ArticleAntimicrobial agents and chemotherapy2011
Evaluation of ceftazidime and NXL104 in two murine models of infection due to KPC-producing Klebsiella pneumoniae.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Pharmacological aspects and spectrum of action of ceftazidime-avibactam: a systematic review.Infection · 2018Pooled it
- Safety and pharmacokinetics of single and multiple ascending doses of avibactam alone and in combination with ceftazidime in healthy male volunteers: results of two randomized, placebo-controlled studies.Clinical drug investigation · 2015Trial
- Rapid emergence of resistance to broad-spectrum direct antimicrobial activity of avibactam.Microbiology spectrum · 2025Article
- Dynamic kinetic resolution-mediated synthesis of C-3 hydroxylated arginine derivatives.Royal Society open science · 2025Article
- TheFrontiers in microbiology · 2025Article
- Using Therapeutic Drug Monitoring to Treat KPC-ProducingOpen forum infectious diseases · 2020Article
- Pharmacokinetics and Efficacy of Ceftazidime-Avibactam in the Treatment of Experimental Pneumonia Caused by Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae in Persistently Neutropenic Rabbits.Antimicrobial agents and chemotherapy · 2020Article
- Evaluating the Efficacies of Carbapenem/β-Lactamase Inhibitors Against Carbapenem-Resistant Gram-Negative BacteriaFrontiers in microbiology · 2019Article
- Roles of 2-oxoglutarate oxygenases and isopenicillin N synthase in β-lactam biosynthesis.Natural product reports · 2018Review
- The Epidemiology, Evolution, and Treatment of KPC-Producing Organisms.Current infectious disease reports · 2018Review
- Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram-Negative Bacterial Infections.Drugs · 2018Review
- Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae.Clinical microbiology reviews · 2018Review
- Review
- Anti-LPS antibodies protect against Klebsiella pneumoniae by empowering neutrophil-mediated clearance without neutralizing TLR4.JCI insight · 2017Article
- Can Ceftazidime-Avibactam and Aztreonam Overcome β-Lactam Resistance Conferred by Metallo-β-Lactamases in Enterobacteriaceae?Antimicrobial agents and chemotherapy · 2017Article
- Low Frequency of Ceftazidime-Avibactam Resistance among Enterobacteriaceae Isolates CarryingAntimicrobial agents and chemotherapy · 2017Article
- Characterization of a Carbapenem-Hydrolyzing Enzyme, PoxB, in Pseudomonas aeruginosa PAO1.Antimicrobial agents and chemotherapy · 2016Article
- Treatment options for infections caused by carbapenem-resistant Enterobacteriaceae: can we apply "precision medicine" to antimicrobial chemotherapy?Expert opinion on pharmacotherapy · 2016Review
- Pharmacodynamics of Ceftazidime and Avibactam in Neutropenic Mice with Thigh or Lung Infection.Antimicrobial agents and chemotherapy · 2016Article
- In vitro activity of aztreonam-avibactam against a global collection of Gram-negative pathogens from 2012 and 2013.Antimicrobial agents and chemotherapy · 2015Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
We evaluated the efficacy of NXL104, a novel β-lactamase inhibitor, in combination with ceftazidime (CAZ) in two murine infection models (septicemia and thigh infection). We chose two KPC-producing Klebsiella pneumoniae strains (VA-361 and VA-406) showing MICs of CAZ of ≥256 μg/ml. Septicemia was induced by the intraperitoneal injection of KPC-producing K. pneumoniae followed 30 min later by a single subcutaneous treatment with CAZ alone or CAZ-NXL104 in ratios of 2:1, 4:1, 8:1, and 16:1. In this model, the median effective doses for 50% (ED(50)) of the animals for CAZ alone versus VA-361 and VA-406 were 1,578 and 709 mg/kg of body weight, respectively. When combined with NXL104 at 2:1, 4:1, 8:1, and 16:1 ratios, the CAZ ED(50)s for VA-361 and VA-406 were reduced to 8.1 and 3.5 mg/kg, 15.1 and 3.8 mg/kg, 16.9 and 7.2 mg/kg, and 29.5 and 12.1 mg/kg, respectively. For thigh infection, neutropenia was induced by the intraperitoneal injection of cyclophosphamide at days -4 and -1 preinfection. Infection was established by the intramuscular injection of KPC-producing K. pneumoniae into the right thigh. Mice were treated 1.5 h postinfection with either CAZ alone or CAZ-NXL104 at constant ratios of 4:1. When thighs were removed at 24 h postinfection, a >2-log CFU reduction was observed for mice treated with CAZ-NXL104 at doses of ≥128:32 mg/kg. In contrast, CAZ doses of ≥1,024 mg/kg were unable to reduce the numbers of CFU. Despite resistance to CAZ and possessing a complex β-lactamase background, NXL104 combined with CAZ proved to be very effective in murine models of infection due to contemporary highly resistant KPC-producing K. pneumoniae isolates.
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