Knowledge, awareness, and risk practices related to bacterial contamination of antiseptics, disinfectants, and hand hygiene products among healthcare workers in sub-saharan Africa: a cross-sectional survey in three tertiary care hospitals (Benin, Burkina Faso, and DR Congo).

BACKGROUND: Antiseptics, disinfectants, and hand hygiene products can be contaminated with bacteria and cause healthcare-associated infections, which are underreported from low- and middle-income countries. To better understand the user-related risk factors, we conducted a knowledge, awareness, and practice survey among hospital staff in sub-Saharan Africa. METHODS: Self-administered questionnaire distributed among healthcare workers in three tertiary care hospitals (Burkina Faso, Benin, Democratic Republic of the Congo). RESULTS: 617 healthcare workers (85.3% (para)medical and 14.7% auxiliary staff) participated. Less than half (45.5%) had been trained in Infection Prevention & Control (IPC), and only 15.7% were trained < 1 year ago. Near two-thirds (64.2%) preferred liquid soap for hand hygiene, versus 33.1% for alcohol-based hand rub (ABHR). Most (58.3%) expressed confidence in the locally available products. Knowledge of product categories, storage conditions and shelf-life was inadequate: eosin was considered as an antiseptic (47.5% of (para)medical staff), the shelf life and storage conditions (non-transparent container) of freshly prepared chlorine 0.5% were known by only 42.6% and 34.8% of participants, respectively. Approximately one-third of participants approved using tap water for preparation of chlorine 0.5% and liquid soap. Most participants (> 80%) disapproved recycling soft-drink bottles as liquid soap containers. Nearly two-thirds (65.0%) declared that bacteria may be resistant to and survive in ABHR, versus 51.0% and 37.4% for povidone iodine and chlorine 0.5%, respectively. Depicted risk practices (n = 4) were ignored by 30 to 40% of participants: they included touching the rim or content of stock containers with compresses or small containers, storing of cotton balls soaked in an antiseptic, and hand-touching the spout of pump dispenser. Filling containers by topping-up was considered good practice by 18.3% of participants. Half (52.1%) of participants acknowledged indefinite reuse of containers. Besides small differences, the findings were similar across the study sites and professional groups. Among IPC-trained staff, proportions recognizing all 4 risk practices were higher compared to non-trained staff (35.9% versus 23.8%, p < 0.0001). CONCLUSIONS: The present findings can guide tailored training and IPC implementation at the healthcare facility and national levels, and sensitize stakeholders' and funders' interest.

Examining geospatial and temporal distribution of invasive non-typhoidal Salmonella disease occurrence in sub-Saharan Africa: a systematic review and modelling study.

BACKGROUND: Invasive non-typhoidal Salmonella (iNTS) disease is a significant health concern in sub-Saharan Africa. While our knowledge of a larger-scale variation is growing, understanding of the subnational variation in iNTS disease occurrence is lacking, yet crucial for targeted intervention. METHOD: We performed a systematic review of reported occurrences of iNTS disease in sub-Saharan Africa, consulting literature from PubMed, Embase and Web of Science published since 2000. Eligibility for inclusion was not limited by study type but required that studies reported original data on human iNTS diseases based on the culture of a normally sterile site, specifying subnational locations and the year, and were available as full-text articles. We excluded studies that diagnosed iNTS disease based on clinical indications, cultures from non-sterile sites or serological testing. We estimated the probability of occurrence of iNTS disease for sub-Saharan Africa on 20 km × 20 km grids by exploring the association with geospatial covariates such as malaria, HIV, childhood growth failure, access to improved water, and sanitation using a boosted regression tree. RESULTS: We identified 130 unique references reporting human iNTS disease in 21 countries published from 2000 through 2020. The estimated probability of iNTS occurrence grids showed significant spatial heterogeneity at all levels (20 km × 20 km grids, subnational, country and subregional levels) and temporal heterogeneity by year. For 2020, the probability of occurrence was higher in Middle Africa (0.34, 95% CI: 0.25 to 0.46), followed by Western Africa (0.33, 95% CI: 0.23 to 0.44), Eastern Africa (0.24, 95% CI: 0.17 to 0.33) and Southern Africa (0.08, 95% CI: 0.03 to 0.11). Temporal heterogeneity indicated that the probability of occurrence increased between 2000 and 2020 in countries such as the Republic of the Congo (0.05 to 0.59) and Democratic Republic of the Congo (0.10 to 0.48) whereas it decreased in countries such as Uganda (0.65 to 0.23) or Zimbabwe (0.61 to 0.37). CONCLUSION: The iNTS disease occurrence varied greatly across sub-Saharan Africa, with certain regions being disproportionately affected. Exploring regions at high risk for iNTS disease, despite the limitations in our data, may inform focused resource allocation. This targeted approach may enhance efforts to combat iNTS disease in more affected areas.

Affordable blood culture systems from China: in vitro evaluation for use in resource-limited settings.

BACKGROUND: Bloodstream infections (BSI) pose a significant threat due to high mortality rates and the challenges posed by antimicrobial resistance (AMR). In 2019, an estimated 4.95 million deaths were linked to bacterial AMR. The highest impact was seen in resource-limited settings (RLS). For diagnosis of BSI, performant continuously-monitoring blood culture systems (CMBCS) have been optimized. However, in RLS, the implementation of CMBCS is hindered by budget constraints and unsuitable environmental conditions. Manufacturers from growing economies are currently producing affordable in vitro diagnostics, which could fill the gap in capacity, but so far these are not established outside their domestic markets. METHODS: This study evaluated the performance, usability, and interchangeability of Chinese CMBCS in a laboratory setting using simulated blood cultures with a panel of 20 BSI-associated strains. Four systems were selected for the assessment: Autobio BC60, Mindray TDR60, Scenker Labstar50, and DL-biotech DL-60. FINDINGS: Overall, all evaluated CMBCS demonstrated good performance with high yield (96.7-100%) and specificity (97.5-100%), comparable to the reference system (bioMérieux 3D). In addition, when used as "manual" blood cultures in a conventional incubator with visual growth detection, performance was also satisfactory: yield was between 90 and 100% and specificity was 100% for all BCBs. Both the CMBCS and the BCBs were easy to use and lot-to-lot variability in BCBs was minimal. The interchangeability testing indicated that the BCBs from different brands (all except Scenker) were compatible with the various automates, further highlighting the potential for a harmonized "universal BCB." INTERPRETATION: Based on this in vitro study, we recommend the use of these systems in settings with challenging environments and limited resources. The Autobio system performed best for automatic detection and DL-Biotech BCBs for manual cultures respectively (combination of performance, price, usability). The appropriateness for use in RLS should still be confirmed in a field study. FUNDING: The study was funded by FIND.

Invasive non-typhoidal Salmonella from stool samples of healthy human carriers are genetically similar to blood culture isolates: a report from the Democratic Republic of the Congo.

Invasive non-typhoidal Salmonella (iNTS) (serotypes Typhimurium and Enteritidis) are major causes of bloodstream infections in sub-Saharan Africa, but their reservoir is unknown. Aiming to demonstrate human carriers as a reservoir, we assessed an iNTS disease endemic rural community (Kikonka health area, Democratic Republic of the Congo) for intestinal carriage of iNTS. After a census, healthy subjects from randomly selected households provided three successive stool samples for Salmonella culture. We next compared the stool isolates for genetic relatedness with time and health area-matched blood culture isolates obtained from hospitalized patients by multiple locus variable-number tandem repeat analysis (MLVA) and performed whole genome sequencing (WGS) on a subset of stool and blood isolates. Among 2,354 eligible subjects, 2,234 (94.9%) consented and provided at least one stool sample, and 2,219 (94.3%) provided three stool samples. The cumulative proportion of Salmonella carriers after 3 days was 4.4% (n = 98). S. Typhimurium and Enteritidis were found in 26 and 3 carriers, respectively, representing 1.3% (29 out of 2,234) of participants living in 6.0% (26 out of 482) of households. MLVA types of all 26 S. Typhimurium stool isolates matched with the corresponding MLVA types of blood isolates. The MLVA type of one out of three Enteritidis stool isolates matched the single MLVA type of the five Enteritidis blood isolates. WGS analysis of S. Typhimurium (n = 20) and S. Enteritidis (n = 4) isolates revealed Typhimurium multilocus sequence type (ST)313 Lineage 2 and Enteritidis ST11 Central/Eastern African and Outlier clades and confirmed the MLVA clustering. More than three-quarters of Typhimurium isolates showed combined multidrug resistance, ceftriaxone resistance, and fluoroquinolone non-susceptibility. In conclusion, the present study demonstrated iNTS carriage among healthy community members, with stool isolates that were genetically similar to blood culture isolates obtained in patients from the same community. These findings contribute to the evidence of a human reservoir of iNTS.

Knowledge, attitude and practice survey of bacterial contamination of blood for transfusion in the Democratic Republic of the Congo.

BACKGROUND: We assessed healthcare worker's knowledge-attitude-practice regarding bacterial contamination of blood products in the Democratic Republic of the Congo. MATERIALS AND METHODS: In three hospitals and the National Blood Transfusion Centre (NBTC), two multiple-choice surveys were completed on a tablet computer: one each, for blood bank (31 questions) and for clinical ward staff (20 questions). A score was calculated for 11 overlapping knowledge questions. RESULTS: Among 247 participants (blood bank No.=62, ward No.=185), median (range) knowledge score was 10 (2-19) on a maximum of 20, with blood bank staff (12/20) scoring higher than clinical ward staff (9/20) (p<0.0001). Half (50.2%) of 247 participants recalled previous training in transfusion medicine. Participants had limited understanding of and compliance with NBTC-recommended preventive measures: incorrect assumption that wearing gloves prevents bacterial contamination (83.8%) and that blood banks test donor blood for bacteria (59.9%). Half (50.0%) of blood bank staff did not acknowledge the NBTC-recommended antisepsis procedure, 62.1% did not apply the appropriate number of antisepsis steps, and 32.3% saw no harm in touching the venipuncture site after antisepsis. Presence of bacteria on healthy skin (62.3%) and blood bank fomites (examination gloves: 30.8%, soap: 62.8%) was underestimated. Although 92.4% of clinical ward staff said to easily recognize transfusion reactions, only 15.7% recognized septic reactions and post-transfusion antibiotic treatment practices were not consistent. Challenges reported by blood bank staff and particular for low-resource settings were: frequent power cuts (98.4%), transport of blood products by patient attendants (41.1%), without cooling elements (64.4%), and reuse of finished antiseptic/disinfectant containers (75.4%). DISCUSSION: The present study points to gaps in knowledge, attitudes, practices along sampling, cold chain and transfusion which can feed customized training and monitoring.

Intestinal carriage of invasive non-typhoidal Salmonella among household members of children with Salmonella bloodstream infection, Kisangani, DR Congo.

Introduction: Invasive non-typhoidal Salmonella (iNTS), mainly Salmonella Typhimurium and Salmonella Enteritidis, causes a severe burden in sub-Saharan Africa; however, its reservoir (animal or environmental) is unclear. The present study assessed healthy household members of index patients for intestinal carriage of Salmonella. Methods: Index patients were admitted to the University Hospital of Kisangani (DR Congo), and Salmonella was grown from blood cultures. Household members were asked to provide three stool samples for culture for Salmonella. Salmonella Typhimurium and S. Enteritidis isolates from index patients, and household members were assessed for genetic relatedness using the multiple-locus variable number of tandem repeat analysis (MLVA), and the multilocus sequence type (ST) was determined by whole genome sequencing. Results: Between May 2016 and January 2020, 22 households were visited. The index patient serotypes were Typhimurium, Enteritidis, Typhi, and Paratyphi C; II:42:r:-; and I:7:y:- (n = 8, 7, 5, and each 1, respectively). The median (range) delay between the index patient and household sampling was 25 days (2 days to 7.3 months); 203 household members provided at least one stool sample. In all, 15 (7.3%) Salmonella carriers were found in nine of 22 households. For one index patient, the household comprised S. Typhimurium in four household members, including the index patient, sampled 27 days after bloodstream infection; the MLVA types of these five isolates were similar. They belonged to ST313 lineage 2 and were closely related [0-1 allelic distance (AD) among the stool isolates and eight AD with the blood culture isolate]. In another household, the stool culture of the index patient (obtained 67 days after bloodstream infection) grew S. Enteritidis of the same MLVA type; both isolates belonged to the ST11 Central/Eastern African clade and were closely related (three AD). Discussion: The present study provides evidence of household clustering of S. Typhimurium ST313 and intestinal carriage of iNTS several weeks after bloodstream infection.

Challenges of Antibiotic Formulations and Administration in the Treatment of Bloodstream Infections in Children Under Five Admitted to Kisantu Hospital, Democratic Republic of Congo.

Severe bacterial infections in children need prompt, appropriate antibiotic treatment. We report challenges observed within a prospective, cohort study on antibiotic efficacy in non-typhi Salmonella bloodstream infection (NCT04850677) in Kisantu district hospital (Democratic Republic of Congo). Children (aged > 28 days to < 5 years) admitted with suspected bloodstream infection (August 1, 2021 through July 31, 2022) were enrolled and followed until day 3 or discharge for non-typhi Salmonella patients. Antibiotics were administered to 98.4% (1,838/1,867) of children, accounting for 2,296 antibiotic regimens (95.7% intravenous, 4.3% oral). Only 78.3% and 61.8% of children were, respectively, prescribed and administered antibiotics on the admission day. At least one dose was not administered in 3.6% of children, mostly because of mismatch of the four times daily cefotaxime schedule with the twice-daily administration rounds. Inappropriate intravenous administration practices included multidose use, air-venting, and direct injection instead of perfusion. There was inaccurate aliquoting in 18.0% (32/178) of intravenous ciprofloxacin regimens, and thus administered doses were > 16% below the intended dose. Dosing accuracy of oral suspensions was impaired by lack of instructions for reconstitution, volume indicators, and/or dosing devices. Adult-dose tablets were split without/beyond scoring lines in 84.4% (27/32) of tablets. Poor availability and affordability of age-appropriate oral formulations contributed to low proportions of intravenous-to-oral switch (33.3% (79/237) of non-typhi Salmonella patients). Other quality issues included poor packaging, nonhomogeneous suspensions, and unsafe water for reconstitution. In conclusion, poor antibiotic products (no age-appropriate formulations, poor quality and access), processes (delayed prescription/administration, missed doses), and practices (inaccurate doses, [bio]safety risks) must be urgently addressed to improve pediatric antibiotic treatment.

A genomic appraisal of invasive Salmonella Typhimurium and associated antibiotic resistance in sub-Saharan Africa.

Invasive non-typhoidal Salmonella (iNTS) disease manifesting as bloodstream infection with high mortality is responsible for a huge public health burden in sub-Saharan Africa. Salmonella enterica serovar Typhimurium (S. Typhimurium) is the main cause of iNTS disease in Africa. By analysing whole genome sequence data from 1303 S. Typhimurium isolates originating from 19 African countries and isolated between 1979 and 2017, here we show a thorough scaled appraisal of the population structure of iNTS disease caused by S. Typhimurium across many of Africa's most impacted countries. At least six invasive S. Typhimurium clades have already emerged, with ST313 lineage 2 or ST313-L2 driving the current pandemic. ST313-L2 likely emerged in the Democratic Republic of Congo around 1980 and further spread in the mid 1990s. We observed plasmid-borne as well as chromosomally encoded fluoroquinolone resistance underlying emergences of extensive-drug and pan-drug resistance. Our work provides an overview of the evolution of invasive S. Typhimurium disease, and can be exploited to target control measures.

Methicillin-Resistant Staphylococcus aureus Bloodstream Infections in Hospitalized Patients in Peru.

There is a knowledge gap in the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) causing bloodstream infections (BSIs) in Peru. Through a surveillance study in 13 hospitals of 10 Peruvian regions (2017-2019), we assessed the proportion of MRSA among S. aureus BSIs as well as the molecular typing of the isolates. A total of 166 S. aureus isolates were collected, and 36.1% of them were MRSA. Of note, MRSA isolates with phenotypic and genetic characteristics of the hospital-associated Chilean-Cordobes clone (multidrug-resistant SCCmec I, non-Panton-Valentine leukocidin [PVL] producers) were most commonly found (70%), five isolates with genetic characteristics of community-associated MRSA (CA-MRSA)-SCCmec IV, PVL-producer-(8.3%) were seen in three separate regions. These results demonstrate that hospital-associated MRSA is the most frequent MRSA found in patients with BSIs in Peru. They also show the emergence of S. aureus with genetic characteristics of CA-MRSA. Further studies are needed to evaluate the extension of CA-MRSA dissemination in Peru.

Prevalence of Antimicrobial Resistance in Gram-Negative Bacteria Bloodstream Infections in Peru and Associated Outcomes: VIRAPERU Study.

Surveillance of antimicrobial resistance among gram-negative bacteria (GNB) is of critical importance, but data for Peru are not available. To fill this gap, a non-interventional hospital-based surveillance study was conducted in 15 hospitals across Peru from July 2017 to October 2019. Consecutive unique blood culture isolates of key GNB (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter spp.) recovered from hospitalized patients were collected for centralized antimicrobial susceptibility testing, along with linked epidemiological and clinical data. A total of 449 isolates were included in the analysis. Resistance to third-generation cephalosporins (3GCs) was present in 266 (59.2%) GNB isolates. Among E. coli (n = 199), 68.3% showed 3GC resistance (i.e., above the median ratio for low- and middle-income countries in 2020 for this sustainable development goal indicator). Carbapenem resistance was present in 74 (16.5%) GNB isolates, with wide variation among species (0% in E. coli, 11.0% in K. pneumoniae, 37.0% in P. aeruginosa, and 60.8% in Acinetobacter spp. isolates). Co-resistance to carbapenems and colistin was found in seven (1.6%) GNB isolates. Empiric treatment covered the causative GNB in 63.3% of 215 cases. The in-hospital case fatality ratio was 33.3% (92/276). Pseudomonas aeruginosa species and carbapenem resistance were associated with higher risk of in-hospital death. In conclusion, an important proportion of bloodstream infections in Peru are caused by highly resistant GNB and are associated with high in-hospital mortality.

Growth of Gram-Negative Bacteria in Antiseptics, Disinfectants and Hand Hygiene Products in Two Tertiary Care Hospitals in West Africa-A Cross-Sectional Survey.

Antiseptics, disinfectants, and hand hygiene products can act as reservoirs of Gram-negative bacteria causing healthcare-associated infections. This problem is rarely documented in low- and middle-income countries, particularly in sub-Saharan Africa. In a cross-sectional survey, we assessed the bacterial contamination of antiseptics, disinfectants, and hand hygiene products in two university hospitals in Burkina Faso and Benin. During ward visits and staff interviews, in-use products were cultured for the presence of Gram-negative bacteria. The growth of Gram-negative bacteria was absent or rare in alcohol-based products, povidone iodine, and Dakin solution. Contamination was highest (73.9% (51/69)) for liquid soap products (versus antiseptic/disinfectants (4.5%, 7/157) (p < 0.0001)), mostly used in high-risk areas and associated with high total bacterial counts (>10,000 colony-forming units/mL). Contaminating flora (105 isolates) included Enterobacterales and the Vibrio non-cholerae/Aeromonas group (17.1%) and non-fermentative Gram-negative rods (82.8%). Multidrug resistance was present among 9/16 Enterobacterales (Klebsiella and Enterobacter spp.) and 3/12 Acinetobacter spp., including carbapenem resistance (Acinetobacter baumannii: NDM, Pseudomonas stutzeri: VIM). The risk factors for contamination included the type of product (cleaning grade and in-house prepared liquid soap), use of recycled disposable containers and soft drink bottles, absence of labeling, topping-up of containers, dilution with tap water (pharmacy and ward), and poor-quality management (procurement, stock management, expiry dates, and period after opening).

A global genomic analysis of Salmonella Concord reveals lineages with high antimicrobial resistance in Ethiopia.

Antimicrobial resistant Salmonella enterica serovar Concord (S. Concord) is known to cause severe gastrointestinal and bloodstream infections in patients from Ethiopia and Ethiopian adoptees, and occasional records exist of S. Concord linked to other countries. The evolution and geographical distribution of S. Concord remained unclear. Here, we provide a genomic overview of the population structure and antimicrobial resistance (AMR) of S. Concord by analysing genomes from 284 historical and contemporary isolates obtained between 1944 and 2022 across the globe. We demonstrate that S. Concord is a polyphyletic serovar distributed among three Salmonella super-lineages. Super-lineage A is composed of eight S. Concord lineages, of which four are associated with multiple countries and low levels of AMR. Other lineages are restricted to Ethiopia and horizontally acquired resistance to most antimicrobials used for treating invasive Salmonella infections in low- and middle-income countries. By reconstructing complete genomes for 10 representative strains, we demonstrate the presence of AMR markers integrated in structurally diverse IncHI2 and IncA/C2 plasmids, and/or the chromosome. Molecular surveillance of pathogens such as S. Concord supports the understanding of AMR and the multi-sector response to the global AMR threat. This study provides a comprehensive baseline data set essential for future molecular surveillance.

Salmonella Typhi whole genome sequencing in Rwanda shows a diverse historical population with recent introduction of haplotype H58.

Salmonella enterica serovar Typhi (S. Typhi) is the cause of typhoid fever, presenting high rates of morbidity and mortality in low- and middle-income countries. The H58 haplotype shows high levels of antimicrobial resistance (AMR) and is the dominant S. Typhi haplotype in endemic areas of Asia and East sub-Saharan Africa. The situation in Rwanda is currently unknown and therefore to reveal the genetic diversity and AMR of S. Typhi in Rwanda, 25 historical (1984-1985) and 26 recent (2010-2018) isolates from Rwanda were analysed using whole genome sequencing (WGS). WGS was locally implemented using Illumina MiniSeq and web-based analysis tools, thereafter complemented with bioinformatic approaches for more in-depth analyses. Whereas historical S. Typhi isolates were found to be fully susceptible to antimicrobials and show a diversity of genotypes, i.e 2.2.2, 2.5, 3.3.1 and 4.1; the recent isolates showed high AMR rates and were predominantly associated with genotype 4.3.1.2 (H58, 22/26; 84,6%), possibly resulting from a single introduction in Rwanda from South Asia before 2010. We identified practical challenges for the use of WGS in endemic regions, including a high cost for shipment of molecular reagents and lack of high-end computational infrastructure for the analyses, but also identified WGS to be feasible in the studied setting and giving opportunity for synergy with other programs.

Characterization of Typhoid Intestinal Perforation in Africa: Results From the Severe Typhoid Fever Surveillance in Africa Program.

Background: Typhoid intestinal perforation (TIP) remains the most serious complication of typhoid fever. In many countries, the diagnosis of TIP relies on intraoperative identification, as blood culture and pathology capacity remain limited. As a result, many cases of TIP may not be reported as typhoid. This study demonstrates the burden of TIP in sites in Burkina Faso, Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria. Methods: Patients with clinical suspicion of nontraumatic intestinal perforation were enrolled and demographic details, clinical findings, surgical records, blood cultures, tissue biopsies, and peritoneal fluid were collected. Participants were then classified as having confirmed TIP, probable TIP, possible TIP, or clinical intestinal perforation based on surgical descriptions and cultures. Results: A total of 608 participants were investigated for nontraumatic intestinal perforation; 214 (35%) participants had surgically-confirmed TIP and 33 participants (5%) had culture-confirmed typhoid. The overall proportion of blood or surgical site Salmonella enterica subspecies enterica serovar Typhi positivity in surgically verified TIP cases was 10.3%. TIP was high in children aged 5-14 years in DRC, Ghana, and Nigeria. We provide evidence for correlation between monthly case counts of S. Typhi and the occurrence of intestinal perforation. Conclusions: Low S. Typhi culture positivity rates, as well as a lack of blood and tissue culture capability in many regions where typhoid remains endemic, significantly underestimate the true burden of typhoid fever. The occurrence of TIP may indicate underlying typhoid burden, particularly in countries with limited culture capability.

Coherence of output gaps in the euro area: The impact of the COVID-19 shock.

Using the measures proposed by Mink et al. (2012), we reexamine the coherence of business cycles in the euro area using a long sample period. We also analyze the impact of the COVID-19 pandemic on business cycle coherence and examine whether our measures for business cycle coherence indicate a core versus periphery within EMU. Our results suggest that business cycle coherence did not increase monotonically. The COVID-19 pandemic made that the signs of the output gaps of euro area countries became more similar, but we find large differences in the amplitude of the output gaps across countries.

Not recommended fixed-dose antibiotic combinations in low- and middle-income countries - the example of Tanzania.

BACKGROUND: Fixed-dose combinations (FDC) are medicine formulations that combine two or more ingredients in fixed ratios in a single dose form. Although advantageous in tuberculosis and malaria (efficacy, adherence, protection against resistance), only a few antibiotic FDC (FDC-AB) have been developed along full microbiological, pharmacological and clinical validation and safety studies. The World Health Organization (WHO) database of Access, Watch and Reserve (AWaRe) antibiotics contains, since 2021, a list of "Not Recommended" FDC-AB (n = 103) which are rejected for use in clinical practice. BODY: The share of non-recommended FDC-AB in global antimicrobial use (2000-2015) was < 3% but substantially higher in middle income countries. The share increases over time, but recent data particular concerning sub-Saharan Africa are rare. Along three non-recommended FDC-AB listed in the Tanzanian National Essential Medicine List (ampicillin-cloxacillin, flucloxacillin-amoxicillin and ceftriaxone-sulbactam) we discuss the concerns and reasons behind use of these products. Non-recommended FDC-AB have poor rationale (ratios of both ingredients), lack evidence of efficacy (pharmacological, microbiological and clinical), have difficulties in dosing (underdosing of the single ingredients, absence of pediatric dosing) and risks of safety (additive toxicity). They are expected to fuel antimicrobial resistance (unnecessary broad spectrum coverage) and are incompatible with antimicrobial stewardship. The specific context of low- and middle-income countries contributes to their increased use: at the side of prescriber and supplier are the lack of diagnostics, poor training in antibiotic prescribing, patients' preferences, role-model of senior prescribers and pharmaceutical promotion. International market mechanisms include economic motivation for development, branding and promotion, poor access to the single antibiotic forms and weak national regulatory capacity. CONCLUSION AND IMPLICATIONS: There is an urgent need for monitoring consumption of non-recommended FDC-AB in low- and middle-income countries, particular in Sub-Saharan Africa. A multinational and multisectoral antimicrobial stewardship strategy is needed in order to abolish the use of non-recommended FDC-AB.

Health itinerary-related survival of children under-five with severe malaria or bloodstream infection, DR Congo.

BACKGROUND: Prompt appropriate treatment reduces mortality of severe febrile illness in sub-Saharan Africa. We studied the health itinerary of children under-five admitted to the hospital with severe febrile illness in a setting endemic for Plasmodium falciparum (Pf) malaria and invasive non-typhoidal Salmonella infections, identified delaying factors and assessed their associations with in-hospital death. METHODOLOGY: Health itinerary data of this cohort study were collected during 6 months by interviewing caretakers of children (>28 days - <5 years) admitted with suspected bloodstream infection to Kisantu district hospital, DR Congo. The cohort was followed until discharge to assess in-hospital death. PRINCIPAL FINDINGS: From 784 enrolled children, 36.1% were admitted >3 days after fever onset. This long health itinerary was more frequent in children with bacterial bloodstream infection (52.9% (63/119)) than in children with severe Pf malaria (31.0% (97/313)). Long health itinerary was associated with in-hospital death (OR = 2.1, p = 0.007) and two thirds of deaths occurred during the first 3 days of admission. Case fatality was higher in bloodstream infection (22.8% (26/114)) compared to severe Pf malaria (2.6%, 8/309). Bloodstream infections were mainly (74.8% (89/119)) caused by non-typhoidal Salmonella. Bloodstream infections occurred in 20/43 children who died in-hospital before possible enrolment and non-typhoidal Salmonella caused 16 out of these 20 bloodstream infections. Delaying factors associated with in-hospital death were consulting traditional, private and/or multiple providers, rural residence, prehospital intravenous therapy, and prehospital overnight stays. Use of antibiotics reserved for hospital use, intravenous therapy and prehospital overnight stays were most frequent in the private sector. CONCLUSIONS: Long health itineraries delayed appropriate treatment of bloodstream infections in children under-five and were associated with increased in-hospital mortality. Non-typhoidal Salmonella were the main cause of bloodstream infection and had high case fatality. TRIAL REGISTRATION: NCT04289688.

Phylogenomic investigation of an outbreak of fluoroquinolone-resistant Salmonella enterica subsp. enterica serovar Paratyphi A in Phnom Penh, Cambodia.

In early 2020, the Medical Biology Laboratory of the Pasteur Institute of Cambodia isolated an unusually high number of fluoroquinolone-resistant Salmonella enterica subspecies enterica serovar Paratyphi A strains during its routine bacteriological surveillance activities in Phnom Penh, Cambodia. A public-health investigation was supported by genome sequencing of these Paratyphi A strains to gain insights into the genetic diversity and population structure of a potential outbreak of fluoroquinolone-resistant paratyphoid fever. Comparative genomic and phylodynamic analyses revealed the 2020 strains were descended from a previously described 2013-2015 outbreak of Paratyphi A infections. Our analysis showed sub-lineage 2.3.1 had remained largely susceptible to fluoroquinolone drugs until 2015, but acquired chromosomal resistance to these drugs during six separate events between late 2012 and 2015. The emergence of fluoroquinolone resistance was rapidly followed by the replacement of the original susceptible Paratyphi A population, which led to a dramatic increase of fluoroquinolone-resistant blood-culture-confirmed cases in subsequent years (2016-2020). The rapid acquisition of resistance-conferring mutations in the Paratyphi A population over a 3 year period is suggestive of a strong selective pressure on that population, likely linked with fluoroquinolone use. In turn, emergence of fluoroquinolone resistance has led to increased use of extended-spectrum cephalosporins like ceftriaxone that are becoming the drug of choice for empirical treatment of paratyphoid fever in Cambodia.

Antibiotic use by poultry farmers in Kiambu County, Kenya: exploring practices and drivers of potential overuse.

BACKGROUND: Antibiotic resistance is a global concern threatening achievements in health care since the discovery of antibiotics. In Kenya, this topic remains understudied in a context of rising demand for livestock products, intensification and the concomitant increase in antibiotic use. Our study investigates drivers and practices of antibiotic use in poultry farming. The study was conducted in Kiambu County, Kenya. METHODS: A qualitative research methodology was employed: fourteen key informant interviews, twenty in-depth interviews, and four focus group discussions were undertaken. The interviews were semi-structured. Themes and subthemes from the interviews were generated through inductive analysis. FINDINGS: Of the farmers interviewed, sixty eight percent were female, thirty three percent of the sampled farmers could not read, and the majority (eight five percent) of farmers had reared poultry for at least ten years. Research findings showed that farmers extensively used antibiotics. Antibiotic use was influenced by factors such as high disease burden, access to medicines and economic pressure. Common practices included prophylactic use, use of antibiotics to enhance production, self-prescription use, use of combination antibiotics (A combination antibiotic is one in which two or more antibiotics are added together for additional therapeutic effect.), and antibiotics classified as critically important in human medicine. Key information sources for the farmers were agro- veterinary dispensers, sellers of day-old chicks, and peer-learning. External factors driving the inappropriate use of antibiotics included access to the antibiotics, influence by marketers such as sellers of day-old chicks, and branding. Use of antibiotics was also driven by economic factors among the farmers, sellers of day-old chicks and agro-veterinary dispensers. CONCLUSIONS: Our findings indicate widespread use of antibiotics among poultry farmers in our study site. The use of antibiotics is influenced by an interplay of issues at the farmers' level as well as broader social, economic and structural level factors. A multifaceted One Health approach focusing on regulatory frameworks, knowledge transfer, and research is required to promote stewardship and judicious use of antibiotics.

Presence of Gram-negative bacteria and Staphylococcus aureus on the skin of blood donors in the Democratic Republic of the Congo.

BACKGROUND: Skin bacteria may contaminate blood products but few data are available on sub-Saharan Africa (sSA). We assessed the presence of Gram-negative bacteria and Staphylococcus aureus on blood donor skin and evaluated skin antisepsis in the Democratic Republic of the Congo (DRC). STUDY DESIGN AND METHODS: Among blood donors at the National Blood Transfusion Center (NBTC) and at a rural hospital, the antecubital fossa skin of the non-disinfected arm (not used for blood collection) was swabbed (25cm2 surface) and cultured for total and Gram-negative bacterial counts. Bacteria were identified with MALDI-TOF and tested for antibiotic susceptibility by disk diffusion. For evaluation of the NBTC antisepsis procedure (i.e., ethanol 70%), the culture results of the disinfected arm (used for blood collection) were compared with those of the non-disinfected arm. RESULTS: Median total bacterial counts on 161 studied non-disinfected arms were 1065 Colony-Forming Units (CFU) per 25 cm2 , with 43.8% (70/160) of blood donors growing Gram-negative bacteria and 3.8% (6/159) Staphylococcus aureus (2/6 methicillin-resistant). Non-fermentative Gram-negative rods predominated (74/93 isolates, majority Pseudomonas spp., Acinetobacter spp.). Enterobacterales comprised 19/93 isolates (mostly Pantoea spp. and Enterobacter spp.), 5/19 were multidrug-resistant. In only two cases (1.9%, 2/108) the NBTC antisepsis procedure met the acceptance criterion of ≤2 CFU/25 cm2 . CONCLUSION: Skin bacterial counts and species among blood donors in DRC were similar to previously studied Caucasian populations, including cold-tolerating species and bacteria previously described in transfusion reactions. Prevention of contamination (e.g., antisepsis) needs further evaluation and customization to sSA.