A rare case of Colistin-resistant Salmonella Enteritidis meningitis in an HIV-seropositive patient

Abstract

Background: Non-typhoidal salmonellae (NTS) have been associated with invasive disease, notably meningitis, in immunocompromised individuals. Infections of this nature carry high rates of morbidity and mortality. Colistin resistance in salmonellae is a rare finding, more so in an invasive isolate such as cerebrospinal fluid (CSF). Colistin resistance has important infection control implications and failure to manage this phenomenon may lead to the loss of our last line of defence against multi-drug resistant Gram-negative organisms. To our knowledge, this is the first reported clinical case of colistin-resistant Salmonella Enteritidis meningitis in South Africa.

Case presentation: We report a case of a young male patient with advanced human immunodeficiency virus (HIV) infection who presented to hospital with symptoms of meningitis. Cerebrospinal fluid (CSF) cultured a Salmonella Enteritidis strain. Antimicrobial susceptibility testing (AST) of the isolate, revealed the strain to be colistin resistant. Despite early and aggressive antimicrobial therapy, the patient succumbed to the illness after a short stay in hospital. Subsequent genomic analysis of the isolate showed no presence of the mcr genes or resistance-conferring mutations in phoPQ, pmrAB, pmrHFIJKLME/arnBCADTEF, mgrB, and acrAB genes, suggesting the presence of a novel colistin resistance mechanism.

Conclusion: Invasive non-typhoidal salmonellae infection should be suspected in patients with advanced immunosuppression who present with clinical features of meningitis. Despite early and appropriate empiric therapy, these infections are commonly associated with adverse outcomes to the patient. Combination therapy with two active anti-Salmonella agents may be a consideration in the future to overcome the high mortality associated with NTS meningitis. Colistin resistance in clinical Salmonella isolates, although a rare finding at present, has significant public health and infection control implications. The causative mechanism of resistance should be sought in all cases.

Keywords: Colistin resistance; HIV; Meningitis; Non-typhoidal Salmonella; Salmonella Enteritidis.

Fig. 1

Prophages found in S. Enteritidis strain EC20120916. Six prophages were found in the strain, with only two being intact. Prophages are biomarker signatures that can be used to identify specific clones and strains of Salmonellae. Prophages reportedly found in African strains were found in this strain

Fig. 2

Phylogenetic tree of S. Enteritidis strains obtained worldwide. a Relationship between strain EC20120916 and S. Enteritidis strains of international origin isolated between 2005 and 2019. b Relationship between strain EC20120916 and S. Enteritidis strains of international origin isolated between 1953 and 2005. There was greater relationship between the strain EC20120916 and recent strains isolated between 2005 and 2019 than between those isolated from 1953 to 2005, showing that this strain has recently evolved. It’s closeness to Brazilian and USA strains of human origin suggests that is of the international epidemic clade and anthroponotic