Ceftazidime-avibactam a potential alternative to colistin in KPC-producing CRE infections
Ceftazidime-avibactam appears to offer a reasonable alternative to colistin in the treatment of Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant Enterobacteriaceae (CRE) infections, according to a study.
Researchers looked at patients initially treated with either ceftazidime-avibactam (n=38) or colistin (n=99) for CRE infections. They used intent-to-treat analyses with partial credit and the desirability of outcome ranking (DOOR) approaches in the efficacy, safety and benefit-risk analyses.
Disposition at day 30 after initiating treatment (home vs not home but not observed to die in the hospital vs hospital death) was used as the basis of the ordinal efficacy outcome. All analyses were controlled for confounding with the use of inverse probability of treatment weighting (IPTW).
In the cohort, a large number of patients received additional anti-CRE agents as part of their treatment. The most common infections were that of the bloodstream (n=63; 46 percent) and of respiratory (n=30; 22 percent).
PTW-adjusted all-cause hospital mortality at 30 days after starting treatment was 9 percent in patients on ceftazidime-avibactam vs 32 percent in colistin-treated patients (difference, 23 percent; p=0.0012).
When analysing disposition at 30 days, the ceftazidime-avibactam group had an IPTW-adjusted 64 percent (95 percent CI, 57 to 71) probability of a better outcome compared with the colistin group. Furthermore, ceftazidime-avibactam showed superiority over colistin in partial credit analyses.
CRE may result in a number of serious infection types (eg, intra-abdominal infections, pneumonia, urinary tract, device-associated infections) or asymptomatic colonization. CRE has also been reported to confer broad resistance to most beta-lactam antibiotics, including “last-line” carbapenems. Carbapenem resistance develops when porin deficiencies, which facilitate decreased entry of the beta-lactam into the cell membrane, are combined with extended spectrum beta-lactamases. [Open Forum Infect Dis 2015;2:ofv050]