Correlation between ratio of serum doxycycline concentration to MIC and rapid decline of antibody levels during treatment of Q fever endocarditis

Endocarditis is the major clinical manifestation of chronic Q fever. Although doxycycline along with hydroxychloroquine remains the mainstay of medical therapy for Q fever endocarditis, there are wide variations in the rapidity of the patient's decline of antibody levels during such therapy. We undertook a retrospective examination of whether there was any correlation between the ratio of serum concentration to MIC of doxycycline and response to treatment in patients with Q fever endocarditis. Included herein are 16 patients from whom Coxiella burnetii was isolated from cardiac valve materials. Serology and measurement of doxycycline and hydroxychloroquine serum levels were performed and recorded after I year of treatment. The MIC of doxycycline for C. burnetii isolates was determined using the shell vial assay in a real-time quantitative PCR assay. At the completion of a yearlong therapy with doxycycline-hydroxychloroquine, all those that showed a low decline of antibody levels (n = 6) (i.e., < 2-fold decrease in antibody titer to phase I C. burnetii antigen) had a ratio of serum doxycycline concentration to MIC between 0.5 and 1. In contrast, those having a ratio of;!:I showed a rapid decline of phase I antibody levels (n = 9; P < 0.05). The only patient who died had a serum doxycycline-to-MIC ratio of < 0.5, and the isolate of C. burnetii cultured from this patient was resistant to doxycycline (MIC = 8 mu g/ml). The ratio of serum doxycycline concentration to MIC should be monitored during the course of therapy in patients with Q fever endocarditis.