Carbapenem resistance in West Africa: a systematic review

Abstract

OBJECTIVES: The World Health Organization (WHO) has reported carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Acinetobacter baumannii (CRAb), and carbapenem-resistant Pseudomonas aeruginosa (CRPa) as critical priority pathogens for human health. Therefore, this study aimed to review clinical carbapenem resistance systematically and comprehensively in West Africa.

DATA SOURCES: A total of 102 research articles on carbapenem resistance from the sixteen countries forming the West African region were included in this review.

DATA SYNTHESIS: Carbapenem-resistant bacteria (CRB) were isolated mainly from urine 73/300 (24.3%) and pus/wounds of patients 69/300 (23%). The mean prevalence of CRB in West Africa was 4.6% (1902/41635), ranging from 1.6% to 18.6%. CRB identified were mainly Escherichia spp. (34/130; 26.1%), Klebsiella spp. (27/130, 20.8%), Pseudomonas spp. (26/130, 20%), and Acinetobacter spp. (25/130; 19.2%). Bacteria isolated in West African countries produced carbapenemases that belong to the four Ambler classes and include 13 types. The bla _OXA-type (34/104; 32.7%), bla _NDM (31/104; 29.8%), and bla _VIM (13/104; 12.5%) were the most common carbapenemase genes. These genes are carried by plasmids, composite transposons, and integrons. The Kirby-Bauer disc diffusion method (74/172; 43.0%), PCR (38/172; 22.1%), and whole genome sequencing (17/172; 9.9%) were the most common methods for carbapenem resistance detection. The most reported alternative antibiotics active against CRB were amikacin, colistin, and fosfomycin.

CONCLUSION: There is an urgent need to take synergistic action to delay, as much as possible, the occurrence of CRB epidemics in West Africa.

Main article text

INTRODUCTION

Carbapenems are the last-resort antibiotics used to treat severe infections caused by multidrug-resistant bacteria [1, 2]. Unfortunately, the world has been witnessing the spread of carbapenem-resistant bacteria (CRB) for the last two decades [3-5]. According to the World Health Organization (WHO), carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa should be considered critical priority pathogens, posing the greatest threat to human health [6].

Three major mechanisms can lead to carbapenem resistance: (i) production of carbapenemases (enzymes hydrolyzing carbapenems); (ii) overexpression of efflux pumps; and (iii) quantitative loss of and/or mutations in outer membrane porins combined with the production of extended-spectrum β-lactamases (ESBL) or cephalosporinases [1, 7, 8].

As new antibiotics are rarely discovered [9], it is imperative to conduct epidemiological, preventive, and curative actions in every part of the globe to contain or postpone the occurrence of carbapenem-resistant bacterial epidemics as much as possible. Currently, there is no information on the overall status of carbapenem resistance in West Africa. With an area of 6,064,060 km², West Africa consists of 16 countries with a population of 442,006,171, representing approximately 5.47% of the world population [10].

This study aimed to conduct a systematic and comprehensive review of clinical carbapenem resistance in West Africa. The specific objectives were to: (i) report the prevalence of CRB in West Africa; (ii) describe the genetic determinants involved in carbapenem resistance in West Africa, such as resistance genes and mobile genetic elements; (iii) discuss methods used to study carbapenem resistance in West Africa; and (iv) list the alternative antibiotics with good activity against CRB isolated in the West African region.

MATERIALS AND METHODS

Literature review

Keywords (carbapenem resistance, carbapenemase, West Africa, and country name) were used to perform a comprehensive literature search covering PubMed, Embase, Google Scholar, African Journals Online, and Scopus. All articles published in French or English from January 1, 2000, to August 25, 2023, were included to ensure comprehensive and relevant data.

Study selection criteria

This study included peer-reviewed research articles published in French or English, reporting clinical carbapenem-resistant bacterial samples collected from one of the 16 West African countries. These countries are Benin, Burkina Faso, Cape Verde, Côte d’Ivoire or Ivory Coast, Gambia, Ghana, Guinea, Guinea-Bissau, Liberia, Mali, Mauritania, Niger, Nigeria, Senegal, Sierra Leone, and Togo. The articles that reported at least one isolated bacterium resistant to carbapenem, the prevalence of carbapenem resistance, or a bacterium and its carbapenemase gene(s) were included in the study. Data on bacteria from human populations (from hospitals and communities) of all ages were included in this study. As this review focused on carbapenem-resistant bacteria of human origin, data on bacteria isolated from animal and environmental samples were excluded. Articles reporting clinical CRB collected from outside the sixteen West African countries were also excluded.

Data extraction and synthesis

The following data were extracted from the publications: country in which the samples were collected, year of sampling, type of study, number of isolates tested for carbapenem resistance, carbapenem resistance prevalence, the species (or genera) of the CRB, sample type, carbapenemase genes and their prevalences, mobile genetic elements, method used to detect CRB, community-acquired or hospital-acquired strains, age group, antibiotics active against CRB, and references (Table 1). To calculate the total prevalence of CRB, we only considered data displaying both the number of CRB and the total number of samples.

Table 1.

Review of studies on carbapenem resistance in West Africa

Country	Year of sampling	Type of study	CR isolates / total tested (%)	Species (number of strains studied)	Isolate source	Carbapenemase genes (prevalence among the studied strains, %)	Mobile genetic element	Method used	Setting (age group)	Effective antibiotic against CRB	Ref.
Benin	2019-2020	Descriptive cross-sectional	12/180 (6.7)	E. coli, P. aeruginosa, P. mendocina, E. cloacae, A. baumaimii	Pus	bla OXA-48(33-3), bla NDM (33-3), bla VIM(33.3)	NA	Kirby-Bauer DDM, PCR	Hospital (adult)	Amikacin	[11]
	2021-2022	NA	28/103 (27.18)	Enterobacteriaceae	Urine	NA	NA	Kirby-Bauer DDM	Hospital, community (children, adults, seniors)	NA	[12]
	2021-2022	Prospective descriptive	(100) (30) 0	P. putida, S. paucimobilis, K. pneumonia, E. coli	Urine	- bla NDM(11.1), bla NDM(10)	NA	Kirby-Bauer DDM, Vitek 2 (AST-N233 card), standard PCR	Hospital, community (children, adults, seniors)	NA	[13]
	NA	NA	(9) (25)	E. coli, P. aeruginosa	Wound	NA	NA	Kirby-Bauer DDM	Hospital	NA	[14]
	2012-2013	NA	3/84 (3.6)	E. coli	Urine, pus, VS, sperm, blood, CSF	NA	NA	Kirby-Bauer DDM	Hospital	NA	[15]
	2017-2020	Prospective antimicrobial resistance surveillance	2/49 (4.1) 2/44 (4.5)	E. coli E. cloacae	Blood	NA	NA	Kirby-Bauer DDM, E-Test	Hospital (children, adults)	NA	[16]
	2019-2020	Crosssectional	3/21 (14.3) 1/20 (5) 3/38 (8) 5/62 (8)	E. cloacae, A. baumannii, P. aeruginosa, E. coli	Pus, wound	NA	NA	Kirby-Bauer DDM, microdilution	Hospital	NA	[17]
	2005	Prospective	2/39 (5) 3/150 (2)	E. coli, Non ESBL E. coli	Urine, wound, blood, VS, rectal swab	NA	NA	Kirby-Bauer DDM	Hospital	NA	[18]
Burkina-Faso	2009-2010	Prospective sectional	2/5 (40)	E. coli (5 pathotypes)	Stool	bla KPC(40), bla VIM (40), bla IMP (40)	NA	Kirby-Bauer DDM, PCR	NA (children)	Ciprofloxacin, netilmicin	[19]
	2020	Retrospective	15/53 (28.3)	E. coli (15 strains)	Urine, pus	bla NDM(86.7),bla VIM(33.3)	NA	PCR, Kirby-Bauer DDM	Hospital, community (adults, children, seniors)	NA	[20]
	NA	Case report	4*	E. coli	Urine, pus	bla OXA-181	Tn20l3 transposons located on IncX3-type plasmids	E-test, PCR, DNA sequencing, PRaseT, PCR-based replicon typing	NA (adults, children, seniors)	NA	[21]
	2013-2015	NA	5/31 (16.1)	E. coli	Stool	NA	NA	PCR, Kirby-Bauer DDM	Hospital, community (children)	Ciprofloxacin	[22]
	2022	Retrospective descriptive	3/123 (2.4)	E. coli, K. pneumoniae	NA	NA	NA	Kirby-Bauer DDM	NA	NA	[23]
	2016	NA	17/601 (2.8)	Enterobacteriaceae, Acinetobacter spp.	Urine, wound, pus, stool, blood	bla NDM-1’bla OXA-58’ bla OXA-181’bla VIM-2	IncX3-, IncXl-, IncF-type plasmids	Kirby-Bauer DDM, PCR, PRaseT	Hospital, community (children, adults, seniors)	Amikacin	[24]
	2009-2013	NA	2/17(11.8)	Klebsiella spp.	Urine, pus, CSF	bla IMP(17.6)	NA	Kirby-Bauer DDM, PCR	NA (children)	NA	[25]
	NA	NA	5/52 (9.6)	P. aeruginosa, S. maltophilia	blood, urine, pus, VS, stool	NA	NA	Kirby-Bauer DDM, Vitek 2	NA	NA	[26]
	2014-2015	Cross-sectional	1/486 (0.2)	Enterobacteriaceae	Urine, pus, blood, stool, VS, PF	NA	NA	Kirby-Bauer DDM	NA (children, adults, seniors)	NA	[27]
	2013-2015	NA	2/53 (3.8)	Salmonella spp.	Stool	NA	NA	Kirby-Bauer DDM	Hospital, community (children)	NA	[28]
Cape Verde	2021	NA	6/98 (6.1)	Enterobacteriaceae	Rectal swab	bla OXA-181(66.7), bla OXA-48(16.7), bla OXA-244(16.7)	IncFI-, IncX3-types plasmids	Kirby-Bauer DDM, PCR-based replicon typing	Hospital (adult)	Ceftazidime/avibactam	[29]
Côte d’Ivoire	2010-2016	Transverse	14/174 (8)	P. aeruginosa	Urine, pus, blood, CSF, catheter, BF, PF	NA	NA	Kirby-Bauer DDM	Hospital, community	NA	[30]
	2002-2012	NA	8/48 (16.7)	P. aeruginosa	NA	bla VIM-2	NA	Kirby-Bauer DDM, PCR, Sequencing	Hospital	NA	[31]
	2009-2011	NA	12*	P. aeruginosa	Urine, blood	bla VlM-2	Class 1 integron	PCR, DNA sequencing	Hospital	Aztreonam,colistin	[32]
	NA	NA	4/20 (20)	A. baumannii, A. nosocomialis	Urine	bla NDM-1’ bla OXA-58’ bla OXA-66	Tn125	Kirby-Bauer DDM, PCR, WGS	Hospital (children, adults)	NA	[33]
Gambia	2015	Cross-sectional	16/89(18)	Enterobacteriaceae, Pseudomonas spp.	Stool	NA	NA	Kirby-Bauer DDM	Community (adults)	NA	[34]
	2015	Cross-sectional	1/28 (3.6)	Enterobacteriaceae	Stool	NA	NA	Kirby-Bauer DDM	Community (adults)	NA	[35]
	2017	Cross-sectional cohort	112*	E. coli, K. pneumoniae, Acinetobacter spp.	Perianal, skin, rectovaginal	bla SHV-75’ bla SHV-65’ bla SHV-61,XYBbla SHV-27’ bla SHV-187’ bla SHV-157’ bla SHV-13’ bla SHV-106’ bla MBL’ bla CTX-M-27,	NA	WGS	Hospital, community (children, adults)	NA	[36]
Ghana	2016-2017	NA	2/36 (5.6)	Acinetobacter spp.	Urine, sputum, wound, HVS, blood, semen, CSF	bla OXA-23’ bla OXA-58’ bla OXA-420’ bla OXA-70’ bla OXA-699’ bla OXA-51	Tn2007, IS 15DII, plasmids	WGS, broth microdilution	NA	Amikacin, minocycline	[37]
	2014-2015	Retrospective	52/87 (59.8)	Acinetobacter spp.	Wound, urine, aspirate, ear, eye swab	bla NDM	NA	Kirby-Bauer DDM, PCR	NA (children, adults)	Amikacin	[38]
	2020-2021	Cross-sectional	8/144 (5.6)	E. coli, K. pneumoniae	Wound, urine, sputum, blood, pus, PF, aspirate, ear, eye swab, HVS	bla OXA-48(80), bla NDM(20)	NA	Kirby-Bauer DDM, MIC, PCR	NA (children, adults, seniors)	NA	[39]
	2012-2014	Prospective	111/3840 (2.9)	A. baumannii, Enterobacteriaceae, P. aeruginosa	Wound, urine	bla NDM-1(14.4), bla VIM-1(7.2), bla OXA-48(1.8)	NA	Kirby-Bauer DDM, E-test, PCR, sequencing	Hospital (children, adults, seniors)	NA	[40]
	NA	NA	43/600 (7.2)	Enterobacteriaceae, A. baumannii	NA	NA	NA	Kirby-Bauer DDM, E-test	NA	Amikacin, colistin, fosfomycin	[41]
	2017-2021	Cross-sectional	42/14554 (0.3) 1/48 (2.1) 19/100 (19) 56/3090 (1.8) 3/1110(0.3)	E. coli, Acinetobacter spp., Pseudomonas spp., Klebsiella spp., Proteus spp.	Urine	NA	NA	Kirby-Bauer DDM	NA (adults, children, seniors)	NA	[42]
	NA	Case report	2*	E. coli	Stool	bla OXA-181	IS 26 forming composite transposon on IncX3-, IncFIC(FII)-type plasmids	Broth microdilution, WGS	NA (children)	NA	[43]
	2017-2018	Prospective	22/45 (48.9)	A. baumaimii (22 strains)	Wound	bla NDM-1(90.9), bla OXA-23(90.9), bla OXA-420(9.1), bla OXA-378(13.6), bla OXA-69(77.3)	NA	Broth microdilution, Vitek 2 (AST-N248 card), PCR, Sequencing	NA	NA	[44]
	2017-2018	NA	27/91 (29.7) 18/48 (37.5)	K. pneumonia, K. oxytoca	Blood, HVS, sputum, urine, wound	bla OXA-48(2.2), bla NDM(0.7)	NA	Kirby-Bauer DDM, PCR	Hospital (adults)	Amikacin	[45]
	2018-2019	Cross sectional	2/135 (1.5)	E. coli	Urine	NA	NA	Kirby-Bauer DDM	Hospital, community (children, adults, seniors)	NA	[46]
	2017-2018	Laboratory surveillance of antimicrobial resistance	35/168 (21)	Enterobacteriaceae	Urine, wound, blood, throat swab, stool, ear swab	bla OXA-48’ bla NDM’ bla KPC	NA	Kirby-Bauer DDM, microscan auto-SCAN system, PCR	Hospital, community	NA	[47]
	2017-2019	NA	29*	K. pneumoniae	Swabs of neonates, blood	bla OXA-181	IncX3-, In-cFlB (Mar)-, IncOl-, IncColKP3-type plasmids	WGS	Hospital (children)	NA	[48]
	2019	Cross-sectional	2/19 (10.5)	K. pneumoniae	Stool	NA	NA	Vitek 2	Community (children)	NA	[49]
	NA	Cross-sectional	2/736 (0.3)	Enterobacteriaceae	NA	bla NDM-1’ bla CMY-2	NA	NA	Community	NA	[50]
	2015	Cross-sectional analytical	22/220 (10)	Enterobacteriaceae	Urine	NA	NA	E-test	Community (children, adults)	NA	[51]
Mail	2001-2008	Screening program	41*	Salmonella spp.	Stool	bla SHV-12(51-2)	NA	Kirby-Bauer DDM, PCR, Sanger DNA sequencing	Community (children)	NA	[52]
	2010-2019	Retrospective	5/317 (1.6)	P. aeruginosa	Urine, pus, VS, sputum, blood, PF, CSF, ProF, PeriF, BAF, AF, GF	NA	NA	Kirby-Bauer DDM	Hospital, community	Colistin, ceftazidime, amikacin, piperacillin	[53]
	2019-2022	NA	2/48 (4.2)	K. pneumoniae	Urine, pus, sputum, blood, PL	NA	NA	Kirby-Bauer DDM	NA	NA	[54]
	2014	Prospective	1/31 (3.2)	E. coli	Blood	bla OXA-181	NA	Kirby-Bauer DDM, E-test, PCR, sequencing	Hospital (adults, children, seniors)	NA	[55]
Mauritania	2014	Prospective	4/366 (1.1)	E. coli	Urine	NA	NA	Kirby-Bauer DDM	Hospital, community	NA	[56]
	2019-2020	Retrospective	4/120 (3.3)	Enterobacteriaceae	Urine	NA	NA	Vitek 2, Kirby-Bauer DDM	Hospital, community (adults, children)	NA	[57]
Niger	2021	Descriptive cross-sectional	4/50 (8) 7/9 (77.8)	Enterobacteriaceae P. aeruginosa	Urine, pus, stool	NA	NA	Kirby-Bauer DDM	Hospital, community (children, adults, seniors)	NA	[58]
	2019	Prospective descriptive, epidemiological	19/292 (6.5)	Enterobacteriaceae	Urine, sputum, stool	bla NDM-5(71.4), bla OXA-181(28.6)	NA	RT-PCR, modified Kirby-Bauer DDM	NA	NA	[59]
	2016-2020	Antimicrobial resistance surveillance	54/86 (62.8) 2* 16*	A. baumannii, A. haemolyticus, A. nosocomialis	Rectal swab, blood, CSF	bla OXA-23(34.9), bla NDM-1(27.9), bla OXA-214’ bla OXA-420’ bla OXA-58(11.6)	Tn2006, Tn2006-like, Tn 125	Vitek 2 (AST N281 card), WGS	Hospital	Minocyclin, tigecycline	[60]
	2015	Cross-sectional	13/64 (20.4) 21/108 (19.4)	E. coli, K pneumoniae	Urine	NA	NA	Modified Kirby-Bauer DDM	NA (children, adults, seniors)	NA	[61]
	2019	NA	16/200 (8)	Enterobacteriaceae	NA	bla NDM-7(12.5), bla SHV-37’bla ACT-29	NA	E-test, BDM, standard PCR, WGS	NA	Amikacin, colistin, tigecyclin	[62]
	NA	NA	13/25 (52) 11/35 (31.4) 9/30 (30)	K pneumoniae, E. coli, P. aeruginosa	Urine	NA	NA	Kirby-Bauer DDM	NA	NA	[63]
	2019	NA	47/158 (29.7)	Enterobacteriaceae, P. aeruginosa	Urine, wound, eye swab, sputum, tracheal aspirate	NA	NA	EDTA double-disc synergy test, mCIM	Hospital, community	NA	[64]
	2015-2016	NA	17/46 (37)	Klebsiella spp.	Urine, sputum, ear swab, wound, VS	NA	NA	Kirby-Bauer DDM	NA	NA	[65]
	2017-2018	NA	105/1741 (6)	A. baumannii, Enterobacteriaceae, P. aeruginosa	Urine, wound, stool, sputum, VS, ear swab, PF	bla NDM(24.8), bla VIM(3.8)	NA	MicroScan Walk-Away40, RT-PCR	NA	NA	[66]
	2018	NA	7/21 (33.3)	A. baumannii	Urine, CSF, wound, blood, sputum, tissue	bla NDM-1’bla OXA-51’ bla OXA-58’bla OXA-67’ bla OXA-68’bla OXA-69’ bla OXA-23’bla OXA-180’ bla OXA-91’bla OXA-130’ bla OXA-64’bla OXA-91’ bla OXA-203’bla OXA-235	NA	WGS, Kirby-Bauer DDM	NA (children, adults, seniors)	NA	[67]
	2014	Descriptive cross-sectional	28/225 (12.4)	Enterobacteriaceae	Blood, urine, CSF, stool	bla KPC-1(47.8%), bla NDM-1(21.4), bla VIM(30.4%)	NA	Kirby-Bauer DDM, PCR	Hospital (children, adults, seniors)	NA	[68]
	2014-2015	Laboratory-based	35/171 (20.5)	P. aeruginosa	Urine, wound, blood, bone	NA	NA	Kirby-Bauer DDM	NA	NA	[69]
	2018	Retrospective, epidemiological and surveillance	39/177 (22)	Enterobacteriaceae, A. baumannii, P. aeruginosa	Urine, pus, wound, tracheal aspirate, tissue biopsy, sputum	NA	NA	Kirby-Bauer DDM	Hospital, community (children, adults, seniors)	Colistin, nitrofurantoin	[70]
	2016-2017	Cross-sectional	19/59(32.2)	Enterobacteriaceae	Blood, urine	NA	NA	Kirby-Bauer DDM	Hospital (children, adults, seniors)	NA	[71]
	2016-2021	NA	32/49 (65.3)	Enterobacteriaceae (49 species)	Blood, urine, wound	bla NDM-1(35), bla NDM-5(25), bla OXA-181(3), bla OXA-48(9.1), bla SHV-67(6.1), bla SHV-187(44.9), bla SHV-11(4.1), bla OXA-320(2), bla OXA-534(2), bla OXA-9(2)	1SEc33, IS5, IS Kpnl9, ISKra4 family, IncFII-type plasmids	BD Phoenix Automated Microbiology System, WGS	Community	Tigecycline, fosfomycin, amikacin, colistin	[72]
	2018	Descriptive cross-sectional	8/76 (10.5)	Enterobacteriaceae	Blood, urine, sputum, tracheal aspirate	bla VIM(62.5), bla NDM(25), bla KPC(12.5)	NA	Kirby-Bauer DDM, PCR	Hospital (children, adults)	NA	[73]
	2018-2019	NA	55/128 (43.0)	K. pneumoniae (128 phenotypes)	Urine, blood, sputum, wound, HVS, pus, stool, tracheal aspirate, semen	bla VIM(43), bla OXA-48(28.9), bla IMP(22.7), bla NDM(17.2), bla KPC(13.3)	NA	Kirby-Bauer DDM, broth microdilution methods, PCR	Hospital, community (children, adults, seniors)	Polymyxin B	[74]
	2018-2019	NA	54/123 (44)	P. aeruginosa	Wound, urine, sputum/tracheotomy aspirates, ear swabs, VS	bla VIM-2’ bla VIM-5-like, bla NDM-1’bla GES-5’ bla GES-1’bla GES-9	Plasmids	Vitek 2 (AST-N-232 card), WGS	Hospital, community (adults)	NA	[75]
	2016-2019	NA	33/95 (34.7)	Enterobacteriaceae	Stool, urine	bla SHV-11’ bla SHV-28	IncFIB-, IncFIB(K)-, IncFII-, IncFIA-, IncFII(K)-, IncR-type plasmids	broth dilution method, Kirby-Bauer DDM, WGS	NA	NA	[76]
	2011	NA	67/182 (36.8)	Enterobacteriaceae, Pseudomonas spp.	Urine, wound, stool, blood, sputum, ear swab	bla NDM’bla VIM’ bla GES	Plasmids	Kirby-Bauer DDM, PCR, sequencing	Hospital, community	NA	[77]
	2015	NA	9/218 (4.1)	Enterobacteriaceae	Urine, peritoneal fluid, endocervical swab	bla NDM-1’bla OXA-48’ bla OXA-181’bla SHV-11’ bla SHV-28’bla ACT-5	IncL/M-type plasmids	Kirby-Bauer DDM, E-test method, WGS	NA	NA	[78]
	2012	NA	3/5 (60)	A. baumannii	NA	kk*OXA-23	NA	RT-PCR, standard PCR	NA	Colistin	[79]
	2016-2018	Antimicrobial resistance sentinel surveillance	134*	K. pneumoniae	Blood, cerebrospinal fluid, urine	bla NDM-1(6), bla NDM-5(1.5), bla OXA-48(0.7), bla SHV-89’ bla SHV-80’ bla SHV-32’bla SHV-215’ bla SHV-36’bla SHV-212’ bla SHV-223’bla SHV-75’ bla SHV-172’bla SHV-84	IncL/M-, IncFIB- (AP001918), IncN-, IncR-types plasmids	Vitek 2, WGS	NA	NA	[80]
	NA	NA	66/140(47.1) 48/108(44.4)	E.coli, K. pneumoniae	Urine, wound, abscess	NA	NA	Modified Kirby-Bauer DDM,	NA	NA	[81]
	2016-2018	NA	48/175 (27.4)	Enterobacteriaceae (48 species)	Urine, wound, blood	bla NDM(85.4), bla OXA-181(25), bla OXA-48(2.1), bla CMY-2(22.9)	NA	Vitek 2, standard PCR, isothermal amplification, WGS	NA (children, adults, seniors)	Fosfomycin, ceftazidim/avibactam/aztreonam	[82]
	NA	NA	(12.5)	Enterobacteriaceae	NA	NA	NA	Kirby-Bauer DDM	Hospital	Colistin, tigecycline	[83]
	2013	NA	27/177 (15.2)	Enterobacteriaceae	Urine, blood, sputum, wound, pus	NA	NA	Modified Kirby-Bauer DDM	Hospital	NA	[84]
	2020	Prospective descriptive	3/8 (37.5)	K. pneumoniae	Urine, sputum, wound	NA	NA	Kirby-Bauer DDM, PCR	NA	NA	[85]
	2013-2014	Prospective cross-sectional	1/220 (0.5)	E. coli	Urine, blood, diverse aspirates	NA	NA	Kirby-Bauer DDM	Hospital, community (children, adults, seniors)	NA	[86]
	2014	NA	52/157(33.1)	Enterobacteriaceae, P. aeruginosa	Urine, blood, wound, sputum, semen, HVS, endo cervical swab	NA	NA	Kirby-Bauer DDM	NA	NA	[87]
	NA	NA	9/97 (9.3)	E. coli, K pneumoniae	Urine, blood, CSF, genitals	NA	NA	Kirby-Bauer DDM	(children, adults)	NA	[88]
Senegal	2018-2020	Retrospective	10/66(15.2)	K pneumoniae	Urine, pus, sputum, BF, VS	NA	NA	Kirby-Bauer DDM	Hospital, community (children, adults, seniors)	NA	[89]
	2018-2020	Retrospective	3/78 (3.8)	E. coli	Urine, pus, sputum, BF, VS	NA	NA	Kirby-Bauer DDM	Hospital, community (children, adults, seniors)	Fosfomycin	[90]
	2014-2018	Prospective	30/807 (3.7) 23/295 (7.8) 20/95 (21.1)	E. coli, Klebsiella spp., Enterobacter spp.	Urine	NA	NA	Kirby-Bauer DDM	Hospital, community (children, adults, seniors)	NA	[91]
	2019-2022	Prospective	13/240 (5.4)	Enterobacteriaceae	Urine, pus, blood, VS, puncture fluid, sputum	bla NDM(5.4), bla OXA-48(5.8)	NA	Kirby-Bauer DDM, RT-PCR, standard PCR	Hospital, community (children, adults)	Colistin	[92]
	2015-2016	Retrospective	12/1185 (1)	Enterobacteriaceae	Urine	NA	NA	Kirby-Bauer DDM	Hospital, community	NA	[93]
	NA	NA	NA/49	K. pneumoniae (5 isolates)	Urine	bla OXA-48(100), bla SHV-28(40), bla SHV-11(20), bla SHV-61(20), bla SHV-110(20)	Tn 2999.2-type trans-poson located on IncL/M-type plasmids	PCR, WGS	NA	NA	[94]
	2018-2021	Retrospective	10/28 (35.7)	K. pneumoniae	Urine, blood, wound	bla OXA-48(21.4)	NA	Kirby-Bauer DDM, PCR	Hospital	NA	[95]
	2016	Cross-sectional	62/1205 (5.1)	Enterobacteriaceae	Wound, urine, LF, genitals, blood, stool	NA	NA	Kirby-Bauer DDM	Hospital, community (adults, seniors)	Amikacin, fosfomycin	[96]
	NA	NA	29/29 (100)	A. baumannii (29 strains)	Urine, BS, pus, PL, blood	bla OXA-51(100), bla OXA-23(89.7), bla NDM-1(3.4)	NA	Kirby-Bauer DDM, standard PCR	Hospital	Amikacin, colistin	[97]
	2011	Case report	3*	A. baumannii	BAL,blood	bla OXA-23’ bla OXA-51	ISAba1	Genome sequencing	Hospital (children, adults)	Netilmicin,colistin	[98]
	2008-2009	NA	2/11 (18.2)	Enterobacteriaceae	Urine, post-surgical specimen	bla OXA-48	Tn1999 transposon located on a plasmid	Kirby-Bauer DDM, E-test method, PCR	Hospital, community	NA	[99]
	2008-2011	Prospective	2*	A. baumannii	Stool	bla OXA-23	NA	PCR, E-test	Community (children, adults)	Colistin, rifampicin	[100]
Sierra-Leone	2010-2011	Molecular epidemiology surveillance program	20*	Enterobacteriaceae, Pseudomonas spp.	NA	bla OXA-51-like, bla NDM-1(14.4)	Class 1 integron, ISA-ba3-related transposons	PCR, DNA sequencing, WGS	NA	NA	[101]
	2018	Cross-sectional	1/1 (8.7) (13)	B. cepacia, A. baumannii E. cloacae	Urine, sputum	NA	NA	Vitek 2	Hospital (adults, seniors)	NA	[102]
	2018	NA	56*	NA	Stool	bla NDM(10.7), bla OXA-48-like(1.8), bla PER(1.8),	Class 1 integron, ISCR1	RT-PCR	Hospital	NA	[103]
	2019-2020	NA	4*	M. morganii, Proteus spp.	Wound	NA	NA	Vitek 2 (AST-N214 card), Kirby-Bauer DDM	Hospital, community (children, adults, seniors)	NA	[104]
	2013-2014	NA	2/70 (2.9)	Enterobacteriaceae	Urine	NA	NA	Kirby-Bauer DDM, E-test	Community (children, adults)	Tigecycline	[105]
	2021	Prospective	1/2(50) 2/6(33)	P. mirabilis P. aeruginosa	Surgical wound, urinary catheter	NA	NA	Vitek 2	Hospital (adults, seniors)	Amikacin	[106]
Togo	2016	Cross-sectional	28/903 (3.1)	A. baumannii, E. cloacae, P. aeruginosa, K pneumoniae, E. coli	Urine, pus, CSF	NA	NA	Kirby-Bauer DDM	Hospital, community	Tobramycin, amikacin, colistin	[107]
	2016	NA	8/152 (5.2)	E. xiangfangensis, E. cloacae subsp. cloacae, E. hormaechei subsp. oharae, E. coli, K pneumoniae	Urine, pus	bla NDM-5’bla ACT-16’ bla ACT-7’bla OXA-18’ bla OXA-9	IncX3-,ColKP3-type plasmids	WGS	Hospital, community (children, adults)	Fosfomycin	[108]
	2013-2015	Retrospective	7/1979(0.35) 5/197 (2.5)	E. coli, A. baumannii, P. aeruginosa,	Pus, spit, urine, sperm, stool, articular fluids, ascitic fluids, BS	NA	NA	Kirby-Bauer DDM	Hospital, community	NA Amikacin	[109]
	2017-2018	NA	4/35 (11.4)	E. coli	NA	NA	NA	Kirby-Bauer DDM	Hospital, community	Gentamicin	[110]
Togo	2009-2011	NA	(0.68) (3.7)	E. coli, Klebsiella spp.	VS, urine, pus, blood	NA	NA	Kirby-Bauer DDM	NA	NA	[111]
	2013-2015	Prospective	2/91(2.2) 1/64(1.6)	E. coli, K pneumoniae	Urine, VS, pus, sperm, wound, sputum	NA	NA	Kirby-Bauer DDM	NA	NA	[112]

NA - not available; CRB - carbapenem-resistant bacteria; CSF - cerebrospinal fluid; WGS - whole genome sequencing; * - tested isolates; BF - bronchial fluid; VS - vaginal secretion; LF - liquid of effusion; BS - bronchial secretion; PL - puncture liquid; BAL - bronchoalveolar lavage; CR - carbapenem-resistant; BDM - broth dilution method; PF - pleural fluid; ProF - prostatic fluid; PeriF - peritoneal fluid; BAF - bronchoalveolar fluid; AF -articular fluid; GF - gastric fluid; MLST - multilocus sequence typing; PBRT - PCR-based replicon typing method; HVS - high vaginal swabs; mCIM - modified carbapenem inactivation method; CIM - carbapenem inactivation method; MIC - minimum inhibitory concentration; Kirby-Bauer DDM - Kirby-Bauer disk diffusion method; RS - respiratory secretion; PRaseT - plasmid relaxase gene typing.

Method for obtaining the number of samples types

In studies reporting carbapenem-resistant bacteria (CRB) isolated from urine, pus, and blood the number of sample types equals 3. Similarly, in studies reporting CRB isolated only from urine, the number of sample types is equal to 1.

Method for calculating CRB prevalence

The prevalence of carbapenem-resistant bacteria was determined by studies that specified both the number of CRB and the total number of strains tested. Therefore, at the West African or country level, the prevalence of CRB was calculated as the ratio of the total number of CRB reported in the corresponding studies to the total number of strains tested in these studies.

Method for carbapenemase gene type description

For example, in a study reporting bla _NDM-1, bla _NDM-2, bla _NDM-3, bla _OXA-48, and bla _OXA-181, the number of carbapenemase gene types will be equal to bla _NDM=1 and bla _OXA=1. Additionally, a single study can report several bacterial strains (or bacterial pathotypes), each of which contains more than one carbapenemase gene (or gene type). This can lead to the sum of percentages of carbapenemase genes (or gene types) exceeding 100%.

Method for calculating values of other parameters

The number of cases with a defined parameter was divided by the total number of cases in which this type of parameter was studied.

Statistical analysis

Statistical analyses were performed by the χ² test at 5% level of significance using Microsoft Excel 2016.

RESULTS

Literature search and eligible studies

A literature search of databases such as PubMed, Embase, Google Scholar, African Journals Online, and Scopus generated 547 research articles. Subsequently, 329, 72, and 44 research articles were excluded due to duplication, data from countries outside West Africa, and data from animal and environmental sources, respectively. The data from the remaining 102 research articles were included in this systematic review (Fig. 1).

Fig. 1.

Selection process of research articles included in this systematic review.

Sample collection and article publication periods

Out of the 102 studies included in this review, 89 (87.3%) reported the year of the sample collection. The sample collection period was from 2001 to 2022. The number of articles published per year ranged from 0 (2008, 2009, 2010) to 19 (January to August 2023) (Fig. 2).

Fig. 2.

Number of studies reporting CRB and/or carbapenemase genetic determinants in West African countries (2007 – August 2023).

Number of studies in each country

The number of articles published on carbapenem resistance per country was 30 (29.4%) in Nigeria, 15 (14.7%) in Ghana, 12 (11.8%) in Senegal, 10 (9.8%) in Burkina-Faso, 8 (7.8%) in Benin, 6 (5.9%) in Togo, 6 (5.9%) in Sierra Leone, 4 (3.9%) in Côte d’Ivoire, 4 (3.9%) in Mali, 3 (2.9%) in Gambia, 2 (2%) in Mauritania, 1 (1%) in Cape Verde, and 1 (1%) in Niger. We did not find any published studies on carbapenem resistance in Guinea, Guinea-Bissau, or Liberia (Fig. 3).

Fig. 3.

Map of the West African region with the number of studies per country (adapted from https://www.mewc.org/index.php/countries/west-africa).

Type of studies

The type of study was specified in 57 publications (55.9%), including prospective, retrospective, descriptive, cross-sectional, case report, antimicrobial resistance surveillance, and screening program studies.

Samples

The origin of the samples of CRB strains was specified in 93 studies (total 300 cases). The number of sample types per study varied from 1 to 12. CRB were mainly isolated from urine and wound/pus samples (p<0.0001). The sample types included isolates from urine 73/300 (24.3%), pus/wounds 69/300 (23%), blood 39/300 (13%), sputum’s/tracheal aspirates 29/300 (9.7%), stool/rectal samples 26/300 (8.7%), vaginal and endocervical samples 24/300 (8%), samples from pleural fluids 13/300 (4.3%), cerebrospinal fluids 11/300 (3.7%), semen samples 7/300 (2.3%), articular fluids 2/300 (0.7%), peritoneal fluids 2/300 (0.7%), tissues 2/300 (0.7%), bone samples 1/300 (0.3%), skin swabs 1/300 (0.3%), and samples from gastric fluids 1/300 (0.3%) (Table 1, Fig. 4). Eye and ear swabs were considered pus samples.

Fig. 4.

Distribution of sample types from which CRB were isolated in West African countries.

Prevalence of carbapenem-resistant bacteria in West Africa

The average prevalence of CRB in West Africa was (1902/41635; 4.6%), and the prevalence of CRB per country ranged from 1.6% to 18.6%. More specifically, Niger (11/59; 18.6%) and Nigeria (968/5396; 17.9%) exhibited the highest prevalence of CRB, followed by Gambia (17/117; 14.5%), Côte d’Ivoire (26/262; 9.9%), Benin (64/790; 8.1%), Sierra Leone (6/79; 7.6%), Cape Verde (6/98; 6.1%), Senegal (214/4039; 5.3%), Burkina Faso (52/1421; 3.7%), Mali (8/396; 2%), Ghana (467/25071; 1.9%), Mauritania (8/486; 1.6 %), and Togo (55/3421; 1.6%), according to the antibiotic susceptibility assays reported in the articles incorporated into this systematic review (Fig. 5).

Fig. 5.

Prevalence of CRB in West African countries.

Distribution of carbapenem-resistant genera in West Africa

All studies included in this review reported CRB belonging to the order Enterobacterales. In total, 101 studies mentioned carbapenem-resistant bacterial species, genera, or families. Among 101 studies, 36 cases of the Enterobacteriaceae family were reported without a specified genus. Studies that specified genera or species (total 130 cases) reported a total of 11 genera, including Escherichia spp. 34/130 (26.1%), Klebsiella spp. 27/130 (20.8%), Pseudomonas spp. 26/130 (20%), Acinetobacter spp. 25/130 (19.2%), Enterobacter spp. 9/130 (6.9%), Proteus spp. 3/130 (2.3%), Salmonella spp. 2/130 (1.5%), Sphingomonas spp. 1/130 (0.8%), Stenotrophomonas spp. 1/130 (0.8%), Burkholderia spp. 1/130 (0.8%), and Morganella spp. 1/130 (0.8%) (Fig. 6, Table 1). CRB were mainly Escherichia spp., Klebsiella spp., Pseudomonas spp., and Acinetobacter spp. (p<0.0001).

Fig. 6.

Prevalence of carbapenem-resistant bacterial genera in West African countries.

Carbapenemase genes reported in West Africa

Fifty studies (49%) from 11 countries described the carbapenemase genes involved in bacterial carbapenem resistance (total 104 cases). Carbapenemases encoded by these genes belonged to the four Ambler classes and included 13 types: bla _OXA-type carbapenemases (34/104; 32.7%), bla _NDM (31/104; 29.8%), bla _VIM (13/104; 12.5%), bla _SHV-type carbapenemases (8/104; 7.7%), bla _KPC (4/104; 3.8%), bla _ACT (3/104; 2.9%), bla _IMP (3/104; 2.9), bla _CMY-type carbapenemases (2/104; 1.9%), bla _GES (2 /104; 1.9%), bla _CTX-M-type carbapenemases (1/104; 1%), bla _PER (1/104; 1%), bla _DIM (1/104; 1%), and ble _MBL-type carbapenemases (1/104; 1%) (Table 1, 2). OXA-type and NDM-type carbapenemases were the most prevalent in West Africa (p<0.0001). The distribution of carbapenemase genes by country is shown in Table 2.

Table 2.

Carbapenemase genes reported in studies from West African countries

Country	Carbapenemase genes
	Class A					Class B					Class C		Class D
	bla KPC	bla CTX-M *	bla SHV *	bla GES	bla PER	blaNDM	bla VIM	bla IMP	bla DIM	ble MBL	bla ACT	bla CMY *	bla OXA *
Nigeria
Ghana
Senegal
Burkina-Faso
Benin
Togo
Sierra-Leone
Côte d’Ivoire
Mali
Gambia
Cape Verde

Gray color means that a carbapenemase gene was reported in study from this country; *gene encoding carbapenem hydrolyzing enzyme variants

Carbapenemase genes reported in West Africa

Fifty studies (49%) from 11 countries described the carbapenemase genes involved in bacterial carbapenem resistance (total 104 cases). Carbapenemases encoded by these genes belonged to the four Ambler classes and included 13 types: bla _OXA-type carbapenemases (34/104; 32.7%), bla _NDM (31/104; 29.8%), bla _VIM (13/104; 12.5%), bla _SHV-type carbapenemases (8/104; 7.7%), bla _KPC (4/104; 3.8%), bla _ACT (3/104; 2.9%), bla _IMP (3/104; 2.9), bla _CMY-type carbapenemases (2/104; 1.9%), bla _GES (2 /104; 1.9%), bla _CTX-M-type carbapenemases (1/104; 1%), bla _PER (1/104; 1%), bla _DIM (1/104; 1%), and ble _MBL-type carbapenemases (1/104; 1%) (Table 1, 2). OXA-type and NDM-type carbapenemases were the most prevalent in West Africa (p<0.0001). The distribution of carbapenemase genes by country is shown in Table 2.

Mobile genetic elements carrying carbapenemase genes

Twenty-one out of 102 studies (20.6%) reported and specified mobile genetic elements carrying the genetic determinants of carbapenemases (Table 1). The mobile genetic elements included plasmids, integrons, and composite transposons delimited by insertion sequences (IS). The gene bla _NDM-1 in Acinetobacter spp. described in studies from Nigeria and Côte d’Ivoire was generally carried by IncF-type plasmids or Tn125 composite transposons delimited by ISAba125 (Table 1). The gene bla _NDM-5 was usually carried by IncX3-type plasmids. The gene bla _NDM-5 carried by E. xiangfangensis isolated in Togo was part of composite transposons delimited by IS5 (Table 1). The gene bla _OXA-181 carried by Enterobacter spp., Klebsiella spp., and E. coli (studies from Togo, Ghana, and Burkina-Faso) was generally carried by IncX3-, ColKP3-, IncFIC(FII)-, and IncFI-type plasmids. When bla _OXA-181 was carried by IncX3-like plasmids, it was part of Tn2013 (Table 1). The gene bla _OXA-48 reported in papers from Burkina-Faso, Senegal, and Cape Verde was located on Tn1999 or Tn1999.2 carried by IncL/M-type plasmids. Moreover, several IncFI- and IncX3-type plasmids were reported to be bla _OXA-48 carriers (Table 1). In Acinetobacter spp. reported in studies from Nigeria and Senegal, bla _OXA-23 was mainly associated with Tn2006 and Tn2007, delimited respectively by ISAba1 and ISAba4 (Table 1). In studies from Ghana and Nigeria, the bla _OXA-58 gene carried by Acinetobacter spp. was found within composite transposons delimited by ISAba3 (Table 1). The gene bla _OXA-420 was part of a composite transposon delimited by ISAba3-like insertion sequence, while bla _VIM-2, carried by P. aeruginosa, was part of class 1 integrons (Table 1).

Methods used to study carbapenem resistance in West Africa

One hundred and one studies have reported total 172 cases where phenotypic and genotypic methods were used to assess carbapenem resistance in West Africa. The Kirby-Bauer disc diffusion method (74/172; 43.0%) was the most used phenotypic method (p<0.0001), followed by the Vitek 2 automated system (12/172; 7.0%), E-test (12/172; 7.0%), broth dilution and microdilution methods (7/172; 4.1%), MicroScan WalkAway Plus System (2/172; 1.2%), and the BD Phoenix^™ automated system (1/172; 0.6%) (Table 3). Among genotypic methods, PCR (standard PCR and RT-PCR) was the most used (38/172; 22.1%) (p=0.03), followed by whole-genome sequencing (17/172; 9.9%), and partial genome sequencing (9/172; 5.2%) (Table 3).

Table 3.

Summary of methods used to study carbapenem resistance in West Africa

	Method	n/N (%)	p value
Phenotypic	Kirby-Bauer Disc diffusion method	74/172 (43.0)	<0.0001
	Vitek 2 automated system	12/172 (7.0)
	E-test	12/172 (7.0)
	Broth dilution and microdilution method	7/172 (4.1)
	MicroScan WalkAway plus System	2/172 (1.2)
	BD Phoenix™ automated system	1/172 (0.6)
Genotypic	Standard PCR and RT-PCR	38/172 (22.1)	0.03
	Whole genome sequencing	17/172 (10.0)
	Partial genome sequencing	9/172 (5.2)

n- the number of particular tests; N- the total number of tests. Data were compared by χ ² test.

Origins and age groups of CRB carriers

The origin of CRB was reported in 104 cases published in 67 out of 102 studies. CRB were mainly hospital-acquired (59/104; 56.7%), whereas community-acquired CRB accounted for 43.3% (45/104; p=0.003). In addition, 54 studies specified the age groups of people carrying CRB (total 118 cases) including adults (46/118; 39.0%), children/neonates (45/118; 38.1%), and elderly people (27/118; 22.9%). Overall CRB were most frequently isolated from adults and children/neonates (p=0.0002).

Alternative antibiotics retaining good activity against CRB

According to the antimicrobial susceptibility testing results in thirty-one studies (30.4%), 51 successful cases of antibiotics with good activity against CRB were reported. The list of antibiotics active against CRB includes amikacin 14/51 (27.5%), colistin 12/51 (23.5%), fosfomycin 6/51 (11.8%), tigecycline 4/51 (7.8%), netilmicin 2/51 (3.9%), gentamicin 2/51 (3.9%), ciprofloxacin 2/51 (3.9%), minocycline 2/51 (3.9%), nitrofurantoin 1/51 (2%), polymyxin B 1/51 (2%), ceftazidime/avibactam/aztreonam 1/51 (2%), rifampicin 1/51 (2%), tobramycin 1/51 (2%), ceftazidime/avibactam 1/51 (2%), and aztreonam 1/51 (2%) (Fig. 7). Amikacin and colistin were the two most frequently reported alternative antibiotics (p=0.002).

Fig. 7.

Antibiotics active against CRB in countries of West Africa.

DISCUSSION

This systematic review revealed that, in the countries of West Africa, CRB were mostly isolated from patients’ urinary tracts (24.3%), pus/wounds (23%), blood (13%), sputum/tracheal aspirates (9.7%), stool/rectal samples (8.7%), and vaginal/endocervical samples (8%). Overall, this aligns with studies conducted in other regions of the world. Thus, a significant number of CRB were isolated from the urinary tract (19%) and wound/pus (18%) samples of patients in East Africa, although the distribution was shifted towards the respiratory tract (23%) and blood (22%) samples [113]. In the USA [114], CRB were isolated mainly from patients’ urine (87.1%) and blood (10.8%). In Japan [115], the urinary tract was also the main source of CRB (33%), followed by the respiratory tract (21%) and blood (11%). The urinary tract, pus/wound, blood, and respiratory tract appear to be the main sources of CRB worldwide.

The average prevalence of CRB in West Africa was 4.6% (1902/41635), ranging from 1.6% to 18.6%. This average of 4.6% is low compared to the prevalence of CRB reported on the Indian subcontinent (18-31%) [116, 117], Africa and the Middle East (5.7-26.9%) [118], and Saudi Arabia 38-46% [119]. However, the prevalence of CRB reported in the USA was 4.5% [120]. In addition, prevalence rates of up to 7% for CR-E. coli, 33.4% for CR-K. pneumoniae, 38.2% for CR-P. aeruginosa spp., and 82.1% for CR-Acinetobacter spp. were reported in endemic areas of Europe (Albania, Greece, Romania, and Croatia) [121]. The reason for the significant variation in CRB prevalence among West African countries (1.6% to 18.6%) remains to be determined. Larger-scale studies, especially in countries where no studies on CRB have been conducted yet, could help estimate the average prevalence of CRB in West Africa more accurately.

This systematic review identified that the most reported CRB genera in West Africa were Escherichia spp. (26.1%), followed by Klebsiella spp. (20.8%), Pseudomonas spp. (20%), and Acinetobacter spp. (19.2%). These results are similar to values reported in studies from East Africa and the Asia-Pacific region (P. aeruginosa, 17-18.9%; A. baumannii, 23%) [113, 117]. However, Lee et al. [122] reported a much higher prevalence of carbapenem-resistant A. baumannii (71.7%) in the Asia-Pacific region. Furthermore, it seems that carbapenem-resistant Klebsiella spp. is much more common in Asia and the USA than in West Africa. Indeed, at least two papers [114, 123] reported a 53-73.9% prevalence of CR-K. pneumoniae in Asia and the USA.

In West Africa, 13 types of carbapenemases have been reported, with a predominance of the bla _OXA-type (32.7%) and bla _NDM (29.8%), followed by bla _VIM (12.5%), bla _SHV (7.7%), bla _KPC (3.8%), bla _ACT (2.9%), bla _IMP (2.9%), bla _CMY (1.9%), bla _GES (1.9%), bla _CTX-M (1%), bla _PER (1%), bla _DIM (1%), and ble _MBL (1/104; 1%). These numbers are somewhat similar to results obtained in South Africa and Central Africa, which showed a predominance of bla _NDM-type and bla _OXA-type carbapenemases [124-126]. However, the patterns of carbapenemase genes reported in this review diverge significantly from those observed in the East African region, Asia-Pacific region, Canada, Brazil, and the USA. Six types of carbapenemases have been reported in studies from East Africa, with a predominance of bla _VIM (28.6%), followed by bla _NDM (25%), bla _OXA-type (17.9%), bla _IMP (14.3%), bla _KPC (7.1%), and bla _SPM (7.1%) [113]. Seven types of carbapenemases have been listed in papers from the Asia-Pacific region, with a predominance of bla _VIM (29.0%), followed by bla _NDM (24.9%), bla _VEB (20.8%), bla _IMP (18.0%), bla _GES (5.7%), bla _TEM-type (3.3%), and bla _KPC (1.6%) [117]. Five types of carbapenemases have been described by scientists from the USA: bla _KPC (62.4%), bla _NDM (2%), bla _OXA-type (1.6%), bla _VIM (0.4%), and bla _IMP (0.2%) [127]. In Canada, bla _NDM (37%) and bla _KPC (31%) predominated, while in Brazil and Russia, the prevalence of bla _KPC (94.7%) and bla _OXA-48 (65.6%) correspondingly was reported [126].

The mobile genetic elements (MGE) carrying carbapenemase genes described in this systematic review are very similar to those reported elsewhere. Thus, similar to the results from this review, Pagano et al. [128] noted that the bla _NDM-1 gene is carried by Tn125 composite transposon delimited by ISAba125. Li et al. and Yang et al. [129, 130] reported the bla _NDM-5 gene within composite transposons (delimited by IS5) carried by IncX3-type plasmids in China, which is in accordance with the results obtained in West African countries. The bla _OXA-181 gene was also reported within Tn2013 transposon carried by IncX3- and ColKP3-type plasmids in China, India, and Germany [131-133]. Furthermore, IncL/M-type plasmids carrying the bla _OXA-48 gene were reported in China and Europe [134-137]. Our analysis of literature data showed that, in most cases, the bla _OXA-48 gene was carried by Tn1999.2 and Tn1999 transposons. The bla _OXA-23 gene in A. baumannii was also reported in association with Tn2006 and Tn2007 transposons in studies from Algeria, Spain, Tahiti, France, Turkey, Vietnam, Romania, Libya, Australia, and France [128], which corresponds to our results. In papers from China, Italy, Taiwan, and Lebanon, as in our review, the bla _OXA-58 gene was observed within composite transposons delimited by ISAba3 [128]. Furthermore, the bla _OXA-420 gene was also reported within composite transposons delimited by ISAba3 in a study from India [138], while in papers from Korea, East Africa, and Italy [139-141], the bla _VIM-2 gene was reported as a cassette in class 1 integrons carried by plasmids. An in-depth analysis and comparison of carbapenemase gene-associated MGEs reported from West Africa with the corresponding data from other parts of the world could provide a better understanding of the evolution and dissemination of carbapenemase gene-associated MGEs worldwide.

This systematic review revealed that the Kirby-Bauer disc diffusion (43.0%), PCR (22.1%), whole-genome sequencing (9.9%), Vitek 2-system (7.0%), E-test (7.0%), and partial genome sequencing (5.2%) were the most used methods for the detection of carbapenem resistance. It should be noted that more than one method was used to detect CRB in several studies. With a few exceptions, the methods, and technologies for detecting carbapenem resistance reported in studies from West Africa are the same as those used in Europe and East Africa. To illustrate, according to [121] the disc diffusion method and MIC determination methods were used in 90% of European labs while PCR and WGS – in 50% and 11% of labs correspondingly whereas the disc diffusion method (64.7%), PCR (47.1%), sequencing (23.5%), WGS (5.9%), BD Phoenix^™ automated system (5.9%), and E-test (5.9%) were the most commonly used techniques in the labs of East African countries [113].

This systematic review revealed that amikacin, colistin, fosfomycin, and tigecycline are alternative antibiotics with the highest activity against CRB. In Africa, the Middle East, the Asia-Pacific region, and the USA, the most frequently reported alternative antibiotics active against CRB were amikacin and colistin, followed by ceftazidime/avibactam, tigecycline, ceftolozane/tazobactam, minocycline, and gentamycin [114, 117, 118, 122, 127]. Colistin and amikacin seem to be the two most reported alternative antibiotics worldwide. Therefore, in West Africa, the administration of amikacin and colistin should be strictly monitored to delay, as much as possible, the appearance and generalization of mutant bacterial clones resistant to these antibiotics.

CONCLUSION

Our systematic review shows the past and present of carbapenem resistance in West Africa in detail. According to our results, the West African region has a low prevalence of CRB compared to other African, European, and Asian regions. Additional publications on carbapenem resistance in West Africa may provide more accurate data. It seems that there are similar patterns of carbapenemase gene distribution among bacteria from the West, Central, and Southern Africa while mobile genetic elements carrying carbapenemase genes appeared to be like those reported worldwide. The transfer of bacteria by international travelers may have played an important role in bacterial distribution in Africa and worldwide. Additional WGS, multilocus sequence typing (MLST), and phylogenetic analyses could deepen our understanding of CRB strains circulating in West Africa. Additional funds should be allocated to African researchers to better prevent and counter CRB epidemics. Moreover, the use of the few antibiotics still effective against CRB circulating in West Africa should be restricted to emergency cases to help preserve their activity as much as possible. Preliminary phytotherapy studies have shown that several plants contain natural compounds that may be effective against CRB. Therefore, phytotherapy should be further investigated as a new approach to fighting CRB in West Africa. This could lead to discovering phytomedicines that are highly effective against CRB.

Acknowledgments:

Authors sincerely thank Sylvestre Kossivi Atikako for his invaluable contributions to the literature search and data analysis.

Conflict of interest:

The authors declare that they have no conflict of interest.

REFERENCES

1. Elshamy AA, Aboshanab KM. A review on bacterial resistance to carbapenems: epidemiology, detection and treatment options. Future Sci OA. 2020;6(3):FSO438. https://doi.org/10.2144/fsoa-2019-0098.

2. Codjoe FS, Donkor ES. Carbapenem Resistance: A Review. Med Sci. 2017;6(1):1. https://doi.org/10.3390/medsci6010001.

3. Yin C, Yang W, Lv Y, Zhao P, Wang J. Clonal spread of carbapenemase-producing Enterobacteriaceae in a region, China. BMC Microbiol. 2022;22:81. https://doi.org/10.1186/s12866-022-02497-y.

4. Bonomo RA, Burd EM, Conly J, Limbago BM, Poirel L, Segre JA et al.Carbapenemase-Producing Organisms: A Global Scourge. Clin Infect Dis. 2018;66(8):1290-7. https://doi.org/10.1093/cid/cix893.

5. Habib A, Lo S, Villageois-Tran K, Petitjean M, Malik SA, Armand-Lefèvre L et al. Dissemination of carbapenemase-producing Enterobacterales in the community of Rawalpindi, Pakistan. PLOS ONE. 2022;17(7):e0270707. https://doi.org/10.1371/journal.pone.0270707.

6. World Health Organization. WHO publishes list of bacteria for which new antibiotics are urgently needed, 2017. Available from: https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed.

7. Alizadeh N, Rezaee MA, Kafil HS, Hasani A, Barhaghi MHS, Milani M et al. Evaluation of Resistance Mechanisms in Carbapenem-Resistant Enterobacteriaceae. Infect Drug Resist. 2020; 13:1377-85. https://doi.org/10.2147/IDR.S244357.

8. Tangden T, Adler M, Cars O, Sandegren L, Lowdin E. Frequent emergence of porin-deficient subpopulations with reduced carbapenem susceptibility in ESBL-producing Escherichia coli during exposure to ertapenem in an in vitro pharmacokinetic model. J.Antimicrob Chemother. 2013;68(6):1319-26. https://doi.org/10.1093/jac/dkt044.

9. Davies J. Where have All the Antibiotics Gone? Can J Infect Dis Med. Microbiol. 2006;17(5):287-90. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095086/. PMID: 18382641.

10. Worldometer. Population of Western Africa, 2023. https://www.worldometers.info/world-population/western-africa-population/.

11. Yehouenou CL, Soleimani R, Kpangon AA, Simon A, Dossou FM, Dalleur O. Carbapenem-Resistant Organisms Isolated in Surgical Site Infections in Benin: A Public Health Problem. Trop Med Infect Dis. 2022;7(8):200. https://doi.org/10.3390/tropicalmed7080200.

12. Assouma FF, Sina H, Adjobimey T, Noumavo ADP, Socohou A, Boya B et al. Susceptibility and Virulence of Enterobacteriaceae Isolated from Urinary Tract Infections in Benin. Microorganisms. 2023;11(1):213. https://doi.org/10.3390/microorganisms11010213.

13. Dougnon VT, Sintondji K, Koudokpon CH, Houéto M, Agbankpé AJ, Assogba P et al. Investigating Catheter-Related Infections in Southern Benin Hospitals: Identification, Susceptibility, and Resistance Genes of Involved Bacterial Strains. Microorganisms. 2023;11(3):617. https://doi.org/10.3390/microorganisms11030617.

14. Dougnon VT, Koudokpon H, Chabi Y, Fabiyi K, Legba B, Dougnon J et al. Infection Risks and Antimicrobial Resistance in Tertiary Hospitals in Benin: Study Cases of Sakété-Ifangni and Menontin Hospitals. Int J Infect. 2020;7(1):e99649. https://doi.org/10.5812/iji.99649.

15. Anago E, Ayi-Fanou L, Akpovi CD, Hounkpe WB, Agassounon-Djikpo Tchibozo M, Bankole HS et al. Antibiotic resistance and genotype of beta-lactamase producing Escherichia coli in nosocomial infections in Cotonou, Benin. Ann Clin Microbiol Antimicrob. 2015;14:5. https://doi.org/10.1186/s12941-014-0061-1.

16. Ombelet S, Kpossou G, Kotchare C, Agbobli E, Sogbo F, Massou F et al. Blood culture surveillance in a secondary care hospital in Benin: epidemiology of bloodstream infection pathogens and antimicrobial resistance. BMC Infect Dis. 2022;22:119. https://doi.org/10.1186/s12879-022-07077-z.

17. Yehouenou CL, Kpangon AA, Affolabi D, Rodriguez-Villalobos H, Van Bambeke F, Dalleur O et al. Antimicrobial resistance in hospitalized surgical patients: a silently emerging public health concern in Benin. Ann Clin Microbiol Antimicrob. 2020;19:54. https://doi.org/10.1186/s12941-020-00398-4.

18. Ahoyo AT, Baba-Moussa L, Anago AE, Avogbe P, Missihoun TD, Loko F et al. Incidence d’infections liées à Escherichia coli producteur de bêta lactamase à spectre élargi au Centre hospitalier départemental du Zou et Collines au Bénin. Médecine Mal Infect. 2007;37(11):746-52. https://doi.org/10.1016/j.medmal.2007.03.004.

19. Dembélé R, Soulama I, Kaboré WAD, Konaté A, Kagambèga A, N’Golo DC et al. Molecular Characterization of Carbapenemase-Producing Enterobacterales in Children with Diarrhea in Rural Burkina Faso. J Drug Deliv Ther. 2021;11(1):84-92. https://doi.org/10.22270/jddt.v11i1.4513.

20. Kaboré B, Ouédraogo HS, Zongo O, Ouédraogo GA, Tapsoba F, Bougma S et al. Emergence of New Delhi Metallo-β-Lactamase (NDM) Genes Detected from Clinical Strains of Escherichia coli Isolated in Ouagadougou, Burkina Faso. Int J Microbiol. 2023;2023:e4813225. https://doi.org/10.1155/2023/4813225.

21. Ouédraogo A-S, Compain F, Sanou M, Aberkane S, Bouzinbi N, Hide M et al. First Description of IncX3 Plasmids Carrying blaOXA-181 in Escherichia coli Clinical Isolates in Burkina Faso. Antimicrob Agents Chemother. 2016;60(5):3240-2. https://doi.org/10.1128/AAC.00147-16.

22. Konaté A, Dembélé R, Guessennd NK, Kouadio FK, Kouadio IK, Ouattara MB et al. Epidemiology and Antibiotic Resistance Phenotypes of Diarrheagenic Escherichia Coli Responsible for Infantile Gastroenteritis in Ouagadougou, Burkina Faso. Eur J Microbiol Immunol. 2017;7(3):168-75. https://doi.org/10.1556/1886.2017.00014.

23. Kafando H, Zangréyanogo H, Dionou P, Bayala D, Seihon M,Traoré Netal.Resistanceof Clinical Isolates of Escherichia coli and Klebsiella pneumoniae in “Boucle du Mouhoun, Burkina Faso”: one year’s Experience in Antibiotic Resistance Surveillance. International Journal of Pharmaceutical and Bio Medical Science. 2023;3(8):404-9. https://doi.org/10.47191/ijpbms/v3-i8-04.

24. Sanou S, Ouedraogo AS, Aberkane S, Vendrell J, Ouchar O, Bouzimbi N et al. Prevalence and Molecular Characterization of Extended Spectrum β-Lactamase, Plasmid-Mediated Quinolone Resistance, and Carbapenemase-Producing Gram-Negative Bacilli in Burkina Faso. Microb Drug Resist. 2021;27(1):18-24. https://doi.org/10.1089/mdr.2020.0134.

25. Ouédraogo B, Ouattara AK, Dabiré AM, Tiemtoré RYW, Sougé S, Simporé J. Resistance of Klebsiella to Imipenem by Production of Carbapenemase Gene blaIMP at Centre Hospitalier Universitaire Pédiatrique Charles de Gaulle, Ouagadougou, Burkina Faso. Int J Clin Med. 2023;14(8):347-56. https://doi.org/10.4236/ijcm.2023.148030.

26. Kaboré B, Cisse H, Zongo KJ, Sanou I, Zeba B, Traoré Y et al. Phenotypic detection of Metallo-β-Lactamase in imipenem-resistant Pseudomonas aeruginosa and Stenotrophomonas maltophilia at Schiphra Hospital of Ouagadougou in Burkina Faso. Microbes Infect Dis. 2022;3(1):128-34. https://doi.org/10.21608/mid.2021.70446.1138.

27. Kpoda DS, Guessennd N, Bonkoungou JI, Ouattara MB, Konan F, Ajayi A et al. Prevalence and resistance profile of extended-spectrum -lactamases-producing Enterobacteriaceae in Ouagadougou, Burkina Faso. Afr J Microbiol Res. 2017;11(27):1120-6. https://doi.org/10.5897/AJMR2017.8598.

28. Konaté A, Guessennd NK, Kouadio FK, Dembélé R, Kagambèga A, Kouadio IK et al. Epidemiology and Resistance Phenotypes of Salmonella spp. Strains Responsible for Gastroenteritis in Children less than Five Years of Age in Ouagadougou, Burkina Faso. Arch Clin Microbiol. 2019;10:90. https://doi.org/10.36648/1989-8436.10.2.90.

29. Freire S, Grilo T, Teixeira ML, Fernandes E, Poirel L, Aires-de-Sousa M. Screening and Characterization of Multidrug-Resistant Enterobacterales among Hospitalized Patients in the African Archipelago of Cape Verde. Microorganisms. 2022;10(7):1426. https://doi.org/10.3390/microorganisms10071426.

30. M’Lan-Britoh A, Syndou M, Catherine BC, Stéphane KK, Flore Z, Nathalie G et al. Sensibilité aux antimicrobiens de souches de Pseudomonas aeruginosa isolées dans un Hôpital de niveau tertiaire en Côte d’Ivoire. Revue Bio-Africa. 2017;16:20-5. Available from: https://revues-ufhb-ci.org/fichiers/FICHIR_ARTICLE_2276.pdf.

31. Cholley P, Ka R, Guyeux C, Thouverez M, Guessennd N, Ghebremedhin B et al. Population Structure of Clinical Pseudomonas aeruginosa from West and Central African Countries. PLOS ONE. 2014;9(9):e107008. https://doi.org/10.1371/journal.pone.0107008.

32. Jeannot K, Guessennd N, Fournier D, Müller E, Gbonon V, Plésiat P. Outbreak of metallo-β-lactamase VIM-2-positive strains of Pseudomonas aeruginosa in the Ivory Coast. J Antimicrob Chemother. 2013;68(12):2952-4. https://doi.org/10.1093/jac/dkt296.

33. Gba K, Bonnin R, Abe IA, Tahou E, Makaya N, Dortet L et al. First Detection of Carbapenemases-Producing Acinetobacter baumannii and Acinetobacter nosocomialis in Côte d’Ivoire. J Adv Biol Biotechnol. 2022;25(6):10-23. https://doi.org/10.9734/jabb/2022/v25i630286.

34. Sanneh B, Riley OD, Jallow HS, Kebbeh A, Camara Y, Barrow E et al. High faecal carriage of multi-drug resistant Enterobacteriaceae and other gram negative strains among food handlers in Cosmopolitan Cities of The Gambia. GSC Biol Pharm Sci. 2020;13(02):181-9. https://doi.org/10.30574/gscbps.2020.13.2.0364.

35. Sanneh B, Kebbeh A, Jallow HS, Camara Y, Mwamakamba LW, Ceesay IF et al. Prevalence and risk factors for faecal carriage of Extended Spectrum β-lactamase producing Enterobacteriaceae among food handlers in lower basic schools in West Coast Region of The Gambia. PLOS ONE. 2018;13(8):e0200894. https://doi.org/10.1371/journal.pone.0200894.

36. Bah SY, Kujabi MA, Darboe S, Kebbeh N, Kebbeh BFK, Kanteh A et al.Acquisition and carriage of genetically diverse multi-drug resistant gram-negative bacilli in hospitalised newborns in The Gambia. Commun Med. 2023;3:79. https://doi.org/10.1038/s43856-023-00309-6.

37. Ayibieke A, Kobayashi A, Suzuki M, Sato W, Mahazu S, Prah I et al. Prevalence and Characterization of Carbapenem-Hydrolyzing Class D β-Lactamase-Producing Acinetobacter Isolates From Ghana. Front Microbiol. 2020;11:587398. https://doi.org/10.3389/fmicb.2020.587398.

38. Olu-Taiwo MA, Opintan JA, Codjoe FS, Obeng Forson A. Metallo-Beta-Lactamase-Producing Acinetobacter spp. from Clinical Isolates at a Tertiary Care Hospital in Ghana. BioMed Res Int. 2020;2020:e3852419. https://doi.org/10.1155/2020/3852419.

39. Dwomoh FP, Kotey FCN, Dayie NTKD, Osei M-M, Amoa-Owusu F, Bannah V et al. Phenotypic and genotypic detection of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in Accra, Ghana. PLOS ONE. 2022;17(12):e0279715. https://doi.org/10.1371/journal.pone.0279715.

40. Codjoe FS, Donkor ES, Smith TJ, Miller K. Phenotypic and Genotypic Characterization of Carbapenem-Resistant Gram-Negative Bacilli Pathogens from Hospitals in Ghana. Microb Drug Resist. 2019;25(10):1449-57. https://doi.org/10.1089/mdr.2018.0278.

41. Hackman H. Emergence of Carbapenem-resistant Enterobacteriaceae among Extended-spectrum Beta-lactamase Producers in Accra, Ghana. Journal of Natural Sciences Research. 2017;7(24). Available from: https://api.semanticscholar.org/CorpusID:80296186.

42. Asamoah B, Labi A-K, Gupte HA, Davtyan H, Peprah GM, Adu-Gyan F et al. High Resistance to Antibiotics Recommended in Standard Treatment Guidelines in Ghana: A Cross-Sectional Study of Antimicrobial Resistance Patterns in Patients with Urinary Tract Infections between 2017–2021. Int J Environ Res Public Health. 2022;19(24):16556. https://doi.org/10.3390/ijerph192416556.

43. Prah I, Ayibieke A, Mahazu S, Sassa CT, Hayashi T, Yamaoka S et al. Emergence of oxacillinase-181 carbapenemase-producing diarrheagenic Escherichia coli in Ghana. Emerg Microbes Infect. 2021;10(1):865-73. https://doi.org/10.1080/22221751.2021.1920342.

44. Monnheimer M, Cooper P, Amegbletor HK, Pellio T, Groß U, Pfeifer Y et al. High Prevalence of Carbapenemase-Producing Acinetobacter baumannii in Wound Infections, Ghana, 2017/2018. Microorganisms. 2021;9(3):537. https://doi.org/10.3390/microorganisms9030537.

45. Quansah E, Amoah Barnie P, Omane Acheampong D, Obiri-Yeboah D, Odarkor Mills R, Asmah E et al. Geographical Distribution of β-Lactam Resistance among Klebsiella spp. from Selected Health Facilities in Ghana. Trop Med Infect Dis. 2019;4(3):117. https://doi.org/10.3390/tropicalmed4030117.

46. Deku JG, Duedu KO, Kpene GE, Kinanyok S, Feglo PK. Carbapenemase Production and Detection of Colistin-Resistant Genes in Clinical Isolates of Escherichia Coli from the Ho Teaching Hospital, Ghana. Can J Infect Dis Med Microbiol. 2022;2022:1544624. https://doi.org/10.1155/2022/1544624.

47. Owusu FA, Obeng-Nkrumah N, Gyinae E, Kodom S, Tagoe R, Tabi BKA et al. Occurrence of Carbapenemases, Extended-Spectrum Beta-Lactamases and AmpCs among Beta-Lactamase-Producing Gram-Negative Bacteria from Clinical Sources in Accra, Ghana. Antibiotics. 2023;12(6):1016. https://doi.org/10.3390/antibiotics12061016.

48. LabiA-K,NielsenKL,MarvigRL,BjerrumS,Enweronu-Laryea C, Bennedbæk M et al. Oxacillinase-181 Carbapenemase-Producing Klebsiella pneumoniae in Neonatal Intensive Care Unit, Ghana, 2017-2019. Emerg Infect Dis. 2020;26(9):2235-8. https://doi.org/10.3201/eid2609.200562.

49. Akenten CW, Khan NA, Mbwana J, Krumkamp R, Fosu D, Paintsil EK et al. Carriage of ESBL-producing Klebsiella pneumoniae and Escherichia coli among children in rural Ghana: a cross-sectional study. Antimicrob Resist Infect Control. 2023;12:60. https://doi.org/10.1186/s13756-023-01263-7.

50. Obeng-Nkrumah N, Hansen DS, Awuah-Mensah G, Blankson NK, Frimodt-Møller N, Newman MJ et al. High level of colonization with third-generation cephalosporin-resistant Enterobacterales in African community settings, Ghana. Diagn Microbiol Infect Dis. 2023;106(1):115918. https://doi.org/10.1016/j.diagmicrobio.2023.115918.

51. Owusu-Oduro P. Prevalence of Carbapenemase Producing Enterobacteriaceae in Urinary Tract Infection Patients in Ghana. South Am J Public Health. 2016;4:372-83. Available from: https://api.semanticscholar.org/CorpusID:78247980.

52. Boisramé-Gastrin S, Tandé D, Münck M-R, Gouriou S, Nordmann P, Naas T. Salmonella carriage in adopted children from Mali: 2001–08. J Antimicrob Chemother. 2011;66(10):2271-6. https://doi.org/10.1093/jac/dkr307.

53. Dicko OA, Traoré A, Maiga A, Coulibaly DM, Diarra B, Maiga II. Antimicrobial susceptibility of Pseudomonas aeruginosa strains in Bamako, Mali. Afr J Bacteriol Res. 2021;13(2):16-21. Available from: https://academicjournals.org/journal/JBR/article-abstract/39AB29B67722.

54. Ouédraogo J, Gadi Timbiné L, Traoré B, Karim Sangaré A, Sogodogo E, Haukka K et al. Multirésistance to antibiotics of pathogens isolated from human, animal and environment in the District of Bamako, Mali. MOJ Biol Med. 2023;8(2):58-61. Available from: https://api.semanticscholar.org/CorpusID:261037573.

55. Sangare SA, Rondinaud E, Maataoui N, Maiga AI, Guindo I, Maiga A et al. Very high prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae in bacteriemic patients hospitalized in teaching hospitals in Bamako, Mali. PLOS ONE. 2017;12(2):e0172652. https://doi.org/10.1371/journal.pone.0172652.

56. Hailaji NSM, Ould Salem ML, Ghaber SM. La sensibilité aux antibiotiques des bactéries uropathogènes dans la ville de Nouakchott – Mauritanie. Prog En Urol. 2016;26(6):346-52. https://doi.org/10.1016/j.purol.2016.04.004.

57. Lemine Ould Salem M. Epidemiology and Sensitivity to Antibiotics of Enterobacteriaceae Producing Extended-Spectrum Beta-Lactamases (ESBL) in the Region of Nouakchott (Mauritania). Gen Med Clin Pract. 2022;5(2):063. https://doi.org/10.31579/2639-4162/063.

58. Abdoulaye O, Bacha BSM, Aghali NH, Abdoulaye I, Abdoulaye MB, Lo G et al. Profile of multidrug-resistant clinical bacterial isolates at the National Hospital of Zinder (NHZ), Niger Republic in 2021: Profil des souches bactériennes multirésistantes isolées à l’Hôpital National de Zinder (HNZ), République du Niger en 2021. Afr J Clin Exp Microbiol. 2022;23(4):369-77. https://doi.org/10.4314/ajcem.v23i4.5.

59. Olowo-okere A, Ibrahim YKE, Olayinka BO, Ehinmidu JO, Mohammed Y, Nabti LZ et al. Phenotypic and genotypic characterization of clinical carbapenem-resistant Enterobacteriaceae isolates from Sokoto, northwest Nigeria. New Microbes New Infect. 2020;37:100727. https://doi.org/10.1016/j.nmni.2020.100727.

60. Odih EE, Oaikhena AO, Underwood A, Hounmanou YMG, Oduyebo OO, Fadeyi A et al. High Genetic Diversity of Carbapenem-Resistant Acinetobacter baumannii Isolates Recovered in Nigerian Hospitals in 2016 to 2020. mSphere. 2023;8(3):e00098-23. https://doi.org/10.1128/msphere.00098-23.

61. Onanuga A, Vincent CH, Eboh DD. Carbapenem Resistance among Extended Spectrum Beta-Lactamases Producing Escherichia coli and Klebsiella pneumoniae isolates from Patents with Urinary Tract Infections in Port-Harcourt, Nigeria. Niger J Pharm Appl Sci Res. 2019;8(1):16-23. Available from: https://www.nijophasr.net/index.php/nijophasr/article/view/268.

62. Jamal W, Iregbu K, Fadhli A, Khodakhast F, Nwajiobi-Princewill P, Medugu N et al. A point-prevalence survey of carbapenem-resistant Enterobacteriaceae in two different cities in Kuwait and Nigeria. Afr J Clin Exp Microbiol. 2022;23(4):358-68. https://doi.org/10.4314/ajcem.v23i4.4.

63. Rabiu I, Auwal ZA, Muhammad HA. Detection of Carbapenemase Producing Enterobacteriaceae from Clinical Samples and their Susceptibility to Conventional Antibiotics and Medicinal Plant Extracts. Ann Exp Mol Biol. 2022;4(1):000115. https://doi.org/10.23880/aemb-16000115.

64. Ibadin EE, Eghiomon A, Idemudia NL, Anogie NA, Eriamiatoe RE, Dedekumah EI et al. Phenotypic Distribution of Serine- and Zinc-Type Carbapenemases Among Clinical Bacterial Isolates in a Tertiary Hospital in Benin, Nigeria. Int J Enteric Pathog. 2020;8(1):3-7. https://doi.org/10.34172/ijep.2020.02.

65. Mukail A, Tytler BA, Adeshina GO, Igwe JC. Incidence of carbapenemase production among antibiotic resistant Klebsiella isolates in Zaria, Nigeria. Niger J Biotechnol. 2019;36(1):138-45. https://doi.org/10.4314/njb.v36i1.18.

66. Shettima SA, Tickler IA, dela Cruz CM, Tenover FC. Characterisation of carbapenem-resistant Gram-negative organisms from clinical specimens in Yola, Nigeria. J Glob Antimicrob Resist. 2020;21:42-5. https://doi.org/10.1016/j.jgar.2019.08.017.

67. Ogbolu DO, Alli OAT, Oluremi AS, Ogunjimi YT, Ojebode DI, Dada V et al. Contribution of NDM and OXA-type carbapenemases to carbapenem resistance in clinical Acinetobacter baumannii from Nigeria. Infect Dis. 2020;52(9):644-50. https://doi.org/10.1080/23744235.2020.1775881.

68. Mohammed Y, Zailani SB, Onipede AO. Characterization of KPC, NDM and VIM Type Carbapenem Resistance Enterobacteriaceae from North Eastern, Nigeria. J Biosci Med. 2015;3(11):100-7. https://doi.org/10.4236/jbm.2015.311013.

69. Ettu AO, Oladapo BA, Oduyebo OO. Prevalence of carbapenemase production in Pseudomonas aeruginosa isolates causing clinical infections in Lagos University Teaching Hospital, Nigeria. Afr J Clin Exp Microbiol. 2021;22(4):498-503. https://doi.org/10.4314/ajcem.v22i4.10.

70. Adesanya OA, Igwe HA, Adesanya OA, Igwe HA. Carbapenem-resistant Enterobacteriaceae (CRE) and gram-negative bacterial infections in south-west Nigeria: a retrospective epidemiological surveillance study. AIMS Public Health. 2020;7(4):804-15. https://doi.org/10.3934/publichealth.2020062.

71. Anibijuwon II, Gbala ID, Adebisi OO. Carbapenem-Resistant Enterobacteriaceae among In-Patients of Tertiary Hospitals in Southwest, Nigeria. Not Sci Biol. 2018;10(3):310-7. https://doi.org/10.15835/nsb10310300.

72. Medugu N, Tickler IA, Duru C, Egah R, James AO, Odili V et al. Phenotypic and molecular characterization of beta-lactam resistant Multidrug-resistant Enterobacterales isolated from patients attending six hospitals in Northern Nigeria. Sci Rep. 2023;13:10306. https://doi.org/10.1038/s41598-023-37621-z.

73. Aminu A, Daneji IM, Yusuf MA, Jalo RI, Tsiga-Ahmed FI, Yahaya M et al. Carbapenem-resistant Enterobacteriaceae infections among patients admitted to intensive care units in Kano, Nigeria. Sahel Med J. 2021;24:1. Available from: https://www.smjonline.org/article.asp?issn=1118-8561;year=2021;volume=24;issue=1;spage=1;epage=9;aulast=Aminu;type=0.

74. Odewale G, Jibola-Shittu MY, Ojurongbe O, Olowe RA, Olowe OA. Genotypic Determination of Extended Spectrum β-Lactamases and Carbapenemase Production in Clinical Isolates of Klebsiella pneumoniae in Southwest Nigeria. Infect Dis Rep. 2023;15(3):339-53. https://doi.org/10.3390/idr15030034.

75. Olalekan A, Bader BK, Iwalokun B, Wolf S, Lalremruata A, Dike A et al. High incidence of carbapenemase-producing Pseudomonas aeruginosa clinical isolates from Lagos, Nigeria. JAC-Antimicrob Resist. 2023;5(2):dlad038. https://doi.org/10.1093/jacamr/dlad038.

76. Ngbede EO, Adekanmbi F, Poudel A, Kalalah A, Kelly P, Yang Y et al. Concurrent Resistance to Carbapenem and Colistin Among Enterobacteriaceae Recovered From Human and Animal Sources in Nigeria Is Associated With Multiple Genetic Mechanisms. Front Microbiol. 2021;12:740348. https://doi.org/10.3389/fmicb.2021.740348.

77. Ogbolu DO, Webber MA. High-level and novel mechanisms of carbapenem resistance in Gram-negative bacteria from tertiary hospitals in Nigeria. Int J Antimicrob Agents. 2014;43(5):412-7. https://doi.org/10.1016/j.ijantimicag.2014.01.014.

78. Jesumirhewe C, Springer B, Lepuschitz S, Allerberger F, Ruppitsch W. Carbapenemase-Producing Enterobacteriaceae Isolates from Edo State, Nigeria. Antimicrob Agents Chemother. 2017;61(8). https://doi.org/10.1128/aac.00255-17.

79. Olaitan AO, Berrazeg M, Fagade OE, Adelowo OO, Alli JA, Rolain JM. Emergence of multidrug-resistant Acinetobacter baumannii producing OXA-23 carbapenemase, Nigeria. Int J Infect Dis. 2013;17(6):e469-70. https://doi.org/10.1016/j.ijid.2012.12.008.

80. Afolayan AO, Oaikhena AO, Aboderin AO, Olabisi OF, Amupitan AA, Abiri OV et al. Clones and Clusters of Antimicrobial-Resistant Klebsiella From Southwestern Nigeria. Clin Infect Dis Off Publ Infect Dis Soc Am. 2021;73(Supplement_4):S308-15. https://doi.org/10.1093/cid/ciab769.

81. Ibrahim Y, Sani Y, Saleh Q, Saleh A, Hakeem G. Phenotypic Detection of extended spectrum beta lactamase and carbapenemase co-producing clinical isolates from two tertiary hospitals in Kano, North West Nigeria. Ethiop J Health Sci. 2017;27(1):3-10. https://doi.org/10.4314/ejhs.v27i1.2.

82. Olalekan A, Onwugamba F, Iwalokun B, Mellmann A, Becker K, Schaumburg F. High proportion of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae among extended-spectrum β-lactamase-producers in Nigerian hospitals. J Glob Antimicrob Resist. 2020;21:8-12. https://doi.org/10.1016/j.jgar.2019.09.007.

83. Yusuf I, Arzai A, Getso M, Sherif A, Haruna M. P075: Emergence of carbapenem-resistant enterobacteriaceae in surgical and intensive care units of a hospital with low usage of carbapenem in Kano, North West Nigeria. Antimicrob Resist Infect Control. 2013;2(Supplement 1):P75. https://doi.org/10.1186/2047-2994-2-S1-P75.

84. Oduyebo OO, Falayi OM, Oshun P, Ettu AO. Phenotypic Determination of Carbapenemase Producing Enterobacteriaceae Isolates from Clinical Specimens at a Tertiary Hospital in Lagos, Nigeria. Niger Postgrad Med J. 2015;22(4):223-7. https://doi.org/10.4103/1117-1936.173973.

85. Nkup J, Joseph S, Agabi Y, David V, Hashimu Z, Madubulum CC et al. Molecular detection of carbapenem resistant Klebsiella pneumoniae isolated from clinical specimens in Jos, Nigeria. Microbes Infect Dis. 2023;4(2):555-62. https://doi.org/10.21608/mid.2022.145897.1329.

86. Onyedibe KI, Shobowale EO, Okolo MO, Iroezindu MO, Afolaranmi TO, Nwaokorie FO et al. Low Prevalence of Carbapenem Resistance in Clinical Isolates of Extended Spectrum Beta Lactamase (ESBL) Producing Escherichia coli in North Central, Nigeria. Adv Infect Dis. 2018;8(3):109-20. https://doi.org/10.4236/aid.2018.83011.

87. Umar MK, Mohammed Y, Dabo NT. Prevalence of Carbapenem resistance in clinical bacterial species isolated from Kano, North West Nigeria. Bayero J Pure Appl Sci. 2022;13(1):485-90. Available from: https://www.ajol.info/index.php/bajopas/article/view/227940.

88. Motayo BO, Akinduti PA, Adeyakinu FA, Okerentugba PO, Nwanze JC, Onoh CC et al. Antibiogram and plasmid profiling of carbapenemase and extended spectrum Beta-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae in Abeokuta, South western, Nigeria. Afr Health Sci. 2013;13(4):1091-7. https://doi.org/10.4314/ahs.v13i4.33.

89. Dossouvi KM, Ba BS, Lo G, Cissé A, Ba-Diallo A, Ndiaye I et al. Molecular Characterization of Clinical Strains of Extended-Spectrum ?eta-Lactamases-Producing Klebsiella Pneumoniae Isolated in A Tertiary Hospital in Dakar-Senegal. Arch Microbiol Immunol. 2023;7(1):1-9. https://doi.org/10.26502/ami.93650099.

90. Dossouvi KM, Ba BS, Lo G, Cissé A, Ba-Diallo A, Ndiaye I et al. Molecular characterization of extended-spectrum beta-lactamase-producing extra-intestinal pathogenic Escherichia coli isolated in a university teaching hospital Dakar-Senegal. bioRxiv. 2022;7:20. https://doi.org/10.1101/2022.07.20.500880.

91. Sy A, Diop O, Mbodji M, Faye M, Faye FA, Ndiaye F et al. Profil de résistance aux bêta-lactamines des entérobactéries uropathogènes isolées dans le laboratoire de biologie médicale du Centre Hospitalier Régional de Thiès. Rev Afr Médecine Interne. 2021;8(1):39-47. Available from: http://rafmi.org/index.php/rafmi/article/view/626.

92. Sarr H, Niang AA, Diop A, Mediannikov O, Zerrouki H, Diene SM et al. The Emergence of Carbapenem- and Colistin-Resistant Enterobacteria in Senegal. Pathogens. 2023;12(8):974. https://doi.org/10.3390/pathogens12080974.

93. Sarr H, Diop A, Diallo F, Niang AA, Dièye B, Diagne R et al. Prévalence des entérobactéries productrices de bétalactamase à spectre élargie et résistance à l’imipenème au laboratoire de Bactériologie-virologie du CHNU/Fann - Dakar. Dakar Med. 2021;66(1):53-9. Available from: https://rivieresdusud.uasz.sn/xmlui/bitstream/handle/123456789/1527/sarr_article_2021.pdf.

94. Lo S, Frédéric R, Racha B, Awa B-D, Ahmet NA, Rokhaya D et al. OXA-48 type carbapenemase in Klebsiella pneumoniae producing extended spectrum B-lactamases (ESBL) in Senegal. Afr J Microbiol Res. 2018;12(18):413-8. https://doi.org/10.5897/AJMR2018.8830.

95. Ndiaye I, Ba BS, Thiam F, Boye MM, Sow O, Cissé A et al. Antibiotic Resistance and Virulence Factors of Extended-Spectrum Beta-Lactamase-Producing Klebsiella Pneumoniae Involved in Healthcare-Associated Infections in Dakar, Senegal. Arch Microbiol Immunol. 2023;7(2):65-75. https://doi.org/10.26502/ami.936500105.

96. Camara M, Mane MT, Ba-Diallo A, Dieng A, Diop-Ndiaye H, Karam F et al. Extended-spectrum beta-lactamase- and carbapenemase-producing Enterobacteriaceae clinical isolates in a Senegalese teaching hospital: A cross sectional study. Afr J Microbiol Res. 2017;11(44):1600-5. https://doi.org/10.5897/AJMR2017.8716.

97. Lo G, Dieng A, Ba-Diallo A, Samb M, Tine A, Ndiaye SML et al. Molecular Epidemiology of Carbapenem-resistant Acinetobacter baumannii Isolates in a Senegalese University Teaching Hospital. J Adv Microbiol. 2022;22(3):73-82. https://doi.org/10.9734/jamb/2022/v22i330449.

98. Diene SM, Fall B, Kempf M, Fenollar F, Sow K, Niang B et al. Emergence of the OXA-23 carbapenemase-encoding gene in multidrug-resistant Acinetobacter baumannii clinical isolates from the Principal Hospital of Dakar, Senegal. Int J Infect Dis. 2013;17(3):E209-10. https://doi.org/10.1016/j.ijid.2012.09.007.

99. Moquet O, Bouchiat C, Kinana A, Seck A, Arouna O, Bercion R et al. Class D OXA-48 Carbapenemase in Multidrug-Resistant Enterobacteria, Senegal. Emerg Infect Dis. 2011;17(1):143-4. https://doi.org/10.3201/eid1701.100224.

100. Kempf M, Rolain J-M, Diatta G, Azza S, Samb B, Mediannikov O et al. Carbapenem resistance and Acinetobacter baumannii in Senegal: the paradigm of a common phenomenon in natural reservoirs. PloS One. 2012;7(6):e39495. https://doi.org/10.1371/journal.pone.0039495.

101. Leski TA, Bangura U, Jimmy DH, Ansumana R, Lizewski SE, Li RW et al. Identification of bla OXA-51-like, bla OXA-58, bla DIM-1, and bla VIM Carbapenemase Genes in Hospital Enterobacteriaceae Isolates from Sierra Leone. J Clin Microbiol. 2020;51(7):2435-8. https://doi.org/10.1128/jcm.00832-13.

102. Lakoh S, Li L, Sevalie S, Guo X, Adekanmbi O, Yang G et al. Antibiotic resistance in patients with clinical features of healthcare-associated infections in an urban tertiary hospital in Sierra Leone: a cross-sectional study. Antimicrob Resist Infect Control. 2020;9:38. https://doi.org/10.1186/s13756-020-0701-5.

103. Chen X,Zhang E,Abdulai MK,Tia AB,Ngegba ED,Yin J et al. Dissemination of Antibiotic Resistance Genes Among Patients with Diarrhea - Freetown, Sierra Leone, 2018. China CDC Wkly. 2022;4(49):1093-6. https://doi.org/10.46234/ccdcw2022.221.

104. Schaumburg F, Vas Nunes J, Mönnink G, Falama A-M, Bangura J, Mathéron H et al. Chronic wounds in Sierra Leone: pathogen spectrum and antimicrobial susceptibility. Infection. 2022;50:907-14. https://doi.org/10.1007/s15010-022-01762-6.

105. Leski TA, Taitt CR, Bangura U, Stockelman MG, Ansumana R, Cooper WH et al. High prevalence of multidrug resistant Enterobacteriaceae isolated from outpatient urine samples but not the hospital environment in Bo, Sierra Leone. BMC Infect Dis. 2016;16:167. https://doi.org/10.1186/s12879-016-1495-1.

106. Lakoh S, Yi L, Russell JBW, Zhang J, Sevalie S, Zhao Y et al. The burden of surgical site infections and related antibiotic resistance in two geographic regions of Sierra Leone: a prospective study. Ther Adv Infect Dis. 2022;9:1-15. https://doi.org/10.1177/20499361221135128.

107. Dossim S, Salou M, Azimti A, Bidjada B, Godonou AM, Aoussi E et al. Prevalence of Carbapenems Resistant Bacteria: Case of Three Health Facilities in Lomé, Togo. J Adv Microbiol. 2019;14(3):1-5. https://doi.org/10.9734/JAMB/2019/46219.

108. Dossim S, Bonnin R, Salou M, Tanga K, Virgine G, Dagnra AY et al. Occurrence of carbapenemase-producing Enterobacteriaceae in Togo, West Africa. Int J Antimicrob Agents. 2019;53(4):530-2. https://doi.org/10.1016/j.ijantimicag.2018.11.019.

109. Katawa G, Sadji A, Toudji GA, Touglo K, Tchadié PE, Ritter M et al. Description of Antimicrobial Resistance Patterns at the National Institute of Hygiene in Lome, Togo. Jpn J Infect Dis. 2023;76(2):91-100. https://doi.org/10.7883/yoken.JJID.2022.082.

110. Gambogou B, Ameyapoh Y, Karou SD, Simpore J, Kokou A. Effect of Aqueous garlic extract on biofilm formation and antibiotic susceptibility of multidrug-resistant uropathogenic Escherichia coli clinical isolates in Togo. International Journal of Advanced Multidisciplinary Research. 2018;5(7):23-33. http://dx.doi.org/10.22192/ijamr.2018.05.07.004.

111. Toudji AG, Djeri B, Karou SD,Tigossou S,Ameyapoh Y, de Souza C. Prevalence of Extend Spectrum Beta Lactamases Producing Enterobacteriaceae and their Antibiotic Susceptibility in Lome, Togo. Asian J Life Sci. 2017;1:101. Available from: https://www.gavinpublishers.com/article/view/prevalence-of-extend-spectrum-beta-lactamases-producing-enterobacteriaceae-and-their-antibiotic-susceptibility-in-loma-togo.

112. Salah FD, Soubeiga ST, Ouattara AK, Sadji AY, Metuor-Dabire A, Obiri-Yeboah D et al. Distribution of quinolone resistance gene (qnr) in ESBL-producing Escherichia coli and Klebsiella spp. in Lomé, Togo. Antimicrob Resist Infect Control. 2019;8:104. https://doi.org/10.1186/s13756-019-0552-0.

113. Ssekatawa K, Byarugaba DK, Wampande E, Ejobi F. A systematic review: the current status of carbapenem resistance in East Africa. BMC Res Notes. 2018;11:629. https://doi.org/10.1186/s13104-018-3738-2.

114. Bulens SN, Reses HE, Ansari UA, Grass JE, Carmon C, Albrecht V et al. Carbapenem-Resistant enterobacterales in individuals with and without health care risk factors —Emerging infections program, United States, 2012-2015. Am J Infect Control. 2023;51(1):70-7. https://doi.org/10.1016/j.ajic.2022.04.003.

115. Akeda Y. Current situation of carbapenem-resistant Enterobacteriaceae and Acinetobacter in Japan and Southeast Asia. Microbiol Immunol. 2021;65(6):229-37. https://doi.org/10.1111/1348-0421.12887.

116. Joshi DN, Shenoy B, Mv B, Adhikary R, Shamarao S, Mahalingam A. Prevalence of Carbapenem-Resistant Enterobacteriaceae and the Genes Responsible for Carbapenemase Production in a Tertiary Care Hospital in South India. EMJ Flagship J. 2023; https://doi.org/10.33590/emj/10300425.

117. Lee Y-L, Ko W-C, Hsueh P-R. Geographic Patterns of Carbapenem-Resistant Pseudomonas aeruginosa in the Asia-Pacific Region: Results from the Antimicrobial Testing Leadership and Surveillance (ATLAS) Program, 2015–2019. Antimicrob Agents Chemother. 2022;66(2):e02000-21. https://doi.org/10.1128/AAC.02000-21.

118. Karlowsky JA, Bouchillon SK, Kotb REM, Mohamed N, Stone GG, Sahm DF. Carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa causing infection in Africa and the Middle East: a surveillance study from the ATLAS programme (2018–20). JAC-Antimicrob Resist. 2022;4(3):dlac060. https://doi.org/10.1093/jacamr/dlac060.

119. Aloraifi RI, Alharthi AF, Almefleh AA, Alamri AH, Alobud AS, Bawazeer RA et al. Prevalence of Carbapenem Non-susceptible Gram-Negative Bacteria at Tertiary Care Hospitals in Saudi Arabia. Cureus. 2023;15(1):e33767. https://doi.org/10.7759/cureus.33767.

120. Cai B, Echols R, Magee G, Ferreira JCA, Morgan G, Ariyasu M et al. Prevalence of Carbapenem-Resistant Gram-Negative Infections in the United States Predominated by Acinetobacter baumannii and Pseudomonas aeruginosa. Open Forum Infect Dis. 2017;4(3):ofx176. https://doi.org/10.1093/ofid/ofx176.

121. Kostyanev T, Vilken T, Lammens C, Timbermont L, Van’t Veen A, Goossens H. Detection and prevalence of carbapenem-resistant Gram-negative bacteria among European laboratories in the COMBACTE network: a COMBACTE LAB-Net survey. Int J Antimicrob Agents. 2019;53(3):268-74. https://doi.org/10.1016/j.ijantimicag.2018.10.013.

122. Lee Y-L, Ko W-C, Hsueh P-R. Geographic patterns of Acinetobacter baumannii and carbapenem resistance in the Asia-Pacific Region: results from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program, 2012-2019. Int J Infect Dis. 2023;127:48-55. https://doi.org/10.1016/j.ijid.2022.12.010.

123. Zhang Y, Wang Q, Yin Y, Chen H, Jin L, Gu B et al. Epidemiology of Carbapenem-Resistant Enterobacteriaceae Infections: Report from the China CRE Network. Antimicrob Agents Chemother. 2018;62(2):e01882-17. https://doi.org/10.1128/AAC.01882-17.

124. Osei Sekyere J. Current State of Resistance to Antibiotics of Last-Resort in South Africa: A Review from a Public Health Perspective. Front Public Health. 2016;4:209. https://doi.org/10.3389/fpubh.2016.00209.

125. Dikoumba A-C, Onanga R, Mangouka LG, Boundenga L, Ngoungou E-B, Godreuil S. Molecular Epidemiology of Antimicrobial Resistance in Central Africa: A Systematic Review. Access Microbiol. 2023. https://doi.org/10.1099/acmi.0.000556.v1.

126. Ma J, Song X, Li M, Yu Z, Cheng W, Yu Z et al. Global spread of carbapenem-resistant Enterobacteriaceae: Epidemiological features, resistance mechanisms, detection and therapy. Microbiol Res. 2023;266:127249. https://doi.org/10.1016/j.micres.2022.127249.

127. Castanheira M, Deshpande LM, Mendes RE, Doyle TB, Sader HS. Prevalence of carbapenemase genes among carbapenem-nonsusceptible Enterobacterales collected in US hospitals in a five-year period and activity of ceftazidime/avibactam and comparator agents. JAC-Antimicrob Resist. 2022;4(5):dlac098. https://doi.org/10.1093/jacamr/dlac098.

128. Pagano M, Martins AF, Barth AL. Mobile genetic elements related to carbapenem resistance in Acinetobacter baumannii. Braz J Microbiol. 2016;47(4):785-92. https://doi.org/10.1016/j.bjm.2016.06.005.

129. Li X, Fu Y, Shen M, Huang D, Du X, Hu Q et al. Dissemination of blaNDM-5 gene via an IncX3-type plasmid among non-clonal Escherichia coli in China. Antimicrob Resist Infect Control. 2018;7(1):59. https://doi.org/10.1186/s13756-018-0349-6.

130. Yang HY, Nam YS, Lee HJ. Prevalence of plasmid-mediated quinolone resistance genes among ciprofloxacin-nonsusceptible Escherichia coli and Klebsiella pneumoniae isolated from blood cultures in Korea. Can J Infect Dis Med Microbiol. 2014;25(3):163-9. https://doi.org/10.1155/2014/329541.

131. Ge H, Qiao J, Xu H, Liu R, Chen R, Li C et al. First report of Klebsiella pneumoniae co-producing OXA-181, CTX-M-55, and MCR-8 isolated from the patient with bacteremia. Front Microbiol. 2022;13:1020500. https://doi.org/10.3389/fmicb.2022.1020500.

132. Qin S, Cheng J, Wang P, Feng X, Liu H-M. Early emergence of OXA-181-producing Escherichia coli ST410 in China.JGlobAntimicrobResist.2018;15:215-8. https://doi.org/10.1016/j.jgar.2018.06.017.

133. Xanthopoulou K, Carattoli A, Wille J, Biehl L, Rohde H, Farowski F et al. Antibiotic Resistance and Mobile Genetic Elements in Extensively Drug-Resistant Klebsiella pneumoniae Sequence Type 147 Recovered from Germany. Antibiot Basel Switz. 2020;9(10):675. https://doi.org/10.3390/antibiotics9100675.

134. Wang L, Guo L, Ye K, Yang J. Genetic characteristics of OXA-48-producing Enterobacterales from China. J Glob Antimicrob Resist. 2021;26:285-91. https://doi.org/10.1016/j.jgar.2021.07.006.

135. Arana DM, Saez D, García-Hierro P, Bautista V, Fernández-Romero S, Ángel de la Cal M et al. Concurrent interspecies and clonal dissemination of OXA-48 carbapenemase. Clin Microbiol Infect. 2015;21:P148.e1-148.e4. https://doi.org/10.1016/j.cmi.2014.07.008.

136. Poirel L, Özdamar M, Ocampo-Sosa AA, Türkoglu S, Ozer UG, Nordmann P. NDM-1-Producing Klebsiella pneumoniae Now in Turkey. Antimicrob Agents Chemother. 2012;56(5):2784-5. https://doi.org/10.1128/AAC.00150-12.

137. Power K, Wang J, Karczmarczyk M, Crowley B, Cotter M, Haughton P et al. Molecular analysis of OXA-48-carrying conjugative IncL/M-like plasmids in clinical isolates of Klebsiella pneumoniae in Ireland. Microb Drug Resist. 2014;20(4):270-4. https://doi.org/10.1089/mdr.2013.0022.

138. Vijayakumar S, Wattal C, Oberoi JK, Bhattacharya S, Vasudevan K, Anandan S et al. Insights into the complete genomes of carbapenem-resistant Acinetobacter baumannii harbouring blaOXA-23, blaOXA-420 and blaNDM-1 genes using a hybrid-assembly approach. Access Microbiol. 2020;2(8):acmi000140. https://doi.org/10.1099/acmi.0.000140.

139. Lee K, Jong BL, Jong HY, Yong D, Chong Y, June MK et al. blaVIM-2 cassette-containing novel integrons in metallo-β-lactamase-producing Pseudomonas aeruginosa and Pseudomonas putida isolates disseminated in a Korean hospital. Antimicrob Agents Chemother. 2002;46(4):1053-8. https://doi.org/10.1128/AAC.46.4.1053-1058.2002.

140. Moyo S, Haldorsen B, Aboud S, Blomberg B, Maselle SY, Sundsfjord A et al. Identification of VIM-2-Producing Pseudomonas aeruginosa from Tanzania Is Associated with Sequence Types 244 and 640 and the Location of blaVIM-2 in a TniC Integron. Antimicrob Agents Chemother. 2014;59(1):682-5. https://doi.org/10.1128/aac.01436-13.

141. Pallecchi L, Riccio ML, Docquier J-D, Fontana R, Rossolini GM. Molecular heterogeneity of blaVIM-2-containing integrons from Pseudomonas aeruginosa plasmids encoding the VIM-2 metallo-β-lactamase. FEMS Microbiol Lett. 2001;195(2):145-50. https://doi.org/10.1111/j.1574-6968.2001.tb10512.x.