Keywords
Staphylococcus aureus
Infection
Methicillin-resistant
Infection
Methicillin-resistant
Abstract
Introduction. Methicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen associated with nosocomial and community infections. There is a continual focus on the epidemiology of this public health threat owing to the increase in its spread and rapid development of resistance.
Aim. We aimed to describe the clinical presentations of MRSA infections at an academic health centre by demonstrating the time trend of antibiotic resistance.
Methodology. We retrospectively reviewed cases during an 11-year period (from January 2009 to December 2019) with positive cultures for MRSA from various clinical sites in King Fahad Hospital of the University, to understand their clinical and microbiological profiles. Screening and colonisation samples were excluded.
Results. A total of 1338 MRSA isolates were identified, with an increasing trend from 5.2% to 14.5% during 2009–2019. Skin and soft tissue samples were the most common source (52.4%) of MRSA infections. Vancomycin activity remained stable against MRSA, and only one isolate showed resistance to linezolid (<1%). A significant reduction in susceptibility to clindamycin (p = 0.003), trimethoprim-sulfamethoxazole (p = 0.001), and rifampin (p <0.0001) was detected over the study period.
Conclusion. MRSA infections still represent a significant burden on healthcare systems. Our data support the need for constant local and regional surveillance to devise relevant protocols to manage MRSA infections. Empirical therapy needs to consider the changing antimicrobial susceptibility trends among MRSA isolates.
References
Antibiotic resistance threats in the United States, 2019 [Internet]. Centers for Disease Control and Prevention. 2019 [cited 19 April 2021]. Available from: http://dx.doi.org/10.15620/cdc:82532.
2. Monaco M, Pimentel de Araujo F, Cruciani M, Coccia E, Pantosti A. Worldwide Epidemiology and Antibiotic Resistance of Staphylococcus aureus. Current Topics in Microbiology and Immunology. 2016;:21-56. DOI 10.1007/82_2016_3
3. Boucher H, Miller L, Razonable R. Serious Infections Caused by Methicillin‐Resistant Staphylococcus aureus. Clinical Infectious Diseases. 2010;51(S2):S183-S197.DOI: 10.1086/653519
4. ERIKSEN K, ERICHSEN I. RESISTANCE TO METHICILLIN, ISOXAZOLYL PENICILLINS, AND CEPHALOTHIN IN STAPHYLOCOCCUS AUREUS. Acta Pathologica Microbiologica Scandinavica. 1964;62(2):255-275. DOI: 10.1111/apm.1964.62.2.255
5. Pada S, Ding Y, Ling M, Hsu L, Earnest A, Lee T et al. Economic and clinical impact of nosocomial meticillin-resistant Staphylococcus aureus infections in Singapore: a matched case–control study. Journal of Hospital Infection. 2011;78(1):36-40. DOI: 10.1016/j.jhin.2010.10.016
6. Howden B, Davies J, Johnson P, Stinear T, Grayson M. Reduced Vancomycin Susceptibility in Staphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications. Clinical Microbiology Reviews. 2010;23(1):99-139. DOI: 10.1128/CMR.00042-09
7. van Hal S, Lodise T, Paterson D. The Clinical Significance of Vancomycin Minimum Inhibitory Concentration in Staphylococcus aureus Infections: A Systematic Review and Meta-analysis. Clinical Infectious Diseases. 2012;54(6):755-771. DOI: 10.1093/cid/cir935
8. Yezli S, Shibl A, Livermore D, Memish Z. Antimicrobial resistance among Gram-positive pathogens in Saudi Arabia. Journal of Chemotherapy. 2012;24(3):125-136. DOI: 10.1179/1973947812Y.0000000010
9. Aly M, Balkhy H. The prevalence of antimicrobial resistance in clinical isolates from Gulf Corporation Council countries. Antimicrobial Resistance and Infection Control. 2012;1(1):26. DOI: 10.1186/2047-2994-1-26
10. El Amin N, Faidah H. Methicillin-resistant Staphylococcus aureus in the western region of Saudi Arabia: prevalence and antibiotic susceptibility pattern. Annals of Saudi Medicine. 2012;32(5):513-516. DOI: 10.5144/0256-4947.2012.513
11. Al-Yousef SA, Mahmoud SY, Taha EM. Prevalence of methicillin resistant Staphylococcus aureus in Saudi Arabia: Systemic review and meta-analysis. Afr J Clin Exp Microbiol 2013;14:146-54. DOI: 10.4314/ajcem.v14i3.5
12. Al-Tawfiq J. Incidence and Epidemiology of Methicillin-Resistant Staphylococcus aureus Infection in a Saudi Arabian Hospital, 1999-2003. Infection Control & Hospital Epidemiology. 2006;27(10):1137-1139. DOI: 10.1086/507971
13. Baddour M, Abuelkheir M, Fatani A. Trends in antibiotic susceptibility patterns and epidemiology of MRSA isolates from several hospitals in Riyadh, Saudi Arabia. Annals of Clinical Microbiology and Antimicrobials. 2006;5(1):30. DOI: 10.1186/1476-0711-5-30
14. CLSI. Performance Standards for Antimicrobial Susceptibility Testing; Nineteenth Informational Supplement. CLSI document M100-19. Wayne, PA: Clinical and Laboratory Standards Institute; 2009.
15. Madani T. Epidemiology and Clinical Features of Methicillin-ResistantStaphylococcus aureusin the University Hospital, Jeddah, Saudi Arabia. Canadian Journal of Infectious Diseases. 2002;13(4):245-250. DOI: 10.1155/2002/235213
16. Austin TW, Austin MA, McAlear DE, Coleman BT, Osoba AO, Thaqafi AO, Lamfon MA. MRSA prevalence in a teaching hospital in Western Saudi Arabia. Saudi Med J. 2003 Dec;24(12):1313-6. PMID: 14710275.
17. David M, Daum R. Update on Epidemiology and Treatment of MRSA Infections in Children. Current Pediatrics Reports. 2013;1(3):170-181. DOI:10.1007/s40124-013-0023-7
18. VAN BELKUM A, VANDENBERGH M, KESSIE G, QADRI S, LEE G, VAN DEN BRAAK N et al. Genetic Homogeneity Among Methicillin-ResistantStaphylococcus AureusStrains From Saudi Arabia. Microbial Drug Resistance. 1997;3(4):365-369. DOI: 10.1089/mdr.1997.3.365
19. Bordon J, Master R, Clark R, Duvvuri P, Karlowsky J, Ayesu K et al. Methicillin-resistant Staphylococcus aureus resistance to non–β-lactam antimicrobials in the United States from 1996 to 2008. Diagnostic Microbiology and Infectious Disease. 2010;67(4):395-398.DOI: 10.1016/j.diagmicrobio.2010.03.006
20. Madani T, Al-Abdullah N, Al-Sanousi A, Ghabrah T, Afandi S, Bajunid H. Methicillin-Resistant Staphylococcus aureus in Two Tertiary-Care Centers in Jeddah, Saudi Arabia. Infection Control & Hospital Epidemiology. 2001;22(4):211-216. DOI: 10.1086/501891
21. Bukharie H, Abdelhadi M. The Epidemiology of Methicillin-Resistant Staphylococcus aureus at a Saudi University Hospital. Microbial Drug Resistance. 2001;7(4):413-416.DOI: 10.1089/10766290152773428
22. Frei C, Makos B, Daniels K, Oramasionwu C. Emergence of community-acquired methicillin-resistant Staphylococcus aureus skin and soft tissue infections as a common cause of hospitalization in United States children. Journal of Pediatric Surgery. 2010;45(10):1967-1974. DOI: 10.1016/j.jpedsurg.2010.05.009
23. Almanaa T, Alyahya S, Khaled J, Shehu M, Alharbi N, Kadaikunnan S et al. The extreme drug resistance (XDR) Staphylococcus aureus strains among patients: A retrospective study. Saudi Journal of Biological Sciences. 2020;27(8):1985-1992. DOI: 10.1016/j.sjbs.2020.04.003
24. Al-Hamad A, Alfaraj A, Altowaileb J, Al-Shamlan S, Leskafi H, Alsubeikhy F et al. Incidence and antibiotic susceptibility of MRSA infections in a Saudi Arabian Hospital: a 10-year surveillance study. The Journal of Infection in Developing Countries. 2018;12(06):454-461. DOI: 10.3855/jidc.9778
25. Healthcare Settings | MRSA | CDC [Internet]. Cdc.gov. 2019 [cited 19 April 2021]. Available from: https://www.cdc.gov/mrsa/healthcare/index.html
26. Wenzel R, Perl T. The significance of nasal carriage of Staphylococcus aureus and the incidence of postoperative wound infection. Journal of Hospital Infection. 1995;31(1):13-24. DOI: 10.1016/0195-6701(95)90079-9
27. Hauser C, Wuethrich B, Matter L, Wilhelm JA, Sonnabend W, Schopfer K. Staphylococcus aureus skin colonization in atopic dermatitis patients. Dermatologica. 1985;170(1):35-9. PMID: 3972149.
28. Oztoprak N, Cevik M, Akinci E, Korkmaz M, Erbay A, Eren S et al. Risk factors for ICU-acquired methicillin-resistant Staphylococcus aureus infections. American Journal of Infection Control. 2006;34(1):1-5.DOI: 10.1016/j.ajic.2005.07.005
29. Ali M, Rajab A, Al-Khani A, Ayash S, Basha A, Abdelgadir A et al. Methicillin-resistant Staphylococcus aureus development in intensive care patients. Saudi Medical Journal. 2020;41(11):1181-1186.DOI: 10.15537/smj.2020.11.25465
30. Otto M, Chatterjee. Improved understanding of factors driving methicillin-resistant Staphylococcus aureus epidemic waves. Clinical Epidemiology. 2013;:205. DOI: 10.2147/CLEP.S37071
31. Kaye K, Engemann J, Mozaffari E, Carmeli Y. Reference Group Choice and Antibiotic Resistance Outcomes. Emerging Infectious Diseases. 2004;10(6):1125-1128.DOI: 10.3201/eid1006.020665
32. Mylotte J, McDermott C, Spooner J. Prospective Study of 114 Consecutive Episodes of Staphylococcus aureus Bacteremia. Clinical Infectious Diseases. 1987;9(5):891-907. DOI: 10.1093/clinids/9.5.891
33. Shurland S, Zhan M, Bradham D, Roghmann M. Comparison of Mortality Risk Associated With Bacteremia Due to Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus. Infection Control & Hospital Epidemiology. 2007;28(3):273-279. DOI: 10.1086/512627
34. Antimicrobial resistance: global report on surveillance. Geneva: World Health Organization; 2014.
35. Hiramatsu K, Aritaka N, Hanaki H, Kawasaki S, Hosoda Y, Hori S et al. Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin. The Lancet. 1997;350(9092):1670-1673.DOI: 10.1016/S0140-6736(97)07324-8
36. Fridkin S, Hageman J, McDougal L, Mohammed J, Jarvis W, Perl T et al. Epidemiological and Microbiological Characterization of Infections Caused byStaphylococcus aureuswith Reduced Susceptibility to Vancomycin, United States, 1997–2001. Clinical Infectious Diseases. 2003;36(4):429-439.DOI: 10.1086/346207
37. Geisel R, Schmitz F, Fluit A, Labischinski H. Emergence, Mechanism, and Clinical Implications of Reduced Glycopeptide Susceptibility in Staphylococcus aureus. European Journal of Clinical Microbiology and Infectious Diseases. 2001;20(10):685-697.https://doi.org/10.1007/s100960100595
38. Al-Obeid S, Haddad Q, Cherkaoui A, Schrenzel J, Francois P. First Detection of an Invasive Staphylococcus aureus Strain (D958) with Reduced Susceptibility to Glycopeptides in Saudi Arabia. Journal of Clinical Microbiology. 2010;48(6):2199-2204.DOI: 10.1128/JCM.00954-09
39. Tsiodras S, Gold H, Sakoulas G, Eliopoulos G, Wennersten C, Venkataraman L et al. Linezolid resistance in a clinical isolate of Staphylococcus aureus. The Lancet. 2001;358(9277):207-208.DOI: 10.1016/S0140-6736(01)05410-1
40. Morales G, Picazo J, Baos E, Candel F, Arribi A, Peláez B et al. Resistance to Linezolid Is Mediated by thecfrGene in the First Report of an Outbreak of Linezolid‐ResistantStaphylococcus aureus. Clinical Infectious Diseases. 2010;50(6):821-825. DOI: 10.1086/650574
41. Seke Etet P, Nwabo Kamdje A, Vecchio L, Farahna M, Mahomoodally M. Signaling Pathways Sustaining Antibiotic Resistance. Antibiotic Resistance. 2016;:37-61. DOI: http://dx.doi.org/10.1016/B978-0-12-803642-6.00003-4
42. Diekema D, Pfaller M, Shortridge D, Zervos M, Jones R. Twenty-Year Trends in Antimicrobial Susceptibilities Among Staphylococcus aureus From the SENTRY Antimicrobial Surveillance Program. Open Forum Infectious Diseases. 2019;6(Supplement_1):S47-S53. DOI: 10.1093/ofid/ofy270
43. Miller L, Remington F, Bayer A, Diep B, Tan N, Bharadwa K et al. Clinical and Epidemiologic Characteristics Cannot Distinguish Community-Associated Methicillin-Resistant Staphylococcus aureus Infection from Methicillin-Susceptible S. aureus Infection: A Prospective Investigation. Clinical Infectious Diseases. 2007;44(4):471-482. DOI: 10.1086/511033
44. Tracking Staph Infections | HAIC Activities | HAI | CDC [Internet]. Cdc.gov. 2021 [cited 5 June 2021]. Available from: https://www.cdc.gov/hai/eip/saureus.html
45. Alkharsah K, Rehman S, Alkhamis F, Alnimr A, Diab A, Al-Ali A. Comparative and molecular analysis of MRSA isolates from infection sites and carrier colonization sites. Annals of Clinical Microbiology and Antimicrobials. 2018;17(1). DOI: 10.1186/s12941-018-0260-2
2. Monaco M, Pimentel de Araujo F, Cruciani M, Coccia E, Pantosti A. Worldwide Epidemiology and Antibiotic Resistance of Staphylococcus aureus. Current Topics in Microbiology and Immunology. 2016;:21-56. DOI 10.1007/82_2016_3
3. Boucher H, Miller L, Razonable R. Serious Infections Caused by Methicillin‐Resistant Staphylococcus aureus. Clinical Infectious Diseases. 2010;51(S2):S183-S197.DOI: 10.1086/653519
4. ERIKSEN K, ERICHSEN I. RESISTANCE TO METHICILLIN, ISOXAZOLYL PENICILLINS, AND CEPHALOTHIN IN STAPHYLOCOCCUS AUREUS. Acta Pathologica Microbiologica Scandinavica. 1964;62(2):255-275. DOI: 10.1111/apm.1964.62.2.255
5. Pada S, Ding Y, Ling M, Hsu L, Earnest A, Lee T et al. Economic and clinical impact of nosocomial meticillin-resistant Staphylococcus aureus infections in Singapore: a matched case–control study. Journal of Hospital Infection. 2011;78(1):36-40. DOI: 10.1016/j.jhin.2010.10.016
6. Howden B, Davies J, Johnson P, Stinear T, Grayson M. Reduced Vancomycin Susceptibility in Staphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications. Clinical Microbiology Reviews. 2010;23(1):99-139. DOI: 10.1128/CMR.00042-09
7. van Hal S, Lodise T, Paterson D. The Clinical Significance of Vancomycin Minimum Inhibitory Concentration in Staphylococcus aureus Infections: A Systematic Review and Meta-analysis. Clinical Infectious Diseases. 2012;54(6):755-771. DOI: 10.1093/cid/cir935
8. Yezli S, Shibl A, Livermore D, Memish Z. Antimicrobial resistance among Gram-positive pathogens in Saudi Arabia. Journal of Chemotherapy. 2012;24(3):125-136. DOI: 10.1179/1973947812Y.0000000010
9. Aly M, Balkhy H. The prevalence of antimicrobial resistance in clinical isolates from Gulf Corporation Council countries. Antimicrobial Resistance and Infection Control. 2012;1(1):26. DOI: 10.1186/2047-2994-1-26
10. El Amin N, Faidah H. Methicillin-resistant Staphylococcus aureus in the western region of Saudi Arabia: prevalence and antibiotic susceptibility pattern. Annals of Saudi Medicine. 2012;32(5):513-516. DOI: 10.5144/0256-4947.2012.513
11. Al-Yousef SA, Mahmoud SY, Taha EM. Prevalence of methicillin resistant Staphylococcus aureus in Saudi Arabia: Systemic review and meta-analysis. Afr J Clin Exp Microbiol 2013;14:146-54. DOI: 10.4314/ajcem.v14i3.5
12. Al-Tawfiq J. Incidence and Epidemiology of Methicillin-Resistant Staphylococcus aureus Infection in a Saudi Arabian Hospital, 1999-2003. Infection Control & Hospital Epidemiology. 2006;27(10):1137-1139. DOI: 10.1086/507971
13. Baddour M, Abuelkheir M, Fatani A. Trends in antibiotic susceptibility patterns and epidemiology of MRSA isolates from several hospitals in Riyadh, Saudi Arabia. Annals of Clinical Microbiology and Antimicrobials. 2006;5(1):30. DOI: 10.1186/1476-0711-5-30
14. CLSI. Performance Standards for Antimicrobial Susceptibility Testing; Nineteenth Informational Supplement. CLSI document M100-19. Wayne, PA: Clinical and Laboratory Standards Institute; 2009.
15. Madani T. Epidemiology and Clinical Features of Methicillin-ResistantStaphylococcus aureusin the University Hospital, Jeddah, Saudi Arabia. Canadian Journal of Infectious Diseases. 2002;13(4):245-250. DOI: 10.1155/2002/235213
16. Austin TW, Austin MA, McAlear DE, Coleman BT, Osoba AO, Thaqafi AO, Lamfon MA. MRSA prevalence in a teaching hospital in Western Saudi Arabia. Saudi Med J. 2003 Dec;24(12):1313-6. PMID: 14710275.
17. David M, Daum R. Update on Epidemiology and Treatment of MRSA Infections in Children. Current Pediatrics Reports. 2013;1(3):170-181. DOI:10.1007/s40124-013-0023-7
18. VAN BELKUM A, VANDENBERGH M, KESSIE G, QADRI S, LEE G, VAN DEN BRAAK N et al. Genetic Homogeneity Among Methicillin-ResistantStaphylococcus AureusStrains From Saudi Arabia. Microbial Drug Resistance. 1997;3(4):365-369. DOI: 10.1089/mdr.1997.3.365
19. Bordon J, Master R, Clark R, Duvvuri P, Karlowsky J, Ayesu K et al. Methicillin-resistant Staphylococcus aureus resistance to non–β-lactam antimicrobials in the United States from 1996 to 2008. Diagnostic Microbiology and Infectious Disease. 2010;67(4):395-398.DOI: 10.1016/j.diagmicrobio.2010.03.006
20. Madani T, Al-Abdullah N, Al-Sanousi A, Ghabrah T, Afandi S, Bajunid H. Methicillin-Resistant Staphylococcus aureus in Two Tertiary-Care Centers in Jeddah, Saudi Arabia. Infection Control & Hospital Epidemiology. 2001;22(4):211-216. DOI: 10.1086/501891
21. Bukharie H, Abdelhadi M. The Epidemiology of Methicillin-Resistant Staphylococcus aureus at a Saudi University Hospital. Microbial Drug Resistance. 2001;7(4):413-416.DOI: 10.1089/10766290152773428
22. Frei C, Makos B, Daniels K, Oramasionwu C. Emergence of community-acquired methicillin-resistant Staphylococcus aureus skin and soft tissue infections as a common cause of hospitalization in United States children. Journal of Pediatric Surgery. 2010;45(10):1967-1974. DOI: 10.1016/j.jpedsurg.2010.05.009
23. Almanaa T, Alyahya S, Khaled J, Shehu M, Alharbi N, Kadaikunnan S et al. The extreme drug resistance (XDR) Staphylococcus aureus strains among patients: A retrospective study. Saudi Journal of Biological Sciences. 2020;27(8):1985-1992. DOI: 10.1016/j.sjbs.2020.04.003
24. Al-Hamad A, Alfaraj A, Altowaileb J, Al-Shamlan S, Leskafi H, Alsubeikhy F et al. Incidence and antibiotic susceptibility of MRSA infections in a Saudi Arabian Hospital: a 10-year surveillance study. The Journal of Infection in Developing Countries. 2018;12(06):454-461. DOI: 10.3855/jidc.9778
25. Healthcare Settings | MRSA | CDC [Internet]. Cdc.gov. 2019 [cited 19 April 2021]. Available from: https://www.cdc.gov/mrsa/healthcare/index.html
26. Wenzel R, Perl T. The significance of nasal carriage of Staphylococcus aureus and the incidence of postoperative wound infection. Journal of Hospital Infection. 1995;31(1):13-24. DOI: 10.1016/0195-6701(95)90079-9
27. Hauser C, Wuethrich B, Matter L, Wilhelm JA, Sonnabend W, Schopfer K. Staphylococcus aureus skin colonization in atopic dermatitis patients. Dermatologica. 1985;170(1):35-9. PMID: 3972149.
28. Oztoprak N, Cevik M, Akinci E, Korkmaz M, Erbay A, Eren S et al. Risk factors for ICU-acquired methicillin-resistant Staphylococcus aureus infections. American Journal of Infection Control. 2006;34(1):1-5.DOI: 10.1016/j.ajic.2005.07.005
29. Ali M, Rajab A, Al-Khani A, Ayash S, Basha A, Abdelgadir A et al. Methicillin-resistant Staphylococcus aureus development in intensive care patients. Saudi Medical Journal. 2020;41(11):1181-1186.DOI: 10.15537/smj.2020.11.25465
30. Otto M, Chatterjee. Improved understanding of factors driving methicillin-resistant Staphylococcus aureus epidemic waves. Clinical Epidemiology. 2013;:205. DOI: 10.2147/CLEP.S37071
31. Kaye K, Engemann J, Mozaffari E, Carmeli Y. Reference Group Choice and Antibiotic Resistance Outcomes. Emerging Infectious Diseases. 2004;10(6):1125-1128.DOI: 10.3201/eid1006.020665
32. Mylotte J, McDermott C, Spooner J. Prospective Study of 114 Consecutive Episodes of Staphylococcus aureus Bacteremia. Clinical Infectious Diseases. 1987;9(5):891-907. DOI: 10.1093/clinids/9.5.891
33. Shurland S, Zhan M, Bradham D, Roghmann M. Comparison of Mortality Risk Associated With Bacteremia Due to Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus. Infection Control & Hospital Epidemiology. 2007;28(3):273-279. DOI: 10.1086/512627
34. Antimicrobial resistance: global report on surveillance. Geneva: World Health Organization; 2014.
35. Hiramatsu K, Aritaka N, Hanaki H, Kawasaki S, Hosoda Y, Hori S et al. Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin. The Lancet. 1997;350(9092):1670-1673.DOI: 10.1016/S0140-6736(97)07324-8
36. Fridkin S, Hageman J, McDougal L, Mohammed J, Jarvis W, Perl T et al. Epidemiological and Microbiological Characterization of Infections Caused byStaphylococcus aureuswith Reduced Susceptibility to Vancomycin, United States, 1997–2001. Clinical Infectious Diseases. 2003;36(4):429-439.DOI: 10.1086/346207
37. Geisel R, Schmitz F, Fluit A, Labischinski H. Emergence, Mechanism, and Clinical Implications of Reduced Glycopeptide Susceptibility in Staphylococcus aureus. European Journal of Clinical Microbiology and Infectious Diseases. 2001;20(10):685-697.https://doi.org/10.1007/s100960100595
38. Al-Obeid S, Haddad Q, Cherkaoui A, Schrenzel J, Francois P. First Detection of an Invasive Staphylococcus aureus Strain (D958) with Reduced Susceptibility to Glycopeptides in Saudi Arabia. Journal of Clinical Microbiology. 2010;48(6):2199-2204.DOI: 10.1128/JCM.00954-09
39. Tsiodras S, Gold H, Sakoulas G, Eliopoulos G, Wennersten C, Venkataraman L et al. Linezolid resistance in a clinical isolate of Staphylococcus aureus. The Lancet. 2001;358(9277):207-208.DOI: 10.1016/S0140-6736(01)05410-1
40. Morales G, Picazo J, Baos E, Candel F, Arribi A, Peláez B et al. Resistance to Linezolid Is Mediated by thecfrGene in the First Report of an Outbreak of Linezolid‐ResistantStaphylococcus aureus. Clinical Infectious Diseases. 2010;50(6):821-825. DOI: 10.1086/650574
41. Seke Etet P, Nwabo Kamdje A, Vecchio L, Farahna M, Mahomoodally M. Signaling Pathways Sustaining Antibiotic Resistance. Antibiotic Resistance. 2016;:37-61. DOI: http://dx.doi.org/10.1016/B978-0-12-803642-6.00003-4
42. Diekema D, Pfaller M, Shortridge D, Zervos M, Jones R. Twenty-Year Trends in Antimicrobial Susceptibilities Among Staphylococcus aureus From the SENTRY Antimicrobial Surveillance Program. Open Forum Infectious Diseases. 2019;6(Supplement_1):S47-S53. DOI: 10.1093/ofid/ofy270
43. Miller L, Remington F, Bayer A, Diep B, Tan N, Bharadwa K et al. Clinical and Epidemiologic Characteristics Cannot Distinguish Community-Associated Methicillin-Resistant Staphylococcus aureus Infection from Methicillin-Susceptible S. aureus Infection: A Prospective Investigation. Clinical Infectious Diseases. 2007;44(4):471-482. DOI: 10.1086/511033
44. Tracking Staph Infections | HAIC Activities | HAI | CDC [Internet]. Cdc.gov. 2021 [cited 5 June 2021]. Available from: https://www.cdc.gov/hai/eip/saureus.html
45. Alkharsah K, Rehman S, Alkhamis F, Alnimr A, Diab A, Al-Ali A. Comparative and molecular analysis of MRSA isolates from infection sites and carrier colonization sites. Annals of Clinical Microbiology and Antimicrobials. 2018;17(1). DOI: 10.1186/s12941-018-0260-2