A Combination Antibiogram Evaluation for Pseudomonas aeruginosa in Respiratory and Blood Sources from Intensive Care Unit (ICU) and Non-ICU Settings in U.S. Hospitals.

Pseudomonas aeruginosa is an important pathogen associated with significant morbidity and mortality. U.S. guidelines for the treatment of hospital-acquired and ventilator-associated pneumonia recommend the use of two antipseudomonal drugs for high-risk patients to ensure that ≥95% of patients receive active empirical therapy. We evaluated the utility of combination antibiograms in identifying optimal anti-P.aeruginosa drug regimens. We conducted a retrospective cross-sectional analysis of the antimicrobial susceptibility of all nonduplicate P.aeruginosa blood and respiratory isolates collected between 1 October 2016 and 30 September 2017 from 304 U.S. hospitals in the BD Insights Research Database. Combination antibiograms were used to determine in vitro rates of susceptibility to potential anti-P.aeruginosa combination regimens consisting of a backbone antibiotic (an extended-spectrum cephalosporin, carbapenem, or piperacillin-tazobactam) plus an aminoglycoside or fluoroquinolone. Single-agent susceptibility rates for the 11,701 nonduplicate P.aeruginosa isolates ranged from 72.7% for fluoroquinolones to 85.0% for piperacillin-tazobactam. Susceptibility rates were higher for blood isolates than for respiratory isolates (P < 0.05). Antibiotic combinations resulted in increased susceptibility rates but did not achieve the goal of 95% antibiotic coverage. Adding an aminoglycoside resulted in higher susceptibility rates than adding a fluoroquinolone; piperacillin-tazobactam plus an aminoglycoside resulted in the highest susceptibility rate (93.3%). Intensive care unit (ICU) isolates generally had lower susceptibility rates than non-ICU isolates. Commonly used antipseudomonal drugs, either alone or in combination, did not achieve 95% coverage against U.S. hospital P.aeruginosa isolates, suggesting that new drugs are needed to attain this goal. Local institutional use of combination antibiograms has the potential to optimize empirical therapy of infections caused by difficult-to-treat pathogens.

Acute uncomplicated UTI and E. coli resistance: implications for first-line empirical antibiotic therapy.

BACKGROUND: Uncomplicated urinary tract infection (uUTI) typically affects immunocompetent, anatomically normal women. Escherichia coli (E. coli) accounts for approximately 80% of cases. Given increased E. coli-trimethoprimsulfamethoxazole (TMP-SMX) resistance, practice guidelines advocate first-line alternatives based on local resistance rates above 10%. This paper provides a model incorporating use of a new extended-release formulation of ciprofloxacin, used once daily, to facilitate revision of uUTI treatment policies by managed care organizations (MCOs) and practitioners. METHODS: A cost-minimization model was designed from the MCO perspective, assuming an initial office visit with a urinalysis and empiric, 3-day treatment (TMP-SMX 800/160 mg twice daily or ciprofloxacin XR 500 mg once daily). Persistent infections were assumed to require a second visit. Costs were provided by a major employee health and benefit plan provider; clinical data were based on published information. Five case scenarios were used to compare average treatment costs based on varying E. coli resistance rates to therapy and to identify rates of TMP-SMX resistance where total treatment costs are equal. RESULTS: Using national surveillance resistance data, Case 1 demonstrated average cost savings of 9.59 dollars to 10.21 dollars with ciprofloxacin XR. In Case 2, treatment costs (49.19 dollars) were equal at an E. coli resistance rate of 4.3% for TMP-SMX and 1.0% for ciprofloxacin. Case 3 assumed empiric telephone prescribing, demonstrating that, at 4.3% TMP-SMX resistance, costs are equal for both treatments (4.19 dollars). Case 4 used real-world data on therapy duration, demonstrating that, at 2.8% TMP-SMX resistance, costs are equal for both treatments (54.87 dollars). Case 5 assumed 10% ciprofloxacin-E. coli resistance; at 13.3% TMP-SMX resistance, treatment costs were equal (57.50 dollars). Results from all cases demonstrate that while the per-dose cost of ciprofloxacin XR far exceeds TMP-SMX, average total treatment costs are lower for ciprofloxacin XR at expected local levels of E. coli resistance to TMP-SMX. CONCLUSIONS: The results suggest that in areas where local TMP-SMX E. coli resistance exceeds 10% and resistance to ciprofloxacin remains low, (0.5% to 6%) ciprofloxacin XR is an appropriate alternative to standard empiric treatment. The data provide evidence to MCOs that switching to a more expensive per-dose alternative will not necessarily increase total costs when guideline recommendations are followed. Responsible use of antibiotics for uUTI requires selection and administration of the right dosage of the most suitable antibiotic for an appropriate time period to eliminate pathogens quickly and successfully. The decision to use an alternative first-line therapy for uUTI should be driven by local resistance and susceptibility data--not simply per-dose drug acquisition costs.