News Release

26-year study reveals optimum duration of treatment for Q fever endocarditis

Peer-Reviewed Publication

The Lancet_DELETED

18 months of combined antibiotic therapy with doxycycline and hydroxychloroquine should become the recommended treatment duration for patients with Q fever endocarditis (severe infection of the inner lining of the heart or heart valves), except for patients with prosthetic heart valves* who might require 2 years of treatment, finds an Article published Online First and in the August edition of The Lancet Infectious Diseases. These results are especially important because of the large-scale Q fever outbreak in the Netherlands which has so far infected 3483 people and resulted in six deaths.

Q fever, one of the worlds most infectious diseases (a single bacterium is sufficient to infect a person), is caused by Coxiella burnetii bacteria. The chronic form of Q fever is rare, but 60󈞼% of patients with chronic disease develop endocarditis that is fatal if untreated. Earlier diagnosis and treatment with combined antibiotics (doxycycline and hydroxychloroquine) have reduced death rates from 60% in the 1970s to 5% in the 1990s. However, the optimum duration of treatment is unknown.

In this study, Didier Raoult and colleagues from Université de la Méditerranée, Marseille, France, assessed the long-term outcomes of patients with Q fever endocarditis to examine the effect of treatment duration and used survival analysis to identify prognostic factors associated with death, surgery, and serological cure and relapse.

The researchers followed 104 patients, diagnosed with Q fever endocarditis between 1983 and 2006 at the French National Referral Centre, for a minimum of 3 years. Patients were treated with a combination of doxycycline and hydroxychloroquine and given regular clinical examinations, biological assessments, and serology every month for 6 months, then every 3 months for a year, followed by every 6 months for 2𔃁 years, and then yearly for life. Additionally, excised heart valves were assessed for infection with C burnetii.

Overall, findings showed that treatment for 18 months was sufficient to make infection undetectable in most patients—18 months of treatment sterilised the valves of all but three patients, and after 24 months of treatment all valves were negative for C burnetii except for one "exceptional case". However, six patients experienced serological relapse 15󈞤 months after diagnosis.

Age, stroke at diagnosis, endocarditis on prosthetic valves, and serological factors were all major predictors of death. Predictors of poor serological outcome included being male, a phase I C burnetii IgG antibody titre of 800 or higher, and a delay of more than 12 months before treatment with hydroxychloroquine. Additionally, endocarditis on a prosthetic valve and treatment for less than 18 months were predictors of serological relapse.

Until recently, the duration of treatment depended on serological cure, defined as a phase I C burnetii IgG antibody titre of 800 or less. However, the authors suggest that the best method of determining treatment duration would be to establish the time needed to obtain a heart valve negative for C burnetii and to prevent serological relapse.

They conclude that these results have established the optimum duration of treatment with doxycycline and hydroxychloroquine: "18 months for native valves and 24 months for prosthetic valves. This duration should be extended only in the absence of favourable serological outcomes…Serological monitoring for at least 5 years seems appropriate given the risk of relapse."

In an accompanying Comment, Thomas Marrie from Dalhousie University in Canada says that this study provides the best evidence to date on treatment and follow-up of Q fever endocarditis, but warns that: "ongoing monitoring of antibiotic susceptibility to C burnetii is needed, because resistance to doxycycline will likely emerge with such prolonged treatment—thus the search for new drugs or new regimens of older drugs is necessary." He also questions whether, despite a lack of acceptance of a vaccine strategy for the prevention of Q fever, the development of new vaccines against C burnetii might prevent the problem.

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Professor Didier Raoult, Université de la Méditerranée, Marseille, France.
T) +33 4 91 32 43 76 E) didier.raoult@gmail.com

Dr Thomas Marrie, Dalhousie University, Halifax, Canada.
T) +1 902 494 6592 E) t.marrie@dal.ca

For full Article and Comment see: http://press.thelancet.com/tlidqfever.pdf


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