Background: The characteristics of Staphylococcus aureus that made it the most important cause of wound infections are environmental spread antimicrobials resistance and virulence. Absence of molecular detection of drug resistance and virulence factors in many developing countries limits the epidemiological information. This study conducted to identify PVL virulence gene, and blaOXA-23 and blaOXA-51 drug resistance genes of Staphylococcus aureus isolated from surgical-sites infections (SSIs) and traumatic wounds. Methods: A cross-sectional study was conducted from 2019 to 2021, in which 70 cefepime resistant Staphylococcus aureus were used, the strains were isolated from patients of SSIs and traumatic wounds admitted to the department of General Surgery in Wad Medani Teaching Hospital. Mannitol salt agar was used for primary culture followed by biochemical identification and Kirby Bauer susceptibility testing. Single and multiplex PCR protocols performed for bacterial confirmation and target genes detection. Results: Staphylococcus aureus strains from SSIs constituted 56% (39/70) from which 41% (16/39) possessed PVL gene while 42% (13/31) of wound infections strains were positive for PVL gene. Presence of PVL gene was significantly associated with resistance to meropenem (P. value 0.023) and ceftriaxone (P. value 0.037). blaOXA-23 was significantly detected with resistance to meropenem, augmentin and ceftriaxone. While blaOXA-51 was significantly identified among Staphylococcus aureus strains that showed resistance to meropenem and ciprofloxacin. Conclusion: This is the first study in Sudan that identified blaOXA-23 and blaOXA-51 in Staphylococcus aureus and correlated them to resistance to commonly used antimicrobials. Meropenem resistant Staphylococcus aureus were significantly positive for PVL, blaOXA-23 and baOXA-51 genes.
References
[1]
Shettigar, K. and Murali, T.S. (2020) Virulence Factors and Clonal Diversity of Staphylococcus aureus in Colonization and Wound Infection with Emphasis on Diabetic Foot Infection. European Journal of Clinical Microbiology & Infectious Diseases, 39, 2235-2246. https://doi.org/10.1007/s10096-020-03984-8
[2]
Pal, S., Sayana, A., Joshi, A. and Juyal, D. (2019) Staphylococcus aureus: A Predominant Cause of Surgical Site Infections in a Rural Healthcare Setup of Uttarakhand. Journal of Family Medicine and Primary Care, 8, 3600-3606.
https://doi.org/10.4103/jfmpc.jfmpc_521_19
[3]
Rajkumari, N., Sharma, K., Mathu, P., Kumar, S. and Gupta, A. (2014) A Study on Surgical Site Infections after Trauma Surgeries in a Tertiary Care Hospital in North India. Indian Journal of Medical Research, 140, 691-694.
[4]
Guo, Y., Song, G., Sun, M., Wang, J. and Wang, Y. (2020) Prevalence and Therapies of Antibiotic-Resistance in Staphylococcus aureus. Frontiers in Cellular and Infection Microbiology, 10, Article No. 107. https://doi.org/10.3389/fcimb.2020.00107
https://www.frontiersin.org/articles/10.3389/fcimb.2020.00107/full
[5]
Negut, I., Grumezescu, V. and Grumezescu, A.M. (2018) Treatment Strategies for Infected Wounds. Molecules, 23, Article No. 2392.
https://doi.org/10.3390/molecules23092392
[6]
Cheung, G.Y.C., Bae, J.S. and Otto, M. (2021) Pathogenicity and Virulence of Staphylococcus aureus. Virulence, 12, 547-569.
https://doi.org/10.1080/21505594.2021.1878688
[7]
Hu, D.L., Li, S., Fang, R. and Ono, H.K. (2021) Update on Molecular Diversity and Multipathogenicity of Staphylococcal Superantigen Toxins. Animal Diseases, 1, Article No. 7. https://doi.org/10.1186/s44149-021-00007-7
[8]
Shallcross, L.J., Fragaszy, E., Johnson, A.M. and Hayward, A.C. (2013) The Role of the Panton-Valentine Leucocidin Toxin in Staphylococcal Disease: A Systematic Review and Meta-Analysis. The Lancet Infectious Diseases, 13, 43-54.
https://doi.org/10.1016/S1473-3099(12)70238-4
[9]
Jiang, B., Wang, Y., Feng, Z., Xu, L., Tan, L., Zhao, S., et al. (2017) Panton-Valentine Leucocidin (PVL) as a Potential Indicator for Prevalence, Duration, and Severity of Staphylococcus aureus Osteomyelitis. Frontiers in Microbiology, 8, Article No. 2355. https://doi.org/10.3389/fmicb.2017.02355
[10]
Oogai, Y., Matsuo, M., Hashimoto, M., Kato, F., Sugai, M. and Komatsuzawa, H. (2011) Expression of Virulence Factors by Staphylococcus aureus Grown in Serum. Applied and Environmental Microbiology, 77, 8097-8105.
https://doi.org/10.1128/AEM.05316-11
[11]
Li, X., Huang, T., Xu, K., Li, C. and Li, Y. (2019) Molecular Characteristics and Virulence Gene Profiles of Staphylococcus aureus Isolates in Hainan, China. BMC Infectious Diseases, 19, Article No. 873. https://doi.org/10.1186/s12879-019-4547-5
[12]
Misha, G., Chelkeba, L. and Melaku, T. (2021) Bacterial Profile and Antimicrobial Susceptibility Patterns of Isolates among Patients Diagnosed with Surgical Site Infection at a Tertiary Teaching Hospital in Ethiopia: A Prospective Cohort Study. Annals of Clinical Microbiology and Antimicrobials, 20, Article No. 33.
https://doi.org/10.1186/s12941-021-00440-z
[13]
Duran, N., Ozer, B., Duran, G.G., Onlen, Y. and Demir, C. (2012) Antibiotic Resistance Genes & Susceptibility Patterns in Staphylococci. Indian Journal of Medical Research, 135, 389-396.
[14]
Hope, D., Ampaire, L., Oyet, C., Muwanguzi, E., Twizerimana, H. and Apecu, R.O. (2019) Antimicrobial Resistance in Pathogenic Aerobic Bacteria Causing Surgical Site Infections in Mbarara Regional Referral Hospital, Southwestern Uganda. Scientific Reports, 9, Article No. 17299. https://doi.org/10.1038/s41598-019-53712-2
[15]
Nomura, R., Nakaminami, H., Takasao, K., Muramatsu, S., Kato, Y., Wajima, T., et al. (2020) A Class A β-Lactamase Produced by Borderline Oxacillin-Resistant Staphylococcus aureus Hydrolyses Oxacillin. Journal of Global Antimicrobial Resistance, 22, 244-247. https://doi.org/10.1016/j.jgar.2020.03.002
[16]
Bonko, M.D.A., Lompo, P., Tahita, M.C., Kiemde, F., Karama, I., Somé, A.M., et al. (2021) Antibiotic Susceptibility of Staphylococcus aureus and Streptococcus pneumoniae Isolates from the Nasopharynx of Febrile Children under 5 Years in Nanoro, Burkina Faso. Antibiotics, 10, Article No. 444.
https://doi.org/10.3390/antibiotics10040444
[17]
Darboe, S., Dobreniecki, S., Jarju, S., Jallow, M., Mohammed, N.I., Wathuo, M., et al. (2019) Prevalence of Panton-Valentine Leukocidin (PVL) and Antimicrobial Resistance in Community-Acquired Clinical Staphylococcus aureus in an Urban Gambian Hospital: A 11-Year Period Retrospective Pilot Study. Frontiers in Cellular and Infection Microbiology, 9, Article No. 170.
https://doi.org/10.3389/fcimb.2019.00170
[18]
Castellazzi, M.L., Bosis, S., Borzani, I., Tagliabue, C., Pinzani, R., Marchisio, P., et al. (2021) Panton-Valentine Leukocidin Staphylococcus aureus Severe Infection in an Infant: A Case Report and a Review of the Literature. Italian Journal of Pediatrics, 47, Article No. 158. https://doi.org/10.1186/s13052-021-01105-5
[19]
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. Journal of Pathogens, 2018, Article ID: 4518541.
https://doi.org/10.1155/2018/4518541
[20]
Meletis, G. (2016) Carbapenem Resistance: Overview of the Problem and Future Perspectives. Therapeutic Advances in Infectious Disease, 3, 15-21.
https://doi.org/10.1177/2049936115621709
[21]
Gurung, S., Kafle, S., Dhungel, B., Adhikari, N., ThapaShrestha, U., Adhikari, B., et al. (2020) Detection of OXA-48 Gene in Carbapenem-Resistant Escherichia coli and Klebsiella pneumoniae from Urine Samples. Infection and Drug Resistance, 13, 2311-2321. https://doi.org/10.2147/IDR.S259967
[22]
Sugumar, M., Kumar, K.M., Manoharan, A., Anbarasu, A. and Ramaiah, S. (2014) Detection of OXA-1β-Lactamase Gene of Klebsiella pneumoniae from Blood Stream Infections (BSI) by Conventional PCR and In-Silico Analysis to Understand the Mechanism of OXA Mediated Resistance. PLOS ONE, 9, e91800.
https://doi.org/10.1371/journal.pone.0091800
[23]
Mlynarcik, P., Chalachanova, A., Vagnerova, I., Holy, O., Zatloukalova, S. and Kolar, M. (2020) PCR Detection of Oxacillinases in Bacteria. Microbial Drug Resistance, 26, 1023-1037. https://doi.org/10.1089/mdr.2019.0330
Ali, D.O. and Nagla, M.M.A. (2020) Molecular Detection of bla OXA-48 Gene Encoding Carbapenem Resistance Pseudomonas aeruginosa Clinical Isolates from Khartoum State Hospitals, Sudan. medRxiv.
http://medrxiv.org/lookup/doi/10.1101/2020.06.22.20137034
https://doi.org/10.1101/2020.06.22.20137034
[26]
Mahmoud, N.E., Altayb, H.N. and Gurashi, R.M. (2020) Detection of Carbapenem-Resistant Genes in Escherichia coli Isolated from Drinking Water in Khartoum, Sudan. Journal of Environmental and Public Health, 2020, Article ID: 2571293.
https://doi.org/10.1155/2020/2571293
[27]
Anane, Y.A., Apalata, T., Vasaikar, S., Okuthe, G.E. and Songca, S. (2020) Molecular Detection of Carbapenemase-Encoding Genes in Multidrug-Resistant Acinetobacter baumannii Clinical Isolates in South Africa. International Journal of Microbiology, 2020, Article ID: 7380740. https://doi.org/10.1155/2020/7380740
[28]
Zhao, Y., Hu, K., Zhang, J., Guo, Y., Fan, X., Wang, Y., et al. (2019) Outbreak of Carbapenem-Resistant Acinetobacter baumannii Carrying the Carbapenemase OXA-23 in ICU of the Eastern Heilongjiang Province, China. BMC Infectious Diseases, 19, Article No. 452. https://doi.org/10.1186/s12879-019-4073-5
[29]
Yousif, S.M., Abakar, A.D., Nour, B.Y.M., Ibrahim, S.O., Elhasan, O.M.A., Yousif, M.A., et al. (2021) Frequency and Antimicrobials Susceptibility Pattern of Staphylococcus aureus Associated with Wound Infections in Surgery Department, Wad Madani Teaching Hospital, Sudan. Pharmacology & Pharmacy, 12, 334-343.
https://doi.org/10.4236/pp.2021.1212028
[30]
Chen, Y.L., Lee, C.C., Lin, Y.L., Yin, K.M., Ho, C.L. and Liu, T. (2015) Obtaining Long 16S rDNA Sequences Using Multiple Primers and Its Application on Dioxin-Containing Samples. BMC Bioinformatics, 16, Article No. S13.
https://doi.org/10.1186/1471-2105-16-S18-S13
[31]
Dayie, N.T.K.D., Osei, M.M., Opintan, J.A., Tetteh-Quarcoo, P.B., Kotey, F.C.N., Ahenkorah, J., et al. (2021) Nasopharyngeal Carriage and Antimicrobial Susceptibility Profile of Staphylococcus aureus among Children under Five Years in Accra. Pathogens, 10, Article No. 136. https://doi.org/10.3390/pathogens10020136
[32]
Joshi, P.R., Acharya, M., Kakshapati, T., Leungtongkam, U., Thummeepak, R. and Sitthisak, S. (2017) Co-Existence of bla OXA-23 and bla NDM-1 Genes of Acinetobacter baumannii Isolated from Nepal: Antimicrobial Resistance and Clinical Significance. Antimicrobial Resistance & Infection Control, 6, Article No. 21.
https://doi.org/10.1186/s13756-017-0180-5
[33]
Amin, D.H.M., Guler, E. and Baddal, B. (2020) Prevalence of Panton-Valentine Leukocidin in Methicillin-Resistant Staphylococcus aureus Clinical Isolates at a University Hospital in Northern Cyprus: A Pilot Study. BMC Research Notes, 13, Article No. 490. https://doi.org/10.1186/s13104-020-05339-0
[34]
Ma, Y., Zhao, Y., Tang, J., Tang, C., Chen, J. and Liu, J. (2018) Antimicrobial Susceptibility and Presence of Resistance & Enterotoxins/Enterotoxin-Likes Genes in Staphylococcus aureus from Food. CyTA—Journal of Food, 16, 76-84.
https://doi.org/10.1080/19476337.2017.1340341
[35]
Wolters, M., Frickmann, H., Christner, M., Both, A., Rohde, H., Oppong, K., et al. (2020) Molecular Characterization of Staphylococcus aureus Isolated from Chronic Infected Wounds in Rural Ghana. Microorganisms, 8, Article No. 2052.
https://doi.org/10.3390/microorganisms8122052
[36]
Deyno, S., Toma, A., Worku, M. and Bekele, M. (2017) Antimicrobial Resistance Profile of Staphylococcus aureus Isolates Isolated from Ear Discharges of Patients at University of Hawassa Comprehensive Specialized Hospital. BMC Pharmacology Toxicology, 18, Article No. 35. https://doi.org/10.1186/s40360-017-0141-x
[37]
Azab, K.S.M., Abdel-Rahman, M.A., El-Sheikh, H.H., Azab, E., Gobouri, A.A. and Farag, M.M.S. (2021) Distribution of Extended-Spectrum β-Lactamase (ESBL)-Encoding Genes among Multidrug-Resistant Gram-Negative Pathogens Collected from Three Different Countries. Antibiotics, 10, Article No. 247.
https://doi.org/10.3390/antibiotics10030247
[38]
Papastergiou, P. and Tsiouli, E. (2018) Healthcare-Associated Transmission of Panton-Valentine Leucocidin Positive Methicillin-Resistant Staphylococcus aureus: The Value of Screening Asymptomatic Healthcare Workers. BMC Infectious Diseases, 18, Article No. 484. https://doi.org/10.1186/s12879-018-3404-2
[39]
Ahmed, O.B. (2020) Prevalence of Methicillin-Resistant Staphylococcus aureus and Classical Enterotoxin Genes among Sudanese Food Handlers. Cureus, 12, e12289.
https://www.cureus.com/articles/47546-prevalence-of-methicillin-resistant-staphylococcus-aureus-and-classical-enterotoxin-genes-among-sudanese-food-handlers
https://doi.org/10.7759/cureus.12289
Sun, H., Xiao, G., Zhang, J., Pan, Z., Chen, Y. and Xiong, F. (2019) Rapid Simultaneous Detection of blaoxa-23, Ade-B, int-1, and ISCR-1 in Multidrug-Resistant Acinetobacter baumannii Using Single-Tube Multiplex PCR and High Resolution Melting Assay. Infection and Drug Resistance, 12, 1573-1581.
https://doi.org/10.2147/IDR.S207225
[42]
Hou, C. and Yang, F. (2015) Drug-Resistant Gene of blaOXA-23, blaOXA-24, blaOXA-51 and blaOXA-58 in Acinetobacter baumannii. International Journal of Clinical and Experimental Medicine, 8, 13859-13863.
[43]
Vakili, B., Fazeli, H., Shoaei, P., Yaran, M., Ataei, B., Khorvash, F. and Khaleghi, M. (2014) Detection of Colistin Sensitivity in Clinical Isolates of Acinetobacter baumannii in Iran. Journal of Research in Medical Sciences, 19, S67-S70.
[44]
Wang, Y., Batra, A., Schulenburg, H. and Dagan, T. (2022) Gene Sharing among Plasmids and Chromosomes Reveals Barriers for Antibiotic Resistance Gene Transfer. Philosophical Transactions of the Royal Society B, 377, Article ID: 20200467.
https://doi.org/10.1098/rstb.2020.0467
[45]
Bhatta, D.R., Cavaco, L.M., Nath, G., Kumar, K., Gaur, A., Gokhale, S., et al. (2016) Association of Panton Valentine Leukocidin (PVL) Genes with Methicillin Resistant Staphylococcus aureus (MRSA) in Western Nepal: A Matter of Concern for Community Infections (a Hospital Based Prospective Study). BMC Infectious Diseases, 16, Article No. 199. https://doi.org/10.1186/s12879-016-1531-1
