Comparative efficacy of doripenem versus meropenem for hospital-acquired and ventilator-associated pneumonia.

BACKGROUND: Doripenem shows good in vitro activity against common nosocomial pathogens, such as extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii. However, the use of doripenem for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) remains controversial. The aim of this study was to compare the efficacy and safety between doripenem and meropenem for patients with HAP or VAP. METHODS: Adult patients diagnosed with HAP and VAP at National Taiwan University Hospital, who received doripenem or meropenem for more than 48 h between January 2015 and November 2017, were retrospectively reviewed. All-cause mortality on the 30th day was used as the primary outcome measurements. RESULTS: Fifty-seven patients with doripenem and 252 patients with meropenem were analyzed. Compared to the meropenem group, the doripenem group was younger and had a higher Sequential Organ Failure Assessment (SOFA) score. Multivariable Cox regression analysis revealed that presence of solid organ malignancies (adjusted hazard ratio [AHR], 1.82; 95% CI, 1.04-3.19, p = 0.003) and SOFA score (AHR, 1.10; 95% CI, 1.03-1.17, p = 0.003) were independent factors associated with mortality. There was no survival difference of 30-day mortality between patients receiving doripenem and meropenem for HAP or VAP (log-rank p = 0.113). However, a poorer outcome was observed among patients with hematological disease in the doripenem group (log-rank p = 0.012). CONCLUSION: Our results demonstrate that doripenem has similar efficacy as meropenem in HAP or VAP patients. With an aim to enhance antibiotic diversity, doripenem could be an alternative choice for patients with HAP or VAP, except for those with hematological malignancies.

Elimination of Doripenem during Dialysis and Pharmacokinetic Evaluation of Posthemodialysis Dosing for Patients Undergoing Intermittent Renal Replacement Therapy.

Doripenem is a broad-spectrum parenteral carbapenem with enhanced activity against Pseudomonas aeruginosa and Enterobacteriaceae Current dosing regimens recommend the administration of 0.25 to 0.5 g once daily in patients undergoing intermittent renal replacement therapy. As patients are usually dialyzed thrice weekly, we aimed to investigate a 1-g posthemodialysis regimen, thus reducing treatment costs and enhancing patient compliance. A second objective of this trial was to describe the pharmacokinetics of intradialytic doripenem. Ten oliguric or anuric patients in need of intermittent renal replacement therapy were included in this trial. All patients suffered from a septic episode. The mean hemofilter clearance was 123.46 ± 42.03 ml/min, and the total body clearance between hemodialysis sessions was 16.79 ± 6.02 ml/min. The average prehemodialysis trough concentration was 2.4 ± 1.3 mg/liter, while the EUCAST resistance breakpoint for Enterobacteriaceae is set at 2 mg/liter. The interpatient variability was considerably higher than the intrapatient variability. Apart from one patient who suffered an allergic reaction, doripenem was tolerated well by all patients. Our data indicate that posthemodialysis administration of 1 g of doripenem results in sufficient plasma levels in anuric but not oliguric patients during the entire dosing interval. (This trial was registered with EudraCT under registration no. 2009-018010-18 and at ClinicalTrials.gov under registration no. NCT02018939.).