Kim Jeong Myeong, Ahn Youngbeom, LiPuma John J, Hussong David, Cerniglia Carl E
Division of Microbiology, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR, 72079-9502, USA.
J Ind Microbiol Biotechnol. 2015 Jun;42(6):905-13. doi: 10.1007/s10295-015-1605-x. Epub 2015 Mar 21.
The Burkholderia cepacia complex (BCC) includes opportunistic pathogenic bacteria that have occasionally been recovered from various pharmaceutical products, including antiseptics and disinfectants. Plausible reasons for the contamination include intrinsic sources, such as inadequate process controls, especially for water or equipment used during product manufacture, or extrinsic sources, such as improper handling and dilution or distribution in contaminated containers. Because the survival of BCC in antiseptics is a concern to the public health and pharmaceutical industry, we determined minimum inhibitory concentrations (MICs) of 36 BCC strains against the antiseptics, following exposure to chlorhexidine gluconate (CHX) and benzalkonium chloride (BZK) solutions (1-500 µg/ml for each chemical). Susceptibility to CHX and BZK varied across the BCC strains and was recorded as mean 90.3 and 111.1 µg/ml, respectively, at initial inoculation, which was significantly higher than the 46.4 and 61.1 µg/ml levels measured for BCC incubated in water for 40 days. After determining antiseptic MICs of individual BCC strains, BCC recovery was measured on Tryptic Soy Agar (TSA), Reasoner's Second Agar (R2A) and diluted preparations of these media under their sub-MICs. The survival of BCC was monitored for 14 days (336 h) in sub-MICs diluted to less than their antiseptic susceptible concentration value. Diluted TSA and R2A media exhibited greater efficiency of recovery for most BCC strains from the CHX and BZK solutions than full strength TSA or R2A. For BCC survival in antiseptic solutions, the cell number of BCC decreased rapidly within the first 20 min in both antiseptics, but after this, recovery remained constant in CHX and increased in BZK over the 14 day incubation period. The results indicate that BCC in water can remain viable with low susceptibility to antiseptics for 14 days, which suggests the necessity for improved detection methods and control measures to monitor BCC contamination in pharmaceutical products.
洋葱伯克霍尔德菌复合体(BCC)包含一些机会致病菌,这些细菌偶尔会从包括防腐剂和消毒剂在内的各种药品中分离出来。污染的可能原因包括内在来源,如工艺控制不足,特别是产品生产过程中使用的水或设备;或外在来源,如处理不当、在受污染容器中稀释或分发。由于BCC在防腐剂中的存活情况关乎公众健康和制药行业,我们测定了36株BCC菌株在接触葡萄糖酸氯己定(CHX)和苯扎氯铵(BZK)溶液(每种化学品浓度为1 - 500μg/ml)后的防腐剂最低抑菌浓度(MIC)。不同BCC菌株对CHX和BZK的敏感性各不相同,初始接种时平均MIC分别记录为90.3和111.1μg/ml,显著高于在水中培养40天的BCC所测得的46.4和61.1μg/ml水平。在确定各个BCC菌株的防腐剂MIC后,在胰蛋白胨大豆琼脂(TSA)、Reasoner's第二代琼脂(R2A)以及这些培养基低于其MIC的稀释制剂上测定BCC的回收率。在稀释至低于其防腐剂敏感浓度值的亚MIC中监测BCC的存活情况14天(336小时)。对于大多数BCC菌株而言,稀释的TSA和R2A培养基从CHX和BZK溶液中的回收率高于全强度的TSA或R2A。对于BCC在防腐剂溶液中的存活情况,在两种防腐剂中,BCC细胞数量在前20分钟内迅速减少,但在此之后,在CHX中回收率保持恒定,而在BZK中在14天的培养期内有所增加。结果表明,水中的BCC在14天内可保持存活且对防腐剂敏感性较低,这表明需要改进检测方法和控制措施以监测药品中的BCC污染。