ArticleAntimicrobial agents and chemotherapy1994
In vivo efficacy of a broad-spectrum cephalosporin, ceftriaxone, against penicillin-susceptible and -resistant strains of Streptococcus pneumoniae in a mouse pneumonia model.
Article in Antimicrobial agents and chemotherapy, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 55 citations in OpenAlex.
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- Inhibiting the copper efflux system in microbes as a novel approach for developing antibiotics.PloS one · 2019Article
- Pyrrolamide DNA gyrase inhibitors: fragment-based nuclear magnetic resonance screening to identify antibacterial agents.Antimicrobial agents and chemotherapy · 2012Article
- Animal models of Streptococcus pneumoniae disease.Clinical microbiology reviews · 2008Review
- In vitro and in vivo antibacterial activities of CS-023 (RO4908463), a novel parenteral carbapenem.Antimicrobial agents and chemotherapy · 2005Article
- Efficacy of BAL5788, a prodrug of cephalosporin BAL9141, in a mouse model of acute pneumococcal pneumonia.Antimicrobial agents and chemotherapy · 2004Article
- Efficacy of BB-83698, a novel peptide deformylase inhibitor, in a mouse model of pneumococcal pneumonia.Antimicrobial agents and chemotherapy · 2004Article
- Streptococcus pneumoniae strain-dependent lung inflammatory responses in a murine model of pneumococcal pneumonia.Intensive care medicine · 2003Article
- Pharmacodynamic assessment of clarithromycin in a murine model of pneumococcal pneumonia.Antimicrobial agents and chemotherapy · 2002Article
- In vivo activity and pharmacokinetics of ziracin (SCH27899), a new long-acting everninomicin antibiotic, in a murine model of penicillin-susceptible or penicillin-resistant pneumococcal pneumonia.Antimicrobial agents and chemotherapy · 2000Article
- Development of a new experimental model of penicillin-resistant Streptococcus pneumoniae pneumonia and amoxicillin treatment by reproducing human pharmacokinetics.Antimicrobial agents and chemotherapy · 1999Article
- Management of infections due to antibiotic-resistant Streptococcus pneumoniae.Clinical microbiology reviews · 1998Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The increasing emergence of penicillin-resistant (Pr) strains of Streptococcus pneumoniae could pose a therapeutic problem in the next few years. Ceftriaxone (CRO), a broad-spectrum cephalosporin, exhibits a smaller increase in MICs against Pr S. pneumoniae strains than amoxicillin (AMO) (usually referred as to the "gold standard" therapy for pneumococcal infections). Therefore, we compared their respective efficacies in a leukopenic Swiss mouse model of pneumococcal pneumonia. Infection was induced with two serotype 19 strains: a penicillin-susceptible (Ps) strain (MICs of < 0.01 for penicillin, 0.03 for AMO, and 0.03 for CRO) and a Pr strain (MICs of 4 for penicillin, 2 for AMO, and 0.5 for CRO). Untreated mice died within 2 or 3 days. Against the Ps strain, the minimal protective dose (two subcutaneous injections at 12-h intervals for 3 days) for both CRO and AMO was 5 mg/kg of body weight (87% survivors). Ten-fold-increased doses of CRO (50 mg/kg) gave similar protection (75% survivors) against the Pr strain, whereas 20- and 40-fold-increased doses of AMO protected 0 and 34% of the animals, respectively, against the Ps strain. CRO had a marked and prolonged antibacterial effect in the lungs (2.7-log-unit reduction of CFU in 24 h after a single 50-mg/kg injection) against the Pr strain in comparison with AMO. A standard dosage of 50 mg of CRO per kg in mice resulted in peak levels in serum and protein binding comparable to those observed with 1 g given intravenously in humans. This dosage remained effective against a highly Pr S. pneumoniae strain in this model. The microbiological activity and pharmacodynamic and pharmacokinetic properties of CRO (time during which concentrations exceed the MIC for the test pathogen [delta t MIC], > or less than 8 h; and peak/MIC ratio, >90 for free active drug) accounted for its efficacy relative to AMO (50 mg/kg: delta t MIC, <2; peak/MIC ratio, <25) against the highly Pr S. pneumoniae strain used in this study.
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