Activity of Ceftazidime–Avibactam Against Clinical Isolates of <i>Klebsiella pneumoniae</i>, Including KPC-Carrying Isolates, Endemic to New York City

Manning, Nyla; Balabanian, Gregory; Rose, Michael T.; Landman, David; Quale, John

doi:10.1089/mdr.2016.0293

Cited by 15 publications

(7 citation statements)

References 17 publications

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“…[10,25] The combination of PMB and ceftazidime has been demonstrated to have a synergistic effect on CRKP in vitro. [26] The prevalence of total adverse effects was 11.4% in our study. The prevalence of nephrotoxicity was 4.2%, which is lower than that in the study by Mattos and colleagues (40.5%), [27] Oliveira and co-workers (26.8%), [28] and Agarwal and collaborators (11.8%).…”

Section: Discussionsupporting

confidence: 44%

Clinical Effects of Polymyxin B in Patients infected with Carbapenem-resistant organisms

et al. 2020

Preprint

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Purpose: Carbapenem-resistant organisms (CROs) pose great challenges for clinical treatment. Polymyxin B (PMB) is one of the “last resort” choices of CRO infections. We explored the possible factors affecting PMB efficacy. Methods: This retrospective study involved CRO infected patients treated with PMB for ≥72 h. The endpoint indicator was clinical efficacy. We compared the characteristics (demographics, pathogenic bacteria, PMB treatment) between patients who had “clinical success” (CS) and “clinical failure” (CF).Results: A total of 192 patients were enrolled: 110 in the CS group and 82 in the CF group. The total cumulative dose for the CS group was higher than the CF group [1100 (700–1443.75) vs. 800 (500–1112.5) mg; P = 0.001]. Treatment duration in the CS group was longer than the CF group [11 (8–14) vs. 8 (6–11) days; P < 0.000]. Multivariate logistic regression analysis showed mechanical ventilation, vasoactive agents, multiple-site infection, and total cumulative dose to be independently associated with clinical efficacy. Cox survival analysis for 30-day mortality also showed that the use of vasoactive agents and the total cumulative dose of PMB could influence survival time and mortality rate independently.Conclusion: PMB had good efficacy and a low prevalence of adverse reactions. The total cumulative dose，duration of PMB treatment, mechanical ventilation, vasoactive agents, and multiple-site infection were factors associated with the clinical efficacy of PMB.

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Section: Discussionsupporting

confidence: 44%

Clinical Effects of Polymyxin B in Patients infected with Carbapenem-resistant organisms

et al. 2020

Preprint

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“… 11 , 26 The combination of PMB and ceftazidime has been demonstrated to have a synergistic effect on CRKP in vitro. 27 However, a recent study had also shown that the combination of colistin and meropenem cannot produce clinical benefits, despite the synergistic effects in vitro. 28 …”

Section: Discussionmentioning

confidence: 99%

Clinical Efficacy of Polymyxin B in Patients Infected with Carbapenem-Resistant Organisms

Lu¹,

Li²,

Qu³

et al. 2021

IDR

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Purpose Carbapenem-resistant organisms (CROs) pose great challenges for clinical treatment. Polymyxin B (PMB) is one of the “last resort” choices of CRO infections. We explored the possible factors affecting PMB efficacy. Patients and Methods This retrospective study involved CRO-infected patients treated with PMB for ≥72 h. The endpoint indicator was clinical efficacy. We compared the characteristics (demographics, pathogenic bacteria, PMB treatment) between patients who had “clinical success” (CS) and “clinical failure” (CF). Results A total of 191 patients were enrolled: 110 in the CS group and 81 in the CF group. The total cumulative dose for the CS group was higher than the CF group [1100 (700–1443.75) vs 800 (500–1112.5) mg; P = 0.001]. Treatment duration in the CS group was longer than the CF group [11 (8–14) vs 8 (6–11) days; P < 0.000]. Multivariate logistic regression analysis showed mechanical ventilation, vasoactive agents, multiple-site infection, and total cumulative dose to be independently associated with clinical efficacy. Cox survival analysis for 30-day mortality also showed that the use of vasoactive agents and the total cumulative dose of PMB could influence survival time and mortality rate independently. Conclusion PMB had good efficacy and a low prevalence of adverse reactions. The total cumulative dose, duration of PMB treatment, mechanical ventilation, vasoactive agents, and multiple-site infection were factors associated with the clinical efficacy of PMB.

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“…But little work has been done to evaluate the efficacy of available antibiotics against heteroresistant strains. Ceftazidime/avibactam, a β-lactam/β-lactamase inhibitor combination, has been proposed as a new salvage therapy for severe KPC-Kp infections (Barber et al, 2018; Manning et al, 2018; Tumbarello et al, 2019). The objective of this study was to evaluate the in vitro effect of ceftazidime/avibactam in combination with polymyxin B against polymyxin B heteroresistance Klebsiella pneumoniae .…”

Section: Introductionmentioning

confidence: 99%

Ceftazidime/avibactam Improves the Antibacterial Efficacy of Polymyxin B Against Polymyxin B Heteroresistant KPC-2-Producing Klebsiella pneumoniae and Hinders Emergence of Resistant Subpopulation in vitro

et al. 2019

Front. Microbiol.

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Due to the increasing multidrug resistance and limited antibiotics, polymyxin B revived as the last resort for the treatment of carbapenemase-producing Klebsiella pneumoniae (CRKP). Unfortunately, the heteroresistance hampers polymyxin B monotherapy treatment via the amplification of resistant subpopulation. Reliable polymyxin B based combinations are demanded. Ceftazidime/avibactam has been regarded as a new salvage therapy against CRKP. The occurrence of heteroresistance was confirmed by population analysis profiling (PAP). Our study demonstrated that polymyxin B and ceftazidime/avibactam combinations improved the in vitro antimicrobial activity of polymyxin B and delayed or suppressed the regrowth of resistant subpopulation by time-kill studies. Ceftazidime/avibactam at around MIC values (0.5–1 × MIC) plus clinically achievable concentrations of polymyxin B (0.5–2 mg/L) resulted in sustained killing against polymyxin B-heteroresistant isolates. Active PmrAB and PhoPQ systems and a pmrA mutation (G53R) in resistant subpopulation might associate with heteroresistance, but further investigation was required. Our findings suggested that the heteroresistance represented barriers to polymyxin B efficacy, and the combination of polymyxin B with ceftazidime/avibactam could be potentially valuable for the treatment of heteroresistant CRKP. Further, in vivo studies need to be performed to evaluate the efficacy of this combination against heteroresistant strains.

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Activity of Ceftazidime–Avibactam Against Clinical Isolates of Klebsiella pneumoniae, Including KPC-Carrying Isolates, Endemic to New York City

Cited by 15 publications

References 17 publications

Clinical Effects of Polymyxin B in Patients infected with Carbapenem-resistant organisms

Clinical Effects of Polymyxin B in Patients infected with Carbapenem-resistant organisms

Clinical Efficacy of Polymyxin B in Patients Infected with Carbapenem-Resistant Organisms

Ceftazidime/avibactam Improves the Antibacterial Efficacy of Polymyxin B Against Polymyxin B Heteroresistant KPC-2-Producing Klebsiella pneumoniae and Hinders Emergence of Resistant Subpopulation in vitro

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