In Vitro Activity of Novel Antimicrobial Combinations against Extensively drug-resistant XXXX .

@entity2892 @entity3273 @entity13757 @entity580 @entity6543 @entity3064
BACKGROUND: Extensively drug-resistant (XDR) @entity3064 spp. has emerged as a cause of @entity580 , especially in intensive care. Unfortunately resistance to @entity3273 is increasing and there is a need for new therapeutic options. We aimed to study the effect of some novel combinations against XDR A. baumannii in an in vitro PKPD model. METHODS: Three non-related clinical strains of XDR A. baumannii were investigated. Antibiotic simulated regimens were @entity3273 3 MU q8h (first dose 6 MU), @entity13757 10 mg/Kg q24h, @entity2892 1g q8h and @entity6543 1g q24h. Combination regimens included @entity3273 plus @entity13757 , @entity3273 plus @entity2892 and @entity2892 plus @entity6543 . Samples were obtained at 0,1,2,4,8 and 24h. RESULTS: Among single agent regimens, only @entity3273 resulted in significant log10CFU/mL reductions compared to control for all the strains tested. Although @entity3273 achieved bactericidal activity at 4h it was not able to reach the limit of detection (1 log10 CFU/mL). One strain had significant regrowth at 24h without emergence of resistance. @entity13757 - @entity3273 combinations lead to significant reduction of log10CFU/mL that outperformed those achieved with @entity3273 as single agent regimen, reaching the limit of detection at 24h against all the strains. @entity2892 plus @entity6543 outperformed @entity3273 regimen although did not reach the limit of detection with significant regrowth at 24h. Similarly, @entity3273 plus @entity2892 combinations reduced log10CFU/mL at 8h, with significant regrowth at 24h but with development of resistance to @entity3273 . CONCLUSIONS: We have shown some potentially useful alternatives for the treatment of extensively drug-resistant A. baumannii. Among them, @entity13757 - @entity3273 combination was the most effective and should be investigated in future studies.
