Predominance of PVL-negative community-associated methicillin-resistant Staphylococcus aureus sequence type 8 in newly diagnosed HIV-infected adults, Tanzania

Joel Manyahi, Sabrina J Moyo, Said Aboud, Nina Langeland, Bjørn Blomberg, Joel Manyahi, Sabrina J Moyo, Said Aboud, Nina Langeland, Bjørn Blomberg

Abstract

Difficult-to-treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are of concern in people living with HIV infection as they are more vulnerable to infection. We aimed to identify molecular characteristics of MRSA colonizing newly diagnosed HIV-infected adults in Tanzania. Individuals newly diagnosed with HIV infection were recruited in Dar es Salaam, Tanzania, from April 2017 to May 2018, as part of the randomized clinical trial CoTrimResist ( ClinicalTrials.gov identifier: NCT03087890). Nasal/nasopharyngeal isolates of Staphylococcus aureus were susceptibility tested by disk diffusion method, and cefoxitin-resistant isolates were characterized by short-reads whole genome sequencing. Four percent (22/537) of patients carried MRSA in the nose/nasopharynx. MRSA isolates were frequently resistant towards gentamicin (95%), ciprofloxacin (91%), and erythromycin (82%) but less often towards trimethoprim-sulfamethoxazole (9%). Seventy-three percent had inducible clindamycin resistance. Erythromycin-resistant isolates harbored ermC (15/18) and LmrS (3/18) resistance genes. Ciprofloxacin resistance was mediated by mutations of the quinolone resistance-determining region (QRDR) sequence in the gyrA (S84L) and parC (S80Y) genes. All isolates belonged to the CC8 and ST8-SCCmecIV MRSA clone. Ninety-five percent of the MRSA isolates were spa-type t1476, and one exhibited spa-type t064. All isolates were negative for Panton-Valentine leucocidin (PVL) and arginine catabolic mobile element (ACME) type 1. All ST8-SCCmecIV-spa-t1476 MRSA clones from Tanzania were unrelated to the globally successful USA300 clone. Carriage of ST8 MRSA (non-USA300) was common among newly diagnosed HIV-infected adults in Tanzania. Frequent co-resistance to non-beta lactam antibiotics limits therapeutic options when infection occurs.

Keywords: Community; Human immunodficiency virus; Methicillin-resistant Staphylococcus aureus (MRSA); Panton-Valentine leukocidin-negative; Sequence type 8 (ST8); Tanzania.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
SNP phylogenetic tree for ST8 MRSA isolates. Blue indicates MRSA isolated from this study, pink indicates MRSA isolated previously from Tanzania, black are MRSA isolated from USA at different point of time, and green is an isolate from Gabon

References

    1. Cosgrove SE, Sakoulas G, Perencevich EN, Schwaber MJ, Karchmer AW, Carmeli Y. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis. 2003;36(1):53–59. doi: 10.1086/345476.
    1. Stenehjem E, Rimland D. MRSA nasal colonization burden and risk of MRSA infection. Am J Infect Control. 2013;41(5):405–410. doi: 10.1016/j.ajic.2012.07.017.
    1. Szumowski JD, Wener KM, Gold HS, Wong M, Venkataraman L, Runde CA, Cohen DE, Mayer KH, Wright SB. Methicillin-resistant Staphylococcus aureus colonization, behavioral risk factors, and skin and soft-tissue infection at an ambulatory clinic serving a large population of HIV-infected men who have sex with men. Clin Infect Dis. 2009;49(1):118–121. doi: 10.1086/599608.
    1. Madhi SA, Petersen K, Madhi A, Khoosal M, Klugman KP. Increased disease burden and antibiotic resistance of bacteria causing severe community-acquired lower respiratory tract infections in human immunodeficiency virus type 1-infected children. Clin Infect Dis. 2000;31(1):170–176. doi: 10.1086/313925.
    1. Naimi TS, LeDell KH, Boxrud DJ, Groom AV, Steward CD, Johnson SK, Besser JM, O'Boyle C, Danila RN, Cheek JE, Osterholm MT, Moore KA, Smith KE. Epidemiology and clonality of community-acquired methicillin-resistant Staphylococcus aureus in Minnesota, 1996-1998. Clin Infect Dis. 2001;33(7):990–996. doi: 10.1086/322693.
    1. Harris SR, Feil EJ, Holden MT, Quail MA, Nickerson EK, Chantratita N, Gardete S, Tavares A, Day N, Lindsay JA, Edgeworth JD, de Lencastre H, Parkhill J, Peacock SJ, Bentley SD. Evolution of MRSA during hospital transmission and intercontinental spread. Science. 2010;327(5964):469–474. doi: 10.1126/science.1182395.
    1. McAdam PR, Templeton KE, Edwards GF, Holden MT, Feil EJ, Aanensen DM, Bargawi HJ, Spratt BG, Bentley SD, Parkhill J, Enright MC, Holmes A, Girvan EK, Godfrey PA, Feldgarden M, Kearns AM, Rambaut A, Robinson DA, Fitzgerald JR. Molecular tracing of the emergence, adaptation, and transmission of hospital-associated methicillin-resistant Staphylococcus aureus. Proc Natl Acad Sci U S A. 2012;109(23):9107–9112. doi: 10.1073/pnas.1202869109.
    1. Ouko TT, Ngeranwa JN, Orinda GO, Bii CC, Amukoye E, Lucy M, Wamae CN. Oxacillin resistant Staphylococcus aureus among HIV infected and non-infected Kenyan patients. East Afr Med J. 2010;87(5):179–186.
    1. Olalekan AO, Schaumburg F, Nurjadi D, Dike AE, Ojurongbe O, Kolawole DO, Kun JF, Zanger P. Clonal expansion accounts for an excess of antimicrobial resistance in Staphylococcus aureus colonising HIV-positive individuals in Lagos, Nigeria. Int J Antimicrob Agents. 2012;40(3):268–272. doi: 10.1016/j.ijantimicag.2012.05.016.
    1. Lemma MT, Zenebe Y, Tulu B, Mekonnen D, Mekonnen Z. Methicillin resistant Staphylococcus aureus among HIV infected pediatric patients in Northwest Ethiopia: carriage rates and antibiotic co-resistance profiles. PLoS One. 2015;10(9):e0137254. doi: 10.1371/journal.pone.0137254.
    1. Reid MJA, Steenhoff AP, Mannathoko N, Muthoga C, McHugh E, Brown EL, Fischer RSB. Staphylococcus aureus nasal colonization among HIV-infected adults in Botswana: prevalence and risk factors. AIDS Care. 2017;29(8):961–965. doi: 10.1080/09540121.2017.1282600.
    1. Kumburu HH, Sonda T, Leekitcharoenphon P, van Zwetselaar M, Lukjancenko O, Alifrangis M, Lund O, Mmbaga BT, Kibiki G, Aarestrup FM. Hospital epidemiology of methicillin-resistant Staphylococcus aureus in a tertiary care hospital in Moshi, Tanzania, as determined by whole genome sequencing. Biomed Res Int. 2018;2018:2087693. doi: 10.1155/2018/2087693.
    1. Clinical and Laboratory Standards Institute . Performance standards for antimicrobial susceptibility testing; twenty-eighth informational supplement CLSI document M100–S20. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.
    1. Moyo SJ, Aboud S, Blomberg B, Mkopi N, Kasubi M, Manji K, Lyamuya EF, Maselle SY, Langeland N. High nasal carriage of methicillin-resistant Staphylococcus aureus among healthy Tanzanian under-5 children. Microb Drug Resist. 2014;20(1):82–88. doi: 10.1089/mdr.2013.0016.
    1. Uhlemann AC, Dordel J, Knox JR, Raven KE, Parkhill J, Holden MT, Peacock SJ, Lowy FD. Molecular tracing of the emergence, diversification, and transmission of S. aureus sequence type 8 in a New York community. Proc Natl Acad Sci U S A. 2014;111(18):6738–6743. doi: 10.1073/pnas.1401006111.
    1. Schaumburg F, Ngoa UA, Kösters K, Köck R, Adegnika AA, Kremsner PG, Lell B, Peters G, Mellmann A, Becker K. Virulence factors and genotypes of Staphylococcus aureus from infection and carriage in Gabon. Clin Microbiol Infect. 2011;17(10):1507–1513. doi: 10.1111/j.1469-0691.2011.03534.x.
    1. Popovich KJ, Hota B, Aroutcheva A, Kurien L, Patel J, Lyles-Banks R, Grasso AE, Spec A, Beavis KG, Hayden MK, Weinstein RA. Community-associated methicillin-resistant Staphylococcus aureus colonization burden in HIV-infected patients. Clin Infect Dis. 2013;56(8):1067–1074. doi: 10.1093/cid/cit010.
    1. Srinivasan A, Seifried S, Zhu L, Bitar W, Srivastava DK, Shenep JL, Bankowski MJ, Flynn PM, Hayden RT. Short communication: methicillin-resistant Staphylococcus aureus infections in children and young adults infected with HIV. AIDS Res Hum Retrovir. 2009;25(12):1219–1224. doi: 10.1089/aid.2009.0040.
    1. Utsi L, Pichon B, Arunachalam N, Kerrane A, Batten E, Denton M, Townsend R, Agwuh KN, Hughes GJ, Kearns A. Circulation of a community healthcare-associated multiply-resistant meticillin-resistant Staphylococcus aureus lineage in South Yorkshire identified by whole genome sequencing. J Hosp Infect. 2019;103(4):454–460. doi: 10.1016/j.jhin.2019.08.006.
    1. De Boeck H, Vandendriessche S, Hallin M, Batoko B, Alworonga JP, Mapendo B, Van Geet C, Dauly N, Denis O, Jacobs J. Staphylococcus aureus nasal carriage among healthcare workers in Kisangani, the Democratic Republic of the Congo. Eur J Clin Microbiol Infect Dis. 2015;34(8):1567–1572. doi: 10.1007/s10096-015-2387-9.
    1. Vandendriessche S, De Boeck H, Deplano A, Phoba MF, Lunguya O, Falay D, Dauly N, Verhaegen J, Denis O, Jacobs J. Characterisation of Staphylococcus aureus isolates from bloodstream infections, Democratic Republic of the Congo. Eur J Clin Microbiol Infect Dis. 2017;36(7):1163–1171. doi: 10.1007/s10096-017-2904-0.
    1. Driebe EM, Sahl JW, Roe C, Bowers JR, Schupp JM, Gillece JD, Kelley E, Price LB, Pearson TR, Hepp CM, Brzoska PM, Cummings CA, Furtado MR, Andersen PS, Stegger M, Engelthaler DM, Keim PS. Using whole genome analysis to examine recombination across diverse sequence types of Staphylococcus aureus. PLoS One. 2015;10(7):e0130955. doi: 10.1371/journal.pone.0130955.
    1. Strauss L, Stegger M, Akpaka PE, Alabi A, Breurec S, Coombs G, Egyir B, Larsen AR, Laurent F, Monecke S, Peters G, Skov R, Strommenger B, Vandenesch F, Schaumburg F, Mellmann A. Origin, evolution, and global transmission of community-acquired Staphylococcus aureus ST8. Proc Natl Acad Sci U S A. 2017;114(49):E10596–e10604. doi: 10.1073/pnas.1702472114.
    1. Khodabandeh M, Mohammadi M, Abdolsalehi MR, Alvandimanesh A, Gholami M, Bibalan MH, Pournajaf A, Kafshgari R, Rajabnia R. Analysis of resistance to macrolide-Lincosamide-Streptogramin B among mecA-positive Staphylococcus aureus isolates. Osong Public Health Res Perspect. 2019;10(1):25–31. doi: 10.24171/j.phrp.2019.10.1.06.
    1. Phaku P, Lebughe M, Strauss L, Peters G, Herrmann M, Mumba D, Mellmann A, Muyembe-Tamfum JJ, Schaumburg F (2016) Unveiling the molecular basis of antimicrobial resistance in Staphylococcus aureus from the Democratic Republic of the Congo using whole genome sequencing. Clin Microbiol Infect 22 (7):644.e641-645
    1. Steward CD, Raney PM, Morrell AK, Williams PP, McDougal LK, Jevitt L, McGowan JE, Jr, Tenover FC. Testing for induction of clindamycin resistance in erythromycin-resistant isolates of Staphylococcus aureus. J Clin Microbiol. 2005;43(4):1716–1721. doi: 10.1128/JCM.43.4.1716-1721.2005.
    1. Kyany'a C, Nyasinga J, Matano D, Oundo V, Wacira S, Sang W, Musila L. Phenotypic and genotypic characterization of clinical Staphylococcus aureus isolates from Kenya. BMC Microbiol. 2019;19(1):245. doi: 10.1186/s12866-019-1597-1.
    1. Enström J, Fröding I, Giske CG, Ininbergs K, Bai X, Sandh G, Tollström UB, Ullberg M, Fang H. USA300 methicillin-resistant Staphylococcus aureus in Stockholm, Sweden, from 2008 to 2016. PLoS One. 2018;13(11):e0205761. doi: 10.1371/journal.pone.0205761.
    1. Raz R. Fosfomycin: an old--new antibiotic. Clin Microbiol Infect. 2012;18(1):4–7. doi: 10.1111/j.1469-0691.2011.03636.x.
    1. McCaughey G, Diamond P, Elborn JS, McKevitt M, Tunney MM. Resistance development of cystic fibrosis respiratory pathogens when exposed to fosfomycin and tobramycin alone and in combination under aerobic and anaerobic conditions. PLoS One. 2013;8(7):e69763. doi: 10.1371/journal.pone.0069763.
    1. Sahuquillo Arce JM, Colombo Gainza E, Gil Brusola A, Ortiz Estévez R, Cantón E, Gobernado M. In vitro activity of linezolid in combination with doxycycline, fosfomycin, levofloxacin, rifampicin and vancomycin against methicillin-susceptible Staphylococcus aureus. Rev Esp Quimioter. 2006;19(3):252–257.
    1. Alonzo F, 3rd, Benson MA, Chen J, Novick RP, Shopsin B, Torres VJ. Staphylococcus aureus leucocidin ED contributes to systemic infection by targeting neutrophils and promoting bacterial growth in vivo. Mol Microbiol. 2012;83(2):423–435. doi: 10.1111/j.1365-2958.2011.07942.x.
    1. van Wamel WJ, Rooijakkers SH, Ruyken M, van Kessel KP, van Strijp JA. The innate immune modulators staphylococcal complement inhibitor and chemotaxis inhibitory protein of Staphylococcus aureus are located on beta-hemolysin-converting bacteriophages. J Bacteriol. 2006;188(4):1310–1315. doi: 10.1128/JB.188.4.1310-1315.2006.

Source: PubMed

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