Medicine in Brief

Prescribing for : Avoid fl uoroquinolones?

Jane P. Gagliardi, MD

toms of bacterial cystitis are dysuria and Principal Source: Johnson L, Sabel A, Burman WJ, et al. Emergence of fl uoroquinolone urinary frequency; additional symptoms resistance in outpatient urinary include urgency, suprapubic pain, and isolates. Am J Med. 2008;121:876-884. hematuria.5 Being familiar with UTI symptoms can ore than 8 million urinary tract infec- help expedite diagnosis and treatment be- tions (UTIs) are diagnosed annually cause you might be a psychiatric patient’s Robert M. McCarron, DO M Series Editor in the United States1 and UTI is thought to primary contact with the healthcare sys- be the most common bacterial infection.2 tem. Also, psychiatric inpatients could Half of all women report having a UTI at® Dowdentest positive for Health UTIs during Media routine med- some time in their lives.2,3 UTI is rare in ical screening. A 1-day urinalysis study men, occurring in an estimated 5 to 8 of ev- of psychiatric inpatients without urinary ery 10,000 young to middle-agedCopyright men,For4 but personalcatheters detected use UTIs only in approximately increases with age such that UTI rates in 5% of patients.6 In addition, UTI is a com- men age >70 are approximately one-third mon cause of delirium. the rates in women.2 Up to 85% percent of UTIs are attribut- ed to Escherichia coli.3 The hallmark symp- Screening The utility of routine screening urinalysis Dr. Gagliardi is assistant professor of psychiatry and behavioral is under debate, and testing is best used in sciences and assistant clinical professor of medicine, Duke University School of Medicine, Durham, NC. cases of suspected UTI. However, medical

Table resistance among levofl oxacin-resistant and levofl oxacin-susceptible strains ofE coli*

Percent of levofl oxacin- Percent of levofl oxacin- resistant strains of E coli susceptible strains of E coli Antibiotic resistant to antibiotic resistant to antibiotic Amoxicillin/clavulanate 9.8% 0% Ampicillin 78.0% 40.2% Cefazolin 26.8% 9.8% Ceftriaxone 4.9% 0% Gentamicin 24.4% 1.2% Nitrofurantoin 4.9% 1.2% TMP/SMZ 65.9% 29.3%

*41 patients with levofl oxacin-resistantE coli compared with 81 matched controls with levofl oxacin-susceptibleE coli TMP/SMZ: / Current Psychiatry Source: Reference 1 Vol. 8, No. 7 49 continued on page 56

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continued from page 49 disorders frequently are not recognized E coli rose almost 10-fold, from 1% in 1999 in psychiatric patients, especially in older to 9.4% in 2005. A detailed analysis of 2005 patients7 or those with risk factors for UTI. E coli isolates showed that previous levo- Sexually transmitted diseases (STDs) are fl oxacin prescription was strongly associ- not major contributors to UTI risk; howev- ated with FQ resistance (odds ratio 5.6, er, they may share common symptoms and 95% confi dence interval: 2.1 to 27.5). Levo- urinalysis fi ndings. If patients report symp- fl oxacin-resistant strains ofE coli also were toms of UTI (urgency, dysuria, frequency), more likely than levofl oxacin- sensitive urinalysis is indicated. In a urinalysis, >2 to strains to be resistant to other antibiot- 5 leukocytes per high-powered fi eld in an ics—90% compared with 43% for control uncontaminated centrifuged speci- specimens (Table, page 49). men without a high number of squamous The use of FQs as fi rst-line treatment of epithelial cells suggest UTI. UTIs also is leading to resistant strains of In patients with abnormal urinalysis, ask Streptococcus pneumoniae,10 Salmonella,11,12 about dysuria, urinary frequency, history of Neisseria meningitides,13 and other bacteria. UTIs, and use of . Antibiotic use From an individual and public health per- Clinical Point in the preceding 12 months is associated spective, it is important that psychiatrists Hallmark symptoms with increased risk of bacterial resistance.1 monitor local resistance patterns and treat- of UTI are dysuria Assess for symptoms of complicated UTI ment recommendations. such as fever, fl ank pain, nausea, and vom- In areas without widespread bacterial and urinary iting. Urine culture is not recommended for resistance to TMP/SMZ, a 3-day course frequency; additional uncomplicated UTI but may be necessary of TMP/SMZ could be considered fi rst- symptoms include when symptoms do not resolve or signs of line treatment for uncomplicated UTI in urgency, suprapubic complicated UTI emerge. Consider possible patients without allergies or contraindica- STDs in patients with sterile pyuria.5 tions. However, in areas where resistance pain, and hematuria to TMP/SMZ is high, a 7-day course of ni- trofurantoin is recommended for uncom- Treatment and antibiotic plicated cystitis. Resistance patterns can resistance vary from hospital to hospital and even For patients with uncomplicated UTI, a among units in the same hospital;14 there- short course of empiric antibiotics is ap- fore, refer to local microbiology labs for propriate even in the absence of confi rma- “antibiograms” or information regarding tory culture data. Fluoroquinolones (FQs), resistance patterns.

such as ciprofl oxacin and levofl oxacin, Related Resource have been used as a fi rst-line treatment. • National Guideline Clearinghouse. Urinary tract infection. www.guidelines.gov/summary/summary.aspx?doc_ However, FQs are associated with: id=7407. • QTc-prolongation, a concern when co- Drug Brand Names administered with antipsychotics8 Ampicillin • Principen • delirium Cefazolin • Ancef Ceftriaxone • Rocephin • increased risk of tendinitis and tendon Ciprofl oxacin • Ciloxan, Cipro, Cipro XR, ProQuin XR rupture9 Gentamicin • Garamycin Levofl oxacin • Levaquin • antibiotic resistance. Nitrofurantoin • Furadantin, Macrodantin, Macrobid, Urotoin Trimethoprim/Sulfamethoxazole • Bacter-Aid DS, Bactrim, Septra, A study of a comprehensive urban pub- Sulfatrim, Sultrex lic health system in Denver, CO, showed Tobramycin • Nebcin ONLINE ONLY that rates of FQ-resistant E coli increased Disclosure after levofl oxacin was established as fi rst- Dr. Gagliardi reports no fi nancial relationship with any company Visit this article at line therapy for UTIs. This occurred after whose products are mentioned in this article or with manufactur- CurrentPsychiatry.com ers of competing products. to view an algorithm E coli strains developed high resistance to for managing UTI in an earlier fi rst-line therapy, trimethoprim/ References nonpregnant adults 1 1. Johnson L, Sabel A, Burman WJ, et al. Emergence of sulfamethoxazole (TMP/SMZ). Using fl uoroquinolone resistance in outpatient urinary Escherichia pharmacy and laboratory databases, in- coli isolates. Am J Med. 2008;121:876-884. vestigators found that as levofl oxacin pre- 2. Foxman B. Epidemiology of urinary tract infections: Current Psychiatry incidence, morbidity, and economic costs. Am J Med. 56 July 2009 scriptions increased, rates of FQ- resistant 2002;113:5S-13S.

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3. Hooten TM, Stamm WE. Acute cystitis in women. Up To Infect Control Hosp Epidemiol. 2006;27(7):682-687. Date. Available at: http://www.utdol.com/online/content/ 14. Woo BK, Daly JW, Allen EC, et al. Unrecognized medical topic.do?topicKey=uti_infe/6763. Accessed March 24, 2009. disorders in older psychiatric inpatients in a senior 4. Hooten TM, Stamm WE. Acute cystitis and asymptomatic behavioral health unit in a university hospital. J Geriatr in men. Up To Date. Available at: http://www. Psychiatry Neurol. 2003;16(2):121-125. utdol.com/online/content/topic.do?topicKey=uti_infe/ 5503&selectedTitle=1~150&source=search_result. Accessed June 1, 2009. 5. Meyrier A. Urine sampling and culture in the diagnosis of urinary tract infection in adults. Up To Date. Available at: http://www.utdol.com/ online/content/topic.do?topicKey=uti_infe/ Practice Points 4805&selectedTitle=10~150&source=search_result. Accessed March 24, 2009. • Widespread use of FQs to treat UTIs has 6. Eveillard M, Bourlioux F, Manuel C, et al. Association been associated with increasing bacterial between the use of anticholinergic agents and asymptomatic bacteriuria. Eur J Clin Microbiol Infect Dis. 2000;19(2):149- resistance to FQs and other antibiotics. 150. 7. Falagas ME, Rafailidis PI, Rosmarakis ES. Arrhythmias • FQs are associated with tendonitis and associated with fl uoroquinolone therapy. Int J Antimicrob tendon rupture, QTc prolongation—a Agents. 2007;29(4):374-379. 8. U.S. Food and Drug Administration. Fluoroquinolone concern when coadministered with antimicrobial drugs. Available at: http://www. antipsychotics—and delirium. fda.gov/safety/medwatch/safetyinformation/ safetyalertsforhumanmedicalproducts/ucm089652.htm. Accessed April 7, 2009. • For uncomplicated UTI in the absence 9. Chen DK, McGeer A, de Azavedo JC, et al. Decreased of contraindications, consider treating susceptibility of Streptococcus pneumoniae to fl uoroquinolones nonpregnant patients in areas with in Canada. Canadian Bacterial Surveillance Network. N Engl J Med. 1999;341(4):233-239. low TMP/SMZ resistance with TMP/ 10. Olsen SJ, DeBess EE, McGivern TE, et al. A nosocomial SMZ for 3 days or nitrofurantoin for outbreak of fl uoroquinolone-resistantSalmonella infection. N Engl J Med. 2001;344(21):1572-1579. 7 days, but consider nitrofurantoin 11. Chiu CH, Wu TL, Su LH, et al. The emergence in Taiwan as a fi rst-line treatment in areas with of fl uoroquinolone resistance inSalmonella enterica serotype choleraesuis. N Engl J Med. 2002;346(6):413-419. high resistance to TMP/SMZ. 12. Wu HM, Harcourt BH, Hatcher CP, et al. Emergence of ciprofl oxacin-resistant Neisseria meningitides in North • Refer patients with symptoms America. N Engl J Med. 2009;360(9):886-892. of complicated UTIs to a primary 13. Binkley S, Fishman NO, LaRosa LA, et al. Comparison of unit-specifi c and hospital-wide antibiograms: potential care physician for treatment. implications for selection of empirical antimicrobial therapy.

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