Prospective observational study of the impact of VIM-1 metallo-beta-lactamase on the outcome of patients with Klebsiella pneumoniae bloodstream infections

Abstract

VIM-1-producing Klebsiella pneumoniae (VPKP) is an emerging pathogen. A prospective observational study was conducted to evaluate the importance of VIM production on outcome of patients with K. pneumoniae bloodstream infections (BSIs). Consecutive patients with K. pneumoniae BSIs were identified and followed up until patient discharge or death. A total of 162 patients were included in the analysis; 67 (41.4%) were infected with VPKP, and 95 were infected with non-VPKP. Fourteen of the patients infected with VPKP were carbapenem resistant (Carb(r)) (MIC > 4 mug/ml), whereas none of the non-VPKP exhibited carbapenem resistance. The patients infected with a Carb(r) organism were more likely (odds ratio, 4.08; 95% confidence interval [CI], 1.29 to 12.85; P = 0.02) to receive inappropriate empirical therapy. The all-cause 14-day mortality rates were 15.8% (15 of 95) for patients infected with VIM-negative organisms, 18.9% (10 of 53) for those infected with VIM-positive carbapenem-susceptible organisms, and 42.9% (6 of 14) for those infected with VIM-positive Carb(r) organisms (P = 0.044). In Cox regression analysis, age (hazard ratio [HR], 1.03; 95% CI, 1.01 to 1.06; P = 0.021), rapidly fatal underlying disease (HR, 2.84; 95% CI, 1.26 to 6.39; P = 0.012), and carbapenem resistance (HR, 2.83; 95% CI, 1.08 to 7.41; P = 0.035) were independent predictors of death. After adjustment for inappropriate empirical or definitive therapy, the effect of carbapenem resistance on outcome was reduced to a level of nonsignificance. In patients with K. pneumoniae BSIs, carbapenem resistance, advanced, age, and severity of underlying disease were independent predictors of outcome, whereas VIM production had no effect on mortality. The higher mortality associated with carbapenem resistance was probably mediated by the failure to provide effective therapy.

FIG. 1.

Kaplan-Meier curves of survival probability of patients with K. pneumoniae bloodstream infections according to susceptibility of the infecting organism to carbapenems. Patients infected with a VIM-positive organism for which the MICs of both imipenem and meropenem were >4 μg/ml were more likely to die than those infected with a VIM-positive carbapenem-susceptible or VIM-negative organism (log rank = 6.27, P = 0.044).