MICHIGAN MEDICINE GUIDELINES FOR TREATMENT OF URINARY TRACT INFECTIONS IN ADULTS

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When to Order a Urine Culture: Asymptomatic bacteriuria is often treated unnecessarily, and accounts for a substantial burden of unnecessary antimicrobial use. National guidelines recommend against testing for asymptomatic bacteriuria, except in select circumstances. Therefore urine cultures should only be obtained on adult inpatients for appropriate reasons. In the absence of signs or symptoms (see below) attributable to a urinary tract infection, patients with a positive urine culture and/or pyuria should not be treated with antibiotics irrespective of high bacterial colony count, or a multi-drug resistant organism. The following is an effective strategy for how and when to order a urinalysis and/or urine culture. NOTE: this does not apply to patients being screened for asymptomatic bacteruria (see subsequent page for recommendations in such patients). When to order a Urinalysis or Urine Culture Recommendations for when to order a urinalysis or urine culture Does your adult patient have any of the following without alternate explanation? Fever >38 o C or rigors without alternative cause Urgency, frequency, dysuria Suprapubic pain or tenderness Costovertebral pain or tenderness New onset mental status changes with leukocytosis, hypotension, or >/= 2 SIRS criteria 1 Acute hematuria Spasticity or autonomic dysreflexia in patients with spinal cord injury YES NO Order "UA with reflex culture if indicated"* (Note: For neutropenic patients, send culture without UA) Do NOT send a urine culture or urinalysis *: With this order, a urine culture will only be performed if a urinalysis result indicates infection. This is a strategy to decrease unnecessary in samples indicative of colonization and not infection 6 a SIRS Criteria: Heart rate greater than 90bpm, respiratory rate greater than 20 breaths per minute, temperature less than 36 o C, white blood count less than 4,000 cells/mm3, temperature greater than 38o C, white blood count greater than 12,000 cells/mm3.

Asymptomatic Bacteriuria 1 No symptoms of UTI (listed below) UTI symptoms include (without alternative explanation): - Fever >38 o C or rigors without alternative cause - Urgency, frequency, dysuria - Suprapubic pain or tenderness - Costovertebral pain or tenderness - New onset mental status changes with leukocytosis, hypotension, or >/= 2 SIRS criteria a - Acute hematuria - Spasticity or autonomic dysreflexia in patients with spinal cord injury In most circumstances, asymptomatic bacteriuria should not be treated, regardless of pyuria, bacterial density, or isolation of resistant organisms. No Antibiotic Treatment for ASB Recommendation in the absence of signs or symptoms attributable to a urinary tract infection, patients with a positive urine culture and/or pyuria should not be treated with antibiotics irrespective of high bacterial colony count, or a multi-drug resistant organism *Exceptions to this recommendation include pregnant patients and patients bacteriuria prior to a urologic Cystitis 3 (Non-pregnant female without obstruction, catheters, flank pain, or co-morbid conditions except well-controlled diabetes mellitus) Lower UTI or Cystitis Preferred Nitrofurantoin 100 mg po BID (contraindicated if CrCl <50 ml/min. Due to the cost of fosfomycin, nitrofurantoin is preferred if not contraindicated) Fosfomycin 3 gm po once Alternative Cephalexin* 500 mg po BID TMP/SMX* 1DS tab po BID Nitrofurantoin: 5 days Fosfomycin: 1 dose Cephalexin: 7 days TMP/SMX: 3 days Fluoroquinolones are no longer recommended as 1 st - line agents due to high rates of E coli resistance and propensity for collateral damage (resistance, C difficile infection). Use should be reserved when other options are not feasible; duration of therapy should be 3 days. Extended spectrum betalactamase positive cases of uncomplicated cystitis can be treated with piperacillin/tazobactam, ampicillin/sulbactam, amoxicillin/clavulanate, cefepime, ceftriaxone or aztreonam when susceptible 5

Lower Urinary Tract Infection Without Sepsis or Bacteremia 4 (Male, urinary catheter present or removal within the last 48 hrs, recent GU instrumentation, anatomic abnormality or obstruction, pregnancy or other significant comorbid conditions such as uncontrolled diabetes or immunosuppression) Lower UTI without sepsis/bacteremia Preferred oral regimens: Nitrofurantoin 100 mg po BID (contraindicated if CrCl <50 ml/min) Fosfomycin 3 gm po X 3 doses given every 48 hours Alternative oral regimens Cephalexin* 500 mg po QID TMP/SMX* 1 DS tab po BID (if susceptibility confirmed) Preferred IV option if patient cannot take PO medications Cefazolin* 1g IV Q8H Alternative IV option in patients with anaphylactic Aztreonam* 1g IV q8h History of resistant Gram-negative bacteria Not responding to PO antibiotics Piperacillin-tazobactam* 4.5 gm IV q8h Non-Catheterassociated: Treatment duration depends on patient characteristics and clinical response, 7 days usually appropriate Catheter-associated: Prompt resolution of symptoms: 7 days Delayed response to therapy: 10-14 days Special Populations: Women <65 y/o without upper tract symptoms after catheter removal: 3 days Asymptomatic bacteriuria in catheterized patients, even in the presence of pyuria, is NOT an indication for treatment Remove urinary catheter whenever possible No antibiotic treatment for ASB Nitrofurantoin and Fosfomycin should be avoided if pyelonephritis is suspected Definitive antimicrobial choice should be adjusted based on urine culture and susceptibility testing Alternative in patients with anaphylactic Aztreonam* 1g IV q8h

Pyelonephritis 3 (healthy non-pregnant female) Pyelonephritis antibiotic treament Preferred Ceftriaxone 1 gm IV daily followed by step-down to oral TMP/SMX* 1 DS tab po BID if susceptible Alternative in patients with anaphylactic Ciprofloxacin* 500 mg po BID or 400 mg iv BID + Gentamicin 2 mg/kg X 1 dose TMP/SMX: 14 days Ciprofloxacin: 7days Beta-lactams: 14 days Urine culture and susceptibility testing should be obtained Step-down to oral therapy is dependent on the susceptibility of the organism Fluoroquinolones may cause tendinopathy and tendon rupture especially among patients who are older (>60 yo), malnourished, and on oral glucocorticoids Fluoroquinolones may lead to potentially fatal arrhythmias in patients with QT interval prolongation, electrolyte abnormalities, clinically significant bradycardia, and in patients receiving antiarrhythmic medications

Urinary Tract Infection with Sepsis or Bacteremia, Pyelonephritis Community-acquired: Ceftriaxone 1 gm IV daily Critically ill, septic shock, healthcare- or hospital-acquired: Piperacillin/tazobactam* 4.5gm IV q 8 hrs Alternative PCN without anaphylaxis, angioedema, or urticaria Cefepime* 1 gm IV q 8h + Vancomycin ** Anaphylactic Vancomycin** + Aztreonam* 2gm IV q8h Sepsis w/o bacteremia: 10-14 days, can stepdown to oral therapy when stable (see comment) Sepsis with bacteremia: 14 days from first negative blood culture with IV antibiotics or oral quinolone if susceptible gram-negative Pyelonephritis: 14 days Pyelonephritis and UTI with Bacteremia Last updated 12/15/2015 (revision to Page 1 made 2/22/2018) *Renal Dosing Recommendations: https://pharmwebsp.med.umich.edu/ac/antimicrobial%20use%20guidelines/antimicrobial%20dosing%20 Guidelines/Antimicrobial_dosing_recommendations_4-9-2014.pdf a SIRS Criteria: Heart rate greater than 90bpm, respiratory rate greater than 20 breaths per minute, temperature less than 36 o C, white blood count less than 4,000 cells/mm3, temperature greater than 38o C, white blood count greater than 12,000 cells/mm3. 1 Nicolle LE, et al. Infectious Diseases Society of America Guidelines for the Diagnosis and Asymptomatic Bacteriuria in Adults. Clin Infect Dis 2005;40:643-654. 2 Sousa R, et al. Is Asymptomatic Bacteriuria a Risk Factor for Prosthetic Joint Infection? Clin Infect Dis 2014;59:41-47. 3 Gupta K, et al. International Clinical Practice Guidelines for the Acute Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011;52:e103-e120. 4 Hooton TM, et al. Diagnosis, Prevention, and Catheter- Associated Urinary Tract Infection in Adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis 2010;50:625-663. 5 Harris PN, et al. β-lactam and β-lactamase inhibitor combinations in the treatment of extended-spectrum β- lactamase producing Enterobacteriaceae: time for a reappraisal in the era of few antibiotic options? Lancet Infect Dis 2015;15:475-485. 6 Gandhi T, et al. Importance of urinary tract infection to antibiotic use among hospitalized patients. Infect Control Hosp Epidemiol 2009;30:193-5.