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| |  Study Reveals Optimum Duration of Treatment for Q Fever Endocarditis NEW YORK -- July 14, 2010 -- Combined antibiotic therapy with doxycycline and hydroxychloroquine for 18 months should become the recommended treatment duration for patients with Q fever endocarditis, except for patients with prosthetic heart valves who might require 2 years of treatment, according to a study published online first and appearing 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 6 deaths. The chronic form of Q fever is rare, but 60% to 80% of patients with chronic disease develop endocarditis that is fatal if untreated. Earlier diagnosis and treatment with combined antibiotics have reduced death rates from 60% in the 1970s to 5% in the 1990s. However, the optimum duration of treatment is unknown. In the study, Didier Raoult, MD, Université de la Méditerranée, Marseille, France, and colleagues 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 1 year, followed by every 6 months for 2 to 3 years, and then yearly for life. Additionally, excised heart valves were assessed for infection with Coxiella 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 3 patients, and after 24 months of treatment all valves were negative for C burnetii except for 1 "exceptional case". However, 6 patients experienced serological relapse 15 to 56 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 1 C burnetii Immunoglobin G (IgG) antibody titre of >=800, and a delay of more than 12 months before treatment with hydroxychloroquine. Additionally, endocarditis on a prosthetic valve and treatment for <18 months were predictors of serological relapse. Until recently, the duration of treatment depended on serological cure, defined as a phase 1 C burnetii IgG antibody titre of <=800. However, the authors suggested 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 concluded 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, MD, Dalhousie University, Halifax, Nova Scotia, said 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 questioned 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.
SOURCE: The Lancet Infectious Diseases
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