The effect of measuring serum doxycycline concentrations on clinical outcomes during treatment of chronic Q fever.

Background: First choice treatment for chronic Q fever is doxycycline plus hydroxychloroquine. Serum doxycycline concentration (SDC) >5 mu g/mL has been associated with a favourable serological response, but the effect on clinical outcomes is unknown. Objectives: To assess the effect of measuring SDC during treatment of chronic Q fever on clinical outcomes. Methods: We performed a retrospective cohort study, to assess the effect of measuring SDC on clinical outcomes in patients treated with doxycycline and hydroxychloroquine for chronic Q fever. Primary outcome was the first disease-related event (new complication or chronic Q fever-related mortality); secondary outcomes were all-cause mortality and PCR-positivity. Multivariable analysis was performed with a Cox proportional hazards model, with shared-frailty terms for different hospitals included. Results: We included 201 patients (mean age 68 years, 83% male): in 167 patients (83%) SDC was measured, 34 patients (17%) were treated without SDC measurement. First SDC was >5 mu g/mL in 106 patients (63%), all with 200 mg doxycycline daily. In patients with SDC measured, dosage was adjusted in 41% (n = 68), concerning an increase in 64 patients. Mean SDC was 4.1 mu g/mL before dosage increase, and 5.9 mu g/mL afterwards. SDC measurement was associated with a lower risk for disease-related events (HR 0.51, 95% CI 0.26-0.97, P = 0.04), but not with all-cause mortality or PCR-positivity. Conclusions: SDC measurement decreases the risk for disease-related events, potentially through more optimal dosing or improved compliance. We recommend measurement of SDC and striving for SDC >5 mu g/mL and <10 mu g/mL during treatment of chronic Q fever.