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

Abstract

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 miniimum 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 ,ug/ml) in the presence of 5-fluorouracil, bioassay results were in error by as much as 100%. The data indicate that bioassay procedures for the determination of antibacterial drug levels may need to be modified for those patients receiving antitumor therapy with 5-fluorouracil, doxorubicin, or dactinomycin.

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).…”

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

“…These concentrations, however, are above therapeutic serum levels. Wright and Matsen [19] found that methotrexate had no antibacterial activity against one strain each of K. pneumoniae, S. aureus, and S. epidermidis, whereas 5-fluorouracil inhibit ed the 3 bacterial species with MICs com parable to those in this study. Moody et al [13] reported that in the presence of daunorubicin and cytosine arabinoside the activ ity of gentamicin and amikacin was re duced against K. pneumoniae and P. aeru ginosa.…”

5-Fluorouracil sensitivity varies among oral micro-organisms

“…Changes in the composition of the oral micro-organisms have been reported for chemotherapy treatment in human studies (Lucas et al, 1997;Napeñas et al, 2010) and for 5-FU specifically in a rat study (Von Bültzingslöwen et al, 2003), with a shift towards more Gram-negative rods and bacterial translocation to cervical and mesenteric lymph nodes following treatment with 5-FU. A number of studies have been looking at the antibacterial effect of 5-FU on monocultures of mainly pathogenic strains such as Pseudomonas, Klebsiella and Staphylococcus (Wright & Matsen, 1980;Ueda et al, 1983;Bodet et al, 1985;Takahata et al, 1986). Although 5-FU was shown to have substantial antibacterial effects, the tested concentrations in these studies were much higher than what is usually present in vivo.…”