Meropenem/vaborbactam: a next generation β-lactam β-lactamase inhibitor combination

Novelli, Andréa; Giacomo, Paola Del; Rossolini, Gian María; Tumbarello, Mario

doi:10.1080/14787210.2020.1756775

Cited by 80 publications

(74 citation statements)

References 73 publications

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“…Ceftazidime-avibactam is active on organisms harboring serine-carbapenemase, but shows no effects on metallo-βlactamase (MBL) producers (6)(7)(8). Meropenem-vaborbactam has activity against KPC-producing pathogens, while it remains ineffective to OXA-48-like and MBL-producing Enterobacterales (9). Therefore, the identification of carbapenemases is important for making effective treatment decisions.…”

Section: Introductionmentioning

confidence: 99%

Carbapenemase detection by NG-Test CARBA 5—a rapid immunochromatographic assay in carbapenem-resistant Enterobacterales diagnosis

Zhu

Jia

et al. 2021

Ann Transl Med

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Background:The global spread of carbapenem-resistant Enterobacterales (CRE) represents a serious public health concern as these organisms are associated with limited treatment options, high mortality rate and rapid transmissibility. The identification of carbapenemase remains a challenge in microbiological laboratories as no single method is perfect when considering cost, carbapenemase coverage, accuracy, handling complexity and TATs together.Methods: NG-Test CARBA 5 assay and modified carbapenem inactivation method in conjunction with EDTA carbapenem inactivation method (mCIM/eCIM) were challenged with a collection of 299 molecularly characterized CRE isolates in China in order to evaluate the performance in detecting five major carbapenemases (bla KPC , bla NDM , bla VIM , bla IMP , and bla OXA-48 ) among Enterobacterales.Results: NG-Test CARBA 5 detected all KPC-, NDM-, VIM-and OXA-48-producing isolates perfectly with a weak false-positive signal for NDM in an IMP-4 producer, which makes the specificity for NDM decreases to 99.6%. The overall specificity/sensitivity were 99.9%/100% for NG-Test CARBA 5. mCIM/ eCIM achieved high specificity of 100%/100% and sensitivity of 99.6%/97.4%, with one S. marcescens isolate harboring VIM-2 undetected.Conclusions: Both NG-Test CARBA 5 and mCIM/eCIM showed excellent results in the tested carbapenemase (bla KPC , bla NDM , bla VIM , bla IMP , and bla OXA-48 ) detection compared with molecular genotypic test.As every assay has its own limitations, suitable methods should be combined for the establishment of the CRE diagnostic pathways.

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Section: Introductionmentioning

confidence: 99%

Carbapenemase detection by NG-Test CARBA 5—a rapid immunochromatographic assay in carbapenem-resistant Enterobacterales diagnosis

Zhu

Jia

et al. 2021

Ann Transl Med

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“…Meropenem–vaborbactam was the first combination of antibiotics, a novel, cyclic, boronic acid-based β-lactamase inhibitor, and a carbapenem, to treat infections caused by carbapenem-resistant Gram-negative pathogens [ 28 , 29 , 30 ]. Vaborbactam presents biochemical, microbiologic, and pharmacologic properties adjusted for use with a carbapenem.…”

Section: Old and New Beta-lactamase Inhibitorsmentioning

confidence: 99%

Old and New Beta-Lactamase Inhibitors: Molecular Structure, Mechanism of Action, and Clinical Use

et al. 2021

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The β-lactams have a central place in the antibacterial armamentarium, but the increasing resistance to these drugs, especially among Gram-negative bacteria, is becoming one of the major threats to public health worldwide. Treatment options are limited, and only a small number of novel antibiotics are in development. However, one of the responses to this threat is the combination of β-lactam antibiotics with β-lactamase inhibitors, which are successfully used in the clinic for overcoming resistance by inhibiting β-lactamases. The existing inhibitors inactivate most of class A and C serine β-lactamases, but several of class D and B (metallo-β-lactamase) are resistant. The present review provides the status and knowledge concerning current β-lactamase inhibitors and an update on research efforts to identify and develop new and more efficient β-lactamase inhibitors.

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“…The addition of vaborbactam to meropenem restores its activity against Enterobacteriales producing Ambler class A carbapenemases, especially against KPC-CRE. Vaborbactam does not inhibit Ambler class B or D carbapenemases [ 57 ]. Meropenem/vaborbactam is FDA- and EMA0approved for the treatment of cUT Ion the strength of the TANGO I trial, and is also EMA approved for the treatment of cIAIs and HAP including VAP [ 58 ].…”

Section: Meropenem/vaborbactammentioning

confidence: 99%

“…The TANGO II Phase 3 study supported the efficacy of M/V for the treatment of serious (cUTI, cIAI, HAP, VAP, and BSI) infections caused by CRE, since this combination was associated with improved clinical cure, decreased mortality, and fewer adverse events than the best available therapy in resistant pathogens [ 61 ], and presented better results in patients without prior antimicrobial failure [ 62 ]. Despite the paucity of data, M/V has promising efficacy in the setting of pneumonia and/or other severe KPC producing-CRE infections in a real-world setting [ 57 , 63 ]. In addition, the potential for resistance selection appears to be lower overall than that observed for CAZ/AVI and colistin.…”

Section: Meropenem/vaborbactammentioning

confidence: 99%

Treatment of Bloodstream Infections Due to Gram-Negative Bacteria with Difficult-to-Treat Resistance

et al. 2020

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The rising incidence of bloodstream infections (BSI) due to Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) has been recognized as a global emergency. The aim of this review is to provide a comprehensive assessment of the mechanisms of antibiotic resistance, epidemiology and treatment options for BSI caused by GNB with DTR, namely extended-spectrum Beta-lactamase-producing Enterobacteriales; carbapenem-resistant Enterobacteriales; DTR Pseudomonas aeruginosa; and DTR Acinetobacter baumannii.

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Meropenem/vaborbactam: a next generation β-lactam β-lactamase inhibitor combination

Cited by 80 publications

References 73 publications

Carbapenemase detection by NG-Test CARBA 5—a rapid immunochromatographic assay in carbapenem-resistant Enterobacterales diagnosis

Carbapenemase detection by NG-Test CARBA 5—a rapid immunochromatographic assay in carbapenem-resistant Enterobacterales diagnosis

Old and New Beta-Lactamase Inhibitors: Molecular Structure, Mechanism of Action, and Clinical Use

Treatment of Bloodstream Infections Due to Gram-Negative Bacteria with Difficult-to-Treat Resistance

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