Colistin is increasingly used as last-line therapy againstwere examined by using an inhibitory sigmoid maximum-effect model. Nonlinearity in the PKs of colistin, including its plasma protein binding, was observed. The PK/PD index that correlated best with its efficacy was fAUC/MIC in both the thigh infection model (R 2 ‫؍‬ 87%) and the lung infection model (R 2 ‫؍‬ 89%). The fAUC/MIC targets required to achieve 1-log and 2-log kill against the three strains were 15.6 to 22.8 and 27.6 to 36.1, respectively, in the thigh infection model, while the corresponding values were 12.2 to 16.7 and 36.9 to 45.9 in the lung infection model. The findings of this in vivo study indicate the importance of achieving adequate time-averaged exposure to colistin. The results will facilitate efforts to define the more rational design of dosage regimens for humans.

This study indicates the importance of achieving adequate time-averaged exposure to colistin and defined target fAUC/MIC values for various magnitudes of kill. Amplification of resistant subpopulations indicates the importance of investigating rational combinations with colistin. The results will facilitate efforts to optimize colistin use in humans.

The present study compared the effectiveness of two antimicrobials, tetracycline and metronidazole, in reducing subgingival microorganisms in periodontal pockets using an ethyl cellulose strip as the delivery medium. The study involved 30 patients, with a minimum of 3 periodontal pockets with probing depths > 6 mm throughout the oral cavity. Patients were given supragingival scaling and then divided into 5 groups, depending on the length of time the medication was in place. Sites were marked for tetracycline, metronidazole, and placebo. Sites were wiped and isolated, and baseline microbiology samples were taken for Gram staining and culture methods. After treatment, subgingival microbiological samples were taken again. The ethyl cellulose strips were removed and analyzed for any remaining drug. Results showed that tetracycline and metronidazole can both be applied locally to periodontal sites using ethyl cellulose strips and markedly suppress the subgingival bacteria over a period of several days. The tetracycline showed a faster release; however, the metronidazole required a lesser concentration to achieve complete reduction of the subgingival flora.

The results of our long-term stability study have significant implications for those involved in conducting clinical PK and PK/PD studies with CMS/colistin.