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Working Grp. Fig 3 represents the age distribution of NTS and its serotypes. The median age of O5-positive Salmonella Typhimurium 15 months P 10—26 months was slightly lower compared to O5-negative Salmonella Typhimurium and Salmonella Enteritidis 18 months P 12—30 and 19 months P 11—36 months. Of all NTS, 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. The recurrences occurred 3—14 weeks after the initial episode in patients who were 1 to 5 years old. Data of antibiotic susceptibility testing were available for out of NTS isolates Table 2 ogives an overview of the antibiotic resistance profiles per serotype. MDR was present in The median MIC of ciprofloxacin was 0. However, prior use of antibiotics was associated with a higher proportion of azithromycin resistance with prior antibiotic use: Multidrug resistance was less frequent in adults The proportions of DCS, ceftriaxone or azithromycin resistance from all NTS isolates were not significantly different in children and adults.
Data are presented in percentages with the corresponding number of NTS isolates between brackets. This increase was associated with an increase of the average number of suspected BSI per month. Salmonella Typhi, Klebsiella spp. The latter was associated with a decrease in blood culture positivity rate, although it remained within the quality range.
Unless otherwise specified, data in the tables are displayed as the number of bloodstream infections BSI. As demonstrated in Fig 2 , the predominant serotype varied over time at Kisantu hospital. In , an outbreak of Salmonella Enteritidis occurred [ 32 ]. Since , the proportion of O5-negative Salmonella Typhimurium from all NTS linearly increased with an average of 5.
Over all the surveillance periods, the Typhimurium—to—Enteritidis ratio varied between minimum 1 : 3. In addition, the serotype distribution varied over the provinces. In , an outbreak of O5-positive Salmonella Typhimurium occurred in Equateur. More detailed data on the spatiotemporal evolution of the serotype distribution can be found in S2 Table. At Kisantu hospital, the proportion of MDR was similar over the different surveillance periods, also when analyzed per age category.
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 NTS isolates, from which were O5-negative Salmonella Typhimurium, were O5-positive Salmonella Typhimurium, were Salmonella Enteritidis and 7 were other Salmonella enterica serotypes.
The latter were not displayed separately, due to their low number. The year was also not displayed, since only 1 NTS isolate was confirmed at Kisantu hospital during this year. Typhimurium: O5-positive Salmonella Typhimurium. This percentage slightly increased over the difference surveillance periods — , albeit not statistically significant. The serotype distribution varied over time and province. At Kisantu general referral hospital, there was an annual increase of around 5.
MDR was widespread This publication reports on the first decade of a national microbiological surveillance in DRC, a country where diagnostic microbiological facilities are nearly absent. Sampled and processed free of charge and embedded in the routine clinical practice of the participating health care facilities as a capacity building project, the microbiological surveillance network has built up the largest collection of NTS isolates in Central-Africa.
Furthermore, the healthcare facility-based surveillance approach allowed to sample a large patient population, including the most vulnerable patients, in a cost-effective way. However, the healthcare facility-based approach also provoked some important limitations. Firstly, since no detailed data on population size, healthcare seeking behavior and referral itinerary were available, it was not possible to calculate population-based incidence rates.
Secondly, the absence of a dedicated study team may have had an impact on the intensity and quality of blood culture sampling and laboratory work-up. The intensity and quality of blood culture surveillance were further challenged by the well-known technical, logistical an human resource constraints in a low-resource setting [ 34 — 36 ]. Thirdly, detailed clinical data were not registered as part of the surveillance.
Finally, the high level of antibiotic use prior to blood culture sampling impacts blood culture sensitivity and may have altered the distribution of pathogens isolated, e. Over the different surveillance periods, NTS consistently ranked first among bacteria causing BSI in children and the second in adults. By contrast, the most recent calculations of the global NTS burden [ 37 ] were lower than previous estimates [ 3 , 38 ]. In DRC however, the already immense burden of P.
Alternatively, high disease transmission, high pathogenicity and altered health care seeking behavior might also play a role [ 4 ]. The serotype distribution varied each year and differed per province. Local outbreaks impacted the serotype distribution [ 32 , 33 , 43 ].
Similar to the results presented in this study, the Typhimurium—to—Enteritidis ratio varied between to between countries [ 44 ]. Variations in serotype distribution over time or between centers have been recently described in Malawi, Burkina Faso and Mali [ 45 — 47 ]. They were sporadically observed since , but emerged gradually at Kisantu hospital since O5-negative Salmonella Typhimurium have been described as zoonotic pathogens isolated from birds, cattle, swine and pets that can cause foodborne illness in both industrialized and non-industrialized countries [ 48 — 55 ].
In accordance with its MDR-phenotype in the present study, the previously described zoonotic O5-negative Salmonella Typhimurium frequently carried various antibiotic resistance genes [ 48 , 50 , 54 , 56 ]. If the O5-negative Salmonella Typhimurium from the present study have a zoonotic origin, their emergence may reflect environmental changes influencing the animal reservoir. Alternatively, they could be descendants of Salmonella Typhimurium ST, as genetic changes in the oafA gene can result in a loss of acetylation of the abequose residue of the O4 epitope and thus cause the loss of the O5 epitope [ 57 , 58 ].
This loss might have important consequences, as the O-antigen structure plays a role in pathogenicity and immunogenicity [ 59 ]. Of note, it is not excluded that O5-negative Salmonella Typhimurium account for some of the Salmonella Typhimurium BSI in other sub-Saharan African countries too, as the O5-antigen is not included in routine serotyping, particularly not in non-reference laboratories.
For the period —, a third of them was resistant to ceftriaxone and azithromycin and one out of eight were DCS. Pefloxacin disk diffusion methods flawlessly predicted DCS and nalidixic acid performed relatively well. Resistance to azithromycin in NTS BSI has not been reported in other sub-Saharan African countries yet, but this may be partially due to the absence of international consensus breakpoints to interpret azithromycin susceptibility testing [ 14 , 18 ].
Moreover, 3 PDR NTS isolates were found, leaving only carbapenems or other reserve antibiotics as possible, but in a low-resource setting mostly unaffordable, treatment options. However, to improve our understanding of the driving forces of this persistence, environmental and climate factors, including urbanization and climate change, should be studied. A better understanding of the driving forces of NTS and ongoing efforts to elucidate the reservoir and transmission will direct public health interventions.
The persistence of NTS BSI and worrisome emergence of co resistance to key access and watch group antibiotics are a large public health threat. The potential benefits of a vaccine for NTS are clear, even more because of the probably human reservoir [ 4 ].
Several NTS vaccines are being developed and are progressing towards clinical trials [ 68 ]. Most NTS vaccines, i. As this report shows rapid changes in serotype distribution, multivalent vaccines are needed. The risk for serotype replacement after vaccine introduction, as known from streptococci [ 72 ] and meningococci [ 73 ], is real and vigilant monitoring of NTS-serotypes is warranted.
Furthermore, the absence of the O5-epitope can impact vaccine immunogenicity of this strain. Alongside with in vitro and in vivo vaccine efficacy studies, the burden and genomics of O5-negative Salmonella Typhimurium should be clarified. In an era of limited treatment options, antibiotic stewardship becomes even more important.
After the early emergence of widespread MDR in NTS [ 1 , 4 , 5 ], antibiotic treatment has often relied on watch group antibiotics. Treatment of NTS with ceftriaxone or ciprofloxacin is experience-based [ 5 ], i. In line with Salmonella Typhi, azithromycin is a possible alternative for oral treatment in case of DCS, although validated breakpoints to interpret azithromycin susceptibility testing are still pending.
The favorable pharmacokinetic profile of azithromycin with good oral absorption, intracellular accumulation and long half-life could make it the ideal candidate for intravenous to oral switch of antibiotic treatment [ 74 , 75 ]. Its value in the initial treatment of NTS BSI can be questioned as high plasma concentrations are warranted in sepsis [ 76 ]. Full treatment with azithromycin monotherapy is efficacious in typhoid fever, but typhoidal serovars do not typically elicit septic shock [ 77 ].
Dedicated observational studies and clinical trials assessing the pharmacokinetics, pharmacodynamics and treatment efficacy of watch group antibiotics are urgently needed to develop evidence-based treatment guidelines for NTS BSI.
This present study reports valuable information for surveillance, treatment and disease prevention public health interventions and vaccination of NTS BSI. In contrast to other countries, the frequency of NTS BSI did not decline over the years, which might possibly be explained by the increasing incidence of P.
As the absence of the O5-epitope can impact immunogenicity and therefore vaccine development, the O5 antigen should actively be monitored in reference settings. Antibiotic resistance to watch group antibiotics was observed in a substantial proportion of NTS isolates. Moreover, combined resistance, incl. Field studies assessing the efficacity of different antibiotic treatment regimens are urgently needed to feed evidence-based antibiotic stewardship.
Data are presented in percentages with the corresponding number of NTS isolates between brackets for the most recent and total surveillance period. The authors thank all local clinical and laboratory staff for their contribution and dedication to the microbiological surveillance network. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Read article at publisher's site DOI : Hengkrawit K , Tangjade C.
Infect Drug Resist , , 29 Mar Diagnostics Basel , 12 3 , 18 Mar Infection , 50 2 , 11 Jan Cited by: 0 articles PMID: Sci Rep , 11 1 , 03 Nov This data has been text mined from the article, or deposited into data resources. To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.
Deborggraeve S 3 ,. Jacobs J 1 ,. Lunguya O 2. Affiliations 4 authors 1. Share this article Share with email Share with twitter Share with linkedin Share with facebook. Methods As part of a national surveillance network, blood cultures were sampled in patients with suspected BSI admitted to Kisantu referral hospital from Free full text.
Published online Apr 2. PMID: Lisette M. Marianne A. Florian Marks, Editor. Author information Article notes Copyright and License information Disclaimer. Received Jul 10; Accepted Feb 7. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article has been cited by other articles in PMC.
Go to:. S1 Table: Democratic Republic of the Congo country profile according to reference 1—4. Methods As part of a national surveillance network, blood cultures were sampled in patients with suspected BSI admitted to Kisantu referral hospital from — Reference testing: Serotyping and antibiotic susceptibility testing At INRB and ITM, identification and antibiotic susceptibility testing of pathogens were repeated in batch for all isolates.
Open in a separate window. Ethics statement The present study complies with the WHO [ 29 ] and international Council for International Organizations of Medical Sciences [ 30 ] and European Centre for Disease Prevention and Control [ 31 ] guidelines on antibiotic surveillance and antibiotic stewardship for which no recommendation for an informed consent has been issued.
Overview of sampling from — Most BSI were sampled in children From till , 11, blood cultures, accounting for 11, suspected BSI, were sampled at Kisantu hospital. Fig 1. Overview of NTS BSI per surveillance site and breakdown of blood cultures sampled at Kisantu general referral hospital from till 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.
Patient characteristics: NTS mainly affected children under the age of two years At Kisantu general referral hospital, the median age of patients from which NTS were isolated was 17 months P Fig 3. Age distribution of NTS bloodstream infections sampled at Kisantu general referral hospital from — Antibiotic resistance profile: MDR was widespread and watch group antibiotics were affected Data of antibiotic susceptibility testing were available for out of NTS isolates Table 2 Antibiotic resistance profile per NTS-serotype isolated at Kisantu general referral hospital from — Fig 4.
Longitudinal analysis of blood culture sampling and NTS isolation according to age group at Kisantu general referral hospital. Comparison with previous surveillance periods: NTS-serotype distribution varies As demonstrated in Fig 2 , the predominant serotype varied over time at Kisantu hospital.
Comparison with previous surveillance periods: resistance against watch group antibiotics increased At Kisantu hospital, the proportion of MDR was similar over the different surveillance periods, also when analyzed per age category. Fig 5. Proportional overview of antibiotic resistance in NTS bloodstream infections at Kisantu general referral hospital. 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.
Limitations and strengths This publication reports on the first decade of a national microbiological surveillance in DRC, a country where diagnostic microbiological facilities are nearly absent. Comparison with other sub-Saharan African countries Over the different surveillance periods, NTS consistently ranked first among bacteria causing BSI in children and the second in adults. Conclusion This present study reports valuable information for surveillance, treatment and disease prevention public health interventions and vaccination of NTS BSI.
DOC Click here for additional data file. S1 Table Democratic Republic of the Congo country profile according to reference 1—4. DOCX Click here for additional data file. Incidence of invasive salmonella disease in sub-Saharan Africa: a multicentre population-based surveillance study.
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