Cefotaxime in combination with other antibiotics for the treatment of severe methicillin-resistant staphylococcal infections

Abstract

Methicillin-resistant staphylococci (M-R staphylococci) represent 30% of the staphylococcal strains isolated in our hospital and pose important therapeutic problems. In a preliminary in vitro checkerboard study the bactericidal effect of various cephalosporins (cephalothin, cefamandole, cefotaxime and cefoperazone) in combination with other antibiotics (netilmicin, amikacin, vancomycin and fosfomycin) was studied on ten M-R staphylococcal strains. The combinations of cefoperazone with amikacin, cephalothin with vancomycin and of the four cephalosporins with fosfomycin were synergistic on the ten strains (FBC indexes less than or equal to 0.75). According to the CSF and bone levels achieved by these antibiotics and their bactericidal concentrations in combination, the combination of cefotaxime and fosfomycin was the most interesting, a concentration of less than or equal to 2 mg/l cefotaxime being bactericidal on five homogeneous M-R Staphylococcus aureus when combined with 4 mg/l of fosfomycin. This combination of cefotaxime (25 mg/kg, i.v. infusion over 30 min) and fosfomycin (50 mg/kg, i.v. infusion over three hours) three to four times daily was used to treat 16 patients: three patients with meningitis, six with bone and joint infections and seven with persistent bacteremia. The FBC indexes were less than or equal to 0.625 for the 12 strains studied. All the patients were cured without relapses. The concentrations of cefotaxime, desacetyl cefotaxime and fosfomycin in the CSF during meningitis three hours after the end of the infusion on the second day of treatment were 8.76, 6.82 and 58.0 mg/l, respectively, for patient one and 2.0, 0.53 and 31.0 mg/l, respectively, for patient two.(ABSTRACT TRUNCATED AT 250 WORDS)