In vitro synergism of rifampin-cephalosporin combinations against Haemophilus influenzae type b.

The in vitro susceptibility of Haemophilus influenzae type b to rifampin, cefotaxime, ceftazidime, ceftriaxone and cefuroxime was examined at inocula of 10(5) and 10(7) CFU/ml. Time-kill curves were then obtained using antibiotic concentrations at one-half the MIC for each drug at the two inocula with combinations of rifampin plus each of the cephalosporins. There was a pronounced inoculum effect with all of the cephalosporins except for cefuroxime, but the MIC values were also higher for the latter drug. The rare failure of some cephalosporins to promptly sterilize the cerebrospinal fluid in meningitis should encourage investigation of the relationship between the inoculum effect, minimum bactericidal concentration and cerebrospinal fluid antibiotic levels in these clinical situations. A marked synergistic effect was noted for most of the isolates, and therefore, cephalosporin-rifampin combinations might show clinical utility.