hai mortality—mdr gram-negative bacteria and mrsa 849
literature by examining both in-hospital and overall mortality during these 2 time windows.
methods Study Design and Population
We used a historical cohort design with data from the US Department of Veterans Affairs (VA) system. The VA is the largest integrated healthcare system in the United States, with more than 5 million veterans receiving care annually.12 Our study population was drawn from veterans admitted to a VA hospital at least once between October 1, 2007, and November 30, 2010. Patients could have been hospitalized multiple times
during the time frame of our study, but we included only the first such hospitalization in this analysis. Because our study
was focused on hospital-onset infections that could potentially have been prevented with additional prevention efforts, we excluded patients with a positive culture for MRSA, Acinetobacter, Pseudomonas aeruginosa,or Enterobacteriaceae on admission or during the first 48 hours after admission. Finally,we excluded patientswho died within the first 48 hours after admission and those who did not have at least 365 days of observation in the VA prior to their hospital admission.
Data
The results from microbiology tests performed in the VA are entered into a patient’s electronic medical record in the form of free text. In its original form, this unstructured data cannot be used for statistical analyses. However, our team developed a natural language processing tool to extract information regarding organism, antibiotic susceptibility, and specimen location.13 Mortality was assessed using data from the VA Corporate Data Warehouse (CDW), a national repository for electronic data from several different administrative and clin- ical data sources in the VA. The VA CDW was also the source for patient demographic data. Finally, International Classifica- tion of Disease, Ninth Revision (ICD-9) codes were obtained from VA Medical SAS datasets.
Outcome
The outcome of interest in our study was all-cause mortality. We identified this outcome within several different settings and time frames following the index date (ie, the positive culture for MRSA, Acinetobacter, Pseudomonas aeruginosa,or Enterobacteriaceae): in hospital any time, in hospital within 30 days, in hospital within 90 days, within 30 days regardless of location (in hospital or postdischarge), and within 90 days regardless of location.
Independent Variables
The key independent variable in our analyses was a positive culture for MRSA, Acinetobacter, Pseudomonas aeruginosa,or
Enterobacteriaceae during hospitalization. Using the historical Centers for Disease Control and Prevention (CDC)’s National Healthcare Safety Network (NHSN)’s surveillance definition for hospital-onset infections, we considered positive cultures identified more than 48 hours after hospital admission.14 We considered positive gram-negative cultures to be MDR if they were resistant to 3 or more drug classes. Supplemental Table 1 lists the antibiotics identified in our data as well as the drug classes to which they belong. The positive cultures that we identified may have been evidence of a true infection, or they may have indicated noninfection-related colonization. For gram-negative bacteria, we categorized positive cultures by whether they were invasive or noninvasive based onwhether the site fromwhich they were obtained is typically a sterile site or not. An invasive antibiotic- resistant positive culture was defined as a culture taken from one of the following sterile sites: blood, bone, bone marrow, cerebrospinal fluid, pleural fluid, synovial fluid, and lymph node. Positive cultures from all other sites were considered noninvasive. For patients with both an invasive and non- invasive positive culture, we considered only the invasive cul- ture when the cultures were taken within 7 days of each other. Otherwise, we considered only a patient’s first positive culture. For MRSA, we used a recently published algorithm that
classifies positive MRSA cultures as infections based on site (blood, bone, or device) or if the patient was treated with MRSA-active antimicrobials (vancomycin, daptomycin, line- zolid, clindamycin, doxycycline, and trimethoprim-sulfa- methoxazole) in the 5 days prior to or following the positive culture using electronic data in the VA.15 Using this algorithm, we classified positive cultures as either an MRSA colonization or HAI. Other independent variables in our analyses included demographic characteristics (age, race, marital status, insur- ance status, gender); body mass index (BMI); VA outpatient costs in the 365 days prior to admission; admitting diagnosis; indicator for surgery prior to the index date as well as the type of surgery (abdominal-pelvic; cardiothoracic; head, neck, or brain; orthopedic; or other); number of days in the medical or surgical intensive care unit prior to the index date, indicator for mechanical ventilation; peritoneal dialysis or hemodialysis prior to index date; and comorbidities as measured using a risk index that combines the Charlson and Elixhauser indices.16
Statistical Analysis
Descriptive statistics were used to summarize the baseline demographic and clinical characteristics of patients with and without positive cultures. Covariate balance was evaluated using standardized differences of means, a comparison method that is not influenced by sample size.17 For each patient with a positive culture, up to 4 patients
were selected from the pool of patients who had not had a positive culture up to that point during their hospitalization using a propensity score matching technique. Through this
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