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[Combination between fosfomycin and oxacillin or cefotaxime against methicillin-resistant Staphylococci and
Abstract:
The resistance of Gram positive cocci to oxacillin and cephalosporins do not appear to be in relation with the synthesis of a beta-lactamase, thus fosfomycin (FOS) could enhance the action of beta-lactam antibiotics by blocking another stage of the peptidoglycan synthesis. When FOS is combined with oxacillin (OXA) or cefotaxime (CTX) against fosfomycin sensitive strains (25 S. aureus 4-16 mg/l, 20 S. epidermidis 2-32 mg/l and 20 Enterococci 16-64 mg/l) one can see a dramatic synergistic effect of these two combinations. Respectively with S. aureus, S. epidermidis and Enterococci, FIC indices are 0.17-0.39 and 0.43 for FOS-OXA and 0.29-0.47 and 0.29 for FOS-CTX. If one considers the CSF concentrations of these three antibiotics, the combination of fosfomycin with oxacillin or cefotaxime may be used in the treatment of meningitis due to methicillin resistant Staphylococci.
Insights
Fosfomycin (FOS) enhances beta-lactam antibiotics like oxacillin (OXA) and cefotaxime (CTX) against Gram-positive cocci. This synergistic effect shows potential for treating meningitis caused by resistant Staphylococci.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Gram-positive cocci resistance to oxacillin and cephalosporins is not linked to beta-lactamase synthesis.
- Fosfomycin (FOS) may enhance beta-lactam action by inhibiting other stages of peptidoglycan synthesis.
Purpose of the Study:
- To investigate the synergistic effects of combining fosfomycin with oxacillin or cefotaxime against Gram-positive cocci.
- To evaluate the potential of these combinations for treating meningitis caused by methicillin-resistant Staphylococci.
Main Methods:
- Tested fosfomycin-sensitive strains of S. aureus, S. epidermidis, and Enterococci.
- Combined fosfomycin with oxacillin (OXA) or cefotaxime (CTX).
- Determined Fractional Inhibitory Concentration (FIC) indices for synergistic effects.
Main Results:
- Significant synergistic effects observed for FOS-OXA and FOS-CTX combinations.
- FIC indices indicated synergy across S. aureus, S. epidermidis, and Enterococci strains.
- Specific FIC ranges: FOS-OXA (0.17-0.39, 0.43) and FOS-CTX (0.29-0.47, 0.29).
Conclusions:
- The combination of fosfomycin with oxacillin or cefotaxime demonstrates significant synergy against Gram-positive cocci.
- Considering CSF concentrations, these combinations hold promise for treating meningitis caused by methicillin-resistant Staphylococci.