Positive antibiotic interactions for MRSA bacteraemia tied to lower 14-day mortality

Patients with positive in-vitro antibiotic interactions with vancomycin or daptomycin plus an antistaphylococcal β-lactam for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia appear to have greater survival at 2 weeks, as shown in a post hoc analysis of the CAMERA-2* study.

“The CAMERA-2 study revealed that augmenting treatment (vancomycin or daptomycin) with antistaphylococcal β-lactam did not show significant improvements in … 90-day mortality, persistent bacteraemia at day 5, microbiological relapse, or microbiological treatment failure,” said co-author ALH Kwa from Singapore General Hospital, Singapore, who presented the study at ESCMID Global Congress 2024.

“As the interaction between antibiotics is bacterial strain-specific, it is not known if positive interactions observed with vancomycin or daptomycin combined with such β-lactam may improve clinical outcomes in MRSA infections,” Kwa added.

To address this knowledge gap, a post hoc analysis was conducted. Patients from the CAMERA-2 combination arm were grouped into either “positive interactions” (synergy or additivity) or “negative interactions” (antagonism or indifference).

Kwa and colleagues then carried out synergy testing through microdilution broth checkerboard assay using the mean fractional inhibitory concentration method to examine the interaction of the combined antibiotic therapy.  

Finally, the authors compared all-cause mortality at days 14, 42, and 90; microbiological treatment failure; and microbiological relapse (primary composite endpoint), as well as persistent bacteraemia at days 2 and 5 (secondary endpoint), between the positive- and negative-interaction groups.

A total of 352 patients participated in the study, of whom 174 were randomly assigned to receive the combination therapy. Twenty-four patients with no available bacterial isolate or missing outcome data were excluded, and the remaining 150 (86.2 percent) were included in the post hoc analysis. [ESCMID Global 2024, abstract O0811]

Demographic data, such as age (mean age 63 and 65 years, respectively) and sex (males: 70.2 percent and 68.9 percent, respectively), did not significantly differ between the positive- and negative-interaction groups. Except for 14-day all-cause mortality, the primary and secondary endpoints did not differ as well between the two groups.

The number of patients who survived at day 14 was significantly higher in the positive-interaction group than in the negative-interaction group (100/103 vs 41/47 participants; p=0.027).

For all-cause mortality at day 42, the proportion of survivors was 91 of 103 in the positive-interaction group and 39 of 47 in the negative-interaction group (p=0.439). At day 90, 85 patients in the positive-interaction group and 36 in the negative-interaction group remained alive (p=0.394).

After adjusting for Charlson’s Comorbidity Index, Pitt bacteraemia score, and sequential organ failure assessment (SOFA) score, the protective benefit of the combined antibiotic therapy against all-cause death at day 14 persisted among patients in the positive-interaction arm (adjusted hazard ratio, 0.23, 95 percent confidence interval, 0.06‒0.94).

“Positive in-vitro antibiotic-interaction testing between vancomycin or daptomycin with an antistaphylococcal β-lactam for MRSA bacteraemia was associated with lower 14-day all-cause mortality,” according to Kwa and colleagues.

*Combination Antibiotic for MRSA