Molecular Epidemiology and Mechanisms of Antibiotic Resistance in Gram-positive Bacteria in Africa: A Systematic Review and Meta-Analysis from a One Health Perspective

Abstract

15 16 17 18 19 [2]HIGHLIGHTS 20  There is substantial resistance to antibiotics among Gram-positive bacteria (GPB) in Africa 21  Multidrug-resistant (MDR) S. aureus, E. faecium, E. faecalis, S. pyogenes, and S. 22 haemolyticus of the same clones were common in humans, animals and the environment. 23  MDR clones such as S. aureus ST5 and E. faecium ST80 were found in humans, animals and 24 the environment. 25  mecA, ermB, ermC, tetM/K/L, and vanA/B/C were common in GPB, including in VRSA. 26 Meta-analysis confirmed a high mean rate of drug resistance in GPB from humans (35.68%), 27 animals (69.63%) and the environment (88.33%) (p-value= 0.0301) in Africa. 28 SCCmec, IS16, and Tn916 mobilized mecA, ermB and tetM respectively across various GPB 29 species in animals, humans, and the environment. 30  A One Health approach to studying resistance mechanisms and molecular epidemiology of 31 antibiotic-resistant GPB is warranted. 32ABSTRACT 33 The emergence and dissemination of antibiotic resistance (ABR) in bacteria are being driven by 34 antibiotics use in humans, animals and the environment, threatening global health and 35 strengthening calls for a One Health approach to contain ABR. 36 A systematic search in PubMed for English research articles reporting on ABR in Gram-positive 37 bacteria in Africa within the last ten years from 2007 to 2017 was undertaken. This finally yielded 38 76 articles that were included in this review and all statistical analysis. [3]The same ABR Gram-positive bacterial clones, resistance genes, and mobile genetic elements 40 (MGEs) were found in humans, animals and the environment. IS16 and Tn916 were highly 41 associated with erm (B) and tet(M) in E. faecium (ST18, ST80 and ST910), S. agalactiae (ST612, 42 ST616 and ST617), E. faecalis and S. pyogenes (emm18, emm42, emm76 and emm118) whilst 43 SCCmec was associated with mecA in S. aureus (ST5, ST80, ST8, and ST88) and S. haemolyticus. 44 The resistance genes, mecA, erm (B), erm(C), tet(M), tet(K), tet(L), van(B), van(A), van(C), and 45 tet(O), were found in isolates from humans, animals and the environment. An ABR rate of 39.55% 46 in Gram-positive bacteria is estimated in Africa. Meta-analysis reveal that isolates were most 47 resistant to erythromycin (≥ 2 482) (37.37%), rifampicin (≥ 2 323) (33.42%), tetracycline (≥ 2 181) 48 (40.72%), penicillin (≥ 2 127) (73.47%), sulfamethoxazole/trimethoprim (≥1 377) (45.97%), 49 ciprofloxacin (≥846) (35.37%), gentamicin (≥805) (23.87%), vancomycin (≥712) (42.24%), 50 ampicillin (≥691) (48.25%), streptomycin (≥551) (32.03%) and chloramphenicol (≥376) (11.50%) 51 (p-value <0.0001). 52There is substantial resistance to antibiotics among Gram-positive bacteria in clinical and 53 environmental settings in Africa, mediated by clonal and polyclonal expansion as well as 54 horizontal transmission of resistance genes. A One Health approach to research, surveillance, and 55 molecular epidemiology, as well as antibiotic stewardship to contain ABR in humans, animals and ...