In vitro and in vivo evaluation of synergistic effects of combinations of antibacterials for the treatment of infections due to KPC and OXA-type carbapenemase-producing multidrug-resistant gram-negative bacteria endemic in Brazil

Abstract

The hospital infection is a serious public health problem, which is usuallyassociated with multidrug-resistant (MDR) bacteria, and with high morbidity/mortality rates. For these infections, the use of extended-spectrum antibiotics is recommended. Unfortunately, the overuse or misuse of antibiotics has selected resistant strains exhibiting versatile and emerging mechanisms of resistance,contributing to the endemicity of MDR species in Brazil, such as, KPC-producing Klebsiella pneumoniae, Acinetobacter baumannii producing carbapenemases OXA-23- and OXA-143-like, and metallo-beta-lactamase (SPM-1)-producing Pseudomonas aeruginosa. The aim of this study is to investigate therapeutic alternatives based on synergistic activity (assessed by"checkerboard", "time-kill", and inhibitory/bactericidal activity) resulting from thecombination of two antibiotics (different classes), including new antibiotics (eg, tigecycline). Effective combinations will be evaluated in vivo by using a murine model of infection. The results are intended to contribute to the establishment of new therapeutic schemes to be implemented in health services. (AU)