ArticleAntimicrobial agents and chemotherapy1999
Development of a new experimental model of penicillin-resistant Streptococcus pneumoniae pneumonia and amoxicillin treatment by reproducing human pharmacokinetics.
Article in Antimicrobial agents and chemotherapy, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Preclinical Pharmacokinetics and Pharmacodynamics of Antibiotic Adjuvants.ACS infectious diseases · 2026Review
- Predicting Antimicrobial Activity at the Target Site: Pharmacokinetic/Pharmacodynamic Indices versus Time-Kill Approaches.Antibiotics (Basel, Switzerland) · 2021Review
- Animal Models ofInternational journal of molecular sciences · 2019Review
- Hydrogen peroxide release by bacteria suppresses inflammasome-dependent innate immunity.Nature communications · 2019Article
- Preventing lung pathology and mortality in rabbit Staphylococcus aureus pneumonia models with cytotoxin-neutralizing monoclonal IgGs penetrating the epithelial lining fluid.Scientific reports · 2019Article
- Mechanical ventilation and Streptococcus pneumoniae pneumonia alter mitochondrial homeostasis.Scientific reports · 2018Article
- Streptococcus pneumoniae secretes hydrogen peroxide leading to DNA damage and apoptosis in lung cells.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Article
- In vivo efficacy of ceftaroline fosamil in a methicillin-resistant panton-valentine leukocidin-producing Staphylococcus aureus rabbit pneumonia model.Antimicrobial agents and chemotherapy · 2014Article
- Ceftaroline versus ceftriaxone in a highly penicillin-resistant pneumococcal pneumonia rabbit model using simulated human dosing.Antimicrobial agents and chemotherapy · 2011Article
- Animal models of Streptococcus pneumoniae disease.Clinical microbiology reviews · 2008Review
- Direct examination and cultures of bronchoalveolar lavage in pneumonia diagnosis: a comparative experimental study.Intensive care medicine · 2007Article
- Amoxicillin is effective against penicillin-resistant Streptococcus pneumoniae strains in a mouse pneumonia model simulating human pharmacokinetics.Antimicrobial agents and chemotherapy · 2007Article
- Influence of positive end-expiratory pressure (PEEP) on histopathological and bacteriological aspects of pneumonia during low tidal volume mechanical ventilation.Intensive care medicine · 2004Article
- Mutant selection window in levofloxacin and moxifloxacin treatments of experimental pneumococcal pneumonia in a rabbit model of human therapy.Antimicrobial agents and chemotherapy · 2004Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The increase of penicillin-resistant Streptococcus pneumoniae (PRSP) pneumonia results in a greater risk of antibiotic treatment failure. In vitro data are not sufficient predictors of clinical efficacy, and animal models may be insufficiently contributive, since they often use immunocompromised animals and do not always respect the human pharmacokinetics of antibiotics. We developed an experimental PRSP pneumonia model in immunocompetent rabbits, by using intrabronchial instillation of PRSP (MIC = 4 mg/liter), without any adjuvant. This reproducible model was used to assess amoxicillin efficacy by reproducing human serum pharmacokinetics following 1-g oral or intravenous administrations of amoxicillin every 8 h. Evaluation was performed by using clinical, CT scan, macroscopic, histopathologic, and microbiological criteria. Experimental pneumonia in untreated rabbits was similar to untreated severe human bacteremic untreated pneumonia; in both rabbits and humans, (i) cumulative survival was close to 50%, (ii) red or gray lung congestion and pleuritis were observed, and (iii) lung and spleen concentrations reached 5 and 4 log(10) CFU/g. A 48-h treatment resulted in a significant bacterial clearance in the lungs (1.53 versus 5.07 log(10) CFU/ml, P < 0.001) and spleen (1.00 versus 4.40 log(10) CFU/ml, P < 10(-6)) and a significant decrease in mortality (0% versus 50%, P = 0.02) in treated versus untreated rabbits. No difference was observed on macroscopic and histopathologic lesions between treated and untreated rabbits (P = 0.36 and 0.78, respectively). Similar results were obtained by using a fully penicillin-susceptible S. pneumoniae strain (MIC = 0.01 mg/liter). Our findings suggest that (i) this new model can be contributive in the evaluation of antibacterial agents and (ii) 1 g of amoxicillin three times a day may be sufficient to treat PRSP pneumonia in immunocompetent humans.
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