ABSTRACT
Objective To analyze the colistin heteroresistance in Pseudomonas aeruginosa strains and their in vitro susceptibility to antibiotics used in combination.Methods Two hundred and ninety-seven carbapenem-resistant Pseudomonas aeruginosa strains were selected for this study.Broth microdilution method was used to determine the minimum inhibitory concentrations of colistin and other antimicrobials against the Pseudomonas aeruginosa strains.The colistin heterogeneity of 20 colistin sensitive strains was analyzed by using population analysis profiles.The time-kill curves of 3 randomly selected colistin heteroresistant strains were used to determine the bacteriostatic activity of colistin.Chequer-board method was used to measure the combination efficacy of colistin with other antimicrobials including imipenem,meropenem,biapenem,ceftazidime,levofloxcin,piperacillin/tazobactam and cefoperazone/sulbactam.Results The colistin sensitive Pseudomonas aeruginosa strains accounted for 99.66％ of the 297 isolates.Population analysis profiles displayed that 35％ of the 20 isolates were colistin heteroresistant and 20％ of the 20 isolates were heterogeneous.It showed that when colistin was used in combination with other drugs,they mainly had synergistic and additive effects on heteroresistant isolates,but additive and indifferent effects on non-heterogeneous isolates.Conclusion Multidrug resistant Pseudomonas aeruginosa strains were highly susceptible to colistin,but heteroresistant and heterogeneous strains were common.The efficacy of colistin against heteroresistant isolates could be enhanced by using in combination with other drugs.
ABSTRACT
Objective To evaluate antimicrobial activity of fosfomycin combined with tigecycline against Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae and study the mechanism of drug resistance to fosfomycin. Methods Broth microdilution method was used to independently determine the minimum inhibitory concentrations (MIC)of fosfomycin and tigecycline against 42 Klebsiella pneumoniae isolates (including 20 KPC-producing and 22 KPC non-producing isolates).Checkerboard design method was applied to evaluate combined effect of different concentrations on antimicrobial susceptibility and calculate the fractional inhibitory concentration index (FICI).FICI=MICfosfomycin joint/MICfosfomycin monotherapy +MICtigecycline joint/MICtigecycline monotherapy .Related interpretation criteria were as following:FICI≤0.5 means synergy;0.5 2 means antagonism.The fosfomycin resistant genes in KPC-producing Klebsiella pneumoniae isolates were screened.The data were analyzed by t test.Results Antimicrobial susceptibility testing results indicated the fosfomycin and tigecycline susceptibility rates in KPC-producing isolates were 35 .0%(7/20)and 70.0% (14/20 ),respectively.The susceptibility rates of drug combination increased to 50.0% (10/20 )and 95 .0% (19/20 ),respectively,with both MIC decreased.MIC of tigecycline decreased significantly after combination therapy and showed a statistical significance compared with the MIC of monotherapy (t = - 2.596,P = 0.013 ),whereas there was no significant difference between single and combined therapy of fosfomycin (t=-1 .274,P =0.211).FICI indicated that a total of 60.0%isolates showed synergy and additive effects between two antimicrobial agents,followed by indifference (40.0%),but there was no antagonism effect.Among 22 KPC non-producing isolates,there were 54.5 %showing indifference effects,followed by additive (31 .8%)and synergy (13.6%)effects.No antagonism effect was found.The study also identified two isolates with fosA resistant gene which located on the same plasmid as well as the bla KPC gene.The plasmid sizes in the two isolates were 138.9 kb and 104.5 kb, respectively.Conclusions KPC-producing Klebsiella pneumoniae are more susceptible to tigecycline. Combined use of two antimicrobial agents mainly exerts synergy and additive effect rather than antagonism,which may suggest the combination therapy strategy could inhibit the activity of KPC-producing Klebsiella pneumoniae .