JAC Advance Access originally published online on October 21, 2005
Journal of Antimicrobial Chemotherapy 2006 57(1):150-151; doi:10.1093/jac/dki394
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Correspondence |
Linezolid use in sepsis due to methicillin-susceptible Staphylococcus aureus
Department of Clinical Microbiology, Beaumont Hospital, Dublin, Ireland
* Corresponding author. E-mail: cfbdeg{at}hotmail.com
Keywords: S. aureus , cytokines , exotoxins , antimicrobial activity
Sir,
We read with interest the correspondence from De Bels et al.1 Given the tissue penetration data available on the two agents in question, however, it is not surprising that linezolid proved to be successful where vancomycin had failed in a case of septic arthritis.2 We present a similar case, but of methicillin-susceptible Staphylococcus aureus (MSSA)-induced sepsis, which only responded to antimicrobial therapy after linezolid had been added to a regimen of flucloxacillin, fusidic acid and gentamicin. Whilst linezolid's capacity to reduce S. aureus virulence factor expression has been described previously,3 it has not been reported to date in a clinical setting.
A 57-year-old man was admitted to hospital complaining of back pain and lower limb weakness. He had undergone two spinal operations in the past: cervical discectomy 9 years previously and lumbar discectomy 5 weeks prior to this presentation. MRI of the spine revealed degenerative disc disease in the cervical and lumbar regions with spinal stenosis and disc protrusion respectively at C5-6 and L3-4. On admission he had a raised white cell count of 14 000/mL with an erythrocyte sedimentation rate of 77 mm/h. Liver function tests and urea and electrolytes were normal. Three days post-admission, he became febrile and profoundly hypotensive, with a concurrent deterioration of his renal and liver functions. He was transferred to the intensive care unit (ICU) for haemodynamic support. Examination revealed bilateral inflamed elbows and an inflamed right knee, which were presumed to be the source of sepsis. The working diagnosis at this point was metastatic infection from his operative wound. However, inspection of the wound revealed no evidence of infection and MRI of the spine revealed no underlying abscess. He was commenced on broad-spectrum antimicrobial therapy of benzylpenicillin, vancomycin, gentamicin and piperacillin/tazobactam. Blood drawn for culture on admission to ICU yielded MSSA. His antimicrobial therapy was rationalized to high-dose flucloxacillin (2 g every 4 h), fusidic acid (500 mg every 8 h) and gentamicin (3 mg/kg) daily, with daily monitoring of gentamicin levels. However, he remained febrile; his inotrope requirement increased and he required haemodialysis. There was no apparent source for continued infection: repeat blood cultures were sterile; chest X-ray was clear; joint washouts were performed, and were sterile despite the use of enrichment techniques. However, these washouts were performed after antimicrobial therapy had been commenced. Trans-oesophageal echocardiogram and CT abdomen were normal. No definitive source of infection was identified. His clinical condition continued to worsen. On day 4 of his ICU admission, intravenous linezolid 600 mg 12-hourly was commenced (Figure 1). His intravascular devices were changed: line tips were sterile. Within 16 h, his fever settled and he was weaned off inotropic support. After 72 h of continued improvement, linezolid and gentamicin were ceased in an endeavour to reduce his antimicrobial burden. Within 18 h of this change in therapy, he deteriorated, as measured by an increasing inotrope requirement (Figure 1). Linezolid was recommenced and his intravascular devices were again changed (line tips sterile). His clinical progress thereafter was slow but continuous. He was discharged to the ward 2 weeks later.
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We believe that linezolid played a significant role in the recovery of this patient. Given that the patient continued to deteriorate despite appropriate MSSA therapy—which succeeded in sterilizing blood drawn for culture—we suggest that the possibility of the clinical improvement being related to an anti-toxin effect of linezolid has to be considered. Gemmell and Ford3 have shown that sub-MIC linezolid concentrations impair production of coagulase,
-haemolysin and 
-haemolysin: these virulence factors are likely to play a role in the infection process. Bernardo et al.4 have also reported the effects of subinhibitory concentrations of linezolid on the secretion of the S. aureus virulence factors. Nakamura et al.5 have described a case of invasive group A streptococcus infection successfully treated with linezolid, whereas Coyle et al.6 have documented the effect of linezolid on the release of streptococcal pyrogenic exotoxin A. In the present case, the absence of specific assays and measurements of inflammatory mediators and virulence factors means that all we can do at this point is hypothesize. However, given the in vitro data, it is not unreasonable to assume that some of this anti-toxin activity is maintained in vivo, as is the case with clindamycin. Therefore, whilst currently invaluable almost solely in the treatment of resistant Gram-positive infections such as methicillin-resistant S. aureus, linezolid may yet have a broader role to play in the treatment of Gram-positive sepsis.
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References
1.
De Bels D, Garcia-Filoso A, Jeanmarie M et al. Successful treatment with linezolid of septic shock secondary to methicillin-resistant Staphylococcus aureus arthritis. J Antimicrob Chemother 2005; 55: 812–13.
2.
Kutscha-Lissberg F, Hebler U, Muhr G et al. Linezolid penetration into bone and joint tissues infected with methicillin-resistant staphylococci. Antimicrob Agents Chemother 2003; 47: 3964–6.
3. Gemmell CG, Ford CW. Virulence factor expression by Gram-positive cocci exposed to subinhibitory concentrations of linezolid. J Antimicrob Chemother 2002; 50: 667–72.
4. Bernardo K, Pakulat N, Fleer S et al. Subinhibitory concentrations of linezolid reduce Staphylococcus aureus virulence factor expression. Antimicrob Agents Chemother 2004; 48: 544–6.
5. Nakamura S, Yanagihara K, Kaneko Y et al. A case of invasive group A Streptococcus infection which was successfully treated with linezolid. Kansenshogaku Zasshi 2004; 78: 446–50.[Medline]
6.
Coyle E, Cha R, Rybak M. Influences of linezolid, penicillin, and clindamycin, alone and in combination, on streptococcal pyrogenic exotoxin A release. Antimicrob Agents Chemother 2003; 47: 1752–5.
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