Journal of Clinical & Experimental Pathology
Open Access

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 K. 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 K. 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 re-growth at 24 h 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 48h 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 24 h, 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.

Biography

Maria Teresa Mascellino has completed her MD from University �??La Sapienza�?� of Rome and specialization studies in Clinical Microbiology and Infectious Diseases from University �??La Sapienza�?� of Rome. She is Director of Microbiology Laboratory in the Department of Infectious Diseases. She has published more than 80 papers in reputed journals and has been serving as an Editorial Board Member of repute. She is member of many scientific societies and has participated in relevant International Research Projects.