药品生产环境污染凝固酶阴性葡萄球菌的耐药谱研究

目的：研究药品生产环境中污染凝固酶阴性葡萄球菌（coagulase-negative staphylococcus，CoNS）的耐药谱，为药品微生物监控提供数据支持。方法：收集药品生产环境中污染的葡萄球菌分离株，采用VITEK生化鉴定系统、16S rRNA特征序列比对、血浆凝固酶试验等方法进行菌种鉴定；采用革兰阳性需氧菌药敏检测板（含15种抗生素），测定85株CoNS的最低抑菌浓度（minimal inhibitory concentration，MIC）。结果：药品生产环境中收集的葡萄球菌主要为科氏葡萄球菌（33株）和表皮葡萄球菌（27株）；耐药分析结果显示，85株CoNS中只有4株对15种抗生素全部敏感，其余81株（95.3%）均对1种或多种抗生素具有抗性，其中对青霉素的耐药率最高（94.1%），其次为红霉素（80.0%）、头孢西丁（80.0%）、苯唑西林（63.5%），未检出耐万古霉素、利奈唑胺、达托霉素、呋喃妥因菌株。进一步分析发现，81株耐药菌可分为36个耐药谱型，其中OXC-ERY-PEN-CFX为最主要的耐药谱型（25株）。值得注意的是，有2株菌同时对9种抗生素具有抗性，分别为表皮葡萄球菌和溶血葡萄球菌。多重耐药菌（MDR）共有37株，占43.5%。结论：药品生产环境污染CoNS的耐药现状较严重，药品生产企业应加强生产过程微生物控制能力，防止强耐药CoNS污染药品，以降低用药风险。

Objective: To study the drug resistancespectrum of contaminated coagulase-negative staphylococci (CoNS) in drug production environment, and to provide data support for improving drug quality and microbiological supervision.Methods: Staphylococcus isolates contaminated in the drug production environment were collected and identified by VITEK biochemical identification system, 16S rRNA sequencing alignment method, and plasma coagulase test.The MIC of 85 CoNS isolates were determined by using the Gram-positive aerobic susceptibility test board (including 15 antibiotics).Results: The strain identification showed that the contaminated Staphylococci in the drug production environment were mainly Staphylococcus cohnii (33 strains) and Staphylococcus epidermidis (27 strains).According to the antibiotic sensitivity test results of 85 CoNS isolates, only 4 cases were sensitive to all the tested 15 kinds of antibiotics, the rest (95.3%) isolates were resistant to one or more antibiotics.Among them, penicillin resistance rate was the highest (94.1%), followed by erythromycin (80.0%), cefoxitin (80.0%), and oxacillin (63.5%).Vancomycin, linezolid, daptomycin and nitrofurantoin resistant strains were not detected.Furthermore, 81 resistant strains could be classified as 36 drug-resistant spectrum.Among them, OXC-ERY-PEN-CFX was the main drug resistant type (25 strains).It was worth noting that two strains were resistant to 9 antibiotics, distributed in Staphylococcus epidermidis and Staphylococcus hemolyticus respectively.There were 37 strains of multi-drug resistant bacteria (MDR), accounting for 43.5%.Conclusion: The present situation of drug resistance of CoNS isolated from drug production environment is serious.Therefore drug manufacturers should strengthen the control ability of microorganism in production process to prevent drug contamination with strong drug-resistant CoNS.

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