Methicillin-Resistant Staphylococcus aureus ...

infection control and hospital epidemiology

january 2009, vol. 30, no. 1

concise communication

Methicillin-Resistant Staphylococcus aureus Bacteremia in Patients With End-Stage Renal Disease in Taiwan: Distinguishing Between CommunityAssociated and Healthcare-Associated Strains Chung-Chih Lin, MD; Jiun-Ling Wang, MD; Chi-Ying Lin, MD; Shey-Ying Chen, MD; Jann-Tay Wang, MD; Kwan-Dun Wu, MD, PhD; Shan-Chwen Chang, MD, PhD We reviewed genotyping and medical records of 53 patients with endstage renal disease and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in a medical center in Taiwan. In multivariate analysis, hospitalization within the previous year was independently negatively associated with infection with community-associated MRSA strains, and an increased number of years of dialysis predicted the recovery of patients infected with community-associated MRSA strains. Infect Control Hosp Epidemiol 2009; 30:000-000

Because of the introduction of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains to patients with healthcare-associated MRSA (HA-MRSA) infections, defining CA-MRSA infection by the absence of certain risk factors has led to an underestimate of its true burden.1–4 The incidence of invasive MRSA infection among patients undergoing dialysis was reported as 45.2 cases per 1,000 population.5 A recent literature review found that few articles have studied the CA-MRSA strains that are responsible for infection of patients undergoing dialysis.4 Johnson et al.4 concluded that patients infected with CA-MRSA strains and patients infected with HA-MRSA strains had similar demographic characteristics and outcomes. However, the small number of patients in that study makes it difficult to compare CA-MRSA strains with HA-MRSA strains for infected patients undergoing dialysis.4 In the present study, we used genotyping to classify isolates as community associated or healthcare associated among adult patients with MRSA bacteremia who were undergoing dialysis. Then we compared the patients’ demographic characteristics and clinical manifestations, to identify risk factors for infection with community-associated or healthcare-associated strains, and we compared the patients’ clinical outcomes.

methods This study was performed at the National Taiwan University Hospital (Taipei, Taiwan). CA-MRSA infection was defined as illness compatible with staphylococcal disease in which MRSA was recovered from culture of specimens obtained from the site of infection in an outpatient setting or less than 48 hours after hospital admission and that occurred in a patient who had none of the following healthcare-associated risk factors: hospitalization, surgery, dialysis, or residence in a long-term-care facility within the year before illness onset; a permanent indwelling catheter or percutaneous medical device; or a previous culture result that was positive for MRSA.1 We used a hospital database about HA-MRSA bacteremia to identify patients with end-stage renal disease who were receiving dialysis and had MRSA bacteremia at any time between July 1, 2005, and February 1, 2008. All patients were evaluated using a structured recording form. Medical records were evaluated for healthcare-associated risk factor for MRSA infection, clinical course of infection, and infection foci of bacteremia. The identification of infection focus was based on clinical, bacteriological, and radiological investigations. The presence of the Panton-Valentine leukocidin gene (PVL) lukF-lukS and the SCCmec elements (types I–V) were determined according to methods described elsewhere.6–8 We classified an MRSA isolate as belonging to a CA-MRSA strain if the SCCmec type IV or type V was present and as belonging to an HA-MRSA strain if the SCCmec type II or type III was present. The x2 test or Fisher exact test was used for univariate analysis of categorical variables and for multivariate analysis of logistical regressions. Data were analyzed with SPSS software, version 15.0 (SPSS), for Windows.

results From July 1, 2005, through February 1, 2008, we identified 53 consecutive adult patients with end-stage renal disease and MRSA bacteremia (Table 1). Each MRSA isolate was from a unique bacteremic patient. Of 53 MRSA isolates, 3 (5.7%) were SCCmec type II, 39 (73.6%) were SCCmec type III, 7 (13.2%) were SCCmec type IV, and 4 (7.5%) were SCCmec type V. In the 42 patients (79.2%) infected with a healthcareassociated strain, 22 (52.4%) had onset of infection in the community and 20 (47.6%) had onset of infection in the hospital. In the 11 patients (20.8%) infected with a community-associated strain, 6 (54.5%) had onset in the community and 5 (45.5%) had onset in the hospital. Table 1 compares comorbidities of patients infected with

000



table 1. Demographic and Clinical Characteristics of Patients With End-Stage Renal Disease Who Were Infected With Healthcare-Associated Methicillin-Resistant Staphylococcus aureus (HAMRSA) or Community-Associated Methicillin-Resistant S. aureus (CA-MRSA) Strains Patient group Variable Male sex Age, mean years Ⳳ SD Age 165 years Hospital onseta ICU onsetb Time of index culture after hospital admission, days Comorbid condition Diabetes mellitus Cancer Cirrhosis Congestive heart failure Cardiovascular disease Bedridden status Previous steroid use Nursing home resident Recent surgery Recent hospital admission Charlson score 16 Duration of dialysis, years Mean Ⳳ SD Median (interquartile range) Modality of dialysis Peritoneal dialysis Hemodialysis

HA-MRSA (n p 42)

CA-MRSA (n p 11)

All (n p 53)

Univariate P value

16 (38.1) 70.1 Ⳳ 13.2 32 (76.2) 20 (47.6) 17 (40.5)

4 (36.4) 66.5 Ⳳ 11.6 8 (72.7) 5 (45.5) 2 (18.2)

20 (37.7) 69.3 Ⳳ 12.8 40 (75.5) 25 (47.2) 19 (35.8)

1.999

27.36 Ⳳ 66.58

6.36 Ⳳ 7.71

23.00 Ⳳ 59.8

.126

30 8 6 13 30 22 6 18 12 40 21

(71.4) (19.0) (14.3) (31.0) (71.4) (52.4) (14.3) (42.9) (28.6) (95.2) (50.0)

1.47 Ⳳ 1.72 0.8 (0.4–1.9) 1 (2.4) 41 (97.6)

5 2 0 2 2 2 2 1 0 5 2

(45.5) (18.2) (0) (18.2) (18.2) (18.2) (18.2) (9.1) (0) (45.5) (18.2)

5.48 Ⳳ 5.97 3.3 (1–14.4) 2 (18.2) 9 (81.8)

35 10 6 15 32 24 8 19 12 45 23

(66.0) (18.9) (11.3) (28.3) (60.4) (45.3) (15.1) (35.8) (22.6) (84.9) (43.4)

2.31 Ⳳ 3.44 1.0 (0.5–2.3) 3 (5.7) 50 (94.3)

.422 1.999 1.999

.290

.154 1.999

.324 .482 .004 .043 .665 .074 .052 !.001 .089 !.001

.106 .106

note. a b

Data are no. (%) of patients, unless otherwise indicated. ICU, intensive care unit. More than 72 hours in the hospital before detection of MRSA bacteremia. Admission to ICU more than 72 hours before detection of MRSA bacteremia.

HA-MRSA and patients infected with CA-MRSA strains. Univariate analysis indicated that patients infected with HAMRSA strains were more likely to have cardiovascular disease, bedridden status, and a history of hospitalization in the year preceding a positive culture result (P ! .05). Patients infected with CA-MRSA strains were more likely to have been undergoing dialysis for a long time (mean Ⳳ SD, 5.48 Ⳳ 5.97; median, 3.3 years; P ! .001). Infection with HA-MRSA strains had a stronger association with septic shock status at the initial stage of bacteremia, compared with infection with CAMRSA strains (P p .001). No HA-MRSA isolates carried the PVL gene; 3 (27.3%) of 11 CA-MRSA isolates carried the PVL gene. For infection focus, there was no statistically significant difference between the 2 groups (Table 2). Multivariate analysis (Table 3) indicated that hospital admission within the previous year (odds ratio, 0.042 [95% confidence interval, 0.007–0.265]) was an independent factor negatively associated with CA-MRSA infection and that an increased number of years of dialysis (odds ratio, 1.375 [95% confidence interval, 1.059–1.785]) was the only independent

factor associated with the presence bacteremia due to CAMRSA–related strains. The 7- and 30-day mortality rates associated with infection with HA-MRSA strains and infection with CA-MRSA were no different (Table 2). The length of hospital stay (Ⳳ standard deviation) after the index culture indicating MRSA bacteremia was 30.8 Ⳳ 25.5 days for patients infected with HAMRSA strains and was 18.1 Ⳳ 12.4 days for patients infected with CA-MRSA strains (P p .116). After adjustment for age, sex, and underlying comorbidities, infection with CA-MRSA strains was not associated with mortality rates that were higher than for infection with HA-MRSA strains (hazard ratio, 0.41; 95% confidence interval, 0.56–3.011; P p .381).

discussion Infection with strains of MRSA that are traditionally considered to be community-associated strains is more frequently diagnosed in healthcare institutions and among dialysis-de-

mrsa bacteremia in patients undergoing dialysis

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table 2. Infection Focus and Outcome for Patients With Healthcare-Associated Methicillin-Resistant Staphylococcus aureus (HA-MRSA) and Patients With Community-Associated Methicillin-Resistant S. aureus (CAMRSA) Patient group HA-MRSA (n p 42)

Variable PVL gene detected by PCR Infectious signs and symptoms at hospital admission Fever Shockb Infection focus Primary bacteremia Skin and soft tissue Nonvascular access catheter–related infection Surgical site or prosthesis related Pneumonia Infective endocarditis Septic arthritis and/or osteomyelitis Empirical glycopeptide therapy X48 hours after hospitalization Outcome Length of hospital stay after onset of MRSA bacteremia, mean Ⳳ SD, days Persistent bacteremia after 7 days of treatment Death within 7 days after onset of MRSA bacteremia Death within 30 days after onset of MRSA bacteremia

CA-MRSA (n p 11)

P

3 (27.3)

3 (5.7)

.007

10 (90.9) 0 (0)

43 (81.1) 22 (41.5)

.667 .001

a

0 (0) 33 (78.6) 22 (52.4) 2 4 5 6 10 2 2

All (n p 53)

(4.8) (9.5) (11.9) (14.3) (23.8) (4.8) (4.8)

2 0 2 1 3 0 0

(18.2) (0) (18.2) (9.1) (27.3) (0) (0)

4 4 7 7 13 2 2

(7.5) (7.5) (13.2) (13.2) (24.5) (3.8) (3.8)

.187 .569 .626 1.999 1.999 1.999 1.999

31 (73.8)

9 (81.8)

40 (75.5)

.711

30.8 Ⳳ 25.5 6 (14.3) 6 (14.3) 10 (23.8)

18.1 Ⳳ 12.4 0 (0) 0 (0) 2 (18.2)

28.2 Ⳳ 23.8 6 (11.3) 6 (11.3) 12 (22.6)

.116 .324 .324 1.999

note. a b

Data are no. (%) of patients, unless otherwise indicated. PCR, polymerase chain reaction; SD, standard deviation. All the PVL-positive strains of CA-MRSA were SCCmec type V. Septic shock was defined as systolic blood pressure !90 mm Hg, despite adequate fluid resuscitation.

pendent patients.2–4 In our study, 20% of patients with endstage renal disease and MRSA bacteremia were infected with community-associated strains. This is similar to the results of the ABC (Active Bacterial Core) surveillance system of invasive MRSA infection, which showed that 14% of 126 MRSA isolates were community-associated strains.5 The predominant HA-MRSA clones in Taiwan were SCCmec type III, not SCCmec type II, which is predominant in the United

States.7 In our institution during 2006, the distribution of HA-MRSA isolates, by SCCmec type, was 20% SCCmec type II, 57% SCCmec type III, 12% SCCmec type IV, and 11% SCCmec type V (authors’ unpublished data). A recent study by David et al.3 concluded that association with the healthcare environment has little predictive value for distinguishing patients with infection due to multidrugresistant MRSA from patients with infection due to CA-

table 3. Results of Univariate and Multivariate Logistic Regression Analyses of Factors Associated With Infection With Community-Associated Methicillin-Resistant Staphylococcus aureus Odds ratio (95% confidence interval) Variable Diabetes mellitus Cardiovascular disease Bedridden status Nursing home resident Greater duration, in years, of dialysis Charlson score 16 Greater time, in days, to index culture result after hospital admission Hospital admission 1 year before onset Modality of peritoneal dialysis

Univariate analysis 0.333 0.089 0.202 0.133 1.367 0.222

(0.085–1.302) (0.017–0.473) (0.039–1.049) (0.016–1.138) (1.064–1.756) (0.043–1.154)

0.966 (0.916–1.018) 0.042 (0.007–0.265) 9.111 (0.743–111.724)

Multivariate analysis

1.375 (1.059–1.785)

0.042 (0.007–0.265)

000



MRSA isolates. Our study, which used the SCCmec type to identify CA-MRSA strains, showed that a history of hospitalization in the year before a positive culture result independently predicted the presence of HA-MRSA (compared with CA-MRSA) in patients with MRSA bacteremia who were undergoing dialysis. Our study also showed that, for patients with MRSA bacteremia who were undergoing dialysis, a longer duration of dialysis was associated with the presence of community-associated strains. There are few data available about the relationship between duration of dialysis and the presence of different classes of strains of staphylococcal bacteremia. Greiner et al.9 showed that the mean duration of dialysis for patients with community-acquired S. aureus bacteremia (3.6 years) was longer than for those with nosocomial S. aureus bacteremia (2.1 years). Another study, by Reed et al.,10 that compared patients with methicillin-susceptible S. aureus bacteremia and patients with MRSA bacteremia showed that patients with methicillin-susceptible S. aureus bacteremia were undergoing dialysis for a longer period (2.2 years vs. 1.5 years). A limitation of our study is that some differences between patients infected with CA-MRSA strains and patients infected with HA-MRSA strains may have gone undetected in our limited sample. In addition, because our study was conducted in Taiwan, the different genotypes of CA-MRSA that we identified may not apply to bacteremia in other geographic regions. The predominant CA-MRSA clones in Taiwan included SCCmec type IV–PVL-negative and SCCmec type V– PVL-positive strains.8 In conclusion, our study of 53 patients with MRSA bacteremia and end-stage renal disease identified factors associated with CA-MRSA and HA-MRSA strains. Hospitalization within the previous year independently predicted the presence of HA strains, and longer time of dialysis predicted the presence of CA-MRSA strains.

acknowledgments Financial support. National Science Council in Taiwan (grant NSC-96-2314B-002-031). Potential conflicts of interest. All authors report no conflicts of interest relevant to this article.

From the Departments of Internal Medicine (C.-C.L., J.-L.W., C.-Y.L., J.T.W., K.-D.W., S.-C.C.) and Emergency Medicine (S.-Y.C), National Taiwan University Hospital, the Section of Nephrology, Department of Internal Med-

icine, China Medical University Hospital (C.-C.L.), and the Department of Internal Medicine, E-Da Hospital/I-Shou University (J.-L.W.), Taipei, Taiwan. C.-C.L. and J.-L.W. contributed equally to this work. Address reprint requests to Shan-Chwen Chang, Section of Infectious Disease, Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei 100, Taiwan ([email protected]), or Kwan-Dun Wu, Section of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei 100, Taiwan ([email protected]). Received July 14, 2008; accepted September 4, 2008; electronically published December 1, 2008. 䉷 2008 by The Society for Healthcare Epidemiology of America. All rights reserved. 0899-823X/2009/3001-00XX$15.00. DOI: 10.1086/593122

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