Global, regional, and national burdens: An overlapping meta-analysis on Staphylococcus aureus and its drug-resistant strains

Abstract

Objective: To provide an inclusive blend of extant meta-analyses on the burden of Staphylococcus ( S.) aureus and its resistant strains across diverse study populations, settings, and temporal contexts.
Methods: The study has adopted PRISMA 2020-based guides and registered its protocol on Open Science Framework with an extensive literature search. Study quality was assessed by QUOROM and AMSTAR techniques. Data analysis included parsing of study-level statistical power, assessment of primary study overlap, pooling of meta-analysis results, subgroup and temporal analysis.
Results: Totally 41 studies (64 meta-analyses) were selected by the inclusion criteria. The summary meta-analysis revealed global prevalence rates for S. aureus [24.8%, 95%CI 0.248(0.204–0.293), I² = 93%], methicillin resistant S. aureus (MRSA) [5.8%, 95%CI 0.058(0.044–0.073), I² = 92%], vancomycin intermediate S. aureus [1.7%, 95%CI 0.017(0.013–0.021), I² = 36.4%], heterogeneous vancomycin intermediate S. aureus [5.2%, 95%CI 0.052(0.038–0.056), I² = 36.4%], community-associated methicillin-resistant S. aureus [19.9%, 95%CI 0.199(-0.170–0.568), I² = 96.67%), livestock-associated-MRSA [13.6%, 95%CI 0.136(-0.028–0.243), I² = 97.7%], and mupirocin resistant S. aureus [7.6%, 95%CI 0.076(0.062–0.090), I² = 0%]. Temporal analysis revealed that the burden community-associated methicillin-resistant S. aureus notably increased from 1.3% in 2003 to 39.0% in 2014. Coagulase-negative staphylococci rose from 23.2% in 2021 to 29.8% in 2022. Vancomycin resistant S. aureus peaked at 9.0% in 2018, declining to 2.6% in 2020. Livestock-associated-MRSA significantly increased to 19.0% in 2020. MRSA fluctuated, peaking at 52.7% in 2012 and 31.0% in 2022.
Conclusions: The study reveals a considerable global prevalence of S. aureus at 24.8%. Regional differences were apparent, with Africa facing a high burden of MRSA at 40.8% of S. aureus and temporal trends exposed a dynamic state.

Keywords

Vancomycin-resistant Staphylococcus aureus / Methicillin resistant Staphylococcus aureus / Livestock-associated (LA)-MRSA strain / Meta-analysis / Antimicrobial resistance

Conflict of interest statement

The authors claim there is no conflict of interest.

Funding

This study receives no extramural funding.

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon request.

Authors’ contributions

The work undertaken by Adeiza SS included conceptualization, data curation, formal analysis, investigation, methodology, and writing of the original draft, as well as review and editing. Shittu A, Adeiza SS and Islam MA contributed to methodology, provided resources, managed software, supervised the project, ensured validation, and participated in reviewing and editing the manuscript.

References

[1] Nandhini P, Kumar P, Mickymaray S, Alothaim AS, Somasundaram J, Rajan M. Recent developments in methicillin-resistant Staphylococcus aureus (MRSA) treatment: A review. Antibiotics 2022; 11(5): 606.

[2] Larsen J, Raisen CL, Ba X, Sadgrove NJ, Padilla-González GF, Simmonds MS, et al. Emergence of methicillin resistance predates the clinical use of antibiotics. Nature 2022; 602(7895): 135-141.

[3] Al-Saleh A, Shahid M, Farid E, Bindayna K. Trends in methicillin-resistant Staphylococcus aureus in the Gulf Cooperation Council countries: Antibiotic resistance, virulence factors and emerging strains. East Mediterr Health J 2022; 28(6): 434-443.

[4] Kitcher LM, Coombs G, Mowlaboccus S, Mullally C. Genomic epidemiology of multilocus sequence type 5 methicillin-resistant Staphylococcus aureus causing bacteraemia in Australia. PhD Thesis. Murdoch University; 2022.

[5] Vena A, Castaldo N, Magnasco L, Bavastro M, Limongelli A, Giacobbe DR, et al. Current and emerging drug treatment strategies to tackle invasive community-associated methicillin-resistant Staphylococcus aureus (MRSA) infection: What are the challenges? Expert Opin Pharmacother 2023; 24(3): 331-346.

[6] Tuominen KS, Lewerin SS, Widgren S, Rosendal T. Assessment of control measures against livestock-associated methicillin-resistant Staphylococcus aureus in a farrow-to-finish pig herd using infectious disease modelling. Animal 2023; 17(6): 100840.

[7] Chen C, Wu F. Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) colonisation and infection among livestock workers and veterinarians: A systematic review and meta-analysis. Occup Environ Med 2020; 78(7): oemed-2020-106418.

[8] Kler R, Gangurde R, Elmirzaev S, Hossain MS, Vo NV, Nguyen TV, et al. Optimization of meat and poultry farm inventory stock using data analytics for green supply chain network. Discrete Dyn Nat Soc 2022; 2022: 1-8.

[9] Liang J, Hu Y, Fu M, Li N, Wang F, Yu X, et al. Resistance and molecular characteristics of methicillin-resistant Staphylococcus aureus and heterogeneous vancomycin-intermediate Staphylococcus aureus. Infect Drug Resist 2023: 16: 379-388.

[10] Esposito S, Blasi F, Curtis N, Kaplan S, Lazzarotto T, Meschiari M, et al. New antibiotics for Staphylococcus aureus infection: An update from the world association of infectious diseases and immunological disorders (WAidid) and the Italian society of anti-infective therapy (SITA). Antibiotics 2023; 12(4): 742.

[11] Liu C, Shen Y, Yang M, Chi K, Guo N. Hazard of staphylococcal enterotoxins in food and promising strategies for natural products against virulence. J Agric Food Chem 2022; 70(8): 2450-2465.

[12] Li X, Zhang J, Zhang H, Shi X, Wang J, Li K, et al. Genomic analysis, antibiotic resistance, and virulence of Staphylococcus aureus from food and food outbreaks: A potential public concern. Int J Food Microbiol 2022; 377: 109825.

[13] Kim J, Ahn J. Emergence and spread of antibiotic-resistant foodborne pathogens from farm to table. Food Sci Biotechnol 2022; 31(12): 1481-1499.

[14] Suleiman AS, Abbass M, Hossain M, Choudhary P, Bhattacharya P, Islam MA. Impact of antibiotic-coated sutures on surgical site infections: A second-order meta-analysis. Int J Surg 2024; 110(1): 507-519.

[15] Henig O, Chikly A, Marchaim D. Multidrug-resistant Gram-negative Bacilli: Infection prevention considerations. In: Bearman G, Morgan DJ, Murthy RK, Hota S. (eds). Infection Prevention. Heidelberg: Springer, Cham; 2022.

[16] Aslam B, Ahmad M, Tariq MU, Muzammil S, Siddique AB, Khurshid M, et al. Antibiotic resistance: Retrospect and prospect. Amsterdam: Academic Press; 2023, pp. 1-37.

[17] Adeiza SS. Clovibactin and Staphylococcus aureus: A new guard against resistant strains. GMS Hyg Infect Control 2024; 19: Doc34.

[18] Limmathurotsakul D, Dunachie S, Fukuda K, Feasey NA, Okeke IN, Holmes AH, et al. Improving the estimation of the global burden of antimicrobial resistant infections. Lancet Infect Dis 2019; 19(11): e392-398.

[19] Suleiman AS, Islam MA, Akter MS, Amin MR, Werkneh AA, Bhattacharya P. A meta-meta-analysis of co-infection, secondary infections, and antimicrobial resistance in COVID-19 patients. J Infect Public Health 2023; 16(10): 1562-1590.

[20] Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021; 372: n71.

[21] Islam MA, Ahammed T, Noor ST, Hasan MN, Hoque MN, Tiwari A, et al. An estimation of five-decade long monkeypox case fatality rate: Systematic review and meta-analysis. JPAM 2022; 16(suppl 1): 3036-3047.

[22] Islam MA, Hasan MN, Ahammed T, Anjum A, Majumder A, Siddiqui MN, et al. Association of household fuel with acute respiratory infection (ARI) under-five years children in Bangladesh. Front Public Health 2022; 10: 985445.

[23] Santos AP, Gonçalves LC, Oliveira AC, Queiroz PH, Ito CR, Santos MO, et al. Bacterial co-infection in patients with COVID-19 hospitalized (ICU and Not ICU): Review and meta-analysis. Antibiotics 2022; 11(7): 894.

[24] Bougioukas KI, Vounzoulaki E, Mantsiou CD, Savvides ED, Karakosta C, Diakonidis T, et al. Methods for depicting overlap in overviews of systematic reviews: An introduction to static tabular and graphical displays. J Clinic Epidemiol 2021; 132: 34-45.

[25] Bracchiglione J, Meza N, Bangdiwala SI, Niño de Guzmán E, Urrútia G, Bonfill X, et al. Graphical representation of overlap for overviews: GROOVE tool. Research Synth Methods 2022; 13(3): 381-388.

[26] Pieper D, Antoine SL, Mathes T, Neugebauer EAM, Eikermann M. Systematic review finds overlapping reviews were not mentioned in every other overview. J Clinic Epidemiol 2014; 67(4): 368-375.

[27] Adeiza SS, Aminul I. Meta-meta-analysis of the mortality risk associated with MRSA compared to MSSA bacteraemia. Le Infezioni in Medicina 2024; 32(2): 131-137.

[28] Quintana DS. A guide for calculating study-level statistical power for meta-analyses. Adv Methods Pract Psychol Sci 2023; 6(1): 25152459221147260.

[29] Borenstein M. Comprehensive meta-analysis software. In: Egger M, Higgins JPT, Smith GD (eds). New Jersey: Wiley Online Library; 2022, p. 535-548.

[30] Adeiza SS, Ademola Onaolapo J, Olalekan Olayinka B. Prevalence and antimicrobial susceptibility profile of methicillin-resistant Staphylococcus aureus (MRSA) obtained from nares of patients and staff of Sokoto State-owned hospitals in Nigeria. SSRN Electronic J 2020; 15: 1-17.

[31] Suleiman S, Onaolapo JA, Olayinka BO. Nasal colonization as a risk factor for staphylococcal infection: A systematic review and meta-analysis. J Microbiol 2018; 32(1): 4220-4235.

[32] Shankar N, Soe PM, Tam CC. Prevalence and risk of acquisition of methicillin-resistant Staphylococcus aureus among households: A systematic review. Int J Infect Dis 2020; 92: 105-113.

[33] Chelkeba L, Fanta K, Mulugeta T, Melaku T. Bacterial profile and antimicrobial resistance patterns of common bacteria among pregnant women with bacteriuria in Ethiopia: A systematic review and meta-analysis. Arch Gynecol Obstet 2022; 306(3): 663-686.

[34] Baseri N, Najar-Peerayeh S, Amiri FB. Prevalence of vancomycin-intermediate Staphylococcus aureus among clinical isolates in Iran: A systematic review and meta-analysis. J Global Antimicrob Resist 2018; 15: 178-187.

[35] Ribeiro CM, Stefani LM, Lucheis SB, Okano W, Cruz JC, Souza GV, et al. Methicillin-resistant Staphylococcus aureus in poultry and poultry meat: A meta-analysis. J Food Protect 2018; 81(7): 1055-1062.

[36] Zelellw DA, Dessie G, Worku Mengesha E, Balew Shiferaw M, Mela Merhaba M, Emishaw S. A systemic review and meta-analysis of the leading pathogens causing neonatal sepsis in developing countries. BioMed Res Int 2021; 2021: 1-20.

[37] Wong JW, Ip M, Tang A, Wei VW, Wong SY, Riley S, et al. Prevalence and risk factors of community-associated methicillin-resistant Staphylococcus aureus carriage in Asia-Pacific region from 2000 to 2016: A systematic review and meta-analysis. Clinic Epidemiol 2018; 10: 1489-1501.

[38] Emaneini M, Jabalameli F, Rahdar H, Leeuwen WB, Beigverdi R. Nasal carriage rate of methicillin resistant Staphylococcus aureus among Iranian healthcare workers: A systematic review and meta-analysis. Revista da Sociedade Brasileira de Med Tropic 2017; 50: 590-597.

[39] Karanika S, Kinamon T, Grigoras C, Mylonakis E. Colonization with methicillin-resistant Staphylococcus aureus and risk for infection among asymptomatic athletes: A systematic review and meta-analysis. Clinical Infect Dis 2016; 63(2): 195-204.

[40] Wu M, Tong X, Liu S, Wang D, Wang L, Fan H. Prevalence of methicillin-resistant Staphylococcus aureus in healthy Chinese population: A system review and meta-analysis. PLoS One 2019; 14(10): e0223599.

[41] Gagnaire J, Verhoeven PO, Grattard F, Rigaill J, Lucht F, Pozzetto B, et al. Epidemiology and clinical relevance of Staphylococcus aureus intestinal carriage: A systematic review and meta-analysis. Expert Rev Anti Infect Ther 2017; 15(8): 767-785.

[42] Adeiza SS, Shuaibu AB, Shuaibu GM. Random effects meta-analysis of COVID-19/S. aureus partnership in co-infection. GMS Hyg Infect Control 2020; 15: Doc29.

[43] Askari E, Soleymani F, Arianpoor A, Tabatabai SM, Amini A, NaderiNasab M. Epidemiology of mecA-methicillin resistant Staphylococcus aureus (MRSA) in Iran: A systematic review and meta-analysis. Iran J Basic Med Sci 2012; 15(5): 1010.

[44] Santaniello A, Sansone M, Fioretti A, Menna LF. Systematic review and meta-analysis of the occurrence of ESKAPE bacteria group in dogs, and the related zoonotic risk in animal-assisted therapy, and in animal-assisted activity in the health context. Int J Environment Res Public Health 2020; 17(9): 3278.

[45] Kalligeros M, Shehadeh F, Karageorgos SA, Zacharioudakis IM, Mylonakis E. MRSA colonization and acquisition in the burn unit: A systematic review and meta-analysis. Burns 2019; 45(7): 1528-1536.

[46] Memariani M, Memariani H, Shahidi-Dadras M, Tehranchinia Z, Ghalamkarpour F, Moravvej H. Contemporary systematic review and meta-analysis of exfoliative toxin-producing Staphylococcus aureus strains isolated from patients in Iran. Rev Res Medic Microbiol 2020; 31(1): 1.

[47] Awulachew EW, Diriba K, Anja A, Wudneh F. Nasopharyngeal carriage of Staphylococcus aureus and its antimicrobial resistance pattern among healthy people: Systematic review and meta-analysis. J Bacteriol Parasitol 2020; 11: 383.

[48] Ou J, Wang J, Xu Y, Tao ZZ, Kong YG, Chen SM, et al. Staphylococcus aureus superantigens are associated with chronic rhinosinusitis with nasal polyps: A meta-analysis. Europ Arch Oto-Rhino-Laryngol 2014; 271: 2729-2736.

[49] Stacey HJ, Clements CS, Welburn SC, Jones JD. The prevalence of methicillin-resistant Staphylococcus aureus among diabetic patients: A meta-analysis. Acta diabetologica 2019; 56: 907-921.

[50] Eshetie S, Tarekegn F, Moges F, Amsalu A, Birhan W, Huruy K. Methicillin resistant Staphylococcus aureus in Ethiopia: A meta-analysis. BMC Infect Dis 2016; 16(1): 689.

[51] Shittu AO, Kaba M, Abdulgader SM, Ajao YO, Abiola MO, Olatimehin AO. Mupirocin-resistant Staphylococcus aureus in Africa: A systematic review and meta-analysis. Antimicrob Resist Infect Control 2018; 7(1): 101.

[52] Nikmanesh Y, Foolady Azarnaminy A, Avishan P, Taheri M, Sabeghi P, Najibzadeh E, et al. A Middle East systematic review and meta-analysis of prevalence and antibiotic susceptibility pattern in MRSA Staphylococcus aureus isolated from patients with cystic fibrosis. J Health Popul Nutr 2022; 41(1): 26.

[53] Sabbagh P, Riahi SM, Gamble HR, Rostami A. The global and regional prevalence, burden, and risk factors for methicillin-resistant Staphylococcus aureus colonization in HIV-infected people: A systematic review and meta-analysis. Ame J Infect Control 2019; 47(3): 323-333.

[54] Adeiza SS, Ademola Onaolapo J, Olalekan Olayinka B. Nasal colonization as a risk factor for Staphylococcal infection: A systematic review and meta-analysis. J Microbiol 2018; 32(1): 4220-4235.

[55] Dehkordi MK, Shamsabadi MG, Banimehdi P. The occurrence of Staphylococcus aureus, enterotoxigenic and methicillin-resistant strains in Iranian food resources: A systematic review and meta-analysis. Ann Ig 2019; 31(3): 263-278.

[56] Li S, Li J, Qiao Y, Ning X, Zeng T, Shen X. Prevalence and invasiveness of community-acquired methicillin-resistant Staphylococcus aureus: A meta-analysis. Indian J Pathol Microbiol 2014; 57(3): 418-422.

[57] Girmay G. Systematic review and meta-analysis on Staphylococcus aureus in Ethiopia. J Biotechnol Bioinforma Res 2022; 4(3): 1-8.

[58] Shariati A, Dadashi M, Chegini Z, van Belkum A, Mirzaii M, Khoramrooz SS, et al. The global prevalence of Daptomycin, Tigecycline, Quinupristin/Dalfopristin, and Linezolid-resistant Staphylococcus aureus and coagulase-negative staphylococci strains: A systematic review and meta-analysis. Antimicrob Res Infect Control 2020; 9: 1-20.

[59] Li Z, Zhuang H, Wang G, Wang H, Dong Y. Prevalence, predictors, and mortality of bloodstream infections due to methicillin-resistant Staphylococcus aureus in patients with malignancy: Systemic review and meta-analysis. BMC Infect Dis 2021; 21(1): 74.

[60] Salgado CD, Farr BM, Calfee DP. Community-acquired methicillin-resistant Staphylococcus aureus: A meta-analysis of prevalence and risk factors. Clinic Infect Dis 2023; 36(2): 131-139.

[61] Okomo U, Akpalu EN, Le Doare K, Roca A, Cousens S, Jarde A, et al. Aetiology of invasive bacterial infection and antimicrobial resistance in neonates in sub-Saharan Africa: A systematic review and meta-analysis in line with the STROBE-NI reporting guidelines. Lancet Infect Dis 2019; 19(11): 1219-1234.

[62] Lin J, Peng Y, Xu P, Zhang T, Bai C, Lin D, Ou Q, Yao Z. Methicillin-resistant Staphylococcus aureus nasal colonization in Chinese children: A prevalence meta-analysis and review of influencing factors. PLoS One 2016; 11(7): e0159728.

[63] Oskouie YA, Abbasi-Asl M, Zonouz AT, Pashazadeh F, Oskouie SA, Leylabadlo HE. Prevalence of Staphylococcus aureus nasal carriage and methicillin-resistant S. aureus among medical students: A systematic review and meta-analysis. Jundishapur J Microbiol 2020; 13(11): e111125.

[64] Patil SS, Suresh KP, Shinduja R, Amachawadi RG, Chandrashekar S, Pradeep S, et al. Prevalence of methicillin-resistant Staphylococcus aureus in India: A systematic review and meta-analysis. Oman Medic J 2022; 37(4): e440.

[65] Zhang S, Sun X, Chang W, Dai Y, Ma X. Systematic review and meta-analysis of the epidemiology of vancomycin-intermediate and heterogeneous vancomycin-intermediate Staphylococcus aureus isolates. PLoS One 2015; 10(8): e0136082.

[66] Zigmond J, Pecan L, Hájek P, Raghubir N, Omrani AS. MRSA infection and colonization rates in Africa and Middle East: A systematic review and meta-analysis. Int J Infect Dis 2014; 21: 391.

[67] Giri S, Ghimire A, Mishra A, Acharya K, Kuikel S, Tiwari A, et al. Prevalence of methicillin-resistant Staphylococcus aureus carriage among healthcare workers in South Asia in non-outbreak settings: A systematic review and meta-analysis. Am J Infect Control 2023; 51(2): 184-193.

[68] Zacharioudakis IM, Zervou FN, Ziakas PD, Mylonakis E. Meta-analysis of methicillin-resistant Staphylococcus aureus colonization and risk of infection in dialysis patients. J Am Soc Nephrol 2014; 25(9): 2131-2141.

[69] Dadashi M, Hajikhani B, Darban-Sarokhalil D, van Belkum A, Goudarzi M. Mupirocin resistance in Staphylococcus aureus: A systematic review and meta-analysis. J Global Antimicrob Res 2020; 20: 238-247.

[70] Ziakas PD, Anagnostou T, Mylonakis E. The prevalence and significance of methicillin-resistant Staphylococcus aureus colonization at admission in the general ICU Setting: A meta-analysis of published studies. Crit Care Med 2014; 42(2): 433-444.

[71] Suleiman AS, Ademola OJ, Olalekan OB. Constellation of methicillin-resistant genomic islands (SCCmec) among nasal meticillin-resistant Staphylococcus aureus isolates. Acta facultatis medicae Naissensis 2021; 38(4): 360-370.

[72] Adeiza SS, Onaolapo JA, Olayinka BO. Genetic profiling of methicillin-resistant Staphylococcus aureus in an African hospital by multiplex-PCR. J Microbiol Infect Dis 2020; 10(3): 144-153.

[73] Adeiza SS, Shuaibu MG, Shuaibu AB. Knowledge mapping of Nigeria’s scientific contribution to antimicrobial resistance research: A visualized investigation using VOS viewer and Cite Space. Microb Infect Dis 2024; 5(2): 584-598.

[74] Gajewska J, Zakrzewski A, Chajęcka-Wierzchowska W, Zadernowska A. Meta-analysis of the global occurrence of S. aureus in raw cattle milk and artisanal cheeses. Food Control 2023; 147: 109603.

[75] Hasanpour AH, Sepidarkish M, Mollalo A, Ardekani A, Almukhtar M, Mechaal A, et al. The global prevalence of methicillin-resistant Staphylococcus aureus colonization in residents of elderly care centers: A systematic review and meta-analysis. Antimicrob Resist Infect Control 2023; 12(1): 76.

[76] Shuaibu A, Ibrahim Y, Olayinka B, Atata R. Aerobic bacteria from surgical wound infections in obstetrics and gynecology ward in specialist hospital Sokoto-North West Nigeria. Asian J Med Health 2017; 3(4): 1-6.

[77] Adeiza SS, Onaolapo JA, Olayinka BO. Methylase genotypes among D+ methicillin-resistant Staphylococcus aureus strains in Sokoto, Nigeria. Mediterr J Infect Microbes Antimicrob 2019; 8: 39-44.

[78] Jacob JT, DiazGranados CA. High vancomycin minimum inhibitory concentration and clinical outcomes in adults with methicillin-resistant Staphylococcus aureus infections: A meta-analysis. Int J Infect Dis 2013; 17(2): e93-100.

[79] Uçar Ş, Duman YÜ, Tanrıverdi EL, Tekerekoğlu ME, Otlu BA. Investigation of the VISA and hVISA presence in methicillin-resistant Staphylococcus aureus isolates by various methods. Mikrobiyol Bul 2022; 56(4): 593-605.

[80] Adeiza SS, Onaolapo JA, Olayinka BO. Prevalence, risk-factors, and antimicrobial susceptibility profile of methicillin-resistant Staphylococcus aureus (MRSA) obtained from nares of patients and staff of Sokoto state-owned hospitals in Nigeria. GGMS Hyg Infect Control 2020; 15: Doc25.