Prevalence and factors associated with extended-spectrum βlactamase producing Enterobacteriaceae bacteraemia in University Hospital of Befelatanana, Madagascar

Background: The extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae are a major cause of nosocomial bacteraemia. The objectives of this study are to describe the antibiotic resistance pattern of ESBL producing Enterobacteriaceae responsible for bacteraemia and identify factors associated with these infections in a University Hospital in Madagascar.Methodology: This is a descriptive cross-sectional study of 300 randomly selected patients with clinical features of bacteraemia whose blood cultures were processed for isolation and identification of bacterial pathogens over a period of six months (October 2019 to March 2020) at the laboratory of the University Hospital of Befelatanana. Blood culture samples were processed by conventional microbiological method for isolation of Enterobacteriaceae, which were identified to species level using Analytical Profile Index (API) 20E® test system. Antibiotic susceptibility of each isolate was performed by the disk diffusion technique and ESBL production was detected by the ‘synergy’ method.Results: Of the 300 patients, 54 were positive for bacteria, giving a prevalence rate of 18% for microbiologically documented bacteraemia. Of the 54 bacterial pathogens, Enterobacteriaceae isolates constituted 37 (68.5%), with 23 (42.6%) being ESBL producing and 14 (25.9%) non-ESBL producing isolates, 14 (25.9%) were staphylococci and 3 (5.6%) were streptococci isolates. All 23 (100%) ESBL producing Enterobacteriaceae isolates were resistant to amoxicillin, amoxicillin-clavulanic acid and the third generation cephalosporins (3GC), 19 (82.6%) to gentamycin and 18 (78.3%) to cotrimoxazole. On the other hand, the non-ESBL producing isolates were more sensitive because only 10 (71%) were resistant to amoxicillin, 7 (50%)to cotrimoxazole, 2 (14%) to amoxicillin-clavulanic acid, 1 (7.1%) to gentamycin, and none (0%) was resistant to 3GC. All 54 Enterobacteriaceae isolates were sensitive to amikacin and imipenem. Age less than 20 years (93.8%) (p=0.001) and hospitalization in intensive care units (90.9%) (p=0.04) were significant risk factors associated with infection by ESBL producing Enterobacteriaceae.Conclusion: ESBL producing Enterobacteriaceae responsible for bacteraemia in University Hospital of Befelatanana, Madagascar, are resistant to many classes of antibiotics. Carbapenems and amikacin are the antibiotics of choice. Keywords: ESBL, Enterobacteriaceae, bacteraemia, antibiotic resistance   French Title: Prevalence et facteurs associes a la bacteriemie a enterobacteries productrices de β-lactamases a spectre etendu dans l'hopital universitaire de Befelatanana, Madagascar Contexte: Les enterobacteries productrices de β-lactamases a spectre etendu (BLSE) sont une cause majeurede bacteriemie nosocomiale. Les objectifs de cette etude sont de decrire le profil de resistance aux antibiotiques des enterobacteries productrices de BLSE responsables de bacteriemie et d'identifier les facteurs associes a ces infections dans un hopital universitaire de Madagascar.Methodologie: Il s'agit d'une etude transversale descriptive de 300 patients selectionnes au hasard presentantdes caracteristiques cliniques de bacteriemie dont les hemocultures ont ete traitees pour l'isolement etl'identification des bacteries pathogenes sur une periode de six mois (octobre 2019 a mars 2020) au laboratoiredu Hopital universitaire de Befelatanana. Les echantillons d'hemoculture ont ete traites par une methodemicrobiologique conventionnelle pour l'isolement des enterobacteries, qui ont ete identifiees au niveau del'espece a l'aide du systeme de test Analytical Profile Index (API) 20E®. La sensibilite aux antibiotiques dechaque isolat a ete realisee par la technique de diffusion sur disque et la production de BLSE a ete detectee parla methode «synergie».Resultats: Sur les 300 patients, 54 etaient positifs pour les bacteries, ce qui donne un taux de prevalence de18% pour une bacteriemie microbiologiquement documentee. Parmi les 54 bacteries pathogenes, les isolatsd'enterobacteries constituaient 37 (68,5%), 23 (42,6%) produisant des BLSE et 14 (25,9%) isolats neproduisant pas de BLSE, 14 (25,9%) etaient des staphylocoques et 3 (5,6%) l'etaient isolats de streptocoques.Les 23 isolats (100%) de BLSE produisant des Enterobacteriaceae etaient tous resistants a l'amoxicilline, al'amoxicilline-acide clavulanique et aux cephalosporines de troisieme generation (3GC), 19 (82,6%) a lagentamycine et 18 (78,3%) au cotrimoxazole. En revanche, les isolats non producteurs de BLSE etaient plussensibles car seuls 10 (71%) etaient resistants a l'amoxicilline, 7 (50%) au cotrimoxazole, 2 (14%) al'amoxicilline-acide clavulanique, 1 (7,1%) a la gentamycine, et aucun (0%) n'etait resistant a la 3GC. Les 54isolats d'Enterobacteriaceae etaient tous sensibles a l'amikacine et a l'imipeneme. L'âge de moins de 20 ans(93,8%) (p=0,001) et l'hospitalisation en unite de soins intensifs (90,9%) (p=0,04) etaient des facteurs derisque importants associes a l'infection par les enterobacteries productrices de BLSE.Conclusion: Les enterobacteries productrices de BLSE responsables de bacteriemie a l'hopital universitaire deBefelatanana, Madagascar, sont resistantes a de nombreuses classes d'antibiotiques. Les carbapenemes etl'amikacine sont les antibiotiques de choix. Mots cles: BLSE, enterobacteries, bacteriemie, resistance aux antibiotiques