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.

Antibacterial Susceptibilities of Escherichia coli from Community-Acquired Urinary Tract Infections in the Faroe Islands, Associations with Antibacterial Sales, and Comparison with Iceland and Denmark.

Currently, data on Escherichia coli antibacterial susceptibilities in the Faroe Islands are lacking. The aim was to investigate the antibacterial susceptibilities of E. coli from patients with community-acquired urinary tract infections in the Faroe Islands, correlate with antibacterial sales, and compare with Iceland and Denmark. From 2009 to 2010 and in 2012, 12 general practitioners from the Faroe Islands were recruited to provide urine samples from patients. Antibacterial susceptibilities were determined by disc diffusion testing according to the Clinical and Laboratory Standards Institute methods and criteria. Logistic regression (quasibinomial) of the antibacterial resistance proportions versus mean sales during the period of 2008-2011 was used to determine association. Nonsusceptibility to at least 1 of the 14 antibacterial drugs investigated was found in 54% of the E. coli isolates and was most common to ampicillin (46%), followed by sulfamethoxazole (39%), trimethoprim (27%), trimethoprim/sulfamethoxazole (27%), and <10% to the remaining 10 antibiotics. The resistance prevalence did not change significantly with time. From logistic regression modeling, we find significant associations between antibacterial mean sales and antibacterial resistances. For the resistances in the Faroe Islands compared with data from Denmark and Iceland, we infer two groups of resistances indicating different responses-one steep and one gradual-to antibacterial sales. For these two groups, we find ß1 = 4.77 (Std. Error = 0.624, p-value = 0.002) and ß1 = 0.26 (Std. Error = 0.020, p-value = 4e-7) for the steep and gradual groups, respectively. This knowledge can potentially be used to predict and control the future increase in E. coli resistance with antibacterial sales.

Toltrazuril and sulphonamide treatment against naturally Isospora suis infected suckling piglets: is there an actual profit?

A study was carried out to assess the efficacy and the economic profit of prophylactic treatment against Isopsora suis with toltrazuril or with a sulfamethazine/trimethoprim combination in piglets from an intensive pig farm. Thirty-one litters were included in study. Eight litters were treated once with toltrazuril (20 mg/kg b.w.) at 3 days of age (Toltra group); 8 litters were treated with 2 ml/animal of a [corrected] sulphonamide combination (sodium sulfamethazine 250 [DOSAGE ERROR CORRECTED] mg and trimethoprim 50 [DOSAGE ERROR CORRECTED] mg/kg b.w.) for 3 consecutive days starting at 3 days of age (Sulfa group), and 15 litters were untreated (control group). Counts of oocyst per gram on pooled feces sampled from each litter were carried out on Days 7, 14, 21 and 28 and diarrhea was registered daily from pooled samples. Piglets were weighed on Days 1, 7 and 28 and mean weight gain (WG) and daily weight gain (DWG) were evaluated. The economic profit of treatment was evaluated comparing the WG of piglets of each treatment group from the day of birth to Day 28. On Days 14, 21 and 28, toltrazuril showed a better efficacy in controlling fecal oocyst output, diarrhea and weight gain compared with sulphamidic treatment (P<0.001). The budgeting analysis showed a return of economic benefit of euro 0.915 per toltrazuril-treated piglets and an additional cost of euro 1.155 per sulphonamide-treated piglets.

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.