Abstract
Carbapenem-resistant Acinetobacter baumannii (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.
Highlights
IntroductionEnterobacteriaceae (CR-E), CR Acinetobacter baumannii (CR-Ab) and multidrug-resistant bacteria (MDR) Pseudomonas aeruginosa (MDR-Pa) has become a public health concern, especially in some countries where the diffusion of carbapenem-resistant microorganisms is nowadays endemic [1,2]
The rapid spread of multidrug-resistant bacteria (MDR) such as carbapenem-resistant (CR)Enterobacteriaceae (CR-E), CR Acinetobacter baumannii (CR-Ab) and MDR Pseudomonas aeruginosa (MDR-Pa) has become a public health concern, especially in some countries where the diffusion of carbapenem-resistant microorganisms is nowadays endemic [1,2]
MEM + TIG was in-vitro effective against COL-sensitive strain, in the presence of low-level of COL resistance the bactericidal activity, still present, occurred only after 24 h and, in the presence of high-level of COL resistance, the activity was completely absent. The latter is of particular importance due to main points: i) in the presence of kidney failure or other side effects related to the use of COL, MEM + TIG combination might be considered a better option to treat COL
Summary
Enterobacteriaceae (CR-E), CR Acinetobacter baumannii (CR-Ab) and MDR Pseudomonas aeruginosa (MDR-Pa) has become a public health concern, especially in some countries where the diffusion of carbapenem-resistant microorganisms is nowadays endemic [1,2]. Therapeutic options are severely limited [2,6] and are mainly based on colistin-containing combinations. The ability of CR-Ab to acquire resistance even to colistin (COL) further limits, if not completely precludes, the therapeutic choices. In this scary scenario, the lack of activity of new antimicrobials nowadays available in many countries imposes new efforts in finding the best therapeutic approach against this pathogen [7]. In the pipeline there are several promising agents with activity towards all CR microorganisms including CR-Ab (i.e., cefiderocol), they are still in in early clinical development of and will be eventually available only in the coming years [8]
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