Treatment of KPC-producing Enterobacteriaceae: suboptimal efficacy of polymyxins

Abstract

Treatment of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae infections (KPC-EI) remains a challenge. Combined therapy has been proposed as the best choice, but there are no clear data showing which combination therapy is superior. Our aim was to evaluate the effectiveness of antimicrobial regimens for treating KPC-EI. This was a retrospective cohort study of KPC-EI nosocomial infections (based on CDC criteria) between October 2009 and June 2013 at three tertiary Brazilian hospitals. The primary outcomes were the 30-day mortality for all infections and the 30-day mortality for patients with bacteraemia. Risk factors for mortality were evaluated by comparing clinical variables of survivors and nonsurvivors. In this study, 118 patients were included, of whom 78 had bacteraemia. Catheter-related bloodstream infections were the most frequent (43%), followed by urinary tract infections (n = 27, 23%). Monotherapy was used in 57 patients and combined treatment in 61 patients. The most common therapeutic combination was polymyxin plus carbapenem 20 (33%). Multivariate analysis for all infections (n = 118) and for bacteremic infections (n = 78) revealed that renal failure at the end of treatment, use of polymyxin and older age were prognostic factors for mortality. In conclusion, polymyxins showed suboptimal efficacy and combination therapy was not superior to monotherapy.

A prospective study of treatment of carbapenem-resistant Enterobacteriaceae infections and risk factors associated with outcome

“…CRE resistance to colistin has been reported in several countries in the last years [4–7] and infections caused by these bacteria are associated with high mortality [8–10]. KPC is the most frequent carbapenemase described in Enterobacteriaceae in Brazil with great mortality [8, 11]. One cohort study in Brazil described 118 patients with CRE infections in a period of almost four years.…”

Carbapenemase-Producing Klebsiella pneumoniae, a Key Pathogen Set for Global Nosocomial Dominance

“…Colistin has become the most popular agent for the treatment of infections due to K. pneumoniae with carbapenemases (101,102). Colistin monotherapy has been associated with mortality rates exceeding 50% when used for severe infections (111), and one Brazilian study showed that combination therapy was not superior to monotherapy (112). Recent understanding of the pharmacokinetics of colistin has resulted in the use of doses higher than those used in early studies.…”

Is This the Carbapenemase Test We've Been Waiting for? A Multicenter Evaluation of the Modified Carbapenem Inactivation Method

“…Data are available to support the use of combination therapy for the treatment of serious infections (10,11); however, these benefits may primarily be limited to those patients with severe underlying conditions (12). Collectively, inclusion of a carbapenem in the treatment of carbapenemaseproducing Enterobacteriaceae appears to be associated with lower mortality rates compared to carbapenem-sparing treatment regimens, but this has not been borne out in all observational studies (13). Without unequivocal outcome data supporting the 2010 CLSI and EUCAST guidelines, physicians may be reluctant to treat CP-CRE with a susceptible carbapenem.…”