Isolate and Patient Characteristics for 300 Veterans who had Staphylococcus aureus bacteremia
at 4 Veterans Affairs Medical Centers, USA, 2004–2008*
Infection Characteristics for 300 Veterans who had Staphylococcus aureus Bacteremia
at 4 Veterans Affairs Medical Centers, USA, 2004–2008
Patient and Infection Characteristics for 300 Veterans with Staphylococcus aureus Bacteremia
and Association with Illicit Drug Use at 4 Veterans Affairs Medical Centers, USA, 2004–2008*
Patient and Infection Characteristics for 300 Veterans with Staphylococcus aureus Bacteremia
and Association with USA300 MRSA at 4 Veterans Affairs Medical Centers, USA, 2004–2008*
Independent Risk Factors for USA300 MRSA Bacteremia
Among 300 Veterans at 4 Veterans Affairs Medical Centers, USA, 2004–2008*
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A multicenter retrospective cohort study was conducted by using patients from the population of veterans enrolled from January 2004 through June 2008 at the Veterans Affairs medical centers (VAMCs) in Baltimore, Maryland; Washington, DC; Buffalo, New York; and Richmond, Virginia. Patients who used illicit drugs were compared with those who did not use illicit drugs with respect to having USA300 MRSA bacteremia vs. bacteremia caused by all other types of S. aureus (this group includes non-USA300 MRSA and methicillin-susceptible S. aureus [MSSA]). Inclusion criteria for patients included in the study were the following: 1) age ≥18 years, 2) enrollment in patient care services at 1 of the 4 VAMCs, 3) a positive blood culture for S. aureus, 4) having first known invasive infection caused by S. aureus, and 5) having a bacterial isolate from the infection available for testing. We excluded patients from the analysis for whom the infection was found to be polymicrobial, or for whom the bacteremic episode was considered to be clinically insignificant (i.e., the patient did not have clinical symptoms consistent with the presence of infection, such as fever).[18] The Institutional Review Boards at all participating sites approved this protocol.
Data were collected from patient electronic medical records, which included administrative coding data. An infection control nurse, who was blinded to the outcome of each patient, conducted chart review by using a standardized form. Illicit drug use was defined by International Classification of Diseases, 9th Revision (ICD-9), codes indicating abuse of or dependence on cocaine (ICD-9 codes: 304.21, 304.20, 304.23, 305.61, 305.62, 305.60) or opioids (ICD-9 codes: 304.01, 304.71, 304.00, 305.51, 304.73), designated at any hospitalization up to 1 year prior to the time of the patient's presentation. The electronic medical record of any patient identified as an illicit drug user was further evaluated to determine whether the abuse was by injection.
An infection was defined as nosocomial if the patient's blood culture was positive for S. aureus >48 hours after hospital admission, if the patient was transferred from another healthcare facility, or if the infection was central-line associated. Infections were defined as central-line associated if a primary source was identified (i.e., no other source of infection could be found) and if the patient had a central line in place for 48 hours before the onset of bacteremia.[19] If the patient had pneumonia, a skin and soft tissue infection, a urinary tract infection, or some other source that could explain the basis for infection, the bacteremia was defined as a secondary infection. Infective endocarditis was defined by using the modified Duke criteria.[20]
Information on risk factors for MRSA acquisition and infection was also obtained. They included whether the patient had been hospitalized, had surgery, resided in a long-term care facility, or had undergone hemodialysis in the year before infection, as well as if any foreign medical device was present at the time of infection or if the patient had been previously colonized or infected with MRSA. The presence of HIV was assessed, as well as the presence of comorbid conditions to calculate each patient's Charlson score.[21]
All S. aureus isolates were sent for testing to the Baltimore VAMC. S. aureus was confirmed by standard mi-crobiologic techniques. Any isolate with growth on oxacillin screen agar was defined as MRSA; any isolate without growth on this agar was defined as MSSA. All S. aureus isolates were screened for the presence of the Panton-Valentine leukocidin gene (PVL; luk-F-PV, luk-S-PV), as previously described.[22] Further screening for the presence 1420 of the arginine catabolic mobile element gene (ACME; arcA) and sequencing of the protein A (spa) gene hypervariable region was also performed on MRSA isolates only, as previously described.[23,24] Patient sequences were compared with sequences found in the Ridom spa Server (www.ridom.de/spaserver).
USA300 MRSA isolates were identified by using an algorithm previously described.[5] Any MRSA isolate that tested positive for the genes for PVL and ACME, and was spa type motif MBQBLO, was classified as USA300 MRSA. These isolates were confirmed as USA300 MRSA by pulsed-field gel electrophoresis (PFGE) by using a 24% random sample (13/55 suspected USA300 MRSA isolates were tested).[11] MRSA isolates that were negative for all 3 genetic factors were classified as non-USA300 MRSA. A 26% random sample of the non-USA300 MRSA isolates was also confirmed by PFGE (27/103 suspected non-USA300 MRSA isolates were tested).[11] All MRSA isolates testing positive for at least 1 of the 3 (PVL, ACME, or spa type motif MBQBLO) were further characterized by PFGE to determine whether any were the USA300 MRSA strain. If pulsed-field type USA300 by PFGE, the isolates were classified as USA300 MRSA. All other MRSA isolates (non-USA300 MRSA) and MSSA isolates were classified as "all other S. aureus" The Fingerprinting II software was used to analyze the electronic images of the gels (Bio-Rad Laboratories, Hercules, CA, USA). The banding patterns of each isolate were compared with the USA PFGE types described by McDougal et al.;[11] the similarity between isolates was assessed by using the criteria established by Tenover et al.[25]
Data were analyzed by using the SAS statistical software package, version 9.1 (SAS Institute Inc., Cary, NC, USA). The Pearson χ2 or Fisher exact tests were used to compare categorical variables, and the Student t test or Wilcoxon signed-rank test was used to compare continuous variables. A p value ≤0.05 was considered significant. Unadjusted relative risks (RR) were calculated to estimate the association between illicit drug use and USA300 MRSA bacteremia. Stratified analyses were conducted to test for effect modification and confounding; any variable with a Breslow-Day p value ≤0.05 was considered significant, while a 10% difference between the unadjusted and adjusted RR was used to identify confounding. A binomial regression using a log link was fit to estimate the association between illicit drug use and USA300 MRSA bacteremia, adjusting for identified confounders and/or effect modifiers.