A Simple Disk Stacking Plus Micro-Elution Method for Rapid Detection of the Synergistic Effect of Aztreonam and Ceftazidime/Avibactam Against Metallo-β-Lactamase Producing Enterobacterales

Liu, Zhou; Hang, Xiubing; Yan, Tao; Chu, Wenwen; Zhang, Gong; Liu, Yanyan; Dai, Yuanyuan; Yang, Min; Li, Jiabin; Zhou, Qiang

doi:10.2147/idr.s402275

Cited by 5 publications

(1 citation statement)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies of synergism have been described for ATM and CZA: MIC:MIC ratio technique [ 18 , 19 , 21 , 22 , 23 ]; strip crossing [ 17 , 21 , 22 ]; double-disk [ 16 , 19 ]; combined disk [ 16 ]; and several other variations [ 20 , 21 , 24 , 25 , 26 ]. However, only a few have tested and correlated their results to the in vitro standard assay for synergism detection, the time–kill curve (TKC) assay [ 16 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Aztreonam and Ceftazidime/Avibactam Synergism against Klebsiella pneumoniae by MALDI-TOF MS

Wilhelm

Inamine²,

Martins

et al. 2023

Antibiotics

View full text Add to dashboard Cite

Introduction: Resistance to carbapenems due to the co-production of NDM and ESBL or NDM and KPC is increasing. Therefore, combined therapy with aztreonam (ATM) plus ceftazidime/avibactam (CZA) has been recommended. Then, it is necessary to develop and evaluate fast and simple methods to determine synergism in vitro in microbiology laboratories. Objective: To develop a method to determine the synergism of ATM and CZA by MALDI-TOF MS (SynMALDI). Method: Klebsiella pneumoniae (n = 22) isolates with blaNDM and/or blaKPC genes were tested. The time–kill curve assay was performed for four isolates (three positives for blaNDM and blaKPC and one positive for blaNDM only). For SynMALDI, each isolate was incubated for 3 h in 4 tubes containing brain–heart infusion broth with the following: (1) no antibiotic; (2) ATM at 64 mg/L; (3) CZA at 10/4 mg/L; and (4) ATM at 64 mg/L plus CZA at 10/4 mg/L. After incubation, the bacterial protein extract was analyzed by MALDI-TOF MS, and the relative growth (RG) was determined for each isolate, considering intensities of the peaks of the bacterium incubated with antibiotic (tubes 2, 3, and 4) to the same bacterium incubated without antibiotic (tube 1), as follows: RG = IntensityWith antibiotic/IntensityWithout antibiotic. The combination was determined as synergistic when there was an RG decrease of 0.3 in the antibiotic combination in relation to the RG of the most active antibiotic alone. Results: The combination of ATM plus CZA proved to be synergic by time–kill curve assay. All isolates tested with the SynMALDI method also presented synergism. Conclusions: Detection of synergism for ATM plus CZA combination can be determined by MALDI-TOF MS, providing fast results in order to improve patient treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

Evaluation of Aztreonam and Ceftazidime/Avibactam Synergism against Klebsiella pneumoniae by MALDI-TOF MS

Wilhelm

Inamine²,

Martins

et al. 2023

Antibiotics

View full text Add to dashboard Cite

show abstract

In vitro synergy of the combination of sulbactam-durlobactam and cefepime at clinically relevant concentrations against A. baumannii, P. aeruginosa and Enterobacterales

Fouad,

Nicolau,

Gill

2023

Journal of Antimicrobial Chemotherapy

View full text Add to dashboard Cite

Background Sulbactam-durlobactam is a potent combination active against Acinetobacter baumannii; however, it lacks activity against other nosocomial pathogens. Cefepime is a common first-line therapy for hospital/ventilator-associated pneumonia caused by Gram-negative pathogens including Pseudomonas aeruginosa and Enterobacterales. With increasing resistance to cefepime, and the significant proportion of polymicrobial nosocomial infections, effective therapy for infections caused by Acinetobacter baumannii, P. aeruginosa and Enterobacterales is needed. This study investigated the in vitro synergy of sulbactam-durlobactam plus cefepime against relevant pathogens. Methods Static time–kills assays were performed in duplicate against 14 cefepime-resistant isolates (A. baumannii, n = 4; P. aeruginosa, n = 4; Escherichia coli, n = 3; Klebsiella pneumoniae, n = 3). One WT K. pneumoniae isolate was included. Antibiotic concentrations simulated the free-steady state average concentration of clinically administered doses in patients. Results Sulbactam-durlobactam alone showed significant activity against A. baumannii consistent with the MIC values. Sulbactam-durlobactam plus cefepime showed synergy against one A. baumannii isolate with an elevated MIC to sulbactam-durlobactam (32 mg/L). Against all P. aeruginosa isolates, synergy was observed with sulbactam-durlobactam plus cefepime. For the Enterobacterales, one E. coli isolate demonstrated synergy while the others were indifferent due to significant kill from sulbactam-durlobactam alone. The combination of sulbactam-durlobactam plus cefepime showed synergy against one of the K. pneumoniae and additive effects against the other two K. pneumoniae tested. No antagonism was observed in any isolates including the WT strain. Conclusions Synergy and no antagonism was observed with a combination of sulbactam-durlobactam and cefepime; further in vivo pharmacokinetic/pharmacodynamics data and clinical correlation are necessary to support our findings.

show abstract

Rapid Aztreonam/Avibactam NP test for detection of aztreonam/avibactam susceptibility/resistance in Enterobacterales

Viguier,

Bouvier,

Sadek

et al. 2023

J Clin Microbiol

View full text Add to dashboard Cite

Aztreonam-avibactam (AZA), a newly developed β-lactam/β-lactamase inhibitor combination , is a treatment option for infections due to carbapenem-resistant Enterobacterales (CRE), including metallo-ß-lactamase producers, regardless of additional production of broad-spectrum serine-ß-lactamases. However, AZA-resistance has already been reported in Enterobacterales and its early detection could be a valuable tool for faster and more accurate clinical decision-making. We therefore developed a rapid culture-based test for the identification of AZA resistance among multidrug-resistant Enterobacterales. The Rapid Aztreonam/Avibactam NP test is based on resazurin reduction when bacterial growth occurs in the presence of AZA at 8/4 µg/mL (protocol 1) or 12/4 µg/mL (protocol 2). Given the absence of guidelines on AZA susceptibility testing, two tentative breakpoints were indeed used to categorize AZA-susceptible isolates: ≤4 µg/mL in protocol 1 and ≤ 8 µg/mL in protocol 2. Bacterial growth was visually detectable by a blue-to-purple or blue-to-pink color change of the medium. A total of 78 enterobacterial isolates (among which 34 AZA-resistant and 13 AZA-resistant according to protocols 1 and 2, respectively) were used to evaluate the test performance using protocol 1 or protocol 2. The sensitivity and specificity of the test were found to be 100% and 97.7%, respectively, following protocol 1 and 100% and 100%, respectively, following protocol 2, in comparison with broth microdilution. All results were obtained within 4.5 hours corresponding to a time saving of ca. 14 hours compared with currently available methods for AZA susceptibility testing. The Rapid Aztreonam/Avibactam NP test is rapid, highly sensitive, specific, easily interpretable, and easy to implement in routine.

show abstract

A Simple Disk Stacking Plus Micro-Elution Method for Rapid Detection of the Synergistic Effect of Aztreonam and Ceftazidime/Avibactam Against Metallo-β-Lactamase Producing Enterobacterales

Cited by 5 publications

References 15 publications

Evaluation of Aztreonam and Ceftazidime/Avibactam Synergism against Klebsiella pneumoniae by MALDI-TOF MS

Evaluation of Aztreonam and Ceftazidime/Avibactam Synergism against Klebsiella pneumoniae by MALDI-TOF MS

In vitro synergy of the combination of sulbactam-durlobactam and cefepime at clinically relevant concentrations against A. baumannii, P. aeruginosa and Enterobacterales

Rapid Aztreonam/Avibactam NP test for detection of aztreonam/avibactam susceptibility/resistance in Enterobacterales

Contact Info

Product

Resources

About