A Multicountry Molecular Analysis of Salmonella enterica Serovar Typhi With Reduced Susceptibility to Ciprofloxacin in Sub-Saharan Africa.

Abstract

BACKGROUND: Salmonella enterica serovar Typhi is a predominant cause of bloodstream infections in sub-Saharan Africa (SSA). Increasing numbers of S. Typhi with resistance to ciprofloxacin have been reported from different parts of the world. However, data from SSA are limited. In this study, we aimed to measure the ciprofloxacin susceptibility of S. Typhi isolated from patients with febrile illness in SSA. METHODS: Febrile patients from 9 sites within 6 countries in SSA with a body temperature of ≥38.0°C were enrolled in this study. Blood samples were obtained for bacterial culture, and Salmonella isolates were identified biochemically and confirmed by multiplex polymerase chain reaction (PCR). Antimicrobial susceptibility of all Salmonella isolates was performed by disk diffusion test, and minimum inhibitory concentrations (MICs) against ciprofloxacin were measured by Etest. All Salmonella isolates with reduced susceptibility to ciprofloxacin (MIC > 0.06 µg/mL) were screened for mutations in quinolone resistance-determining regions in target genes, and the presence of plasmid-mediated quinolone resistance (PMQR) genes was assessed by PCR. RESULTS: A total of 8161 blood cultures were performed, and 100 (1.2%) S. Typhi, 2 (<0.1%) Salmonella enterica serovar Paratyphi A, and 27 (0.3%) nontyphoid Salmonella (NTS) were isolated. Multidrug-resistant S. Typhi were isolated in Kenya (79% [n = 38]) and Tanzania (89% [n = 8]) only. Reduced ciprofloxacin-susceptible (22% [n = 11]) S. Typhi were isolated only in Kenya. Among those 11 isolates, all had a Glu133Gly mutation in the gyrA gene combined with either a gyrA (Ser83Phe) or gyrB mutation (Ser464Phe). One Salmonella Paratyphi A isolate with reduced susceptibility to ciprofloxacin was found in Senegal, with 1 mutation in gyrA (Ser83Phe) and a second mutation in parC (Ser57Phe). Mutations in the parE gene and PMQR genes were not detected in any isolate. CONCLUSIONS: Salmonella Typhi with reduced susceptibility to ciprofloxacin was not distributed homogenously throughout SSA. Its prevalence was very high in Kenya, and was not observed in other study countries. Continuous monitoring of antimicrobial susceptibility is required to follow the potential spread of antimicrobial-resistant isolates throughout SSA.

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Published Version (Please cite this version)

10.1093/cid/civ788

Publication Info

Al-Emran, Hassan M, Daniel Eibach, Ralf Krumkamp, Mohammad Ali, Stephen Baker, Holly M Biggs, Morten Bjerregaard-Andersen, Robert F Breiman, et al. (2016). A Multicountry Molecular Analysis of Salmonella enterica Serovar Typhi With Reduced Susceptibility to Ciprofloxacin in Sub-Saharan Africa. Clin Infect Dis, 62 Suppl 1. pp. S42–S46. 10.1093/cid/civ788 Retrieved from https://hdl.handle.net/10161/13761.

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Scholars@Duke

Crump

John Andrew Crump

Adjunct Professor in the Department of Medicine

I am an Adjunct Professor of Medicine, Pathology, and Global Health. My work with Duke University is primarily based in northern Tanzania where I am former Site Leader and current Principal Investigator on projects linked to Duke University’s collaborative research program at Kilimanjaro Christian Medical Centre. I oversee the design and implementation of research studies on infectious diseases, particularly febrile illness, invasive bacterial disease, zoonotic infections, and infectious diseases diagnostics. In addition, I am Professor of Medicine, Pathology, and Global Health at the University of Otago and a medical epidemiologist with the US Centers for Disease Control and Prevention (CDC). My CDC work focuses on non-malaria febrile illness.

Hertz

Julian T Hertz

Associate Professor of Emergency Medicine

Julian Hertz, MD, MSc, is an Associate Professor of Emergency Medicine & Global Health. He graduated summa cum laude from Princeton University and attended medical school at Duke University, where he received the Dean's Merit Scholarship and the Thomas Jefferson Award for leadership. He completed his residency training in emergency medicine at Vanderbilt University Medical Center and his fellowship in Global Health at Duke.

Dr. Hertz's primary interests include global health, implementation science, and undergraduate and graduate medical education. Dr. Hertz's research focuses on using implementation science methods to improve cardiovascular care both locally and globally. His current projects involve developing interventions to improve acute myocardial infarction care in Tanzania, to improve management of hypertension among Tanzanians with HIV, and to improve post-hospital care among patients with multimorbidity in East Africa.

Dr. Hertz has received numerous awards for clinical, educational, and research excellence, including the Duke Emergency Medicine Faculty Teacher of the Year Award, the Duke Emergency Medicine Faculty Clinician of the Year Award, and the Duke Emergency Medicine Faculty Researcher of the Year Award. He has also received the Golden Apple Teaching Award from the Duke medical student body, the Duke Master Clinician/Teacher Award, and the Global Academic Achievement Award from the Society of Academic Emergency Medicine.


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