Journal article
Evaluation of Double- and Triple-Antibiotic Combinations for VIM- and NDM-Producing Klebsiella pneumoniae by In Vitro Time-Kill Experiments
Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden1
Clinical Microbiology, MTC, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden2
Combination therapy is recommended for infections with carbapenemase-producing Klebsiella pneumoniae. However, limited data exist on which antibiotic combinations are the most effective. The aim of this study was to find effective antibiotic combinations against metallo-beta-lactamase-producing K. pneumoniae (MBL-KP).
Two VIM- and two NDM-producing K. pneumoniae strains, all susceptible to colistin, were exposed to antibiotics at clinically relevant static concentrations during 24-h time-kill experiments. Double- and triple-antibiotic combinations of aztreonam, ciprofloxacin, colistin, daptomycin, fosfomycin, meropenem, rifampin, telavancin, tigecycline, and vancomycin were used.
Synergy was defined as a ≥2 log10 decrease in CFU/ml between the combination and its most active drug after 24 h, and bactericidal effect was defined as a ≥3 log10 decrease in CFU/ml after 24 h compared with the starting inoculum. Synergistic or bactericidal activity was demonstrated for aztreonam, fosfomycin, meropenem, and rifampin in double-antibiotic combinations with colistin and also for aztreonam, fosfomycin, and rifampin in triple-antibiotic combinations with meropenem and colistin.
Overall, the combination of rifampin-meropenem-colistin was the most effective regimen, demonstrating synergistic and bactericidal effects against all four strains. Meropenem-colistin, meropenem-fosfomycin, and tigecycline-colistin combinations were not bactericidal against the strains used. The findings of this and other studies indicate that there is great potential of antibiotic combinations against carbapenemase-producing K. pneumoniae.
However, our results deviate to some extent from those of previous studies, which might be because most studies to date have included KPC-producing rather than MBL-producing strains. More studies addressing MBL-KP are needed.
Language: | Undetermined |
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Publisher: | American Society for Microbiology |
Year: | 2014 |
Pages: | 1757-1762 |
ISSN: | 10986596 and 00664804 |
Types: | Journal article |
DOI: | 10.1128/AAC.00741-13 |
Aminoglycosides Anti-Bacterial Agents Aztreonam Ciprofloxacin Colistin Daptomycin Drug Resistance, Multiple, Bacterial Drug Synergism Experimental Therapeutics Fosfomycin In Vitro Techniques Klebsiella pneumoniae Lipoglycopeptides Meropenem Microbial Sensitivity Tests Minocycline Rifampin Thienamycins Tigecycline Vancomycin beta-Lactamases telavancin