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Antibiotic synergism and response in gram-negative bacteremia in granulocytopenic cancer patients.

To determine whether antimicrobial synergism affects the outcome of gram-negative bacteremia among profoundly (less than 100/microliter) neutropenic cancer patients, the clinical courses of 75 such patients who received empiric therapy with combination, broad-spectrum antibiotics were analyzed. Twenty-nine of 34 (85 percent) patients whose granulocyte count increased to more than 100/microliter during therapy improved, whereas only 12 of 41 (29 percent) patients with no increase in granulocyte count showed improvement (p = 0.0002). The critical group for further analysis was, therefore, those patients with persistent, profound granulocytopenia. Among these 41 patients, synergism was associated with a substantially better response rate: eight of 18 (44 percent) improved compared with none of 13 in whom synergism was not detected (p = 0.005); presence or absence of synergism could not be assessed for the pathogens isolated from the remaining 10 patients because the organisms were exquisitely susceptible to one of the two antibiotics used. Further evaluation of these persistently neutropenic patients indicated that synergism appeared critical even when the pathogen was susceptible to both antibiotics. Thus, seven of 11 (64 percent) showed response when the two drugs were synergistic in activity, compared with none of six when synergism was not present (p = 0.01). These data again demonstrate the importance of granulocyte recovery to patient response and further indicate that synergistic combinations of antibiotics are indicated for cancer patients with gram-negative bacteremia and persistent, profound granulocytopenia.