This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Madariaga, M. G.
Right arrow Articles by McKee, E. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Madariaga, M. G.
Right arrow Articles by McKee, E. E.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 2007, p. 1130, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.01357-06

LETTER TO THE EDITOR

Oxazolidinones and Human Immunodeficiency Virus


arrow
LETTER
 
We would like to comment on the potential implications of the article published by McKee et al. (5) on the management of human immunodeficiency virus (HIV)-infected patients.

McKee et al. demonstrated that linezolid (and other oxazolidinones) inhibits mitochondrial protein synthesis in rodents (5), confirming similar results in other animal models (4, 6) and in case reports of three humans exposed to linezolid, in which the spectrophotometric determination of enzyme activity for mitochondrial respiratory-chain complex IV in mononuclear cells was found to be low (7). The consequences of this mitochondrial toxicity may include bone marrow suppression, peripheral and optical neuropathy, and lactic acidosis.

A recent report from the XVI International AIDS Conference showed a significant increase in the incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections among HIV patients (2). The authors concluded that HIV-infected patients had an 18-fold-higher risk of acquiring CA-MRSA than non-HIV-infected patients. Although the initial therapy for CA-MRSA infection is usually a tetracycline or trimethoprim-sulfamethoxazole (plus appropriate debridement), linezolid is commonly used in more severe CA-MRSA infections.

Although no reports of enhanced toxicity have been published, we foresee a potential risk with the concurrent use of linezolid and antiretroviral therapy. Nucleoside reverse transcriptase inhibitors (NRTIs), which are the cornerstone of current antiretroviral combinations, also have the potential for inhibiting mitochondrial DNA. The toxicity can occur with any member of the pharmacological class, although lamivudine and newer NRTIs such as emtricitabine, tenofovir, and abacavir have less toxicity than zalcitabine, stavudine, or didanosine (8). Mitochondrial toxicity related to NRTIs manifests as myopathy, peripheral neuropathy, and lactic acidosis but may also be associated with metabolic disorders including lipoatrophy, insulin resistance, and dyslipidemia.

We suggest caution with the concurrent use of oxazolidinones and NRTIs, particularly if the former are planned for long courses of therapy. Clinicians may also want to avoid the additional use of other drugs that may worsen mitochondrial dysfunction. Metformin, which is becoming more commonly used among HIV-infected patients as a consequence of insulin resistance, is a mild inhibitor of respiratory chain complex 1 (3). Ethambutol, a first-line agent in the treatment of tuberculosis, probably causes optic neuropathy by inducing mitochondrial damage (1). If evidence of adverse interactions between oxazolidinones and NRTIs becomes available, additional research into this potential toxicity should be encouraged.


arrow
REFERENCES
 
    1
  1. Carelli, V., F. N. Ross-Cisneros, and A. A. Sadun. 2002. Optic nerve degeneration and mitochondrial dysfunction: genetic and acquired optic neuropathies. Neurochem. Int. 40:573-584.[CrossRef][Medline]
    2. 2
  2. Crum-Cianflone, N., B. Hale, A. Burgi, et al. 2006. Increasing rates of community-acquired MRSA infections among HIV-infected persons, abstr. MOAB304/5672. AIDS 2006: XVI International AIDS Conference, Toronto, Ontario, Canada.
    3. 3
  3. Detaille, D., B. Guigas, C. Chauvin, et al. 2005. Metformin prevents high-glucose-induced endothelial cell death through a mitochondrial permeability transition-dependent process. Diabetes 54:2179-2187.[Abstract/Free Full Text]
    4. 4
  4. De Vriese, A. S., R. V. Coster, J. Smet, et al. 2006. Linezolid-induced inhibition of mitochondrial protein synthesis. Clin. Infect. Dis. 42:1111-1117.[CrossRef][Medline]
    5. 5
  5. McKee, E. E., M. Ferguson, A. T. Bentley, and T. A. Marks. 2006. Inhibition of mammalian mitochondrial protein synthesis by oxazolidinones. Antimicrob. Agents Chemother. 50:2042-2049.[Abstract/Free Full Text]
    6. 6
  6. Nagiec, E. E., L. Wu, S. M. Swaney, et al. 2005. Oxazolidinones inhibit cellular proliferation via inhibition of mitochondrial protein synthesis. Antimicrob. Agents Chemother. 49:3896-3902.[Abstract/Free Full Text]
    7. 7
  7. Soriano, A., O. Miro, and J. Mensa. 2005. Mitochondrial toxicity associated with linezolid. N. Engl. J. Med. 353:2305-2306.[Free Full Text]
    8. 8
  8. Wohl, D., G. McComsey, P. Tebas, et al. 2006. Current concepts in the diagnosis and management of metabolic complications of HIV and its therapy. Clin. Infect. Dis. 43:645-653.[CrossRef][Medline]
Miguel G. Madariaga*
Susan Swindells
HIV Clinic
University of Nebraska Medical Center
Omaha, Nebraska 68198-5400

* Phone: (402) 559-8664, E-mail: mmadariaga{at}unmc.edu


Author's Reply


arrow
LETTER 
 
Madariaga and Swindells have commented on our recent article that demonstrated that linezolid inhibited mitochondrial protein synthesis in a variety of rat tissues. In this well-reasoned comment letter, Madariaga and Swindells urge the judicious use of linezolid in AIDS patients with CA-MRSA, noting that many of these patients have been treated long term with nucleoside reverse transcriptase inhibitors, which are known to adversely affect mitochondrial biogenesis. The authors reason that such individuals may be especially sensitive to linezolid, which may reduce mitochondrial function further. We agree and would add that the same judicious use of linezolid be given to individuals with known or suspected mitochondrial diseases, who also experience reduced mitochondrial function (1) and may also be particularly sensitive to treatment with linezolid.


arrow
REFERENCE 
 
    1
  1. Schapira, A. 2006. Mitochondrial disease. Lancet 368:70-82.[CrossRef][Medline]
E. E. McKee*
Indiana University School of Medicine—South Bend
1234 Notre Dame Ave.
South Bend, Indiana 46617

* Phone: (574) 631-7193, Fax: (574) 631-7821, E-mail: McKee.6{at}nd.edu

Antimicrobial Agents and Chemotherapy, March 2007, p. 1130, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.01357-06





This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Madariaga, M. G.
Right arrow Articles by McKee, E. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Madariaga, M. G.
Right arrow Articles by McKee, E. E.

Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»