Antibiotic combinations for the empiric treatment of the febrile neutropenic patient.

Empiric antimicrobial therapy in the granulocytopenic patient has traditionally consisted of a combination of an aminoglycoside plus a cephalosporin or aminoglycoside plus an antipseudomonal penicillin. These combinations have been proven reasonably effective and only moderately toxic. In some centers trimethoprim-sulfamethoxazole combined with an aminoglycoside or antipseudomonal penicillin has been used, again with good efficacy and minimal toxicity. The newer extended spectrum penicillins and cephalosporins has made possible two-drug combinations with aminoglycosides that provide double coverage of nearly all of the common bacterial pathogens while concurrently providing synergy against most of these same organisms. Further, it is now possible to have a double beta-lactam combination of a penicillin and cephalosporin which has the advantages of broad spectrum by both antimicrobials and, at times, synergistic activity but without the ototoxicity and nephrotoxicity of aminoglycosides. The double beta-lactam combination would be especially useful in the neutropenic patient with established renal insufficiency or a history of previous courses of aminoglycoside therapy. Care should be taken in choosing such a regimen, however, because some combinations demonstrate antagonism. There is increasing data to indicate that patients with profound (less than 100 microliters), persistent (greater than 14 days) granulocytopenia and concurrent gram-negative bacteremia respond best if treated with two active, bactericidal antibiotics, preferably synergistic in action. The potential for synergistic activity of the drugs selected should be, therefore, carefully considered. The duration of therapy should be adjusted according to the severity of infection, the response of the infection to antimicrobial therapy, and rate of recovery of the patient's granulocyte count.