Removal of bacterial growth inhibition of anticancer drugs by using complexation materials

Abstract

In the context of batch production of cytotoxic drugs in hospital pharmacies with the need of sterility testing, the objective was to validate the use of Rapid Microbiological Method (RMM), and to develop adequate neutralization method in case of inhibition of bacterial growth. The potential microbiological growth inhibitory effect of three anticancer drugs (5 fluorouracil, irinotecan and oxaliplatin) selected for batch production was assessed on BacT/ALERT® system. Among cytotoxic drugs, only 5FU exhibited inhibitory effect on microbiological growth using rapid microbiological method. To counteract this effect our purpose was to use neutralizing agents complexing the drug i. e. activated carbon or ion exchange resins. The microbiological bactericidal concentration of 5FU was very low (1.10–4 mg/mL) indicating the absolute need to neutralize the whole drug before sterility test. The complexation was validated by High Performance Liquid Chromatography control of the residual 5FU concentration in solution after the use of neutralizing agents. Only activated carbon was able to fully capture 5FU when previously diluted at 5 mg/mL. Conversely, the resins, in the condition of the study, were not able to fully capture 5FU whatever the dilution. The microbiological growth on BacT/ALERT® system after active carbon treatment was successfully confirmed with Staphylococcus aureus. Based on this validation results a method was then developed to routinely be able to perform sterility test of the batches produced and was confirmed on five microbiological species (i. e. S. aureus, Pseudomonas aeruginosa, Bacillus subtilis, Candida albicans, Aspergillus brasiliensis). Our work gives a new insight for considering sterility testing by rapid microbiological method even for drugs exhibiting inhibitory effect on microbiological growth.

Enhanced Efficiency of the Removal of Cytostatic Anthracycline Drugs Using Immobilized Mycelium of Bjerkandera adusta CCBAS 930

“…Research by Kim et al (2000) showed that the anthracycline antibiotic Da2B at concentrations in the range of 7.5-10 µg/mL inhibited the growth of yeast Saccharomyces cerevisiae and Bacillus subtilis bacteria [56]. Other anticancer drugs (5-fluorouracil, irinotecan and oxaliplatin) are characterized by their antimicrobial activity against B. subtilis [57]. The research carried out in this study shows that during the biodegradation of anthracycline antibiotics by immobilized mycelium of B. adusta CCBAS 930, no toxic compounds for plants or microorganisms are formed.…”

Viability of selected microorganisms in parenteral preparations for novel systemic anti-cancer therapy

“…Several studies regarding the potential of microbial growth in cytotoxic and non-cytotoxic RTA parenteral preparations have been published. 4,[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Viability tests are missing for numerous recently licensed monoclonal antibodies (mAb), filgrastim, and few small molecules introduced in anti-cancer therapy in recent years. The aim of this viability study was to investigate the potential growth promoting nature of 20 RTA parenteral preparations used for SACT.…”