Risk factors for wound infection caused by Methicillin Resistant Staphylococcus aureus among hospitalized patients: a case control study from a tertiary care hospital in India

Background Methicillin Resistant Staphylococcus aureus (MRSA) causes infection in hospitals and communities. The prevalence and risk factors of MRSA infection is not homogenous across the globe. Objective To find the risk factors of MRSA infection among hospitalized patients. Methods Cross-sectional case control study was conducted at a tertiary care hospital in India. The risk factors were collected using checklist from 130 MRSA and 130 Methicillin sensitive staphylococcus aureus (MSSA) infected patients. The pathogens were isolated from the wound swabs according to Clinical and Laboratory Standards Institute guidelines. Results Both the groups were comparable in terms of age, gender, diabetic status, undergoing invasive procedures, urinary catheterization and smoking (p>0.05). Multivariate logistic regression revealed surgical treatment (OR 4.355; CI 1.03, 18.328; p=0.045), prolonged hospitalization (OR 0.307; CI 0.11, 0.832; p=0.020), tracheostomy (OR 5.298, CI 1.16, 24.298; p=0.032), pressure/venous ulcer (OR 7.205; CI 1.75, 29.606; p=0.006) and previous hospitalization (OR 2.883; CI 1.25, 6.631; p=0.013) as significant risk factors for MRSA infection. Conclusion Surgical treatment, prolonged and history of hospitalization, having tracheostomy for ventilation and pressure/venous ulcer were the key risk factors. Therefore, special attention has to be given to the preventable risk factors while caring for hospitalized patients to prevent MRSA infection.


Introduction
Methicillin Resistant Staphylococcus aureus (MRSA) is a Gram-positive pathogen, having the ability to cause hospital associated infection and/or community acquired infection. Hospital associated MRSA infection is one of the major problems affecting both patients and care providers 1 . MRSA colonization is predominantly present in the nose and skin of humans 2 . Nasal colonization of Staphylococcus aureus and MRSA are the independent predictors of MRSA infection 3 . Colonized inpatient in a neonatal or surgical ICU and poor infection control practices [7][8][9][10][11][12] . The host related factors are age over 65 years, any conditions that suppress immune system function, open wound or injuries, unsanitary or crowded living conditions like dormitories or military barracks, sharing towels or other personal items [7][8][9][10][11][12] . Comorbidities such as diabetes mellitus (66%), hypertension (66%) and sickle cell diseases (33%) are also the threat for acquiring MRSA infection 13 .
MRSA contaminates the hands of healthcare professionals (59.6%) 7 . Even the dress of healthcare professionals can spread MRSA. According to the society for Healthcare Epidemiology of America (SHEA) report (2014), HCPs opine that their attire, including footwear, is important in preventing transmission of infection 14 . Also, MRSA is found on hospital surfaces, disinfectant areas and reusable equipment 15 . Though the cleaning of patient surroundings in ICU has shown a significant reduction in MRSA, after 24 hours of cleaning, the risk of MRSA growth in the patient environment remained high 16 .
Although some similar strains of MRSA are seen in many countries depicting international dissemination, the spread is not homogenous around the globe 17 . Most of the studies have been conducted in developed countries 3,12,18. No published information on risk factors of MRSA infection is traced in India. Therefore, we aimed at identifying the risk factors of MRSA infection in an Indian hospital to institute appropriate preventive measures.

Study design
The study has adopted a cross-sectional case control study design (1:1) with a quantitative approach.

Study setting
The study was carried out in a tertiary care hospital in South India. The hospital has almost all the super specialties with 2032 beds and provides both in-patient and outpatient healthcare services. It caters to the health needs of a large population. It is a private university hospital meeting the teaching needs of many health science courses such as medical, dental, nursing and other allied health courses. The hospital had more than 80% occupancy during the study period. The hospital is certified by the International Organization for Standardization, (ISO) 14001: 2015 ISO 50001:2011and accredited by National Accreditation Board for Hospitals & Healthcare Providers (NABH).

Participants and sample size
Hospitalized patients infected with MRSA were the cases. Patients with Methicillin Sensitive Staphylococcus aureus (MSSA) infections were considered as controls.
The sample size for identifying the risk factors of MRSA infection was calculated based on the previous study reports by using the following formula 19 The proportion at baseline was 0.73 and the expected outcome set was 0.53 (based on the previous hospitalization as the risk factor) 19

Ethical consideration
Ethical permission was obtained from the Institutional Ethics Committee (IEC). The study was registered at 'clinical trail registry -India' (CTRI/2018/01/011510). Administrative approval was taken from the Medical Superintendent and Chief Operating Officer of the hospital. Informed written consent from study participants was obtained.

Data analysis
The data were coded and entered in Statistical Package for Social Sciences (SPSS 16.0) version and the anal-ysis was performed using logistic regression. The demographic characteristics are given in frequency and percentage.

Data collection procedure
We collected the data from June 2017 to May 2018. The hospitalized patients, whose wound swab grew MRSA or MSSA were approached as presented in the flow diagram (figure 1). After obtaining the consent, investigators collected information from the patients and the medical records using a risk assessment checklist. A total of 260 (130 MRSA infected and 130 MSSA infected) patients were recruited.

Results
Both MRSA and MSSA infection groups were comparable in terms of age, gender, admission status, immunity, diabetes mellitus, smoking status, having undergone invasive diagnostic procedures, presence of a catheter, feeding tubes and duration of surgery as shown in Table 1. The mean duration of hospital stay was 9.9 days (range: 1-38 days) for the MRSA infected patients and 9.7 days (range: 1-30 days) for the MSSA infected patients. Both the MRSA and MSSA infected patients were comparable (Table 1) as the odds ratio was not significant at p<0.05. Hence, the groups were considered for further statistical analysis to identify the risk factors.
The risk factors given in Table 2 were considered for multiple logistic regression since the univariate analysis indicated statistical significance. The risk factors along with the odds ratio and 95% confidence interval are given in Table 2.

Discussion
Staphylococcus aureus remains the most common pathogen causing infection in wounds 20 . World Health Organization has stressed that MRSA is one of the high priority multidrug-resistant organism 21 . MRSA infection is high in Asia and the region is considered as 'hospital associated MRSA endemic area' 17 .
In the present study, undergoing surgery, prolonged hospitalization, presence of tracheostomy tube, pressure/venous ulcer and recent hospitalization were the significant independent risk factors causing MRSA infection among hospitalized patients.  22 . In contrast, none of these factors were significant in the present study. Therefore, it can be inferred that the risk factors of MRSA infection differ around the globe.
Patients who have undergone surgical debridement within one year (adjusted odds ratio, 2.6; 95% CI, 1.4-5.0, p=0.002) and obesity (adjusted OR 3.4, 95% CI 1.4-8.8, p=0.008) were at risk of developing recurrent MRSA infection 24 . Vascular ulcer increases the risk of MRSA infection 25 . In agreement to this, the presence of vascular ulcer in the present study was one of the significant risk of causing MRSA infection. Vascular ulcer reduces the blood flow to distal areas. In the absence of oxygen, wound healing is delayed. Non-healing of the ulcer increases the risk of infection. In the current study, bed occupancy was more than 80%. The studies have proven that the occupancy rate in the hospital is directly proportional to the incidence of HAIs 26 . The previous hospitalization is a proven cause of MRSA bacteremia 27 9 . Hospital is a source of multiple pathogens, and transmission of such pathogens from the hospital to the host is common. MRSA is seen in hospital environmental surface (38.9%) which increases the risk of causing infection 17 . The ICU environment (67.3%) is an additional well-known risk factor of getting MRSA infection 7 . MRSA was detected in ventilators (33%) 7 , ultrasound transducers (17%) 28 and stethoscopes used in the hospital 29,30 . Also, MRSA is detected on the hands of 59.6% healthcare professionals 7 .
Old age and nursing home residences are found to be independent risk factors of MRSA infection related death 31 . Pre-prosthetic infection with MRSA is increasing (44%) among orthopedic surgery patients 32 and arthroplasty patients have a higher risk (OR 0.11; 0.02-0.56) than internal fixation 9 which also increases the treatment costs. Most of the time, removal of the prosthesis is the treatment for prosthetic infection and this infection indicates the failure of treatment. MRSA infection can have an adverse effect on the life of infected patients. The consequence of the infection can be repeated hospitalization, increased healthcare cost, increased mortality and morbidity 11 . A retrospective study carried out in Texas showed that 21% MRSA infected patients developed recurrent infection 22 . A two year retrospective study of amputated patients showed 7.3% re-hospitalization due to stump infection. Among the re-admitted patients, MRSA was the leading pathogen causing infection and the most common cause of death 33 . The occurrence of surgical site infection with MRSA among orthopedic and transplant surgery patients is in late post-operative days compared to general surgical patients 34 . This indicates that a longer duration of hospitalization is a threat for the development of infection. Longer hospitalization not only causes wound infection but also can result in MRSA bacteremia. In the present study, prolonged hospitalization (OR 0.307; CI 0.11, 0.832; p=0.020) was a significant contributing factor of MRSA infecton. The mean duration of the hospitalized MRSA infected patients was 9.9 days. The duration of the hospitalization differs for each disease condition. However, for patients with minor surgeries, more than three days of hospitalization and more than seven days for major surgeries were considered as prolonged hospitalization. For patients, without surgical procedures (only medical treatment) the duration of hospitalization was compared with our hospital policy.
In the present study, undergoing surgery emerged as a risk factor. As surgical procedure disrupts the integrity of the skin, a pathogen can enter into the body easily. It is also noted that, more personnel in the operation room increases the risk of infection 35 . However, the operating room team is bigger in teaching hospitals as students are posted in the operation room to develop surgical skills. Therefore, additional measures need to be implemented to reduce risk.
Presence of endotracheal or tracheostomy tubes and vascular ulcers result in infection. Though ulcers can be prevented, managing the patient with endotracheal or tracheostomy is unavoidable in many situations. Therefore, additional emphasis is needed for infection control. These patients need to stay for a longer time in the hospital. A systematic review revealed that the cost of treating MRSA infection is high 36 . Though hospitalization cannot be completely eliminated, the hospital must take necessary measures to reduce the duration of hospitalization and avoid repeated admissions.

Limitation
The study conducted at a single center with convenient sampling lacks the generalizability. Perhaps further studies are required covering diverse geographical and clinical areas which may help in developing appropriate guidelines to prevent MRSA infection.

Conclusion
We identified that the damage to the skin and mucosal barriers such as undergoing surgical procedures and the existence of pressure or venous ulcers increase the risk of acquiring MRSA infection. Prolonged length of hospital stay and the history of recent hospitalization African Health Sciences, Vol 21 Issue 1, March, 2021 are the other risk factors. In addition, tracheostomy escalates the threat of MRSA infection in wounds of patients admitted to the hospital. Hence, controlling these risk factors may help in reducing the burden of infection.