Levchuk J W, Nolly R J, Lander N
Department of Pharmaceutics, University of Tennessee, Memphis 38163.
Am J Hosp Pharm. 1988 Jun;45(6):1311-21.
A test for determining the sterility of a total nutrient admixture (TNA) containing equal quantities of 10% fat emulsion (Liposyn II), 8.5% amino acids injection, and 50% dextrose injection using the USP membrane filtration procedure was developed and evaluated. Membrane filter selection was determined by analysis of flow rates, membrane fluid compatibility, bubble point stability, and rinse fluid requirements. Microbial challenges employing five organisms (Bacillus subtilis, Escherichia coli, Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa) and both soybean casein digest and fluid thioglycollate media were used to confirm the ability of the test to detect low-level microbial contamination. A polyvinylidene fluoride membrane was determined to be the most appropriate of the membrane types studied because of its superior flow rate and membrane-fluid compatibility. Bubble point testing revealed no detrimental effects on the membrane. The potential problem of haziness caused by retention of the TNA by the membrane with subsequent release in the culture media (which could result in false-positive growth determinations) was diminished by using a sterile 0.1% peptone solution rinse and careful observation techniques. Performance of the sterility test by six hospital pharmacists required an average of 14.2 minutes. Sterility testing of alternate TNAs compounded with Intralipid and Nutralipid was not feasible because of prolonged filtration times. The basic USP membrane filtration procedure for large-volume injections can be used by hospital pharmacists for testing the sterility of TNAs. When fat emulsions are used in compounding, sterility-testing procedures specific to the emulsion product used should be developed and evaluated.
开发并评估了一种使用美国药典膜过滤程序来测定含等量10%脂肪乳剂（Liposyn II）、8.5%氨基酸注射液和50%葡萄糖注射液的全营养混合液（TNA）无菌性的试验。通过分析流速、膜与液体的兼容性、泡点稳定性和冲洗液要求来确定膜过滤器的选择。采用五种微生物（枯草芽孢杆菌、大肠杆菌、白色念珠菌、金黄色葡萄球菌和铜绿假单胞菌）以及大豆酪蛋白消化液和硫乙醇酸盐流体培养基进行微生物挑战试验，以确认该试验检测低水平微生物污染的能力。由于聚偏二氟乙烯膜具有优异的流速和膜与液体的兼容性，因此被确定为所研究的膜类型中最合适的一种。泡点测试表明对该膜没有有害影响。通过使用无菌0.1%蛋白胨溶液冲洗和仔细的观察技术，减少了因TNA被膜截留并随后在培养基中释放而导致模糊不清（这可能导致生长测定出现假阳性）的潜在问题。六名医院药剂师进行无菌试验平均需要14.2分钟。由于过滤时间延长，对与英脱利匹特和纽迪希亚混合配制的替代TNA进行无菌测试不可行。医院药剂师可使用美国药典大容量注射剂的基本膜过滤程序来检测TNA的无菌性。当在配制中使用脂肪乳剂时，应开发并评估特定于所用乳剂产品的无菌测试程序。
