Azithromycin resistance in nontyphoidal <i>Salmonella</i> in an urban informal settlement in Nairobi, Kenya

Nontyphoidal <i>Salmonella</i> (NTS) poses a significant burden of bacteremia in sub-Saharan Africa (SSA). Antimicrobial resistance (AMR) complicates the management of NTS infections. The NTS carriage of mobile genetic elements harboring AMR genes can result in the spread of resistance. We investigated the AMR profiles and genomic characteristics of 74 NTS isolates recovered from children under 5 years of age during acute disease, post-treatment shedding, and in healthy carriers. Whole genome sequencing data were used to identify AMR genes, plasmid replicons, and virulence determinants. Of the 74 NTS isolates, 63.5% (47) were <i>Salmonella</i> Enteritidis, the rest being <i>Salmonella</i> Typhimurium. More than a third, 37.8% (2874), were resistant to at least one antibiotic. A small proportion, 8.1% (6/74), were multidrug resistant, with a majority (5/6) being <i>S</i>. Typhimurium. Resistance to azithromycin, one of the current drugs of choice for treating invasive nontyphoidal <i>Salmonella</i> (iNTS), was observed in 13.5% (10/74) of the isolates. Notably, the macrolide resistance gene <i>mph(A</i>) was detected in one isolate. Extended-spectrum β-lactamase (ESBL) genes (<i>bla</i> _CTX-M-3 and <i>bla</i> _TEM) were identified in 8.1% of the isolates, all of which were <i>S</i>. Typhimurium. Six plasmid replicons were detected, with epidemic plasmids IncFIB(S)_1 and IncFII(S)_1 observed in all isolates. The ESBL gene <i>bla</i> _CTX-M-3 was harbored in the IncI1_1_Alpha plasmid replicon. A total of 117 virulence determinants were identified, with only one isolate carrying the <i>shdA</i> gene associated with prolonged fecal shedding. Resistance and reduced susceptibility of NTS to antibiotics could result in treatment failure and underscore the need for continued surveillance, vaccine introduction, and antimicrobial stewardship.IMPORTANCEAntimicrobial resistance is a huge public health concern globally, particularly in low-resource settings due to a high burden of infectious diseases, limited access to quality healthcare, and misuse and/or overuse of antibiotics. Azithromycin is one of the antibiotics used in the treatment of iNTS; notably, 13.5% of the NTS isolates in this study showed resistance to azithromycin. The detection of AMR determinants and plasmids highlights the possibility of these determinants spreading, resulting in increased resistance. Resistance of NTS to azithromycin and other antibiotics in this setting could lead to treatment failure, resulting in poor patient outcomes. These findings emphasize the need for vaccine introduction and antimicrobial stewardship in health facilities in low-resource settings.