Viability of Microorganisms in Fluorouracil and Small-volume Injections

Holmes, Clifford J.; Kubey, W.; Love, Debra I.

doi:10.1093/ajhp/45.5.1089

Cited by 6 publications

(12 citation statements)

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“…For routine evaluation, a 1/10 dilution of initial cytotoxic solution should be systematically applied to limit risk of false negative. Nevertheless, as previously published for 5 Fluorouracil [33,38], and evidenced in our study for gemcitabine, microbiological growth of some strains could be difficult. Thus it is justifying to complete microbiological investigation with endotoxin control [44] able to evidence Gram-negative bacteria [45,46].…”

Section: Discussionsupporting

confidence: 65%

“…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.…”

Section: Discussionmentioning

confidence: 94%

“…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].…”

Section: Discussionmentioning

confidence: 99%

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

Matheron

Guerault

Vazquez

et al. 2020

Pharmaceutical Technology in Hospital Pharmacy

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ObjectivesThe objectives were to assess the microbiological stability and the physical enclosure integrity of the overwrapping for batch production of standard cytotoxic injectable solutions.MethodsBroth culture media were used in place of cytotoxic drugs to assess the worst case in term of microbiological contamination risk. Iterative sterility tests on batches were performed for 60 days using rapid microbiological method. Validation of microbiological growth of culture media was assessed by direct inoculation of <100 CFU/mL of six microbiological strains recommended by European Pharmacopeia. Validation of the ability of growth of microorganisms in 11 cytotoxic solutions and one monoclonal antibody was assessed using eight strains. In addition, the physical integrity of the seal of the overwrapping containing cytotoxic preparations was assessed by dynamometric method and dye penetration test.ResultsNo microbiological contamination was observed on all units of batches for 60 days of investigation. The ability to detect microbiological growth in cytotoxic solutions was validated for the eight challenge microorganisms after 1/10 dilution for cytotoxic investigated, except for 5 Fluorouracil, gemcitabine and cisplatin. In addition, physical integrity testing of the seal of overwrapping pointed out the need of specific validation of heatsealer and operator education.ConclusionsBesides physico-chemical testing, microbiological stability testing combined to physical integrity testing is the additional part of the development method for batch production of sterile drugs in hospital.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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

Matheron

Guerault

Vazquez

et al. 2020

Pharmaceutical Technology in Hospital Pharmacy

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“…3,4,13,14 The antibacterial activity of oxaliplatin, especially against Pseudomonas, and its lack of antifungal activity are comparable with the antibacterial activities of the platinum analogs cisplatin and carboplatin that have been tested previously. 3,4,15 In all cases, samples were withdrawn up to 120 hours after inoculation regardless of the physicochemical stability of the drug solutions. The pH values of the solutions were not measured, and the influence of pH was not evaluated.…”

Section: Discussionmentioning

confidence: 99%

Viability of microorganisms in novel antineoplastic and antiviral drug solutions

Krämer¹

1998

J Oncol Pharm Pract

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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.

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“…1 -6 In most of them, the authors used concentrations that were widely different from those used clinically. Thus, Holmes et al 5 and Patel et al 6 used undiluted solutions of 5 -fluorouracil, cisplatin, or topotecan, whereas Hamilton -Miller, 1 Kramer and Wenchel, 2,3 and Kramer 4 used concentrations lower than those used clinically.…”

Section: Introductionmentioning

confidence: 99%

Viability of microorganisms in bags of cytotoxic drugs

Favier

Latour

Fuhrmann

2001

J Oncol Pharm Pract

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Objectives. The aim of this report was to study the viability of five microorganisms (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, S epidermidis and Candida albicans) in chemotherapeutic solutions made up 1-2 days before administration. Methods. The four preparations studied were 0.5 mg/mL cisplatin, 1.8 mg/mL doxorubicin, 5 mg/mL 5-fluorouracil, and 5 mg/mL cyclophosphamide. All four solutions were tested at a temperature of 258C, and doxorubicin and cyclophosphamide were also tested at 48C. The concentrations of the microorganisms in the preparations were determined 2, 24, 48, 72, and 96 hours after inoculation. Results. No microbial growth was found; on the contrary, bacterial and fungal growth decreased rapidly and substantially with cisplatin and doxorubicin (by 2log after 24 hours), moderately with 5-fluorouracil, and weakly or not at all with cyclophosphamide. Refrigeration at 48C appeared to slow the decreased growth of the microorganisms when compared with storage at 258C. Conclusion. As no bacterial or fungal growth was seen in the four solutions of cytotoxic agents tested, the practice of preparing such solutions under a hood with vertical laminar ventilation according to good practice in the preparation of sterile solutions 1 or 2 days before administration to patients is validated. J Oncol Pharm Practice (2001) 6, 167-171.

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Viability of Microorganisms in Fluorouracil and Small-volume Injections

Cited by 6 publications

References 0 publications

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

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

Viability of microorganisms in novel antineoplastic and antiviral drug solutions

Viability of microorganisms in bags of cytotoxic drugs

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