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The number of patients treated for UTIs in US emergency rooms was 2. Million in 2006 and 2. Million in 2009. Recurrent UTIs have a considerable impact on quality of life, not only due to pain and discomfort but also by disrupting sexual activity. There is no consensus regarding a single superior strategy for the prevention of UTIs.
The number of patients treated for UTIs in US emergency rooms was 2. Million in 2006 and 2. Million in 2009. Recurrent UTIs have a considerable impact on quality of life, not only due to pain and discomfort but also by disrupting sexual activity. There is no consensus regarding a single superior strategy for the prevention of UTIs.
The number of patients treated for UTIs in US emergency rooms was 2. Million in 2006 and 2. Million in 2009. Recurrent UTIs have a considerable impact on quality of life, not only due to pain and discomfort but also by disrupting sexual activity. There is no consensus regarding a single superior strategy for the prevention of UTIs.
Prevention of Urinary Tract Infection Kalpana Gupta 1,2 and Nahid Bhadelia 3,4 1 Infectious Diseases, Veterans Affairs Boston Healthcare System, West Roxbury, 2 Infectious Diseases, Boston University School of Medicine, 3 Hospital Epidemiology, Boston Medical Center, and 4 Section of Infectious Diseases, Boston University School of Medicine, Massachusetts (See the Major Article by Eells et al on pages 14760.) Keywords. UTI; non-antimicrobial prevention; self-initiated therapy; patient-centered. Urinary tract infection (UTI) is a common and costly infection; a recent study estimated that the number of patients treated for UTIs in US emergency rooms was 2.0 million in 2006 and 2.3 million in 2009. The overall estimated annual direct and indirect cost of UTI in the United States in 2010 was $2.3 billion [1]. The excess cost of emergency room care, when compared to healthcare services provided in the outpatient setting, is >$1.5 billion annually [2]. Beyond direct healthcare costs, the human cost of re- current UTIs is broader and more difcult to quantify in term of dollars and cents. Recurrent UTIs have a considerable impact on quality of life, not only due to pain and discomfort but also by disrupting sexual activity [3]. Furthermore, patients and employers may suffer signicantly from lost revenue due to missed work resulting from symptoms and the time needed to access medical care. Reduction of UTI has the potential to decrease healthcare and societal costs by billions of dollars annually. There is no consensus regarding a single superior strategy for the prevention of UTIs. Prior Cochrane reviews demonstrated a decrease in UTIs through use of continuous low-dose antibiotics compared to placebo; however, the treatment arm also experienced higher rates of adverse events [4]. A similar review comparing cranberry juice to no intervention failed to demonstrate a clear benet [5]. Moreover, there are no trials comparing the relative efcacy of all of the pre- vention and management options with an evaluation of their relative benets to both individual patients and the healthcare system as a whole. Eells et al present a well-organized decision analysis addressing the comparative effectiveness of different prevention options [6]. They evaluate the impact of 5 strategies, chosen based on the availability of adequate published data, on reducing recurrent UTIs in women. Strategies evaluated in the model include daily nitrofur- antoin prophylaxis, topical estrogen prophylaxis, daily cranberry prophylaxis, monthly acupuncture sessions, and self-directed treatment with ciprooxacin at the earliest symptom. The authors evaluate the reduction in the absolute number of UTIs, as well as improve- ment in quality-adjusted life-days (QALDs) and cost per QALD gained. The models are constructed from both the payer and the patient perspectives and evalu- ate both high (>8 UTIs per year) and moderate (>3 UTIs per year) recurrence rates. Daily prophylactic use of nitrofurantoin resulted in the lowest number of UTIs per year (0.4) and the highest payer cost, but also the most QALDs gained per year. Surprisingly, acupuncture resulted in the second- highest QALDs gained and decreased UTIs to 0.7. The authors remark that this could be secondary to publica- tion bias resulting from the relatively small number of studies on acupuncture. Cranberry juice and estrogen Received 10 September 2013; accepted 12 September 2013; electronically published 24 September 2013. Correspondence: Kalpana Gupta, MD, MPH, VA Boston HCS, 1400 VFW Parkway, MED 111, West Roxbury, MA (kalpana.gupta@va.gov). Clinical Infectious Diseases 2014;58(2):1613 Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2013. This work is written by (a) US Government employee(s) and is in the public domain in the US. DOI: 10.1093/cid/cit648 EDITORIAL COMMENTARY CID 2014:58 (15 January) 161
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replacement each also reduced recurrent UTI rates with slightly more modest gains in QALDs. Symptomatic self-treatment was the cheapest to both payers and patients as it resulted in de- creased utilization of the healthcare system, but it did not result in signicant QALDs gained as there was no reduction in the number of UTIs per year. It would be interesting to assess if the inclusion of economic costs to the consumer through workdays missed would improve the overall attractiveness of this strategy. Furthermore, these studies did not evaluate the psychological benet to the patient of being able to exercise control over a painful and capricious illness, as permitted by self-initiated therapy. As the authors suggest, daily antibiotic use is the most studied and effective prevention strategy. If we take these nd- ings at face value, many of our patients who have opted for other nonantimicrobial management strategies would start using regular prophylactic antibiotics instead. The impact of this shift is difcult to quantitate, but includes increased rates of antibiotic-related adverse events, antimicrobial resistance (direct as well as collateral), and possibly other as yet undeter- mined outcomes associated with alterations of the microbiome related to antibiotic use. Antimicrobial resistance is an escalating problem in the am- bulatory setting, even with apparently simple clinical problems, such as uncomplicated cystitis [7, 8]. Although the frequency of resistant organisms varies by patient population and geography, multidrug-resistant uropathogens including extended-spectrum -lactamase (ESBL)producing gram-negative bacteria raise considerable concern about the ability of clinicians to treat UTIs with orally available agents in the outpatient setting [9]. Currently, a signicant percentage of ESBL and enterococcal isolates remain sensitive to nitrofurantoin [1012]. The barrier to development of nitrofurantoin resistance is high. However, widespread adoption of daily nitrofurantoin therapy among a large cohort of women might lead to rapid emergence of resis- tance. Other classes of antimicrobials such as cephalosporins, uoroquinolones, or trimethoprim-sulfamethoxazole that are frequently used for UTI prophylaxis certainly have a propensity for propagating resistance, even with short-term use. Eells model is constructed to account for a certain number of treatment failures, which lead to further healthcare costs due to subsequent visits or hospitalizations. In reality, the per- centage of failures will increase with time as rates of resistance rise; hence, whether the strategy remains cost effective in the long run is unclear. Certainly, the attractiveness of the use of chronic suppressive antimicrobials will worsen over time. Fur- thermore, the daily antimicrobial prophylaxis strategy is mired with the possibility of adverse reactions secondary to the antimicrobial itself, an outcome not easily captured in the model [13]. Variations in dosing (daily vs less frequent post- coital or thrice-weekly regimens) and in the agents used for prophylaxis and treatment are also not easily incorporated into the model, in part due to limited availability of compara- tive data. How do we balance the UTI reduction benets garnered by daily antibiotic prophylaxis with the societal cost of resistance or adverse drug reactions? Before adopting this strategy en masse, we should recall the insight of famed statistician George E. Box: Essentially, all models are wrong, but some are useful [14]. Fundamentally, all models, even the best ones, are based on estimates and approximations. Although they may provide powerful, thought-provoking information, we should proceed with caution prior to incorporating modeling results into clini- cal practice. Instead of interpreting the work of Eells et al as a call for antibi- otic prophylaxis as the optimal prevention strategy, we must think beyond the decision model and consider approaches to prevention that are novel and informed by the model. Results of decision analysis models are driven by publicly available data from individ- ual clinical trials and epidemiological studies. Hence, only single or studied combinations of interventions or strategies can be reli- ably incorporated into the analyses. However, clinicians are not limited to using only approaches evaluated in the decision model. In real-world practice, clinicians often use mixed combinations of strategies. Combining approaches may result in additive or perhaps even synergistic benets to patients. For example, in an individual case, a clinician and patient working together may opt to use acupuncture in combination with cranberry juice and self- directed therapy at the rst sign of symptoms. Further complicating the issue is that different payers may choose to cover varied aspects of the prevention strategies avail- able in the clinical toolbox. The overall efcacy and QALDs yielded from each of these combination approaches is unknown, and may differ according to both the risk of UTI and patient ac- ceptance of complementary and alternative medical treatments. The decision model presented in this issue provides esti- mates for each strategy and serves as a starting point for patient counseling; less predictable Xfactors such as patient beliefs, preferences, and values will ultimately determine the best option for an individual. This integrated approach is similar to the bundle concept directed toward the prevention of health- care-associated infections, with the notable difference that the bundle in this case is modied based on individual patient inputperhaps best termed a patient-centered bundle for UTI prevention. The work of Eells and colleagues contributes to this patient-centered decision making being a more in- formed and effective process, while illustrating the importance of additional clinical trials examining bundled strategies for this common clinical problem. Notes Acknowledgments. We greatly appreciate the critical review of the manuscript draft by Dr Westyn Branch-Elliman. 162 CID 2014:58 (15 January) EDITORIAL COMMENTARY
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Potential conicts of interest. K. G. has served as a consultant for Paratek Pharmaceutical and is an equity holder in Aegis Womens Health Technologies, Inc. N. B. reports no potential conicts. Both authors have submitted the ICMJE Form for Disclosure of Potential Conicts of Interest. Conicts that the editors consider relevant to the content of the manuscript have been disclosed. References 1. Foxman B. The epidemiology of urinary tract infection. Nature reviews. Urology 2010; 7:65360. 2. Sammon JD, Ghani KR, Sukumar S, et al. Socioeconomic trends and utilization in the emergency department treatment of urinary tract in- fections. In: American Urological Association 2013 Annual Meeting, San Diego, CA, 48 May, 2013. Abstract 1062. 3. Ciani O, Grassi D, Tarricone R. An economic perspective on urinary tract infection: the costs of resignation. Clin Drug Investig 2013; 33:25561. 4. Albert X, Huertas I, Pereiro II, Sanfelix J, Gosalbes V, Perrota C. Antibiotics for preventing recurrent urinary tract infection in non- pregnant women. Cochrane Database Syst Rev 2004; CD001209. 5. Jepson RG, Craig JC. Cranberries for preventing urinary tract infec- tions. Cochrane Database Syst Rev 2008; CD001321. 6. Eells SJ, Bharadwa K, McKinnell JA. Recurrent urinary tract infections among adult women: comparative effectiveness of 5 prevention and management strategies using a Markov chain Monte Carlo model. Clin Infect Dis 2014; 58:14760. 7. Zalmanovici Trestioreanu A, Green H, Paul M, Yaphe J, Leibovici L. Antimicrobial agents for treating uncomplicated urinary tract infection in women. Cochrane Database Syst Rev 2010; CD007182. 8. Doi Y, Park YS, Rivera JI, et al. Community-associated extended- spectrum beta-lactamase-producing Escherichia coli infection in the United States. Clin Infect Dis 2013; 56:6418. 9. Meier S, Weber R, Zbinden R, Ruef C, Hasse B. Extended-spectrum beta-lactamaseproducing gram-negative pathogens in community- acquired urinary tract infections: an increasing challenge for antimicro- bial therapy. Infection 2011; 39:33340. 10. Auer S, Wojna A, Hell M. Oral treatment options for ambulatory patients with urinary tract infections caused by extended-spectrum-beta- lactamase-producing Escherichia coli. Antimicrob Agents Chemother 2010; 54:40068. 11. Garau J. Other antimicrobials of interest in the era of extended- spectrum beta-lactamases: fosfomycin, nitrofurantoin and tigecycline. Clin Microb Infect 2008; 14(suppl 1):198202. 12. Swaminathan S, Alangaden GJ. Treatment of resistant entero- coccal urinary tract infections. Curr Infect Dis Rep 2010; 12: 45564. 13. Cetti RJ, Venn S, Woodhouse CR. The risks of long-term nitro- furantoin prophylaxis in patients with recurrent urinary tract in- fection: a recent medico-legal case. BJU Internat 2009; 103: 5679. 14. Box GEP, Draper NR. Empirical model-building and response surfaces. New York: Wiley, 1987. EDITORIAL COMMENTARY CID 2014:58 (15 January) 163
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