1887

Abstract

Tackling antimicrobial resistance (AMR) is particularly challenging in low-resource settings such as Fort Portal Regional Referral Hospital (FPRRH) in Western Uganda. Specific knowledge of local AMR epidemiology is required to inform evidence-based improvement of antibiotic stewardship measures in the hospital. To address this, we combined existing antimicrobial susceptibility testing (AST) from FPRRH, with whole genome sequencing (WGS) of 41 isolates (2017–2019). AST revealed 73 % (30 of 41) of isolates were resistant to one or more antibiotics and 29 % (12 of 41) were multi-drug resistant (MDR). Resistance phenotypes were largely explained by the presence of antibiotic resistance genes in WGS data. Five isolates were methicillin-resistant (MRSA) and MDR. Although all isolates were susceptible to clindamycin, a 24 % carriage of genes suggests potential for rapid development of resistance. We inferred a population structure for the isolates by comparing their core genomes. Twenty isolates formed a tight cluster corresponding to multilocus sequence typing clonal complex (CC) 152, a CC found to be particularly prevalent in northern Africa. The frequency of genes associated with methicillin, chloramphenicol and ciprofloxacin resistance were significantly lower among CC152 strains than non-CC152 strains; thus, in keeping with previous work, we find that CC152 is almost exclusively methicillin-sensitive (MSSA). Also, in agreement with other studies, we observed that the occurrence of Panton–Valentine leukocidin toxin-encoding genes was significantly higher among CC152 strains than non-CC152 strains. However, we also observed that the coagulase gene was over-represented in this CC, further defining the virulence strategy of this important pathogen. By generating detailed information about the epidemiology of circulating and their antibiotic susceptibility, our study has provided, for the first time, data on which evidence-based infection and AMR interventions at FPRRH can be based.

Funding
This study was supported by the:
  • THET Commonwealth Partnerships for Antimicrobial Stewardship (Award AMSB03)
    • Principle Award Recipient: HelenLouise Ackers
  • This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.001000
2021-05-25
2022-01-24
Loading full text...

Full text loading...

/deliver/fulltext/micro/167/5/mic001000.html?itemId=/content/journal/micro/10.1099/mic.0.001000&mimeType=html&fmt=ahah

References

  1. World Health Organization Antimicrobial resistance and primary health care (no.WHO/HIS/SDS/2018.57; 2018 https://apps.who.int/iris/bitstream/handle/10665/326454/WHO-HIS-SDS-2018.56-eng.pdf
  2. World Health Organisation World Health Statistics Overview 2019: Monitoring Health for the SDGs, Sustainable Development Goals (no.WHO/DAD/2019.1) 2019
    [Google Scholar]
  3. Ugandan National Academy of Sciences Antibiotic Resistance in Uganda: Situation Analysis and Recommendations Kampala, Uganda: Uganda National Academy of Sciences. Center for Disease Dynamics, Economics & Policy; 2015
    [Google Scholar]
  4. Vialle‐Valentin C, Lecates R, Zhang F, Desta A, Ross‐Degnan D. Predictors of antibiotic use in African communities: evidence from medicines household surveys in five countries. Trop Med Int Health 2012; 17:211–222
    [Google Scholar]
  5. Omulo S, Thumbi SM, Njenga MK, Call DR. A review of 40 years of enteric antimicrobial resistance research in Eastern Africa: what can be done better?. Antimicrob Resist Infect Control 2015; 4:1 [View Article][PubMed]
    [Google Scholar]
  6. Ugandan National Academy of Sciences Antimicrobial Resistance National Action Plan (NAP) Center for Disease Dynamics, Economics & Policy; 2018
    [Google Scholar]
  7. Moirongo RM, Lorenz E, Ntinginya NE, Dekker D, Fernandes J et al. Regional variatigional Variation of Extended-Spectrum Beta-Lactamase (ESBL)-producing Enterobacterales, fluoroquinolone-resistant Salmonella enterica and methicillin-resistant Staphylococcus aureus among febrile patients in Sub-Saharan Africa. Front Microbiol 2020; 11:567235 [View Article][PubMed]
    [Google Scholar]
  8. Wangai FK, Masika MM, Maritim MC, Seaton RA. Methicillin-resistant Staphylococcus aureus (MRSA) in East Africa: red alert or red herring?. BMC Infect Dis 2019; 19:596 [View Article][PubMed]
    [Google Scholar]
  9. Seni J, Bwanga F, Najjuka CF, Makobore P, Okee M et al. Molecular characterization of Staphylococcus aureus from patients with surgical site infections at Mulago Hospital in Kampala, Uganda. PLoS One 2013; 8:e66153 [View Article][PubMed]
    [Google Scholar]
  10. Asiimwe BB, Baldan R, Trovato A, Cirillo DM. Prevalence and molecular characteristics of Staphylococcus aureus, including methicillin resistant strains, isolated from bulk can milk and raw milk products in pastoral communities of South-West Uganda. BMC Infect Dis 2017; 17:422 [View Article][PubMed]
    [Google Scholar]
  11. Kitara LD, Anywar AD, Acullu D, Odongo-Aginya E, Aloyo J. Antibiotic susceptibility of Staphylococcus aureus in suppurative lesions in Lacor Hospital, Uganda. Afr Health Sci 2011; 11:S34–39
    [Google Scholar]
  12. World Health Organization Joint External Evaluation of IHR Core Capacities of the Republic of Uganda: Executive Summary, June 26-30, 2017 Geneva: World Health Organization; 2017
    [Google Scholar]
  13. Kateete DP, Namazzi S, Okee M, Okeng A, Baluku H. High prevalence of methicillin resistant Staphylococcus aureus in the surgical units of Mulago hospital in Kampala, Uganda. BMC Res Notes 2011; 4:326 [View Article][PubMed]
    [Google Scholar]
  14. Kajumbula H, Fujita AW, Mbabazi O, Najjuka C, Izale C. Antimicrobial drug resistance in blood culture isolates at a tertiary hospital, Uganda. Emerging Infect Dis 2018; 24:174 [View Article]
    [Google Scholar]
  15. Bebell LM, Ngonzi J, Bazira J, Fajardo Y, Boatin AA et al. Antimicrobial-resistant infections among postpartum women at a Ugandan referral hospital. PloS one 2017; 12:e0175456 [View Article][PubMed]
    [Google Scholar]
  16. Odongo CO, Anywar DA, Luryamamoi K, Odongo P. Antibiograms from community-acquired uropathogens in Gulu, northern Uganda--a cross-sectional study. BMC Infect Dis 2013; 13:193 [View Article][PubMed]
    [Google Scholar]
  17. Weiss D, Wallace RM, Rwego IB, Gillespie TR, Chapman CA. Antibiotic-resistant Escherichia coli and class 1 integrons in humans, domestic animals, and wild primates in Rural Uganda. Appl Environ Microbiol 2018; 84:21
    [Google Scholar]
  18. Asiimwe BB, Baldan R, Trovato A, Cirillo DM. Molecular epidemiology of Panton-valentine leukocidin-positive community-acquired methicillin resistant staphylococcus aureus isolates in pastoral communities of rural south western Uganda. BMC Infect Dis 2017; 17:24 [View Article][PubMed]
    [Google Scholar]
  19. Kateete DP, Asiimwe BB, Mayanja R, Mujuni B, Bwanga F. Nasopharyngeal carriage, spa types and antibiotic susceptibility profiles of Staphylococcus aureus from healthy children less than 5 years in Eastern Uganda. BMC Infect Dis 2019; 19:1023
    [Google Scholar]
  20. Kateete DP, Kimani CN, Katabazi FA, Okeng A, Okee MS. Identification of Staphylococcus aureus: DNase and Mannitol salt agar improve the efficiency of the tube coagulase test. Ann Clin Microbiol Antimicrob 2010; 9:23 [View Article][PubMed]
    [Google Scholar]
  21. Hendriksen RS, Bortolaia V, Tate H, Tyson G, Aarestrup FM. Using genomics to track global antimicrobial resistance. Front Public Health 2019; 7:242 [View Article][PubMed]
    [Google Scholar]
  22. Ackers L, Ackers-Johnson G, Seekles M, Odur J, Opio S. Opportunities and challenges for improving anti-microbial stewardship in low- and middle-income countries; Lessons learnt from the maternal sepsis intervention in western Uganda. Antibiotics (Basel) 2020; 9:315 [View Article][PubMed]
    [Google Scholar]
  23. Matuschek E, Brown DF, Kahlmeter G. Development of the EUCAST disk diffusion antimicrobial susceptibility testing method and its implementation in routine microbiology laboratories. Clin Microbiol Infect 2014; 20:O255–266 [View Article][PubMed]
    [Google Scholar]
  24. Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 2012; 19:455–477 [View Article][PubMed]
    [Google Scholar]
  25. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article][PubMed]
    [Google Scholar]
  26. Alcock BP, Raphenya AR, TTY L, Tsang KK, Bouchard M. CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database. Nucleic Acids Res 2020; 48:D517–D525
    [Google Scholar]
  27. Liu B, Zheng D, Jin Q, Chen L, Yang J. VFDB 2019: a comparative pathogenomic platform with an interactive web interface. Nucleic Acids Res 2019; 47:D687–D692 [View Article][PubMed]
    [Google Scholar]
  28. Jolley KA, Bray JE, Maiden MCJ. Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications. Wellcome Open Res 2018; 3:124 [View Article][PubMed]
    [Google Scholar]
  29. Seemann T. Snippy: Fast Bacterial Variant Calling from Ngs Reads 2015
    [Google Scholar]
  30. Price MN, Dehal PS, Arkin AP. FastTree: computing large minimum evolution trees with profiles instead of a distance matrix. Mol Biol Evol 2009; 26:1641–1650 [View Article][PubMed]
    [Google Scholar]
  31. Page AJ, Cummins CA, Hunt M, Wong VK, Reuter S. Roary: rapid large-scale prokaryote pan genome analysis. Bioinformatics 2015; 31:3691–3693 [View Article][PubMed]
    [Google Scholar]
  32. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18:268–281 [View Article][PubMed]
    [Google Scholar]
  33. Kateete DP, Asiimwe BB, Mayanja R, Najjuka CF, Rutebemberwa E. Species and drug susceptibility profiles of Staphylococci isolated from healthy children in Eastern Uganda. PLoS One 2020; 15:e0229026 [View Article]
    [Google Scholar]
  34. George M, Iramiot JS, Muhindo R, Olupot-Olupot P, Nanteza A. Bacterial aetiology and antibiotic susceptibility profile of post-operative sepsis among surgical patients in a tertiary hospital in rural Eastern Uganda. Microbiol Res J Int 2018; 24: [View Article][PubMed]
    [Google Scholar]
  35. World Health Organisation Antimicrobial resistance: Global report on surveillance 2014; 2014
  36. Kumar N, Raven KE, Blane B, Leek D, Brown NM. Evaluation of a fully automated bioinformatics tool to predict antibiotic resistance from MRSA genomes. J Antimicrob Chemother 2020; 75:1117–1122 [View Article][PubMed]
    [Google Scholar]
  37. Mshangila B, Paddy M, Kajumbula H, Ateenyi-Agaba C, Kahwa B. External ocular surface bacterial isolates and their antimicrobial susceptibility patterns among pre-operative cataract patients at Mulago National Hospital in Kampala, Uganda. BMC Ophthalmol 2013; 13:71 [View Article][PubMed]
    [Google Scholar]
  38. Khoramrooz SS, Dolatabad SA, Dolatabad FM, Marashifard M, Mirzaii M. Detection of tetracycline resistance genes, aminoglycoside modifying enzymes, and coagulase gene typing of clinical isolates of Staphylococcus aureus in the Southwest of Iran. Iran J Basic Med Sci 2017; 20:912–919 [View Article][PubMed]
    [Google Scholar]
  39. Berglund F, Bohm ME, Martinsson A, Ebmeyer S, Osterlund T. Comprehensive screening of genomic and metagenomic data reveals a large diversity of tetracycline resistance genes. Microb Genom 2020; 6:11 [View Article]
    [Google Scholar]
  40. Basulira Y, Olet SA, Alele PE. Inappropriate usage of selected antimicrobials: Comparative residue proportions in rural and urban beef in Uganda. PLoS One 2019; 14:e0209006 [View Article][PubMed]
    [Google Scholar]
  41. Iramiot JS, Kajumbula H, Bazira J, Kansiime C, Asiimwe BB. Antimicrobial resistance at the human-animal interface in the pastoralist communities of Kasese District, south western Uganda. Sci Rep 2020; 10:14737 [View Article][PubMed]
    [Google Scholar]
  42. Mukonzo JK, Namuwenge PM, Okure G, Mwesige B, Namusisi OK. Over-the-counter suboptimal dispensing of antibiotics in Uganda. J Multidiscip Healthc 2013; 6:303–310 [View Article][PubMed]
    [Google Scholar]
  43. Fowler PW, Cole K, Gordon NC, Kearns AM, Llewelyn MJ et al. Robust prediction of resistance to trimethoprim in Staphylococcus aureus . Cell Chem Biol 2018; 25:339–349e334 [View Article][PubMed]
    [Google Scholar]
  44. Nurjadi D, Olalekan AO, Layer F, Shittu AO, Alabi A. Emergence of trimethoprim resistance gene dfrG in Staphylococcus aureus causing human infection and colonization in sub-Saharan Africa and its import to Europe. J Antimicrob Chemother 2014; 69:2361–2368 [View Article]
    [Google Scholar]
  45. Ojulong J, Mwambu TP, Joloba M, Bwanga F, Kaddu-Mulindwa DH. Relative prevalence of methicilline resistant Staphylococcus aureus and its susceptibility pattern in Mulago Hospital, Kampala, Uganda. Tanzan J Health Res 2009; 11:149–153 [View Article][PubMed]
    [Google Scholar]
  46. William B, Rwenyonyi CM, Swedberg G, Kironde F. Cotrimoxazole prophylaxis specifically selects for cotrimoxazole resistance in Streptococcus mutans and Streptococcus sobrinus with Varied Polymorphisms in the target genes folA and folP. Int J Microbiol 2012; 2012:916129 [View Article][PubMed]
    [Google Scholar]
  47. Marwa KJ, Mushi MF, Konje E, Alele PE, Kidola J et al. Resistance to cotrimoxazole and other antimicrobials among isolates from HIV/AIDS and NON-HIV/AIDS patients at Bugando Medical Centre, Mwanza, Tanzania. AIDS Res Treat 2015; 2015:103874 [View Article]
    [Google Scholar]
  48. Mwambi B, Iramiot J, Bwanga F, Nakaye M, Itabangi H et al. Clindamycin resistance among staphylococcus aureus isolated at Mbarara regional referral hospital, in south western Uganda. Br Microbiol Res J 2014; 4:1335–1344 [View Article]
    [Google Scholar]
  49. Tumuhamye J, Sommerfelt H, Bwanga F, Ndeezi G, Mukunya D. Neonatal sepsis at Mulago national referral hospital in Uganda: Etiology, antimicrobial resistance, associated factors and case fatality risk. PLoS One 2020; 15:e0237085 [View Article]
    [Google Scholar]
  50. Ross JI, Eady EA, Cove JH, Cunliffe WJ, Baumberg S. Inducible erythromycin resistance in Staphylococci is encoded by a member of the ATP-binding transport super-gene family. Mol Microbiol 1990; 4:1207–1214 [View Article][PubMed]
    [Google Scholar]
  51. Drinkovic D, Fuller ER, Shore KP, Holland DJ, Ellis-Pegler R. Clindamycin treatment of Staphylococcus aureus expressing inducible clindamycin resistance. J Antimicrob Chemother 2001; 48:315–316 [View Article][PubMed]
    [Google Scholar]
  52. Mshana S, Kamugisha E, Miramb M, Chalya P, Rambau P. Prevalence of clindamycin inducible resistance among methicillin-resistant Staphylococcus aureus at Bugando Medical Centre, Mwanza, Tanzania. Tanzan J Health Res 2009; 11:
    [Google Scholar]
  53. Davis MA, Besser TE, Orfe LH, Baker KN, Lanier AS. Genotypic-phenotypic discrepancies between antibiotic resistance characteristics of Escherichia coli isolates from calves in management settings with high and low antibiotic use. Appl Environ Microbiol 2011; 77:3293–3299 [View Article][PubMed]
    [Google Scholar]
  54. Blumberg HM, Rimland D, Carroll DJ, Terry P, Wachsmuth IK. Rapid development of ciprofloxacin resistance in methicillin-susceptible and -resistant Staphylococcus aureus . J Infect Dis 1991; 163:1279–1285 [View Article][PubMed]
    [Google Scholar]
  55. Ruimy R, Maiga A, Armand-Lefevre L, Maiga I, Diallo A. The carriage population of Staphylococcus aureus from Mali is composed of a combination of pandemic clones and the divergent Panton-Valentine leukocidin-positive genotype ST152. J Bacteriol 2008; 190:3962–3968 [View Article][PubMed]
    [Google Scholar]
  56. Schaumburg F, Alabi AS, Peters G, Becker K. New epidemiology of Staphylococcus aureus infection in Africa. Clin Microbiol Infect 2014; 20:589–596 [View Article][PubMed]
    [Google Scholar]
  57. Kyany’a C, Nyasinga J, Matano D, Oundo V, Wacira S et al. Phenotypic and genotypic characterization of clinical Staphylococcus aureus isolates from Kenya. BMC Microbiol 2019; 19:245 [View Article][PubMed]
    [Google Scholar]
  58. Obasuyi O, McClure J, Oronsaye FE, Akerele JO, Conly J et al. Molecular characterization and pathogenicity of Staphylococcus aureus isolated from Benin-city, Nigeria. Microorganisms 2020; 8: [View Article][PubMed]
    [Google Scholar]
  59. Thomas S, Liu W, Arora S, Ganesh V, YP K. The Complex fibrinogen interactions of the Staphylococcus aureus coagulases. Front Cell Infect Microbiol 2019; 9:106 [View Article]
    [Google Scholar]
  60. Cao Z, Casabona MG, Kneuper H, Chalmers JD, Palmer T. The type VII secretion system of Staphylococcus aureus secretes a nuclease toxin that targets competitor bacteria. Nat Microbiol 2016; 2:16183 [View Article][PubMed]
    [Google Scholar]
  61. Monecke S, Slickers P, Ellington M, Kearns A, Ehricht R. High diversity of Panton–Valentine leukocidin-positive, methicillin-susceptible isolates of Staphylococcus aureus and implications for the evolution of community-associated methicillin-resistant S. aureus . Clin Microbiol Infect 2007; 13:1157–1164 [View Article][PubMed]
    [Google Scholar]
  62. Gillaspy AF, Worrell V, Orvis J, Roe BA, Dyer DW. The Staphylococcus aureus NCTC 8325 Genome. Gram-Positive Pathogens, 2nd ed. American Society of Microbiology; 2006 pp 381–412
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.001000
Loading
/content/journal/micro/10.1099/mic.0.001000
Loading

Data & Media loading...

Supplements

Supplementary material 1

EXCEL

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error