Drug Resistance Genes and Source of Methicillin Resistant Staphylococcus aureus Strains amongst HIV Patients in Fako Division of Cameroon: A Case-Control Study
Background: Methicillin Resistant Staphylococcus aureus and severe antimicrobial resistance is worsened in HIV positive patients, driven by the presence of drug resistance traits. This study aimed to determine the prevalence of MRSA, antibiotic susceptibility, source of infection and the distribution of drug resistance genes amongst HIV positive and HIV negative participants in Fako-Cameroon. Methods: Urine and nasal samples were cultured on CLED and MSA agar respectively following standard procedures. The clinical isolates were characterized biochemically and comfirmed by nuc gene detection of S. aureus. Antimicrobial susceptibility with selected locally prescribed antibiotics was done using the Kirby Bauer disc diffusion technique. Drug resistance genes (vanA, mecA, ermA, sul3 and ermC) were determined using PCR amplification. Data was analyzed using Microsoft Excel 2016 and SPSS version 25; Chi square was set at P ≤ 0.05. Results: The overall prevalence of MRSA was 28.8%. MRSA was higher (P = 0.0001) in HIV positive patients (19.4%) than in HIV negative individuals (9.4%). Amongst HIV positive and HIV negative participants, high sensitivity of urogenital S. aureus was observed amongst Aminoglycosides [Amikacin (26.3% vs 52.9%)] and Nitrofurans [Nitrofurantoin (25.2% vs 53.1%)]. Resistance was seen against Ciprofloxacin [39.5% vs 41.2%] in HIV positive and HIV negative participants respectively. MAR index of urogenital S. aureus was higher amongst HIV positive patients (0.9) compared to HIV negative individuals (0.7). Majority (38.0%) of S. aureus clinical isolates cultured from the urine of HIV positive patients were not identical to isolates from the nostrils of the same patients. The overall detection rate of drug resistance genes were distributed as follows; vanA (30.8%), ermA (29.6%), mecA (28.6%), sul3 (21.6%) and ermC (18.0%). Conclusion: Methicillin resistant Staphylococcus aureus is more common amongst HIV positive patients, with the clinical isolates being, more resistant to commonly prescribed antimicrobial agents. The clinical isolates causing urinary tract infections in HIV positive patients are usually not from the normal flora (the nostrils).
References
[1]
Turner, N.A., Sharma-Kuinkel, B.K., Maskarinec, S.A., Eichenberger, E.M., Shah, P.P., Carugati, M., et al. (2019) Methicillin-Resistant Staphylococcus aureus: An Overview of Basic and Clinical Research. NatureReviewsMicrobiology, 17, 203-218. https://doi.org/10.1038/s41579-018-0147-4
[2]
Hiramatsu, K., Katayama, Y., Matsuo, M., Sasaki, T., Morimoto, Y., Sekiguchi, A., et al. (2014) Multi-Drug-Resistant Staphylococcus aureus and Future Chemotherapy. JournalofInfectionandChemotherapy, 20, 593-601. https://doi.org/10.1016/j.jiac.2014.08.001
[3]
Ndedy, M.M., Nyasa, R.B., Esemu, S.N., Kfusi, J.A., Keneh, N.K., Masalla, T.N., et al. (2023) A Cross-Sectional Study on the Prevalence and Drug Susceptibility Pattern of Methicillin-Resistant Staphylococcus aureus Isolated from Patients in the Buea Health District, Cameroon. PanAfricanMedicalJournal, 45, Article 28. https://doi.org/10.11604/pamj.2023.45.28.36860
[4]
Vestergaard, M., Frees, D. and Ingmer, H. (2019) Antibiotic Resistance and the MRSA Problem. MicrobiologySpectrum, 7, 1-23. https://doi.org/10.1128/microbiolspec.gpp3-0057-2018
[5]
Talebi, G., Hashemia, A., Goudarzi, H., Shariati, A., Bostanghadiri, N., Sharahi, J.Y., et al. (2019) Survey of ermA, ermB, ermC and mecA Genes among Staphylococcus aureus Isolates Isolated from Patients Admitted to Hospitals in Tehran, Iran by PCR and Sequencing. BiomedicalResearch, 30, 259-263. https://doi.org/10.35841/biomedicalresearch.30-18-1152
[6]
Worku, S., Abebe, T., Seyoum, B., Alemu, A., Shimelash, Y., Yimer, M., et al. (2023) Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus among Patients Diagnosed with Surgical Site Infection at Four Hospitals in Ethiopia. Antibiotics, 12, Article 1681. https://doi.org/10.3390/antibiotics12121681
[7]
Adeyemi, F.M., Ako-Nai, K.A., Adejuyigbe, E., Ebhodaghe, B.I., et al. (2015) Molecular Characterization and Antibiotic Resistance Profiles of Bacterial Isolates Cultured from HIV Seropositive Patients. Archives of Clinical Microbiology, 6, 2.
[8]
David, M.Z. and Daum, R.S. (2017) Treatment of Staphylococcus aureus Infections. In: Bagnoli, F., Rappuoli, R. and Grandi, G., Eds., Staphylococcus aureus, Springer, 325-383. https://doi.org/10.1007/82_2017_42
[9]
Mahjabeen, F., Saha, U., Mostafa, M.N., Siddique, F., Ahsan, E., Fathma, S., et al. (2022) An Update on Treatment Options for Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia: A Systematic Review. Cureus, 14, e31486. https://doi.org/10.7759/cureus.31486
[10]
Steward, C.D., Raney, P.M., Morrell, A.K., Williams, P.P., McDougal, L.K., Jevitt, L., et al. (2005) Testing for Induction of Clindamycin Resistance in Erythromycin-Resistant Isolates of Staphylococcus aureus. JournalofClinicalMicrobiology, 43, 1716-1721. https://doi.org/10.1128/jcm.43.4.1716-1721.2005
[11]
Kasiulevicius, V., Sapoka, V. and Filipaviciūte, R. (2006) Sample Size Calculation in Epidemiological Studies. Gerontologija, 7, 225-231.
[12]
Javid, F., Taku, A., Bhat, M.A., Badroo, G.A., Mudasir, M. and Sofi, T.A. (2018) Molecular Typing of Staphylococcus aureus Based on Coagulase Gene. VeterinaryWorld, 11, 423-430. https://doi.org/10.14202/vetworld.2018.423-430
[13]
CLSI (2016) Performance Standards for antimicrobial Susceptibility Testing: CLSI Supplement M100S. Clinical and Laboratory Standards Institute Wayne.
[14]
Kruasuwan, W., Sawatwong, P., Jenjaroenpun, P., Wankaew, N., Arigul, T., Yongkiettrakul, S., et al. (2024) Comparative Evaluation of Commercial DNA Isolation Approaches for Nanopore-Only Bacterial Genome Assembly and Plasmid Recovery. ScientificReports, 14, Article No. 27672. https://doi.org/10.1038/s41598-024-78066-2
[15]
Lee, P.Y., Costumbrado, J., Hsu, C. and Kim, Y.H. (2012) Agarose Gel Electrophoresis for the Separation of DNA Fragments. JournalofVisualizedExperiments, No. 62, Article 3923. https://doi.org/10.3791/3923-v
[16]
Louie, L., Goodfellow, J., Mathieu, P., Glatt, A., Louie, M. and Simor, A.E. (2002) Rapid Detection of Methicillin-Resistant Staphylococci from Blood Culture Bottles by Using a Multiplex PCR Assay. JournalofClinicalMicrobiology, 40, 2786-2790. https://doi.org/10.1128/jcm.40.8.2786-2790.2002
[17]
Hoegh, S.V., Skov, M.N., Boye, K., Worning, P., Jensen, T.G. and Kemp, M. (2014) Variations in the Staphylococcus aureus-Specific nuc Gene Can Potentially Lead to Misidentification of Meticillin-Susceptible and-Resistant S. aureus. JournalofMedicalMicrobiology, 63, 1020-1022. https://doi.org/10.1099/jmm.0.076638-0
[18]
García, A., Martínez, C., Juárez, R.I., Téllez, R., Paredes, M.A., Herrera, M.d.R., et al. (2019) Resistencia a la meticilina y producción de biopelícula en aislamientos clínicos de Staphylococcus aureus y Staphylococcus coagulasa negativa en México. Biomédica, 39, 513-523. https://doi.org/10.7705/biomedica.4131
[19]
Wang, N., Yang, X., Jiao, S., Zhang, J., Ye, B. and Gao, S. (2014) Sulfonamide-Resistant Bacteria and Their Resistance Genes in Soils Fertilized with Manures from Jiangsu Province, Southeastern China. PLOSONE, 9, e112626. https://doi.org/10.1371/journal.pone.0112626
[20]
Strommenger, B., Kettlitz, C., Werner, G. and Witte, W. (2003) Multiplex PCR Assay for Simultaneous Detection of Nine Clinically Relevant Antibiotic Resistance Genes in Staphylococcus aureus. JournalofClinicalMicrobiology, 41, 4089-4094. https://doi.org/10.1128/jcm.41.9.4089-4094.2003
[21]
Nelson, R.E., Evans, M.E., Simbartl, L., Jones, M., Samore, M.H., Kralovic, S.M., et al. (2018) Methicillin-Resistant Staphylococcus aureus Colonization and Pre-and Post-Hospital Discharge Infection Risk. ClinicalInfectiousDiseases, 68, 545-553. https://doi.org/10.1093/cid/ciy507
[22]
Oliva, A., Lichtner, M., Mascellino, M.T., etal. (2013) Study of Methicillin-Resistant Staphylococcus aureus (MRSA) Carriage in a Population of HIV-Negative Migrants and HIV-Infected Patients Attending an Outpatient Clinic in Rome. AnnalidiIgiene, MedicinaPreventivaediComunita, 25, 99-107.
[23]
Karmakar, A., Jana, D., Dutta, K., Dua, P. and Ghosh, C. (2018) Prevalence of Panton-Valentine Leukocidin Gene among Community Acquired Staphylococcus aureus: A Real-Time PCR Study. JournalofPathogens, 2018, Article ID: 4518541. https://doi.org/10.1155/2018/4518541
[24]
Zigmond, J., Pecan, L., Hájek, P., Raghubir, N. and Omrani, A.S. (2014) MRSA Infection and Colonization Rates in Africa and Middle East: A Systematic Review & Meta-Analysis. InternationalJournalofInfectiousDiseases, 21, 391. https://doi.org/10.1016/j.ijid.2014.03.1227
[25]
Boison, D., Akwetey, S.A., Osei, S.A., Kelechi, S. and Barnie, P.A. (2022) Nasal Colonization of Methicillin-Resistant Staphylococcus aureus in HIV-Infected Patients at the Cape Coast Teaching Hospital, Ghana. FrontiersinTropicalDiseases, 3, Article 976567. https://doi.org/10.3389/fitd.2022.976567
[26]
Neupane, K., Rayamajhee, B., Acharya, J., Rijal, N., Shrestha, D., Binod, G.C., et al. (2018) Comparison of Nasal Colonization of Methicillin-Resistant Staphylococcus aureus in HIV-Infected and Non-HIV Patients Attending the National Public Health Laboratory of Central Nepal. CanadianJournalofInfectiousDiseasesandMedicalMicrobiology, 2018, Article ID: 4508757. https://doi.org/10.1155/2018/4508757
[27]
Popovich, K.J., Hota, B., Aroutcheva, A., Kurien, L., Patel, J., Lyles-Banks, R., et al. (2013) Community-Associated Methicillin-Resistant Staphylococcus aureus Colonization Burden in HIV-Infected Patients. ClinicalInfectiousDiseases, 56, 1067-1074. https://doi.org/10.1093/cid/cit010
[28]
Kengne, M., Fotsing, O., Ndomgue, T. and Mbekem Nwobegahay, J. (2019) Antibiotic Susceptibility Patterns of Staphylococcus aureus Strains Isolated at the Yaounde Central Hospital, Cameroon: A Retro Prospective Study. PanAfricanMedicalJournal, 32, Article 103. https://doi.org/10.11604/pamj.2019.32.103.15743
[29]
Kengne, M., Fotie, H.B.N., Nwobegahay, J.M., Achiangia, P.N., Tamoufe, U., Goon, D.T., et al. (2020) Antibiotic Sensitivity Profile of Staphylococcus aureus Isolated from HIV/AIDS Patients Presenting with Pyoderma, at the Yaounde Central Hospital, Cameroon. PanAfricanMedicalJournal, 37, Article 185. https://doi.org/10.11604/pamj.2020.37.185.14595
[30]
Samje, M., Yongwa, O., Mbi Enekegbe, A. and Njoya, S. (2020) Prevalence and Antibiotic Susceptibility Pattern of Bacteriuria among HIV-Seropositive Patients Attending the Bamenda Regional Hospital, Cameroon. AfricanHealthSciences, 20, 1045-1052. https://doi.org/10.4314/ahs.v20i3.7
[31]
Gebremedhn, G., Gebremariam, T.T., Wasihun, A.G., Dejene, T.A. and Saravanan, M. (2016) Prevalence and Risk Factors of Methicillin-Resistant Staphylococcus aureus Colonization among HIV Patients in Mekelle, Northern Ethiopia. SpringerPlus, 5, Article No. 877. https://doi.org/10.1186/s40064-016-2613-7
[32]
Egyir, B., Oteng, A.A., Owusu, E., Newman, M.J., Addo, K.K. and Rhod-Larsen, A. (2016) Characterization of Staphylococcus aureus from Human Immunodeficiency Virus (HIV) Patients in Accra, Ghana. TheJournalofInfectioninDevelopingCountries, 10, 453-456. https://doi.org/10.3855/jidc.7428
[33]
Igwe, J.C., Nkom, P.J., Durowaiye, M.T., Obajuluwa, A.F. and Parom, S.K. (2023) Methicillin Resistant Staphylococcus aureus Colonization among HIV Patients. SciMedicineJournal, 5, 107-117. https://doi.org/10.28991/scimedj-2023-05-03-03
[34]
Khairalla, A.S., Wasfi, R. and Ashour, H.M. (2017) Carriage Frequency, Phenotypic, and Genotypic Characteristics of Methicillin-Resistant Staphylococcus aureus Isolated from Dental Health-Care Personnel, Patients, and Environment. ScientificReports, 7, Article No. 7390. https://doi.org/10.1038/s41598-017-07713-8
[35]
Agbo, M.C., Ezeonu, I.M., Onodagu, B.O., Ezeh, C.C., Ozioko, C.A. and Emencheta, S.C. (2024) Antimicrobial Resistance Markers Distribution in Staphylococcus aureus from Nsukka, Nigeria. BMCInfectiousDiseases, 24, Article No. 320. https://doi.org/10.1186/s12879-024-09126-1
[36]
Alfeky, A.E., Tawfick, M.M., Ashour, M.S. and El-Moghazy, A.A. (2022) High Prevalence of Multi-Drug Resistant Methicillin-Resistant Staphylococcus aureus in Tertiary Egyptian Hospitals. TheJournalofInfectioninDevelopingCountries, 16, 795-806. https://doi.org/10.3855/jidc.15833
[37]
Abdulrahim, U., Oche, D.A., Kachallah, M., Adeshina, G.O. and Olayinka, B.O. (2023) Emergence of Clinical VanA-Type Vancomycin-Resistant Staphylococcus aureus Isolates in National Orthopaedic Hospital Dala, Kano, Nigeria. AfricanJournalofClinicalandExperimentalMicrobiology, 24, 250-257. https://doi.org/10.4314/ajcem.v24i3.4
[38]
Geofrey, M.A., Sauli, E., Kanje, L.E., Beti, M., Shayo, M.J., Kuchaka, D., et al. (2024) Genomic Characterization of Methicillin-Resistant Staphylococcus aureus Isolated from Patients Attending Regional Referral Hospitals in Tanzania. BMCMedicalGenomics, 17, Article No. 211. https://doi.org/10.1186/s12920-024-01979-4
[39]
González-Vázquez, R., Córdova-Espinoza, M.G., Escamilla-Gutiérrez, A., Herrera-Cuevas, M.D.R., González-Vázquez, R., Esquivel-Campos, A.L., et al. (2024) Detection of mecA Genes in Hospital-Acquired MRSA and SOSA Strains Associated with Biofilm Formation. Pathogens, 13, Article 212. https://doi.org/10.3390/pathogens13030212
[40]
Idrees, M.M., Saeed, K., Shahid, M.A., Akhtar, M., Qammar, K., Hassan, J., et al. (2023) Prevalence of mecA-and mecC-Associated Methicillin-Resistant Staphylococcus aureus in Clinical Specimens, Punjab, Pakistan. Biomedicines, 11, Article 878. https://doi.org/10.3390/biomedicines11030878
[41]
Kapali, S., Pokhrel, A., Bastola, A., Tuladhar, R. and Joshi, D.R. (2021) Methicillin-resistant Staphylococcus aureus Nasal Colonization in People Living with HIV and Healthy People in Kathmandu, Nepal. FutureScienceOA, 8, Article ID: FSO769. https://doi.org/10.2144/fsoa-2021-0103
[42]
Eyoh, A., Ehlers, M., Mbamyah, E.L., Antiabong, J., Fokunang, C., Kock, M., et al. (2021) Molecular Diversity of Staphylococcus aureus from the Nares of Hospital Personnel, HIV-Positive and Diabetes Mellitus Patients in Yaounde Cameroon. AdvancesinMicrobiology, 11, 740-756. https://doi.org/10.4236/aim.2021.1112053
[43]
Timsina, R., Shrestha, U., Singh, A. and Timalsina, B. (2020) Inducible Clindamycin Resistance and erm Genes in Staphylococcus aureus in School Children in Kathmandu, Nepal. FutureScienceOA, 7, Article ID: FSO361. https://doi.org/10.2144/fsoa-2020-0092
[44]
Fasihi, Y., Saffari, F., Kandehkar Ghahraman, M.R. and Kalantar-Neyestanaki, D. (2016) Molecular Detection of Macrolide and Lincosamide-Resistance Genes in Clinical Methicillin-Resistant Staphylococcus aureus Isolates from Kerman, Iran. ArchivesofPediatricInfectiousDiseases, 5, e37761. https://doi.org/10.5812/pedinfect.37761
[45]
Ghanbari, F., Ghajavand, H., Havaei, R., Jami, M., Khademi, F., Heydari, L., et al. (2016) Distribution of Erm Genes among Staphylococcus aureus Isolates with Inducible Resistance to Clindamycin in Isfahan, Iran. AdvancedBiomedicalResearch, 5, 62. https://doi.org/10.4103/2277-9175.179184
[46]
Khoshnood, S., Shahi, F., Jomehzadeh, N., Montazeri, E.A., Saki, M., Mortazavi, S.M., et al. (2019) Distribution of Genes Encoding Resistance to Macrolides, Lincosamides, and Streptogramins among Methicillin-Resistant Staphylococcus aureus Strains Isolated from Burn Patients. ActaMicrobiologicaetImmunologicaHungarica, 66, 387-398. https://doi.org/10.1556/030.66.2019.015
[47]
Goudarzi, G., Tahmasbi, F., Anbari, K. and Ghafarzadeh, M. (2016) Distribution of Genes Encoding Resistance to Macrolides among Staphylococci Isolated from the Nasal Cavity of Hospital Employees in Khorramabad, Iran. IranianRedCrescentMedicalJournal, 18, e25701. https://doi.org/10.5812/ircmj.25701
[48]
Aydeniz Ozansoy, F., Cevahir, N. and Kaleli, İ. (2015) Investigation of Macrolide, Lincosamide and Streptogramin B Resistance in Staphylococcus aureus Strains Isolated from Clinical Samples by Phenotypical and Genotypical Methods. MikrobiyolojiBulteni, 49, 1-14. https://doi.org/10.5578/mb.8790
[49]
Keneh, N.K., Kenmoe, S., Bowo-Ngandji, A., Tatah Kihla Akoachere, J., Gonsu Kamga, H., Ndip, R.N., et al. (2023) A Mapping Review of Methicillin-Resistant Staphylococcus aureus Proportions, Genetic Diversity, and Antimicrobial Resistance Patterns in Cameroon. PLOSONE, 18, e0296267. https://doi.org/10.1371/journal.pone.0296267