Viability of microorganisms in novel antineoplastic and antiviral drug solutions

Abstract

Introduction. In determining the expiration-dates of ready-to-use antineoplastic and antiviral drug solu tions, microbiological aspects must be considered. This is especially true because many antineoplastic drugs introduced into the market are already known to lack antimicrobial activity. The purpose of this study is to evaluate the growth of four different microorganisms in ready-to-use solutions of 14 differ ent novel antineoplastic and antiviral drugs. Methods. The lowest concentrations of 14 dif ferent antineoplastic and antiviral drugs prescribed in our hospital were prepared in polyvinyl chloride bags or a polyethylene container (paclitaxel) containing 0.9% sodium chloride or 5% dextrose solution. Inoc ulations were performed by adding 9 mL of a freshly prepared drug solution to a 1 mL suspension of bacteria or fungi (Staphylococcus aureus, Enterococ cus faecium, Pseudomonas aeruginosa, Candida albicans). Resulting concentrations were about 104 microorganisms per milliliter. Pure 0.9% sodium chlo ride and 5% dextrose solutions served as positive controls. Inoculated solutions were stored at elevated temperatures (22°C or 37°C). Samples of each test solution were withdrawn at 0, 15, 30, and 60 minutes and at 2, 3, 4, 24, 48, and 120 hours after inoculation, transferred to tryptic soy agar, and incubated at 37°C. After 24 hours, colony-forming units were counted. Results. In the concentrations tested, no antimi crobial activity was registered with most of the drugs tested. There were only two cases of significant antibacterial activity, involving treosulfan and oxali platin against P. aeruginosa, respectively. Moderate antifungal activity was seen with foscarnet, ganciclo vir, pentostatin, and treosulfan. Conclusions. The lack of antimicrobial proper ties should be considered when assigning extended expiration dates to ready-to-use antineoplastic and antiviral drug solutions. Solutions should be kept under refrigeration whenever possible to minimize the growth of any contaminating microorganism. With the exception of treosulfan, end-product steril ity testing may be performed without further dilution or inactivation.

Microbiological stability tests with simulated broth preparations and integrity testing for sterile standard cytotoxic preparations

“…According to our results, when using Bactec® culture media, most of the challenged microorganisms were able to grow with concentrated cytotoxic solution except for gemcitabine and 5 Fluorouracil. The inhibitory effect of 5 Fluorouracil and gemcitabine on growth was previously described in literature [32,33,35,38]. Among literature, it is possible to find opposite results on inhibitory effect of anticancer drugs.…”

“…For routine evaluation of sterility of our batch produced, we needed to check that the rapid microbiological method was able to detect the growth of microorganisms which may contaminate cytotoxic solutions. Some controversies arose from literature about microbicidal or microbiostatic activity of antitumor agents [24,[31][32][33][34], but some studies showed the possible growth inside cytotoxic solutions [14,[35][36][37] justifying our assessment. We choose challenge microorganism recommended by European pharmacopeia [15], but also we choose to investigate the growth of additional microorganisms coming from human contamination, as a potential source of contamination in clean rooms [19].…”

Stability of topotecan infusion solutions in polyvinylchloride bags and elastomeric portable infusion devices

“…Despite the pronounced physicochemical stability, the lack of bacteriostatic and antifungal properties of diluted topotecan solutions 15 should be considered when preparing the solutions and assigning extended expiration dates.…”

Stability of Reconstituted and Diluted Mitomycin C Solutions in Polypropylene Syringes and Glass Vials

“…Microbiological stability of the MMC solutions have not been tested, but it is known that MMC is an antibiotic with a significant antibacterial activity [14], and all of the preparation are made in aseptic conditions in accordance with a quality assurance program including environmental and team monitoring.…”