Background: Clinical trials of new antimicrobials for CRE infections are critical for translating nonclinical findings to patients. While prior studies have examined the characteristics of patients with severe infections due to CRE, most have involved patients from a single geographic region. This study was conducted to examine the characteristics of patients with three common infections associated with CRE (cUTI/AP, HABP/VABP, and bacteremia), and provide an external control patient population for an ongoing phase 3 study of Carbavance (meropenem/RPX7009) in patients with severe CRE infections. To our knowledge, it is the first study to examine differences in characteristics of patients with CRE infection by both geographic region and indication with the goal of informing on clinical trial design.
Methods: A retrospective analysis was conducted at 22 centers in 4 countries (US, UK, Italy and Greece) over a 6 month period. Baseline data, treatment, and outcomes were collected in patients with cUTI, AP, HABP, VABP or bacteremia, due to CRE.
Results: 257 patients were analyzed, of which 76 had cUTI/AP, 41 had HABP/VABP and 140 had bacteremia. The 28-day mortality rate was significantly higher in patients from European sites (Table 1), and was associated with a higher proportion of bacteremia in Europe and a higher proportion of cUTI/AP in the US (Figure 1). On comparison of all cases from the US and Europe, patients from European sites had a longer mean duration of hospitalization prior to CRE infection (29 vs. 15 days) and higher mean APACHE II score (25.3 vs. 17.8) though neither was statistically significant.
Conclusion: Results of this study indicate region-specific differences in the types of infections associated with CRE infections, with associated differences in mortality. These results demonstrate the need to study new agents targeting CRE organisms across multiple indications and regions to best determine efficacy in the eventual target population of patients with known or suspected CRE infections.
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