Does exposure of antineoplastic agents induce antimicrobial resistance in bacteria?
Background: Children with cancer treated with antineoplastic agents are at great risk of suffering from infections during neutropenia. They often receive empiric antimicrobial therapy, and are at risk of aquiring bacteria with antibiotic resistance. There are studies that show an antibacterial effect of antineoplastic agents but we couldn t find the answer to the question: can repeated exposure to antineoplastic agents induce antibiotic resistance in pure cultures of bacteria?
Material and methods: We created a very simple trial using the agar-diffusion method to expose five different antineoplastic agents (methotrexate, vincristine, 5-fluorouracil, doxorubicin and cytarabine) at serum concentration levels each to Eschericia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853) on Mueller-Hinton-agar. The experiment involved 50 overnight growth cycles. All the antineoplastic agents except 5-FU are used in protocols for treatment of childhood cancer, and we used parallel exposure to NaCl as controls. The bacteria were susceptibility tested to 10 different antibacterial agents by Etest® before and after exposure to antineoplastic agents.
Results: MIC-values from Etest® before and after exposure of antineoplastic agents for probably more than 10,000 doubling cycles did not differ significantly.
Conclusion: Repeated exposure to antineoplastic agents did not lead to reduced susceptibility or resistance against antibacterial agents in E. coli or P. aeruginosa under our experimental conditions. The conditions (time, complicated ecological situation with many species in close proximity etc.) in natural ecological niches in the normal flora of patients are however very different from our experimental method.