Double carbapenem as a rescue strategy for the treatment of severe carbapenemase-producing Klebsiella pneumoniae infections: a two-center, matched case–control study

Abstract

BackgroundRecent reports have suggested the efficacy of a double carbapenem (DC) combination, including ertapenem, for the treatment of carbapenem-resistant Klebsiella pneumoniae (CR-Kp) infections. We aimed to evaluate the clinical impact of such a regimen in critically ill patients.MethodsThis case–control (1:2), observational, two-center study involved critically ill adults with a microbiologically documented CR-Kp invasive infection treated with the DC regimen matched with those receiving a standard treatment (ST) (i.e., colistin, tigecycline, or gentamicin).ResultsThe primary end point was 28-day mortality. Secondary outcomes were clinical cure, microbiological eradication, duration of mechanical ventilation and of vasopressors, and 90-day mortality. Forty-eight patients treated with DC were matched with 96 controls. Occurrence of septic shock at infection and high procalcitonin levels were significantly more frequent in patients receiving DC treatment (p < 0.01). 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).ConclusionsImproved 28-day mortality was associated with the DC regimen compared with ST for severe CR-Kp infections. A randomized trial is needed to confirm these observational results.Trial registrationClinicalTrials.gov NCT03094494. Registered 28 March 2017.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1769-z) contains supplementary material, which is available to authorized users.

Epidemiology, Treatment, and Prevention of Nosocomial Bacterial Pneumonia

“…A Spanish study investigating the outcomes of ICU patients with VAP caused by P. aeruginosa observed that initial use of antibiotic combination therapy (mainly anti-pseudomonal β-lactam plus an aminoglycoside or an anti-pseudomonal fluoroquinolone agent) indeed significantly reduced the likelihood of inappropriate therapy, which was strongly associated with higher case-fatality risk [97]. Nevertheless, in distinction from two guidelines [11,14], there were many diversified regimens of antibiotic combinations proposed against clinical infections due to isolates of CR-Acinetobacter baumannii complex species [59,75,80,[98][99][100], as well as CRE [34,69,94,101]. Despite no reduction of mortality rates [11], a useful de-escalation of an antibiotic has the benefit of decreasing resistance burden.…”

Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae

“…Ertapenem and meropenem have been found to be synergistic in vitro against other types of carbapenemase-producing Enterobacteriaceae (209). A comparison of 28-day mortality was carried out recently between ICU patients with carbapenem-resistant K. pneumoniae infections (90% were KPC producers) who received double carbapenems, with ertapenem as targeted therapy (48 patients; 35 of these received a third drug), and 96 patients who received other treatment regimens (52 received a combination of drugs) (254). Patients in both treatment arms were matched by SAPS-II score at admission and SOFA score at diagnosis of infection.…”

Review of therapeutic options for infections with carbapenem-resistant Klebsiella pneumoniae

“…After exclusion of one review article and one poster abstract, the remaining ten articles were checked for eligibility and removed if not freely accessible. Five studies published between 2015 and 2018 were eligible for a qualitative assessment of which four were RCTs [ 27–30 ] and one was a retrospective, observational study [ 31 ] ( Tables 1 and 2 ). Additional six publications that were not entirely fulfilling the inclusion criteria were at least included in the screening, but not eligible for comparisons (i.e., no comparative treatment regimens, missing control cohorts, too small sample sizes, not explicitly referring to K. pneumoniae infections) [ 32–37 ].…”