Drug Interaction Report

MONITOR: Limited, primarily in vitro, data suggest that chloramphenicol may antagonize the bactericidal activity of cephalosporins against certain clinical isolates of gram-negative rods, group B streptococci, and Staphylococcus aureus. This antagonism appears to occur against strains for which chloramphenicol is bacteriostatic, and has been demonstrated with cefoperazone, cefotaxime, and ceftriaxone. The proposed mechanism is inhibition of protein synthesis by chloramphenicol, resulting in less protein substrate for cephalosporins to act on as inhibitors of bacterial cell wall synthesis. The clinical relevance of these findings is unknown. Potential antagonism was suspected in two case reports of treatment failure in patients with gram-negative bacterial meningitis who received a cephalosporin in combination with chloramphenicol. One patient, a 2.5-month-old infant with Salmonella enteritidis group D meningitis, was subsequently treated with the cephalosporin (ceftazidime) alone and recovered uneventfully. The other, a 51-year-old male with Klebsiella pneumoniae meningitis, was subsequently treated with the cephalosporin (cefotaxime) plus amikacin and became afebrile, but later died with progressive neurologic disease. Autopsy findings were consistent with subacute spongiform encephalopathy (Creutzfeldt-Jakob disease).

MANAGEMENT: The manufacturers recommend to avoid concomitant use . However, if concurrent administration cannot be avoided, the possibility of antagonism should be considered, and patients should be monitored for altered therapeutic effect.