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Activity of Simulated Human Dosage Regimens of Meropenem and Vaborbactam against Carbapenem-Resistant Enterobacteriaceae in an Hollow-Fiber Model. | LitMetric

AI Article Synopsis

  • - The studies aimed to evaluate the effective exposure levels of meropenem and vaborbactam that can provide antibacterial activity and prevent resistance in KPC-producing strains, using an experimental model over 32 hours at a specific bacterial concentration.
  • - Dosage regimens tested included 1 to 2 g of meropenem combined with 1 to 2 g of vaborbactam, with findings showing that 2 g of both drugs were effective in killing KPC-producing strains with specific resistance levels (MICs) of up to 16 mg/liter.
  • - Adjusting the vaborbactam levels to those observed in phase 3 clinical trials showed not only bactericidal effects against resistant strains

Article Abstract

The objective of these studies was to evaluate the exposures of meropenem and vaborbactam that would produce antibacterial activity and prevent resistance development in carbapenem-resistant carbapenemase (KPC)-producing strains when tested at an inoculum of 10 CFU/ml. Thirteen isolates, three isolates, and one isolate were examined in an hollow-fiber model over 32 h. Simulated dosage regimens of 1 to 2 g of meropenem with 1 to 2 g of vaborbactam, with meropenem administered every 8 h by a 3-h infusion based on phase 1 or phase 3 patient pharmacokinetic data, were studied in the model. A dosage of 2 g of meropenem in combination with 2 g of vaborbactam was bactericidal against , , and strains, with meropenem-vaborbactam MICs of up to 8 mg/liter. When the vaborbactam exposure was adjusted to the levels observed in patients enrolled in phase 3 trials (24-h free AUC, ∼550 mg · h/liter, versus 320 mg · h/liter in the phase 1 studies), 2 g of meropenem with 2 g of vaborbactam was also bactericidal against strains with meropenem-vaborbactam MICs of 16 mg/liter. In addition, this level of vaborbactam also suppressed the development of resistance observed using phase 1 exposures. In this pharmacodynamic model, exposures similar to 2 g of meropenem in combination with 2 g of vaborbactam administered every 8 h by a 3-h infusion in phase 3 trials produced antibacterial activity and suppressed the development of resistance against carbapenem-resistant KPC-producing strains of .

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786802PMC
http://dx.doi.org/10.1128/AAC.01969-17DOI Listing

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