2017年 7月 Critical Care に発表された、イタリア2施設で行われた CP-KPに対するダブルカルバペネム療法 vs 標準治療のケースコントロール研究。
Eligibility criteria were as follows: age ≥ 18 years; ICU admission between November 2012 and December 2015; documented CR-Kp invasive infection (i.e., pneumonia, bloodstream infection, complicated intra-abdominal, skin and soft tissue, and urinary tract infections); and targeted antibiotic therapy lasting ≥ 72 hours.
Meropenem and ertapemen were administered every 8 hours and 12/24 hours, respectively, at a daily dose of 6 g and 2 g, respectively, adopting the extended infusion strategy (at least 3 hours)
Colistin was administered every 12 hours at a daily dose of 9 million international units (MIU), after a 9 MIU loading dose.
Gentamicin was administered every 24 hours at a daily per-kilogram dose of 5/7 mg.
Tigecycline was administered at 100 mg every 12 hours after a 200 mg loading dose.
Dosages were not changed during continuous renal replacement therapy (CRRT), including the colistin total daily dose, and were reduced in the presence of renal failure (except for tigecycline). Aminoglycoside therapeutic drug monitoring (TDM) was performed routinely.
The 28-day mortality was significantly higher in patients receiving ST compared with the DC group (47.9% vs 29.2%, p = 0.04).
Similarly, clinical cure and microbiological eradication were significantly higher when DC was used in patients infected with CR-Kp strains resistant to colistin (13/20 (65%) vs 10/32 (31.3%), p = 0.03 and 11/19 (57.9%) vs 7/27 (25.9%), p = 0.04, respectively).
In the logistic regression and multivariate Cox-regression models, the DC regimen was associated with a reduction in 28-day mortality (OR 0.33, 95% CI 0.13–0.87 and OR 0.43, 95% CI 0.23–0.79, respectively).
First, although both centers adopted an electronic medical record, due to the observational nature we cannot exclude that unmeasured confounders may have influenced the strong association between DC use and improved survival.
Second, synergistic assays for confirming DC in-vitro efficacy were not done routinely, although CR-Kp strains were studied according to genetic testing.
Third, we did not check plasmatic carbapenem concentrations, so we can only assume that by optimizing dosages and administration modalities we achieved bactericidal meropenem levels at the infection site.
Fourth, due to the use of the Vitek system, we cannot exclude that a small proportion of strains could display meropenem MIC values closer to the susceptibility breakpoint.
Finally, we did not use either fosfomycin or ceftazidime–avibactam because both molecules were not available at our centers during the observation period.