Title:Pre-clinical Impact of the Synergistic Mechanism of Daptomycin and Ceftaroline on Patients with Methicillin-resistant Staphylococcus aureus Bacteremia Infections
Volume: 16
Issue: 4
Author(s): Jennyflore Eliazar, Tevin Johnson and Christiane Chbib*
Affiliation:
- Department of Pharmaceutical Sciences, Larkin University College of Pharmacy, 18301 N. Miami Ave, Miami, FL33169,United States
Keywords:
Daptomycin-ceftaroline synergism, methicillin-resistant Staphylococcus aureus bacteremia infections, infectious
disease, intravenous, pneumonia, cyclic lipopeptide.
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 ± 0.03a log10 CFU/mL, VAN 6.82 ± 0.04a log10
Colony Forming Unit (CFU)/mL, CFT 4.63 ± 0.19a log10 CFU/mL, DAP + CFT 1.15 ± 0.20b log10
CFU/mL, VAN + CFT 3.18 ± 0.49a log10 CFU/mL. (a meaning significantly different than DAP
plus CFT, P< equal to 0.001b 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.
