In Vitro Activity Comparison of Ceftazidime–Avibactam and Aztreonam–Avibactam Against Bloodstream Infections With Carbapenem-Resistant Organisms in China

Yu, Wei; Xiong, Luying; Luo, Qixia; Chen, Yunbo; Ji, Jinru; Chen, Ying; Liu, Zhiying; Xiao, Yonghong

doi:10.3389/fcimb.2021.780365

Cited by 17 publications

(11 citation statements)

References 20 publications

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“…Recent surveillance data reported the lower MIC of AZA (MIC 90 = 0.5/4 mg/L) against CRE, especially for metallo-β-lactamase (MBL)-producing isolates ( Sader et al., 2021 ). Our previous data also showed that the MIC 90 of AZA was 1/4 mg/L, extending the observations for BSI CR-Kp ( Yu et al., 2021 ). In the present study, we found the decreased susceptibility mechanisms of AZAH-Kp strains isolated from patients without history of previous AZA exposure.…”

Section: Discussionsupporting

confidence: 85%

Epidemiology and Genomic Characteristics of Bloodstream Infection Caused by Carbapenem-Resistant Klebsiella pneumoniae With Decreased Susceptibility to Aztreonam/Avibactam in China

Shen²,

Chen³

et al. 2022

Front. Cell. Infect. Microbiol.

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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.

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Section: Discussionsupporting

confidence: 85%

Epidemiology and Genomic Characteristics of Bloodstream Infection Caused by Carbapenem-Resistant Klebsiella pneumoniae With Decreased Susceptibility to Aztreonam/Avibactam in China

Shen²,

Chen³

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Also, 60% activity was identified against NDM-1 carbapenemase, which contradicts literature describing poor activity of CZA against MBL-producing organisms. 42 This discrepancy could be allocated to other undetermined mechanisms that need future validation.…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms Mediating Ceftazidime/Avibactam Resistance Amongst Carbapenem-Resistant Klebsiella pneumoniae Isolates from Cancer Patients

El-Kady¹,

Elbaiomy²,

Elnagar³

2022

IDR

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Background A growing body of evidence suggests that ceftazidime/avibactam (CZA) is a potential therapeutic option for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections; however, resistant strains are increasingly emerged worldwide. Herein, we deemed to investigate the susceptibility profile of CRKP isolates from cancer patients to CZA and to identify the underlying resistance mechanisms. Methods Clinical samples were obtained from adult patients admitted to the Oncology Center of Mansoura University, Mansoura, Egypt. The antibiotic susceptibility pattern of K. pneumonia e isolates to different antibiotics was tested by the modified Kirby Bauer’s disc diffusion method. Minimum inhibitory concentrations of CZA were assessed using broth microdilution method. Screening for carbapenemase-producing strains was achieved by the modified Hodge test. Multiplex polymerase chain reactions (PCRs) were conducted for uncovering of carbapenemase-encoding genes ( bla KPC , bla VIM , bla IMP , bla NDM-1 , and bla OXA-48 ), and outer membrane porin genes ( ompK35 and ompK36 ). Results A total of 12 CZA-resistant isolates were identified out of 47 CRKP isolates (25.5%). The MIC 50 and MIC 90 of CZA against CRKP were 1 and 64 µg/mL, respectively. Risk factors for CZA resistance included chronic kidney disease, mechanical ventilation, longer length of hospital stay, and ICU admission. The multivariate logistic regression demonstrated that longer length of hospital stay ( P =0.03) was the only independent predictor for acquisition of CZA-resistant isolates. The leading mechanism for CZA resistance was sustained by bla KPC (50%), meanwhile 16.7% and 8.3% of the CZA-resistant isolates harbored bla OXA-48 and bla OXA-48 / bla NDM-1 , respectively. The MBL-encoding genes bla NDM-1 and bla IMP were detected in 16.7% and 8.3% of the isolates, respectively. Absence of both ompK35 and ompK36 was observed in 58.3% of the CZA-resistant isolates. Conclusion CZA has displayed superior in vitro activity against CRKP isolates in comparison to other antibiotics; however, thorough molecular characterization of resistant strains is highly recommended in future studies to detect and monitor the emergence of further tackling strains.

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“…A total of non-duplicate 318 BSIs-CRKP isolates were collected by Blood Bacterial Resistant Investigation Collaborative System (BRICS) program from 34 hospitals in 2019 in China ( Wei et al, 2021 ). Multi-locus sequence typing (MLST) was performed using the scheme of Pasteur database ( Supplementary Table S1 ).…”

Section: Methodsmentioning

confidence: 99%

“…The minimum inhibitory concentration (MIC) of 24 antibiotics (including CZA and AZA) were determined in our previous study ( Wei et al, 2021 ). Carbapenemase-producing isolates were further identified using modified Hodge test according to Clinical and Laboratory Standards Institute (CLSI) guidelines ( Clinical and Laboratory S, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Antibacterial Activity and Optimal Treatment of Ceftazidime-Avibactam and Aztreonam-Avibactam Against Bloodstream Infections Caused by Carbapenem-Resistant Klebsiella pneumoniae

Chen

Shen

et al. 2021

Front. Pharmacol.

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Objectives: This work was to investigate the activity and optimal treatments of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections caused by carbapenem resistant Klebsiella pneumoniae (BSIs-CRKP).Methods: A total of 318 nonduplicate BSIs-CRKP isolates were collected from Blood Bacterial Resistant Investigation Collaborative System (BRICS) program. The minimum inhibitory concentration (MIC) of CZA and AZA were determined by agar dilution method. Carbapenemase genes and multilocus sequence typing were amplified by PCR. Monte Carlo simulation (MCS) was conducted to calculate cumulative fraction of response (CFR) of different CZA or AZA administrations.Results: The MIC90 of CZA and AZA were 128/4 and 1/4 mg/L, respectively. There are 87.4 and 3.5% isolates carried blaKPC-2 and blaNDM-1. A total of 68 ST types were identified and 29 novel ST types. ST11 accounted for 66.6%. Further MCS showed CFR of CZA using two-step infusion therapy (rapid first-step 0.5 h infusion and slow second-step 3 h infusion, TSIT) (2.5 g 0.5 h, 3.75 g every 8 h with 3 h infusion and 3.75 g 0.5 h, 2.5 g every 8 h with 3 h infusion) was above 89%. The CFR of AZA with TSIT was above 96%.Conclusion: TSIT with sufficient pharmacokinetic conditions could be useful for enhancing the therapeutic efficacy of CZA and AZA against BSIs-CRKP.

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In Vitro Activity Comparison of Ceftazidime–Avibactam and Aztreonam–Avibactam Against Bloodstream Infections With Carbapenem-Resistant Organisms in China

Cited by 17 publications

References 20 publications

Epidemiology and Genomic Characteristics of Bloodstream Infection Caused by Carbapenem-Resistant Klebsiella pneumoniae With Decreased Susceptibility to Aztreonam/Avibactam in China

Epidemiology and Genomic Characteristics of Bloodstream Infection Caused by Carbapenem-Resistant Klebsiella pneumoniae With Decreased Susceptibility to Aztreonam/Avibactam in China

Molecular Mechanisms Mediating Ceftazidime/Avibactam Resistance Amongst Carbapenem-Resistant Klebsiella pneumoniae Isolates from Cancer Patients

Antibacterial Activity and Optimal Treatment of Ceftazidime-Avibactam and Aztreonam-Avibactam Against Bloodstream Infections Caused by Carbapenem-Resistant Klebsiella pneumoniae

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