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

Patients receiving antitumor chemotherapy are at increased risk of developing nosocomial infections, and the antibacterial therapy of such infections is often monitored by bioassay. The effect of antitumor agents on seven bioassay procedures using strains of Sarcina, Klebsiella, Clostridium, Pseudomonas, Staphylococcus aureus, and S. epidermidis or Bacillus was evaluated. The minimum inhibitory concentrations of six antitumor drugs, cytarabine, dactinomycin, doxorubicin, 5-fluorouracil, methotrexate, and vinblastine, determined for each of the test organisms, showed that 5-fluorouracil, dactinomycin, and doxorubicin are used at blood levels sufficient to interfere with bioassay procedures. The other drugs have minimum inhibitory concentrations as much as 100 times the expected blood levels. Antibiotic (gentamicin, kanamycin, cephalothin, and carbenicillin) recovery experiments in the presence of therapeutic levels of antitumor agents showed no in vitro inactivation of antibiotic. However, at low cephalothin concentrations (less than 20 microgram/ml) in the presnce of 5-fluorouracil, bioassay results were in error by as much as 100%. The data indicate that bioassay procedures for the determining of antibacterial drug levels may need to be modified for those patients receiving antitumor therapy with 5-fluorouracil, doxorubicin, or dactinomycin.