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Multiple-Dose Oral Fosfomycin for Treatment of Complicated Urinary Tract Infections in the Outpatient Setting.

ABSTRACT: Background:Few published studies exist to describe the off-label use of multiple-dose fosfomycin for outpatient treatment of complicated urinary tract infections (UTI). The purpose of this study was to characterize the patients, infections, drug susceptibilities, and outcomes of multiple-dose fosfomycin episodes for outpatient UTI treatment. Methods:This retrospective study evaluated patients who received an outpatient prescription for multiple-dose fosfomycin between July 1999 and June 2018. Multiple-dose fosfomycin prescriptions dispensed for UTI prophylaxis were excluded. The primary outcome was clinical resolution (complete resolution of signs and symptoms) of infection within 30 days. Secondary outcomes included descriptions of antibiotics and cultures before and after treatment, 30-day bacteriologic resolution (posttreatment urine culture <103 colony-forming units of the original pathogen), and 90-day healthcare utilizations for UTI or pyelonephritis. Data were analyzed using descriptive statistics. Results:Of 171 multiple-dose fosfomycin treatment episodes, the most common regimen was 1 dose every 3 days, mean duration of 6.1 days. Clinical resolution occurred in 115 of 171 (67.3%) episodes, and bacteriologic resolution occurred in 37 of 76 (48.7%) episodes with posttreatment cultures. Most patients used antibiotics or had urine cultures before treatment (81.9% and 97.7%, respectively). Additional antibiotic use, urine cultures, and healthcare utilizations within 90 days posttreatment occurred in 51.5%, 66.1%, and 24.6% of patients, respectively. Conclusions:For treating complicated UTI with multiple-dose fosfomycin, clinical resolution occurred in 2 of 3 treatment episodes and bacteriologic resolution occurred in one-half of treatment episodes. Future research is necessary to determine the relative efficacy and safety and optimal dosing regimen, duration, and population for UTI treatment with multiple-dose fosfomycin.

SUBMITTER: Derington CG

PROVIDER: S-EPMC7036595 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Multiple-Dose Oral Fosfomycin for Treatment of Complicated Urinary Tract Infections in the Outpatient Setting.

Derington Catherine G CG Benavides Nancy N Delate Thomas T Fish Douglas N DN

Open forum infectious diseases 20200129 2

<h4>Background</h4>Few published studies exist to describe the off-label use of multiple-dose fosfomycin for outpatient treatment of complicated urinary tract infections (UTI). The purpose of this study was to characterize the patients, infections, drug susceptibilities, and outcomes of multiple-dose fosfomycin episodes for outpatient UTI treatment.<h4>Methods</h4>This retrospective study evaluated patients who received an outpatient prescription for multiple-dose fosfomycin between July 1999 an ...[more]

PMID: 32123690

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Project description:Oral fosfomycin is approved in Canada for the treatment of acute uncomplicated cystitis. Several studies have reported "off label" use of oral fosfomycin in the treatment of patients with complicated lower urinary tract infection (cLUTI). This review summarizes the available literature describing the use of oral fosfomycin in the treatment of patients with cLUTI. Collectively, these studies support the use of a regimen of 3 grams of oral fosfomycin administered once every 48 or 72 hours for a total of 3 doses for patients who have previously failed treatment with another agent, are infected with a multidrug-resistant (MDR) pathogen, or cannot tolerate first-line treatment due to intolerance or adverse effects. Additionally, a Phase 2/3 clinical trial, known as the ZEUS study, assessed the efficacy and safety of intravenous (IV) fosfomycin versus piperacillin-tazobactam in the treatment of patients with complicated upper urinary tract infection (cUUTI) or acute pyelonephritis (AP) including in patients with concomitant bacteremia. IV fosfomycin was reported to be noninferior to piperacillin-tazobactam in treating patients with cUUTI and AP; however, when outcomes were independently evaluated according to baseline diagnosis (i.e., cUUTI versus AP), IV fosfomycin was superior to piperacillin-tazobactam in the treatment of patients with cUUTI and demonstrated superior microbiological eradication rates, across all resistant phenotypes including extended-spectrum β-lactamase- (ESBL-) producing Escherichia coli and Klebsiella spp. and carbapenem-resistant (CRE), aminoglycoside-resistant, and MDR Gram-negative bacilli (primarily Enterobacterales). Based on the ZEUS study, IV fosfomycin dosed at 6 grams every 8 hours for 7 days (14 days in patients with concurrent bacteremia) appears to be a safe and effective therapeutic option in treating patients with upper urinary tract infections, particularly those with cUUTI caused by antimicrobial-resistant Enterobacterales.

Project description:Ceftolozane-tazobactam, a combination of the novel antipseudomonal cephalosporin ceftolozane and the well-established extended-spectrum β-lactamase inhibitor tazobactam, is approved for treating complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI) in adults. To determine doses likely to be safe and efficacious in phase 2 pediatric trials for the same indications, single-dose ceftolozane-tazobactam plasma pharmacokinetic data from a recently completed phase 1 trial in pediatric patients (birth to <18 years old) with proven/suspected Gram-negative bacterial infections, along with pharmacokinetic data from 12 adult studies, were integrated into a population pharmacokinetic (popPK) analysis. Two-compartment linear models with first-order elimination described the concentration-time profiles of ceftolozane and tazobactam in pediatric patients well. Renal function and body weight were identified to be significant predictors of ceftolozane-tazobactam pharmacokinetics. Renal function, as measured by the estimated glomerular filtration rate (eGFR), significantly affected the clearance of both ceftolozane and tazobactam. Body weight significantly affected clearance and the distribution volume, also of both ceftolozane and tazobactam. Patients with infections had a 32.3% lower tazobactam clearance than healthy volunteers. Using the final popPK models, simulations of various dosing regimens were conducted to assess each regimen's plasma exposure and the probability of pharmacokinetic/pharmacodynamic target attainment. Based on these simulations, the following doses are recommended for further clinical evaluation in phase 2 pediatric trials for cUTI and cIAI (in patients with an eGFR of ≥50 ml/min/1.73 m2 only): for children ≥12 years old, 1.5 g ceftolozane-tazobactam (1 g ceftolozane with 0.5 g tazobactam), and for neonates/very young infants, infants, and children <12 years old, 20/10 mg/kg of body weight ceftolozane-tazobactam, both via a 1-h intravenous infusion every 8 h.

Project description:BackgroundOveruse of fluoroquinolone antibiotics is associated with outbreaks of methicillin-resistant Staphylococcus aureus and of Clostridium difficile-associated diarrhea and increasing resistance in gram-negative organisms. Over the past decade, resistance of Escherichia coli to ciprofloxacin has increased in the Regina Qu'Appelle Health Region. In August 2011, an exploratory audit of the Regina General Hospital (RGH) emergency department showed that 20% of new antibiotic orders were for fluoroquinolones, and 60% of these new fluoroquinolone orders were for ciprofloxacin. It was postulated that ciprofloxacin was predominantly prescribed for outpatients with urinary tract infection.ObjectiveTo develop, implement, and evaluate a best-practice algorithm for the empiric treatment of uncomplicated urinary tract infection in the RGH emergency department, as part of an educational initiative for emergency physicians.MethodsA literature review was conducted and local antibiogram data were analyzed to establish a best-practice algorithm for treatment of uncomplicated urinary tract infection in outpatients seen in the emergency department. A chart review was conducted from January to March 2011 to establish a baseline of empiric antibiotic use. An educational strategy targeting emergency physicians described changes in antibiotic resistance patterns in the health region, principles of antimicrobial stewardship, drivers of resistance, and the results of a literature review of best practice for urinary tract infection in outpatients. A post-intervention audit was conducted from January to March 2012 to determine changes in practice.ResultsComparison of results from the post-intervention audit with baseline data showed that adherence to best practice increased significantly, from 41% (39/96) before the intervention to 66% (50/76) after the intervention (odds ratio [OR] 2.81, 95% confidence interval [CI] 1.51-5.25; p < 0.001). There was also a significant change in overall antibiotic selection (OR 0.25, 95% CI 0.11-0.58; p < 0.001). Further analysis suggested that this significant change was driven by a decrease in use of ciprofloxacin, from 32% (31/96) to 11% (8/76).ConclusionCreation of a best-practice algorithm and education focused on emergency physicians significantly increased adherence to best practice and optimized antibiotic prescribing for outpatients with uncomplicated urinary tract infection by limiting overuse of fluoroquinolones, primarily ciprofloxacin.

Dataset Information

Multiple-Dose Oral Fosfomycin for Treatment of Complicated Urinary Tract Infections in the Outpatient Setting.

Publications

Multiple-Dose Oral Fosfomycin for Treatment of Complicated Urinary Tract Infections in the Outpatient Setting.

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