Pham Thanh Duy, Karkey Abhilasha, Dongol Sabina, Ho Thi Nhan, Thompson Corinne N, Rabaa Maia A, Arjyal Amit, Holt Kathryn E, Wong Vanessa, Tran Vu Thieu Nga, Voong Vinh Phat, Ha Thanh Tuyen, Pradhan Ashish, Shrestha Saroj Kumar, Gajurel Damoder, Pickard Derek, Parry Christopher M, Dougan Gordon, Wolbers Marcel, Dolecek Christiane, Thwaites Guy E, Basnyat Buddha, Baker Stephen
The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Kathmandu, Nepal.
Elife. 2016 Mar 11;5:e14003. doi: 10.7554/eLife.14003.
The interplay between bacterial antimicrobial susceptibility, phylogenetics and patient outcome is poorly understood. During a typhoid clinical treatment trial in Nepal, we observed several treatment failures and isolated highly fluoroquinolone-resistant Salmonella Typhi (S. Typhi). Seventy-eight S. Typhi isolates were genome sequenced and clinical observations, treatment failures and fever clearance times (FCTs) were stratified by lineage. Most fluoroquinolone-resistant S. Typhi belonged to a specific H58 subclade. Treatment failure with S. Typhi-H58 was significantly less frequent with ceftriaxone (3/31; 9.7%) than gatifloxacin (15/34; 44.1%)(Hazard Ratio 0.19, p=0.002). Further, for gatifloxacin-treated patients, those infected with fluoroquinolone-resistant organisms had significantly higher median FCTs (8.2 days) than those infected with susceptible (2.96) or intermediately resistant organisms (4.01)(pS. Typhi clade internationally, but there are no data regarding disease outcome with this organism. We report an emergent new subclade of S. Typhi-H58 that is associated with fluoroquinolone treatment failure.
目前对细菌抗菌药敏性、系统发育学与患者治疗结果之间的相互作用了解甚少。在尼泊尔进行的一项伤寒临床治疗试验中，我们观察到了几例治疗失败的情况，并分离出了对氟喹诺酮高度耐药的伤寒沙门氏菌（伤寒杆菌）。对78株伤寒杆菌分离株进行了全基因组测序，并按谱系对临床观察结果、治疗失败情况和发热清除时间（FCT）进行了分层。大多数对氟喹诺酮耐药的伤寒杆菌属于一个特定的H58亚分支。使用头孢曲松治疗伤寒杆菌-H58导致治疗失败的频率（3/31；9.7%）显著低于加替沙星（15/34；44.1%）（风险比0.19，p = 0.002）。此外，对于接受加替沙星治疗的患者，感染耐氟喹诺酮类病原体的患者的中位FCT（8.2天）显著高于感染敏感病原体（2.96天）或中度耐药病原体（4.01天）的患者（p<0.001）。全球范围内，伤寒杆菌分支的疾病结局数据尚无报道。我们报告了一种新出现的伤寒杆菌-H58亚分支，它与氟喹诺酮治疗失败有关。
