RESUMO
Objective To study the effects of efflux pump inhibitors(CCCP and PAβN)on carbapenems in Pseudomonas aernginosa(P.aeruginosa)clinical isolates and investigate the association between the resistance to imipenem or meropenem and expression levels of efflux pumps of P.aeruginosa.Methods MICs of imipenem or meropenem combined with efflux pump inhibitors including carbonyl cyanide m-chlorophenylhydrazone(CCCP,107 strains)and Phe-Arg-β-naphthylamide(PAβN,71 strains)against imipenem-resistant strains were determined by agar dilution method,and changes of MICs were observed.For 32 strains with different resistant phenotypes to imipenem and meropenem,the mRNA expression levels of three efflux pump genes(mexA,mexD and mexF)were quantified by real time fluorescent quantitative PCR.Results The resistance rate of imipenem and meropenem didn't prove any significant difference in the presence of efflux pump inhibitors.The X2 value of imipenem combined with CCCP and PAβN were 0.338 and 0.086,respectively(P＞0.05),while that of meropenem combined with CCCP and PAβN were 1.065 and 1.458(P＞0.05).No significant in MICs of carbapenems were seen in over half of P. aeruginesa isolates. MICs of carbapenems was significantly downregulated for 4-fold or above in eight isolates. Overexpression of efflux pumps genes were present in 24 of 27 carbapenem-resistant isolates(88. 9% ). Efflux pumps genes including MexAB-OprM, MexCD-OprJ and MexEF-OprN were all overexpressed in 13 isolates,constituting 54. 2% of all carbapenem-resistant isolates. There were 3 isolates in which beth MexAB-OprM and MexCD-OprJ showed overexpression,constituting 12. 5%. Also,MexAB-OprM and MexEF-OprN overexpressed in 3 isolates. There were 2 isolates (8.3%) showing MexEF-OprN overexpression and MexAB-OprM alone. MexCD-OprJ didn't showed overexpression alone. Furthermore,the expression levels of efflux pumps genes mexA,mexD and mexF in isolates susceptible to both in imipenem and meropenem were 0. 48±0. 48,0. 48±0. 53 and 0. 30±0. 41,respectively,which were much lower than that in carbapenem-resistant ones (P＜0. 05 ). MexA gene was expressed at a higher level in meropenemresistant isolates than meropenem-susceptible ones (P＜0. 05 ). Conclusions When the concentration of CCCP and PAβN were 5 μg/ml and 20 μg/ml respectively,the efforts on the carhapenems resistance of P.aeruginosa were small Overexpression of MexAB-OprM might play an important role in meropenemresistance in P. aerugines. Overexpression of MexCD-OprJ and MexEF-OprN was associated with imipenemresistance. However,the relationship between them and meropenem-resistance need to be explored in the future.
RESUMO
The objective of this study was to compare the efficacy and safety of piperacillin-sulbactam (PIP-SBT) and piperacillin-tazobactam (PIP-TAZ) in the treatment of bacterial respiratory and urinary tract infections. A randomised, single-blind, controlled clinical trial was performed. Differences in clinical efficacy, bacteriology and safety between the two groups were subjected to statistical analysis, including intent-to-treat (ITT) analysis. A total of 215 cases were enrolled, with 203 complete cases (99 PIP-SBT, 104 PIP-TAZ). A total of 209 cases (103 PIP-SBT, 106 PIP-TAZ) were included in the ITT analysis and a total of 212 cases (104 PIP-SBT, 108 PIP-TAZ) were included in the safety analysis. Overall efficacy rates of PIP-SBT and PIP-TAZ were 93.2% and 93.4%, respectively. Overall bacterial eradication rates of the two groups were 95% and 97.59%, respectively. Among the PIP-SBT group, eight patients (7.69%) had adverse events, including four probable drug-related events. Among the PIP-TAZ group, nine patients (8.33%) had adverse events, including one definitely drug-related and four probable drug-related events. All differences between the two groups were insignificant. PIP-SBT could be a suitable replacement for PIP-TAZ in the therapy of community-acquired respiratory and urinary tract infections caused by beta-lactamase-producing bacterial isolates.