| Summary: | <p>Abstract</p> <p>Background</p> <p>Infections sustained by multidrug-resistant (MDR) and pan-resistant <it>Acinetobacter baumannii </it>have become a challenging problem in Intensive Care Units. Tigecycline provided new hope for the treatment of MDR <it>A. baumannii </it>infections, but isolates showing reduced susceptibility have emerged in many countries, further limiting the therapeutic options. Empirical combination therapy has become a common practice to treat patients infected with MDR <it>A. baumannii</it>, in spite of the limited microbiological and clinical evidence supporting its efficacy. Here, the <it>in vitro </it>interaction of tigecycline with seven commonly used anti-<it>Acinetobacter </it>drugs has been assessed.</p> <p>Methods</p> <p>Twenty-two MDR <it>A. baumannii </it>isolates from Intensive Care Unit (ICU) patients and two reference strains for the European clonal lineages I and II (including 3, 15 and 6 isolates that were resistant, intermediate and susceptible to tigecycline, respectively) were tested. Antimicrobial agents were: tigecycline, levofloxacin, piperacillin-tazobactam, amikacin, imipenem, rifampicin, ampicillin-sulbactam, and colistin. MICs were determined by the broth microdilution method. Antibiotic interactions were determined by chequerboard and time-kill assays. Only antibiotic combinations showing synergism or antagonism in both chequerboard and time-kill assays were accepted as authentic synergistic or antagonistic interactions, respectively.</p> <p>Results</p> <p>Considering all antimicrobials in combination with tigecycline, chequerboard analysis showed 5.9% synergy, 85.7% indifference, and 8.3% antagonism. Tigecycline showed synergism with levofloxacin (4 strains; 16.6%), amikacin (2 strains; 8.3%), imipenem (2 strains; 8.3%) and colistin (2 strains; 8.3%). Antagonism was observed for the tigecycline/piperacillin-tazobactam combination (8 strains; 33.3%). Synergism was detected only among tigecycline non-susceptible strains. Time-kill assays confirmed the synergistic interaction between tigecycline and levofloxacin, amikacin, imipenem and colistin for 5 of 7 selected isolates. No antagonism was confirmed by time-kill assays.</p> <p>Conclusion</p> <p>This study demonstrates the <it>in vitro </it>synergistic activity of tigecycline in combination with colistin, levofloxacin, amikacin and imipenem against five tigecycline non-susceptible <it>A. baumannii </it>strains, opening the way to a more rationale clinical assessment of novel combination therapies to combat infections caused by MDR and pan-resistant <it>A. baumannii</it>.</p>
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