ArticleAntimicrobial agents and chemotherapy2002
Pharmacodynamic assessment of clarithromycin in a murine model of pneumococcal pneumonia.
Article in Antimicrobial agents and chemotherapy, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 75 citations in OpenAlex.
- Antimicrobial treatment guidelines for acute bacterial rhinosinusitis.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2004Guideline
- Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2003Guideline
- Modeling the autoinhibition of clarithromycin metabolism during repeated oral administration.Antimicrobial agents and chemotherapy · 2009Trial
- Intravenous Clarithromycin in Critically Ill Adults: A Population Pharmacokinetic Study.Antibiotics (Basel, Switzerland) · 2025Article
- Clarithromycin Inhibits Pneumolysin Production via Downregulation ofMicrobiology spectrum · 2021Article
- Post-exposure prophylaxis (PEP) efficacy of rifampin, rifapentine, moxifloxacin, minocycline, and clarithromycin in a susceptible-subclinical model of leprosy.PLoS neglected tropical diseases · 2020Article
- C-Reactive Protein-Based Strategy to Reduce Antibiotic Dosing for the Treatment of Pneumococcal Infection.Frontiers in immunology · 2020Article
- Treatment of Pneumococcal Infection by Using Engineered Human C-Reactive Protein in a Mouse Model.Frontiers in immunology · 2020Article
- Animal Models ofInternational journal of molecular sciences · 2019Review
- High-Dose Rifamycins Enable Shorter Oral Treatment in a Murine Model of Mycobacterium ulcerans Disease.Antimicrobial agents and chemotherapy · 2019Article
- Pharmacokinetics and Pharmacodynamics of Gamithromycin Treatment ofFrontiers in pharmacology · 2019Article
- A strain-independent method to induce progressive and lethal pneumococcal pneumonia in neutropenic mice.Journal of biomedical science · 2015Article
- Resistance of M. leprae to quinolones: a question of relativity?PLoS neglected tropical diseases · 2013Article
- Efficacy of increasing dosages of clarithromycin for treatment of experimental Mycoplasma pneumoniae pneumonia.The Journal of antimicrobial chemotherapy · 2011Article
- In vitro pharmacokinetic and pharmacodynamic evaluation of S-013420 against Haemophilus influenzae and Streptococcus pneumoniae.Antimicrobial agents and chemotherapy · 2010Article
- Efficacy of clarithromycin against experimentally induced pneumonia caused by clarithromycin-resistant Haemophilus influenzae in mice.Antimicrobial agents and chemotherapy · 2010Article
- Animal models of Streptococcus pneumoniae disease.Clinical microbiology reviews · 2008Review
- Pharmacodynamic characterization of ceftobiprole in experimental pneumonia caused by phenotypically diverse Staphylococcus aureus strains.Antimicrobial agents and chemotherapy · 2008Article
- Comparative efficacies of different antibiotic treatments to eradicate nontypeable Haemophilus influenzae infection.BMC infectious diseases · 2008Article
- Pharmacokinetics of single- and multiple-dose oral clarithromycin in soft tissues determined by microdialysis.Antimicrobial agents and chemotherapy · 2007Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pharmacodynamic profile of clarithromycin (CLR) was evaluated with a murine model of pneumonia. Eight Streptococcus pneumoniae isolates, including three macrolide-sensitive and five macrolide-resistant strains, were inoculated intratracheally into immunocompromised ICR mice as 10(8)-CFU bacterial suspensions. Orally administered CLR daily doses ranging from 5 to 600 mg/kg of body weight were given over 5 days, during which animal survival was monitored. The bacterial density in lung tissues was examined after 24 h of CLR treatment and in control groups. Pharmacokinetic analysis of CLR in mice demonstrated that the regimen of 150 mg/kg twice a day was representative of human pharmacokinetics and was used to compare the efficacy of CLR against sensitive and resistant S. pneumoniae strains. Immunocompetent CBA/J mice were also infected and treated as described above and evaluated for bacterial density and survival to assess the effect of the presence of leukocytes. All three pharmacodynamic parameters, the duration (percent) of the time that serum CLR concentrations remain above the MIC (%T>MIC), the ratio of the area under the concentration-time curve from 0 to 24 h (AUC(0-24)) to the MIC, and the ratio of the maximum concentration of drug in serum to the MIC, were found to be closely correlated to CLR bacterial efficacy (P < 0.001). Furthermore, all parameters had close correlation to bacterial density (r(2) = 0.72 to 0.82), median survival (r(2) = 0.93 to 0.94), and total percent survival (r(2) = 0.91 to 0.92). These in vivo data suggest that the bacterial activity of CLR is closely correlated with all three parameters over a wide range of exposures and, as a consequence of parameter interdependency, AUC(0-24)/MIC is the most reasonable predictor of antibiotic efficacy. In this neutropenic pneumonia model, CLR was less efficacious against S. pneumoniae strains for which MICs were >or=4 microg/ml. However, the presence of leukocytes in the immunocompetent mice resulted in improved bactericidal activity, relative to that in the neutropenic animals, despite an MIC of 4 microg/ml.
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