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JAC Advance Access published online on May 5, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh234
© 2004 by The British Society for Antimicrobial Chemotherapy
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Received December 19, 2003
Revised March 9, 2004
Accepted March 11, 2004

Brief report

Relationship between myalgias/arthralgias occurring in patients receiving quinupristin/dalfopristin and biliary dysfunction

Issam Raad 1*, Ray Hachem 1, Hend Hanna 1

1 M.D. Anderson Cancer Center, Department of Infectious Diseases, 1515 Holcombe Blvd, Unit 402, Houston, TX 77030, USA

* To whom correspondence should be addressed. E-mail: iraad{at}mdanderson.org.


  Abstract

Objectives: To determine whether myalgias/arthralgias occurring in cancer patients who receive quinupristin/dalfopristin are associated with biliary tract dysfunction.

Methods: We studied 56 patients with vancomycin-resistant enterococcal infections who were treated with quinupristin/dalfopristin 7.5 mg/kg every 8 h for a mean duration of 12 days (range 2-52 days). Liver function tests, including a test for alkaline phosphatase, were performed before, during and after the end of therapy. All patients were followed for 1 month after completion of therapy.

Results: Thirty-eight (68%) of the 56 patients responded. Myalgias/arthralgias were the leading adverse events occurring in 20 (36%) of the patients. Patients with myalgias/arthralgias had significantly higher levels of alkaline phosphatase (mean 318.7 IU/L) during the mid-term therapy cycle compared with patients without any joint or muscular pain (mean 216.3 IU/L, P = 0.05). In addition, 3/18 (16.6%) patients with myalgias/arthralgias had more than five-fold the normal levels of alkaline phosphatase, which did not occur in any of the other patients who did not develop myalgias/arthralgias (P = 0.04). All myalgias/arthralgias resolved after the discontinuation of quinupristin/dalfopristin. By univariate analysis, other factors associated with myalgias/arthralgias were relapse of haematological malignancy (P = 0.01), receiving tacrolimus within 1 month prior to treatment (P = 0.04) and receiving methotrexate during antimicrobial therapy (P = 0.05).

Conclusions: Myalgias/arthralgias occur frequently in cancer patients receiving quinupristin/dalfopristin and may be associated with biliary tract dysfunction, as measured by alkaline phosphatase or other factors that could lead to intra-hepatic cholestasis, such as relapse of haematological malignancy or treatment with tacrolimus or methotrexate.

Key Words: Keywords: alkaline phosphatase, vancomycin-resistant enterococci, VRE


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