Evaluation of Low-Dose, Extended-Interval Clindamycin Regimens against Staphylococcus aureus and Streptococcus pneumoniae Using a Dynamic In Vitro Model of Infection

Russell E Lewis; Michael E Klepser; Erika J Ernst; Brian C Lund; Douglas J Biedenbach; Ronald N Jones

doi:10.1128/AAC.43.8.2005

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Evaluation of Low-Dose, Extended-Interval Clindamycin Regimens against Staphylococcus aureus and Streptococcus pneumoniae Using a Dynamic In Vitro Model of Infection

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Evaluation of Low-Dose, Extended-Interval Clindamycin Regimens against Staphylococcus aureus and Streptococcus pneumoniae Using a Dynamic In Vitro Model of Infection

Russell E Lewis, Michael E Klepser, Erika J Ernst, Brian C Lund, Douglas J Biedenbach and Ronald N Jones

Antimicrobial agents and chemotherapy, Vol.43(8), pp.2005-2009

08/01/1999

DOI: 10.1128/AAC.43.8.2005

PMCID: PMC89405

PMID: 10428927

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Abstract

We have previously described the activity of low-dose clindamycin in extended-interval dosing regimens by determination of bactericidal titer in serum. In this study, we used a one-compartment in vitro dynamic infection model to compare the pharmacodynamics of clindamycin in three intravenous-dosing regimens (600 mg every 8 h [q8h], 300 mg q8h, and 300 mg q12h) against three clinical isolates ofStaphylococcus aureus and two clinical isolates ofStreptococcus pneumoniae. Test organisms were added to the central compartment of the model to yield a starting inoculum of 106 CFU/ml. Clindamycin was injected as a bolus into the central compartment at appropriate times over 48 h to simulate the q8h or q12h dosing regimens. Drug-free culture medium was then pumped through the system to mimic a half-life of 2.4 h. At predetermined time points during the experiment, samples were removed from the central compartments for colony count determination and drug concentration analysis. The rates of killing did not significantly differ among the three clindamycin dosing regimens against eitherS. aureus or S. pneumoniae (P= 0.88 or 0.998, respectively). Likewise, no significant differences in activities were detected among the three regimens against staphylococci (P = 0.677 and 0.667) or pneumococci (P = 0.88 and 0.99). Against an S. aureusisolate exhibiting inducible macrolide-lincosamide-streptogramin B resistance, none of the three clindamycin regimens prevented regrowth of the resistance phenotype in the model. In this model, clindamycin administered at a low dose in an extended-interval regimen (300 mg q12h) exhibited antibacterial activity equivalent to that of the 300- or 600-mg-q8h regimen.

Anti-Bacterial Agents

Clindamycin

Experimental Therapeutics

Pneumococcal Infections

Staphylococcal Infections

Staphylococcus aureus

Streptococcus pneumoniae

Details

Title: Subtitle: Evaluation of Low-Dose, Extended-Interval Clindamycin Regimens against Staphylococcus aureus and Streptococcus pneumoniae Using a Dynamic In Vitro Model of Infection
Creators: Russell E Lewis - American Association of Colleges of Pharmacy
Michael E Klepser - American Association of Colleges of Pharmacy
Erika J Ernst - American Association of Colleges of Pharmacy
Brian C Lund - American Association of Colleges of Pharmacy
Douglas J Biedenbach - Medicine,#N#2#N# Iowa City, Iowa
Ronald N Jones - Medicine,#N#2#N# Iowa City, Iowa
Resource Type: Journal article
Publication Details: Antimicrobial agents and chemotherapy, Vol.43(8), pp.2005-2009
DOI: 10.1128/AAC.43.8.2005
PMID: 10428927
PMCID: PMC89405
NLM abbreviation: Antimicrob Agents Chemother
ISSN: 0066-4804
eISSN: 1098-6596
Publisher: American Society for Microbiology
Language: English
Date published: 08/01/1999
Academic Unit: Epidemiology; Emergency Medicine; Pharmacy Practice and Science
Record Identifier: 9984365883702771

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