Escherichia coli antimicrobial susceptibility profile and cumulative antibiogram to guide empirical treatment of uncomplicated urinary tract infections in women in the province of Québec, 2010-15.

OBJECTIVES: Empirical treatment of uncomplicated urinary tract infections (UTIs) in women should be based on local susceptibility data. We aimed to generate regional and provincial cumulative antibiograms combining data from different laboratory information systems and determine the impact of basic patient characteristics on susceptibility results. METHODS: All positive urine samples for Escherichia coli obtained from women aged 18-65 years old in outpatient settings between 1 April 2010 and 31 March 2015 from four hospitals in Quebec, Canada, were included. The cumulative antibiogram for ciprofloxacin, nitrofurantoin and trimethoprim/sulfamethoxazole was calculated. A clinically significant difference in susceptibility profile was defined as factor(s) that lowered the susceptibility proportion below 80%. RESULTS: A total of 36 293 positive urine cultures were analysed. In the last year of the study, the proportion of susceptibility for ciprofloxacin, nitrofurantoin and trimethoprim/sulfamethoxazole was 90.3%, 95.4% and 81.9%, respectively. The susceptibility proportion was <80% for trimethoprim/sulfamethoxazole in the Montreal region (73.4%; 95% CI 71.1%-75.9%), whereas it remained >80% for the other regions. A significant decrease in susceptibility with time was identified for ciprofloxacin (92.1%-90.3%, P < 0.001) and nitrofurantoin (97.1%-95.4%, P < 0.001). Increasing age, recent hospitalization and site of collection were associated with an increase in resistance for certain antibiotics. CONCLUSIONS: Overall, all first-line antimicrobials remain acceptable choices for empirical treatment of uncomplicated UTIs in women in Quebec. The regional variability in susceptibility data within a single province emphasizes the importance of local susceptibility data to inform the development of empirical treatment guidelines for UTIs.

Pharmacokinetics of an extended 4-hour infusion of piperacillin-tazobactam in critically ill patients undergoing continuous renal replacement therapy.

STUDY OBJECTIVE: To evaluate the pharmacokinetic and pharmacodynamic profiles of piperacillin-tazobactam administered as a 4-hour infusion in critically ill patients undergoing continuous renal replacement therapy (CRRT). DESIGN: Prospective, observational, pharmacokinetic study. SETTING: Intensive care unit of a tertiary care hospital in Montréal, Canada. PATIENTS: Twenty critically ill adults who were undergoing continuous venovenous hemodiafiltration and receiving a 4-hour infusion of piperacillin 4 g-tazobactam 0.5 g every 8 hours for a documented or suspected infection. INTERVENTION: Blood samples were collected every hour over an 8-hour dosing interval. Prefilter and postfilter blood samples, and effluent and urine samples were also collected. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion of patients who achieved an unbound piperacillin plasma concentration above a target minimum inhibitory concentration (MIC) of 64 mg/L (MIC that inhibits 90% of isolates for Pseudomonas aeruginosa) for at least 50% of the dosing interval; 18 (90%) of the 20 patients achieved this outcome. In all patients, the free piperacillin concentrations were above the Pseudomonas aeruginosa breakpoint of 16 mg/L for the entire time interval. Regarding piperacillin pharmacokinetic parameters, the median (interquartile range) minimum unbound plasma concentration was 65.15 mg/L (51.30-89.30), maximum unbound plasma concentration was 141.3 mg/L (116.75-173.90), sieving coefficient was 0.809 (0.738-0.938), total clearance was 65.82 ml/minute (53.79-102.87), and renal clearance was 0.16 ml/minute (0.05-3.04). The median CRRT dose was 32.0 ml/kg/h (25.0-39.8). CONCLUSIONS: Administration of a 4-hour infusion of piperacillin-tazobactam was associated with a favorable pharmacodynamic profile in patients undergoing CRRT. Concentrations associated with maximal activity were attained in our patients.