850 infection control & hospital epidemiology july 2017, vol. 38, no. 7
method, called exposure density sampling, patients who were selected as controls early in their hospitalization remained eligible to have a positive culture later in their hospitaliza- tion.18 For example, we matched up to 4 patients who had not had a positive culture on or before day 3 to each of the patients who had a positive culture on day 3, and so on, for each day of the hospitalization until day 40. Matching was done using a nearest neighbor matching method. The date of a positive test was assigned as an index date to each patient with a positive test result. The index date for each of the control patients without a positive test was the index date of the patient to whom each was matched. The propensity score was generated using a multivariate logistic regression to model the prob- ability of a positive test using the independent variables listed above. By matching the likelihood of having a positive clinical culture for the antibiotic-resistant organism, important pre- index factors associated with both infection and mortality risk were balanced across patients with and without a positive culture, thus reducing the bias due to measured confounding in our mortality estimates.19 After matching, a log-binomial regression was performed to
examine the association between positive clinical cultures and mortality. The results from these regressions are presented as risk differences, which we define as the attributable mortality rate, as well as risk ratios (RRs).
results Patient Characteristics
Table 1 shows the characteristics of the gram-negative analysis cohort, which included 14,591 control patients, 218 patients with an MDR Acinetobacter HAI, 1,026 patients with an MDR Pseudomonas HAI, and 3,498 patients with an MDR Enter- obacteriaceae HAI. The average age in these groups ranged from 68.1 to 70.3 years. Most of the patients in each group were male (97.0%to 99.1%), and the most frequent races were white (59.6% to 65.8%) and black (17.6% to 18.8%). The patient characteristics of the 12,499 patients without a positive culture and the 3,471 patients with a positive culture included in the MRSA analysis are shown in Table 2. Average age (67.0 vs 67.3), percent male (96.7% vs 96.6%), and race (66.7% vs 67.9%white, 21.5%to 20.2%black) were similar between the 2 groups. As shown in Table 3, of the pathogens examined, the
incidence was highest for positive cultures of MDR Enterobacteriaceae (1.624 per 1,000 patient days at risk; 95% CI: 1.581–1.668) and MRSA (1.516 per 1,000 patient days at risk; 95% CI, 1.480–1.248). Figure 1 shows the attributable mortality rate for both the
30- and 90-day time windows regardless of location (ie, either in hospital or postdischarge). For the 30-day time window, patients with a positive culture for a gram-negative bacteria from a sterile site had a 4.9% (95% CI, 3.7%–6.1%) risk of mortality within 30 days, while those with an MRSA HAI had a
5.9% (95% CI, 4.5%–7.2%) risk of mortality during this time period, respectively. In general, the magnitude of risk for mortality from positive cultures from sterile sites was sub- stantially greater than those from unsterile sites. In addition, among the gram-negative bacteria, MDR Acinetobacter was associated with the largest risk of death. These trends held true for both the 30- and 90-day time windows. The RRs for mortality are shown in Table 4 for both the 30-
and 90-day time windows. For the 30-day time window, the RR was 2.32 (95% CI, 1.85–2.92) for patients with an invasive positive culture for a gram-negative bacterium, while this RR was 1.33 (95% CI, 1.22–1.44) for those with noninvasive positive cultures. For the specific antibiotic-resistant bacteria, patients with MDR Acinetobacter had the highest risk of death (3.34; 95% CI, 1.97–5.66), while the estimate was similar for patients with MDR Pseudomonas aeruginosa (2.08; 95% CI, 1.22–3.56) and MDR Enterobacteriaceae (2.07; 95% CI, 1.64– 2.60) invasive positive cultures. The RRs for death for patients with noninvasive positive cultures were significant for all but MDR Enterobacteriaceae, but they were smaller in magnitude than those for invasive positive cultures. The RR was 2.77 (95% CI, 2.39–3.21) for positive MRSA cultures classified as infections and 1.35 (95% CI, 1.22–1.50) for positive MRSA cultures classified as colonizations by the electronic algorithm. The results were similar for the 90-day time window. Supplemental Tables 2 and 3 show similar results for in-hospital mortality at 30 days, 90 days, and any time. For the most part, the effect estimates were smaller when the mortality time window extended beyond discharge.
discussion
Using a propensity-score matching method, we found that a positive culture for MDR bacteria significantly elevated the 30- and 90-day risk of mortality. This was true for both invasive cultures, which are likely to be true infections, and noninvasive cultures, which may represent infection or colo- nization. The increased mortality effect was significant and substantial across all antibiotic-resistant pathogens studied, with a slightly greater effect among patients with invasive cultures than those with noninvasive cultures. Comparing differences in mortality in this study population, we estimate that 4.9% of patients with anMDR gram-negative and 5.9% of patients with a MRSA infection die within 30 days as a con- sequence of the organism being antibiotic resistant. This attributable mortality increases slightly, to 8.5% and 7.4%, respectively, when patients are followed for 90 days. These results are important because they underscore the mortality burden attributable to antimicrobial-resistant infections and because they provide a baseline that can be used to assess the impact of improvements in infection con- trol, such as methods to improve hand hygiene adherence, improved surveillance and patient isolation techniques, or antimicrobial stewardship programs. Evaluations of the effec- tiveness of these interventions should include economic
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