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Antibacterial effects of amoxicillin-clavulanate against Streptococcus pneumoniae and Haemophilus influenzae strains for which MICs are high, in an in vitro pharmacokinetic model.
Antimicrob Agents Chemother. 2004 Jul; 48(7):2599-603.AA

Abstract

The antibacterial effect of amoxicillin-clavulanate in two formulations, pharmacokinetically enhanced 16:1 amoxicillin-clavulanate twice a day (b.i.d.) and standard 7:1 amoxicillin-clavulanate b.i.d., were studied in an in vitro pharmacokinetic model of infection. Five strains of Streptococcus pneumoniae and two of Haemophilus influenzae, all associated with raised MICs (2 to 8 mg/liter), were used. The antibacterial effect was measured over 24 h by the area under the bacterial kill curve (AUBKC) and the log change in viable count at 24 h (Delta24). A high 10(8) CFU/ml and low 10(6) CFU/ml initial inocula were used. Employing the Delta24 effect measure, the time above MIC (T>MIC) 50% maximum effect (EC(50)) for S. pneumoniae was in the range 21 to 28% with an 80% maximal response of 41 to 51%, for the AUBKC measure, the value was 26 to 39%, irrespective of inoculum. For H. influenzae, the T>MIC EC(50) was 28 to 37%, and the 80% maximum response was 32 to 48% for the Delta24 measure and 20 to 48% for AUBKC. The maximum response occurred at a T>MIC of 50 to 60% for both species and inocula. The S. pneumoniae data were analyzed by analysis of variance to assess the effect of inoculum, formulation, and MIC on antibacterial effect. Standard and enhanced formulations had different effects depending on MIC, with the standard formulation less effective at higher amoxicillin-clavulanate MICs. This is explained by the greater T>MICs of the enhanced formulation. Although resistant to amoxicillin-clavulanate by conventional breakpoints, S. pneumoniae and H. influenzae strains for which MICs are 2 or 4 mg/liter may well respond to therapy with pharmacokinetically enhanced formulation amoxicillin-clavulanate.

Authors+Show Affiliations

Bristol Centre for Antimicrobial Research & Evaluation, Department of Medical Microbiology, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, United Kingdom. alasdair.macgowan@north-bristol.swest.nhs.ukNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15215115

Citation

MacGowan, Alasdair P., et al. "Antibacterial Effects of Amoxicillin-clavulanate Against Streptococcus Pneumoniae and Haemophilus Influenzae Strains for Which MICs Are High, in an in Vitro Pharmacokinetic Model." Antimicrobial Agents and Chemotherapy, vol. 48, no. 7, 2004, pp. 2599-603.
MacGowan AP, Noel AR, Rogers CA, et al. Antibacterial effects of amoxicillin-clavulanate against Streptococcus pneumoniae and Haemophilus influenzae strains for which MICs are high, in an in vitro pharmacokinetic model. Antimicrob Agents Chemother. 2004;48(7):2599-603.
MacGowan, A. P., Noel, A. R., Rogers, C. A., & Bowker, K. E. (2004). Antibacterial effects of amoxicillin-clavulanate against Streptococcus pneumoniae and Haemophilus influenzae strains for which MICs are high, in an in vitro pharmacokinetic model. Antimicrobial Agents and Chemotherapy, 48(7), 2599-603.
MacGowan AP, et al. Antibacterial Effects of Amoxicillin-clavulanate Against Streptococcus Pneumoniae and Haemophilus Influenzae Strains for Which MICs Are High, in an in Vitro Pharmacokinetic Model. Antimicrob Agents Chemother. 2004;48(7):2599-603. PubMed PMID: 15215115.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antibacterial effects of amoxicillin-clavulanate against Streptococcus pneumoniae and Haemophilus influenzae strains for which MICs are high, in an in vitro pharmacokinetic model. AU - MacGowan,Alasdair P, AU - Noel,Alan R, AU - Rogers,Chris A, AU - Bowker,Karen E, PY - 2004/6/25/pubmed PY - 2004/9/8/medline PY - 2004/6/25/entrez SP - 2599 EP - 603 JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 48 IS - 7 N2 - The antibacterial effect of amoxicillin-clavulanate in two formulations, pharmacokinetically enhanced 16:1 amoxicillin-clavulanate twice a day (b.i.d.) and standard 7:1 amoxicillin-clavulanate b.i.d., were studied in an in vitro pharmacokinetic model of infection. Five strains of Streptococcus pneumoniae and two of Haemophilus influenzae, all associated with raised MICs (2 to 8 mg/liter), were used. The antibacterial effect was measured over 24 h by the area under the bacterial kill curve (AUBKC) and the log change in viable count at 24 h (Delta24). A high 10(8) CFU/ml and low 10(6) CFU/ml initial inocula were used. Employing the Delta24 effect measure, the time above MIC (T>MIC) 50% maximum effect (EC(50)) for S. pneumoniae was in the range 21 to 28% with an 80% maximal response of 41 to 51%, for the AUBKC measure, the value was 26 to 39%, irrespective of inoculum. For H. influenzae, the T>MIC EC(50) was 28 to 37%, and the 80% maximum response was 32 to 48% for the Delta24 measure and 20 to 48% for AUBKC. The maximum response occurred at a T>MIC of 50 to 60% for both species and inocula. The S. pneumoniae data were analyzed by analysis of variance to assess the effect of inoculum, formulation, and MIC on antibacterial effect. Standard and enhanced formulations had different effects depending on MIC, with the standard formulation less effective at higher amoxicillin-clavulanate MICs. This is explained by the greater T>MICs of the enhanced formulation. Although resistant to amoxicillin-clavulanate by conventional breakpoints, S. pneumoniae and H. influenzae strains for which MICs are 2 or 4 mg/liter may well respond to therapy with pharmacokinetically enhanced formulation amoxicillin-clavulanate. SN - 0066-4804 UR - https://www.unboundmedicine.com/medline/citation/15215115/Antibacterial_effects_of_amoxicillin_clavulanate_against_Streptococcus_pneumoniae_and_Haemophilus_influenzae_strains_for_which_MICs_are_high_in_an_in_vitro_pharmacokinetic_model_ L2 - https://journals.asm.org/doi/10.1128/AAC.48.7.2599-2603.2004?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -