Non-typhoidal Salmonella blood stream infection in Kuwait: Clinical and microbiological characteristics

Non-typhoidal Salmonella (NTS) bacteremia is a significant cause of morbidity and mortality worldwide. It is considered to be an emerging and neglected tropical disease in Africa. We studied this in two tertiary hospitals–Al Farwaniya and Al Amiri–in Kuwait, a subtropical country, from April 2013-May 2016. NTS bacteremia was present in 30 of 53,860 (0.75%) and 31 of 290,36 (1.33%) blood cultures in the two hospitals respectively. In Al Farwaniya hospital, one-third of the patients were from some tropical developing countries of Asia. About 66% of all patients (40/61) had diarrhea, and of these, 65% had the corresponding blood serovar isolated from stool culture. A few patients had Salmonella cultured from urine. Patients were either young or old. Most of the patients had co-morbidities affecting the immune system. Two patients each died in both hospitals. The number of different serovars cultured in each hospital was 13, and most infections were due to S. Enteritidis (all sequence type [ST]) 11) and S. Typhimurium (all ST19) except in a subgroup of expatriate patients from tropical developing countries in Al Farwaniya hospital. About a quarter of the isolates were multidrug-resistant. Most patients were treated with a cephalosporin with or without other antibiotics. S. Enteritidis and S. Typhimurium isolates were typed by pulsed field-gel electrophoresis (PFGE) and a selected number of isolates were whole-genome sequenced. Up to four different clades were present by PFGE in either species. Whole-genome sequenced isolates showed antibiotic-resistance genes that showed phenotypic correlation, and in some cases, phenotypes showed absence of specific genes. Whole-genome sequenced isolates showed presence of genes that contributed to blood-stream infection. Phylogeny by core genome analysis showed a close relationship with S. Typhimurium and S. Enteritidis from other parts of the world. The uniqueness of our study included the finding of a low prevalence of infection, mortality and multidrug-resistance, a relatively high prevalence of gastrointestinal infection in patients, and the characterization of selected isolates of S. Typhimurium and S. Enteritidis serovars by whole-genome sequencing that shed light on phylogeny, virulence and resistance. Similarities with studies from developing countries especially Africa included infection in patients with co-morbidities affecting the immune system, predominance of S. Typhimurium and S. Enteritidis serovars and presence of drug-resistance in isolates.
Author summary Salmonella organisms are classified into typhoidal Salmonella (causing enteric fever) and non-typhoidal Salmonella (NTS) (causing infections other than enteric fever). Apart from causing other infections, NTS causes blood-stream infection (bacteremia and septicemia). NTS blood stream infection (NTS-BI) is considered to be an emerging and neglected tropical disease in Africa. It causes a very high morbidity and mortality in Africa. The individuals affected in Africa are children, malnourished people, patients with malaria or HIV etc. These conditions affect the immune system and make them vulnerable to infection with NTS. In these patients, diarrheal disease due to NTS is rare. The majority of infections are due to two types of NTS: Typhimurium and Enteritidis. There is a very high prevalence of multidrug-resistance in NTS making the infection difficult to treat. NTS-BI is also present in other parts of the world including developed countries albeit at a lower prevalence. Kuwait is a high-income, subtropical country in transition (from a developing to developed country), located in the Middle East. We studied NTS-BI in Al Farwaniya and Al Amiri hospitals in Kuwait during April 2013 to May 2016. Out of nearly 30,000 to more than 50,000 blood cultures done in these hospitals, NTS was present in 0. 75 to 1.33% of blood cultures, representing a very small proportion of blood cultures, unlike in Africa. This showed that 31 patients in Al Farwaniya hospital and 30 patients in Al Amari hospital had NTS-BI. Most of these patients had underlying illnesses such as diabetes, lung infection, cancer etc. that affect the immune system, as in Africa. Many patients also had diarrheal disease caused by the same NTS that caused blood stream infection, unlike in Africa. Only two patients in each hospital died, a low mortality, unlike in Africa. The majority of the isolates belonged to Typhimurium and Enteritidis as in Africa. Even though resistance to drugs was a problem, about quarter of the isolates only were multidrug-resistant, a lower prevalence compared to in Africa. In Kuwait, we performed a detailed genetic study of a selected number of Typhimurium and Enteritidis isolates by a modern technique called whole genome sequencing. This revealed genetic determinants encoding drug-resistance and virulence causing blood-stream infection. This type of study was not performed in African isolates. Thus, our study revealed similarities and differences with studies of NTS-BI in Africa.