制药环境常见微生物数据库的建立及控制消杀研究

Research on the Disinfecting Effect of Common Bacteria in Pharmaceutical Production Environment

关键词:  制药环境  环境微生物  芽孢杆菌  生物膜  消杀效果

Key words:  pharmaceutical environment  environmental microorganisms  Bacillus  bioflim  disinfecting effect

摘要:

目的 调研文献与药企制药环境污染微生物,收集并建立制药环境常见微生物数据库,对制药生产环境中常见微生物开展常用消毒剂的消杀效果研究,为制药行业环境微生物的消杀提供参考。方法 收集制药生产环境中常见微生物菌株74株,分别为革兰氏阳性菌36株(包含23株芽孢杆菌)、革兰氏阴性菌19株和真菌19株。利用悬液法开展复合醇消毒剂、过氧化氢和戊二醛杀孢子剂对上述微生物的消杀效果。同时选择铜绿假单胞菌和抗性较强的4株芽孢杆菌在制药环境常见6种载体上进行生物膜成膜前后的消杀研究。结果 悬液法试验中3种消毒剂对74株微生物的消杀效果均达到下降5个log值的标准,过氧化氢杀孢子剂对蜡样芽孢杆菌、平流层芽孢杆菌、苏云金杆菌等8株芽孢杆菌的消杀效果均优于戊二醛消毒剂。载体法消杀试验中无论4株芽孢杆菌是否形成生物膜,复合醇和过氧化氢消毒剂消杀效果均无法达到下降3个log值的标准；而铜绿假单胞菌无论是否形成生物膜,上述消毒剂的消杀效果均良好。结论 本试验中3种消毒剂对制药环境中常见微生物均可达到即时消杀要求,其中过氧化氢杀孢子对芽孢杆菌的消杀效果最优；载体法消杀试验中,复合醇和过氧化氢对芽孢杆菌消杀效果较差,而如铜绿假单胞菌类革兰氏阴性菌形成生物膜后,消杀也易于芽孢杆菌；其中复合醇消毒剂与在载体上形成生物膜的芽孢杆菌作用后,微生物数量并未减少,反而有增殖趋势。建议制药企业在实际环境中消杀应关注环境微生物的特性,并针对是否形成生物膜采用合适的清洁和消毒策略。

Abstract:

ABSTRACT: OBJECTIVE To collect and establish a database of common microorganisms in pharmaceutical production environments by researching on literature and pharmaceutical environmental pollution microorganisms. Researching the eliminate virus effect of common disinfectants in the pharmaceutical production environment, to provide a reference for the disinfection of environmental microorganisms in the pharmaceutical industry. METHODS 74 strains of common bacteria in a pharmaceutical production environment are collected, including 36 strains of gram-positive bacteria (including 23 strains of Bacillus), 19 strains of gram-negative bacteria, and 19 strains of fungi. The suspension method is used to study the eliminate virus effect and resistance of compound alcohol disinfectant, hydrogen peroxide, and glutaraldehyde sporicides to the above-mentioned common microorganisms. At the same time, Pseudomonas aeruginosa and 4 strains of Bacillus with strong resistance are selected to conduct research on the disinfecting of microorganisms before and after film formation on 6 common carriers in pharmaceutical environments. RESULTS The disinfection effects of three disinfectants on 74 strains of microorganisms all reached the standard of decreasing 5 log values, and no strains resistant to disinfectants were found. The eliminated virus effect of hydrogen peroxide sporicide on 8 strains of Bacillus cereus, Bacillus stratosphere, and Bacillus thuringiensis was better than that of glutaraldehyde disinfectant. In the carrier-based disinfecting experiment, the complex alcohol and hydrogen peroxide disinfectants fail to achieve a 3 log reduction in efficacy, regardless of whether 4 strains of Bacillus formed biofilms or not. Conversely, for Pseudomonas aeruginosa, the above-mentioned disinfectants exhibit good effects regardless of biofilm formation. CONCLUSION In this test, the three disinfectants meet the requirements for immediate disinfecting of common microorganisms in the pharmaceutical environment, and hydrogen peroxide has the best sporicidal effect on Bacillus. In the carrier method disinfecting test, complex alcohol and hydrogen peroxide have the best killing effect on Bacillus. The disinfecting effect of Bacillus and Pseudomonas aeruginosa with biofilm is poor. In the carrier-based disinfecting experiment, the complex alcohol and hydrogen peroxide disinfectants exhibit limited efficacy against Bacillus. On the other hand, it is observed that the disinfecting effect is easier than Bacillus when Pseudomonas aeruginosa，a Gram-negative bacterium, formed biofilms. After the compound alcohol disinfectant interacts with Bacillus that forms biofilm on the carrier, the number of microorganisms does not decrease, but has a tendency to proliferate. It is recommended that pharmaceutical companies should pay attention to the characteristics of environmental microorganisms when disinfecting them in actual environments, and adopt appropriate cleaning and disinfection strategies to determine whether biofilms are formed.