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Comparative bacteriological efficacy of pharmacokinetically enhanced amoxicillin-clavulanate against Streptococcus pneumoniae with elevated amoxicillin MICs and Haemophilus influenzae.
Antimicrob Agents Chemother. 2005 Mar; 49(3):908-15.AA

Abstract

A new pharmacokinetically enhanced formulation of amoxicillin-clavulanate (2,000 mg of amoxicillin/125 mg of clavulanate twice a day; ratio 16:1) has been designed, with sustained-release technology, to allow coverage of bacterial strains with amoxicillin-clavulanic acid MICs of at least 4/2 mug/ml. The bacteriological efficacy of amoxicillin-clavulanate, 2,000/125 mg twice a day, ratio 16:1, was compared in a rat model of respiratory tract infection versus four other amoxicillin-clavulanate formulations: 8:1 three times a day (1,000/125 mg), 7:1 three times a day (875/125 mg), 7:1 twice a day (875/125 mg), and 4:1 three times a day (500/125 mg); levofloxacin (500 mg once a day); and azithromycin (1,000 mg on day 1 followed thereafter by 500 mg once a day). Bacterial strains included Streptococcus pneumoniae, with amoxicillin-clavulanic acid MICs of 2/1 (one strain), 4/2, or 8/4 microg/ml (three strains each), and Haemophilus influenzae, one beta-lactamase-positive strain and one beta-lactamase-negative, ampicillin-resistant strain. Animals were infected by intrabronchial instillation. Antibacterial treatment commenced 24 h postinfection, with doses delivered by computer-controlled intravenous infusion to approximate the concentrations achieved in human plasma following oral administration. Plasma concentrations in the rat corresponded closely with target human concentrations for all antimicrobials tested. Amoxicillin-clavulanate, 2,000/125 mg twice a day, ratio 16:1, was effective against all S. pneumoniae strains tested, including those with amoxicillin-clavulanic acid MICs of up to 8/4 microg/ml and against beta-lactamase-producing and beta-lactamase-negative ampicillin-resistant H. influenzae. These results demonstrate the bacteriological efficacy of pharmacokinetically enhanced amoxicillin-clavulanate 2,000/125 mg twice a day (ratio 16:1) against S. pneumoniae with amoxicillin-clavulanic acid MICs of at least 4/2 microg/ml and support clavulanate 125 mg twice a day as sufficient to protect against beta-lactamase in this rat model.

Authors+Show Affiliations

GlaxoSmithKline, Collegeville, PA, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15728883

Citation

Berry, Valerie, et al. "Comparative Bacteriological Efficacy of Pharmacokinetically Enhanced Amoxicillin-clavulanate Against Streptococcus Pneumoniae With Elevated Amoxicillin MICs and Haemophilus Influenzae." Antimicrobial Agents and Chemotherapy, vol. 49, no. 3, 2005, pp. 908-15.
Berry V, Hoover J, Singley C, et al. Comparative bacteriological efficacy of pharmacokinetically enhanced amoxicillin-clavulanate against Streptococcus pneumoniae with elevated amoxicillin MICs and Haemophilus influenzae. Antimicrob Agents Chemother. 2005;49(3):908-15.
Berry, V., Hoover, J., Singley, C., & Woodnutt, G. (2005). Comparative bacteriological efficacy of pharmacokinetically enhanced amoxicillin-clavulanate against Streptococcus pneumoniae with elevated amoxicillin MICs and Haemophilus influenzae. Antimicrobial Agents and Chemotherapy, 49(3), 908-15.
Berry V, et al. Comparative Bacteriological Efficacy of Pharmacokinetically Enhanced Amoxicillin-clavulanate Against Streptococcus Pneumoniae With Elevated Amoxicillin MICs and Haemophilus Influenzae. Antimicrob Agents Chemother. 2005;49(3):908-15. PubMed PMID: 15728883.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative bacteriological efficacy of pharmacokinetically enhanced amoxicillin-clavulanate against Streptococcus pneumoniae with elevated amoxicillin MICs and Haemophilus influenzae. AU - Berry,Valerie, AU - Hoover,Jennifer, AU - Singley,Christine, AU - Woodnutt,Gary, PY - 2005/2/25/pubmed PY - 2005/5/10/medline PY - 2005/2/25/entrez SP - 908 EP - 15 JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 49 IS - 3 N2 - A new pharmacokinetically enhanced formulation of amoxicillin-clavulanate (2,000 mg of amoxicillin/125 mg of clavulanate twice a day; ratio 16:1) has been designed, with sustained-release technology, to allow coverage of bacterial strains with amoxicillin-clavulanic acid MICs of at least 4/2 mug/ml. The bacteriological efficacy of amoxicillin-clavulanate, 2,000/125 mg twice a day, ratio 16:1, was compared in a rat model of respiratory tract infection versus four other amoxicillin-clavulanate formulations: 8:1 three times a day (1,000/125 mg), 7:1 three times a day (875/125 mg), 7:1 twice a day (875/125 mg), and 4:1 three times a day (500/125 mg); levofloxacin (500 mg once a day); and azithromycin (1,000 mg on day 1 followed thereafter by 500 mg once a day). Bacterial strains included Streptococcus pneumoniae, with amoxicillin-clavulanic acid MICs of 2/1 (one strain), 4/2, or 8/4 microg/ml (three strains each), and Haemophilus influenzae, one beta-lactamase-positive strain and one beta-lactamase-negative, ampicillin-resistant strain. Animals were infected by intrabronchial instillation. Antibacterial treatment commenced 24 h postinfection, with doses delivered by computer-controlled intravenous infusion to approximate the concentrations achieved in human plasma following oral administration. Plasma concentrations in the rat corresponded closely with target human concentrations for all antimicrobials tested. Amoxicillin-clavulanate, 2,000/125 mg twice a day, ratio 16:1, was effective against all S. pneumoniae strains tested, including those with amoxicillin-clavulanic acid MICs of up to 8/4 microg/ml and against beta-lactamase-producing and beta-lactamase-negative ampicillin-resistant H. influenzae. These results demonstrate the bacteriological efficacy of pharmacokinetically enhanced amoxicillin-clavulanate 2,000/125 mg twice a day (ratio 16:1) against S. pneumoniae with amoxicillin-clavulanic acid MICs of at least 4/2 microg/ml and support clavulanate 125 mg twice a day as sufficient to protect against beta-lactamase in this rat model. SN - 0066-4804 UR - https://www.unboundmedicine.com/medline/citation/15728883/Comparative_bacteriological_efficacy_of_pharmacokinetically_enhanced_amoxicillin_clavulanate_against_Streptococcus_pneumoniae_with_elevated_amoxicillin_MICs_and_Haemophilus_influenzae_ L2 - https://journals.asm.org/doi/10.1128/AAC.49.3.908-915.2005?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -