Add on Exebacase to antibiotics Falls Short in Treating MRSA Bacteremia, reveals study

• Clinical response rates at Day 14 in the MRSA population were 50.0% for exebacase + antibiotics vs. 60.6% for antibiotics alone, with no statistically significant difference (P = 0.392).

• Notably, adverse events were similar across groups, and no hypersensitivity events related to exebacase were reported.

The DISRUPT study's unexpected outcome challenges the promising phase 2 data that demonstrated the potential of exebacase + antibiotics in MRSA bacteremia/endocarditis. The higher-than-expected clinical response rate in the antibiotics alone group further complicates the interpretation. Heterogeneity within the study population and the relatively small sample size might have contributed to imbalances in Day 14 clinical outcomes. These results emphasize the complexity of studying S. aureus bacteremia/endocarditis and provide crucial lessons for future research in this field.

The DISRUPT study highlights the need for caution in interpreting phase 2 data, emphasizing the importance of large, well-designed phase 3 trials. Future studies in S. aureus bacteremia/endocarditis should carefully consider population heterogeneity and adequately power the study to minimize the risk of imbalances in outcomes.

Reference:

Fowler, V. G., Das, A. F., Lipka-Diamond, J., Ambler, J. E., Schuch, R., Pomerantz, R., Cassino, C., Jáuregui-Peredo, L., Moran, G. J., Rupp, M. E., Lachiewicz, A. M., Kuti, J. L., Wise, R. A., Kaye, K. S., Zervos, M. J., & Nichols, W. G. Exebacase in addition to standard-of-care antibiotics for staphylococcus aureus bloodstream infections and right-sided infective endocarditis: A phase 3, superiority-design, placebo-controlled, randomized clinical trial (DISRUPT). Clinical Infectious Diseases,2024;ciae043. https://doi.org/10.1093/cid/ciae043