2160. Performance of the Cepheid Rapid PCR Test for Patient Screening and Association with Efficacy of Suvratoxumab, A Novel Anti-Staphylococcus aureus Monoclonal Antibody, During the Phase 2 SAATELLITE study

BACKGROUND: Patients with lower airway Staphylococcus aureus (SA) colonization are at great risk (> 20%) of early-onset ventilator-associated pneumonia (VAP). Thus, a rapid test is required to identify patients at risk. Suvratoxumab (formerly MEDI4893) is a human monoclonal antibody that neutralizes SA alpha toxin. SAATELLITE, a phase 2 study of safety and efficacy of suvratoxumab for reducing the incidence of SA pneumonia (NCT02296320) was conducted and recently completed within the consortium for Combatting Bacterial Resistance in Europe. We investigated the performance of a rapid PCR test (Xpert MRSA/SA SSTI™, Cepheid) as a screening tool during the study and the association between SA load and suvratoxumab efficacy. METHODS: The PCR assay was used to detect SA and methicillin-resistant SA (MRSA) in lower respiratory tract (LRT) samples. Culture was performed on PCR SA+ LRT samples according to local procedures. PCR SA+ subjects were randomized 1:1 to either a single intravenous infusion of 5000 mg suvratoxumab (n = 96) or placebo (n = 100) and followed for 190 days post dose. Efficacy of suvratoxumab was defined as relative risk reduction (RRR) in incidence of SA pneumonia within 30 days post-dose compared with placebo. RESULTS: 299 (41.5%) out of 720 screened subjects were SA+ by PCR. Of 209 subjects with culture data, there were 162 (77.5%) SA+, 47 (22.5%) SA- and 9 (5.6%) MRSA by culture. Culture results could have been affected by antibiotic use and site variability in limits of detection ranging from 3.3 to 100,000 colony-forming units per mL (CFU/mL). No discordance was noted between PCR and culture for MRSA detection. An inverse linear correlation was observed between the PCR cycle threshold (Ct) values for SA protein A gene (spa) and SA CFU/mL counts from quantitative culture. In subjects with low SA load (Ct ≥ 29; n = 72), suvratoxumab provided 66.7% RRR [90% confidence interval (CI): 21.3%, 86.2%] compared with 31.9% RRR [90% CI: -7.5%, 56.8%] in total study population. CONCLUSION: Cepheid Xpert PCR assay was easy to perform, sensitive and standardized, and provided better sensitivity than conventional culture for detection of SA. Additionally, quantitative PCR Ct output was associated with the efficacy of suvratoxumab in reducing SA pneumonia incidence. DISCLOSURES: All authors: No reported disclosures.