Evaluation of low-dose, extended-interval clindamycin regimens against Staphylococcus aureus and Streptococcus pneumoniae using a dynamic in vitro model of infection

We have previously described the activity of low-dose clindamycin in extend ed-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 thr ee clinical isolates of Staphylococcus aureus and two clinical isolates of Streptococcus pneumoniae, Test organisms were added to the central compartm ent of the model to yield a starting inoculum of 10(6) CFU/ml. Clindamycin was injected as a bolus into the central compartment at appropriate times o ver 48 h to simulate the q8h or q12h dosing regimens. Drug-free culture med ium was then pumped through the system to mimic a half-life of 2.4 h, At pr edetermined time points during the experiment, samples were removed from th e central compartments for colony count determination and drug concentratio n analysis. The rates of killing did not significantly differ among the thr ee clindamycin dosing regimens against either S. aureus or S. pneumoniae (P = 0.88 or 0.998, respectively). Likewise, no significant differences in ac tivities 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. aureus i solate exhibiting inducible macrolide-lincosamide-streptogramin B resistanc e, none of the three clindamycin regimens prevented regrowth of the resista nce phenotype in the model. In this model, clindamycin administered at a lo w dose in an extended-interval regimen (300 mg q12h) exhibited antibacteria l activity equivalent to that of the 300- or 600-mg-q8h regimen.