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IMIPENEM-CILASTATIN TREATMENT OF OSTEO-ARTICULAR INFECTIONS CAUSED BY MULTIRESISTANT GRAM NEGATIVE RODS



Abstract

Introduction: The emergence of multidrug resistant Gram negative bacilli susceptible to hardly any beta lactam compound has led to infections close to a therapeutic dead end. In such circumstances, Imipenem-cilastatin (I-C) is often the only remaining therapeutic option. We report our experience with the prolonged administration of high-doses of I-C in the treatment of osteoarticular infections with bacteria resistant to other beta-lactam agents (or 4l generation cephalosporins in 14 cases).

Materials and methods: Our retrospective study over 7 years included 29 patients with septic arthritis (n=3) continuous osteitis (n=6), septic non-union(n=12) and prosthetic joint infections (n=8). Treatment included an extensive surgical debridement and post-operative combination antibiotherapy with intravenous I-C and aminoside (54%) and/or fluoroquinolones (46%) and/or fosfomycin (29%). Associated microorganisms requiring yet additional antimicrobial agents were associated in 17 (59%) cases. I-C was maintained for an average of 46 days (extremes 21–90), at an average dose of 3,8g/day (extremes 2–6). The bacteria warranting I-C were cephalosporinase hyperproducing Enterobacter cloacae (38%), extended spectrum beta-lactamases producing enterobacteria (31%), Pseudomonas aeruginosa (21%) and/or Acinetobacter baumanii (21%).

Results: Early outcome was favorable in 24 patients (82%). Two patients relapsed with the bacteria requiring I-C. Three failed to negate succion fluid cultures : one was discharged with no change in his condition, one agreed to a leg amputation and the third died of candidemic septic shock in SICU with drainage fluid still bactériologie ally positive. Repeated secondary colonization and systemic infection with yeasts led to a monitoring of yeast load. Per os amphotencin B and immediate treatment of urinary colonization prevented further systemic dissemination of candical infections. No other tolerance incidents were noted. Acquired resistance occurred only once in a P. aeruginosa isolate while Imipenem-cilastatin was chosen to cover an ESBL producing Escherichia coli. Secondary treatment with ceftazidime was then successful in eradicating P. aeruginosa.

Conclusion: I-C has been widely used for the treatment of mixed flora infections as a wide spectrum antibiotic.

We report good tolerance of high posology long term administration in documented osteoarticular indications if yeast colonization is properly monitored, and eradication rates are comparable to those reported in infections with susceptible bacteria.

The abstracts were prepared by editorial secretary, Mrs K. Papastefanou. Correspondence should be addressed to Professor K.N. Malizos, Department of Orthopaedic Surgery, School of Medicine, University of Thessalia, Larissa, 41222 GREECE