Systematic Review and Meta-Analysis of the Occurrence of ESKAPE Bacteria Group in Dogs, and the Related Zoonotic Risk in Animal-Assisted Therapy, and in Animal-Assisted Activity in the Health Context

Animal-assisted interventions are widely implemented in different contexts worldwide. Particularly, animal-assisted therapies and animal-assisted activities are often implemented in hospitals, rehabilitation centers, and other health facilities. These interventions bring several benefits to patients but can also expose them to the risk of infection with potentially zoonotic agents. The dog is the main animal species involved used in these interventions. Therefore, we aimed at collecting data regarding the occurrence of the pathogens ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) in dogs, in order to draft guidelines concerning the possible monitoring of dogs involved in animal-assisted therapies and animal-assisted activities in healthcare facilities. We performed a literature search using the PRISMA guidelines to examine three databases: PubMed, Web of Science, and Scopus. Out of 2604 records found, 52 papers were identified as eligible for inclusion in the review/meta-analysis. Sixteen papers reported data on E. faecium; 16 on S. aureus; nine on K. pneumoniae; four on A. baumannii; eight on P. aeruginosa; and six on Enterobacter spp. This work will contribute to increased awareness to the potential zoonotic risks posed by the involvement of dogs in animal-assisted therapies, and animal-assisted activities in healthcare facilities

Molecular epidemiology of antibiotic resistant ESKAPE pathogens isolated from public sector hospitals in uMgungundlovu District, KwaZulu-Natal, South Africa.

Doctor of Philosophy in Medical Microbiology. University of KwaZulu-Natal. Durban, 2017.Multi-drug resistant Enterococcus faecium, staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp termed ESKAPE pathogens are commonly implicated in difficult-to-treat infectious diseases in developed and developing countries. The prevalence, risk factors, phenotypic and genotypic profiles including but not limited to clonal relatedness, genetic diversity, resistance and virulence associated with ESKAPE bacteria were investigated in carriage and clinical isolates from patients in a rural, district and an urban tertiary hospital in the public health sector in uMgungundlovu District, Kwazulu- Natal, South Africa. The overall carriage of MDR ESKAPE Gram-negative bacteria in both hospitals was 37.21%, 42.31% and 57.14% at admission, after 48 hours and at discharge, respectively. The prevalence of MDR ESKAPE Gram-negative bacteria in faecal carriage (46%) was higher than clinical samples (28%) and colonization was mainly associated with referral from the district to the tertiary hospital with high statistical significance (OR: 14.40, 95% CI 0.98-210.84). blaCTX-M-group-9, blaCTX-M-group-1 and blaSHV were the main resistance genes identified. Similarly, the overall prevalence of faecal VRE carriage was 53% with patients at the district hospital being more likely to be colonized by VRE at admission (44%), after 48 hours (64%) and discharge (100%) than those of the tertiary level. Fifteen (39%) E. faecium and 23 (61%) E. faecalis, were detected and displayed high level of antibiotic resistance. Extensive genetic diversity of E. faecalis and E. faecium and clonal dissemination of various lineages were observed across wards and within hospitals. The high levels of resistance in S. aureus were attributed to the multi-drug resistant efflux pumps mepA, mexE, AcrB, MATE, qac and qacA. Whole genome analysis revealed that the circulating S. aureus isolates belonged to the extremely virulent ST121 clone that harboured a total of 18 virulence genes. The high prevalence, genetic diversity and virulence of antibiotic-resistant ESKAPE bacteria elucidated in this study necessitates routine screening and surveillance in communities and hospitals, stringent infection prevention and control measures and antibiotic stewardship to monitor epidemiological changes, to contain their spread and inform appropriate antibiotic treatment options respectively

Mobile genetic elements causing plasticity in E. faecium

The paper 3 of this thesis is not available in Munin. Paper 3: Sivertsen, A., Pedersen, T., Janice, J., Hegstad, K.: “The Enterococcus Cassette Chromosome: an SCCmec-like mobilisable element”. (Manuscript).I helseinstitusjoner vancomycin-resistente enterokokker en fryktet bakterie som kan lage alvorlig infeksjonssykdom i pasienter med dårlig immunforsvar, og er vanskelig å behandle. Avhandlingen fokuserer på vancomycin-resistente enterokokker (VRE), og hvordan disse bakteriene gjennom å overføre gener mellom hverandre kan utvikle resistens mot antibiotika. Vi har analysert to utbrudd av VRE i Sverige og i Norge, og har funnet at VRE kan være på vei til å bli et mer vanlig patogen i skandinaviske sykehus. Dagens diagnostiske verktøy er ikke i stand til å fange opp alle typer VRE. Dette har konsekvenser for både diagnostikk, resistensovervåkning og risiko for feilbehandling av svært syke pasienter. Nye gensekvenseringsteknologier kan forbedre denne type diagnostikk ved å kunne se på genotypen i tillegg, noe som er viktig da vancomycinresistensgener kan være tilstede i bakterien uten at bakterien har fenotype for dette. I begge utbruddene var diagnostikken utilfredsstillende, da bakterien kunne bli tolket som følsom. I det ene utbruddet utviklet VRE resistens under behandling på grunn av for eksempel mobile genetiske elementer kalt IS-elementer hoppet rundt i vancomycinresistensgenene og påvirket uttrykket deres. Resultater fra doktorgraden har allerede ført til en endring i rådgiving på diagnostikk av VRE hos svært syke pasienter. Vi har også funnet at mobile genetiske elementer (MGE), DNA-et som flytter seg mellom bakterier, har en stor evne til å rekombinere seg og danne varianter med ulikt geninnhold. Inntil nå har strukturen på disse elementene vært vanskelig å rekonstruere. Dermed har betydningen av MGE’er for bakterienes resistenspotensiale vært vanskelig å vurdere. Man kan observere at disse elementene oppfører seg som Babushka-dukker ved å koble seg på hverandre. Såkalte long-read sekvenseringsmetoder er i stand til å rekonstruere strukturen på slike elementer, og det at de kun har vært kommersielt tilgjengelige de siste 3-4 år gjør at der fortsatt er mye å lære om mobile genetiske elementer og deres innvirkning på resistensutvikingen av bakterier

Análisis de elementos genéticos móviles en "Enterococcus faecium": coste biológico e impacto en la diversificación clonal

La prevalencia de infecciones hospitalarias causadas por especies del género Enterococcus ha sido baja desde su descripción como patógenos oportunistas al inicio del siglo XX, hasta finales de los años 70s, coincidiendo con la aparición de las primeras cepas resistentes a antibióticos. La especie Enterococcus faecium es actualmente uno de los principales patógenos nosocomiales debido en parte a la alta prevalencia de cepas resistentes a ampicilina y vancomicina. La estructura poblacional de E. faecium ha sido analizada mayoritariamente considerando cepas resistentes a antibióticos y de origen hospitalario pero se desconoce su diversidad en individuos no hospitalizados o de diferentes edades. El conocimiento de los elementos genéticos móviles (EGM) que facilitan la transferencia de genes de resistencia a antibióticos entre clones de la misma o diferente especie, principalmente vancomicina (una de las ultimas opciones terapéuticas para el tratamiento de bacterias Gram positivas multi resistentes a los antibióticos), es también muy reducido. El principal objetivo de esta tesis de doctorado es determinar la influencia en la estructura poblacional y evolvabilidad de E. faecium de los determinantes de resistencia y de los EGM que facilitan su adquisición, transferencia y persistencia. Los capítulos 1 y 2 consisten en el análisis Bayesiano (BAPS) de los datos de MLST procedentes de heces de pacientes hospitalizados y no-hospitalizados de diferentes edades y de aislados de E. faecium causantes de bacteriemias. Este análisis permitió separar los linajes clonales que constituyen el complejo clonal (CC)17 que había sido identificado con la aplicación de metodologías previas en tres líneas clonales de diferente origen, ST18, ST17 y ST78. El aislamiento de cepas de E. faecium pertenecientes a grupos BAPS asociados con la flora comensal humana (BAPS 1 y BAPS 3.3b) sugiere la frecuente adquisición endógena a partir de la microbiota intestinal de las bacteriemias causadas por E. faecium, bien forma directa o a través de infecciones en territorios cercanos (infección urinaria, infección abdominal). Los cambios ocurridos en la microbiota intestinal de los pacientes hospitalizados debido a factores asociados al hospedador (edad) o diferentes presiones selectivas en el medio hospitalario, habrían facilitado la selección (aumento de la densidad poblacional) y la consecuente expansión de las poblaciones de clones de E. faecium resistentes a antibióticos y aumentando por tanto las oportunidades de infección y transmisión de E. faecium..

Characterisation of multidrug resistant Klebsiella pneumoniae and Enterococcus faecium isolates by spectroscopic and genotypic method

Karlova Univerzita v Praze Farmaceutická fakulta v Hradci Králové Katedra farmakologie a toxikologie Student: Jan Bavlovič Školitelé: PharmDr. Lukáš Červený, Ph.D. Prof. Doutora Luísa Peixe Konzultanti: Doutora Ângela Novais Doutora Ana Freitas Název diplomové práce: Charakterizace multirezistentních izolátů Klebsiella pneumoniae a Enterococcus faecium spektroskopickými a genotypickými metodami Stále se zvyšující antimikrobiální rezistence je v současné době celosvětovým problémem. Mezi významné metody charakterizace antimikrobiální rezistence patří tradičně genomické postupy. Cílem této studie bylo zhodnotit potenciál metody Fourier transform infrared spectroscopy se zeslabeným kompletním odrazem (FTIR-ATR) pro identifikaci multirezistentních karbapenemasu produkujících K. pneumoniae a E. faecium izolátů. Analyzovali jsme 20 klinických K. pneumoniae izolátů získaných z různých laboratoří v Portugalsku v období od března 2014 do září 2015 a 143 dříve popsané vankomycin-rezistentní E. faecium izoláty získaných od lidí, zvířat a životního prostředí v 26 zemích mezi lety 1992 a 2015. Izoláty byly primárně charakterizovány genotypovými metodami, včetně testování antimikrobiální citlivosti, detekce karbapenemáz a betalaktamáz s rozšířeným spektrem (ESBLs), identifikace odolnosti vůči antibiotikům...Charles University in Prague Faculty of Pharmacy Hradec Králové Department of Pharmacology and Toxicology Student: Jan Bavlovič Supervisors: PharmDr. Lukáš Červený, Ph.D. Prof. Doutora Luísa Peixe Co-advisors: Doutora Ângela Novais Doutora Ana Freitas Title: Characterisation of multidrug resistant Klebsiella pneumoniae and Enterococcus faecium isolates by spectroscopic and genotypic methods. Ever increasing antimicrobial resistance is currently a worldwide problem, traditionally addressed by DNA-based approaches. This study aimed to evaluate the potential of Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR) for the characterization of multidrug resistant carbapenemase-producing K. pneumoniae and E. faecium isolates. We analysed 20 clinical K. pneumoniae isolates obtained from different community laboratories from Portugal between March 2014 and September 2015 and 143 previously characterized vancomycin-resistant E. faecium isolates obtained from humans, animals, and the environment in 26 countries between 1992 and 2015. Isolates were primarily characterized by genotypic methods including antimicrobial susceptibility testing, detection of carbapenemases and extended-spectrum β-lactamases (ESBLs), identification of antibiotic resistance coding transposons (Tn) and...Katedra farmakologie a toxikologieDepartment of Pharmacology and ToxicologyFaculty of Pharmacy in Hradec KrálovéFarmaceutická fakulta v Hradci Králov

Karakterisering av fekale melkesyrebakterier isolert fra etiopiske spedbarn : bakteriocin produksjon og antibiotika sensitivitet

In this thesis lactic acid bacteria (LAB) were isolated from fecal samples of healthy Ethiopian infants, identified to species level, screened for bacteriocin production and tested for antibiotic susceptibility. Enterococci were also screened for the production of cytolysin and gelatinase. Among 150 LAB isolates, 81 lactobacilli, 54 enterococci and 15 streptococci were identified by 16S rRNA gene sequence analysis. Most of the lactobacilli were obtained from breast-fed infants, while most of the enterococci and the streptococci were from mixed-fed infants. Lactobacillus fermentum, Enterococcus avium and Enterococcus faecalis were the most frequently isolated species. About 10% of the LAB produced bacteriocins. The majority of the producers were enterococci, indicating a higher prevalence of bacteriocin production in enterococci compared to lactobacilli. For some of the bacteriocins, the producers were found to occur in high numbers in fecal samples, suggesting that bacteriocin renders the producers the capacity to outcompete other bacteria. Six new bacteriocins were detected, two of which showed strong activity against pathogenic bacteria and thus were purified and characterized at biochemical and genetic levels. These are a 4288.2 Da pediocin-like bacteriocin (avicin A) and a 3466.55 Da trypsin-resistant, nisin-like lantibiotic bacteriocin (salivaricin D). Avicin A, produced by E. avium strains, is active against the food-borne pathogen Listeria monocytogenes. Sequence analysis showed that avicin A gene was found on a 7 Kb locus that contains genes encoding bacteriocin synthesis, export, immunity and regulation. Avicin A is similar to mundticin KS and enterocin CRL 35, but its locus resembles that of sakacin X. We showed that the production of avicin A is inducible and regulated by a quorum sensing regulatory system. Salivaricin D is produced by S. salivarius isolates which appeared to account for over 60% of the fecal LAB flora of an infant. It is active against the important pathogens S. pyogenes and S. pneumoniae, which cause a wide variety of diseases. Sequence analysis showed that salivaricin D is located on a 16.5 kb locus that consists of genes responsible for its synthesis, modification, export, processing, immunity and regulation. The primary structure and locus of salivaricin D is similar to that of nisin Q. Avicin A and salivaricin D may be potential chemotherapeutic agents that might control infections due to the respective pathogens they inhibit. Moreover, the producing strains may be used as potential probiotic strains in appropriate settings. Avicin A and salivaricin D share some common features that may increase the chance of the two bacteriocins or their producers to be used as chemical or biological control agents (probiotics), respectively. Different patterns of antibiotic susceptibility were observed among the LAB. Nearly all lactobacilli were sensitive to chloramphenicol, erythromycin and tetracycline. Most lactobacilli were resistant to aminoglycosides and vancomycin which is intrinsic. Many enterococci showed resistance mainly to tetracycline which might have been acquired, but ampicillin and vancomycin resistance was almost absent. Multidrug resistance as well as resistance to high level of aminoglycosides was common among the E. faecalis and E. faecium strains. The streptococci were generally susceptible to the antibiotics. These results suggest that transferrable antibiotic resistance is common among the enterococci, but not among the lactobacilli and streptococci. A very low prevalence of cytolysin and gelatinase production was observed among the enterococci, suggesting that infant enterococci may not cause diseases.I denne avhandlingen ble melkesyrebakterier (LAB) isolert fra fekale prøver av friske etiopiske spedbarn, identifisert til artsnivå, screenet for bacteriocin produksjon og testet for sensitivitet av antibiotika. Enterokokker ble også screenet for produksjon av cytolysin og gelatinase. Blant 150 LAB isolater, ble 81 laktobasiller, 54 enterokokker og 15 streptokokker identifisert ved 16S rRNA gensekvensanalyse. De fleste av laktobasiller ble isolert fra diende spedbarn, mens det meste av enterokokker og streptokokker var fra blandings-matede spedbarn. Rundt 10% av LAB produserte bakteriociner. Flertallet av produsentene var enterokokker, noe som indikerer en høyere prevalens av bacteriocinproduksjon i enterokokker sammenlignet med laktobasiller. For noen av bakteriocinene, ble produsentene funnet oftere i høye tall i fecal prøver, som kan tyde på at bacteriociner øker produsentenes kapasitet til å utkonkurrere andre bakterier. Seks nye bakteriociner ble oppdaget, to av dem viste sterk aktivitet mot sykdomsfremkallende/patogene bakterier og bel derfor renset og karakterisert biokjemisk og genetisk. Disse er et 4288,2 Da pediocin-lignende bacteriocin (avicin A) og en 3466,7 Da trypsinresistent, Nisin-lignende lantibiotisk bacteriocin (salivaricin D). Avicin A, produsert av E. avium stammer, er aktivt mot mat-borne patogen Listeria monocytogenes. Sekvensanalyse viste at avicin A lokuset er 7,5 Kb og inneholder gener som koder for produksjon, eksport, immunitet og regulering av avicin A. Avicin A er lik mundticin KS og enterocin CRL 35, men dens locus minner om Sakacin X. Vi viste at produksjonen av avicin A er induserbar og regulert av et quorum sensing system. Salivaricin D er produsert av S. salivarius isolater som utgjorde over 60% av fekal LAB flora hos et spedbarn. Den er aktiv mot viktige patogener inkludert S. pyogenes og S. pneumoniae som forårsaker en rekke sykdommer. Sekvensanalysen viste at salivaricin D ligger på et 16,5 kb locus som består av gener ansvarlig for produksjon, modifikasjon, eksport, prosessering, immunitet og regulering. Primærstrukturen og av salivaricin D og genlocuset ligner Nisin Q. Avicin A og salivaricin D er potensielle kjemoterapeutika som kan kontrollere infeksjoner av respektive patogener de ble vist å hemme. Videre kan de produserende stammene potensielt brukes som probiotiske stammer i visse betingelser. Avicin A og salivaricin D har noen felles funksjoner som kan fremme muligheten for at de to bakteriocinene eller deres produsenter kan brukes som henholdsvis kjemiske eller biologiske kontrollagenser (probiotika). Ulike mønstre av mottakelighet for antibiotika ble observert blant LAB. Nesten alle lactobacilli var følsomme for kloramfenikol, erytromycin og tetracyklin. De fleste lactobaciller var iboenderesistente mot aminoglykosider og vankomycin. Mange enterokokker viste ervervet tetracyklinresistens, mens resistens mot ampicillin og vankomycin var nesten fraværende. Multiresistens samt resistens mot høye nivåer av aminoglykosider var vanlig blant E. faecalis og E. faecium stammer. Streptokokker var generelt sett antibiotikasensitive. Disse resultatene tyder på at overførbar antibiotikaresistens er utbredt blant enterokokker, men ikke blant laktobasiller og streptokokker. En svært lav prevalens av cytolysin og gelatinase produksjon ble observert blant enterokokker, som kan tyde på at enterokokker fra spedbarn ikke forårsaker sykdommer

Genomic analysis of diverse bacterial pathogens

Bacterial pathogens have been a historical scourge for the entirety of human existence but have been significantly thwarted since the 20th century due to the development of antibiotics. However, owing to the large selection pressure of antibiotics on bacterial populations, phenotypic antibiotic resistance from the development of vertically transmitted mutations and horizontally acquired antibiotic resistance genes (ARGs) is increasing. The sum has produced multidrug resistant organisms (MDROs) which have extremely limited treatment options. Epidemiological studies have determined that carbapenem resistant Enterobacteriaceae (CRE), Acinetobacter baumannii, and vancomycin resistant Enterococcus (VRE) are some of the most problematic MDRO infections. The advent of cost-effective and accurate next-generation sequencing has resulted in a proliferation of bacterial genomes available. ARGs, antibiotic resistance conferring single nucleotide polymorphism (SNPs), and virulence genes can be identified within an assembled genome by comparison to known databases. The combination of the genetic information encoded within the genome of an isolate along with metadata related to important phenotypes or clinical context can be used to identify trends in ARG carriage, evolution over time, and viii differences in gene burden. This information can also be used in understanding the effects of antibiotic treatment on multi organism infections such as bacterial vaginosis. My thesis intends to investigate features related to natural populations of bacterial isolates in the Enterobacteriaceae family and Acinetobacter baumannii in Chapters 2, 3, 4 and the Gram-positive organisms Enterococcus faecium, Gardnerella, and Corynebacterium in Chapters 5, 6, and 7. In Chapter 2 we identify the carbapenem resistance gene blaIMP-27 in a clinical isolate of carbapenem resistance Providencia rettgeri. We then acquired two blaIMP-27 bearing Proteus mirabilis and determine that one isolate (PM187) also has it on a plasmid. We were able to completely close the blaIMP-27 bearing plasmids pPR1 and pPM187 and determine that the local genetic context was similar but the background of the plasmids were different. In Chapter 3 we collect a cohort of longitudinally antibiotic resistant organisms recovered from hospital surfaces in the United States and Pakistan. We compare the phenotypic identification with the genomic identification to determine that several isolates represent novel taxonomic groups, we identify a severe degree of phenotypic antibiotic resistance in the collected important human pathogens and elucidate a network of ARGs common amongst the bacteria. Importantly, we demonstrate that E. faecium and A. baumannii co-occur greater than predicted by chance a lone and that laboratory strains of these organisms are capable of forming synergistic growth in biofilms. In Chapter 4 we collect a cohort of Klebsiella variicola from Washington University and use whole genome sequencing to determine the population structure of all publicly available K. variicola genomes and identify genes relevant for infection related phenotypes. We show that these differences may have a functional consequence as some K. variicola strains can be more competent uropathogens than Klebsiella pneumoniae. In Chapter 5 we compare linezolid resistance mechanisms within a cohort to VRE from the United States and Pakistan to determine that all of the US isolates were resistant due to SNPs in the 23S rRNA sequence, but the Pakistan isolates all had acquired ARGs. Two of six these ARGs were the limited scope efflux pumps optrA and poxtA but the other ARGs are novel variants of the cfr family. In Chapter 6 we analyze a set of publicly available Gardnerella vaginalis genomes and metatranscriptomes of women with bacterial vaginosis to determine that what is commonly considered a single species can be interpreted as 9 different species with differences in accessory genome function and varying presence in bacterial vaginosis cases. Different genomospecies are present at varying abundance and putative virulence genes have high expression values during infection. Finally, in chapter 7 we determine the effects of acquired daptomycin resistance on the biology of Corynebacterium striatum. In summation this work provides novel insights on the relatedness of important human pathogens to one another and the content of their genes relevant toward infection across a wide range of species

The impact of inpatient bloodstream infections caused by antibiotic-resistant bacteria in low- and middle-income countries: A systematic review and meta-analysis.

BACKGROUND: Bloodstream infections (BSIs) produced by antibiotic-resistant bacteria (ARB) cause a substantial disease burden worldwide. However, most estimates come from high-income settings and thus are not globally representative. This study quantifies the excess mortality, length of hospital stay (LOS), intensive care unit (ICU) admission, and economic costs associated with ARB BSIs, compared to antibiotic-sensitive bacteria (ASB), among adult inpatients in low- and middle-income countries (LMICs). METHODS AND FINDINGS: We conducted a systematic review by searching 4 medical databases (PubMed, SCIELO, Scopus, and WHO's Global Index Medicus; initial search n = 13,012 from their inception to August 1, 2022). We only included quantitative studies. Our final sample consisted of n = 109 articles, excluding studies from high-income countries, without our outcomes of interest, or without a clear source of bloodstream infection. Crude mortality, ICU admission, and LOS were meta-analysed using the inverse variance heterogeneity model for the general and subgroup analyses including bacterial Gram type, family, and resistance type. For economic costs, direct medical costs per bed-day were sourced from WHO-CHOICE. Mortality costs were estimated based on productivity loss from years of potential life lost due to premature mortality. All costs were in 2020 USD. We assessed studies' quality and risk of publication bias using the MASTER framework. Multivariable meta-regressions were employed for the mortality and ICU admission outcomes only. Most included studies showed a significant increase in crude mortality (odds ratio (OR) 1.58, 95% CI [1.35 to 1.80], p < 0.001), total LOS (standardised mean difference "SMD" 0.49, 95% CI [0.20 to 0.78], p < 0.001), and ICU admission (OR 1.96, 95% CI [1.56 to 2.47], p < 0.001) for ARB versus ASB BSIs. Studies analysing Enterobacteriaceae, Acinetobacter baumanii, and Staphylococcus aureus in upper-middle-income countries from the African and Western Pacific regions showed the highest excess mortality, LOS, and ICU admission for ARB versus ASB BSIs per patient. Multivariable meta-regressions indicated that patients with resistant Acinetobacter baumanii BSIs had higher mortality odds when comparing ARB versus ASB BSI patients (OR 1.67, 95% CI [1.18 to 2.36], p 0.004). Excess direct medical costs were estimated at $12,442 (95$6,693 to $18,191]) for ARB versus ASB BSI per patient, with an average cost of$41,103 (95% CI [$30,931 to$51,274]) due to premature mortality. Limitations included the poor quality of some of the reviewed studies regarding the high risk of selective sampling or failure to adequately account for relevant confounders. CONCLUSIONS: We provide an overview of the impact ARB BSIs in limited resource settings derived from the existing literature. Drug resistance was associated with a substantial disease and economic burden in LMICs. Although, our results show wide heterogeneity between WHO regions, income groups, and pathogen-drug combinations. Overall, there is a paucity of BSI data from LMICs, which hinders implementation of country-specific policies and tracking of health progress