Emergence of ceftazidime/avibactam resistance in KPC-8–producing Klebsiella pneumoniae in South America

Garcia, Javier A.; Nastro, Marcela; Cejas, Daniela; Santana, Gabriela dos Santos; Mancino, María Belen; Hidalgo, Mariana; Maccallini, Gustavo; Vay, Carlos; Radice, Marcela; Dabos, Laura; Famiglietti, Ángela; Rodríguez, Hernán B.

doi:10.1016/j.cmi.2020.03.013

Cited by 13 publications

(4 citation statements)

References 8 publications

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“…Although ceftazidime-avibactam-resistant K. pneumoniae isolates belonging to ST11 were previously reported in Argentina, they produced KPC-8 displaying enhanced catalytic efficiency toward ceftazidime ( 24 ). KPC-31 presents a single point mutation (Asp179Tyr) in the Ω-loop, assumed to be responsible for ceftazidime-avibactam resistance and restoration of the in vitro susceptibility to imipenem and meropenem ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Outbreak of Klebsiella pneumoniae ST11 Resistant To Ceftazidime-Avibactam Producing KPC-31 and the Novel Variant KPC-115 during COVID-19 Pandemic in Argentina

et al. 2022

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Section: Discussionmentioning

confidence: 99%

Outbreak of Klebsiella pneumoniae ST11 Resistant To Ceftazidime-Avibactam Producing KPC-31 and the Novel Variant KPC-115 during COVID-19 Pandemic in Argentina

et al. 2022

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“…In the present work, unlike other studies [9], 12 isolates co-producing KPC-2 were included and AVI was able to restore AZT activity in all of them. The prevalence of KPC-producing isolates with weaker affinity towards AVI is still low [22] in our region, and the co-production with a MBL has not been reported yet. In the same line, decreased susceptibility to AZT-AVI due to the combination of overexpressed intrinsic β-lactamases and efﬂux pumps has recently been reported [20].…”

Section: Discussionmentioning

confidence: 99%

In vitro synergistic activity of aztreonam (AZT) plus novel and old β-lactamase inhibitor combinations against metallo-β-lactamase-producing AZT-resistant Enterobacterales

Cervino

Gonzalez

Nastro

et al. 2021

Journal of Medical Microbiology

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The emergence of metallo-β-lactamase (MBL)-producing Enterobacterales , mainly New Delhi metallo-β-lactamase (NDM), represents a clinical threat due to the limited therapeutic alternatives. Aztreonam (AZT) is stable to MBLs, but most MBL-producing Enterobacterales isolates usually co-harbour other β-lactamases that confer resistance to AZT and, consequently, its use is restricted in these isolates. We compared the ability of sulbactam (SUL), tazobactam (TAZ), clavulanic acid (CLA) and avibactam (AVI) to restore the AZT activity in MBL-producing AZT-resistant Enterobacterales isolates. A collection of 64 NDM-producing AZT-resistant Enterobacterales from five hospitals in Buenos Aires city, Argentina, were studied during the period July–December 2020. MICs were determined using the agar dilution method with Mueller–Hinton agar according to Clinical and Laboratory Standards Institute (CLSI) recommendations. AVI, SUL and TAZ were used at a fixed concentration of 4 mg l−1, whereas CLA was used at a fixed concentration of 2 mg l−1. A screening method based on disc diffusion to evaluate this synergy was also conducted. Detection of bla KPC, bla OXA, bla NDM, bla VIM, bla CTXM-1, bla PER-2 and bla CIT was performed by PCR. The AZT-AVI combination restored the AZT activity in 98.4 % of AZT-resistant strains, whereas CLA, TAZ and SUL did so in 70.3, 15.6 and 12.5 %, respectively, in isolates co-harbouring extended-spectrum β-lactamases, but were inactive in isolates harbouring AmpC-type enzymes and/or KPC. The synergy screening test showed an excellent negative predictive value to confirm the absence of synergy, but positive results should be confirmed by a quantitative method. The excellent in vitro performance of the AZT-CLA combination represents a much more economical alternative to AZT-AVI, which could be of use in the treatment of MBL-producing, AZT-resistant Enterobacterales .

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“…Notably, the recommended doses and intervals may not be sufficient for patients with a unique physiology, such as haemodialysis, obesity, edematous state, and renal failure 16,17 . In addition, the emergence of CAZ/AVI resistance has been documented worldwide 18–20 . Therefore, therapeutic drug monitoring (TDM) of CAZ/AVI in patients to evaluate the PK/PD targets achievement and PK/PD‐based dosage adjustment are beneficial for obtaining its antibacterial effect and delaying the emergence of bacterial resistance due to suboptimal concentration in plasma.…”

Section: What Is Known and Objectivementioning

confidence: 99%

“…16,17 In addition, the emergence of CAZ/AVI resistance has been documented worldwide. [18][19][20] Therefore, therapeutic drug monitoring (TDM) of CAZ/AVI in patients to evaluate the PK/PD targets achievement and PK/PD-based dosage adjustment are beneficial for obtaining its antibacterial effect and delaying the emergence of bacterial resistance due to suboptimal concentration in plasma.…”

Section: What Is Known and Objectivementioning

confidence: 99%

Rapid, simple, and economical LC–MS/MS method for simultaneous determination of ceftazidime and avibactam in human plasma and its application in therapeutic drug monitoring

Cheng

Chen

Zhang

et al. 2022

Clinical Pharmacy Therapeu

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What is Known and Objective: Carbapenem-resistant Gram-negative bacterial pathogens continue to threaten public health. Avibactam (AVI), a novel non-β-lactam β-lactamase inhibitor, has been approved for use with ceftazidime (CAZ) mainly against carbapenem-resistant Enterobacteriaceae. Therapeutic drug monitoring (TDM) is urgently needed to optimize dosage regimens to maximize efficacy, minimize toxicity, and delay the emergence of resistance. This study aims to develop and validate a rapid, simple, and economical LC-MS/MS method for simultaneous determination of CAZ/AVI in human plasma.Methods: Samples were processed by simple protein precipitation, and gradient elution strategy was applied to separate CAZ and AVI on a reverse-phase C18 column; with subsequent detection by the mass spectrometer in a positive and negative ion switching mode. Plasma samples from patients were analysed.Results and Discussion: A 4-min run of LC-MS/MS was developed. The precision, trueness, matrix effect, extraction recovery, carry-over, dilution integrity, and stability were all acceptable for a bioanalytical method. The method was successfully applied to the determination of CAZ and AVI in patients, and a considerable PK variability of CAZ/AVI was observed among patients.What is New and Conclusion: A robust, rapid, simple, and economical LC-MS/MS method for the simultaneous determination of CAZ and AVI was developed. The considerable PK variability of CAZ/AVI among patients demonstrates the clinical significance of TDM.

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Emergence of ceftazidime/avibactam resistance in KPC-8–producing Klebsiella pneumoniae in South America

Cited by 13 publications

References 8 publications

Outbreak of Klebsiella pneumoniae ST11 Resistant To Ceftazidime-Avibactam Producing KPC-31 and the Novel Variant KPC-115 during COVID-19 Pandemic in Argentina

Outbreak of Klebsiella pneumoniae ST11 Resistant To Ceftazidime-Avibactam Producing KPC-31 and the Novel Variant KPC-115 during COVID-19 Pandemic in Argentina

In vitro synergistic activity of aztreonam (AZT) plus novel and old β-lactamase inhibitor combinations against metallo-β-lactamase-producing AZT-resistant Enterobacterales

Rapid, simple, and economical LC–MS/MS method for simultaneous determination of ceftazidime and avibactam in human plasma and its application in therapeutic drug monitoring

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