RefCheck Maintenance Notice

On Monday, December 3, 2018, from 16:00-18:00 EST, RefCheck will be undergoing maintenance. RefCheck is the process where, during copyediting, all references are extracted from the manuscript file, parsed, matched against various databases (eg, PubMed and CrossRef), and automatically corrected. For more information on RefCheck, please visit our Knowledge Base.

Who will be affected?

Advertisement

Citing this Article

Right click to copy or hit: ctrl+c (cmd+c on mac)

Published on 06.06.18 in Vol 7, No 6 (2018): June

Preprints (earlier versions) of this paper are available at http://preprints.jmir.org/preprint/10219, first published Feb 26, 2018.

This paper is in the following e-collection/theme issue:

    Protocol

    Relationship Between Staphylococcus aureus Carriage and Surgical Site Infections Following Total Hip and Knee Arthroplasty in the South Asian Population: Protocol for a Prospective Cohort Study

    Corresponding Author:

    Syed H Mufarrih, MBBS

    Department of Orthopedic Surgery

    Aga Khan University Hospital

    Stadium Road

    Karachi, 74800

    Pakistan

    Phone: 92 3028888047

    Email:


    ABSTRACT

    Background: Surgical site infections following total hip or knee arthroplasties have a reported rate of 0.49%-2.5% and can cause significant morbidity as well as tripling the cost of health care expenses. Both methicillin sensitive and methicillin resistant strains of Staphylococcus aureus surgical site infections have been established as a major risk factor for postoperative surgical site infections. S. aureus colonizes the nose, axillae, and perineal region in up to 20%-30% of individuals. Although the literature has reported a higher prevalence of methicillin resistant S. aureus in the South Asian population, routine preoperative screening and prophylaxis have not yet been implemented.

    Objective: The primary objective of our study is to identify the relationship between preoperative colonization status of S. aureus and incidence of postoperative surgical site infections in patients undergoing following total hip and knee arthroplasties. As part of the secondary objectives of this study, we will also investigate patient characteristics acting as risk factors for S. aureus colonization as well as the outcomes of total hip and knee arthroplasty patients which are affected by surgical site infections.

    Methods: This prospective cohort study will comprise of screening all patients older than 18 years of age admitted to the Aga Khan University Hospital for a primary total hip or knee arthroplasty for preoperative colonization with S. aureus. The patients will be followed postoperatively for up to one year following the surgery to assess the incidence of surgical site infections. The study duration will be 2 years (March 2018 to March 2020). For the purpose of screening, pooled swabs will be taken from the nose, axillae, and groin of each patient and inoculated in a brain heart infusion, followed by subculture onto mannitol salt agar and sheep blood agar. For methicillin resistant S. aureus identification, a cefoxitin disk screen will be done. Data will be analyzed using SPSS v23 and both univariate and multivariate regression analysis will be conducted.

    Results: Data collection for this study will commence at the Aga Khan University Hospital, Pakistan during March 2018.

    Conclusions: This study will not only estimate the true burden caused by S. aureus in the population under study but will also help identify the patients at a high risk of surgical site infections so that appropriate interventions, including prophylaxis with antibiotics such as muciprocin ointment or linezolid, can be made. Given the differences in lifestyle, quality, and affordability of health care and the geographical variation in patterns of antibiotic resistance, this study will contribute significantly to providing incentive for routine screening and prophylaxis for S. aureus including methicillin resistant S. aureus colonization in the South Asian population.

    Registered Report Identifier: RR1-10.2196/10219

    JMIR Res Protoc 2018;7(6):e10219

    doi:10.2196/10219

    KEYWORDS

    Crowdfunding campaign to support this specific research

    We help JMIR researchers to raise funds to pursue their research and development aimed at tackling important health and technology challenges. If you would like to show your support for this author, please donate using the button below. The funds raised will directly benefit the corresponding author of this article (minus 8% admin fees). Your donations will help this author to continue publishing open access papers in JMIR journals. Donations of over $100 may also be acknowledged in future publications.

    keyboard with crowdfunding key instead of enter key

    Suggested contribution levels: $20/$50/$100



    Introduction

    Background and Rationale

    Although orthopedic surgeries are generally classified as clean, with strict aseptic techniques and antimicrobial prophylaxis commonly being employed, surgical site infections (SSIs) continue to be a critical complication. Several studies have reported high surgical site infection rates ranging from 0.49% up to 2.5% following hip and knee arthroplasties [1-8]. Although rare, the cost of an SSI to both the patient and the health care system is tremendous. By prolonging hospital stay by a median of 2 weeks, SSIs cause significant morbidity, and with the added rehospitalization costs, they can more than triple overall health care expenses [9].

    Needless to say, the prevention of SSIs requires identification of risk factors with appropriate interventions [10]. Staphylococcus aureus is a major pathogen which colonizes the nose, axillae and perineal region in up to 20%-30% of individuals [11-15], with the most established risk factor for colonization being the extremes of age [16,17]. The association between S. aureus carrier status with an increased risk of S. aureus infections was first recorded by Danbolt in 1931 [18]. It has been shown that carriers of S. aureus are 2 to 9 times more likely to acquire S. aureus SSIs than noncarriers [19-21]. In fact, a study has shown that nasal carriage was the only independent risk factor found for S. aureus SSIs in patients undergoing orthopedic implant surgery [5]. Furthermore, in patients who acquire S. aureus SSIs, paired S. aureus isolates from the wound match those from the nares 85% of the time [22]. Additionally, and more importantly, methicillin resistant Staphylococcus aureus (MRSA), a variant of S. aureus which is becoming an increasingly common pathogen, constitutes 2.58% of S. aureus isolates. MRSA colonization has been found to be associated with worse clinical outcomes after surgery and higher rates of mortality [23].

    It has been reported previously that preoperative identification and decolonization with muciprocin ointment decreased the risk of staphylococcal infections from 2.6% to 1.5%. In addition to this, the number of non-staphylococcal infections is also decreased [24].

    Knowledge of geographical variation in antibiotic resistance patterns is not new. Studies have reported a higher prevalence of MRSA in South Asian countries, approximately as high as 10.7%-19.51% [25-27]. However, the results of our hospital data from the past two years show a total of 3 SSIs following knee arthroplasty, none of which were caused by S. aureus [28]. This data suggests that S. aureus may not be the priority concern when it comes to SSIs following knee arthroplasties in our population. Given the resource limitation and fee for service policy in this part of the world, it is best to focus prophylaxis on the organisms shown to be responsible for SSIs in our data, such as gram negative bacteria. Therefore, this study will play a role in establishing whether S. aureus is truly a major concern in this population and whether it is cost effective to make it the primary target for prophylactic therapies. The aim of our study is to estimate the incidence of SSIs caused by S. aureus and the prevalence of methicillin sensitive Staphylococcus aureus (MSSA) and/or MRSA colonization in the population presenting for elective orthopedic surgeries. To our knowledge, similar studies have not been conducted in the South Asian population and we hope that the results from our study will allow for appropriate interventions to be sought and implemented to promote superior health care practices for all.

    Objectives

    Primary Objective

    The primary objective of this study is to determine the relationship between preoperative colonization of the nose, axillae, and groin by MSSA and/or MRSA and postoperative SSIs by MSSA and/or MRSA following elective total knee or hip arthroplasties.

    Secondary Objectives

    The secondary objectives of this study are listed below.

    1. To estimate the incidence of surgical site infections caused by MSSA and/or MRSA following elective total hip or knee arthroplasty.
    2. To identify patient characteristics associated with MSSA and/or MRSA colonization.
    3. To evaluate the outcomes of total hip or knee arthroplasty in patients who are preoperatively colonized with S. aureus and postoperatively have an SSI with MRSA and/or MSSA.

    Methods

    Study Design

    In this prospective cohort study, over the course of a year, patients admitted to a single tertiary care hospital for an elective total hip or knee arthroplasty will be screened for preoperative colonization with S. aureus (MRSA and/or MSSA). Postoperative follow-ups with these patients will then occur for up to one year to assess and document SSIs, among other outcome variables.

    Setting

    The study will be conducted at the Aga Khan University in Pakistan over a period of 2 years beginning March 2018. The expected completion date of the study is March 2020. Screening will be conducted for all patients admitted during the first year. The next year will be utilized to complete the one year of follow-up of each patient.

    Participants

    Inclusion Criteria

    The inclusion criteria for participants in this study are as follows:

    • All patients admitted for an elective total hip arthroplasty.
    • All patients admitted for an elective total knee arthroplasty.
    • Patients older than 18 years of age.
    Exclusion Criteria

    The exclusion criteria for participants in this study are as follows:

    • Patients with history of MRSA infections in the last one month (based on culture positivity or having received treatment for MRSA).
    • Patients undergoing revision arthroplasty.

    Sample Size

    We used Sample Size Determination in Health Studies (Version 2.0, 1998, WHO) to apply a formula for hypothesis testing using relative risk in cohort studies. In a previous study, Prince et al reported that the rate of infection in colonized groups is 4.7%, while it is 1% in noncolonized groups [15]. Thus, assuming the rate of infection in the colonized group is 4.7% versus 1% in the noncolonized group, we take the value of the relative risk due to colonization to be 4.7% with a level of significance at 5% and power of 0.9. This calculation showed the need for a minimum sample size of 423 subjects. Therefore, we intend to recruit 500 subjects to account for the losses in follow-up.

    Variables

    Both independent and dependent variables, as well as potential confounders, will be recorded in this study. The independent variable in this study is the carrier status of the patient, either positive (carrier of MRSA or MSSA or both) or negative.

    The dependent variables in this study are as follows: surgical site status (infected or not), postoperative length of hospital stay (prolonged or not), postoperative complications (yes or no), and rehospitalizations due to surgical site infection (yes or no). A prolonged hospital stay will be defined as >1 SD from the mean hospital stay calculated for total hip or knee arthroplasties in our sample.

    Potential confounders identified in this study are as follows: patient’s sex (male or female), age at operation (≥65 years or <65 years), body mass index (≥30 kg/m2 or <30k g/m2), comorbid conditions (yes or no), type of procedure (hip vs knee), duration of surgery (prolonged vs non prolonged), American Society of Anaesthesiologist’s status (≥3 or <3), previous hospital admissions within 6 months (yes or no), and antibiotic therapy within one month of current admission (yes or no). A prolonged duration of surgery will be defined as >1 SD from the mean duration of surgery calculated for total hip or knee arthroplasties in our sample.

    Data Sources and Collection

    Patients eligible to participate in the study as per the inclusion and exclusion criteria will be approached by 2 trained researchers, 1 male and 1 female, at their respective beds in the wards on the day of admission, prior to the commencement of standard preparation for surgery. The researchers will explain the purpose and procedure to them in the local language and obtain consent. They will provide a written consent form (Multimedia Appendix 1) which the patients will be asked to sign if they accept the invitation to participate in the study. If any patient is unable to consent for themselves for reasons including, but not limited to, cognitive impairment or physical incapacitation, consent will be obtained from the health care proxy as applicable. During this first interaction with the patient, samples will be taken and sent to the microbiology lab to determine colonization, if any, by S. aureus (details of sample collection are described below) and all questions pertaining to the patient’s demographics and preoperative characteristics will be recorded in the questionnaire (Multimedia Appendix 2). The patient will undergo the planned surgery the following day. Postoperatively, the patient’s medical record files will be used to document the details of the surgical variables relevant to this study. As per guidelines for arthroplasties, all patients receive a cefazolin dose intraoperatively and 3 doses postoperatively. Any variations in this regimen will be noted and included in the analysis.

    Patient Follow-up

    Follow-ups of patients included in this study will be conducted via phone calls made by the research officer at 2 weeks, 2 months, 3 months, 6 months, and 1 year after discharge from the hospital stay following the initial surgery. If any symptoms reported by the patients are suspicious, they will be advised to visit their primary physician for a follow-up where documentation of an SSI will occur using the criteria listed below. Following examination, if an infection is suspected, attending surgeons will be encouraged to send samples from the surgical site to culture so identification of MSSA and/or MRSA can be conducted. Patients lost to follow-up will be excluded from the analysis.

    Study Outcome Definition

    Diagnosis of an SSI will be based on the criteria put forward by the Centers for Disease Control and Prevention [10]. An SSI will be classified into one of 3 groups listed below.

    1. Superficial incisional surgical site infection occurring within 30 days of surgery.
    2. Deep incisional surgical site infection.
    3. Organ or space surgical site infections occurring within 30 days of surgery if no implant is left in place or within 1 year if the implant was in place and the infection appeared to be related to the surgery.

    All pathogens will be examined for all SSI cases. An SSI with MRSA will be assessed using the same culture method as used for assessment of nasal MRSA.

    Sample Collection

    For the purpose of screening for MRSA or MSSA, pooled swabs will be taken from the nose, axillae, and groin of each patient. A total of 3 transport swabs will be used for each patient, one for both nares, one for both axillae, and one for the bilateral groin region. For adequate sampling, each swab will be rubbed for a total of 5-6 seconds in each region. Three transport swabs for each patient will be labelled with a single code and transported to the microbiology lab for further processing.

    Laboratory Procedure

    Pooled swabs from each patient will be inoculated in a brain heart infusion for 24 hours at 37⁰C, following which the specimen will be subcultured onto mannitol salt agar and sheep blood agar. The agar plates will be assessed after 24 hours. For none or minimal growth, the plate will be reincubated and reassessed at 48 hours. S. aureus will be identified by tube coagulase and deoxyribonucleic acidase production. For MRSA identification, a cefoxitin disk screen will be conducted.

    Statistical Analysis

    Patients admitted several times during the study period will be included only once in the analysis. Data will be analyzed using SPSS v23. The Shapiro-Wilk Test will be used to access normality of the variables. For normally distributed data, means will be reported and comparison will be done using a t test or Wilcoxon signed rank test. For skewed data, medians with interquartile ranges will be reported and comparisons will be conducted using the Mann-Whitney U test. For categorical variables, we will use a chi-square test for comparison. If chi square assumptions are violated, the Fisher exact test will be used. In addition, a Kaplan-Meier survival analysis will be used to compare the two groups; the patients who were tested positive for MRSA or MSSA colonization and patients who were negative for MRSA or MSSA colonization.

    Multiple logistic regression analysis will be performed to estimate adjusted relative risk (odds ratios, ORs) and their 95% CIs. For univariate testing, the threshold for qualifying for further analysis will be P value <0.20. All variables with P values <0.05 in multivariate regression analysis will be declared significant. The test for trend will be performed by including explanatory variables in the model that will be coded by ordinal numbers with increasing categories of exposure.

    Ethical Approval

    Approval for the conduction of this study has been taken from the Ethical Review Committee (ERC) of Aga Khan University Hospital, Pakistan; ERC Number: 4014-Sur-ERC-16.


    Results

    Data collection for this study will commence at the Aga Khan University Hospital, Pakistan, on March 5, 2018.

    As part of the primary objective and secondary objective three, we will demonstrate the relationship between the preoperative carrier status (independent variable) and postoperative SSI (dependent variable for the primary objective) and other dependent variables as a crude and adjusted relative risk (RR), as shown in example Multimedia Appendix 3.

    As part of secondary objective two, we will demonstrate the relationship between the carrier status (independent variable) and potential confounding variables as both crude and adjusted ORs, as shown in example Multimedia Appendix 4.


    Discussion

    Principal Results

    The South Asian population belongs to the developing world. Together with the differences in lifestyle, quality of health care, and the affordability of health care expenses, the geographical variation in patterns of antibiotic resistance makes it imperative to study the incidence of SSIs caused by S. aureus, particularly MRSA, with emphasis on the relationship between preoperative colonization and postoperative infections. This will not only help to identify the patients at a high risk of SSIs, but also allow the staging of appropriate interventions, such as prophylaxis with an antibiotic which provides MRSA coverage (eg, muciprocin ointment).

    Although no study investigating the relationship between preoperative colonization and postoperative infection by S. aureus for orthopedic surgeries has been conducted in our region where the aseptic measures may be stricter, similar studies in other regions have been conducted in the past. In 2001, Ziaullah et al reported that out of 308 hospital personnel, 20.8% were found to be nasal carriers of S. aureus, with MRSA accounting for 10.7% of the samples [27]. In 2014, Anwar and colleagues reported that out of 1660 nasal samples taken from patients’ attendants, a total of 246 (14.82%) samples were positive for growth of S. aureus. Out of the 246 positive samples, 48 (19.51%) isolates were MRSA [26]. In the same year, Khurram et al reported that out of 1431 patients admitted in the ICU, 57 patients developed infections with MRSA. They showed that older (>52 years), diabetic patients with a central venous line in place were at a significantly higher risk of developing these infections [29]. The report also showed that the rate of surgical site infection following clean cardiovascular surgery was 4%; 40% of which was caused by S. aureus [29].

    Our study aims to investigate the relationship between preoperative colonization and postoperative infections by S. aureus. Although this study does justice to the defined objectives within the scope of resources available to us, the elaboration of certain issues and relevant recommendations may help in drawing stronger conclusions from future studies.

    The methodology described will accurately depict a correlation between preoperative carrier status and postoperative infection by S. aureus. However, in order to establish a causal relationship between the two variables, the S. aureus strains need to be typed (eg, by pulse field gel electrophoresis) [30]. The recommendations to administer antibiotic prophylaxis with MRSA coverage could nevertheless still be made if the incidence of postoperative MRSA infections was found to be significant. In addition to preoperative cultures, intraoperative and postoperative cultures, together with cultures at regular follow-up intervals, can be planned for future studies to account for acquisition of S. aureus during and after the surgical procedure.

    In our study, we are using pooled swabs from the nose, axillae, and groin cultured together to establish the carrier status. Although culturing the sample from each region separately would increase the cost, it would allow us to identify the most common area for colonization by S. aureus. This may impact the choice of agent to be used as antibiotic prophylaxis since muciprocin ointment applied locally for intranasal colonization has been a popular choice, but its application over large areas increases its resistance [17]. So, if the axillae and groin were also found to be colonized, systemic antibiotics such as linezolid could be considered as an alternative [31]. Furthermore, quantification of culture results could also aid in the making the decision between local and systemic antibiotics.

    The methodology described in our study for the follow-up of patients up to one year postsurgery has some limitations. Firstly, patients may acquire MRSA from subsequent hospitalizations other than those in our hospital following discharge and may be prescribed antibiotics for infections other than those of the surgical site during the one year of follow-up. Secondly, a long follow-up adds to the potential confounders which may influence the results. Therefore, we recommend a more throrough documentation of potential confounding variables and an elaborate analysis plan to take those factors into account to draw more robust conclusions from future studies.

    Benefits and Potential Risks

    The treatment plan for all patients will follow the standard protocol regardless of participation in the study. Specimen sample collection itself will take a maximum of 15 minutes of the patient’s time if they choose to participate. Results of a positive screening for MSSA or MRSA will be communicated to the patient via telephone, so they can use this information in any future surgeries they undergo.

    Conclusion

    This prospective cohort study will add to the current literature by investigating the relationship between preoperative colonization and the postoperative incidence of SSIs by MSSA and/or MRSA following orthopedic surgeries in the South Asian population. The study will allow for the identification of patients at a higher risk of developing an SSI so that appropriate interventions including local or systemic antibiotic prophylaxis can be planned. This may lead to a reduction in the rates of SSIs following relatively expensive surgeries and decreasing hospital costs for a population which belongs to the developing world.

    Acknowledgments

    SHM and NQQ were involved in writing of the manuscript. AS was the study coordinator and reviewed the manuscript. AZ, SFM, PH and SN helped with the study design and reviewed the manuscript. The primary supervisor was SN. The study was funded by the Department of Surgery of the Aga Khan University, Pakistan.

    Conflicts of Interest

    None declared.

    Multimedia Appendix 1

    Consent form.

    PDF File (Adobe PDF File), 32KB

    Multimedia Appendix 2

    Demographics and preoperative characteristics questionnaire.

    PDF File (Adobe PDF File), 33KB

    Multimedia Appendix 3

    Relative risk of each dependent variable with a positive carrier status for S. aureus.

    PDF File (Adobe PDF File), 13KB

    Multimedia Appendix 4

    The relationship between a positive carrier status of S. aureus and various patient characteristics.

    PDF File (Adobe PDF File), 38KB

    References

    1. Urquhart D, Hanna F, Brennan S, Wluka A, Leder K, Cameron P, et al. Incidence and risk factors for deep surgical site infection after primary total hip arthroplasty: a systematic review. J Arthroplasty 2010 Dec;25(8):1216-22.e1. [CrossRef] [Medline]
    2. Minnema B, Vearncombe M, Augustin A, Gollish J, Simor AE. Risk factors for surgical-site infection following primary total knee arthroplasty. Infect Control Hosp Epidemiol 2004 Jun;25(6):477-480. [CrossRef] [Medline]
    3. Poultsides LA, Ma Y, Della VAG, Chiu Y, Sculco TP, Memtsoudis SG. In-hospital surgical site infections after primary hip and knee arthroplasty--incidence and risk factors. J Arthroplasty 2013 Mar;28(3):385-389. [CrossRef] [Medline]
    4. Mufarrih S, Aqueel T, Ali A, Malik A, Noordin S. Unilateral vs. bilateral total knee arthroplasty with 90-day morbidity and mortality: A retrospective cohort study. International Journal of Surgery Open 2017;8:24-28. [CrossRef]
    5. Kalmeijer MD, van NE, Bogaers-Hofman D, de BGA. Nasal carriage of Staphylococcus aureus is a major risk factor for surgical-site infections in orthopedic surgery. Infect Control Hosp Epidemiol 2000 May;21(5):319-323. [CrossRef] [Medline]
    6. Jung P, Morris AJ, Zhu M, Roberts SA, Frampton C, Young SW. BMI is a key risk factor for early periprosthetic joint infection following total hip and knee arthroplasty. N Z Med J 2017 Sep 01;130(1461):24-34. [Medline]
    7. Roth VR, Mitchell R, Vachon J, Alexandre S, Amaratunga K, Smith S, Canadian Nosocomial Infection Surveillance Program. Periprosthetic Infection following Primary Hip and Knee Arthroplasty: The Impact of Limiting the Postoperative Surveillance Period. Infect Control Hosp Epidemiol 2017 Dec;38(2):147-153. [CrossRef] [Medline]
    8. Honkanen M, Jämsen E, Karppelin M, Huttunen R, Huhtala H, Eskelinen A, et al. The impact of preoperative bacteriuria on the risk of periprosthetic joint infection after primary knee or hip replacement: a retrospective study with a 1-year follow up. Clin Microbiol Infect 2018 Apr;24(4):376-380. [CrossRef] [Medline]
    9. Whitehouse JD, Friedman ND, Kirkland KB, Richardson WJ, Sexton DJ. The impact of surgical-site infections following orthopedic surgery at a community hospital and a university hospital: adverse quality of life, excess length of stay, and extra cost. Infect Control Hosp Epidemiol 2002 Apr;23(4):183-189. [CrossRef] [Medline]
    10. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for Prevention of Surgical Site Infection, 1999. American Journal of Infection Control 1999 Apr;27(2):97-134. [CrossRef]
    11. Tong S, Davis J, Eichenberger E, Holland T, Fowler V. Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management. Clin. Microbiol. Rev 2015 May 27;28(3):603-661 [FREE Full text] [CrossRef] [Medline]
    12. Schwarzkopf R, Takemoto R, Immerman I, Slover J, Bosco J. Prevalence of Staphylococcus aureus colonization in orthopaedic surgeons and their patients: a prospective cohort controlled study. J Bone Joint Surg Am 2010 Aug 04;92(9):1815-1819. [CrossRef] [Medline]
    13. Berthelot P, Grattard F, Cazorla C, Passot J, Fayard J, Meley R, et al. Is nasal carriage of Staphylococcus aureus the main acquisition pathway for surgical-site infection in orthopaedic surgery? Eur J Clin Microbiol Infect Dis 2010 Apr;29(4):373-382. [CrossRef] [Medline]
    14. Bajolet O, Toussaint E, Diallo S, Vernet-Garnier V, Dehoux E. [Is it possible to detect Staphylococcus aureus colonization or bacteriuria before orthopedic surgery hospitalization?]. Pathol Biol (Paris) 2010 Apr 01;58(2):127-130 [FREE Full text] [CrossRef] [Medline]
    15. Price C, Williams A, Philips G, Dayton M, Smith W, Morgan S. Staphylococcus aureus nasal colonization in preoperative orthopaedic outpatients. Clin Orthop Relat Res 2008 Nov;466(11):2842-2847 [FREE Full text] [CrossRef] [Medline]
    16. Williams R. Healthy carriage of Staphylococcus aureus: its prevalence and importance. Bacteriol Rev 1963 Mar;27:56-71 [FREE Full text] [Medline]
    17. Wertheim H, Verveer J, Boelens H, Van Belkum A, Verbrugh H, Vos M. Effect of mupirocin treatment on nasal, pharyngeal, and perineal carriage of Staphylococcus aureus in healthy adults. Antimicrobial agents and chemotherapy 2005;49(4):1465-1467. [CrossRef] [Medline]
    18. Wertheim H, Melles D, Vos M, van Leeuwen W, van Belkum A, Verbrugh H, et al. The role of nasal carriage in Staphylococcus aureus infections. The Lancet Infectious Diseases 2005 Dec;5(12):751-762. [CrossRef]
    19. Kluytmans J, van BA, Verbrugh H. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin Microbiol Rev 1997 Jul;10(3):505-520 [FREE Full text] [Medline]
    20. Perl T, Golub J. New approaches to reduce Staphylococcus aureus nosocomial infection rates: treating S. aureus nasal carriage. Ann Pharmacother 1998 Jan;32(1):S7-16. [CrossRef] [Medline]
    21. Wenzel R, Perl T. The significance of nasal carriage of Staphylococcus aureus and the incidence of postoperative wound infection. J Hosp Infect 1995 Sep;31(1):13-24. [Medline]
    22. Perl T, Cullen J, Wenzel R, Zimmerman M, Pfaller M, Sheppard D, Mupirocin And The Risk Of Staphylococcus Aureus Study Team. Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections. N Engl J Med 2002 Jun 13;346(24):1871-1877. [CrossRef] [Medline]
    23. Engemann J, Carmeli Y, Cosgrove S, Fowler V, Bronstein M, Trivette S, et al. Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection. Clin Infect Dis 2003 Mar 01;36(5):592-598. [CrossRef] [Medline]
    24. Rao N, Cannella B, Crossett LS, Yates AJ, McGough R. A preoperative decolonization protocol for staphylococcus aureus prevents orthopaedic infections. Clin Orthop Relat Res 2008 Jun;466(6):1343-1348 [FREE Full text] [CrossRef] [Medline]
    25. Voss A, Doebbeling BN. The worldwide prevalence of methicillin-resistant Staphylococcus aureus. Int J Antimicrob Agents 1995 Apr;5(2):101-106. [Medline]
    26. Anwar MS, Jaffery G, Rehman BK, Tayyib M, Bokhari SR. Staphylococcus aureus and MRSA nasal carriage in general population. J Coll Physicians Surg Pak 2004 Nov;14(11):661-664. [CrossRef] [Medline]
    27. Ziaullah M, Amber M, Tafazzule Haque M, Nadir Zafar K, Zafar I, Waqar A, et al. Prevalence of nasal carriage of Methicillin Resistant Staphylococcus Aureus (MRSA) in hospital personnel. In: Proceeding Shaikh Zayed Postgrad Med Inst. 2001 Jun 15 Presented at: Proceeding Shaikh Zayed Postgrad Med Inst; 15/6/2001; Shaikh Zayed Hospital Complex, Lahore p. 29-33   URL: http://www.pakmedinet.com/8530
    28. Ashraf I, Mohib Y, Hasan O, Ahmad K, Malik A, Noordin S. Surgical Site Infection Surveillance Following Total Knee Arthroplasty: Tertiary Care Hospital Experience. Annals of Medicine and Surgery 2018 Apr. [CrossRef]
    29. Khurram IM, Khan SA, Khwaja AA, Khan R, Khokher SA, Khawar S, et al. Risk factors for clinical infection in patients colonized with methicillin resistant Staphylococcus aureus (MRSA). J Pak Med Assoc 2004 Aug;54(8):408-412 [FREE Full text] [Medline]
    30. Schlichting C, Branger C, Fournier JM, Witte W, Boutonnier A, Wolz C, et al. Typing of Staphylococcus aureus by pulsed-field gel electrophoresis, zymotyping, capsular typing, and phage typing: resolution of clonal relationships. J Clin Microbiol 1993 Feb;31(2):227-232 [FREE Full text] [Medline]
    31. Schweizer M, Perencevich E, McDanel J, Carson J, Formanek M, Hafner J, et al. Effectiveness of a bundled intervention of decolonization and prophylaxis to decrease Gram positive surgical site infections after cardiac or orthopedic surgery: systematic review and meta-analysis. BMJ 2013 Jun 13;346:f2743 [FREE Full text] [Medline]


    Abbreviations

    ASA: American Society of Anesthesiologists
    ERC: Ethical Review Committee
    MRSA: Methicillin resistant Staphylococcus aureus
    MSSA: Methicillin sensitive Staphylococcus aureus
    OR: odds ratio
    RR: relative risk
    SSI: surgical site infection


    Edited by G Eysenbach; submitted 26.02.18; peer-reviewed by K Clesham, P Haubruck, M Nomali; comments to author 12.04.18; revised version received 22.04.18; accepted 24.04.18; published 06.06.18

    ©Syed H Mufarrih, Nada Q Qureshi, Anum Sadruddin, Pervaiz Hashmi, Syed Faisal Mahmood, Afia Zafar, Shahryar Noordin. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 06.06.2018.

    This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly cited. The complete bibliographic information, a link to the original publication on http://www.researchprotocols.org, as well as this copyright and license information must be included.