Linezolid and inhibitor-protected aminopenicillins to treat foot infections in patients with diabetes mellitus

Foot infections in patients with diabetes mellitus are mainly caused by Gram-positive cocci, many of which are currently resistant to antimicrobials. Since linezolid is active against these pathogens, an open randomized study has been conducted on the efficacy and safety of linezolid administered intravenously and administered orally compared with similar regimens for the use of aminopenicillins protected by an inhibitor (amoxicillin / clavulanate and ampicillin / sulbactam) prescribed in for 7-28 days for patients with diabetes and foot infections.

The study was conducted in 8 countries. The following foot infections have been diagnosed in diabetic patients: cellulitis, paronychia, infected ulcers, deep soft tissue infections, septic arthritis, abscess, osteomyelitis. Prior antibiotic therapy within 72 hours before inclusion, severe limb ischemia and the presence of prostheses were exclusion criteria. Patients were randomized to 3 groups and received linezolid (600 mg every 12 hours iv or orally) or ampicillin / sulbactam (1.5-3 g every 6 hours iv) or amoxicillin / clavulanate (500-875 mg every 8-12 hours indoors). If MRSA is suspected or excreted, treatment of patients receiving beta-lactams may be supplemented with vancomycin. If Gram-negative pathogens were suspected or isolated, treatment of patients in both groups could be supplemented with aztreonam.

The study involved 371 patients, of whom 213 (59%) received outpatient therapy. The average duration of treatment was 17 days. Only 6 patients needed strengthening of vancomycin therapy and 15 patients received additional aztreonam. The clinical recovery rate in the linezolid group was 81%, in the beta-lactam group - 71% (the differences are not statistically significant). Adverse drug reactions were most common in the group of patients receiving linezolid and were represented by diarrhea (8%), nausea (6%), anemia (5%) and thrombocytopenia (4%). The results of clinical efficacy in the nosological and microbiological subgroups are presented in Table 1.

The authors believe that linezolid is at least as effective in treating foot infections in diabetic patients as the inhibitor-protected aminopenicillins.

Comments: This work is the largest published randomized controlled trial for the treatment of foot infections in patients with diabetes mellitus. Indeed, S.aureus is a frequent causative agent of these infections, both independently and in the context of a mixed flora, which determines the interest for treatment with linezolid. There are some difficulties in interpreting the bacteriological results of this study. Coliform bacteria were isolated from 88 patients (24%) and Pseudomonas from 27 (7%), although the isolation of these microorganisms has been largely overlooked due to the frequency of administration of aztreonam. Several previous reports have highlighted the role of anaerobes in this type of infection, but in this work, no cultural study on anaerobes has been carried out, the staining of Gram material, as well as the frequency of purulent discharge, which is also a diagnostic criterion for anaerobic infection has also not been reported. Linezolid is active against many anaerobes, but evidence of clinical efficacy is sparse. Aminopecicillins protected by inhibitors are expected to be very active against anaerobes and most non-nosocomial coliform bacteria. Despite this, the results of treatment with linezolid appear to be more favorable, although the difference is not statistically significant. In the group of patients receiving linezolid, a more frequent development of adverse drug reactions was observed, but all were mild and reversible.