Erratum for Yahav et al., “New β-Lactam–β-Lactamase Inhibitor Combinations”

Yahav, Dafna; Giske, Christian G.; Grāmatniece, Alise; Abodakpi, Henrietta; Tam, Vincent H.; Leibovici, Leonard

doi:10.1128/cmr.00021-21

Cited by 34 publications

(20 citation statements)

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“…Unfortunately, the efficacy of β-lactams against Gram-negative pathogens is continuously threatened by the emergence and spread of new β-lactamases (ESBLs, AmpCs and carbapenemases) ( 1 – 3 ). A proven strategy to address the treatment challenges associated with evolving and proliferating β-lactamases involves the development of new agents that combine a novel β-lactamase inhibitor with an approved β-lactam to prevent its hydrolysis ( 4 , 5 ). In the last decade, several new parenteral β-lactam-β-lactamase inhibitor combinations have been introduced into the clinical use (ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam and ceftolozane-tazobactam) ( 4 , 5 ).…”

Section: Introductionmentioning

confidence: 99%

“…A proven strategy to address the treatment challenges associated with evolving and proliferating β-lactamases involves the development of new agents that combine a novel β-lactamase inhibitor with an approved β-lactam to prevent its hydrolysis ( 4 , 5 ). In the last decade, several new parenteral β-lactam-β-lactamase inhibitor combinations have been introduced into the clinical use (ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam and ceftolozane-tazobactam) ( 4 , 5 ). In contrast, a new orally bioavailable β-lactam-β-lactamase inhibitor combination has not been approved since amoxicillin-clavulanate in the 1980s.…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Activity of Ceftibuten/VNRX-5236 against Urinary Tract Infection Isolates of Antimicrobial-Resistant Enterobacterales

Karlowsky

Hackel²,

Sahm³

2022

Antimicrob Agents Chemother

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Ceftibuten/VNRX-7145 is a cephalosporin/boronate β-lactamase inhibitor combination under development as an oral treatment for complicated urinary tract infections caused by Enterobacterales producing serine β-lactamases (Ambler class A, C and D). In vivo , VNRX-7145 (VNRX-5236 etzadroxil) is cleaved to the active inhibitor, VNRX-5236. We assessed the in vitro activity of ceftibuten/VNRX-5236 against 1,066 urinary isolates of Enterobacterales from a 2014-2016 global culture collection. Each isolate tested was pre-selected to possess a multidrug-resistant (MDR) phenotype that included non-susceptibility to amoxicillin-clavulanate and resistance to levofloxacin. MICs were determined by CLSI broth microdilution. VNRX-5236 was tested at a fixed concentration of 4 μg/ml. Ceftibuten/VNRX-5236 inhibited 90% of all isolates tested (MIC 90 ) at 2 μg/ml; MIC 90 s for ESBL- ( n =566), serine carbapenemase- ( n =116), and acquired AmpC-positive ( n =58) isolate subsets were ≤0.25, >32, and 8 μg/ml, respectively. At concentrations of ≤1, ≤2, and ≤4 μg/ml, ceftibuten/VNRX-5236 inhibited 89.1, 91.7, and 93.1% of all isolates tested; 96.5, 97.7, and 98.4% of ESBL-positive isolates; 75.9, 81.9, and 81.9% of serine carbapenemase-positive isolates; and 70.7, 81.0, and 87.9% of acquired AmpC-positive isolates. Ceftibuten/VNRX-5236 at concentrations of ≤1, ≤2, and ≤4 μg/ml inhibited 85-89, 89-91, and 91-92% of isolates that were not susceptible (defined by CLSI and EUCAST breakpoint criteria) to nitrofurantoin, trimethoprim-sulfamethoxazole, and/or fosfomycin, (as part of their MDR phenotype), oral agents commonly prescribed to treat uncomplicated urinary tract infections. The potency of ceftibuten/VNRX-5236 (MIC 90 , 2 μg/ml) was similar (within one doubling-dilution) to intravenous-only agents ceftazidime-avibactam (MIC 90 2 μg/ml) and meropenem-vaborbactam (MIC 90 1 μg/ml). Continued investigation of ceftibuten/VNRX-5236 is warranted.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In Vitro Activity of Ceftibuten/VNRX-5236 against Urinary Tract Infection Isolates of Antimicrobial-Resistant Enterobacterales

Karlowsky

Hackel²,

Sahm³

2022

Antimicrob Agents Chemother

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“…KPC has been mainly detected in Klebsiella pneumoniae but also in other species of Enterobacteriaceae. All class A carbapenemases confer resistance to carbapenems; they are not inhibited by clavulanic acid or tazobactam but are inhibited by new β-lactamase inhibitors, such as avibactam and vaborbactam [ 36 ].…”

Section: Multi-drug-resistant Organisms (Mdros): Mechanisms Of Resist...mentioning

confidence: 99%

Prevalence and Therapeutic Management of Infections by Multi-Drug-Resistant Organisms (MDROs) in Patients with Liver Cirrhosis: A Narrative Review

et al. 2022

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Bacterial infections are common events that significantly impact the clinical course of patients with cirrhosis. As in the general population, infections caused by multi-drug-resistant organisms (MDROs) are progressively increasing in cirrhotic patients, accounting for up to 30–35% of all infections. Nosocomial acquisition and prior exposure to antimicrobial treatment or invasive procedures are well-known risk factors for MDRO infections. Several studies have demonstrated that infections due to MDROs have a poorer prognosis and higher rates of treatment failure, septic shock, and hospital mortality. Due to the increasing rate of antimicrobial resistance, the approach to empirical treatment in cirrhotic patients with life-threatening infections has become significantly more challenging. In order to ensure a prompt administration of effective antibiotic therapy while avoiding unnecessary antibiotic exposure at the same time, it is of utmost importance to choose the correct antimicrobial therapy and administration schedule based on individual clinical characteristics and risk factors and rapidly adopt de-escalation strategies as soon as microbiological data are available. In the present paper, we aimed to provide an overview of the most frequent infections diagnosed in cirrhotic patients, the prevalence and impact of antimicrobial resistance, and potential therapeutic options in this population.

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“…Recently, new antimicrobials such as cefiderocol, meropenem/vaborbactam (M/V) and imipenem/cilastatin/relebactam have been approved for KPC-Kp with limited indications [9], and real-life data are still lacking [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Meropenem/Vaborbactam Plus Aztreonam as a Possible Treatment Strategy for Bloodstream Infections Caused by Ceftazidime/Avibactam-Resistant Klebsiella pneumoniae: A Retrospective Case Series and Literature Review

et al. 2022

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Objectives: The aim of this study was to describe our experience of a combination treatment including meropenem/vaborbactam (M/V) plus aztreonam (ATM) for bloodstream infections (BSIs) due to ceftazidime/avibactam-resistant Klebsiella pneumoniae (CAZ/AVI-R-Kp), for which gene typing was not available at the time the blood culture (BC) results were obtained. Methods: Between 20 July and 22 August 2021, in our hospital laboratory, the molecular test for carbapenemase gene typing was not available. All Gram-negative bloodstream infections were recorded, and characteristics of patients were analysed. Among them, three patients had positive BCs for CAZ/AVI-R-Kp, and the empirical therapy was switched to M/V plus ATM pending phenotypic testing of sensitivity to M/V. Therapy was subsequently targeted on the basis of the results of this test. Results: KPC and NDM represent the most prevalent carbapenemases in our polyclinic. Three patients with CAZ/AVI-R-Kp sepsis were treated with M/V plus ATM not knowing the carbapenemase gene. Two had an NDM-Kp infection for which, upon obtaining the result of sensitivity to M/V, combination therapy was maintained. The third had KPC-Kp infection for which ATM was discontinued, after the acquisition of an antibiogram reporting full sensitivity to M/V (MIC = 0.25 mg/L). One patient with NDM-Kp infection died due to complications of the underlying disease for which he was hospitalised. Conclusions: Meropenem/vaborbactam plus ATM and subsequent de-escalation could represent a possible therapeutic strategy in severe CAZ/AVI-R-Kp infections when carbapenemase gene typing is not rapidly available.

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Erratum for Yahav et al., “New β-Lactam–β-Lactamase Inhibitor Combinations”

Cited by 34 publications

References 0 publications

In Vitro Activity of Ceftibuten/VNRX-5236 against Urinary Tract Infection Isolates of Antimicrobial-Resistant Enterobacterales

In Vitro Activity of Ceftibuten/VNRX-5236 against Urinary Tract Infection Isolates of Antimicrobial-Resistant Enterobacterales

Prevalence and Therapeutic Management of Infections by Multi-Drug-Resistant Organisms (MDROs) in Patients with Liver Cirrhosis: A Narrative Review

Meropenem/Vaborbactam Plus Aztreonam as a Possible Treatment Strategy for Bloodstream Infections Caused by Ceftazidime/Avibactam-Resistant Klebsiella pneumoniae: A Retrospective Case Series and Literature Review

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