Clinical experience with linezolid in the treatment of resistant Gram-positive infections

This study presents our clinical experience with linezolid in 19 patients w ith serious resistant Gram-positive infections enrolled as part of the comp assionate study. In this prospective, nonrandomized, noncomparative study, 19 patients were enrolled as part of the National Compassionate Study Proto col conducted by Pharmacia-Upjohn. At the time of this writing, these patie nts had not been published in the literature. All of the patients had to ha ve documented evidence of serious Gram-positive infections in normally ster ile sites and should have been unable to tolerate available antimicrobial t herapy or be unresponsive to available drugs. Clinical characteristics, lab oratory values, and pharmacokinetic and pharmacodynamic parameters were obt ained. Patients were followed both short-term and long-term after completio n of therapy. Nineteen patients were enrolled: 13 females and 6 males. The average age wa s 63 years. The average length of therapy with linezolid was 22 days, Methi cillin-resistant Staphylococcus aureus (MRSA) was treated in eight patients , methicillin-resistant Staphylococcus epidermidis (MRSE) in two patients, vancomycin-resistant Enterococcus faecium (VREF) in eight patients, and coa gulase-negative Staphylococcus in two patients. Co-infecting organisms incl ude Enterococcus species colonization in six patients, Pseudomonas species in one patient, Serratia marcenens in one patient, and Candida albicans in one patient. Sterile sites that were infected included bone and joint (wounds and septic joints) in six patients, gastrointestinal system (hepatobiliary, liver abs cess, Crohn's) in five patients, genitourinary (kidney and urine) in two pa tients, blood in five patients, respiratory in one patient, and aortic valv e in I patient. Linezolid was given at 600 mg IV every 12 hours with a mean length of therapy of 22 days. Surgical drainage was used in combination wi th linezolid in I I of the patients. Seventy nine percent of these patients achieved clinical and microbiologic cure, and none of the deaths reported in this series were related to the drug. Adverse events included skin rash in one patient, mild bone marrow suppression in two patients, and mild elev ation in liver function tests in two patients. No life-threatening adverse events were noted, It appears that linezolid, along with surgical intervention (when necessary ), appears to be an effective treatment option for resistant Gram-positive infections. Long-term studies evaluating the possible resistance rates are necessary.