Phenotypic synergy testing of ceftazidime–avibactam with aztreonam in a university hospital having high number of metallobetalactamase producing bacteria

Sahu, Chinmoy; Pal, Sourav; Patel, Sangram Singh; Singh, Sanjay Kumar; Gurjar, Mohan; Ghoshal, Ujjala

doi:10.1080/23744235.2020.1788224

Cited by 10 publications

(8 citation statements)

References 20 publications

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“…al. (18) found more than 80% of the isolates showing synergy for CZA/ AT and 96% of these harboured bla NDM-1 . In comparison, synergy testing was positive in 72% of our isolates.…”

Section: Discussionmentioning

confidence: 97%

In-vitro activity of Cefiderocol against clinical isolates of meropenem-resistant Klebsiella pneumoniae from India

Borde

Mohammed

Sharma

et al. 2022

Preprint

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Background: Cefiderocol (FDC), a novel siderophore drug, is active against gram negative bacteria producing carbapenemases, including metallo-beta-lactamases. Objective: To compare the in-vitro activity of FDC with ceftazidime-avibactam (CZA), CZA/ aztreonam (AT) combination and colistin (CST), in clinical isolates of meropenem-resistant (MER-R) Klebsiella pneumoniae. Methods: From 2052 clinical specimens submitted for culture testing, 245 K. pneumoniae isolates were recovered within a six month period in 2021. 103 non-duplicate, non-outbreak, MER-R (MIC >4 μg/ml) strains were included in the study. Identification and susceptibility was performed using VITEK-2 (bioMérieux). 10 meropenem-susceptible isolates served as controls. For FDC, BMD was performed after in-house standardization. Disc diffusion (Liofilchem, Italy) and broth microdilution (BMD; ComASP, STC, Liofilchem, Italy) were used for susceptibility testing of CZA and CST respectively. Synergy testing for CZA and aztreonam (AT) was performed using disk approximation method. CLSI breakpoints were used for interpretation of results. Results: For FDC, MIC50 and MIC90 was 2 μg/ml and 8 μg/ml, respectively. 80% isolates were susceptible to FDC. 26.2% isolates were susceptible to CZA, synergy testing with CZA/ AT was positive for 74 (72%) of the isolates. 89.3% had intermediate susceptibility to CST. Nine (8.7%) were susceptible only to FDC. Conclusion: FDC is active in-vitro against MER-R K. pneumoniae > CZA/AT> CZA > CST, as observed in this study, applying CLSI criteria. Clinico-microbiological studies should be performed for assessing clinical efficacy of this novel drug in this region with high prevalence of carbapenem resistance among gram-negative organisms.

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“…al. (18) found more than 80% of the isolates showing synergy for CZA/ AT and 96% of these harboured bla NDM-1 . In comparison, synergy testing was positive in 72% of our isolates.…”

Section: Discussionmentioning

confidence: 97%

In-vitro activity of Cefiderocol against clinical isolates of meropenem-resistant Klebsiella pneumoniae from India

Borde

Mohammed

Sharma

et al. 2022

Preprint

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“…However, there are no guidelines for synergy testing between CZA and AT. A study by Sahu et al ( 9 ) found that more than 80% of the isolates showed synergy for CZA/ AT and 96% of these harbored bla NDM-1 . In comparison, synergy testing was positive in 72% of our isolates.…”

Section: Discussionmentioning

confidence: 99%

“…The synergy between CZA and AT was tested for all 103 isolates by observing zone distortion ( Fig. 2 ) between the disks of CZA and AT placed 20 mm apart, as in disk approximation methods ( 8 , 9 ).…”

Section: Methodsmentioning

confidence: 99%

In vitro activity of cefiderocol against comparators (ceftazidime-avibactam, ceftazidime-avibactam/ aztreonam combination, and colistin) against clinical isolates of meropenem-resistant Klebsiella pneumoniae from India

Borde,

Kareem,

Sharma

et al. 2023

Microbiol Spectr

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Cefiderocol (FDC), a novel siderophore drug, is active against Gram-negative bacteria producing carbapenemases, including metallo-beta-lactamases. The objective of this study is to compare the in vitro activity of FDC with ceftazidime-avibactam (CZA), CZA/aztreonam (AT) combination, and colistin (CST), in clinical isolates of meropenem-resistant (MER-R) Klebsiella pneumoniae . From the 2,052 clinical specimens submitted for culture testing, 245 K . pneumoniae isolates were recovered within a 6-month period in 2021. One hundred three non-duplicate, non-outbreak, MER-R (minimum inhibitory concentration, MIC >4 µg/mL) strains were included in the study. Identification and susceptibility were performed using VITEK-2 (bioMérieux). Meropenem-susceptible isolates ( n = 10) served as controls. For FDC, broth microdilution (BMD) was performed after in-house standardization. Disk diffusion (Liofilchem, Italy) and broth microdilution (ComASP, STC, Liofilchem, Italy) were used for susceptibility testing of CZA and CST, respectively. Synergy testing for CZA and AT was performed using disk approximation method. CLSI breakpoints were used for the interpretation of the results. For FDC, MIC 50 and MIC 90 were 2 and 8 µg/mL, respectively. A total of 80% of isolates were susceptible to FDC, 26.2% of isolates were susceptible to CZA, synergy testing with CZA/AT was positive for 74 (72%) of the isolates, and 89.3% were intermediate to CST. Nine (8.7%) were susceptible only to FDC. FDC is active in vitro against MER-R K. pneumoniae >CZA/AT > CZA > CST , as observed in this study, applying CLSI criteria. Clinico-microbiological studies should be performed to assess the clinical efficacy of this novel drug in this region with a high prevalence of carbapenem resistance among Gram-negative organisms. IMPORTANCE Management of infections with multi-drug resistant Klebsiella pneumoniae is a major challenge in hospital settings, with few treatment options. In this study, the authors aim to assess the in vitro susceptibility of these clinical isolates to cefiderocol, a novel siderophore. Comparators are colistin, ceftazidime-avibactam, and ceftazidime-avibactam/aztreonam synergy, which are currently available options for treatment in this region. Baseline-resistance rates against cefiderocol are higher than those in the previously published studies, with MIC50 and MIC90 at 2 and 8 µg/mL, respectively.

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“…Although the Infectious Diseases Society of America (IDSA) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recommend the empiric use of this therapy to treat infections caused by CRE-co-producing NDM and KPC [ 14 , 15 ], it is preferred that the clinical therapy could be guided by synergism experiments in vitro. However, the methodologies for the detection of synergism in vitro are usually labor-intensive and time-consuming [ 16 , 17 , 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

“…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

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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.

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Phenotypic synergy testing of ceftazidime–avibactam with aztreonam in a university hospital having high number of metallobetalactamase producing bacteria

Cited by 10 publications

References 20 publications

In-vitro activity of Cefiderocol against clinical isolates of meropenem-resistant Klebsiella pneumoniae from India

In-vitro activity of Cefiderocol against clinical isolates of meropenem-resistant Klebsiella pneumoniae from India

In vitro activity of cefiderocol against comparators (ceftazidime-avibactam, ceftazidime-avibactam/ aztreonam combination, and colistin) against clinical isolates of meropenem-resistant Klebsiella pneumoniae from India

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

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