Health PEI: Provincial Antibiotic Advisory Team Urinary Tract Infection Empiric Treatment Guidelines

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1 Syndrome Urinary Tract Infection (Antibiotics are listed in the numerical order of preference.) (Tailoring of treatment after susceptibilities are known is highly recommended.) Health PEI: Provincial Antibiotic Advisory Team Urinary Tract Infection Empiric Treatment Guidelines Prevention Cranberry juice?, Estrogenized vaginal mucosa, controlled diabetes and stones. Remove indwelling Foley Catheter Major Hurdles True symptoms?, previous Antibiotics past days (esp. same class), Pregnancy, travel outside of Canada. Considerations prostatitis, vaginitis, PID, urethritis as mimics. Tuberculosis as culture negative disease. Non-SIRS / Pre-SIRS FEMALE CYSTITIS (<6d Symptoms) 1. Nitrofur. x 5d (if CrCl > 60 ml/min)* 2. TMP/SMX x 3d 3. Cefixime x 5-7d 4. Amox/Clav x 5-7d MALE CYSTITIS and EARLY MALE or FEMALE PYELONEPHRITIS 1. Cipro x7d 2. TMP/SMX x10-14d 3. Cefixime x 14d 4. Amox/Clav TID x14d IF in ER or on a unit: Add 1g or Tobra 5mg/kg x1 for pyelonephritis SIRS / Sepsis (2 of 4) >38.3<36.0; HR>; RR>20 or PaCO2<32; WBC <4 >12 or Bands Severe Sepsis(1 of 7+) Mottled, anuria, Lactate>2, Plt<, DIC, ARDS, fastδloc Septic Shock (Pressors) Refractory Septic Sh. (More Pressors) In Absence of Indwelling Foley Catheter or Urinary Stent 1. Amp & Tobra 2. Ceftazidime 3. See Early Pyelo for non-admission Tx. Pip/Tazo & Cipro If penicillin allergy: Mero & Cipro Mero & Tobra Or Mero & Cipro (Renal Sparing) In Presence of Indwelling Foley Catheter or Urinary Stent (Catheter should be removed or changed) Mero, Vanco, &Fluconazole Add Cipro or Tobra if growth of previous P. aeruginosa(d). 1. Pip/Tazo 2. Meropenem If previous culture (d) or stat gram points to yeast, Enterococcus or MRSA -add therapy. As above and add Vanco (or Linezolid if VRE is a concern) Add Fluconazole or Amphotericin-B RE: Penicillin allergy: Avoid pip/tazo, but meropenem is reasonable to give in severe sepsis or greater even with history of anaphylaxis. Consult Inf. Dis. if in doubt. *Nitrofurantoin should not be used with abnormal kidney function (CrCl < 60 ml/min) and is discouraged for long term prophylaxis in the elderly(potential for pulmonary toxicity, inadequate concentrations in the urine in pt with CrCl< 60 ml/min). If financially feasible, Macrobid twice daily versus nitrofurantoin four times daily formulations is strongly preferred for patient adherence. Logic for guidelines: 1. The oral antibiotic that urinary isolates of E. coli in PEI have the highest susceptibility to is nitrofurantoin. As per the Health PEI Antibiogram 2013, the local susceptibilities of urine isolates of E. coli to select antibiotics are as follows: nitrofurantoin %, TMP/SMX 83%, cefixime %, amoxicillin/clavulanate 88%, ciprofloxacin 85%. Cephalexin data (59%) is difficult to interpret due to changes in internationally set breakpoints for susceptibility. Yet cephalexin does concentrate in the urine, which would increase its effectiveness beyond 59%. 2. Avoid collateral damage: nitrofurantoin does not have a serious effect on other bacteria outside the urinary tract, TMP/SMX has lower C. difficle risk than levofloxacin, ciprofloxacin, or amoxicillin/clavulanate. 3. Nitrofurantoin should NOT be used for pyelonephritis or secondary bacteremia due to inadequate tissue and serum concentrations. 4. A recent article reviewed the literature on nitrofurantoin use in renal dysfunction. The authors of this article suggest that nitrofurantoin is effective and safe to use for shortterm treatment ( 1 week) in patients with a CrCl > 40 ml/min. (Oplinger M and Andrews CO 2013 Nitrofurantoin Contraindication in Patients with a Creatinine Clearance Below 60 ml/min: Looking for the Evidence. The Annals of Pharmacotherapy 47: 106.) Approved: May, 2013 This document is designed to aid Prince Edward Island hospital and community practitioners in the appropriate utilization of antimicrobials. Next Review: May, 2015 It does not serve as a substitute for clinical judgment or consultation with Infectious Disease experts.

2 Health PEI: Provincial Antibiotic Advisory Team Urinary Tract Infection Empiric Treatment Guidelines Logic for guidelines (continued): 5. Resistance to levofloxacin and ciprofloxacin is greater than 10% which necessitates conservation (limit use in non-serious infections or prophylaxis) and supplementation (addition of a second agent is recommended for the treatment of serious infections). IDSA guidelines recommend, for treatment of pyelonephritis, when there is >10% fluoroquinolone resistance, an initial one-time IV/IM dose of a long-acting antimicrobial (such as ceftriaxone or an aminoglycoside) be given. Furthermore, fluoroquinolone toxicity is an increasing concern such as retinal detachment, ligament tears in the elderly or on steroids, and QT-interval prolongation (especially in patients with other risk factors). Moxifloxacin should never be used to treat a UTI because it does not concentrate in the urine. The PAAT discussed adding levofloxacin high dose (750 mg po daily) x5 days in addition to having an option for ciprofloxacin 500 mg po bid x 7days for the treatment of early pyelonephritis. Due to the Special Authorization criteria for levofloxacin on the PEI Pharmacare Formulary and lack of clarity on using levofloxacin high dose x 5 days for this indication, we have decided not to include levofloxacin high dose as an option at this time. 6. Enterococcus has relatively low virulence. Enterococcal UTIs are most often nosocomial and/or associated with obstruction, urinary catheterization or instrumentation. In patients with long-term catheterization, urine cultures obtained before and after the catheter was replaced showed that the mean concentration of Enterococci were >10- fold higher in the indwelling catheter than they were in the replacement catheter. 7. Gentamicin vs tobramycin: gentamicin is considered more nephrotoxic than tobramycin and tobramycin has a greater spectrum of activity for empiric treatment of UTIs. References: 1. Epp A. Larochelle A. et al 2010 SOGC Clinical Practice Guidelines Recurrent Urinary Tract Infection. JOGC. 250: Gupta, K. et al 2011 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 for Microbiology and Infectious Diseases. CID 52:e Hooton TM et al Diagnosis, Prevention, and Treatment of Catheter-Associated Urinary Tract Infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America CID 50: Blondel-Hill E. and Fryters S. Bugs & Drugs Capital Health (QE2) Antimicrobial Handbook Vancouver Island Health Authority (VIHA) Cowichan District Hospital. Antimicrobial Empiric Prescribing Guidelines Adults (Edition 2) 7. The Ottawa Hospital (TOH) Guidelines for Empiric Antibiotic Therapy (2012) 8. Drugs for Urinary Tract Infections. The Medical Letter on Drugs and Therapeutics :57 9. Health PEI Antibiogram Etminan M. et al 2012 Oral Fluoroquinolones and the Risk of Retinal Detachment. JAMA 307: Khaliq Y. and Zhanel G Fluoroquinolone-Associated Tendinopathy: A Critical Review of the Literature. CID 36: The American Geriatrics Society 2012 Beers Criteria Update Expert Panel American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 60: Oplinger M and Andrews CO 2013 Nitrofurantoin Contraindication in Patients with a Creatinine Clearance Below 60 ml/min: Looking for the Evidence. The Annals of Pharmacotherapy 47: accessed Feb 4, Bains A. et al A retrospective review assessing the efficacy and safety of nitrofurantoin in renal impairment. CPJ 142: Murray BE Treatment of enterococcal infections. UpToDate (accessed Feb 4, 2013) 17. Solensky R Penicillin-allergic patients: Use of cephalosporins, carbapenems, and monobactams. UpToDate (accessed Jan 3, 2013) 18. Romano A. et al Brief Communication: Tolerability of Meropenem in Patients with IgE-Medicated Hypersensitivity to Penicillins. Annals of Internal Medicine 146: Atanasković-Marković M. et al Tolerability of Meropenem in Children with IgE-mediated Hypersensitivity to Penicillins. Allergy 63: Decker BS. Molitoris BA Pathogenesis and prevention of aminoglycosides nephrotoxicity and ototoxicity. UpToDate (accessed Feb 4, 2013). Health PEI Physician Reviewers: Dr. Lenley Adams, Dr. Scott Campbell, Dr. Greg German, Dr. Kate Ellis-Ghiz, Dr. Gil Grimes, Dr. Michael Irvine, Dr. Ian Reid, Dr. John Sampson Approved: May, 2013 This document is designed to aid Prince Edward Island hospital and community practitioners in the appropriate utilization of antimicrobials. Next Review: May, 2015 It does not serve as a substitute for clinical judgment or consultation with Infectious Disease experts.

3 Provincial Drugs & Therapeutics Committee 16 Garfield Street 16, rue Garfield PO Box 2000, Charlottetown C.P. 2000, Charlottetown Prince Edward Island Île-du-Prince-Édouard Canada C1A 7N8 Canada C1A 7N8 From: Provincial Drugs and Therapeutics Committee To: All Island Physicians, Nurse Practitioners, and Pharmacists Date: May 24, 2013 RE: Provincial Urinary Tract Infection Empiric Treatment Guidelines and Health PEI Antibiogram Consideration of local susceptibly patterns is crucial to empirically treating infections and reducing the spread of antibiotic resistance. Our Island wide Health PEI Antibiogram 2013, based on 2012 data, is attached and available at This data is from all community and hospital specimens received, removing duplicated specimens for better quality. Dr. Greg German, Medical Microbiologist, gave grand round presentations at QEH and PCH in the Fall introducing the antibiogram as it pertains to UTIs and how it may affect your practice. The Provincial Antibiotic Advisory Team (PAAT), of which Dr. German is co-chair, has developed the enclosed UTI Empiric Treatment Guidelines which were adapted and approved by a well-represented committee of Physician Reviewers. The guidelines are based on local susceptibilities and are in keeping with national and international guidelines. Individual medication recommendations do not necessarily take into account coverage by PEI Pharmacare or private drug plans. The guidelines were developed with the desire to appropriately and safely treat urinary tract infections while reducing collateral damage and attempting to save fluoroquinolones for more serious infections. The layout of the guidelines includes preventative and diagnostics tips, followed by a list of empiric treatment options spanning the continuum of patients illness from generally well to septic shock. This standardization should allow for a rapid, consistent, and collaborative approach for almost all patients on the Island. It is important to note that these guidelines were not designed for special populations such as paediatrics, pregnancy or patients with severe renal impairment. The guidelines are further categorized by the following: in patients who are non-sirs or pre-sirs, empiric antibiotic treatment differs for female cystitis (< 6 days of symptoms) versus male cystitis/early male or female pyelonephritis. For patients anywhere across the spectrum from generally well to refractory septic shock, the suggested treatment options differ for those with or without an indwelling Foley catheter or urinary stent.

4 Provincial Drugs & Therapeutics Committee The new guidelines will potentially change routine practices. For example: 1) Nitrofurantoin is suggested as the first option for female cystitis (if no contraindication for use). Fluoroquinolones are not listed as one of the top four agents for the treatment of female cystitis. It is encouraged that fluoroquinolones be reserved for more serious infections. 2) Due to the level of ciprofloxacin resistance (E. coli resistance to ciprofloxacin is 15%), an initial onetime IV dose of a long-acting parenteral antimicrobial (such as ceftriaxone or a consolidated 24h dose of an aminoglycoside) as a second agent is recommended when possible, when treating early pyelonephritis. 3) Ampicillin and tobramycin are recommended as first line therapy in patients with SIRS or sepsis without an indwelling Foley catheter or urinary stent. It is recommended to step-down from ampicillin and tobramycin as early as possible to avoid aminoglycoside toxicities. 4) For SIRS or sepsis patients with an indwelling Foley catheter or urinary stent, the use of a stat urine Gram stain to check for yeast, MRSA or Enterococcus is recommended. 5) The cross reactivity of truly penicillin-allergic patients with meropenem is less than 1%. Meropenem is a reasonable choice to give to serious penicillin-allergic patients in severe disease. The Urinary Tract Infection Empiric Treatment Guidelines is the first of a series of guidelines the Provincial Antibiotic Advisory Team is working on developing. Guidelines for Clostridium difficile and skin and soft tissue infections are to come out in the next few months. For any questions about the Health PEI Antibiogram 2013, please contact Greg German (8-2515; GJGerman@ihis.org). For questions on the Provincial UTI Empiric Treatment Guidelines, you can contact the PAAT co-chairs Greg German or Jennifer Boswell (antimicrobial pharmacist; 8-27; jlboswell@ihis.org). 2

5 URINE Isolates Total (7 months) E. coli 2221 Klebsiella pneumoniae 333 Klebsiella oxytoca 63 Enterobacter 92 Proteus mirabilis (Not P. vulgaris) 124 Pseudomonas aeruginosa 87 Staphylococcus saphrophyticus 147 Enterococcus 352 Nitrofurantoin* AmpIV / AmoxPO Amox + Clav. Acid Cephalexin Cefixime Ciprofloxacin Ceftazidime Ertapenem Piperacillin+Tazo Meropenem Tobramycin ^ ^ 76^ Vancomycin IV or Linezolid PO / IV : Predictably Resistant ; ^Urine inc. levels = likely higher % *Nitrofurantoin activity limited to bladder (uncomplicated UTIs only) ALL Gram Negative ISOLATES (Except URINE) Total (12 Months) E. coli 182 Klebsiella 76 Proteus mirabilis 11 Enterobacter 49 Citrobacter 16 Serratia 22 Acinetobacter 7 Pseudomonas aeruginosa 261 AmpIV /AmoxPO Amox +Clav. Acid Cephalexin Cefprozil Cefixime Ciprofloxacin Cefazolin Ceftazidime Ertapenem Piperacillin+Tazo Meropenem Tobramycin 92 Gram Positive Cocci GPC (Except URINE) Total Number (12 Months) Amp IV or Amox Amox+Clav. Acid Cephalexin or Cefazolin Cefuroxime or Doxycylcine (Tetracycline) Staph. aureus MSSA & MRSA to * Staphylococcus lugdunensis (SL) Coagulase Neg. Staph (Except SL) Enterococcus Sample Group A Strep of 75 ~ Sample Group B Strep of ~ Streptococcus pneumoniae ^ 85^ 85 ~60 ~70 79 ~ *MRSA Rate: 7.4% of Blood Cultures; 18% of Wounds (QEH and PCH Emerg.) ~National data as local data is unavailable. : Predictably Resistant S. pneumoniae and Levofloxacin (%), in vitro testing not reliable for other GPC. ^85% at regular dose, % at high dose in non-central Nervous System Infections. Erythromycin Clindamycin Vancomycin IV Health PEI ANTIBIOGRAM 2013 (Island-wide Antibiotic Susceptibility Results of Non-duplicative Isolates) Medical Microbiologist: Head Microbiology Technologists: Dr. Greg German Andrea Dowling Secretary: # QEH Laboratory # QEH Switchboard for Becky Moore Direct line or Page PCH Laboratory # Anaerobic susceptibilities* Predictably Susceptible: Amoxicillin+Clavulanic Acid, Pipercillin+Tazobactam, Ertapenem, and Meropenem; Also Predictably Susceptible: Metronidazole (Yet Actinomyces or Propionibacterium are intrinsically resistant) Double anaerobic coverage when already on one of above antibiotics is discouraged. NOT-Predictably Susceptible: Moxifloxacin, Doxycycline, Cefoxitin or Clindamycin Note: Most beta-lactamase negative oral anaerobes are susceptible to Amoxicillin. *Bugs and Drugs (Canada) 2012; Susceptibilities available on a case by case basis.