Maria Teresa Mascellino
Sapienza University of Rome, Italy
Title: Activity of a double-carbapenem association in the in vitro susceptibility of Carbapenemase-producing Klebsiella Pneumoniae
Biography
Biography: Maria Teresa Mascellino
Abstract
Klebsiella pneumoniae carbapenemase (KPC)-producing are associated with increased mortality due to the resistance to the most antibacterial agents. Pan-drug resistant (PDR) K. pneumoniae infections have been recognized as an emerging challenge worldwide, due to the lack of therapeutic options . Strains of third-generation-cephalosporin-resistant and carbapenem-resistant K. pneumoniae are rapidly spreading. Preliminary data suggest a role of unconventional antibiotic combinations against colistin-resistant carbapenemase-producing isolates (CP-Kp). Aim of our work was to study the infections due to carbapenemase-producing Kl. pneumoniae , associated with a high mortality rate, belonging to patients hospitalized in a tertiary care setting. In these cases the therapeutic options are limited especially when associated with colistin resistance. In this case , a double carbapenem regimen has been shown to be effective and safe. Herein, we evaluated through antibiotic kill studies the in vitro synergistic activity of meropenem plus ertapenem against MDR Kl. pneumoniae isolated from 3 patients with bacteraemia who were successfully treated with double-carbapenem therapy. The results of time killing analysis showed that ertapenem or meropenem alone exhibited an initial reduction in log CFU/mL followed by a significant regrowth at 24h in all the patients. When the double-carbapenem combination was assessed, a bactericidal and synergistic activity was achieved at 4, 6, 8 h and maintained at 24 h at concentrations of meropenem 0.5xMIC plus ertapenem 1xMIC, meropenem 1xMIC plus ertapenem 1xMIC and meropenem 2xMIC plus ertapenem 1xMIC in all the patients. In our patients, ertapenem plus meropenem induced clinical (defervescence in 48 h) and microbiological (absence of growth in blood cultures performed 48 h after therapy) responses. In the in vitro studies, combination treatment exhibited a higher bacterial killing than monotherapy, even in the presence of high carbapenem MICs. In all the isolates, the combination treatment maintained bactericidal effect up to 24h, thus confirming the clinical efficacy of this innovative regimen. In summary, this report suggests that meropenem plus ertapenem might be considered a promising option in CP-Kp infections, especially in patients for whom colistin treatment is inappropriate due to resistance or toxicity.