Therapeutic impact of the correlation of doxycycline serum concentrations and the decline of phase I antibodies in Q fever endocarditis

Abstract

Endocarditis is the main clinical manifestation of chronic Q fever, a challenging disease due to Coxiella burnetii. The recommended treatment for Q fever endocarditis is a combination of doxycycline and hydroxychloroquine for at least 18 months. However, there is considerable heterogeneity in the biological response to this regimen as measured by the rate of decrease of dilutions of phase I antibodies against C. burnetii. Previous studies have demonstrated that this response heterogeneity was due to variations in the serum concentration of doxycycline in patients when compared with MICs for the isolates. The objective of this study was to evaluate retrospectively the evolution of phase I antibodies in patients with an initial slow serological change, who received higher doses of doxycycline. Among 17 patients with definitive diagnosis of Q fever endocarditis, 12 were defined as slow responders [mean (+/- SD) decrease of dilutions of phase I antibodies of 0.42 +/- 0.51 and mean (+/-SD) serum doxycycline level of 3.44 +/- 1.06 mg/L after 1 year of treatment] and received increased doses of doxycycline. After 1 year of treatment with increased dose, the mean (+/-SD) serum doxycycline concentration increased to 4.86 +/- 1.14 mg/L (P<0.05) and the mean (+/-SD) decrease of dilutions of phase I antibodies increased to 3.42 +/- 1.78 (P<0.05). During the treatment of Q fever endocarditis, serum concentrations of doxycycline should be monitored concomitantly with phase I antibodies in order to adjust the dose of doxycycline to achieve a higher concentration for patients with slow serological evolution.