Department of Clinical Science, University of Medicine, Bergen, Norway.
National Centre for Tropical Infectious Diseases, Haukeland University Hospital, Bergen, Norway.
PLoS Negl Trop Dis. 2024 Apr 17;18(4):e0012132. doi: 10.1371/journal.pntd.0012132. eCollection 2024 Apr.
Typhoid fever is a common cause of febrile illness in low- and middle-income countries. While multidrug-resistant (MDR) Salmonella Typhi (S. Typhi) has spread globally, fluoroquinolone resistance has mainly affected Asia.
Consecutively, 1038 blood cultures were obtained from patients of all age groups with fever and/or suspicion of serious systemic infection admitted at Mnazi Mmoja Hospital, Zanzibar in 2015-2016. S. Typhi were analyzed with antimicrobial susceptibility testing and with short read (61 strains) and long read (9 strains) whole genome sequencing, including three S. Typhi strains isolated in a pilot study 2012-2013.
Sixty-three S. Typhi isolates (98%) were MDR carrying blaTEM-1B, sul1 and sul2, dfrA7 and catA1 genes. Low-level ciprofloxacin resistance was detected in 69% (43/62), with a single gyrase mutation gyrA-D87G in 41 strains, and a single gyrA-S83F mutation in the non-MDR strain. All isolates were susceptible to ceftriaxone and azithromycin. All MDR isolates belonged to genotype 4.3.1 lineage I (4.3.1.1), with the antimicrobial resistance determinants located on a composite transposon integrated into the chromosome. Phylogenetically, the MDR subgroup with ciprofloxacin resistance clusters together with two external isolates.
We report a high rate of MDR and low-level ciprofloxacin resistant S. Typhi circulating in Zanzibar, belonging to genotype 4.3.1.1, which is widespread in Southeast Asia and African countries and associated with low-level ciprofloxacin resistance. Few therapeutic options are available for treatment of typhoid fever in the study setting. Surveillance of the prevalence, spread and antimicrobial susceptibility of S. Typhi can guide treatment and control efforts.
伤寒是中低收入国家常见的发热性疾病病因。虽然多药耐药（MDR）伤寒沙门氏菌（S. Typhi）已在全球传播，但氟喹诺酮耐药主要影响亚洲。
2015-2016 年，在桑给巴尔的 Mnazi Mmoja 医院，连续采集了 1038 份来自各年龄段发热和/或疑似严重全身感染患者的血培养标本。对 S. Typhi 进行了抗菌药物敏感性试验以及短读（61 株）和长读（9 株）全基因组测序分析，包括 2012-2013 年试点研究中分离的 3 株 S. Typhi 菌株。
63 株 S. Typhi 分离株（98%）为携带 blaTEM-1B、sul1 和 sul2、dfrA7 和 catA1 基因的 MDR 菌株。62 株中的 69%（43/62）对环丙沙星呈低水平耐药，其中 41 株存在单个拓扑异构酶突变 gyrA-D87G，而非 MDR 菌株存在单个拓扑异构酶突变 gyrA-S83F。所有分离株均对头孢曲松和阿奇霉素敏感。所有 MDR 分离株均属于 4.3.1 谱系 I（4.3.1.1）基因型，其抗菌药物耐药决定因素位于整合到染色体上的复合转座子上。从系统发生学角度看，具有环丙沙星耐药性的 MDR 亚群与两个外部分离株聚集在一起。
我们报告了桑给巴尔流行的 MDR 和低水平环丙沙星耐药性 S. Typhi 发生率很高，这些菌株属于广泛分布于东南亚和非洲国家的 4.3.1.1 基因型，与低水平环丙沙星耐药性相关。在研究环境中，治疗伤寒的治疗选择有限。对 S. Typhi 的流行情况、传播和抗菌药物敏感性进行监测，可以指导治疗和控制工作。
