A cost-minimization analysis of treatment options for postmenopausal women with dysuria.

BACKGROUND: Empiric therapy for urinary tract infection is difficult in postmenopausal women because of the higher rates of confounding lower urinary tract symptoms and differential resistance profiles of uropathogens in this population. OBJECTIVE: The objective of the study was to determine the least costly strategy for treatment of postmenopausal women with the primary complaint of dysuria. STUDY DESIGN: We performed a cost minimization analysis modeling the following clinical options: (1) empiric antibiotic therapy followed by urine culture, (2) urinalysis with empiric antibiotic therapy only if positive nitrites and leukocyte esterase, or (3) waiting for culture prior to initiating antibiotics. For all strategies we included nitrofurantoin, trimethoprim/sulfamethoxazole, fosfomycin, ciprofloxacin, or cephalexin. Pathogens included Escherichia coli, Enterococcus faecalis, Klebsiella pneumonaie, or Proteus mirabalis. Pathogens, resistance, treatment success, and medication side effects were specific to postmenopausal women. RESULTS: Cost minimization modeling with TreeAge Pro assumed 73.4% of urinary tract infections were caused by Escherichia coli with 24.4% resistance to nitrofurantoin, trimethoprim/sulfamethoxazole. With our assumptions, empiric antibiotics with nitrofurantoin, trimethoprim/sulfamethoxazole was the least costly approach ($89.64/patient), followed by waiting for urine culture ($97.04/patient). Except for empiric antibiotics with fosfomcyin, empiric antibiotics was always less costly than using urinalysis to discriminate antibiotic use. This is due to the cost of urinalysis ($38.23), high rate of both urinary tract infection (91%), and positive urinalysis (69.3%) with dysuria in postmenopausal women and resultant high rate of antibiotic use with or without urinalysis. Options with fosfomycin were the most expensive because of the highest drug costs ($98/dose), and tornado analyses showed fosfomycin cost was the most impactful variable for model outcomes. Sensitivity analyses showed empiric fosfomycin became the least costly option if drug costs were $25.80, a price still more costly than almost all modeled baseline drug costs. This outcome was largely predicated on low resistance to fosfomycin. Conversely, ciprofloxacin was never the least costly option because of higher resistance and side effect cost, even if the drug cost was $0. We modeled 91% positive urine culture rate in postmenopausal women with dysuria; waiting for the urine culture prior to treatment would be the least costly strategy in a population with a predicted positive culture rate of <65%. CONCLUSION: The least costly strategy was empiric antibiotics with nitrofurantoin and trimethoprim/sulfamethoxazole, followed by waiting on culture results. Local resistance patterns will have an impact on cost minimization strategies. Empiric fosfomycin would be least costly with reduced drug costs, even at a level at which drug costs were higher than almost all other antibiotics. In a population with high posttest probability of positive urine culture, urinalysis adds unnecessary cost. Antibiotic stewardship programs should continue efforts to decrease fluoroquinolone use because of high resistance, side effects, and increased cost.

Continuous low-dose antibiotic prophylaxis to prevent urinary tract infection in adults who perform clean intermittent self-catheterisation: the AnTIC RCT.

BACKGROUND: People carrying out clean intermittent self-catheterisation (CISC) to empty their bladder often suffer repeated urinary tract infections (UTIs). Continuous once-daily, low-dose antibiotic treatment (antibiotic prophylaxis) is commonly advised but knowledge of its effectiveness is lacking. OBJECTIVE: To assess the benefit, harms and cost-effectiveness of antibiotic prophylaxis to prevent UTIs in people who perform CISC. DESIGN: Parallel-group, open-label, patient-randomised 12-month trial of allocated intervention with 3-monthly follow-up. Outcome assessors were blind to allocation. SETTING: UK NHS, with recruitment of patients from 51 sites. PARTICIPANTS: Four hundred and four adults performing CISC and predicted to continue for ≥ 12 months who had suffered at least two UTIs in the previous year or had been hospitalised for a UTI in the previous year. INTERVENTIONS: A central randomisation system using random block allocation set by an independent statistician allocated participants to the experimental group [once-daily oral antibiotic prophylaxis using either 50 mg of nitrofurantoin, 100 mg of trimethoprim (Kent Pharmaceuticals, Ashford, UK) or 250 mg of cefalexin (Sandoz Ltd, Holzkirchen, Germany); n = 203] or the control group of no prophylaxis (n = 201), both for 12 months. MAIN OUTCOME MEASURES: The primary clinical outcome was relative frequency of symptomatic, antibiotic-treated UTI. Cost-effectiveness was assessed by cost per UTI avoided. The secondary measures were microbiologically proven UTI, antimicrobial resistance, health status and participants' attitudes to antibiotic use. RESULTS: The frequency of symptomatic antibiotic-treated UTI was reduced by 48% using prophylaxis [incidence rate ratio (IRR) 0.52, 95% confidence interval (CI) 0.44 to 0.61; n = 361]. Reduction in microbiologically proven UTI was similar (IRR 0.49, 95% CI 0.39 to 0.60; n = 361). Absolute reduction in UTI episodes over 12 months was from a median (interquartile range) of 2 (1-4) in the no-prophylaxis group (n = 180) to 1 (0-2) in the prophylaxis group (n = 181). The results were unchanged by adjustment for days at risk of UTI and the presence of factors giving higher risk of UTI. Development of antimicrobial resistance was seen more frequently in pathogens isolated from urine and Escherichia coli from perianal swabs in participants allocated to antibiotic prophylaxis. The use of prophylaxis incurred an extra cost of £99 to prevent one UTI (not including costs related to increased antimicrobial resistance). The emotional and practical burden of CISC and UTI influenced well-being, but health status measured over 12 months was similar between groups and did not deteriorate significantly during UTI. Participants were generally unconcerned about using antibiotics, including the possible development of antimicrobial resistance. LIMITATIONS: Lack of blinding may have led participants in each group to use different thresholds to trigger reporting and treatment-seeking for UTI. CONCLUSIONS: The results of this large randomised trial, conducted in accordance with best practice, demonstrate clear benefit for antibiotic prophylaxis in terms of reducing the frequency of UTI for people carrying out CISC. Antibiotic prophylaxis use appears safe for individuals over 12 months, but the emergence of resistant urinary pathogens may prejudice longer-term management of recurrent UTI and is a public health concern. Future work includes longer-term studies of antimicrobial resistance and studies of non-antibiotic preventative strategies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67145101 and EudraCT 2013-002556-32. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 22, No. 24. See the NIHR Journals Library website for further project information.

Costs and effects of screening and treating low risk women with a singleton pregnancy for asymptomatic bacteriuria, the ASB study.

BACKGROUND: The prevalence of asymptomatic bacteriuria (ASB) in pregnancy is 2-10% and is associated with both maternal and neonatal adverse outcomes as pyelonephritis and preterm delivery. Antibiotic treatment is reported to decrease these adverse outcomes although the existing evidence is of poor quality. METHODS/DESIGN: We plan a combined screen and treat study in women with a singleton pregnancy. We will screen women between 16 and 22 weeks of gestation for ASB using the urine dipslide technique. The dipslide is considered positive when colony concentration ≥105 colony forming units (CFU)/mL of a single microorganism or two different colonies but one ≥105 CFU/mL is found, or when Group B Streptococcus bacteriuria is found in any colony concentration. Women with a positive dipslide will be randomly allocated to receive nitrofurantoin or placebo 100 mg twice a day for 5 consecutive days (double blind). Primary outcomes of this trial are maternal pyelonephritis and/or preterm delivery before 34 weeks. Secondary outcomes are neonatal and maternal morbidity, neonatal weight, time to delivery, preterm delivery rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal admission days and costs. DISCUSSION: This trial will provide evidence for the benefit and cost-effectiveness of dipslide screening for ASB among low risk women at 16-22 weeks of pregnancy and subsequent nitrofurantoin treatment. TRIAL REGISTRATION: Dutch trial registry: NTR-3068.

Nitrofurantoin compares favorably to recommended agents as empirical treatment of uncomplicated urinary tract infections in a decision and cost analysis.

OBJECTIVE: To analyze the costs of nitrofurantoin use compared to those of other antibiotics recommended for treatment of uncomplicated urinary tract infection (UTI). PATIENTS AND METHODS: We used a decision analysis model to perform cost-minimization and sensitivity analyses to determine the level of trimethoprim-sulfamethoxazole (TMP-SMX) and fluoroquinolone resistance that would favor the use of nitrofurantoin as a first-line empirical treatment of uncomplicated UTIs. The model used a program perspective to evaluate costs. RESULTS: Nitrofurantoin was cost-minimizing when the prevalence of fluoroquinolone resistance exceeded 12% among uropathogens or the prevalence of TMP-SMX resistance exceeded 17%. On 2-way sensitivity analysis, variables that had a significant impact on our cost-minimization threshold included cost of antibiotics and probability of clinical cure with antibiotics. CONCLUSION: From a payer perspective, nitrofurantoin appears to be a reasonable alternative to TMP-SMX and fluoroquinolones for empirical treatment of uncomplicated UTIs, especially given the current prevalence of antibiotic resistance among community uropathogens. On the basis of efficacy, cost, and low impact on promoting antimicrobial resistance, clinicians should consider nitrofurantoin as a reasonable alternative to TMP-SMX and fluoroquinolones for first-line therapy for uncomplicated UTIs.

Economic evaluation of an updated guideline for the empiric treatment of uncomplicated urinary tract infection in women.

BACKGROUND: Until recently trimethoprim-sulfamethoxazole was the drug recommended in the Leumit Health Fund for the empiric treatment of uncomplicated urinary tract infection in women. However, due to increased uropathogen resistance to this drug, the fund has designated nitrofurantoin as its new drug of choice. OBJECTIVES: To evaluate the potential economic impact of implementing this new pharmaco-policy. METHODS: Using data derived from the electronic patient records of the Leumit Health Fund, we identified all non-recurrent cases of women aged 18-49 with a diagnosis of acute cystitis or UTI without risk factors for complicated UTI and empirically treated with antibiotics throughout 2003. The final sample comprised 5,489 physician-patient encounters. The proportion of cases treated with each individual drug was calculated, and the excess expenditure due to non-adherence to the new guideline from the perspective of the health fund was evaluated using 5 days of therapy with nitrofurantoin as the reference treatment. RESULTS: Ofloxacin was the most frequently prescribed drug (30.24%), followed by TMP-SMX (22.43%), cephalexin (15.08%), and nitrofurantoin (12.59%). The observed net aggregate drug expenditure was 2.3 times greater than expected had all cases been treated with nitrofurantoin according to the guideline duration of 5 days. The cost of treatment in 53% of the cases exceeded the expected cost of the guideline therapy. CONCLUSIONS: Successful implementation of the new drug will likely improve quality of care and reduce costs to the health fund.

Empiric treatment of uncomplicated UTI in women: wasting money when more is not better.

CONTEXT: Trimethoprim-sulfamethoxazole (TMP-SMX) and nitrofurantoin were until recently the two drugs recommended in clinical guidelines in Israel for empiric treatment of uncomplicated urinary tract infection (UTI) in women. OBJECTIVES: The objective of this study is to evaluate the economic impact of physician non-adherence to these recommendations. DESIGN SETTING AND PATIENTS: Data were derived from the electronic patient records of the Leumit Health Fund. Cases of women aged 18 to 75 with a diagnosis of acute cystitis or UTI that were empirically treated with antibiotics from January 2001 to June 2002 were identified. The final sample comprised 7738 physician-patient encounters. The proportion of cases treated with each individual drug was calculated, and the excess expenditure because of non-adherence to guidelines from the perspective of the Health Maintenance Organization (HMO) was evaluated using 5 days of therapy with nitrofurantoin as the reference treatment. RESULTS: TMP-SMX was the most frequently prescribed drug (25.81%), followed by nitrofurantoin (14.71%) representing a 40.52% rate of adherence to the guidelines. Drugs from the fluoroquinolone family were prescribed in 22.82% of cases. Cost of treatment in approximately 70% of the cases exceeded the expected cost of the guideline therapy. CONCLUSIONS: Suboptimal adherence to the guidelines resulted in a significant and avoidable waste of the health plan's resources in both drugs and money.

Longer than recommended empiric antibiotic treatment of urinary tract infection in women: an avoidable waste of money.

CONTEXT: Current Israeli guidelines for the empiric treatment of uncomplicated urinary tract infection (UTI) in women recommend nitrofurantoin for 5 days. Some physicians nevertheless opt for ofloxacin, which should be prescribed for 3 days according to universally accepted guidelines. OBJECTIVE: To evaluate the economic consequences of longer than recommended durations of antibiotic therapy in the empiric treatment of uncomplicated UTI in women. DESIGN, SETTING AND PATIENTS: Data were derived from the electronic records of one of the four health maintenance organizations in Israel. The sample included all women aged 18-75 years who were diagnosed with acute cystitis or UTI from January 2001 to June 2002 and were empirically treated with antibiotics. Of the 7738 patients identified, 1138 received nitrofurantoin and 1054 ofloxacin. The excess expenditure accrued due to longer than recommended therapy with these drugs was evaluated. RESULTS: The rate of adherence was 22.23% for nitrofurantoin (95% CI=19.81%, 24.65%), and 4.08% for ofloxacin (95% CI=2.88%, 5.28%). The average excess expenditure per case was 5.78 USD (US Dollar) with ofloxacin and 3.43 USD with nitrofurantoin, resulting in an annual loss to the health maintenance organizations of approximately 19,000 USD. When extrapolated to the national population of 6.5 million, the loss due to inappropriate treatment of adult women is 190,000 USD. CONCLUSIONS: The lack of adherence to national and international guidelines with regard to the recommended duration of antibiotic treatment of UTI in women resulted in a significant and avoidable waste of health system resources. This study suggests that drug utilization analyses that concentrate solely on the choice of drug may be overlooking important information.

Economic assessment of three antimicrobial therapies for uncomplicated urinary tract infection in women.

This retrospective cohort study used North Carolina Medicaid paid-claims data to assess clinical and economic outcomes of treatments for urinary tract infection (UTI). The study population comprised female Medicaid recipients, between 15 and 64 years of age, with a paid claim filed for a primary diagnosis of UTI or acute UTI from January 1 to June 30, 1994, who were treated with ciprofloxacin, nitrofurantoin, or trimethoprim/sulfamethoxazole (TMP/SMZ). Patients had follow-up for 6 months after the primary diagnosis. Patients who did not receive further treatment for UTI with 1 of the 3 drugs within 30 days after initial treatment were assumed to be cured. Costs were measured as the sum of reimbursements for UTI-related medical services and drug treatments. Outcomes for 409 patients were assessed. Cure rates of initial treatment with ciprofloxacin, nitrofurantoin, and TMP/SMZ were 81%, 88%, and 93%, respectively. Cost-effectiveness ratios of initial treatment with the 3 drugs were $150.80, $81.20, and $69.00, respectively. When efficacy rates generated from published randomized clinical studies were applied, cost-effectiveness ratios for the 3 drugs were $130.96, $86.17, and $72.00, respectively. A decision model of treatment pattern and associated costs is presented. Several patient variables indicate that the ciprofloxacin group included more severe cases of UTI than did the other groups. Study limitations, confounders, and future research suggestions are discussed. Our results show that treatment for >7 days results in a better cure rate regardless of the drug used than does treatment for < or =7 days and that TMP/SMZ is the most cost-effective of the 3 drugs for UTI or acute UTI.

Randomized comparative trial and cost analysis of 3-day antimicrobial regimens for treatment of acute cystitis in women.

OBJECTIVE: To determine the efficacy, safety, and costs associated with four different 3-day regimens for the treatment of acute uncomplicated cystitis in women. DESIGN: A prospective randomized trial with a cost analysis. STUDY POPULATION: Women with acute cystitis attending a student health center. INTERVENTIONS: Treatment with 3-day oral regimens of trimethoprim-sulfamethoxazole, 160 mg/800 mg twice daily, macrocrystalline nitrofurantoin, 100 mg four times daily, cefadroxil, 500 mg twice daily, or amoxicillin, 500 mg three times daily. RESULTS: Six weeks after treatment, 32 (82%) of 39 women treated with trimethoprim-sulfamethoxazole were cured compared with 22 (61%) of 36 treated with nitrofurantoin (P = .04 vs trimethoprim-sulfamethoxazole), 21 (66%) of 32 treated with cefadroxil (P = .11 vs trimethoprim-sulfamethoxazole), and 28 (67%) of 42 treated with amoxicillin (P = .11 vs trimethoprim-sulfamethoxazole). Persistence of significant bacteriuria was less common with trimethoprim-sulfamethoxazole (3%) and cefadroxil (0%) compared with nitrofurantoin (16%; P = .05 vs trimethoprim-sulfamethoxazole) and amoxicillin (14%; P = .11 vs trimethoprim-sulfamethoxazole). Persistence of bacteriuria was associated with amoxicillin-resistant strains in the amoxicillin group but nitrofurantoin-susceptible strains in the nitrofurantoin group. Trimethoprim-sulfamethoxazole was more successful in eradicating Escherichia coli from rectal cultures soon after therapy and from urethral and vaginal cultures at all follow-up visits compared with the other treatment regimens. Adverse effects were reported by 16 (35%) of 46 patients receiving trimethoprim-sulfamethoxazole, 18 (43%) of 42 receiving nitrofurantoin, 12 (30%) of 40 receiving cefadroxil, and 13 (25%) of 52 receiving amoxicillin. The mean costs per patient were less with trimethoprim-sulfamethoxazole ($114) and amoxicillin ($131) compared with nitrofurantoin ($155) and cefadroxil ($155). CONCLUSIONS: A 3-day regimen of trimethoprim-sulfamethoxazole is more effective and less expensive than 3-day regimens of nitrofurantoin, cefadroxil, or amoxicillin for treatment of uncomplicated cystitis in women. The increased efficacy of trimethoprim-sulfamethoxazole is likely related to its antimicrobial effects against E coli in the rectum, urethra, and vagina.