Thompson Corinne N, Thieu Nga Tran Vu, Vinh Phat Voong, Duc Anh Nguyen, Wolbers Marcel, Vinh Ha, Campbell James I, Ngoc Dung Tran Thi, Hoang Nguyen Van Minh, Thanh Tuyen Ha, The Hao Chung, Nguyen To Nguyen Thi, Lan Nguyen Phu Huong, Parry Christopher M, Chau Nguyen Van Vinh, Thwaites Guy, Thanh Duy Pham, Baker Stephen
Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam Centre for Tropical Medicine, Oxford University, Oxford, UK The London School of Hygiene and Tropical Medicine, London, UK.
Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
J Antimicrob Chemother. 2016 Mar;71(3):807-15. doi: 10.1093/jac/dkv400. Epub 2015 Dec 17.
We aimed to quantify the impact of fluoroquinolone resistance on the clinical outcome of paediatric shigellosis patients treated with fluoroquinolones in southern Vietnam. Such information is important to inform therapeutic management for infections caused by this increasingly drug-resistant pathogen, responsible for high morbidity and mortality in young children globally.
Clinical information and bacterial isolates were derived from a randomized controlled trial comparing gatifloxacin with ciprofloxacin for the treatment of paediatric shigellosis. Time-kill experiments were performed to evaluate the impact of MIC on the in vitro growth of Shigella and Cox regression modelling was used to compare clinical outcome between treatments and Shigella species.
Shigella flexneri patients treated with gatifloxacin had significantly worse outcomes than those treated with ciprofloxacin. However, the MICs of fluoroquinolones were not significantly associated with poorer outcome. The presence of S83L and A87T mutations in the gyrA gene significantly increased MICs of fluoroquinolones. Finally, elevated MICs and the presence of the qnrS gene allowed Shigella to replicate efficiently in vitro in high concentrations of ciprofloxacin.
We found that below the CLSI breakpoint, there was no association between MIC and clinical outcome in paediatric shigellosis infections. However, S. flexneri patients had worse clinical outcomes when treated with gatifloxacin in this study regardless of MIC. Additionally, Shigella harbouring the qnrS gene are able to replicate efficiently in high concentrations of ciprofloxacin and we hypothesize that such strains possess a competitive advantage against fluoroquinolone-susceptible strains due to enhanced shedding and transmission.
我们旨在量化氟喹诺酮耐药性对越南南部接受氟喹诺酮治疗的小儿志贺菌病患者临床结局的影响。此类信息对于指导由这种耐药性日益增强的病原体引起的感染的治疗管理非常重要，该病原体在全球范围内导致幼儿的高发病率和死亡率。
临床信息和细菌分离株来自一项比较加替沙星和环丙沙星治疗小儿志贺菌病的随机对照试验。进行时间杀菌实验以评估最低抑菌浓度（MIC）对志贺菌体外生长的影响，并使用Cox回归模型比较治疗之间的临床结局和志贺菌种类。
接受加替沙星治疗的福氏志贺菌患者的结局明显比接受环丙沙星治疗的患者差。然而，氟喹诺酮类药物的MIC与较差的结局没有显著相关性。gyrA基因中S83L和A87T突变的存在显著增加了氟喹诺酮类药物的MIC。最后，升高的MIC和qnrS基因的存在使志贺菌能够在高浓度环丙沙星中体外有效复制。
我们发现，在低于美国临床和实验室标准协会（CLSI）断点的情况下，小儿志贺菌病感染中MIC与临床结局之间没有关联。然而，在本研究中，无论MIC如何，福氏志贺菌患者接受加替沙星治疗时临床结局较差。此外，携带qnrS基因的志贺菌能够在高浓度环丙沙星中有效复制，我们推测此类菌株由于增强的脱落和传播而对氟喹诺酮敏感菌株具有竞争优势。
