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New Perspectives on Urinary Tract Infection in Men Comment on “Urinary Tract Infection in Male Veterans: Treatment Patterns and Outcomes” and on “Preoperative Urine Cultures at a Veterans Affairs Medical Center”

New Perspectives on Urinary Tract Infection in Men Comment on “Urinary Tract Infection in Male... Most studies on the treatment of acute urinary tract infection (UTI) in outpatients have been performed in women, usually premenopausal women. The most recent treatment guidelines for acute, uncomplicated cystitis issued by the Infectious Diseases Society of America1 specifically exclude men from their recommendations, presumably for a lack of evidence to guide recommendations. The extensive literature on UTI in women recognizes that the pathogenesis, risk factors, and optimal management of UTI may differ by age and by menopausal status. We would expect similar distinctions in male UTI, particularly given the role of age-associated prostatic enlargement in urinary retention, but the available literature neither refutes nor supports this point. Recommendations for the treatment of male UTI generally state that 7 to 14 days of antibiotic therapy are required, without clear evidence to guide this statement.2 Against this background, 2 studies by Drekonja et al3,4 in this issue of the journal stand out in welcome relief. Both studies are from the same research group and patient population, namely, older male veterans at the Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota. Both studies address questions about the field of UTI in which the existing literature is insufficient to guide clinical management. The full article,3 entitled “Urinary Tract Infection in Male Veterans: Treatment Patterns and Outcomes,” focuses on the appropriate duration of antibiotic therapy for outpatient male veterans with UTI. This retrospective study used administrative data and International Classification of Diseases, Ninth Revision codes to examine outpatient male UTI, with attention to whether shorter duration (≤7 days) or longer duration (>7 days) of antibiotic therapy was prescribed. Clinical outcomes studied included recurrence of UTI and Clostridium difficile infection (CDI). Of 33 336 index UTI cases identified, 11 666 patients (35.0%) received shorter-duration treatment and 21 670 patients (65.0%) received longer-duration treatment. An important point to keep in mind is that most of the group receiving shorter-duration therapy received 7 days of antibiotic treatment, while most of the group receiving longer-duration therapy received 10 days of antibiotic treatment, so that the duration of therapy was not dramatically different between groups. Overall, 4449 index cases (13.3%) had a recurrence within 12 months. Treatment duration was not associated with early recurrence (<30 days) in univariate or multivariate analysis, while longer-duration treatment was associated with late recurrence (≥30 days) in univariate and multivariate analyses. Longer-duration therapy was associated with CDI only in univariate analysis; not surprisingly, an increasing Charlson Comorbidity Index was also associated with CDI. The inherent weaknesses in the use of International Classification of Diseases, Ninth Revision codes to identify patients with UTI, as acknowledged by the authors, include a lack of information about what the symptoms of UTI were, how many patients used a urinary catheter, and whether the UTI episodes were complicated or uncomplicated. Furthermore, the study was retrospective, not a randomized controlled trial, and was subject to confounding bias. It is plausible that health care providers prescribed longer courses of antibiotics for sicker patients at higher risk for recurrent UTI; such patients would also have been at higher risk for CDI. The authors discuss this possibility and point out that multiple demographic and clinical characteristics were associated with longer duration of therapy, including a history of UTI, prostatitis, or spinal cord injury. The research letter4 entitled “Preoperative Urine Cultures at a Veterans Affairs Medical Center” addresses whether screening for and treatment of bacteriuria before certain surgical procedures (cardiothoracic, orthopedic, and vascular) confers benefits. Although this study was not specifically focused on older men, the veteran patient population studied was 96% male, with a mean age of 61.8 years, similar to the mean age of 67.9 years in the full article on outpatient male UTI. Of 1934 procedures performed in 1688 patients, a preoperative urine culture was obtained in 489 cases. Of these cultures, 54 were positive, and 16 patients (8 with positive cultures and 8 with low colony counts or negative cultures) were treated with preoperative antibiotics. The fact that patients who received preoperative screening urine cultures were older, more likely to develop CDI, and more likely to develop surgical site infection suggests that unmeasured factors were likely driving providers' decisions about which patients needed preoperative screening. Patients with preoperative bacteriuria were more likely to have a postoperative UTI diagnosed by their provider; this could indicate a higher intrinsic risk for UTI or a higher index of suspicion among the providers. Treated patients were more likely to experience surgical site infections after surgery. However, given the few treated patients and the strong likelihood of confounding variables, this study cannot provide conclusive evidence about the risks and benefits of treating preoperative bacteriuria in older men. What both studies can do, and indeed do effectively, is to call into question current treatment practices concerning bacteriuria in men. We often joke that “mice are not humans” when asking whether animal studies have clinical applicability; the same adage can be applied here, namely, that men are different from women and that older men are different from younger men. Although neither of the retrospective studies published in this issue of the journal can demonstrate causality between antibiotic treatment of bacteriuria and worse outcomes, the associations they report have biologic plausibility and are in concordance with the greater body of literature concerning the overtreatment of bacteriuria. Urinary tract infection and the associated condition of asymptomatic bacteriuria are major drivers of antibiotic use in inpatient and outpatient settings.5 The treatment of asymptomatic bacteriuria in most clinical settings is not necessary and may be harmful in terms of CDI, antibiotic resistance, and unnecessary costs.6 The 2011 Infectious Diseases Society of America1 guidelines on the management of acute cystitis ask providers to consider potential collateral damage to the patient's microbiome when choosing therapy for this common condition. The Infectious Diseases Society of America guidelines on catheter-associated UTI echo this concern by making a strong statement about reducing the duration of treatment from 14 days to 7 days in those patients who respond promptly to therapy.7 A 2012 randomized controlled study8 of asymptomatic bacteriuria in young women found that the treatment of asymptomatic bacteriuria increased the subsequent risk for UTI. Furthermore, the relationships of duration, number, and dosage of antimicrobial agents with subsequent CDI are well established.9 We recommend a culture shift in antibiotic prescribing practices for men with bacteriuria from “more is better” to “less is more.” Widespread antimicrobial resistance, appreciation of the human microbiome, outbreaks of CDI, and emphasis on cost-effective care discourage the indiscriminate use of antibiotics. On the other hand, the studies commented on herein encourage more judicious use of antibiotics by failing to find evidence of clinical benefit with longer courses of antibiotics or with additional courses of preoperative antibiotics. As we continue to explore UTI in the male half of the population, these articles are a timely reminder that standard practice is not always best practice and that critical thinking is required to recognize the difference. Back to top Article Information Published Online: December 3, 2012. doi:10.1001/jamainternmed.2013.1783 Correspondence: Dr Trautner, Section of Infectious Diseases, Health Services Research Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd, Houston, TX 77030 (trautner@bcm.edu). Conflict of Interest Disclosures: None reported. References 1. Gupta K, Hooton TM, Naber KG, et al; Infectious Diseases Society of America; European Society for Microbiology and Infectious Diseases. 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(5):e103-e120.http://www.ncbi.nlm.nih.gov/pubmed/21292654?dopt=Abstract. Accessed September 27, 201221292654PubMedGoogle ScholarCrossref 2. Trautner BW, Gupta K. Urinary tract infections, pyelonephritis, and prostatitis. In: Longo D, Fauci A, Kasper D, Hauser S, Jameson J, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill Companies; 2012 3. Drekonja DM, Rector TS, Cutting A, Johnson JR. Urinary tract infection in male veterans: treatment patterns and outcomes [published online December 3, 2012]. JAMA Intern Med. 2013;173(1):62-68Google Scholar 4. Drekonja DM, Zarmbinski B, Johnson JR. Preoperative urine cultures at a Veterans Affairs medical center [published online December 3, 2012]. JAMA Intern Med. 2013;173(1):71-72Google Scholar 5. Trautner BW. Asymptomatic bacteriuria: when the treatment is worse than the disease. Nat Rev Urol. 2011;9(2):85-93Google ScholarCrossref 6. Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM.Infectious Diseases Society of America; American Society of Nephrology; American Geriatric Society. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005;40(5):643-65415714408PubMedGoogle ScholarCrossref 7. Hooton TM, Bradley SF, Cardenas DD, et al; Infectious Diseases Society of America. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(5):625-66320175247PubMedGoogle ScholarCrossref 8. Cai T, Mazzoli S, Mondaini N, et al. The role of asymptomatic bacteriuria in young women with recurrent urinary tract infections: to treat or not to treat? Clin Infect Dis. 2012;55(6):771-77722677710PubMedGoogle ScholarCrossref 9. Stevens V, Dumyati G, Fine LS, Fisher SG, van Wijngaarden E. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis. 2011;53(1):42-4821653301PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Internal Medicine American Medical Association

New Perspectives on Urinary Tract Infection in Men Comment on “Urinary Tract Infection in Male Veterans: Treatment Patterns and Outcomes” and on “Preoperative Urine Cultures at a Veterans Affairs Medical Center”

JAMA Internal Medicine , Volume 173 (1) – Jan 14, 2013

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Publisher
American Medical Association
Copyright
Copyright © 2013 American Medical Association. All Rights Reserved.
ISSN
2168-6106
eISSN
2168-6114
DOI
10.1001/jamainternmed.2013.1783
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Abstract

Most studies on the treatment of acute urinary tract infection (UTI) in outpatients have been performed in women, usually premenopausal women. The most recent treatment guidelines for acute, uncomplicated cystitis issued by the Infectious Diseases Society of America1 specifically exclude men from their recommendations, presumably for a lack of evidence to guide recommendations. The extensive literature on UTI in women recognizes that the pathogenesis, risk factors, and optimal management of UTI may differ by age and by menopausal status. We would expect similar distinctions in male UTI, particularly given the role of age-associated prostatic enlargement in urinary retention, but the available literature neither refutes nor supports this point. Recommendations for the treatment of male UTI generally state that 7 to 14 days of antibiotic therapy are required, without clear evidence to guide this statement.2 Against this background, 2 studies by Drekonja et al3,4 in this issue of the journal stand out in welcome relief. Both studies are from the same research group and patient population, namely, older male veterans at the Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota. Both studies address questions about the field of UTI in which the existing literature is insufficient to guide clinical management. The full article,3 entitled “Urinary Tract Infection in Male Veterans: Treatment Patterns and Outcomes,” focuses on the appropriate duration of antibiotic therapy for outpatient male veterans with UTI. This retrospective study used administrative data and International Classification of Diseases, Ninth Revision codes to examine outpatient male UTI, with attention to whether shorter duration (≤7 days) or longer duration (>7 days) of antibiotic therapy was prescribed. Clinical outcomes studied included recurrence of UTI and Clostridium difficile infection (CDI). Of 33 336 index UTI cases identified, 11 666 patients (35.0%) received shorter-duration treatment and 21 670 patients (65.0%) received longer-duration treatment. An important point to keep in mind is that most of the group receiving shorter-duration therapy received 7 days of antibiotic treatment, while most of the group receiving longer-duration therapy received 10 days of antibiotic treatment, so that the duration of therapy was not dramatically different between groups. Overall, 4449 index cases (13.3%) had a recurrence within 12 months. Treatment duration was not associated with early recurrence (<30 days) in univariate or multivariate analysis, while longer-duration treatment was associated with late recurrence (≥30 days) in univariate and multivariate analyses. Longer-duration therapy was associated with CDI only in univariate analysis; not surprisingly, an increasing Charlson Comorbidity Index was also associated with CDI. The inherent weaknesses in the use of International Classification of Diseases, Ninth Revision codes to identify patients with UTI, as acknowledged by the authors, include a lack of information about what the symptoms of UTI were, how many patients used a urinary catheter, and whether the UTI episodes were complicated or uncomplicated. Furthermore, the study was retrospective, not a randomized controlled trial, and was subject to confounding bias. It is plausible that health care providers prescribed longer courses of antibiotics for sicker patients at higher risk for recurrent UTI; such patients would also have been at higher risk for CDI. The authors discuss this possibility and point out that multiple demographic and clinical characteristics were associated with longer duration of therapy, including a history of UTI, prostatitis, or spinal cord injury. The research letter4 entitled “Preoperative Urine Cultures at a Veterans Affairs Medical Center” addresses whether screening for and treatment of bacteriuria before certain surgical procedures (cardiothoracic, orthopedic, and vascular) confers benefits. Although this study was not specifically focused on older men, the veteran patient population studied was 96% male, with a mean age of 61.8 years, similar to the mean age of 67.9 years in the full article on outpatient male UTI. Of 1934 procedures performed in 1688 patients, a preoperative urine culture was obtained in 489 cases. Of these cultures, 54 were positive, and 16 patients (8 with positive cultures and 8 with low colony counts or negative cultures) were treated with preoperative antibiotics. The fact that patients who received preoperative screening urine cultures were older, more likely to develop CDI, and more likely to develop surgical site infection suggests that unmeasured factors were likely driving providers' decisions about which patients needed preoperative screening. Patients with preoperative bacteriuria were more likely to have a postoperative UTI diagnosed by their provider; this could indicate a higher intrinsic risk for UTI or a higher index of suspicion among the providers. Treated patients were more likely to experience surgical site infections after surgery. However, given the few treated patients and the strong likelihood of confounding variables, this study cannot provide conclusive evidence about the risks and benefits of treating preoperative bacteriuria in older men. What both studies can do, and indeed do effectively, is to call into question current treatment practices concerning bacteriuria in men. We often joke that “mice are not humans” when asking whether animal studies have clinical applicability; the same adage can be applied here, namely, that men are different from women and that older men are different from younger men. Although neither of the retrospective studies published in this issue of the journal can demonstrate causality between antibiotic treatment of bacteriuria and worse outcomes, the associations they report have biologic plausibility and are in concordance with the greater body of literature concerning the overtreatment of bacteriuria. Urinary tract infection and the associated condition of asymptomatic bacteriuria are major drivers of antibiotic use in inpatient and outpatient settings.5 The treatment of asymptomatic bacteriuria in most clinical settings is not necessary and may be harmful in terms of CDI, antibiotic resistance, and unnecessary costs.6 The 2011 Infectious Diseases Society of America1 guidelines on the management of acute cystitis ask providers to consider potential collateral damage to the patient's microbiome when choosing therapy for this common condition. The Infectious Diseases Society of America guidelines on catheter-associated UTI echo this concern by making a strong statement about reducing the duration of treatment from 14 days to 7 days in those patients who respond promptly to therapy.7 A 2012 randomized controlled study8 of asymptomatic bacteriuria in young women found that the treatment of asymptomatic bacteriuria increased the subsequent risk for UTI. Furthermore, the relationships of duration, number, and dosage of antimicrobial agents with subsequent CDI are well established.9 We recommend a culture shift in antibiotic prescribing practices for men with bacteriuria from “more is better” to “less is more.” Widespread antimicrobial resistance, appreciation of the human microbiome, outbreaks of CDI, and emphasis on cost-effective care discourage the indiscriminate use of antibiotics. On the other hand, the studies commented on herein encourage more judicious use of antibiotics by failing to find evidence of clinical benefit with longer courses of antibiotics or with additional courses of preoperative antibiotics. As we continue to explore UTI in the male half of the population, these articles are a timely reminder that standard practice is not always best practice and that critical thinking is required to recognize the difference. Back to top Article Information Published Online: December 3, 2012. doi:10.1001/jamainternmed.2013.1783 Correspondence: Dr Trautner, Section of Infectious Diseases, Health Services Research Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd, Houston, TX 77030 (trautner@bcm.edu). Conflict of Interest Disclosures: None reported. References 1. Gupta K, Hooton TM, Naber KG, et al; Infectious Diseases Society of America; European Society for Microbiology and Infectious Diseases. 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(5):e103-e120.http://www.ncbi.nlm.nih.gov/pubmed/21292654?dopt=Abstract. Accessed September 27, 201221292654PubMedGoogle ScholarCrossref 2. Trautner BW, Gupta K. Urinary tract infections, pyelonephritis, and prostatitis. In: Longo D, Fauci A, Kasper D, Hauser S, Jameson J, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill Companies; 2012 3. Drekonja DM, Rector TS, Cutting A, Johnson JR. Urinary tract infection in male veterans: treatment patterns and outcomes [published online December 3, 2012]. JAMA Intern Med. 2013;173(1):62-68Google Scholar 4. Drekonja DM, Zarmbinski B, Johnson JR. Preoperative urine cultures at a Veterans Affairs medical center [published online December 3, 2012]. JAMA Intern Med. 2013;173(1):71-72Google Scholar 5. Trautner BW. Asymptomatic bacteriuria: when the treatment is worse than the disease. Nat Rev Urol. 2011;9(2):85-93Google ScholarCrossref 6. Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM.Infectious Diseases Society of America; American Society of Nephrology; American Geriatric Society. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005;40(5):643-65415714408PubMedGoogle ScholarCrossref 7. Hooton TM, Bradley SF, Cardenas DD, et al; Infectious Diseases Society of America. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(5):625-66320175247PubMedGoogle ScholarCrossref 8. Cai T, Mazzoli S, Mondaini N, et al. The role of asymptomatic bacteriuria in young women with recurrent urinary tract infections: to treat or not to treat? Clin Infect Dis. 2012;55(6):771-77722677710PubMedGoogle ScholarCrossref 9. Stevens V, Dumyati G, Fine LS, Fisher SG, van Wijngaarden E. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis. 2011;53(1):42-4821653301PubMedGoogle ScholarCrossref

Journal

JAMA Internal MedicineAmerican Medical Association

Published: Jan 14, 2013

Keywords: urinary tract infections,hospitals, veterans,preoperative care,veterans,urine culture

References