Lübbert Christoph, Baars Christian, Dayakar Anil, Lippmann Norman, Rodloff Arne C, Kinzig Martina, Sörgel Fritz
Division of Infectious Diseases and Tropical Medicine, Department of Gastroenterology and Rheumatology, Leipzig University Hospital, Liebigstr. 20, 04103, Leipzig, Germany.
Interdisciplinary Center for Infectious Diseases, Leipzig University Hospital, 04103, Leipzig, Germany.
Infection. 2017 Aug;45(4):479-491. doi: 10.1007/s15010-017-1007-2. Epub 2017 Apr 26.
High antibiotic and antifungal concentrations in wastewater from anti-infective drug production may exert selection pressure for multidrug-resistant (MDR) pathogens. We investigated the environmental presence of active pharmaceutical ingredients and their association with MDR Gram-negative bacteria in Hyderabad, South India, a major production area for the global bulk drug market.
From Nov 19 to 28, 2016, water samples were collected from the direct environment of bulk drug manufacturing facilities, the vicinity of two sewage treatment plants, the Musi River, and habitats in Hyderabad and nearby villages. Samples were analyzed for 25 anti-infective pharmaceuticals with liquid chromatography-tandem mass spectrometry and for MDR Gram-negative bacteria using chromogenic culture media. In addition, specimens were screened with PCR for bla , bla , bla , bla , and bla resistance genes.
All environmental specimens from 28 different sampling sites were contaminated with antimicrobials. High concentrations of moxifloxacin, voriconazole, and fluconazole (up to 694.1, 2500, and 236,950 µg/L, respectively) as well as increased concentrations of eight other antibiotics were found in sewers in the Patancheru-Bollaram industrial area. Corresponding microbiological analyses revealed an extensive presence of extended-spectrum beta-lactamase and carbapenemase-producing Enterobacteriaceae and non-fermenters (carrying mainly bla , bla , and bla ) in more than 95% of the samples.
Insufficient wastewater management by bulk drug manufacturing facilities leads to unprecedented contamination of water resources with antimicrobial pharmaceuticals, which seems to be associated with the selection and dissemination of carbapenemase-producing pathogens. The development and global spread of antimicrobial resistance present a major challenge for pharmaceutical producers and regulatory agencies.
抗感染药物生产废水中高浓度的抗生素和抗真菌药物可能对多重耐药（MDR）病原体产生选择压力。我们调查了印度南部海得拉巴（全球大宗原料药市场的一个主要生产地区）活性药物成分在环境中的存在情况及其与耐多药革兰氏阴性菌的关联。
2016年11月19日至28日，从大宗原料药生产设施的直接周边环境、两家污水处理厂附近、穆西河以及海得拉巴和附近村庄的栖息地采集水样。采用液相色谱 - 串联质谱法分析25种抗感染药物，使用显色培养基分析耐多药革兰氏阴性菌。此外，用聚合酶链反应（PCR）筛选标本中的bla、bla、bla、bla和bla耐药基因。
来自28个不同采样点的所有环境标本均被抗菌药物污染。在帕坦切尔 - 博拉勒姆工业区的下水道中发现了高浓度的莫西沙星、伏立康唑和氟康唑（分别高达694.1、2500和236,950μg/L）以及其他8种抗生素浓度的增加。相应的微生物学分析显示，超过95%的样本中广泛存在产超广谱β - 内酰胺酶和碳青霉烯酶的肠杆菌科细菌和非发酵菌（主要携带bla、bla和bla）。
大宗原料药生产设施废水管理不善导致水资源受到抗菌药物前所未有的污染，这似乎与产碳青霉烯酶病原体的选择和传播有关。抗菌药物耐药性的发展和全球传播对制药生产商和监管机构构成了重大挑战。
