Optimal treatment of ceftazidime-avibactam and aztreonam-avibactam against bloodstream infections or lower respiratory tract infections caused by extensively drug-resistant or pan drug-resistant (XDR/PDR) Pseudomonas aeruginosa.

Objective: To evaluate the efficacy of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections (BSIs) or lower respiratory tract infections (LRTIs) - caused by extensive drug-resistant or pan drug-resistant (XDR/PDR) Pseudomonas aeruginosa. Method: The two-fold dilution method was used to determine the minimum inhibitory concentrations (MICs) of CZA/AZA against XDR/PDR P. aeruginosa. Whole-genome sequencing was used to analyze the resistance determinants of each isolate. Monte Carlo simulations (MCSs) were used to evaluate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of each CZA/AZA dosing regimen via traditional infusion (TI)/optimized two-step-administration therapy (OTAT). Results: We found that XDR/PDR P. aeruginosa may carry some rare MBLs (e.g.: IND-6, SLB-1, THIN-B). P. aeruginosa isolates producing IMP-45, VIM-1, or VIM-2 were inhibited by AZA at a concentration of 2 to 8 mg/L. All isolates producing IND-6 plus other serine ß-lactamases were high-level resistant to CZA/AZA (MICs >64 mg/L). All simulated dosing regimens of CZA/AZA against BSIs-causing XDR/PDR P. aeruginosa achieved 100% PTA when the MIC was ≤32 mg/L. Conclusion: AZA has been considered as an option for the treatment of infections caused by XDR/PDR P. aeruginosa producing IMP-45, VIM-1, or VIM-2. OTAT with sufficient pharmacodynamic exposure may be an optimal treatment option for XDR/PDR P. aeruginosa with a high-level MIC of CZA/AZA.

Study on the anti-bacteria effects of polymyxin B combined with meropenem against pan-drug-resistant pseudomonas aeruginosa / 中国生化药物杂志

Objective To evaluate the anti-bacteria effects of polymyxin B combined with meropenem against 30 strains pan-drug resistant pseudomonas aeruginosa that separated in clinic. Methods The minimal inhibitory concentration (MICs) of 30 strains pan-drug resistant pseudomonas aeruginosa after treated with polymyxin B and meropenem as single-use or combination use were determined by both microdilution method and checkerboard method. The FIC index was calculated, then the type of combination effect was determined according to FIC index, which was used to determine whether there was synergistic or antagonistic effects. Results The MICs of pan-drug resistant pseudomonas aeruginosa were reduced significantly after polymyxin B combined with meropenem when compared with single-use. The percentages of the FIC index that less than 0.5 and the index between 0.5 and 1 were 60%and 30%respectively. Conclusion The results indicate that the combinations of polymyxin B with meropenem have good synergistic and additive effects against pan-drug resistant pseudomonas aeruginosa, there is no antagonism.

Genes of ?-Lactamase in Pan-drug Resistant Pseudomonas aeruginosa and Phylogenetic Analysis / 中华医院感染学杂志

OBJECTIVE To investigate the presence of ?-lactamase genes in pan-drug resistant Pseudomonas aeruginosa (PDRPA),and the redateness in PDRPA. METHODS The genes of 21 kinds of resistance were detected by polymerase chain reaction and phylogenetic analysis. RESULTS In 33 strains of PDRPA,the positive rates of blaTEM,blaOXA-10cluster,blaPER,blaGES,blaCARB,intⅠ1 and merA were 48.5%,45.5%,33.3%,21.2%,15.2%,78.8% and 69.7%,respectively. There were clone transmitted phenomena. CONCLUSIONS There are very high positive percentages of blaTEM,blaOXA-10cluster,blaPER,blaGES,blaCARB,intⅠ1 and merA genes in PDRPA. The PDRPA can induce clone transmitted hospital infection.

Genes of 16S rRNA Methylase and Aminoglycoside-modifying Enzymes in Pan-drug Resistant Pseudomonas aeruginosa / 中华医院感染学杂志

OBJECTIVE To investigate mechanisms of aminoglycoside resistance in pan-drug resistant Pseudomonas aeruginosa(PDRPA).METHODS The 11 genes of 16S rRNA methylase and aminoglycoside-modifying enzymes were detected by polymerase chain reaction(PCR) and verified by DNA sequencing.RESULTS In 33 strains of PDRPA,the positive rates of rmtB,aac(3)-Ⅱ,aac(6′)-Ⅰb,aac(6′)-Ⅱ,ant(3″)-Ⅰ and ant(2″)-Ⅰ were 42.4%,51.5%,42.4%,57.6%,48.5% and 63.6%.A total of 32 strains identified aminoglycoside modified genes,one strain aminoglycoside-modifying enzyme gene did not discovered,but rmtB positive.CONCLUSIONS The aminoglycoside resistance mechanisms of the PDRPA are the production of 16S rRNA methylase and aminoglycoside-modifying enzymes related.