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J Antimicrob Chemother. 2018 Apr 1;73(4):1068-1076. doi: 10.1093/jac/dkx487.

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

Author information

1
Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
2
Department of Internal Medicine and Infectious Diseases, Radboud university medical center and Radboud Expertise Centre for Q Fever, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
3
Department of Internal Medicine, Medical Center Leeuwarden, Henri Dunantweg 2, 8934 AD, Leeuwarden, The Netherlands.
4
Zanob Pharmacy, Jeroen Bosch Hospital, Henri Dunantstraat 1, 5223 GZ, 's -Hertogenbosch, The Netherlands.
5
Department of Medical Microbiology and Infection Control, Jeroen Bosch Hospital, Henri Dunantstraat 1, 5223 GZ, 's -Hertogenbosch, The Netherlands.

Abstract

Background:

First choice treatment for chronic Q fever is doxycycline plus hydroxychloroquine. Serum doxycycline concentration (SDC) >5 μg/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 μg/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 μg/mL before dosage increase, and 5.9 μg/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 μg/mL and <10 μg/mL during treatment of chronic Q fever.

PMID:
29325142
DOI:
10.1093/jac/dkx487

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