Prevalence and Antimicrobial Resistance of Staphylococcus Species in Operation Room: Systematic Review and Meta-Analysis Protocol.

DOI: https://doi.org/10.21203/rs.3.rs-806140/v1

Abstract

Background

Pathogenic Staphylococcus species in routine medical care settings poses an increased risk of healthcare-associated infections that causes severe infections in humans and increased morbidity and mortality. These species are the most frequently transmitted infectious agents in the operating room that contributed to more than half of surgical site infections. Thus, this study aimed to estimate the global prevalence of staphylococcus species and their antimicrobial resistance profile in operating rooms of health care facilities.

Methods

Nine electronic databases including MEDLINE, Embase, Psych INFO, PubMed, Scopus, Web of Science, google scholar, Science Direct, and CINAHL will be used to collect the articles. To address the articles missed from the above databases, a direct search from google will be made. Similarly, the reference lists of the included articles will be searched manually. The search for the grey literature will be conducted using national or international repositories. Articles written in the English language, and conducted across the world that reported the prevalence of Staphylococcus species in the operating room will be included. Newcastle-Ottawa scale will be used to assess the quality of the included articles. The data will be extracted using Microsoft Excel 2016 and exported to STATA 16.0 software for the analyses. Pooled estimation of the outcome will be performed using DerSimonian-Laird random-effects model. Heterogeneity and publication bias of the studies will be presented with I2 statistics and funnel plots, respectively.

Discussion

Even though several studies laid out sources of microbial contamination as diverse and gram-positive bacteria is a common contaminant in the hospital setting, the prevalence and resistance profile of these contaminants in the operation room is not mentioned. This systematic review will provide evidence on the staphylococcus species in the operation room, the prevalence and antimicrobial resistance of each species. These findings will provide knowledge to clinicians on the level of contamination due to staphylococcus. Only studies published in English will be included and this may limit the current systematic review.

Registration:

Submitted to PROSPERO on 26/7/2021.

Background

Currently, operating theatre contamination with various infectious agents is a major cause of hospital-acquired infections (HAIs) (Bhalla et al., 2007; Hayden et al., 2006). The environment, healthcare workers, and medical equipment are among the sources of infectious agents in the operating site, and is transmitted from patient to patient, health care workers to the patients as well as from the inanimate surfaces to the healthcare workers and/or patients (Russotto et al., 2017; Shiferaw et al., 2016). Globally, the prevalence of HAIs is approximately 4.5 to 15.5% in hospitalized patients (Allegranzi et al., 2011).

During surgical procedures, bacteria-laden airborne particles such as textile fibers, dust particles, skin flakes, and aerosols can enter surgical sites that can cause surgical site infection (Diab-Elschahawi et al., 2011; McHugh et al., 2015; Pasquarella et al., 2020; Sadrizadeh et al., 2014) and these are the major cause of HAIs (Kawakita & Landy, 2017; Mellinghoff et al., 2018; Misha et al., 2021; Mohamed et al., 2021).

Pathogenic bacterial strains such as Staphylococcus aureus, Coagulase-negative Staphylococci (CoNS), Enterococcus species (vancomycin-resistant Enterococci), Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Clostridium difficile, and Acinetobacter baumannii are commonly known to contaminate inanimate surfaces and medical apparatus (Russotto et al., 2015). Operating room (OR) reservoir Staphylococcus aureus (SA) isolates have been caused 50% of surgical site infections (Robinson et al., 2019) also, patients who are colonized with SA are at a 2- to 9-fold higher risk of SA infection (Wenzel & Perl, 1995). SA is a common pathogen in osteomyelitis (Russell et al., 2015) and periprosthetic joint infection (Chen et al., 2015).

Most systematic reviews and meta-analyses focused on Staphylococcus aureus, multi-drug resistance, prevalence on the hands (Montoya et al., 2019), medical equipment (Wolfensberger et al., 2018), personal attire, and mobile phones (Haun et al., 2016; Omran & Taha, 2020). Some reviews and meta-analyses were also focused on the incidence of infection resulted from Staphylococcus aureus (Ning et al., 2020). Even though, increased awareness of the prevalence of pathogenic bacterial strain characteristics may help to improve compliance with intraoperative infection control measures and help septic making OR, there is no systematic review and meta-analysis on the prevalence of different species of Staphylococcus from multiple sources such as the environment, personnel, and equipment in the operating room with antimicrobial resistance profile of Staphylococcus isolates. Two questions also remained unclear; what is the burden of Staphylococcus species (spp.) prevalence on indoor air, personnel, and surgical equipment in the operation room? What is the antimicrobial resistance profile of these contaminants?

To answer these two questions, hence, the quantitative synthesis of studies is important to estimate the level of contamination of OR. For this review, we defined the population as OR and its indoor air, personnel and, and equipment assessed. The primary outcome of interest will be the prevalence of Staphylococcus spp., while the antibiotic resistance status of the Staphylococcus spp. isolates will be considered as a secondary outcome. Therefore, this systematic review and meta-analysis are aimed to estimate the global prevalence of Staphylococcus spp. and their antimicrobial resistance profile in operating rooms (ORs) of the health care facilities.

Methods

This protocol has been written according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P, 2015) (Moher et al., 2015). 

Eligibility Criteria

The studies that reported the prevalence of Staphylococcus species in the working environment, personnel, and equipment used in the operating room will be included in this study. The articles conducted across the world and written in the English language that reported the quantitative outcomes will be included in this study. 

The studies did not report the prevalence of Staphylococcus species, were not conducted in the operating room, and not reported the quantitative outcome will be excluded from this study. Similarly, the articles with inadequate information, editorial reports, short communication and will be excluded from this study.

Data sources and search strategy

The literature search will be carried out by using nine electronic databases and indexing services without any date limit. The MEDLINE, Embase, Psych INFO, PubMed, Scopus, Web of Science, google scholar, Science Direct, and CINAHL databases will be used as major data sources. Whereas, grey literature will be used as supplementary data sources. Keywords and Medical Subject Headings (MeSH) regarding Operation room and pathogen will be used. Examples of search terms include Bacteri* pathogen, microb* contamination, Staphylococcus aureus, S. aureus, methicillin resistant Staphylococcus aureus, antimicrobial resistance, antimicrobial susceptibility, multidrug resistance, operat* room, and operat* theater. Boolean operation (AND, OR, and NOT) will be used to combine these terms in varying ways to identify relevant studies. Search strategies will be customized to suit each database. A draft of the PubMed search strategy is presented in Supplementary material I. The reference lists of all relevant articles will be manually searched to identify any studies missed by electronic database searching. 

Study selection

The records obtained from each database will be merged in Endnote X9 (Thomson Reuters, USA), and duplicates will be removed (Rathbone et al., 2015). Studies obtained through the search strategy will be screened by two independent reviewers according to the inclusion and exclusion criteria. This will be done at two stages; stage one, the reviewers will evaluate the title and abstract of each article and at the second stage, the full text of all eligible studies will be retrieved. If a reviewer is unsure about a study’s eligibility at the first stage, a full-text evaluation will be conducted. Also, if there is any disagreement at these two stages, it will be resolved by consensus and, if unresolved, a third reviewer will be consulted. The degree of agreement between both reviewers will be measured utilizing Cohen’s kappa (Cohen, 1960) and a minimum κ value of 0.75 will be taken to represent high agreement. 

Data extraction

Information extraction will be done by two authors (EM and DA) under the supervision of the other two authors (YT and KB) using a standardized data extraction spreadsheet prepared in Microsoft Excel; study characteristics (study area, first author, year of publication), Methods (study design, sample source, sample type, sample size), and outcome of interests (positive samples for Staphylococcus spp. and resistant profile positive samples for isolates) will be extracted. If information is missing, or further information is needed the authors will be contacted by E-mail. If authors do not reply until the last manuscript draft, the article will be discarded. 

Quality assessment

The quality of studies included will be assessed by the Newcastle-Ottawa scale adapted for cross-sectional studies (Newcastle- Ottawa, 2016) and graded out of 10 points. For ease of assessment, the tool included important indicators categorized into three major sections; the first section assesses the methodological quality of each study and weighs a maximum of five points, the second section considers comparability of the study and takes 2 points, and the remaining section assess outcomes with related statistical analysis. This critical appraisal was conducted to assess the internal and external validity of studies and reduce the risk of biases. Two authors will independently conduct the quality assessment and the mean score of two authors will be taken for final decision and studies with a score greater than or equal to five were included.

Analysis and Data synthesis

We will perform descriptive analysis and report the characteristics of included studies in summary tables and narrative text. The relevant data extracted from selected studies using format prepared in Microsoft Excel will be exported to STATA 16.0 software for analyses of the pooled estimate of outcome measures and subgroup analyses. The primary outcome measure is the prevalence of Staphylococcus spp. isolates in the environment, personnel, and equipment of OR. The pooled prevalence was calculated per Staphylococcus spp. The secondary outcome measure is the antimicrobial resistance status of the Staphylococcus spp. against antimicrobials of different categories. Subgroup analyses will include sources of Staphylococcus spp. in the OR. The prevalence pooled estimates for all pre-specified outcomes of interest will be computed applying random-effects meta-analysis models and reported in forest plots.

Assessment of heterogeneity

The heterogeneity between included studies will be measured using I2 (I Squared test) statistics. The I2 statistic will be calculated to assess inconsistencies in the results of the included studies. The I2 results will be interpreted as follows: unimportant heterogeneity (0%–40%), moderate heterogeneity (30%–60%), substantial heterogeneity (50%–90%), and considerable heterogeneity (75%–100%) (Higgins et al., 2019). Further analysis will be conducted excluding studies with a high risk of bias. To investigate the introduction of publication bias, a random-effects version of Egger’s test will be utilized and visualized through a funnel plot (Sterne et al., 2001). 

Discussion

Several studies laid out the sources of microbial contamination as diverse and it may be from surgical personnel, traffic within the OR, OR tools and equipment, and indoor environment of OR (Emmerson, 1998; Emori & Gaynes, 1993). Approximately 30% of all operating room personnel carry Staphylococcus aureus (Bethune et al., 1965). Traffic and air in the operation room differ when the door was closed, 13.3 average colony-forming units per square foot per hour, with door open was 24.8, and with swinging doors was 19.4. Also in the operating room without being touched 30% of instruments were contaminated (Ritter, 1999). wearing a mask also related with when the individual wore the face mask, 447.3 colony forming units per foot per hour, and when individual not wear a face mask, 449.7 colony forming units per foot per hour observed in OR (Jones et al., 1972).

Due to this fact, the operation room environment, personnel, and equipment are included in this study. The recent systematic review revealed most gram-positive bacteria such as Enterococcus species, Staphylococcus species, and Streptococcus pyogenes survive for months on dry surfaces. Also, many Gram-negative bacteria, such as Acinetobacter species, E. coli, Klebsiella species, Pseudomonas aeruginosa, and Serratia marcescens can survive on inanimate surfaces even for months (Kramer et al., 2006). However, the prevalence of these contaminants from different sources in the operation room is not mentioned.

Understanding the prevalence and antimicrobial resistance of staphylococcus species is important because it is relevant for preventing the transmission of nosocomial pathogens in the operation room. This systematic review will provide evidence on the staphylococcus species in the operation room, the prevalence and antimicrobial resistance of each species. These findings will provide knowledge to clinicians on the level of contamination due to staphylococcus. Moreover, the results will also be available to all scientific communities.

Strengths And Limitations Of The Review

Strengths of this review include clear definitions and inclusion criteria, and a transparent systematic approach to searching, screening, and reviewing studies as well as extracting data using standardized forms and duplication at all stages. Our search area is large enough (global) and our inclusion criteria are specific to the operating room. As much as possible, by using data reported in existing studies, this review will provide comprehensive statistical analyses not previously available. This study includes published articles, although grey literature and hand searching, our findings may still be vulnerable to selective reporting. Another limitation of the review is the inclusion of studies published in English only.

Dissemination

The findings of this review will be submitted for publication in a peer-reviewed journal.

List Of Abbreviations

HAIs

Hospital-acquired infections

SSI

Surgical site infection

Spp.

Species

OR

Operation room

SA

Staphylococcus Aurues

MRSA

Methicillin-resistant Staphylococcus Aurues

PRISMA

Preferred Reporting Items for Systematic Review and Meta-analysis

Declarations

Ethics approval and consent to participate

Not applicable  

Consent for publication 

Not applicable  

Availability of data and materials 

PRISMA-P checklist: http://www.prisma-statement.org/Extensions/Protocols 

Newcastle- Ottawa checklist: https://static-content.springer.com/esm/art%3A10.1186%2F1471-2458-13-154/MediaObjects/12889_2012_5111_MOESM3_ESM.doc

Competing interests 

The authors declare that they have no competing interests.

Funding 

This study is not funded. 

Authors' contributions 

EM and DA contributed to the development of the search strategy, searched and selected the studies, also read the full texts of studies, extracted data, assessed the risk of bias and reported quality of evidence, and contributed to the initial drafting. YM and KB will act as an arbiter in the selection stage. All authors have read and approved the final manuscript for publication. 

Acknowledgments 

Not applicable 

References

  1. Allegranzi B, Nejad SB, Combescure C, Graafmans W, Attar H, Donaldson L, Pittet D. Burden of endemic health-care-associated infection in developing countries: systematic review and meta-analysis. The Lancet. 2011;377(9761):228–41.
  2. Bethune DW, Blowers R, Pask EA. (1965). Dispersal of Staphylococcus aureus by patients and surgical staff. Lancet, 480–483.
  3. Bhalla A, Aron DC, Donskey CJ. Staphylococcus aureus intestinal colonization is associated with increased frequency of S. aureus on skin of hospitalized patients. BMC Infect Dis. 2007;7(1):1–7.
  4. Chen S-Y, Hu C-C, Chen C-C, Chang Y-H, Hsieh P-H. (2015). Two-stage revision arthroplasty for periprosthetic hip infection: mean follow-up of ten years. BioMed Research International, 2015.
  5. Cohen J. A coefficient of agreement for nominal scales. Educ Psychol Measur. 1960;20(1):37–46.
  6. Diab-Elschahawi M, Berger J, Blacky A, Kimberger O, Oguz R, Kuelpmann R, Kramer A, Assadian O. Impact of different-sized laminar air flow versus no laminar air flow on bacterial counts in the operating room during orthopedic surgery. Am J Infect Control. 2011;39(7):e25–9.
  7. Emmerson M. A microbiologist’s view of factors contributing to infection. New Horiz. 1998;6(2 Suppl):3–10.
  8. Emori TG, Gaynes RP. An overview of nosocomial infections, including the role of the microbiology laboratory. Clin Microbiol Rev. 1993;6(4):428–42.
  9. Haun N, Hooper-Lane C, Safdar N. Healthcare personnel attire and devices as fomites: a systematic review. Infection Control Hospital Epidemiology. 2016;37(11):1367–73.
  10. Hayden MK, Bonten MJM, Blom DW, Lyle EA, van de Vijver DAMC, Weinstein RA. Reduction in acquisition of vancomycin-resistant enterococcus after enforcement of routine environmental cleaning measures. Clin Infect Dis. 2006;42(11):1552–60.
  11. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. Cochrane handbook for systematic reviews of interventions. John Wiley & Sons; 2019.
  12. Jones MA, Johnson JC, French MLV, Hart JB, Ritter MA. Unidirectional air flow and surgical face mask exhaust system in the prevention of airborne surgical infection. The American Journal of Surgery. 1972;124(1):49–51.
  13. Kawakita T, Landy HJ. Surgical site infections after cesarean delivery: epidemiology, prevention and treatment. Maternal Health Neonatology Perinatology. 2017;3(1):1–9.
  14. Kramer A, Schwebke I, Kampf G. How long do nosocomial pathogens persist on inanimate surfaces? A systematic review. BMC Infect Dis. 2006;6(1):1–8.
  15. McHugh SM, Hill ADK, Humphreys H. Laminar airflow and the prevention of surgical site infection. More harm than good? The Surgeon. 2015;13(1):52–8.
  16. Mellinghoff SC, Vehreschild JJ, Liss BJ, Cornely OA. Epidemiology of surgical site infections with Staphylococcus aureus in Europe: protocol for a retrospective, multicenter study. JMIR Research Protocols. 2018;7(3):e63.
  17. Misha G, Chelkeba L, Melaku T. Incidence, risk factors and outcomes of surgical site infections among patients admitted to Jimma Medical Center, South West Ethiopia: Prospective cohort study. Annals of Medicine Surgery. 2021;65:102247.
  18. Mohamed AH, Mohamud HA, Arslan E. Epidemiological Characteristics and Predisposing Factors for Surgical Site Infections Caused by Bacterial Pathogens Exhibiting Multidrug-Resistant Patterns. Antibiotics. 2021;10(6):622.
  19. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Systematic Reviews. 2015;4(1):1–9.
  20. Montoya A, Schildhouse R, Goyal A, Mann JD, Snyder A, Chopra V, Mody L. How often are health care personnel hands colonized with multidrug-resistant organisms? A systematic review and meta-analysis. Am J Infect Control. 2019;47(6):693–703.
  21. Newcastle- Ottawa. (2016). Scale customized for cross-sectional studies. https://static-content.springer.com/esm/art%3A10.1186%2F1471-2458-13-154/MediaObjects/12889_2012_5111_MOESM3_ESM.doc.
  22. Ning J, Wang J, Zhang S, Sha X. Nasal colonization of Staphylococcus aureus and the risk of surgical site infection after spine surgery: a meta-analysis. The Spine Journal. 2020;20(3):448–56.
  23. Omran A, Taha MS. Bacterial contamination of mobile phones among health care workers: A meta-analysis study. Journal of Medicine in Scientific Research. 2020;3(2):87.
  24. Pasquarella C, Balocco C, Colucci ME, Saccani E, Paroni S, Albertini L, Vitali P, Albertini R. The influence of surgical staff behavior on air quality in a conventionally ventilated operating theatre during a simulated arthroplasty: a case study at the University Hospital of Parma. International Journal of Environmental Research Public Health. 2020;17(2):452.
  25. Rathbone J, Carter M, Hoffmann T, Glasziou P. Better duplicate detection for systematic reviewers: evaluation of Systematic Review Assistant-Deduplication Module. Systematic Reviews. 2015;4(1):1–6.
  26. Ritter MA. (1999). Operating Room Environment. Clinical Orthopaedics and Related Research®, 369. https://journals.lww.com/clinorthop/Fulltext/1999/12000/Operating_Room_Environment.11.aspx.
  27. Robinson ADM, Dexter F, Renkor V, Reddy S, Loftus RW. Operating room PathTrac analysis of current intraoperative Staphylococcus aureus transmission dynamics. Am J Infect Control. 2019;47(10):1240–7. https://doi.org/https://doi.org/10.1016/j.ajic.2019.03.028.
  28. Russell CD, Ramaesh R, Kalima P, Murray A, Gaston MS. Microbiological characteristics of acute osteoarticular infections in children. J Med Microbiol. 2015;64(4):446–53.
  29. Russotto V, Cortegiani A, Fasciana T, Iozzo P, Raineri SM, Gregoretti C, Giammanco A, Giarratano A. (2017). What healthcare workers should know about environmental bacterial contamination in the intensive care unit. BioMed Research International, 2017.
  30. Russotto V, Cortegiani A, Raineri SM, Giarratano A. Bacterial contamination of inanimate surfaces and equipment in the intensive care unit. Journal of Intensive Care. 2015;3(1):1–8.
  31. Sadrizadeh S, Tammelin A, Ekolind P, Holmberg S. Influence of staff number and internal constellation on surgical site infection in an operating room. Particuology. 2014;13:42–51.
  32. Shiferaw T, Gebr-silasse L, Mulisa G, Zewidu A, Belachew F, Muleta D, Zemene E. (2016). Bacterial indoor-air load and its implications for healthcare-acquired infections in a teaching hospital in Ethiopia. International Journal of Infection Control, 12(1).
  33. Sterne JAC, Egger M, Smith GD. Investigating and dealing with publication and other biases in meta-analysis. Bmj. 2001;323(7304):101–5.
  34. Wenzel RP, Perl TM. The significance of nasal carriage of Staphylococcus aureus and the incidence of postoperative wound infection. J Hosp Infect. 1995;31(1):13–24.
  35. Wolfensberger A, Clack L, Kuster SP, Passerini S, Mody L, Chopra V, Mann J, Sax H. Transfer of pathogens to and from patients, healthcare providers, and medical devices during care activity—a systematic review and meta-analysis. Infection Control Hospital Epidemiology. 2018;39(9):1093–107.