Successful treatment with linezolid of septic shock secondary to methicillin-resistant Staphylococcus aureus arthritis

D. De Bels1,*, A. Garcia-Filoso1, M. Jeanmaire2, T. Préseau2, Y. Miendje3 and J. Devriendt1

1 Intensive Care Department, Brugmann University Hospital, Free University of Brussels, Place Van Gehuchten 4, 1020 Brussels, Belgium; 2 Internal Medicine Department, Brugmann University Hospital, Free University of Brussels, Place Van Gehuchten 4, 1020 Brussels, Belgium; 3 Department of Microbiology, Brugmann University Hospital, Free University of Brussels, Place Van Gehuchten 4, 1020 Brussels, Belgium


* Corresponding author. Tel: +32-2-477-92-93; Fax: +32-2-477-92-94; Email: david.debels{at}chu-brugmann.be

Keywords: oxazolidinones , MRSA , septic arthritis

Sir,

Bacterial sepsis is a major cause of death in the intensive care unit. The growing prevalence of multiresistant strains amongst the involved pathogens is a matter for serious concern, as it drastically limits the number of potentially useful antibiotics. Until recently, the glycopeptides were the sole antibiotics with consistent activity to manage methicillin-resistant Staphylococcus aureus (MRSA) infections, leaving few or no alternatives in case of treatment failure. New antimicrobials have been developed, which now offer an alternative. One of these is linezolid, the first in the new class of oxazolidinone antibiotics. Linezolid exhibits in vitro activity against all medically important Gram-positive organisms, including the staphylococci. Its mode of action is unique in that it blocks protein synthesis at the very first stage of the process, by preventing formation of the initiation complex.1 Its activity is not affected by resistance to other classes of antibiotics, and it is therefore equally potent against methicillin-resistant as it is against methicillin-susceptible staphylococci. We used linezolid successfully to treat a patient with septic shock secondary to MRSA arthritis after treatment failure with vancomycin.

An 85-year-old man was admitted to our hospital with left shoulder pain. He had a history of congestive heart failure, arterial hypertension, non-insulin-dependent diabetes mellitus and chronic obstructive pulmonary disease. Clinical examination showed a warm, red and swollen left shoulder, from which pus was extracted by direct puncture. Culture of the pus yielded Staphylococcus aureus resistant to oxacillin (NCCLS standardized disc test). Blood cultures too were positive, with a similar strain of MRSA as suggested by the antibiogram. Susceptibility of the MRSA isolate to vancomycin was 2 mg/L. The patient underwent a first surgical intervention with lavage and drainage of his shoulder joint, and intravenous vancomycin 1 g every 12 h was started. Vancomycin blood levels were monitored and vancomycin dosing adjusted accordingly to achieve trough concentrations above 8 mg/L. Fever persisted, with daily blood cultures remaining positive for MRSA. Renewed surgical lavage of the affected joint was therefore performed on the 10th day of treatment, but was complicated by a cardiac arrest associated with vasodilation and severe hypovolaemia. The patient was resuscitated but subsequently developed septic shock, for which he was transferred to intensive care. He required ventilator support as well as inotropic and vasopressive support, guided by a Swan–Ganz catheter. Right heart catheterization showed an elevated cardiac index with low peripheral resistance compatible with septic shock. Activated protein C was given according to the Prowess protocol. The patient developed acute renal failure and continuous venovenous haemodiafiltration (CVVHDF) was started. At this time, vancomycin was replaced with intravenous linezolid at the regular dosing scheme of 600 mg every 12 h.2 Sixty minutes after administration of the fourth dose, linezolid levels of 6.9 mg/L and 9.3 mg/L were measured (Regional Antimicrobial Reference Laboratory, Bristol, UK) in synovial fluid and serum, respectively, i.e. levels well in excess of 2 mg/L, the MIC of linezolid (Etest; AB Biodisk, Solna, Sweden) for the infecting MRSA. The condition of the patient improved steadily during linezolid treatment. CVVHDF was discontinued on day 5. The patient was extubated on day 7. Blood cultures were negative for MRSA on day 8, and on day 13 the patient was discharged from the ICU on oral linezolid 600 mg every 12 h for another 8 days. In all, he received 21 days of linezolid with no haematological or other untoward effects.

To our knowledge, this is the first reported case of successful treatment with linezolid in a patient who developed septic shock secondary to MRSA arthritis while under vancomycin. Our patient presented with blood culture-positive MRSA arthritis. Blood cultures, however, continued to grow MRSA despite 10 days of vancomycin therapy started after a first surgical lavage of the affected joint. As vancomycin has been reported to clear MRSA bacteraemia in an average of 7 days,3 a second surgical lavage was performed on day 10 of vancomycin. Linezolid was then substituted for vancomycin. Linezolid exhibits good penetration into bone and joint tissues infected with MRSA.4 The reported synovial fluid concentrations exceed the MIC90 for MRSA, providing rational grounds for its use in arthritis-related MRSA sepsis. We measured a very similar level of linezolid in the synovial fluid of our patient. No control blood cultures were performed between days 2 (last MRSA-positive blood draws) and 8 (first MRSA-negative blood draws) of linezolid. Whether or to what extent the second surgical lavage contributed to the overall success of the therapy is not clear. However, clinical and bacteriological cure were achieved, adding to the available evidence of the efficacy of linezolid in severely ill patients with serious Gram-positive infections.5 Our only concern was about linezolid's known potential to induce transient myelosuppression with prolonged administration,6 but we did not observe any haematological or other untoward effects. The present case illustrates the need for alternative antibiotics when methicillin-resistant staphylococcal sepsis fails to improve under glycopeptide therapy.

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