI: Risk Factors Post-menopausal:estrogen deficiencyurogenital surgeryincontinence, cystocele, post-void residualsMen:Prostatic diseaseBoth Men and Women:Obstruction: stones, tumorComplicated UTI:MDRO, obstruction, stasis, foley catheter, stent, diabetes, pregnancy, renal failure, transplant, immunosuppressionYoung healthy women: recurrent infection in 25% within 6mos of first infection??data for postmenopausal/elderly?Franco AV. Best Pract & Res Clin Obstet & Gynec 2005;19(6):
37What else other than antibiotics? Fluids to promote a dilute urine flowTopical estrogenIn some postmenopausal women it can normalize the vaginal flora and reduce recurrent UTIMethenamineAdhesion blockers (D-mannose)Not evaluated in clinical trialsDrinking cranberry juice or cranberry tabletsClinical Data Cochrane Review 2008Recent studiesPilot Study in LTCESTROGENA randomized, double-blind, placebo-controlled trial in 93 postmenopausal women found that estriol in a vaginal cream (0.5 mg nightly for 2 weeks, then twice weekly for 8 months) significantly reduced the incidence of recurrent UTI. The effect probably is related to the restoration of lactobacilli, which replace Enterobacteriaceae and decrease the vaginal pH. Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med. Sep ;329(11): [Medline]. [Full TextMethenamine salts: lack of selection for resistant organismsSalts are hydrolyzed to (ammonia and) formaldehyde. Formaldehyde denatures proteins and nucleic acids: antimicrobial activity. Activity depends on urinary concentration of formaldehyde, which depends on methenamine concentration, urine pH and time the drug is in the bladder.Vit C at 4-12 g per day to acidify urine2007 Oct 17;(4):CDCOCHRANE:Methenamine hippurate for preventing urinary tract infections.Lee BB, Simpson JM, Craig JC, Bhuta T.SourcePrince of Wales Hospital, Spinal Injuries Unit, High St, Randwick, NSW, Australia,AbstractBACKGROUND:Methenamine salts are often used as an alternative to antibiotics for the prevention of urinary tract infection (UTI).OBJECTIVES:To assess the benefits and harms of methenamine hippurate in preventing UTI.SEARCH STRATEGY:We searched the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library), MEDLINE (from 1950), EMBASE (from 1980), reference lists of articles and abstracts from conference proceedings without language restriction. Manufacturers' of methenamine salts were contacted for unpublished studies and contact was made with known investigators. Date of last search: September 2006SELECTION CRITERIA:Randomised controlled trials (RCT) and quasi-RCTs of methenamine hippurate used for the prevention of UTIs in all population groups were eligible. A comparison with a control/no treatment group was a prerequisite for selection.DATA COLLECTION AND ANALYSIS:Two authors independently assessed study quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI). An exploration of heterogeneity and a detailed description of results, grouped by population, was undertaken.MAIN RESULTS:Thirteen studies (2032 participants) were included. Six studies (654 patients) reported symptomatic UTI and eight studies (796 patients) reported bacteriuria. Overall, study quality was mixed. The overall pooled estimates for the major outcome measures were not interpretable because of underlying heterogeneity. Subgroup analyses suggested that methenamine hippurate may have some benefit in patients without renal tract abnormalities (symptomatic UTI: RR 0.24, 95% CI 0.07 to 0.89; bacteriuria: RR 0.56, 95% CI 0.37 to 0.83), but not in patients with known renal tract abnormalities (symptomatic UTI: RR 1.54, 95% CI 0.38 to 6.20; bacteriuria: RR 1.29, 95% CI 0.54 to 3.07). For short-term treatment duration (1 week or less) there was a significant reduction in symptomatic UTI in those without renal tract abnormalities (RR 0.14, 95% CI 0.05 to 0.38). The rate of adverse events was low.AUTHORS' CONCLUSIONS:Methenamine hippurate may be effective for preventing UTI in patients without renal tract abnormalities, particularly when used for short-term prophylaxis. It does not appear to work in patients with neuropathic bladder or in patients who have renal tract abnormalities. The rate of adverse events was low, but poorly described. There is a need for further large well-conducted RCTs to clarify this question, particularly for longer term use for people without neuropathic bladderCranberry prevents adhesion of bacteria (esp E. coli) to uroepithelial cells.Cochrane review cranberry: Jan 23;(1):CDCranberries for preventing urinary tract infections.Jepson RG, Craig JC.University of Stirling, Cancer Care Research Centre, Unit 1, Scion House, Innovation Park, Stirling, UK FK9 4LA.Cranberries have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs).To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations.We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library) and the Internet. We contacted companies involved with the promotion and distribution of cranberry preparations and checked reference lists of review articles and relevant studies. Date of last search: January 2007.All randomised controlled trials (RCTs) or quasi-RCTs of cranberry products for the prevention of UTIs in all populations.Two authors independently assessed and extracted information. Information was collected on methods, participants, interventions and outcomes (UTIs - symptomatic and asymptomatic, side effects, adherence to therapy). Relative risk (RR) were calculated where appropriate, otherwise a narrative synthesis was undertaken. Quality was assessed using the Cochrane criteria.Ten studies (n = 1049, five cross-over, five parallel group) were included. Cranberry/cranberry-lingonberry juice versus placebo, juice or water was evaluated in seven studies, and cranberries tablets versus placebo in four studies (one study evaluated both juice and tablets). Cranberry products significantly reduced the incidence of UTIs at 12 months (RR 0.65, 95% CI 0.46 to 0.90) compared with placebo/control. Cranberry products were more effective reducing the incidence of UTIs in women with recurrent UTIs, than elderly men and women or people requiring catheterisation. Six studies were not included in the meta-analyses due to methodological issues or lack of available data. However, only one reported a significant result for the outcome of symptomatic UTIs. Side effects were common in all studies, and dropouts/withdrawals in several of the studies were high.There is some evidence that cranberry juice may decrease the number of symptomatic UTIs over a 12 month period, particularly for women with recurrent UTIs. It's effectiveness for other groups is less certain. The large number of dropouts/withdrawals indicates that cranberry juice may not be acceptable over long periods of time. It is not clear what is the optimum dosage or method of administration (e.g. juice, tablets or capsules). Further properly designed studies with relevant outcomes are needed.
38Mayo Clinic Proceedings 2012 Feb;87(2):143-50 Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily: a randomized controlled trial.Stapleton AE, Dziura J, Hooton TM, Cox ME, Yarova-Yarovaya Y, Chen S, Gupta K.SourceDepartment of Medicine, University of Washington, Seattle, USA.AbstractOBJECTIVE:To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice daily.PATIENTS AND METHODS:Premenopausal women with a history of recent UTI were enrolled from November 16, 2005, through December 31, 2008, at 2 centers and randomized to 1 of 3 arms: 4 oz of cranberry juice daily, 8 oz of cranberry juice daily, or placebo juice. Time to UTI (symptoms plus pyuria) was the main outcome. Asymptomatic bacteriuria, adherence, and adverse effects were assessed at monthly visits.RESULTS:A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days. The cumulative rate of UTI was 0.29 in the cranberry juice group and 0.37 in the placebo group (P=.82). The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 0.68 (95% confidence interval, ; P=.29). The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (43.5%) in the cranberry juice group and 8 of 10 (80.0%) in the placebo group (P=.07). The mean dose adherence was 91.8% and 90.3% in the cranberry juice group vs the placebo group. Minor adverse effects were reported by 24.2% of those in the cranberry juice group and 12.5% in the placebo group (P=.07).CONCLUSION:Cranberry juice did not significantly reduce UTI risk compared with placebo. The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger, well-powered studies of women with recurrent UTI. The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity.RECENT STUDIES1) Barbosa-Cesnik C et al. Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection: Results from a Randomized Placebo-Controlled Trial. Clinical Infectious Diseases 2011;52(1);23-30.2) Mayo Clinic Proceedings 2012 Feb;87(2):143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily: a randomized controlled trial.Stapleton AE, Dziura J, Hooton TM, Cox ME, Yarova-Yarovaya Y, Chen S, Gupta K.SourceDepartment of Medicine, University of Washington, Seattle, USA.AbstractOBJECTIVE:To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice daily.PATIENTS AND METHODS:Premenopausal women with a history of recent UTI were enrolled from November 16, 2005, through December 31, 2008, at 2 centers and randomized to 1 of 3 arms: 4 oz of cranberry juice daily, 8 oz of cranberry juice daily, or placebo juice. Time to UTI (symptoms plus pyuria) was the main outcome. Asymptomatic bacteriuria, adherence, and adverse effects were assessed at monthly visits.RESULTS:A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days. The cumulative rate of UTI was 0.29 in the cranberry juice group and 0.37 in the placebo group (P=.82). The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 0.68 (95% confidence interval, ; P=.29). The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (43.5%) in the cranberry juice group and 8 of 10 (80.0%) in the placebo group (P=.07). The mean dose adherence was 91.8% and 90.3% in the cranberry juice group vs the placebo group. Minor adverse effects were reported by 24.2% of those in the cranberry juice group and 12.5% in the placebo group (P=.07).CONCLUSION:Cranberry juice did not significantly reduce UTI risk compared with placebo. The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger, well-powered studies of women with recurrent UTI. The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity.3)MCMURDO relevant b/c in elderly: Cranberry juice tolerable, need larger trials pts males and females in hospital, low infection rate so underpowered, but did have fewer ecoli infections in cranberry juice group.4)PILOT: Juthani-Mehta Oct 2010, small study: 56 pts Sept 2007-July Cranberry capsules 2 doses and placebo. Time to first positive cx and incidence were not signif diff. Basically demonstrated tolerability. Difficulties with followup and contamination of samples. ?appropriate dose.Juthani-Mehta M et al. Journal of the American Geriatric Socety 2010;58(10):
39Cranberry juice and Warfarin? Case reports of cranberry juice or cranberry sauce potentiating the effects of warfarin by elevating the INRClinical trials evaluating this interaction have failed to demonstrate a significant effect on an INR+
40Cochrane Review/Meta-analysis Beerepoot MA, ter Riet G, Nys S, van der Wal WM, de Borgie CA, de Reijke TM, et al. Cranberries vs antibiotics to prevent urinary tract infections: a randomized double-blind noninferiority trial in premenopausal women. Arch Intern Med. Jul ;171(14): [Medline].Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. Jan ;CD [Medline].Kontiokari T, Sundqvist K, Nuutinen M, Pokka T, Koskela M, Uhari M. Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. BMJ. Jun ;322(7302):1571. [Medline]. [Full Text].Wojnicz D, Sycz Z, Walkowski S, Gabrielska J, Aleksandra W, Alicja K, et al. Study on the influence of cranberry extract Zuravit S·O·S(®) on the properties of uropathogenic Escherichia coli strains, their ability to form biofilm and its antioxidant properties. Phytomedicine. Feb ;[Medline].Cochrane Review/Meta-analysisRR 0.21 compared to placebo (95%CI ) NNT 1.85Adverse events: RR 1.78 (95%CI ) NNT for ADR 13.5Rate of recurrence returns to baseline after prophylaxis stoppedRisk for the development of antibiotic resistance is realExhaust all non-pharmacologic methods for UTI prevention prior to resorting to antibiotic prophylaxis, due to cost, risk of adverse effects, and development of antibiotic resistancePoint out that 6 month trial recommended then discontinued and observed…..
41Antimicrobial Prophylaxis Point out that 6 month trial recommended then discontinued and observed…..Cochrane Review/Meta-analysisRR 0.21 compared to placebo (95%CI ) NNT 1.85Adverse events: RR 1.78 (95%CI ) NNT for ADR 13.5Rate of recurrence returns to baseline after prophylaxis stoppedRisk for the development of antibiotic resistance is realExhaust all non-pharmacologic methods for UTI prevention prior to resorting to antibiotic prophylaxis, due to cost, risk of adverse effects, and development of antibiotic resistanceHooton, TM. NEJM 2012;366:
42What about for CA-UTI? Reduce indwelling catheter use Remove catheters the as soon as they are no longer clinically necessaryCathetersCareInsertion with aseptic technique/sterile equipmentClosed drainage systems, with drainage bag and tube always below bladder levelAntimicrobial coatingMay delay onset of CA-bacteriuria in short-termData insufficient to say if antimicrobial-coated catheters reduce CA-UTI in short-term or CA-bacteriuria/CA-UTI in long-term catheterizationHooton TM et al. Clinical Infectious Diseases 2010;50:
43What about for CA-UTI?Methenamine not recommended in long-term catheterizationData unconvincing that it is effectiveMay be effective with intermittent catheterization and short-term catheterization (studied in specific population)Methenamine hippurate 1 g BIDMethenamine mandelate 1g 4 times dailyAnd it may help to acidify urine when using these agents (Vit C?)Cranberry3/4 double-blind placebo controlled trials: no effectStudies are poor, mostly negativeAntimicrobial prophylaxis can reduce CA-ASB, but not CA-UTINot recommended because of cost, potential for adverse effects and development of antimicrobial resistanceMethenamine salts: lack of selection for resistant organismsSalts are hydrolyzed to (ammonia and) formaldehyde. Formaldehyde denatures proteins and nucleic acids: antimicrobial activity. Activity depends on urinary concentration of formaldehyde, which depends on methenamine concentration, urine pH and time the drug is in the bladder.Vit C at 4-12 g per day to acidify urineAnd antimicrobial proph increases antimicrob-resistant bacteriaHooton TM et al. Clinical Infectious Diseases 2010;50:
44In Summary Decide if treatment is necessary Appropriate antibiotic and durationChoice based on patient (allergies/comorbidities/prior history), epidemiologic factors, organismMinimize adverse effects, minimize development of resistance, avoid C.difficileNarrowest spectrum possibleIf empiric therapy is more broad than needed, narrow after culture dataProphylaxisSeveral options that do not affect antimicrobial resistanceAvoid antimicrobial agents if possibleIf such an agent is chosen, would re-evaluate after several monthsIf antimicrob agent chosen for proph, then would re-evaluate after a certain period of time…..
46ReferencesBarbosa-Cesnik C et al. Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection: Results from a Randomized Placebo-Controlled Trial. Clinical Infectious Diseases 2011;52(1);23-30.Beerepoot MAJ et al. Cranberries vs Antibiotics to Prevent Urinary Tract Infections. Archives of Internal Medicine 2011;171(14):Beveridge LA et al. Optimal Management of Urinary Tract Infections in Older People. Clinical Interventions in Aging 2011;6:Boucher HW et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of AmericaClinical Infect Diseases 2009;48:1-12.Das R et al. Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing Home Residents. ICHE 2009;30(11):Franco AV. Recurrent Urinary Tract Infections. Best Pract & Res Clin Obstet & Gynec 2005;19(6):861-73Gupta K et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases. Clinical Infectious Diseases 2011;52(5):eHooton, TM. Uncomplicated Urinary Tract Infection. NEJM 2012;366:Hooton TM et al. Diagnosis, Prevention, and Treatment of Catheter-Associated Urinary Tract Infection in Adults: Internation Clinical Practice Guidelines from the Infectious Diseases Society of America. Clinical Infectious Diseases 2010;50:Jepson RG et al. Cranberries for preventing urinary tract infections. Cochrane Review 2008.Juthani-Mehta M et al. Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection in Long-Term Care Residents. Journal of the American Geriatric Socety 2010;58(10):Mcmurdo MET et al. Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in Hospital? A Double-Blind Placebo-Controlled Trial. Age and Aging 2005;34:Mullane et al. Clin Infect Dis. 2011;53:Nicolle LE et al. Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults. Clinical Infectious Diseases 2005;40:Stapleton AE et al. Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting Cranberry Juice Daily: A Randomized Controlled Trial. Mayo Clinic Proceedings 2012;87(2):