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Aztreonam/avibactam (AZA), as one of the novel β-lactamases and β-lactamase inhibitor combinations, is considered to be a promising option for bloodstream infection (BSI) of carbapenem-resistant Klebsiella pneumoniae (CR-Kp). However, decreased susceptibility of AZA activity in Enterobacterales has been reported. The aim of this study was to identify the mechanisms of BSI CR-Kp with decreased susceptibility of AZA (minimal inhibitory concentration above 16/4 mg/L) (AZAH-Kp). Nine BSI AZAH-Kp isolates were screened from 317 CR-Kp isolates in Blood Bacterial Resistant Investigation Collaborative System (BRICS) program. Whole genome sequencing, bioinformatics analysis, and the relative expression of blaKPC , ompK35 , and ompK37 were explored for CR-Kp with decreased susceptibility to AZA. The results revealed that elevated inhibitory concentration of AZA has emerged in CR-Kp before previous clinical exposure. In addition, decreased AZA susceptibility was associated with higher KPC expression and changes in OmpK35-37. [ABSTRACT FROM AUTHOR]

Aztreonam/avibactam (AZA), as one of the novel β-lactamases and β-lactamase inhibitor combinations, is considered to be a promising option for bloodstream infection (BSI) of carbapenem-resistant Klebsiella pneumoniae (CR-Kp). However, decreased susceptibility of AZA activity in Enterobacterales has been reported. The aim of this study was to identify the mechanisms of BSI CR-Kp with decreased susceptibility of AZA (minimal inhibitory concentration above 16/4 mg/L) (AZAH-Kp). Nine BSI AZAH-Kp isolates were screened from 317 CR-Kp isolates in Blood Bacterial Resistant Investigation Collaborative System (BRICS) program. Whole genome sequencing, bioinformatics analysis, and the relative expression of blaKPC, ompK35, and ompK37 were explored for CR-Kp with decreased susceptibility to AZA. The results revealed that elevated inhibitory concentration of AZA has emerged in CR-Kp before previous clinical exposure. In addition, decreased AZA susceptibility was associated with higher KPC expression and changes in OmpK35-37.

Abstract: The immunodominant trimeric β-barrel outer membrane protein OmpC from Salmonella typhi, the causative agent of typhoid, has been functionally characterized here. The activity in the vesicle environment was studied in vitro using OmpC reconstituted into proteoliposomes. Passage of polysaccharides and polyethyleneglycols through OmpC has been examined to determine the permeability properties. The relative rate of neutral solute flux yields a radius of 1.1 nm for the S. typhi OmpC pore. This is almost double the pore size of Escherichia coli. This provides an example of large pore size present in the porins that form trimers as in the general bacterial porin family. The method used in this study provides a good membrane model for functional studies of porins. [Copyright &y& Elsevier]

Background: Acinetobacter baumannii (A. baumannii), especially the multidrug resistant A. baumannii (MDR-AB) is becoming a common opportunistic pathogen in hospital, and constitutes significant public health threats. This study aimed at investigating the relationship between drug resistance with expression of class A-D β-lactamase genes, mutation in membrane porin and over-expression of efflux pump genes among A. baumannii isolated from Zhengjiang, China., Methods: Antibiotic susceptibility assays were performed using Kirby-Bauer disc diffusion method. PCR was used to detect β-lactamase genes and carO, oprD, adeR, adeS. Real-time PCR was used to assess the mRNA expression level of efflux pump gene adeB. The software of DNAMAN was applied to assemble oprD and carO sequences, and the sequences were compared with those retrieved from GenBank (http://www.ncbi.nlm.nih.gov/)., Results: 27 isolates (61.4%) in this study were MDR-AB, in which five β-lactamases including TEM, CTX-M-2, ADC, OXA-23 and OXA-51 were found, and the positive rate was 96.3% (26), 14.8% (4), 92.6% (25), 88.9% (24) and 92.6% (25), respectively. In addition, the expression level of adeB mRNA was significantly increased in MDR-AB, it might due to adeR mutation. Some mutations were also found in carO and oprD., Conclusion: MDR-AB showed high relationship with β-lactamase, mutation in membrane porin and overexpression of adeB, which may directly relates to the mutation in regulating gene adeR.