Methicillin‐Resistant Staphylococcus aureus: A 5‐Year Review of Surveillance Data in a Tertiary Care Hospital in Saudi Arabia
Background. Staphylococcus aureus is an important pathogen that leads to serious infections in the community and in hospitals. Evidence has shown that the prevalence of infection and colonization with drug‐resistant S. aureus, such as methicillin‐resistant S. aureus (MRSA) and glycopeptide intermediately susceptible S. aureus, is increasing. Authorities must be aware of the prevalence of MRSA infection and colonization in their country in order to implement and monitor infection control policies that help curtail further emergence of this pathogen.
Objectives. To examine the trend of hospital‐acquired MRSA infection and colonization in a tertiary care institution in Saudi Arabia during a 5‐year period in order to identify specific areas at high risk for MRSA transmission, and to review our MRSA decolonization procedure and outcomes.
Methods. Surveillance data prospectively collected from January 1, 2000, through December 31, 2004, on hospital‐acquired (HA) MRSA were analyzed, with an emphasis on the trend of HA‐MRSA infection and colonization, areas of high transmission, risk factors, and effectiveness of the implemented decolonization policy.
Results. During the study period, 442 cases of HA‐MRSA infection and colonization were identified. Of these, 51.2% were infections, and 48.8% were colonizations. An increasing trend in the incidence rates of infection and colonization was noticed during the study period, and most cases were identified on the surgical ward (33.3%) and medical ward (32.1%). Of the 34 infected patients who underwent systematic decolonization, 35.3% were successfully decolonized, and of the 11 who underwent topical decolonization, 63.6% were successfully decolonized.
Conclusion. The increasing trend of HA‐MRSA infections has been a noticeable global problem. We identified a gradual increase in the rates of MRSA colonization and infection in a tertiary care center Saudi Arabia and recognize the importance of abiding by strict infection control policies, including hand hygiene and proper isolation practices. Continued surveillance for MRSA and other emerging multidrug‐resistant pathogens is also needed.
Received October 18, 2006; accepted February 8, 2007; electronically published June 29, 2007.
Staphylococcus aureus is a pathogen of major concern for several reasons. It causes infections with significant morbidity and mortality, and it is well known for developing resistance to many antimicrobials, including glycopeptides.1‐3 Drug‐resistant S. aureus has received global attention because of its emergence as a major cause of healthcare‐associated infections (HAIs) and, more recently, an important cause of community‐acquired infections.4,5 Some of the major risks identified for acquiring methicillin‐resistant S. aureus (MRSA) during hospitalization include excessive and prolonged antibiotic use, overcrowding in the hospital, prolonged hospital stay, severity of illness, and poor compliance with infection control practices, such as hand hygiene.6‐8
At King Abdulaziz Medical City–King Fahad National Guard Hospital (Riyadh, Saudi Arabia), we observed increased rates of MRSA infection and colonization despite an active infection control program. In addition to this upward trend, we also identified intrahospital MRSA transmission, mainly in the surgical and medical wards, as the main source of infection. Therefore, to control MRSA, we adopted the guidelines of the Society for Healthcare Epidemiology of America, which have been shown to be effective in many parts of the world.9,10 However, adherence to these guidelines at our institution may not have been optimal at times. Furthermore, additional efforts that would increase adherence are deficient in our institution, such as judicious use of antibiotics and compliance with hand hygiene. In this article, we examine the trend of healthcare‐associated MRSA (HA‐MRSA) infection and colonization in our institution during a 5‐year period in order to identify specific areas at high risk for MRSA transmission, and we also review our decolonization procedure and outcomes.
Methods
Study Site
Prospective surveillance for HA‐MRSA colonization and infection was conducted from 2000 through 2004 at King Abdulaziz Medical City–King Fahad National Guard Hospital. This tertiary care center is a 700‐bed hospital that includes the following 6 intensive care units: medical, pediatric, burn, adult cardiology, pediatric cardiology, and neonatal. The center also includes a 25‐bed hemodialysis unit that serves a mean of 75 patients a day, liver and kidney transplantation units, and adult and pediatric oncology units. During the study period, the long‐term care facility where many of the MRSA cases are managed was part of the main hospital. The hospital serves Saudi Arabia's National Guard soldiers and their families, as well as the hospital employees. It is also a referral center for most patients from eastern Riyadh with complicated conditions due to motor vehicle accidents or with trauma. It also receives referrals from its sister hospitals in Jeddah (in western Saudi Arabia) and Al Ahsa and Dammam (in eastern Saudi Arabia), particularly for cardiac surgery and for care in the burn intensive care unit.
Study Period
The Infection Prevention and Control Department prospectively collects MRSA surveillance data on selected high‐risk patients admitted to the hospital. Data collected from January 1, 2000, through December 31, 2004, were analyzed, and findings are presented in this study.
Data Collection
Patients with MRSA colonization or infection were identified by 1 of 2 main methods. The first method consists of routine surveillance to identify MRSA colonization in high‐risk patients (see Definitions, below). These patients are screened for MRSA at the time of admission and placed under contact isolation. If the patient tests negative for MRSA, contact isolation is discontinued. The second method comprises daily review of microbiology reports sent to the Infection Prevention and Control Department to identify cultures positive for MRSA. This method identifies most MRSA‐infected patients.
The medical records of all patients identified by either method were reviewed for the following demographic and clinical data: age, sex, admission and discharge dates, referring hospital, comorbidities, and presence and type of MRSA infection. Additional data on the decolonization process and outcome were obtained. Data on patients who died were retrospectively reviewed to identify a possible relationship between death and MRSA infection.
Microbiological Methods
Body sites from which samples were obtained for screening included the anterior nares, any exit catheter site, and open skin areas, such as a tracheostomy site, pressure sores, or surgical wounds. Neonates and patients undergoing liver transplantation or elective cardiac surgery had additional screening samples obtained from both sides of the groin and the axillae. Specimens were collected via a blue‐top sterile cotton tip swab moistened in transport media before swabbing. The same swab was used for identical sites, as follows: 1 swab for both nares, 1 swab for both axilla, and 1 swab for both groin areas. Separate swabs, however, were used to screen other areas. S. aureus was identified using conventional bacteriological methods. Antibiotic susceptibility testing was performed with an automated system (Microscan), and guidelines of the Clinical and Laboratory Standards Institute (previously known as the National Committee for Clinical Laboratory Standards) were followed for interpretation of results.11,12 The presence of MRSA was confirmed with the oxacillin disk diffusion test, using a 1‐μg disk.
Definitions
HA‐MRSA versus community‐associated MRSA. All patients with MRSA isolated more than 48 hours after admission to the hospital were considered to have HA‐MRSA. Patients transferred from another hospital, those who had been hospitalized or who had a medical procedure performed in the year before, and those who had a permanent indwelling catheter or percutaneous device present at the time of specimen collection were considered to have HA‐MRSA, and the referring hospital was identified. The referring hospitals with patients found to be MRSA positive were classified as Ministry of Health, private, military, Ministry of Interior, or other governmental institutions. All patients with an MRSA‐positive specimen within the first 48 hours after admission and those who did not meet the criteria specified above for HA‐MRSA were considered to have community‐acquired MRSA and were excluded from the analysis.
Infection versus colonization. Once their medical record was reviewed, the decision to classify an MRSA‐positive patient as infected or colonized was made. This decision was based on the body site from which MRSA was recovered, the patient's clinical status, and whether the patient received treatment. All cases were then verified by one of the infectious diseases specialists in the Infection Prevention and Control Department. If a patient was found to be colonized with MRSA at one site and infected at the same time at a different site, the patient was classified as infected, not colonized.
Rates. The rates of HA‐MRSA colonization and infection were calculated in relation to the number of hospital admissions (ie, cases per 1,000 admissions). The denominator is provided monthly to the Infection Prevention and Control Department by the main statistical department of the hospital.
Patients eligible for screening. The MRSA screening policy was followed for patients admitted to the intensive care units, those transferred from other hospitals, those treated in another hospital or clinic within the past 6 months, those scheduled to undergo liver or cardiac surgery, those receiving continuous ambulatory peritoneal dialysis, those known to have previously tested positive for MRSA, and additional high‐risk populations of patients as designated by the Infection Prevention and Control Department.
Decolonization policy. The Infection Prevention and Control Department has a standard protocol for decolonization of patients with MRSA who might benefit from such a process. Decolonization is ordered and performed by the infection control practitioner for perioperative patients and patients with colonized nares; decolonization is not performed for patients with an indwelling line, patients with a percutaneous endoscopic gastrostomy tube, and patients with a tracheostomy.
Postdecolonization follow‐up cultures of samples from the nares groin, and axillae were performed 3 days after patients completed the decolonization regimen. For patients who received vancomycin, the serum vancomycin concentration was confirmed to be zero before screening was performed again. Three consecutive samples were obtained for culture at 3‐day intervals from all previous positive sites. Decolonization for patients who completed the decolonization regimen and had negative results of all 3 postdecolonization cultures was categorized as successful. Decolonization for patients who did not complete the decolonization regimen and/or postdecolonization rescreening process was categorized as incomplete; we were unable to identify whether decolonization in such patients was successful.
Topical decolonization. Mupirocin is topically applied to both nares twice per day for 7 days after MRSA is confirmed to be susceptible to mupirocin. Chlorhexidine baths are used on a daily basis for 7 days to reduce or inhibit skin colonization with MRSA. Once the decision to perform topical decolonization was made, treatment with mupirocin and chlorhexidine baths was initiated. Topical decolonization was indicated for liver transplant recipients, cardiac and orthopedic surgery patients, and patients who regularly attend other departments for therapy, such as dialysis and physiotherapy.
Systematic decolonization. Systemic decolonization was defined as receipt of vancomycin for treatment of MRSA colonization, with no other indication for use of this agent. Rifampicin‐based decolonization regimens were purposefully discouraged because our hospital serves a population at risk for tuberculosis13‐15 and brucellosis,16‐18 conditions for which rifampicin is among the first‐line therapeutic agents.
Combined decolonization. Some patients received both topical and systemic decolonization therapy.
Data Analysis
Database management and statistical analysis were performed using Epi Info statistical software, version 6.04d (Centers for Disease Control and Prevention), and SAS software, version 8.2 (SAS Institute).
Results
A total of 442 patients fulfilled the criteria for HA‐MRSA during the study period, with 512 positive cultures identified. Most patients were male (70.1%) and older than 50 years (54.8%) (Table 1). Most patients (69.9%) were admitted through the emergency department, whereas 18.1% were transferred from other hospitals. Of the 512 positive cultures, 51.2% were associated with infection, and 48.8% were associated with colonization. Of the 262 cases of infection, the most common culture‐positive specimens were from wounds (94 cases [35.9%]), respiratory tract (81 [30.9%]), and blood (36 [13.7%]) (Table 2). Of the 250 cases of colonization, the most common culture‐positive specimens were from the nares (67 cases [26.8%]) and wounds (65 [26.0%]) (Table 2).
Incidence Rates of MRSA Colonization and Infection
The mean incidence rate for both HA‐MRSA infection and colonization increased from 2.17 cases per 1,000 admissions in 2000 to 3.90 per 1,000 admissions in 2004 (Figure). The mean incidence rate for HA‐MRSA infection increased from 0.80 to 2.30 per 1,000 admissions during 2000‐2004 (Figure), and the mean incidence rate for HA‐MRSA colonization increased from 1.38 cases per 1,000 admissions in 2000 to 1.60 per 1,000 admissions in 2004.
Figure. Mean incidence rates of healthcare‐associated methicillin‐resistant Staphylococcus aureus (HA‐MRSA) infection and colonization and HA‐MRSA infection only during 2000‐2004 at King Fahad National Guard Hospital (Riyadh, Saudi Arabia).
Epidemiological Features
Most patients were in the surgical ward (33.3%) or medical ward (32.1%) at the time of MRSA detection; 7.9% were in the burn unit (Table 1). Contrary to our expectations, only 18.1% of patients were transferred from other hospitals, with most of the transfers from the Ministry of Health hospitals. Most patients were admitted through the emergency ward; however, only 27.4% had a recent history of hospital discharge. Inclusion of MRSA screening data in the medical records of patients recently discharged was inconsistent, and a clear and consistent flagging system for patients known to have MRSA infection or colonization was lacking.
Outcome
Forty‐seven deaths were identified among the 262 patients with HA‐MRSA infection, 44 of which were unrelated and only 3 possibly related to MRSA infection. Of all patients with HA‐MRSA, decolonization was attempted for 52, using our internal policy and procedure for MRSA decolonization. Systemic decolonization was performed for 34 patients; decolonization was successful in 12 (35.3%), and unsuccessful in 10 (29%), and incomplete in 12 (35%). Topical decolonization, performed for 11 patients, was successful in 7 (63.6%), unsuccessful in 1 (9%), and incomplete in 3 (27%). For patients who received a combination decolonization regimen, 80% of the procedures were incomplete, and 20% were successful. The decolonization regimen was unknown for 2 of 52 patients, so no further assessment could be performed. For patients in whom decolonization was successful, recolonization rates were not available.
Discussion
The emergence of MRSA as a major cause of HAIs and community‐acquired infections in healthcare facilities has been recognized as a global problem.19‐21 In the SENTRY Antimicrobial Surveillance Program study, S. aureus was the pathogen most commonly associated with bloodstream, lower respiratory tract, and skin and soft tissue infections from 1997 through 1999.22 According to the National Nosocomial Infections Surveillance System, more than 50% of S. aureus infections are due to MRSA, with a 13% increase in MRSA rates from 1997 to 2001. In European countries, MRSA prevalence rates varied significantly, from less than 1% in northern European countries, such as Denmark, The Netherlands, and Sweden, to more than 40% in countries such as the United Kingdom, Greece, and Italy.23 In a multicenter study in Bangladesh, the rate of MRSA isolation among 4 hospitals ranged from 32% to 63%, and the rate among outpatients was 40%.24 Japan is a country most worthy of mentioning, because it has the highest identified prevalence rate of MRSA in the world. Of all S. aureus bloodstream isolates recovered in Japan, 60%‐70% are resistant to methicillin.19 In other reports from Japan, Kikuchi et al.25 identified high MRSA rates in a neonatal intensive care unit that were associated with a single MRSA clone, whereas Hiramatsu et al.2 reported that 20%‐40% of all S. aureus strains are community‐acquired MRSA.
With the increasing rate of spread of MRSA in the healthcare system, the rates of MRSA infection and colonization have increased. Because higher rates of S. aureus infection are associated with MRSA colonization than with methicillin‐susceptible S. aureus (MSSA) colonization, the financial burden associated with S. aureus infection has increased. Hence, the simple argument that MRSA infections replace MSSA colonizations with a stable burden of S. aureus infections is clearly debatable.26,27 As a consequence of soaring MRSA rates and the increased use of vancomycin, a noticeable increase in vancomycin‐resistant Enterococcus infections in these hospitals and the appearance of MRSA with intermediate susceptibility to vancomycin have been clearly documented.28 In our study, only 34 patients received systemic therapy during a 5‐year period, because of the importance of limiting the use of vancomycin to avoid the emergence of resistant pathogens.
Several studies of MRSA have been reported from Saudi Arabia. In a study from a university‐affiliated tertiary care hospital in Jeddah, the prevalence rate of MRSA colonization and infection was 38% (6 cases per 1,000 admissions), and MRSA in 74.8% of the patients was estimated to be nosocomially acquired.29 Madani29 noted that the prevalence rate of MRSA colonization and infection was 2% (0.2 cases per 1,000 admissions) in 1988, for a 30‐fold increase in the rate observed 10 years earlier; the prevalence of methicillin resistance among all S. aureus isolates recovered was 38%. In another government hospital affiliated with the Ministry of Health, the rate of MRSA infection and colonization was 8 cases per 1,000 admissions, with 42% of the cases occurring in intensive care units and only 9% associated with a history of a recent hospital admission that alluded to intrahospital transmission as the main source.30 The rate of nosocomial transmission was estimated to be 93.7% in that hospital, and the mortality rate among patients with MRSA infection was estimated to be 35%. In our study, 18.1% of patients transferred from other hospitals, mainly government hospitals and private hospitals. However, we believe that most patients admitted to the emergency department (ie, from the community) might have been recently discharged from another hospital. Critical evaluation of this factor is important because the screening and isolation policy adopted by our hospital would not have been followed for many of these patients. For patients admitted to the hospital without undergoing screening, it is more difficult to determine whether their HAI diagnosis is accurate. In a study from Abha Maternity Hospital, located in Abha, a remote region of Saudi Arabia, microbiology records reviewed during a 2‐year period revealed that the prevalence of methicillin resistance among S. aureus isolates was 71%, whereas 85% of all strains were resistant to multiple drugs.31 No reports are available on colonization or infection with vancomycin‐resistant S. aureus from Saudi Arabia.32‐34
With HA‐MRSA infection rates showing a clear increase in these few reports from Saudi Arabia,34 a national database should be created to verify hospitals in which MRSA has become endemic. Collection of these data would be extremely important, because most patients are transferred back and forth between institutions. The national database would be critical for controlling MRSA and other multidrug‐resistant organisms at all tertiary care hospitals, such as ours, to which patients are referred. A healthcare system in which transferred patients are not accepted without confirmation of their MRSA status would also be a valid option.
One of the more recent approaches to decrease the rate of HAIs in Saudi Arabia involved the participation of the Ministry of Health of Saudi Arabia in the Global Patient Safety Alliance for Hand Hygiene (Clean Care is Safer Care), which was launched on October 13, 2005.35 This program was initiated at King Fahad National Guard Hospital and King Abdulaziz Medical City (Riyadh) and was found to be critical for emphasizing the role of hand hygiene in reducing the rate of HAIs,36 keeping in mind that changing the behavior of healthcare workers is one of the major challenging aspects of infection control.37
A true relationship between death and MRSA infection was difficult to assess in our study, since the data initially collected did not include relevant information. When medical records were reviewed retrospectively, however, 3 deaths were thought to be related to MRSA infection. In the literature, however, higher mortality rates were associated with MRSA infection.38‐40
To our knowledge, the true burden of community‐acquired MRSA has not been studied. Panhotra et al.41 reported low MRSA colonization rates among 122 patients at admission during a 3‐month surveillance period in 2004. This finding is concerning, because MRSA was isolated from 1.1% of patients, and MSSA was isolated from 19.1%. Because of these low rates, routine screening of all patients was not found to be cost‐effective. In report from King Khalid Eye Hospital (Riyadh) in 1999, nasal swab specimens were obtained within 48 hours after admission from 100 patients.42 Of the 306 specimens tested, 33% were MSSA, and none were MRSA. In a 36‐month prospective study at a hospital in Al Khobar, Saudi Arabia, the rate of colonization with community‐acquired MRSA was shown to increase from 5% to 33%. Even though this study did not address the MRSA colonization rate in the community, it raises a red flag regarding the possible emergence of MRSA as a more common pathogen in the community.43 Several studies have shown that the cost to treat a patient with MRSA infection is significantly higher than that for a patient with MSSA infection.44 In a cost‐benefit analysis study, Lucet et al.9 showed that it was more cost‐effective to isolate patients on admission to the intensive care unit and to discontinue isolation after results of surveillance cultures were negative. Hospitals with higher rates of nosocomial transmission should consider implementing these strategies. In addition, use of single‐bed rooms was found to be more cost‐effective for institutions that used a surveillance and isolation policy, because unused beds would be wasted if a patient was isolated in a 2‐bed or 4‐bed room.
In conclusion, the increasing MRSA rates we describe need to be evaluated from several perspectives. First, compliance with the surveillance and isolation policy when admitting patients through the emergency department must be examined. Second, compliance with isolation policies, such as gloving, gowning, and performance of hand hygiene, needs to be measured.9 Third, the appropriateness of antimicrobial use in our hospital and especially in intensive care units should be evaluated.45,46 Finally, early involvement of the infection control department in renovation or expansion projects to increase the number of single‐bed rooms must occur.47
Acknowledgments
Potential conflicts of interest. All authors report no conflicts of interest relevant to this article.
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