Effect of Chemotherapeutic Agents upon Microorganisms Isolated from Cancer Patients

Goldschmidt, Millicent C.; Bodey, Gerald P.

doi:10.1128/aac.1.4.348

Cited by 19 publications

(8 citation statements)

References 10 publications

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“…Another study with rats reported similar shifts, with Gram-negative rods becoming more abundant upon treatment with 5-FU (Von Bültzingslöwen et al, 2003). Also, other chemotherapeutics have been shown to generate differential microbial response to 5-FU leading to infections, as demonstrated for pathogenic P. aeruginosa in leukaemic patients (Goldschmidt & Bodey, 1972). Therefore, microbial 5-FU resistance should be considered as an important risk factor for infections especially in the context of oral mucositis.…”

Section: Discussionmentioning

confidence: 88%

5-Fluorouracil sensitivity varies among oral micro-organisms

Vanlancker

Vanhoecke

Smet

et al. 2016

Journal of Medical Microbiology

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5-Fluorouracil (5-FU), a commonly used chemotherapeutic agent, often causes oral mucositis, an inflammation and ulceration of the oral mucosa. Micro-organisms in the oral cavity are thought to play an important role in the aggravation and severity of mucositis, but the mechanisms behind this remain unclear. Although 5-FU has been shown to elicit antibacterial effects at high concentrations (>100 µM), its antibacterial effect at physiologically relevant concentrations in the oral cavity is unknown. This study reports the effect of different concentrations of 5-FU (range 0.1-50 µM) on the growth and viability of bacterial monocultures that are present in the oral cavity and the possible role in the activity of dihydropyrimidine dehydrogenase (DPD), an enzyme involved in 5-FU resistance. Our data showed a differential sensitivity among the tested oral species towards physiological concentrations of 5-FU. Klebsiella oxytoca, Streptococcus salivarius, Streptococcus mitis, Streptococcus oralis, Pseudomonas aeruginosa and Lactobacillus salivarius appeared to be highly resistant to all tested concentrations. In contrast, Lactobacillus oris, Lactobacillus plantarum, Streptococcus pyogenes, Fusobacterium nucleatum and Neisseria mucosa showed a significant reduction in growth and viability starting from very low concentrations (0.2-3.1 µM). We can also provide evidence that DPD is not involved in the 5-FU resistance of the selected species. The observed variability in response to physiological 5-FU concentrations may explain why certain microbiota lead to a community dysbiosis and/or an overgrowth of certain resistant micro-organisms in the oral cavity following cancer treatment.

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Section: Discussionmentioning

confidence: 88%

5-Fluorouracil sensitivity varies among oral micro-organisms

Vanlancker

Vanhoecke

Smet

et al. 2016

Journal of Medical Microbiology

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“…Antineoplastic therapy often reduces host antimicrobial defenses to a point of considerable vulnerability to serious infections. Although recent reports have shown that some antibacterial benefits may be derived from the use of certain tumor chemotherapeutic agents (1,3), no one, to our knowledge, has investigated the effect that these agents may have on bioassays of concomitantly administered antibiotics.…”

Section: Discussionmentioning

confidence: 99%

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

Wright¹,

Matsen²

1980

Antimicrob Agents Chemother

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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.

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“…Selective suppression of normal bacterial flora by antitumor drugs, thus altering colonization resistance (12), has been proposed as an explanation for Clostridium difficileassociated colitis in cancer patients (2,3). Selective resistance of pathogens such as Pseudomonas aeruginosa to antineoplastic agents has been cited as an explanation for the prevalence of infection caused by this species in leukemic patients (4). Similar resistance of certain normal human microflora, such as Staphylococcus epidermidis and coryneform bacteria, could help to explain their occurrence as opportunistic pathogens in compromised hosts (13)(14)(15).…”

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confidence: 99%