Antibiotic-Resistant Enteric ® Infections Sadia Shakoor, saws", James A. Palts-Mills, wo‘, Rumina Hasan, woes, 0° * = Antibiotic resisiance = Azitromycin + Salmon = Shigella = Gampylobacter * Diarthea * Enteric fever © OneHealin KEY POINTS. «+ Antibiotic resistance among diana! and enteric pathogena ia inceasing and spreading ‘lobally owing to convergence of multiple rik factors among populations. «Widespread ciproloxacn resistance among lata pathogens has rendered His t= Bote wtualy matectve in nfactous cares and entene favr syndromes i hih- burcen regions. + Azttromyein has emerge as an ffectve emptic eatment of enteric infections, except fr populatons with speci nk tctor, suchas men who have sex wih meni Shige fence regina. «+ Emergence of plasmidnorne extended spacina hea lactemases in entre fever isan ‘Samng development and needs urgent control measures ‘= Doveiopment and evaluation of pathogen specific vaccines is needed, folowed by sia. ‘ego implementation m higrbuden countres and rspne. However, the sneuld nat cisvac rom popultion vel measures of wale, santation, and hygiene IMpxoverent, ‘which hve wider benoit, irRoDUCTION Enteric infections claimad an estimated 1.7 milion lives in 2017 global, with the high- ‘est burden in low-income and middle-income countries (LMICs) and at extromes of ‘age.’ This estimate inckides systemic infections, that is, typhoid and paratyphoid, * Pathology and Laboratory Meine. Aga Khan University. Stam Road PO Box 3500, Karachi 74800, Pakistan," Pedi a Child Heath, Aga Khan Univesity Sturm Rood, PO {ox 3800, Karachi 74800, Pasta" Duson of infectious Diseases and inernational Health, Unversity of Vicgina, 200 Jeanette Lancaster Way. Chatlotlewile, VA 22903, USA + Departnent of Pathology and Laboratory Medicine, Ago Khan University, Stadium Rood, PO {Box 3500, Karachi 74800, Pakistan" Faculty of infectious and Topical Disease, London Shoo! fof Hygiene and Topical Medicina, Keppel Sueet, Bloomsbury London WCE TAL UR * conresponding author Department of Pathology and Laboratory Mediine, Agakhan Unive ‘ty Stam Rood, PO Box 350, Karachi 7480, Pakistan ‘Ema address: Rarinahasandaku edu Infect Dis cin W Am 33 2019) 105-1123 Itps/dot orf. 1016 sd 2018.05.007, thedniescom (89158207910 2019 Ever Inc A ights reserved. Dene Ammen i no epi Kove Chico i Fico Och 15,200 ES pal areal No laren poms Cgpge CN le ar A gla106, Shakoor et al {nd lyphoid alone clams hundreds of thousands of ves each year, most in Aska and ‘sub-Saharan Alfica” Although observed incidence and morality rom enteric infec tions are highest among children and those older than 70 years, the epidemiology is ‘changing,’ and risk factors other than age are emerging. As efforts continue to reduce ‘mocalty among chien, and to improve water, sanitation, and hygiene (WASH) mea ‘sures and universal access to health care, new challenges have emerged. Among these isthe rsoin rates of antimicrobial resistance (AMR) in localized andlor invasive sisease caused by enteric pathogens whereby antibiotics are absolute of rolative i= ications," such as Salmonella enterica serovars Typhi and Paratyph, Shigella spp, (Campylobacter spp, Vibrio cholerae, and diamneagenic Escherichia Col (DEC), nonty- ‘Bholdal salmoneliae (NTS), Clostraium dificte, Holcobactor pylon, Giardia spp, and Cryptosporidium spp. Emerging enteric infections reported by the Program for Montoring Emerging Dis- ceases (ProMED-mail) over the past 10 yoars @009-2019) have identified emerging resiatanca inthe fallowing pathogens: S enterica (both typhodal and nontyphoida), DEC, Shigeie spp. Campylobacter spp, and Vibrio spp.” Reports highlight the impor tance of infections in special populations and epidemiolegic modifies in high-risk (groups. Resistance also has been reported with increasing fraqueney in H pylori ‘Table 1 deserbes the most important enteric pathogens for whieh antimicrobial ther- apy can be required and outines pertinent phenotypic and genotypic AMR features, "sk factors, current treatment recommendations for resistant stains, and avalable ‘large proportion of emerging infections Is caused by drug-resistant bacteria owing to the survival beneft in enveonments contaminated with antibiotes and antibiotic residues. Enteric bacteria are naturally adapted to such survival and spread in !microbe-rich intestinal environments, and folowing continued shedding in fecal mat- ter, survval in sewage and “brown water." ‘Notably, emergence of extended-spectrum beta lactamase (ESBL) carrying Salmo- ‘lla Typhi (S Typhi in Pakistan,” and that of aziromycin-resisiant Shigola spp ‘mong men who have sex with mean (MSM) has narrowed treatment options. Wide ‘Spread ciprofloxacin resistance among all clarrheal and enteric pathogens has led to the ineffectiveness of this antibiotic in infectious diarhea and enteric. fe ver 97879858908 44 pylon presents a unique challenge with respect to Inreasing antidote resistance and ineffective treatment regimens leading to itrac- table gastrointestinal lnass, economic loss, and long-term morbidity." Drug resis- tance is rarely observed in vito in parasitic infections; however, clinical resistance and treatment failure have been reported.” ‘Athough pathogen-specif risk factors may be modifiable, and treatment and pre- ventive strategies may be used in areas with high burden, there are overarching fac tors at play that can be improved on to reduce the burden of enteric infections, and prevent the emergence of highly resistant phenotypes. FACTORS CONTRIBUTING TO THE EMERGENCE OF ANTIBIOTIC RESISTANT ENTERIC INFECTIONS. AMF. in enteric pathogens is largely acquired by horizontal gene transfer (HGT) ‘through exchange of resistance-determining mobile genetic elements (MGESs) catied ‘on plasmids or chromosomes of bacteria belonging to diferent taxonomic groupe.” ‘Such exchange occurs in natural reservoirs or microbial ecosystems that serve asres~ {enol of antibiotic-resistance genes (ARGS). The ARG poo! is maintained in environ ‘ments with high selective pressure exerted by contaminating antibiotic and antibiotic Dene Ammen i no epi Kove Chico i Fico Och 15,200 ES pal areal No laren poms Cgpge CN le ar A glai Stara 9 peo pati eyo i a seve os ae Tae [Detal f enteric pathogens with ecgnizad amd emaging shin vestance: tacts for antbitcresatnce, anthicioreitanca ganes reapensbie (ore applicable) rogions reporting resistance wement recommendations for infections. and vacines avaiablo Emergngeemerging Regions ‘Antibite [Orag Rexetance Gene] Reporting Past 10. for Anibiove Therapy Vaccines References uoroauinolones| Pld mechated or or guinolone ‘eanen determining region (ORDA) gyrA. perch ererston ephalsporins [to (Cx, om ne plasmids bloc als TEX a oxal ‘Carbapenems (ome ovetexpresion, ba ‘in bl NO, NP) -Aachromycin mph, ‘mph mets) ‘colstin ner gene mutator 7a, Ai, Europe ‘america Europe sia eorope Europe, Aiea, ‘A, ‘Recommendations van Vaccines candidates for § “Raubicue veatment Typhimurium and S fecommended (or Dublinin development. interes nc young, infant and the Immunocompremie, but rare culture ‘uid. Carte i ‘ier childen and adults usally sat iting. Cute sided asic fteatment for ivasve deca (continued on next page) ou