A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi metallo-beta-lactamase (NDM)–producing Enterobacterales infection

Rawson, Timothy M; Brzeska-Trafny, Ilona; Maxfield, Rosemary; Almeida, Maíra Fernandes de; Gilchrist, Mark; Gonzalo, Ximena; Moore, Luke; Donaldson, Hugo; Davies, Frances

doi:10.1016/j.jgar.2022.01.025

Cited by 19 publications

(13 citation statements)

References 16 publications

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“…Few recent studies had also demonstrated the synergy between CAZ/AVI and ATM in MDR, XDR and PDR isolates by using different testing techniques. [ 3 , 38 – 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…First, the presence of an inverse-D was interpreted as synergy, and that was a qualitative approach. Second, a quantitative approach was used as the zone radius for ATM disc alone was measured, and MIC for CAZ/AVI was read using breakpoints from CLSI M100 [ 3 , 10 ].…”

Section: Methodsmentioning

confidence: 99%

“…are considered to be the most important Enterobacterales that commonly cause health-associated and community-associated infections [ 2 ]. Among multidrug-resistant bacteria, carbapenemase-producing Enterobacterales (CPE) show rapid global dissemination and pose a significant therapeutic challenge [ 1 , 3 ]. This is besides the high threat imposed by extensive drug resistant (XDR) and pan drug resistant (PDR) CPE.…”

Section: Introductionmentioning

confidence: 99%

“…With the advent of a new effective therapeutic option; ceftazidime-avibactam, a 3rd generation cephalosporin combined with a β-lactamase inhibitor, has a wide-spectrum activity against serine β-lactamases but is hydrolyzed by metallo β-lactamases [ 8 ]. In contrast, the aztreonam, monobactam, is stable in the presence of metallo β-lactamases but susceptible to hydrolysis by serine β-lactamases [ 3 ]. Thus, the combination of ceftazidime-avibactam and aztreonam is considered to have a synergistic therapeutic effect against CPE [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Ceftazidime-Avibactam plus aztreonam synergistic combination tested against carbapenem-resistant Enterobacterales characterized phenotypically and genotypically: a glimmer of hope

Taha

Kader²,

Shawky³

et al. 2023

Ann Clin Microbiol Antimicrob

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Background Carbapenemase-producing Enterobacterales (CPE) show rapid global dissemination and pose a significant therapeutic challenge. This study aimed to characterize carbapenemase-producing Klebsiella spp. and Escherichia coli (E. coli) phenotypically and genotypically and evaluate the effect of ceftazidime/ avibactam plus aztreonam combination. Methods A total of 219 Klebsiella species and 390 E. coli strains were isolated from clinical samples, in which 80 Klebsiella spp. and 20 E coli isolates were resistant to tested carbapenems (imipenem, ertapenem, meropenem) by disk diffusion/broth dilution method and Vitek-2 compact system. MASTDISCS Combi Carba plus discs and real time PCR were used to determine type of carbapenemase phenotypically and genotypically, respectively. Interestingly, the synergistic effect between ceftazidime-avibactam (E-test) and aztreonam (disc) was tested against the CPE isolates. Results Out of the carbapenem-resistant isolates, 76.25% Klebsiella spp. isolates were extensively drug-resistant (XDR) while 18.75% were pan drug-resistant (PDR), and 5% were multidrug-resistant (MDR). Regarding E. coli, 5% were PDR, 20% were MDR and 75% were XDR. More than one carbapenemase gene was detected in 99% of the isolates. In comparison between MAST-Carba plus discs and PCR results, sensitivity and specificity were (85.42–97.92%) in Klebsiella spp., and (69.64–100%) in E. coli, respectively. Moreover, a strong association was detected between both test results among Klebsiella spp. (p < 0.001) and E. coli (p = 0.012) isolates. Finally, ceftazidime-avibactam and aztreonam combination showed a synergistic effect in 98.8% of Klebsiella spp. and 95% of E coli. All 16 PDR isolates showed synergy. Conclusion This synergistic effect spots the light on new therapeutics for XDR and PDR CPE.

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“…Few recent studies had also demonstrated the synergy between CAZ/AVI and ATM in MDR, XDR and PDR isolates by using different testing techniques. [ 3 , 38 – 42 ].…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ceftazidime-Avibactam plus aztreonam synergistic combination tested against carbapenem-resistant Enterobacterales characterized phenotypically and genotypically: a glimmer of hope

Taha

Kader²,

Shawky³

et al. 2023

Ann Clin Microbiol Antimicrob

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“…It also inhibits type D β-lactamases (such as OXA-48-like) but has no effect on type B metalloenzymes (such as NDM and IMP). 53 Studies have shown that the combination of ceftazidime-avibactam and aztreonam, a novel enzyme inhibitor compound, can be used as a treatment plan for metalloenzyme-producing CRKP, but there are still uncertainties in the optimal administration strategy and pharmacokinetics-pharmacodynamics (PK-PD) target of combination therapy. 53 Therefore, the emergence of cogenerating bacteria not only increases the difficulty of treatment but also promotes the transmission of drug resistance, which should be given further attention.…”

Section: Discussionmentioning

confidence: 99%

Resistance Phenotype and Molecular Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Isolated from Nanjing Children’s Hospital in Jiangsu Province, China

Tao¹,

Tan²,

Ma³

et al. 2022

IDR

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Objective The drug resistance phenotype and molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) were identified among children in Jiangsu Province, China. Methods CRKP strains were collected from the Children’s Hospital of Nanjing Medical University from December 2020 to March 2022. CRKP strains were characterized for further study: antimicrobial susceptibility testing, carbapenem resistance genes and homology analysis. Results Among 86 strains of CRKP, 85 carried carbapenemase genes; the dominant gene was bla KPC-2 (88.2%, 75/85), followed by bla NDM-1 (4.7%, 4/85), bla NDM-5 (4.7%, 4/85), bla IMP-8 (2.3%, 2/85), and bla OXA-181 (1.2%, 1/85). Among the 86 strains of CRKP, one isolate contained both the bla NDM-5 and bla OXA-181 genes, which is the first time that Klebsiella pneumoniae has been shown to jointly carry these genes in China. Another CRKP strain did not carry any carbapenemase gene. MLST analysis identified a total of 10 different sequence types, among which sequence type (ST) 11 was the most common. PFGE analysis identified 75 bla KPC-2 -producing CRKP ST11 strains, of which 68 were dominant clusters distributed among 11 different wards, mainly the neonatal medical centre (18 strains), neonatal surgery (17 strains) and cardiac care unit (CCU) (8 strains) wards. Conclusion Clonal dissemination of KPC-2-producing CRKP ST11 was observed in multiple departments. Additionally, non-ST11 strains showed high polymorphism based on molecular typing, indicating increasing diversity in CRKP strains. To our knowledge, this is the first report of NDM-5 and OXA-181-coproducing Klebsiella pneumoniae causing infection in children in China, which poses a significant health risk for paediatric patients. Active surveillance and effective control measures are urgently needed to prevent further transmission of these strains among children.

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In vitro activity of ceftazidime-avibactam/aztreonam combination against MBL-producing Pseudomonas aeruginosa strains

Klein,

Jantsch,

Simon

et al. 2024

Infection

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A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi metallo-beta-lactamase (NDM)–producing Enterobacterales infection

Cited by 19 publications

References 16 publications

Ceftazidime-Avibactam plus aztreonam synergistic combination tested against carbapenem-resistant Enterobacterales characterized phenotypically and genotypically: a glimmer of hope

Ceftazidime-Avibactam plus aztreonam synergistic combination tested against carbapenem-resistant Enterobacterales characterized phenotypically and genotypically: a glimmer of hope

Resistance Phenotype and Molecular Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Isolated from Nanjing Children’s Hospital in Jiangsu Province, China

In vitro activity of ceftazidime-avibactam/aztreonam combination against MBL-producing Pseudomonas aeruginosa strains

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