Short Communication: Risk Factors for Methicillin-Resistant Staphylococcus aureus Colonization Among HIV Patients at Hospital Admission

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomial pathogen that has become increasingly prominent in hospitals and the community. HIV-positive patients may be one of the most MRSA-susceptible populations because of their immunocompromised status. At the Communicable Disease Centre, Tan Tock Seng Hospital, Singapore, we implemented a universal MRSA screening program and performed a case-control study to identify risk factors for MRSA colonization among 294 HIV patients at admission from January 2009 to January 2010. Among 54 HIV-positive patients who were MRSA positive at hospital admission, 16 (29.6%) were positive at the nares/axilla/groin (NAG; one combined swab), 14 (25.9%) were NAG and perianal positive, 3 (5.6%) were NAG and throat positive, 10 (18.5%) were NAG, perianal, and throat positive, 6 (11.1%) were throat positive, and 5 (9.3%) were perianal positive. Upon multivariate analysis, we found that age [odds ratio (OR)=1.04, 95% confidence interval (CI): 1.01–1.07, p=0.006] and CD4 count <200/μl within the past 6 months (OR=4.29, 95% CI: 1.83–10.06, p=0.001) were significant risk factors for MRSA colonization. We generated a receiver operating characteristic curve using these two variables and found that the area under the curve was 0.69, indicating that age and CD4 count <200/μl performed moderately well in discriminating between those with MRSA colonization and those without. The results of our study indicate that HIV patients of older age and reduced CD4 count may have increased risk of MRSA colonization. These risk factors may serve as indicators for cohorting or isolating HIV patients at hospital admission.

M ethicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen that can be acquired in the hospital or the community. Colonization with MRSA presents considerable risk for subsequent infection, and this may be more pronounced in vulnerable populations such as the immunocompromised.

HIV patients represent a candidate population that may be susceptible to MRSA infection. Frequent hospital visits and risky behavioral patterns may increase their predisposition to MRSA and other nosocomial infections. High viral load, low CD4 T cell count, presence of a central venous catheter, dermatologic disease, and intravenous drug use have been identified as risk factors for both MRSA colonization and infection in HIV-positive patients.¹ Through a pilot universal MRSA screening program at the Communicable Disease Centre (CDC) at Tan Tock Seng Hospital, Singapore, we aimed to elucidate the risk factors for MRSA carriage in HIV patients at hospital admission.

In Singapore, CDC is the primary HIV referral center, managing close to 90% of all national HIV cases.² A universal MRSA screening program began January 2009 and is ongoing. From January 2009 to December 2010, 115 patients were not screened due to known MRSA positivity, while 2257 patient admissions representing 607 unique patients were screened. Patients admitted to CDC were screened within 24 h of hospital admission using one swab for the nares, axilla, and groin (NAG), one for the throat, and one for the perianal region. Samples were inoculated on chromogenic agar plates (MRSASelect, BioRad, France) and incubated at 37°C for 18–28 h. Growth of mauve colonies was interpreted as MRSA positive; colorless colonies were MRSA negative. On average, turnaround time for results was 25 h.

To determine risk factors for MRSA colonization, a retrospective case-control study from January 5, 2009 to January 4, 2010 was performed. These included 54 HIV patients with at least one MRSA-positive swab at entry and 240 HIV patients who screened negative for MRSA at entry and without prior history of MRSA colonization or infection. Demographic data, comorbidities, previous opportunistic infections (if ever), and other clinical information were collected from patient records by trained medical staff. Variables significant upon univariate analysis were entered into a multivariate logistic regression model to determine independent risk factors associated with MRSA colonization. The final logistic regression model was used to generate the receiver operating characteristic curve. All statistical analyses were conducted at the 5% level of significance and performed using Stata 12 (Stata Corp., College Station, TX). Ethics approval was obtained from the Domain Specific Review Board, National Healthcare Group, Singapore (DSRB E/2011/01655).

Of the 54 cases, 16 (29.6%) were NAG positive, 14 (25.9%) were NAG and perianal positive, 3 (5.6%) were NAG and throat positive, and 10 (18.5%) were NAG, perianal, and throat positive; 6 (11.1%) were throat positive only and 5 (9.3%) were perianal positive only.

Factors associated with MRSA carriage are detailed in Table 1. In univariate analysis, cases were more likely to be colonized with MRSA for every 1 year increase in age compared to controls [odds ratio (OR)=1.03, p=0.01]. Those colonized with MRSA were more likely to have a recent CD4 count (within the past 6 months) less than 200/μl (OR=3.94, p=0.001) and previous cryptosporidiosis infection (OR=7.00, p=0.04). Ethnicity, sexual orientation, bactrim use, and comorbidities such as diabetes, cardiac disease, chronic respiratory disease, and cancer were not significant risk factors for MRSA colonization.

Table 1.

Demographic and Clinical Comparisons Between HIV Inpatients with and without Methicillin-Resistant Staphylococcus Aureus at Admission—Univariate Analysis

Characteristic	Cases (n=54)	Controls (n=240)	Odds ratio (95% CI)	p value
Age, median (IQR)	50 (42–58)	45 (39–52)	1.03 (1.01–1.06)	0.01
Gender, male	52 (96.3)	220 (91.7)	2.36 (0.54–10.43)	0.26
Ethnicity
Chinese	46 (85.2)	186 (77.5)	1.67 (0.74–3.75)	0.22
Malay	5 (9.3)	28 (11.7)	0.77 (0.28–2.10)	0.61
Indian	1 (1.9)	12 (5.0)	0.36 (0.05–2.82)	0.33
Other	2 (3.7)	14 (5.8)	0.62 (0.14–2.82)	0.54
Sexual orientation
Heterosexual	33 (61.1)	142 (59.2)	1.08 (0.59–1.99)	0.79
Homosexual	9 (16.7)	35 (14.6)	1.17 (0.53–2.61)	0.70
Bisexual	2 (3.7)	15 (6.3)	0.58 (0.13–2.60)	0.47
Unknown	10 (18.5)	48 (20.0)	0.91 (0.43–1.93)	0.81
Comorbidities
Diabetes	6 (11.1)	23 (9.6)	1.18 (0.46–3.05)	0.73
Cardiac disease	4 (7.4)	21 (8.8)	0.83 (0.27–2.54)	0.75
Chronic respiratory disease	36 (15.0)	13 (24.1)	1.80 (0.88–3.68)	0.11
Liver disease	15 (27.8)	39 (16.3)	1.98 (1.00–3.94)	0.05
Cancer	16 (6.7)	5 (9.3)	1.42 (0.50–4.07)	0.51
Skin disorder	49 (20.4)	11 (20.4)	1.00 (0.48–2.08)	0.99
Intravenous drug use	4 (7.4)	19 (8.0)	0.93 (0.30–2.84)	0.89
Current use of bactrim	27 (50.0)	96 (40.0)	1.50 (0.83–2.71)	0.18
On antiretroviral therapy for past 12 months	35 (64.8)	179 (74.6)	0.63 (0.33–1.18)	0.15
Recent CD4 count <200/μl	47 (87.0)	150 (62.5)	3.94 (1.71–9.09)	0.001
Previous opportunistic infections, ever
Tuberculosis	11 (20.4)	53 (22.1)	0.90 (0.44–1.87)	0.78
Cytomegalovirus	14 (25.9)	39 (16.3)	1.80 (0.90–3.63)	0.10
Toxoplasmosis	3 (5.6)	8 (3.3)	1.71 (0.44–6.65)	0.44
Bacterial pneumonia	3 (5.6)	22 (9.2)	0.58 (0.17–2.02)	0.40
Cryptococcosis	5 (9.3)	14 (5.8)	1.65 (0.57–4.79)	0.36
Cryptosporidiosis	3 (5.6)	2 (0.83)	7.00 (1.14–42.97)	0.04
Pneumoncystis jiroveci pneumonia	30 (55.6)	107 (44.6)	1.55 (0.86–2.81)	0.15
Lymphoma	3 (5.6)	5 (2.1)	2.76 (0.64–11.94)	0.17
Mycobacterium avium	8 (14.8)	39 (16.3)	0.90 (0.39–2.05)	0.80
Herpes simplex virus	11 (20.4)	50 (20.8)	0.97 (0.47–2.02)	0.94

IQR, interquartile range; CI, confidence interval; recent CD4 count, CD4 count within the past 6 months.

All variables with p<0.20 in univariate analysis were incorporated into a multivariate logistic regression model. Age as a continuous variable was significant in multivariate analysis (OR=1.04, 95% CI: 1.01–1.07, p=0.006), as was CD4 count <200/μl within the past 6 months (OR=4.29, 95% CI: 1.83–10.06, p=0.001). When a receiver operating characteristic (ROC) curve was generated for these two variables, the area under the curve was 0.69.

Since we conducted this case-control study retrospectively, its limitations included the lack of information on patient health-seeking behavior and hospitalization history. In a previous study, Onorato et al. found that the presence of a central venous catheter, broad-spectrum antibiotic use, and dermatologic disease were significant risk factors for MRSA colonization or infection among HIV patients.³ Although we did not have data on the former two variables, information on comorbidities and previous opportunistic infections were available but did not yield any significant findings.

From our data, we were unable to conclude if our patients acquired MRSA from the hospital or the community. There are limited data on community-acquired MRSA (CA-MRSA) in Singapore but it has been described as uncommon in previous studies,^4,5 and the prevalence of CA-MRSA in the hospital or community setting has yet to be determined in the local context. A molecular epidemiology study to understand the evolution and distribution of MRSA isolates from CDC patients over a 2-year period is in progress.

In our analysis, age and CD4 count less than 200/μl were independent risk factors for MRSA colonization. This is consistent with results from Asensio et al., who showed that age was a significant predictor of MRSA colonization and infection⁶ and Ramsetty and colleagues, who demonstrated that CD4 count <200/μl was a risk factor for MRSA colonization or infection in HIV patients.⁷ That low CD4 count is a significant risk factor for MRSA colonization is expected, as the immunocompromised status of HIV patients likely renders them more vulnerable to MRSA and other nosocomial pathogens. We combined age and CD4 <200/μl into an ROC curve to test their utility in triaging isolation by differentiating MRSA carriers from noncarriers. Its use is limited, as the likelihood of missing 31% of MRSA carriers may render isolation strategies ineffective. However, a larger sample size may yield more favorable results.

The use of throat and perianal swabs increased the sensitivity of MRSA detection by 11.1% and 9.3%, respectively, among our cohort of HIV inpatients. A recent study detailing universal MRSA screening at CDC showed that the use of an additional throat or perianal swab increased the sensitivity of NAG screening by 12.5% for HIV patients.⁸ In our cohort, the knowledge of patient risk factors was somewhat useful for predicting MRSA colonization, and we found that in addition to the conventional NAG swab, the use of an additional throat or perianal swab improved MRSA detection.

Footnotes

Acknowledgments

This study was supported by the Communicable Disease Centre, Singapore.

Author Disclosure Statement

No competing financial interests exist.

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