DataSheet_1_Case report: Long-term follow-up of patients who received a FimCH vaccine for prevention of recurrent urinary tract infections caused by antibiotic resistant Enterobacteriaceae: a case report series.xlsx

Urinary tract infections (UTI) caused by carbapenem-resistant Enterobacteriaceae (CRE) are considered one of the most urgent health threats to humans according to the Centers for Disease Control (CDC), and the World Health Organization (WHO). A FimCH Vaccine expanded access study is being conducted in patients with a history of antibiotic resistant UTIs who are considered to be at risk for development of CRE UTI. This case series describes the clinical, safety and immunogenicity findings for four participants who received a FimCH four-vaccine series. Participants were followed for 12 months after administration of the fourth vaccine for safety, general health status and UTI occurrence. The study was later amended to allow additional follow-up of up to five years post vaccine administration to assess long-term health status, UTI occurrences and to obtain blood samples for anti-FimH antibody testing. In our population of 4 study participants, the number of symptomatic UTI occurrences caused by gram-negative bacteria in the 12-month period following peak anti-FimH antibody response were approximately 75% lower than the 12-month period preceding study enrollment. These results are consistent with the 30-patient cohort of a Phase 1 study with the same FimCH Vaccine. UTI occurrences increased during the long-term follow-up period for all 4 participants but did not reach the rate observed pre-vaccination. No new safety concerns related to the FimCH Vaccine were identified during long-term follow-up. This case series has clinical importance and public health relevance since it examines and reports on UTI frequency and recurrence following vaccination with the FimCH Vaccine in a high-risk population of patients with recurrent UTI. Additionally, participants described improved well-being following vaccination which was maintained in the long-term follow-up period.

根据美国疾病控制与预防中心（Centers for Disease Control, CDC）及世界卫生组织（World Health Organization, WHO）的评估，由碳青霉烯类耐药肠杆菌科细菌（Carbapenem-resistant Enterobacteriaceae, CRE）引起的尿路感染（Urinary tract infections, UTI）被认为是人类面临的最紧迫的健康威胁之一。一项针对既往有抗生素耐药性尿路感染病史且被认为有发展成CRE尿路感染风险的患者的FimCH疫苗扩大访问研究正在进行中。本病例系列对接受FimCH四联疫苗系列的四位参与者进行了临床、安全性和免疫原性结果的描述。参与者在接受第四剂疫苗后进行了为期12个月的随访，以评估安全性、总体健康状况及尿路感染的发生情况。该研究随后进行了修订，允许在疫苗接种后进行最长五年的额外随访，以评估长期健康状况、尿路感染的发生率，并采集血液样本进行抗FimH抗体检测。在我们的4名研究参与者群体中，在接受峰值抗FimH抗体反应后的12个月期间，由革兰氏阴性菌引起的症状性尿路感染发生率比研究入组前12个月的12个月期间降低了约75%。这些结果与采用相同FimCH疫苗的30名患者的1期研究队列结果一致。在长期随访期间，所有4名参与者的尿路感染发生率均有所增加，但并未达到疫苗接种前的水平。在长期随访期间，未发现与FimCH疫苗相关的新的安全性问题。本病例系列具有重要的临床意义和公共卫生相关性，因为它考察并报告了高风险复发性尿路感染患者群体在接受FimCH疫苗后尿路感染的频率和复发情况。此外，参与者描述了疫苗接种后的健康状况改善，并在长期随访期间得到了维持。