Thrombin-induced platelet microbicidal protein susceptibility phenotype influences the outcome of oxacillin prophylaxis and therapy of experimental Staphylococcus aureus endocarditis.

We previously showed that in vitro susceptibility profiles of Staphylococcus aureus to thrombin-induced platelet microbicidal protein 1 (tPMP-1) impacted the outcome of vancomycin treatment in experimental infective endocarditis. In this same model, treatment with oxacillin (a more rapid staphylocidal agent than vancomycin) enhanced the clearance of both tPMP-1-susceptible and -resistant cells from vegetations. The extent of clearance was greater for tPMP-1-susceptible cells.

Influence of in vitro susceptibility phenotype against thrombin-induced platelet microbicidal protein on treatment and prophylaxis outcomes of experimental Staphylococcus aureus endocarditis.

Thrombin-induced platelet microbicidal protein-1 (tPMP-1) is a small, cationic staphylocidal peptide from rabbit platelets. In the current study, the outcomes of vancomycin treatment and prophylaxis were compared in experimental infective endocarditis (IE) caused by an isogenic Staphylococcus aureus strain pair differing in tPMP-1 susceptibility (tPMPS) or resistance (tPMPR) in vitro (ISP479C and ISP479R, respectively). Vancomycin therapy (selected for its intrinsically slow bactericidal activity) reduced ISP479C (but not ISP479R) densities in vegetations compared with controls (P<.01). In contrast, prophylactic administration of vancomycin yielded no differences in efficacies for the 2 challenge strains. These data suggest that the tPMPR phenotype in vitro has a negative effect on the antimicrobial therapy (but not the prophylaxis) of experimental S. aureus IE. These disparate results may be explained in part by the requirement for microbicidal effects in the treatment of established IE, whereas prophylactic efficacy depends more on growth inhibitory and antiadhesion effects.

Cefmenoxime therapy for gynecologic and obstetric infections.

Cefmenoxime, a new third-generation cephalosporin, was used as a single drug in the therapy for female genital tract infections. Therapeutic response was considered satisfactory in 21 of 22 cases of pelvic inflammatory disease, six of nine tuboovarian abscesses, two of three severe wound infections, and all five cases of endometritis. Overall, 34 of 39 patients responded. The peak serum antibiotic levels in this study ranged from 15.8 to 64 (average 48.7) micrograms/mL, and the trough level ranged from 0.9 to 4 (average 3.1) micrograms/mL. Cefmenoxime was tested in vitro against 424 isolates of anaerobes including 208 strains of bacteroides of which 80 were Bacteroides fragilis. Cefmenoxime inhibited the growth of 90% or greater of the organisms (minimal inhibitory concentration 90) at less than or equal to 64 micrograms/mL. The minimal inhibitory concentration for 75% of B fragilis was 32 micrograms/mL. This study suggests that cefmenoxime as a single-drug therapy is effective in the treatment of female genital tract infections caused by aerobic (including the gonococcus) and anaerobic bacteria.

Newer beta-lactam antibiotics in the treatment of experimental Staphylococcus aureus endocarditis.

Antistaphylococcal activity of three beta-lactam antibiotics, i.e. cefmenoxime, cefotaxime and latamoxef (moxalactam) was compared with that of nafcillin by studying cure rates of aortic valvular endocarditis caused by one of three clinical isolates of Staphylococcus aureus in New Zealand white male rabbits. The animals were randomly allocated to a control and four antibiotic treatment groups. Each animal except the controls received 60 mg/kg of one antibiotic intramuscularly twice daily for two weeks, beginning 24 h after induction of endocarditis. The aortic valve was sterilized in 11 of 15 (73%) animals treated with cefmenoxime, nine of 13 (69%) treated with cefotaxime, 11 of 13 (85%) treated with latamoxef and 12 of 15 (80%) treated with nafcillin. All nine animals in the control group developed aortic valvular vegetations with an average of 2.4 X 10(9) cfu/g. The differences in sterility rates resulting from treatment with the four antibiotics were not statistically significant (P greater than 0.70).

Clindamycin: a review of fifteen years of experience.

Clindamycin, the 7(S)-chloro-7-deoxy derivative of lincomycin, has stood the test of time in the treatment of anaerobic infections. Clindamycin inhibits protein synthesis by acting on the 50S ribosomal subunits of bacteria. The colitis resulting from the use of clindamycin has been extensively studied and is now easily manageable. Although newer antibiotics active against anaerobes are available, clindamycin remains a reliable and well-tested antibiotic for use in anaerobic infections.