Occurrence of MRSA endocarditis during linezolid treatment.

Abstract

Linezolid is an antimicrobial agent belonging to a new class of antibiotics: the oxazolidinones. It has been approved for the treatment of infections due to grampositive organisms including methicillin-resistant Staphylococcus aureus (MRSA). We report a case of Staphylococcus aureus endocarditis that occurred in a burn patient during treatment with this new antibiotic, despite full in vitro sensitivity. A previously healthy 38-year-old man was referred to our six-bed burn unit 2 h after self immolation with petrol. At entry, physical examination revealed burns estimated to involve 85% of the total body surface. On day 25, his skin became colonized by MRSA and Pseudomonas aeruginosa. MRSA was also isolated from a central venous catheter 5 days later, and two blood cultures taken on day 34 grew MRSA. At this time, no deterioration of the patient’s clinical status was observed, except for a body temperature of 38 C. Cardiac signs were not noted. As investigational therapy, linezolid was started on day 37, first intravenously, then orally at a dose of 600 mg b.i.d. for 16 days. The minimal inhibitory concentration (MIC) of linezolid was 0.75 g/ml at the beginning of treatment and 1.5 g/ml at the end. On day 3 of treatment, one more blood culture resulted positive for MRSA, while MRSA had disappeared from burn wound samples. The patient showed an initial clinical improvement until the last day of linezolid therapy. While still on therapy, fever recurred. Since a blood culture taken on the last day of linezolid treatment again grew MRSA, intravenous vancomycin was administered. At this time, a cardiac murmur was noted and aortic endocarditis was diagnosed by transesophageal echocardiography. The hemodynamic status of the patient then deteriorated; he had to be intubated and mechanically ventilated, and vasoppressor agents were administered. On day 62 following admission, a surgical valve replacement was performed. During surgery, large vegetations were found on the aortic valve extending as an abscess into the ventricular septum. Culture of the native valve grew linezolidsensitive MRSA. Following surgery, the patient completed 4 weeks of vancomycin therapy. He was discharged from hospital on day 120. Linezolid has inhibitory activity against a broad range of gram-positive bacteria, including MRSA. After oral administration, its bioavailability reaches 100% [1]. Its efficacy for treating gram-positive communityor nosocomial-acquired pneumonia as well as soft tissue infections is established [2]. However, data concerning its role in the treatment of severe infections, like endocarditis, are scarce. There is concern about the bacteriostatic property of linzeolid, especially against Staphylococcus spp. However, a Staphylococcus aureus endocarditis model in rabbits showed good results when linezolid trough levels in plasma remained above the MIC for this organism [3]. In humans, successful treatment of vancomycin-resistant Enterococcus endocarditis was reported with oral linezolid given at a dose of 600 mg b.i.d. [4]. Although resistance of a clinical Staphylococcus aureus isolate to linezolid has been reported previously, this did not occur in the case reported here. The strain of Staphylococcus aureus we isolated remained sensitive to linezolid with an MIC value lower than the accepted breakpoint of 4 g/ml [1]. It must be recognized, however, that burn patients are difficult to treat because the pharmacokinetics of many therapeutic agents become altered. In particular, the dose of many antimicrobial E. H. Ben Mansour · E. Jacob · M. Monchi · D. Ledoux · J.-L. Canivet · P. Damas ()) Department of General Intensive Care, University Hospital, Domaine universitaire du Sart-Tilman, 4000 Liege, Belgium e-mail: pdamas@chu.ulg.ac.be Tel.: +32-4-3667495 Fax: +32-4-3668898