Non-typhoidal Salmonella bloodstream infections in Kisantu, DR Congo: Emergence of O5-negative Salmonella Typhimurium and extensive drug resistance

Abstract

Background: Non-typhoidal Salmonella (NTS) are a major cause of bloodstream infection (BSI) in sub-Saharan Africa. This study aimed to assess its longitudinal evolution as cause of BSI, its serotype distribution and its antibiotic resistance pattern in Kisantu, DR Congo.

Methods: As part of a national surveillance network, blood cultures were sampled in patients with suspected BSI admitted to Kisantu referral hospital from 2015-2017. Blood cultures were worked-up according to international standards. Results were compared to similar data from 2007 onwards.

Results: In 2015-2017, NTS (n = 896) represented the primary cause of BSI. NTS were isolated from 7.6% of 11,764 suspected and 65.4% of 1371 confirmed BSI. In children <5 years, NTS accounted for 9.6% of suspected BSI. These data were in line with data from previous surveillance periods, except for the proportion of confirmed BSI, which was lower in previous surveillance periods. Salmonella Typhimurium accounted for 63.1% of NTS BSI and Salmonella Enteritidis for 36.4%. Of all Salmonella Typhimurium, 36.9% did not express the O5-antigen (i.e. variant Copenhagen). O5-negative Salmonella Typhimurium were rare before 2013, but increased gradually from then onwards. Multidrug resistance was observed in 87.4% of 864 NTS isolates, decreased ciprofloxacin susceptibility in 7.3%, ceftriaxone resistance in 15.7% and azithromycin resistance in 14.9%. A total of 14.2% of NTS isolates, that were all Salmonella Typhimurium, were multidrug resistant and ceftriaxone and azithromycin co-resistant. These Salmonella isolates were called extensively drug resistant. Compared to previous surveillance periods, proportions of NTS isolates with resistance to ceftriaxone and azithromycin and decreased ciprofloxacin susceptibility increased.

Conclusion: As in previous surveillance periods, NTS ranked first as the cause of BSI in children. The emergence of O5-negative Salmonella Typhimurium needs to be considered in the light of vaccine development. The high proportions of antibiotic resistance are worrisome.

Fig 1. Overview of NTS BSI per surveillance site and breakdown of blood cultures sampled at Kisantu general referral hospital from 2015 till 2017.

The number of bloodstream infections caused by NTS are presented as part of the number of all confirmed bloodstream infections per surveillance site. Unless otherwise stated, data are presented as first isolates per bloodstream infection episode. In the top 5 of pathogens, the percentages represent the proportion of all pathogens in children <5 years, ≥ 5 years or adults for whom information about age was available (n = 1109, 151 and 110, respectively). The map was developed with QGIS (version 3.4.3), the spatial dataset for the country and province boundaries can be accessed at https://data.humdata.org/dataset/drc-administrative-boundaries-levels-0-2 (date of access 08/10/2018), the location of the surveillance sites was based on open street map data integrated in the QGIS software. Abbreviations: HGR: general referral hospital, HUR: university referral hospital, INRB: National Institute for Biomedical Research, BSI: bloodstream infection.

Fig 2. NTS-serotype distribution per year per province demonstrated variation of the predominant serotype over time and place and the emergence of O5-negative Salmonella Typhimurium.

Bars represent the number of NTS bloodstream infection (BSI). Data below the bars represent the annual proportion (%) of O5-negative Salmonella typhimurium among the total NTS BSI.

Fig 3. Age distribution of NTS bloodstream infections sampled at Kisantu general referral hospital from 2015–2017.

A: Bars represent the number of NTS bloodstream infection (BSI) per age (in years). The proportion (%) of confirmed BSI episodes caused by NTS in the respective age group is displayed below the graph. B: Bars represent the number of NTS BSI per age (in months). During this period, 806/896 NTS BSI were obtained from children < 5 years old. The exact age in months was available for 770/806 NTS BSI from children < 5 years old. Poor knowledge and registration of the exact age in months resulted in artificial peaks of NTS on multiples of 12 months. Abbreviations: BSI: bloodstream infection.

Fig 4. Longitudinal analysis of blood culture sampling and NTS isolation according to age group at Kisantu general referral hospital.

Unless otherwise specified, data in the tables are displayed as the number of bloodstream infections (BSI). The longitudinal increase in the proportion of NTS BSI among all confirmed BSI in both children < 5 years and ≥ 5 years was statistically significant (p<0.001).

Fig 5. Proportional overview of antibiotic resistance in NTS bloodstream infections at Kisantu general referral hospital.

Data on top of the bars represent the number of isolates per year. Overall, data from antibiotic susceptibility testing at reference level were available from 1490 NTS isolates, from which 253 were O5-negative Salmonella Typhimurium, 613 were O5-positive Salmonella Typhimurium, 617 were Salmonella Enteritidis and 7 were other Salmonella enterica serotypes. The latter were not displayed separately, due to their low number. The year 2007 was also not displayed, since only 1 NTS isolate was confirmed at Kisantu hospital during this year. Abbreviations: MDR: multidrug resistance, XDR: extensive drug resistance, PDR: pandrug resistance, Amp: ampicillin, SxT: trimethoprim-sulfamethoxazole, Clr: chloramphenicol, DCS: decreased ciprofloxacin susceptibility, CTRR: ceftriaxone resistance, AZIR: azithromycin resistance, S.: Salmonella, O5+: O5-antigen positive, O5-: O5-antigen negative.

Fig 6. Longitudinal analysis of multidrug resistance combined with decreased ciprofloxacin susceptibility and extensive drug resistance in O5-positive Salmonella Typhimurium at Kisantu general referral hospital.

Data below the graphs represent the proportion (%) of resistant isolates among all O5-positive Salmonella Typhimurium. Abbreviations: MDR: multidrug resistance, XDR: extensive drug resistance, DCS: decreased ciprofloxacin susceptibility, CTRR: ceftriaxone resistance, AZIR: azithromycin resistance, BSI: bloodstream infection, O5+ S. Typhimurium: O5-positive Salmonella Typhimurium.