In-Vitro Evaluation of Different Antimicrobial Combinations with and without Colistin Against Carbapenem-Resistant Acinetobacter Baumannii

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 5; p. 886
• Main Authors: Oliva, Alessandra, Garzoli, Stefania, De Angelis, Massimiliano, Marzuillo, Carolina, Vullo, Vincenzo, Mastroianni, Claudio M, Ragno, Rino
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03-03-2019; MDPI
• Subjects: Antibiotics; Antiinfectives and antibacterials; Antimicrobial agents; antimicrobial combinations; Bactericidal activity; carbapenem-resistant A. baumannii; Clinical isolates; Clinical trials; Cloning; Colistin; Gram-positive bacteria; Infections; Intensive care; Meropenem; Microorganisms; Morbidity; Mortality; Patients; Rifampin; Synergism; synergy; Tigecycline; time-kill studies; Vancomycin; time-kill studies; antimicrobial combinations; vancomycin; synergy; carbapenem-resistant A. baumannii; colistin
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24050886

Carbapenem-resistant
(CR-Ab) infections are associated with high morbidity and mortality. The aim of the study was to evaluate the in-vitro activity of different antimicrobial combinations (with and without colistin, COL) against clinical isolates of CR-Ab collected from patients with CR-Ab infection, including unconventional combinations such as COL + VANcomycin (VAN) and COL + rifampin (RIF). CR-Ab strains were collected from hospitalized patients at Sapienza University of Rome. Antimicrobial susceptibility patterns were determined throughout MIC50/90s whereas the synergistic activity was evaluated by qualitative (i.e., checkerboard) and quantitative (i.e., killing studies) methods. All the strains were found oxacillinase (OXA) producers and tigecycline (TIG) sensitive whereas 2 strains were resistant to COL. Application of the checkerboard method indicated complete synergism in COL combinations at different extension: 21.4%, 57.1%, 42.8%, 35.7% for COL + meropenem (MEM), COL + RIF, COL + VAN and COL + TIG, respectively, with the non-conventional combinations COL + VAN and COL + RIF exhibiting the highest rate of synergism. Regarding COL-free combination, complete synergism was observed in 35.7% of the strains for MEM + TIG. Killing studies showed that the combinations COL + MEM, COL + TIG and MEM + TIG were bactericidal and synergistic against both colistin-sensitive and low colistin-resistant strains whereas only the combinations COL + VAN and COL + RIF showed an early and durable bactericidal activity against all the tested strains, with absence of growth at 24 h. This study demonstrated that COL-based combinations lead to a high level of synergic and bactericidal activity, especially COL + VAN and COL + RIF, even in the presence of high level of COL resistance.