Urinary Tract Infections in Adults

Transcription

1 This Clinical Resource gives subscribers additional insight related to the Recommendations published in March 2018 ~ Resource # Urinary Tract Infections in Adults Urinary tract infections lead to nearly ten million provider visits each year. 14 Common symptoms include urinary urgency or frequency, painful urination, cloudy urine, and pelvic or abdominal pain. 2,14 UTIs occur more frequently in women than men. 2 In fact, uncomplicated urinary tract infection is one of the most common reasons for antibiotic use in women. 1 Treatment decisions are complicated and impacted by antibiotic resistance patterns as well as other factors (e.g., age, renal function, severity of infection, catheter use, pregnancy). The chart below addresses common clinical questions about UTIs in adult patients. Abbreviations: ADR = adverse drug reaction; BID = twice daily; CrCl = creatinine clearance; C&S = culture and sensitivity; IV = intravenously; PO = by mouth; QID = four times daily; q6h = every six hours; q8h = every 8 hours; q12h = every 12 hours; TID = three times daily; TMP/SMX = trimethoprim/sulfamethoxazole; UTI = urinary tract infection. What are risk factors for UTIs? How should uncomplicated cystitis be treated? Continued Female sex 2 Sexual activity 2,3 Certain methods of birth control (e.g., diaphragms, spermicides) 2,3 Menopause 2,3 Urinary tract abnormalities (e.g., neurogenic bladder) 2,3 Blockages (e.g., kidney stones, enlarged prostate) 2,3 Suppressed immune system (e.g., chemotherapy, diabetes) 2 Catheter use 2,3 Recent urinary procedure 2 Incontinence 3 Uncomplicated cystitis: limited to the bladder or lower urinary tract. 1 o Local symptoms only (e.g., frequency, urgency, painful urination). o No fever or flank pain. o Frequently treated empirically without urine cultures or sensitivities. Typical organisms: 1,30 E. coli (75% to 95%) P. mirabilis

2 (Clinical Resource #340309: Page 2 of 10) Cystitis, continued K. pneumoniae S. saprophyticus E. faecalis E. faecium Empiric antibiotics and duration of therapy: Trimethoprim 100 mg or TMP/SMX 160/800 mg BID for three days. 1 o Avoid if resistance exceeds 20% or taken in the previous three months. 1 Nitrofurantoin 100 mg BID for five days. 1,19,30 (Dosing for macrocrystal formulation [e.g., Macrobid].) If the above choices are NOT appropriate (e.g., resistance rates, history of ADR, allergy), consider the following: 1 o Beta-lactams for three to seven days (e.g., amoxicillin-clavulanate 875/125 mg BID, cephalexin 500 mg dosed BID to QID). Avoid empirical ampicillin or amoxicillin monotherapy due to lower efficacy rates. 1 o Consider fosfomycin (Monurol) 3 gm single dose, especially if adherence is an issue. 1,30 o Last-line, fluoroquinolones for three days (e.g., ciprofloxacin 250 mg BID, levofloxacin 250 mg daily). 30 Avoid gemifloxacin and moxifloxacin due to limited urinary concentrations. 12 Acute self-treatment: 4 consider for reliable patients, well-documented recurrence, and good rapport with prescriber. TMP/SMX 160/800 mg BID for three days. Instruct patients to contact prescriber if symptoms continue 48 hours after starting therapy. How should complicated UTIs be treated? Continued Complicated UTIs occur with predisposing factors. 3 o Urinary obstruction (e.g., congenital, enlarged prostate, urinary stones). o Incomplete bladder emptying due to anatomic or neurogenic causes (e.g., spinal cord injury). o Foreign bodies (e.g., catheters, drainage tubes, instruments). o Systemic condition (e.g., diabetes, pregnancy). o Male participating in anal intercourse. Asymptomatic bacteriuria is the most common presentation for complicated UTIs. 18 o Don t treat most patients with asymptomatic bacteriuria, to avoid increasing bacterial resistance. See asymptomatic bacteriuria section below. Symptomatic infection presentation varies from symptoms of uncomplicated cystitis to sepsis. 18 Obtain a urine culture due to potential resistance and the number of possible organsims. 18 Typical organisms: 18 E. coli Other gram-negative organisms (e.g., Citrobacter, Enterobacter, M. Morganii, S. marcescens, P. aeruginosa)

3 (Clinical Resource #340309: Page 3 of 10) Complicated UTIs, continued How should UTIs be treated in the elderly? K. pneumoniae P. mirabilis Antibiotics and duration of therapy (see specific recommendations for PREGNANCY below): 18 Treat complicated UTIs associated with symptoms. Select empiric therapy based on local resistance patterns and patient-specific factors (e.g., severity of symptoms, renal function, allergies). o For oral therapy, consider quinolones (e.g., ciprofloxacin 500 mg BID, levofloxacin 750 mg daily). o For IV therapy, consider ceftriaxone 1 to 2 gms daily, quinolones (e.g., ciprofloxacin 400 mg q12h, levofloxacin 750 mg daily), aminoglycosides (e.g., gentamicin or tobramycin 5 to 7 mg/kg and then adjusted based on kinetics), or ertapenem 1 gm daily. Convert to PO therapy once afebrile and able to take things by mouth. Streamline therapy once culture results are available. Continue treatment for about seven days for infections with only lower UTI symptoms. Continue treatment for ten to 14 days for patients with more severe or systemic infections. Symptoms may be atypical (e.g., mental status changes, lethargy, weakness). 11,23 Typical organisms: 24 Community-dwelling, otherwise healthy: See uncomplicated cystitis section above. Long-term care facilities, without catheter placement: See uncomplicated cystitis section above. Long-term care facilities, with catheter placement: See UTIs in patients with catheter section below. Antibiotics and duration of therapy: 24 Treat uncomplicated UTIs in otherwise healthy, community-dwelling elderly females like an uncomplicated cystitis. See uncomplicated cystitis section above. Treat complicated UTIs for seven to 14 days. See complicated UTIs or UTIs in patients with catheter sections. Cystitis due to chronic bacterial prostatitis may require six to 12 weeks of therapy. 11,23 Adjust doses for impaired renal function Nitrofurantoin (normal dose) can be used short term with CrCl 30 to 60 ml/min. Avoid if CrCl <30 ml/min, especially in patients 65 years old. 20 o Urinary nitrofurantoin levels may not be sufficient in patients with reduced renal function. 20 o Adverse effects may also be increased with use in impaired renal function. 20 Use half of the normal dose of TMP/SMX if CrCl 15 to 30 ml/min. 21,22 o Reduce doses to avoid drug accumulation and associated toxicity (e.g., hyperkalemia, kidney failure). 20 Avoid TMP/SMX if CrCl <15 ml/min. 21,22

4 (Clinical Resource #340309: Page 4 of 10) How should UTIs be treated during pregnancy? See our chart, Antibiotics in Pregnancy and Lactation, for more information. Treat asymptomatic bacteriuria and symptomatic UTIs promptly to avoid progression to pyelonephritis (see asymptomatic bacteriuria and pyelonephritis sections below). 16 o Pyelonephritis is associated with premature delivery and low birthweight babies. 16 Typical organisms Same organisms as in non-pregnant patients, with E. coli remaining the most common. 32,33 Antibiotics and duration of therapy TMP/SMX 160/800 mg BID (contraindicated per Canadian product labeling) or nitrofurantoin (macrocrystal) 100 mg BID for three to seven days (Canada: nitrofurantoin [macrocrystal] 100 mg BID for five days) during the second and early third trimester (e.g., until 36 weeks [nitrofurantoin], until 32 weeks [TMP/SMX]): 19,20,31,33,37,39 o Per a 2017 American College of Obstetricians and Gynecologists (ACOG) committee opinion statement: 31 TMP/SMX or nitrofurantoin in the first trimester can be considered if no safe alternative exists [Evidence Level C]. TMP/SMX or nitrofurantoin may be used first-line during the second and third trimesters [Evidence Level C]. o The ACOG recommendations reflect the following risks, which are based on inconsistent data: TMP exposure in the first trimester has been linked with birth defects (e.g., cardiovascular and neural tube defects). 17 SMX exposure during the third trimester, especially near term, may be linked with hyperbilirubinemia and possible kernicterus. 17,34,38 Nitrofurantoin exposure in the first trimester has mixed evidence and a long history of safe use, but has been weakly linked with birth defects (e.g., cleft lip/palate, heart defects). 17 Nitrofurantoin exposure late in the third trimester has been linked with rare hemolytic anemia in newborns. 17,34 Beta-lactams are safe in pregnancy (e.g., amoxicillin 500 mg TID, amoxicillin-clavulanate 875/125 mg BID, ampicillin 500 mg QID, or cephalexin 500 mg BID to QID for three to seven days). 17,19,33,34,39 Fosfomycin 3 gm single-dose therapy appears safe in pregnancy. 34,39 During the first trimester, if a beta-lactam or fosfomycin is not appropriate (e.g., allergies, urine culture and sensitivity): 39 o Give preference to nitrofurantoin over TMP/SMX. o Reserve TMP/SMX for situations when none of these options are appropriate. Avoid quinolones unless other agents are not an option. 17,30 Treatment for three to seven days is more effective than single-dose regimens (exception fosfomycin). 34 o Data are lacking to compare three- to five-day regimens with seven-day regimens. 35

5 (Clinical Resource #340309: Page 5 of 10) How should catheterassociated UTIs be treated? Definition of catheter-associated UTI: 13 o Indwelling urethral or suprapubic catheter or intermittent catheterization. o Presence of signs or symptoms of UTI with no other identified source of infection. o 10 3 CFU/mL of one bacterial species. o Catheter urine specimen or midstream voided specimen if catheter was removed within 48 hours. Avoid routine antibiotic prophylaxis in patients with catheters. 13 Remove and replace the catheter PRIOR to treatment. Collect the urine specimen for C&S from the NEWLY PLACED CATHETER. 13 Typical organisms (often polymicrobial): 13 P. mirabilis M. morganii K. pneumonia P. aeruginosa P. stuartii Antibiotics and duration of therapy: 13,29 Use local resistance patterns to select therapy. Consider the following options: o Ampicillin 2 gm q6h plus gentamicin 5 mg/kg, then adjusted based on kinetics. o An extended-spectrum beta-lactamase (e.g., piperacillin-tazobactam gm q6h). o Quinolone (e.g., ciprofloxacin 400 mg IV q12h, levofloxacin 750 mg daily). o Carbapenem (e.g., imipenem 0.5 gm IV q12h, meropenem 1 gm IV q8h), reserved for more complicated infections or if suspect extended-spectrum beta-lactamase producing organisms. Treat for seven days in most patients, especially those responding quickly to antibiotics. 13 Treat for ten to 14 days in patients with a delayed response to therapy. 13 Shorter courses may sometimes be appropriate. o Five days of levofloxacin may be considered for patients not severely ill. 13 o Three days may be considered for females 65 years of age WITHOUT upper tract symptoms AFTER catheter has been removed. 13 What is pyelonephritis? Pyelonephritis is a more severe infection, involving the upper urinary tract, including the kidneys. 1 Systemic symptoms (e.g., fever, back pain, flank pain). 1 Requires prompt attention to avoid spread to the bloodstream or urosepsis. 1 o Obtain a urine culture and susceptibility if suspected. Typical organisms include E. coli (75% to 95%), P. mirabilis, K. pneumoniae, S. saprophyticus, E. faecalis, E. faecium. 1

6 (Clinical Resource #340309: Page 6 of 10) How should pyelonephritis be treated? Initiate empiric therapy, based on local resistance rates. 30 Most patients can be treated without hospitalization using oral antibiotics. 30 o Most pregnant women with pyelonephritis should be admitted for intravenous antibiotic therapy. 34 Use IV antibiotics in hemodynamically unstable patients or if unable to tolerate or absorb PO medication. 18 Antibiotics and duration of therapy for patients not requiring hospitalization: 1 In the emergency room, consider ceftriaxone 1 gm times one dose or one 24-hour dose of an aminoglycoside (e.g., gentamicin 5 to 7 mg/kg) prior to starting oral therapy. For oral therapy, consider a quinolone (e.g., levofloxacin 750 mg daily for five days). Consider TMP/SMX 160/800 mg BID for 14 days with documented susceptibility. Avoid other beta-lactams, as they are less effective. Antibiotics and duration of therapy for patients requiring hospitalization or IV therapy: 1,20,28,30 Fluoroquinolone (e.g., ciprofloxacin 400 mg q12h, levofloxacin 750 mg daily). o If possible, avoid in pregnant women due to risk of arthropathies and teratogenicity. 34 Benefits of use may outweigh risks in complicated infections resistant to other antibiotics. 33 Aminoglycoside (e.g., gentamicin 5 mg/kg then dose adjusted for kinetics), with ampicillin 2 gms q4-6h, if suspected Enterococcus. o Gentamicin is the preferred aminoglycoside for pregnant women, due to superior safety profile. 34,39 o Ampicillin is widely used and considered safe in pregnant women. 34,39 In general, cephalosporins are considered safe and can be used as initial therapy, especially in pregnant women (e.g., ceftriaxone). 34,39 Keep in mind, these do not cover Enterococcus. 34 o Ceftriaxone use at the end of the third trimester may displace bilirubin leading to jaundice and kernicterus. 33 An extended-spectrum beta-lactam (e.g., ampicillin-sulbactam 3 gm q6h, piperacillin-tazobactam gm q6h), with an aminoglycoside (e.g., gentamicin 5 mg/kg, then adjust per kinetics), based on local resistance patterns. o Ampicillin-sulbactam and piperacillin-tazobactam are generally considered safe during pregnancy. 39 Carbapenem (e.g., ertapenem 1 gm daily, meropenem 2 gm q8h) if suspect an extended-spectrum beta-lactamaseproducing organism. o Human data are limited in pregnant women (most with imipenem-cilastatin), but neither human nor animal data suggest teratogenic risk. 34,39 Use a total of about seven to 14 days of therapy. Change to oral therapy (e.g., 48 hours after fever and symptoms resolve). 18,33,34 Streamline treatment based on C&S results: 1,34 Recommend TMP/SMX 160/800 mg BID if causative agent is susceptible. o See specific concerns in UTIs in pregnancy section above. Avoid fosfomycin and nitrofurantoin due to inadequate tissue penetration. 28 Oral beta-lactams are less effective than other agents for pyelonephritis. 28 o It may be appropriate to switch to an oral beta-lactam in stable patients if the pathogen is susceptible. 1,33

7 (Clinical Resource #340309: Page 7 of 10) How should hospitalacquired UTIs be treated? How should asymptomatic bacteriuria be addressed? When and what should be used for UTI prophylaxis? Continued UTIs make up about 40% of hospital-acquired infections (infections acquired in the hospital, while being treated for another condition). 25 Most hospital-acquired UTIs are associated with catheter use. 25 o Limit unnecessary catheter use and ensure infection control measures are up to date. Use an extended-spectrum beta-lactam (e.g., piperacillin-tazobactam 3.375gm q6h), with an aminoglycoside (e.g., gentamicin 5 mg/kg, then adjust per kinetics), based on local resistance patterns. 27 Consider a carbapenem (e.g., ertapenem 1 gm daily) for patients with urosepsis, if resistance to extendedspectrum beta-lactams are high. 26 Recommend ampicillin 2 gms q6h plus an aminoglycoside (e.g., gentamicin 5 mg/kg, then adjust per kinetics) for suspected Enterococcus (e.g., patients with urinary obstructions, catheters, urinary instrumentation). 1,27 Who should be screened and treated: Screen with a urine culture. 7 Diagnose if asymptomatic and 10 5 colony-forming units. 7 o Two consecutive isolates needed for women. 7 o Only one isolate needed for men, pregnant women, or specimens collected using a catheter. 7 Pregnant women 6 o Screen with a urine culture at about 12 to 16 weeks gestation. 34 o Treat for three to seven days with drugs and doses recommended in UTIs during pregnancy section. 30 Single-dose regimens may be less effective than three to seven days (exception fosfomycin). 15 Patients prior to invasive urologic procedures (e.g., transurethral resection of the prostate) 6 o TMP/SMX may be preferred over fluoroquinolones due to potential for serious side effects. 36 Unnecessary treatment of asymptomatic bacteriuria promotes the development of resistant organisms. 7 Who should NOT be treated: 6,7 Non-pregnant women, including those with diabetes. Elderly patients, including catheterized. Patients with spinal cord injuries. Consider prophylaxis for patients with recurrent UTIs: 4,5 2 UTIs in six months. 3 UTIs in 12 months. Continuous prophylaxis: use one of the following, once daily at bedtime unless otherwise specified. Can also dose every other night or three nights per week. 4,5 Cephalosporin (e.g., cefaclor 250 mg, cephalexin 125 to 250 mg). Nitrofurantoin 50 to 100 mg

8 (Clinical Resource #340309: Page 8 of 10) UTI prophylaxis, continued o Avoid nitrofurantoin in the elderly due to risk of hepatic and pulmonary toxicity (more common with longterm therapy). 8,9 Trimethoprim 100 mg or TMP/SMX 40/200 mg. Fosfomycin 3 gms EVERY TEN DAYS. Quinolone (e.g., ciprofloxacin 125 mg, norfloxacin 200 mg [Canada only]). Consider vaginal estrogen in postmenopausal women, especially if E. coli resistance 20%. 10,11 Post-coital prophylaxis: consider for women with UTIs 24 to 48 hours after intercourse. 4 Use one of the following within two hours of intercourse. 4,5 Cephalexin 250 mg. Nitrofurantoin 50 to 100 mg. TMP/SMX 40/200 mg to 80/400 mg. Quinolone (e.g., ciprofloxacin 125 mg [1/2 of 250 mg tablet], norfloxacin 200 mg [Canada only], ofloxacin 100 mg). Prophylaxis during pregnancy: 4 Consider continuous or post-coital prophylaxis, until the last four weeks of pregnancy. Use cephalexin 125 to 250 mg or nitrofurantoin 50 to 100 mg. Users of this resource are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication.

9 (Clinical Resource #340309: Page 9 of 10) Levels of Evidence In accordance with our goal of providing Evidence- Based information, we are citing the LEVEL OF EVIDENCE for the clinical recommendations we publish. Level Definition Study Quality A B C Good-quality patient-oriented evidence.* Inconsistent or limited-quality patient-oriented evidence.* 1. High-quality RCT 2. SR/Meta-analysis of RCTs with consistent findings 3. All-or-none study 1. Lower-quality RCT 2. SR/Meta-analysis with low-quality clinical trials or of studies with inconsistent findings 3. Cohort study 4. Case control study Consensus; usual practice; expert opinion; disease-oriented evidence (e.g., physiologic or surrogate endpoints); case series for studies of diagnosis, treatment, prevention, or screening. *Outcomes that matter to patients (e.g., morbidity, mortality, symptom improvement, quality of life). RCT = randomized controlled trial; SR = systematic review [Adapted from Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004;69: Project Leader in preparation of this clinical resource (340309): Beth Bryant, Pharm.D., BCPS, Assistant Editor References 1. Gupta K, Hooton TM, Naber KG, 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 for Microbiology and Infectious Diseases. Clin Infect Dis 2011;52:e Mayo Clinic. Urinary Tract Infection. July 23, (Accessed February 5, 2018). 3. American Urological Association. Medical student curriculum: adult uti. (Accessed February 5, 2018). 4. Epp A, Larochelle A, Lovatsis D, et al. Recurrent urinary tract infection. J Obstet Gynaecol Can 2010;32: Dason S, Dason JT, Kapoor A. Guidelines for the diagnosis and management of recurrent urinary tract infection in women. Can Urol Assoc J 2011;5: Mazzulli T. Diagnosis and management of simple and complicated urinary tract infections (UTIs). Can J Urol 2012;19: Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis 2005;40: Product information for Macrobid. Almatica Pharma. Pine Brook, NJ February Product monograph for Macrobid. Allergan Pharma. Markham, ON L6G 0B5. July Perrotta C, Aznar M, Mejia R, et al. Oestrogens for preventing recurrent urinary tract infection in postmenopausal women. Cochrane Database Syst Rev 2008;(2):CD Matthews SJ, Lancaster JW. Urinary tract infections in the elderly population. Am J Geriatr Pharmacother 2011;9: Wagenlehner FM, Naber KG. Treatment of bacterial urinary tract infections: presence and future. Eur Urol 2006;49: Hooton TM, Bradley SF, Cardenas DD, et al. Diagnosis, prevention, and treatment of catheterassociated urinary tract infection in adults: 2009 international clinical practice guidelines from the Infectious Diseases Society of America. Clin Infect Dis 2010;50: National Kidney Foundation. Urinary tract infections (Accessed February 5, 2018). 15. Widmer M, Lopez I, Gülmezoglu AM, et al. Duration of treatment for asymptomatic bacteriuria during pregnancy. Cochrane Database Syst Rev 2015;(11):CD Gomi H, Goto Y, Laopaiboon M, et al. Routine blood cultures in the management of pyelonephritis in pregnancy for improving outcomes. Cochrane Database Syst Rev 2015;(2):CD Crider KS, Cleves MA, Reefhuis J, et al. Antibacterial medication use during pregnancy and risk of birth defects. Arch Pediatr Adolesc Med 2009;163: Nicolle LE; AMMI Canada Guidelines Committee. Complicated urinary tract infection in adults. Can J Infect Dis Med Microbiol 2005;16: Toronto Central LHIN. Guidelines for the empiric treatment of urinary tract infection in adults. Reviewed January t/files/article_files/uti-guidelines_v1_0.pdf. (Accessed February 6, 2018). 20. Clinical Pharmacology powered by ClinicalKey. Tampa (FL): Elsevier (Accessed February 6, 2018). 21. Product information for Bactrim. Mutual. Philadelphia, PA June 2013.

10 (Clinical Resource #340309: Page 10 of 10) 22. Product monograph for Apo-sulfatrim. Apotex. Toronto, ON M9L 1T9. May Nicolle LE. Urinary tract infections in the elderly. Clin Geriatr Med 2009;25: Genao L, Buhr GT. Urinary tract infections in older adults residing in long-term care facilities. Ann Longterm Care 2012;20: Saint S, Kowalski CP, Kaufman SR, et al. Preventing hospital-acquired urinary tract infection in the United States: a national study. Clin Infect Dis 2008;46: Pitout JD. Infections with extended-spectrum betalactamase-producing Enterobacteriaceae: changing epidemiology and drug treatment choices. Drugs 2010;70: Jones RN, Kugler KC, Pfaller MA, Winokur PL. Characteristics of pathogens causing urinary tract infections in hospitals in North America: results from the SENTRY antimicrobial surveillance program, Diagn Microbiol Infect Dis 1999;35: Johns Hopkins Medicine. Melia M. Pyelonephritis, acute, uncomplicated. Updated August 3, 2016). Hopkins_ABX_Guide/540458/all/Pyelonephritis Ac ute Uncomplicated. (Accessed February 6, 2018). 29. Imam TH. Catheter-associated urinary tract infections (CAUTIs). May Merck Manual. rinary-disorders/urinary-tract-infections-utis/catheterassociated-urinary-tract-infections-cautis. (Accessed February 6, 2018). 30. Imam TH. Bacterial urinary tract infections (UTIs). May Merck Manual. rinary-disorders/urinary-tract-infections-utis/bacterialurinary-tract-infections-utis. (Accessed February 5, 2018). 31. American College of Obstetricians and Gynecologists. ACOG committee opinion. September Guidance-and-Publications/Committee- Opinions/Committee-on-Obstetric- Practice/Sulfonamides-Nitrofurantoin-and-Risk-of- Birth-Defects. (Accessed February 6, 2018). 32. Delzell JE, Lefevre ML. Urinary tract infections during pregnancy. Am Fam Physician 2000;61: Matuszkiewicz-Rowinska J, Malyszko J, Wieliczko M. Urinary tract infections in pregnancy: old and new unresolved diagnostic and therapeutic problems. Arch Med Sci 2015;11: Glaser AP, Schaeffer AJ. Urinary tract infection and bacteriuria in pregnancy. Urol Clin North Am 2015;42: Guinto VT, De Guia B, Festin MR, Downswell T. Different antibiotic regimens for treating asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev 2010;(9):CD American Urological Association. Urologic surgery antimicrobial prophylaxis. Updated July prophylaxis-(2008-reviewed-and-validity-confirmed amended-2012). (Accessed February 6, 2018). 37. Lee M, Bozzo P, Einarson A, Koren G. Urinary tract infections in pregnancy. June t_id=882. (Accessed February 12, 2018). 38. Thyagarajan B, Deshpande SS. Cotrimoxazole and neonatal kernicterus: a review. Drug Chem Toxicol 2014;37: Briggs GG, Freeman RK, Forinash AB, Towers CV. Drugs in Pregnancy and Lactation. 11 th ed. Philadelphia, PA: Lippincott Williams & Wilkins, Cite this document as follows: Clinical Resource, Urinary Tract Infections in Adults. Pharmacist s Letter/Prescriber s Letter. March Evidence and Recommendations You Can Trust 3120 West March Lane, Stockton, CA ~ TEL (209) ~ FAX (209) Copyright 2018 by Therapeutic Research Center Subscribers to the Letter can get clinical resources, like this one, on any topic covered in any issue by going to PharmacistsLetter.com, PrescribersLetter.com, PharmacyTechniciansLetter.com, or NursesLetter.com

11 A Note from Your Pharmacist: Balancing Risks and Benefits of Quinolones Dear, There are new warnings to restrict the use of systemic fluoroquinolones for certain infections (uncomplicated urinary tract infections [UTIs], acute sinusitis, and acute exacerbations of chronic bronchitis). This is due to the risk of quinolone-associated adverse effects, including a rare, disabling, and potentially permanent syndrome involving multiple organ systems. This syndrome can last a month or longer. Most patients (97%) complain of musculoskeletal symptoms involving muscles, joints, or tendons. Other affected systems include neuropsychiatric (68%), peripheral nervous system (63%), and vision or hearing (32%). Less commonly the skin (15%) or cardiovascular systems (12%) are involved. Most often symptoms occur within three to five days of starting a quinolone. However, they can also occur within hours of the first dose or even after completion of therapy. In light of these and other known adverse effects associated with quinolones, the risk of use generally outweighs the benefit for patients with conditions such as acute sinusitis, acute bronchitis, and uncomplicated UTIs. These infections are often viral, don t require antibiotic therapy (e.g., acute sinusitis), or can be treated with other antibiotics. Additionally, increasing quinolone resistance continues to be a concern. When a quinolone is appropriate for your patient, be sure to have them notify you about any serious adverse effects (e.g., tendon, joint, or muscle pain; tingling sensations; confusion; hallucinations). If a patient experiences a serious side effect, advise them to stop their quinolone immediately. Switch them to a non-quinolone antibiotic to complete treatment. Take the time to report serious or unusual side effects. This reporting is important to identify trends and risks associated with medication use. Use the following links to report serious side effects involving fluoroquinolones or any other medication: In the U.S.: In Canada: Sincerely, Pharmacist s Letter/Prescriber s Letter. Copyright 2016 by Therapeutic Research Center.

12 FDA Drug Safety Communication FDA advises restricting fluoroquinolone antibiotic use for certain uncomplicated infections; warns about disabling side effects that can occur together Safety Announcement [ ] The U.S. Food and Drug Administration is advising that the serious side effects associated with fluoroquinolone antibacterial drugs generally outweigh the benefits for patients with acute sinusitis, acute bronchitis, and uncomplicated urinary tract infections who have other treatment options. For patients with these conditions, fluoroquinolones should be reserved for those who do not have alternative treatment options. An FDA safety review has shown that fluoroquinolones when used systemically (i.e. tablets, capsules, and injectable) are associated with disabling and potentially permanent serious side effects that can occur together. These side effects can involve the tendons, muscles, joints, nerves, and central nervous system. As a result, we are requiring the drug labels and Medication Guides for all fluoroquinolone antibacterial drugs to be updated to reflect this new safety information. We are continuing to investigate safety issues with fluoroquinolones and will update the public with additional information if it becomes available. Patients should contact your health care professional immediately if you experience any serious side effects while taking your fluoroquinolone medicine. Some signs and symptoms of serious side effects include tendon, joint and muscle pain, a pins and needles tingling or pricking sensation, confusion, and hallucinations. Patients should talk with your health care professional if you have any questions or concerns. Health care professionals should stop systemic fluoroquinolone treatment immediately if a patient reports serious side effects, and switch to a non-fluoroquinolone antibacterial drug to complete the patient s treatment course. Fluoroquinolone drugs work by killing or stopping the growth of bacteria that can cause illness (see List of Currently Available FDA-approved Fluoroquinolones for Systemic Use). List of Currently Available FDA-approved Fluoroquinolone Antibacterial Drugs for Systemic Use

13 Brand Name Active Ingredient Avelox Moxifloxacin + Cipro Ciprofloxacin + Cipro extended-release* Ciprofloxacin extended-release + Factive Gemifloxacin + Levaquin Levofloxacin + Moxifloxacin Injection Moxifloxacin Ofloxacin* Ofloxacin + available as generic * available only as generic We previously communicated safety information associated with systemic fluoroquinolone antibacterial drugs in August 2013 and July The safety issues described in this Drug Safety Communication were also discussed at an FDA Advisory Committee meeting in November We urge patients and health care professionals to report side effects involving fluoroquinolone antibacterial drugs and other drugs to the FDA MedWatch program, using the information in the Contact FDA box at the bottom of the page. Related Information The FDA's Drug Review Process: Ensuring Drugs are Safe and Effective Thinking it Through: Managing the Benefits and Risks of Medicines Advisory Committees: Critical to the FDA's Product Review Process