Effect of Two Cancer Chemotherapeutic Agents on the Antibacterial Activity of Three Antimicrobial Agents

Abstract

Cancer chemotherapeutic agents and antibacterial antibiotics are often given concomitantly. Daunorubicin, cytosine arabinoside, and three antibiotics (gentamicin, amikacin, and ticarcillin) were tested individually and in combinations to determine their antimicrobial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae , and Escherichia coli . These cytotoxic agents are commonly employed in the therapy of acute nonlymphocytic leukemia for remission induction therapy, and these antimicrobial agents are used in infection therapy. The maximum concentrations of the two cytotoxic drugs were chosen to be twice the known peak plasma levels of commonly employed dosage schedules. Neither of the cancer chemotherapeutic agents, alone or in combination, demonstrated bactericidal activity at the levels tested. However, in the presence of these agents, the antimicrobial activity of gentamicin and amikacin, although not that of ticarcillin, was depressed for 11 of 15 K. pneumoniae strains and 8 of 15 P. aeruginosa strains, but for none of the strains of E. coli . This level of decreased activity occasionally resulted in a minimal inhibitory concentration of the tested aminoglycoside well above the standard serum levels. Daunorubicin was more likely to antagonize gentamicin than was cytosine arabinoside.

Antimicrobial activity of 21 anti-neoplastic agents

“…The findings confirm and extend the fragmentary reports in the literature concerning mitomycin C, doxyrubicin, 5-fluorouracil, cytarabine and methotrexate (Grey & Hamilton-Miller 1977, Moody et al, 1978, Michel et al, 1979, Jacobs et al, 1979, Wright & Matsen 1980) against a limited range of bacteria, and 5-fluorouracil, hydroxyurea, doxyrubicin, vinblastine, cyclophosphamide and cytarabine against C. albicans (Land et al, 1980).…”

“…Following these results, studies on the antimicrobial action of anti-neoplastic agents might be more profitably confined to possible synergistic effects with antibiotics (Moody et al, 1978) …”

Effect of 5-Fluorouracil, Mitoxantrone, Methotrexate, and Vincristine on the Antibacterial Activity of Ceftriaxone, Ceftazidime, Cefotiam, Piperacillin, and Netilmicin

“…Only few authors studied the interac tions between various antibiotics and cy tostatic compounds [8,10,12,13,17].…”

Bioassay of antibiotics in body fluids from patients receiving cancer chemotherapeutic agents

“…Reports (3,5,8) The antibacterial action of the chemotherapeutic agents used in this study was determined independently for each of the test organisms. The MICs of these agents are shown in Table 1 and indicate almost complete resistance of the assay organisms to methotrexate, cytabarine, and vinblastine.…”