SEVERE METICILLIN-RESISTANT STAPHYLOCOCCU S-AUREUS INFECTIONS - EMERGENCE OF RESISTANCE TO FUCIDIC ACID OR FOSFOMYCIN IN PATIENTS GIVEN CONTINUOUS-INFUSION OF VANCOMYCIN

OBJECTIVES: To evaluate the development of resistance to fosfomycin or fucidic acid in severe infections caused by metecillin-resistant Slap hylococcus aureus (MRSA) and to assess the relationship with serum lev els of vancomycin. METHODS: A retrospective study was performed in pat ients hospitalied in our intensive care unit during a 3-year period (1 993-1995) who were treated for severe MRSA infection with continuous i nfusion vacomycin and fosfomycin or fucidic acid. We analyzed the deve lopment of resistance and serum levels of vancomycin. RESULTS: During this period, only 20 patients received continuous infusion vancomycin plus fucidic acid or fosfomycin. MSRA resistant to fucidic or fosfomyc in developed in 9. Vancomycin serum levels were significantly lower in patients who developed resistance to focidic acid or fosfomycin, both during the first 5 days of treatment (16.68 +/- 1.07 mu g/ml vs. 22.6 4 +/- 1.05 mg/ml, p < 0.01) and throughout treatment duration (17.29 /- 1.07 mu g/ml vs. 21.85 +/- 0.78 mu g/ml, p < 0.01). CONCLUSlON: Our findings confirm that in spite of continuous vancomycin infusion at a n initial rate of 2 g/24 h, Staphylococcus aureus resistance to fosfom ycin or fucidic acid an develop during ongoing treatment. Vancomycin l evels of at least 20 mu g/ml should be obtained as rapidly as possible .