The Battle Is on: New Beta-Lactams for the Treatment of Multidrug-Resistant Gram-Negative Organisms

Noval, Mandee; Banoub, Mary; Claeys, Kimberly C; Heil, Emily L.

doi:10.1007/s11908-020-0710-9

Cited by 41 publications

(26 citation statements)

References 39 publications

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“…In vitro models have suggested that MVB has a higher barrier to resistance for KPC-producing Enterobacteriaceae than CZA (20,21). This may be because vaborbactam is able to overcome D179Y mutations at the KPC binding site, which confers resistance to CZA (22). However, recent treatment-emergent MVB nonsusceptibility has also been described (23).…”

Section: Discussionmentioning

confidence: 99%

Meropenem-Vaborbactam versus Ceftazidime-Avibactam for Treatment of Carbapenem-Resistant Enterobacteriaceae Infections

Ackley

Roshdy

Meredith

et al. 2020

Antimicrob Agents Chemother

123

112

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The comparative efficacy of ceftazidime-avibactam and meropenem-vaborbactam for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections remains unknown. This was a multicenter, retrospective cohort study of adults with CRE infections who received ceftazidime-avibactam or meropenem-vaborbactam for ≥72 hours from February 2015 to October 2018. Patients with a localized urinary tract infection and repeat study drug exposures after the first episode were excluded. The primary endpoint was clinical success compared between treatment groups. Secondary endpoints included 30- and 90-day mortality, adverse events (AE), 90-day CRE infection recurrence, and development of resistance in patients with recurrent infection. A post hoc subgroup analysis was completed comparing patients who received ceftazidime-avibactam monotherapy, ceftazidime-avibactam combination therapy, and meropenem-vaborbactam monotherapy. A total of 131 patients were included (ceftazidime-avibactam, n = 105; meropenem-vaborbactam, n = 26), 40% of whom had bacteremia. No significant difference in clinical success was observed between groups (62% versus 69%; P = 0.49). Patients in the ceftazidime-avibactam arm received combination therapy more often than patients in the meropenem-vaborbactam arm (61% versus 15%; P < 0.01). No difference in 30- and 90-day mortality resulted, and rates of AE were similar between groups. In patients with recurrent infection, development of resistance occurred in three patients that received ceftazidime-avibactam monotherapy and in no patients in the meropenem-vaborbactam arm. Clinical success was similar between patients receiving ceftazidime-avibactam and meropenem-vaborbactam for treatment of CRE infections, despite ceftazidime-avibactam being used more often as a combination therapy. Development of resistance was more common with ceftazidime-avibactam monotherapy.

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Section: Discussionmentioning

confidence: 99%

Meropenem-Vaborbactam versus Ceftazidime-Avibactam for Treatment of Carbapenem-Resistant Enterobacteriaceae Infections

Ackley

Roshdy

Meredith

et al. 2020

Antimicrob Agents Chemother

123

112

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“…Cefiderocol, a novel parenteral siderophore cephalosporin, shows potent activities against a wide range of multidrug-resistant Gram-negative bacilli ( 1 – 3 ). Especially, cefiderocol is the only β-lactam antibiotic with activities against both Gram-negative pathogens harboring metallo-type β-lactamase (MBL) and carbapenem-resistant Acinetobacter species ( 4 ). The United States Food and Drug Administration (FDA) approved cefiderocol for the treatment of complicated urinary tract infections with susceptible breakpoints of 2 and 1 μg/ml against Enterobacterales and Pseudomonas aeruginosa , respectively ( 5 ).…”

Section: Textmentioning

confidence: 99%

Activities of Cefiderocol with Simulated Human Plasma Concentrations against Carbapenem-Resistant Gram-Negative Bacilli in an In Vitro Chemostat Model

Matsumoto

Kanazawa

Sato

et al. 2020

Antimicrob Agents Chemother

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Activity of cefiderocol under simulated human plasma concentrations at the recommended dosing regimen of 2 g every 8 h with a 3-h infusion were evaluated using an in vitro chemostat model. Against a total of 6 meropenem-resistant Gram-negative strains with cefiderocol MIC of 0.5 to 4 μg/ml including metallo-β-lactamase producers and carbapenem-resistant Acinetobacter baumannii, cefiderocol treatment showed bactericidal effect within 8 h, and sustained efficacy with no marked bacterial regrowth over 24 h.

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“…The characterization of underlying mechanisms leading to carbapenem resistance of clinical isolates is not undertaken by most clinical microbiology laboratories for therapeutic decision-making; however, understanding if an isolate is CPE has significant epidemiological implications for monitoring local epidemiology and also lead to more effective treatment of infections caused by CPE (e.g. ceftazidime-avibactam or meropenem-vaborbactam, which have activity against KPC-producer) [16].…”

Section: Introductionmentioning

confidence: 99%

Combination of modified carbapenem inactivation method (mCIM) and EDTA-CIM (eCIM) for phenotypic detection of carbapenemase-producing Enterobacteriaceae

Tsai

Wang²,

Chiu

et al. 2020

BMC Microbiol

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Background Carbapenemase-resistant Enterobacteriaceae (CRE) cause many serious infections resulting in increasing treatment cost, prolonged hospitalization, and mortality rate. Reduced expression and/or mutations of porins and the presence of carbapenemase promote Enterobacteriaceae survival under carbapenem treatments. Development of accurate methods for the detection of antimicrobial resistance is required not only for therapy but also to monitor the spread of resistant bacteria or resistance genes throughout the hospital and community. In this study, we aimed to evaluate the phenotypic methods, Modified Hodge test (MHT), modified carbapenem inactivation method (mCIM), and EDTA-CIM (eCIM) for the detection of carbapenemase-producing Enterobacteriaceae (CPE). Results The results showed that mCIM had a sensitivity of 100% and a specificity of 100%, whereas the MHT had a sensitivity of 84.8% and a specificity of 97.8% for the 195 CRE isolates tested (105 CPE and 90 non-CPE isolates). The sensitivity of the mCIM/eCIM to detect metallo-carbapenemases in this study was 89.3% and the specificity was 98.7% as compared to the genotypic PCR detection. Conclusions These findings indicate that the mCIM combined with eCIM is useful for detecting and distinguishing different types of carbapenemase in Enterobacteriaceae.

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The Battle Is on: New Beta-Lactams for the Treatment of Multidrug-Resistant Gram-Negative Organisms

Cited by 41 publications

References 39 publications

Meropenem-Vaborbactam versus Ceftazidime-Avibactam for Treatment of Carbapenem-Resistant Enterobacteriaceae Infections

Meropenem-Vaborbactam versus Ceftazidime-Avibactam for Treatment of Carbapenem-Resistant Enterobacteriaceae Infections

Activities of Cefiderocol with Simulated Human Plasma Concentrations against Carbapenem-Resistant Gram-Negative Bacilli in an In Vitro Chemostat Model

Combination of modified carbapenem inactivation method (mCIM) and EDTA-CIM (eCIM) for phenotypic detection of carbapenemase-producing Enterobacteriaceae

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