A 23-year retrospective investigation of Salmonella Typhi and Salmonella Paratyphi isolated in a tertiary Kathmandu hospital

BackgroundSalmonella serovars Typhi (S. Typhi) and Paratyphi A (S. Paratyphi A), the causative agents of enteric fever, have been routinely isolated organisms from the blood of febrile patients in the Kathmandu Valley since the early 1990s. Susceptibility against commonly used antimicrobials for treating enteric fever has gradually changed throughout South Asia since this time, posing serious treatment challenges. Here, we aimed to longitudinally describe trends in the isolation of Salmonella enterica and assess changes in their antimicrobial susceptibility in Kathmandu over a 23-year period.MethodsWe conducted a retrospective analysis of standardised microbiological data from April 1992 to December 2014 at a single healthcare facility in Kathmandu, examining time trends of Salmonella-associated bacteraemia and the corresponding antimicrobial susceptibility profiles of the isolated organisms.ResultsOver 23 years there were 30,353 positive blood cultures. Salmonella enterica accounted for 65.4% (19,857/30,353) of all the bacteria positive blood cultures. S. Typhi and S. Paratyphi A were the dominant serovars, constituting 68.5% (13,592/19,857) and 30.5% (6,057/19,857) of all isolated Salmonellae. We observed (i) a peak in the number of Salmonella-positive cultures in 2002, a year of heavy rainfall and flooding in the Kathmandu Valley, followed by a decline toward pre-flood baseline by 2014, (ii) an increase in the proportion of S. Paratyphi in all Salmonella-positive cultures between 1992 and 2014, (iii) a decrease in the prevalence of MDR for both S. Typhi and S. Paratyphi, and (iv) a recent increase in fluoroquinolone non-susceptibility in both S. Typhi and S. Paratyphi isolates.ConclusionsOur work describes significant changes in the epidemiology of Salmonella enterica in the Kathmandu Valley during the last quarter of a century. We highlight the need to examine current treatment protocols for enteric fever and suggest a change from fluoroquinolone monotherapy to combination therapies of macrolides or cephalosporins along with older first-line antimicrobials that have regained their efficacy.【背景】伤寒沙门菌（Salmonella Typhi, S. Typhi）与甲型副伤寒沙门菌（Salmonella Paratyphi A, S. Paratyphi A）为肠热症（enteric fever）的致病菌。自20世纪90年代初以来，二者已成为加德满都谷地发热患者血液标本中的常规分离菌株。自彼时起，南亚地区用于治疗肠热症的常用抗菌药物敏感性逐渐发生演变，给临床治疗带来严峻挑战。本研究旨在纵向描述23年周期内加德满都地区肠炎沙门菌（Salmonella enterica）的分离趋势，并评估其抗菌药物敏感性的变化。 【方法】本研究对1992年4月至2014年12月期间，加德满都某单一医疗机构的标准化微生物学数据开展回顾性分析，考察沙门菌相关菌血症的时间分布趋势，以及分离菌株对应的抗菌药物敏感性谱。 【结果】23年间共获取30353份血液培养阳性标本。肠炎沙门菌占所有细菌阳性血液培养标本的65.4%（19857/30353）。伤寒沙门菌与甲型副伤寒沙门菌为优势血清型，分别占所有分离沙门菌的68.5%（13592/19857）与30.5%（6057/19857）。本研究观察到如下特征：（i）沙门菌培养阳性数在2002年达到峰值，该年加德满都谷地遭遇强降雨与洪涝灾害，随后至2014年逐步回落至洪水前的基线水平；（ii）1992年至2014年间，所有沙门菌阳性血液培养标本中甲型副伤寒沙门菌的占比呈上升趋势；（iii）伤寒沙门菌与甲型副伤寒沙门菌的多重耐药（MDR）菌株检出率均有所下降；（iv）近期两类沙门菌分离株的氟喹诺酮类（fluoroquinolone）不敏感性均呈上升态势。 【结论】本研究阐明了过去四分之一世纪内，加德满都谷地肠炎沙门菌流行病学特征的显著变化。我们强调需对当前肠热症的治疗方案进行重新评估，并建议将氟喹诺酮类单药治疗方案调整为大环内酯类（macrolides）或头孢菌素类（cephalosporins）联合疗法，搭配已恢复抗菌活性的经典一线抗菌药物。