Serum bactericidal activity as a therapeutic guide in severely granulocytopenic patients with gram-negative...

The peak and trough levels of bactericidal activity of the serum of 74 severely granulocytopenic patients (less than or equal to 500 polymorphonucleates per microliter) with hematologic malignancies and Gram-negative septicemia were measured using the patient's infectious organism and serum containing the given antibiotics. When the peak titer of bactericidal activity in the serum was greater than 1:8 the septicemia was cured in more than 90% of the cases. However, in order to achieve a satisfactory rate of cure, patients with less than 100 polymorphonucleates/microliter required higher peak levels than patients with 100-500 polymorphonucleates/microliter. Serum bactericidal activity was influenced by the in vitro susceptibility of the offending pathogen and by the presence of in vitro synergism between the given antibiotics. These two variables showed a correlation with the clinical outcome that proved to be increasing with the degree of granulocytopenia. Furthermore, synergistic combination of the antibiotics appeared essential when the in vitro susceptibility shown by the offending pathogen was moderate. These data suggest (i) that determination of the bactericidal activity of the serum may prove to be a useful method to predict the clinical outcome in severely granulocytopenic patients with Gram-negative septicemia; and (ii) under the same conditions, antibiotic combinations that have demonstrable in vitro synergy against the offending pathogen should be given the utmost consideration.