Pre-clinical Impact of the Synergistic Mechanism of Daptomycin and Ceftaroline on Patients with Methicillin-resistant Staphylococcus aureus Bacteremia Infections

Abstract

Background: Our study aims at assessing the pre-clinical impact of the synergistic mechanism of Daptomycin (DAP) and Ceftaroline (CFT) on patients with Methicillin-Resistant Staphylococcus aureus Bacteremia infections (MRSAB).

Methods: A systematic overview was conducted by searching PubMed, Oxford academic, and Cochrane library up to June 2020.

Study selection and data extraction: All English- language clinical trials, in vitro studies, and case reports related to the synergistic drug therapy for MRSAB.

Results: In the case of MRSAB infections, we examined two different in vitro studies that showed effective synergism with DAP and CFT. The Minimum Inhibitory Concentration (MIC) range observed for each is as follow: DAP 0.125-1 mg/L, CFT 0.38-1 mg/L, DAP + CFT 0.094-0.5 mg/L, vancomycin (VAN) 0.75-2 mg/L, VAN + CFT 0.25-2 mg/L. DAP + CFT combination displayed the most efficacy with the lowest MIC. The statistical analysis performed showed that DAP + CFT obtained significantly lower fractional inhibitory concentration (FIC) values (0.941 ± 0.328) compared with VAN + CFT. In vitro activities of regimens tested on DAP non-susceptibility and VAN intermediate after 96 hours showed DAP 8.29 ± 0.03^a log₁₀ CFU/mL, VAN 6.82 ± 0.04^a log₁₀ Colony Forming Unit (CFU)/mL, CFT 4.63 ± 0.19^a log₁₀ CFU/mL, DAP + CFT 1.15 ± 0.20^b log₁₀ CFU/mL, VAN + CFT 3.18 ± 0.49^a log₁₀ CFU/mL. (^a meaning significantly different than DAP plus CFT, P< equal to 0.001^b meaning therapeutic enhancement combination was defined as ≥ 2 log₁₀ CFU/ml reduction over the most active single agent). Based on these results, although DAP was not susceptible, the Colony Forming Unit (CFU) for DAP and CFT had the best therapeutic results.

Conclusion: In vitro studies have shown that a combination DAP and CFT is more efficacious than the combination of VAN and CFT in MRSA bacteremia infections. The synergic effects of DAP (bactericidal) and CFT (bactericidal) is statistically significant, in recent trials, warranting promising evidence for its use in complicated bacteremia infection.

Keywords: Daptomycin-ceftaroline synergism; cyclic lipopeptide.; infectious disease; intravenous; methicillin-resistant Staphylococcus aureus bacteremia infections; pneumonia.