Enteric fever in Cambodian children is dominated by multidrug resistant H58 Salmonella enterica serovar Typhi with decreased susceptibility to ciprofloxacin

Background: Enteric fever (EF) infections with isolates of Salmonella enterica serovar Typhi and Paratyphi A that are multidrug resistant (MDR: resistant to chloramphenicol; ampicillin; trimethoprim-sulphamethoxazole) and have decreased ciprofloxacin susceptibility (DCS) are common in Asia. There is limited data about any EF from Cambodia. Methods: We conducted a retrospective analysis of invasive salmonellosis in Cambodian children at Angkor Hospital for Children in Siem Reap, northwest Cambodia, between January 2007 and December 2011. Results: S.enterica was isolated from blood in 161 children. There were 150 children with EF including 147 with serovar Typhi and 3 with serovar Paratyphi A. A further 11 children had bacteraemia with a non-typhoidal Salmonella (NTS) serovar. 125/147 (85%) of serovar Typhi isolates were MDR and 132/147 (90%) had DCS.Noneof the ParatyphiAisolates wereMDR,all had DCS.Among the 127 children admitted to hospital with EF antimicrobial treatment was ceftriaxone alone in 58 (46%), ceftriaxone followed by oral ciprofloxacin in 25 (20%), by oral azithromycin in 41 (32%), by cefixime in 1 (0.8%) and azithromycin alone in 2 (1.6%). A complication developed in 36/127 (28%) children admitted with EF including gastrointestinal bleeding in 13, jaundice in 9, a lung infection in 9, cholecystitis in 6, haemodynamic shock in 3, encephalopathy in 2, one child required surgery and one child had a blood culture confirmed relapse. NTS blood stream infections were mostly a complication of severe diarrhoea in children <1 year old (5) or HIV infection (4). The case fatality rate among hospital admitted children was 2/10 (20.0%) of those with a NTS bloodstream infection compared with 2/127 (1.6%) of those with EF (OR 15.8; 95%CI 1.3- 190; p = 0.03). In a subset of 102 serovar Typhi strains genotyped by investigation of a subset of single nucleotide polymorphism (SNPs), 94 (92%) belonged to theH58haplotype and had thecommonserine to phenylalanine substitution at codon 83 in the DNA gyrase. Conclusion: EF caused by the H58 haplotype of S.enterica Typhi that is MDR and has DCS is an important problem in Cambodian children. Strategies for its treatment and control are needed.