Effect of blood product medium supplements on the activity of cefotaxime and other cephalosporins against Enterococcus faecalis.
The activities of cefotaxime and other aminothiazoyl oxime cephalosporins against Enterococcus faecalis were enhanced by addition of 5% sheep blood to Mueller-Hinton agar. This effect was not seen with aztreonam (aminothiazoyl oxime monobactam), cefotiam (aminothiazoyl, nonoxime), or other cephalosporins, and it was specific to the syn-configuration of the oxime moiety. Enhancement of cefotaxime activity was demonstrable against approximately 50% of 86 clinical isolates and could only be shown at low bacterial inocula. Human serum, serum alpha 1-, beta- and gamma-globulin fractions and albumin often antagonized or did not affect significantly the antimicrobial activity of cefotaxime, while the alpha 2-globulin fraction usually enhanced drug activity. The in vivo activity of cefotaxime against E. faecalis was examined in a rat peritoneal abscess model. The test organism was resistant to cefotaxime by standard methods (MIC greater than 128 micrograms/ml) but was inhibited by 1.0 microgram/ml when rat serum was presented in the medium. Cefotaxime reduced titers of bacteria within abscesses after 5 days of therapy (5.77 +/- 0.68 log10 CFU/g) in comparison with those in control animals (7.38 +/- 0.28 log10 CFU/g, p less than 0.05). Moxalactam, the in vitro activity of which was not augmented by serum, proved ineffective in the animal model. While these observations do not have direct therapeutic relevance, they offer a possible explanation for the relatively infrequent occurrence of enterococcal superinfection in patients treated with cefotaxime.
Eliopoulos
G M
GM
Department of Medicine, New England Medical School, Boston, Massachusetts.
Reiszner
E
E
Willey
S
S
Novick
W J
WJ
Moellering
R C
RC
D000038:Abscess / Q000188:drug therapy / Q000382:microbiology; D000818:Animals; D001769:Blood; D002439:Cefotaxime / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D002462:Cell Membrane / Q000378:metabolism; D002511:Cephalosporins / Q000494:pharmacology* / Q000627:therapeutic use; D003470:Culture Media; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010532:Peritoneal Diseases / Q000188:drug therapy / Q000382:microbiology; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000494:pharmacology; D012712:Serum Globulins / Q000494:pharmacology; D012756:Sheep / Q000097:blood; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000382:microbiology
D002511:Cephalosporins; D003470:Culture Media; D012709:Serum Albumin; D012712:Serum Globulins; D002439:Cefotaxime