Lecaillet Audrey, Mallet Marie-Noëlle, Raoult Didier, Rolain Jean-Marc
URMITE, CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, 27 Boulevard Jean Moulin, 13385 Marseille cedex 05, France.
J Antimicrob Chemother. 2009 Apr;63(4):771-4. doi: 10.1093/jac/dkp013. Epub 2009 Feb 13.
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.
心内膜炎是慢性Q热的主要临床表现，Q热是一种由伯氏考克斯体引起的具有挑战性的疾病。Q热心内膜炎的推荐治疗方案是多西环素和羟氯喹联合使用至少18个月。然而，根据针对伯氏考克斯体的I相抗体稀释度下降率衡量，该治疗方案的生物学反应存在相当大的异质性。既往研究表明，与分离株的最低抑菌浓度相比，这种反应异质性是由于患者体内多西环素血清浓度的差异所致。
本研究的目的是回顾性评估初始血清学变化缓慢且接受更高剂量多西环素治疗的患者I相抗体的演变情况。
在17例确诊为Q热心内膜炎的患者中，12例被定义为反应缓慢者[治疗1年后I相抗体稀释度平均（±标准差）下降0.42±0.51，血清多西环素水平平均（±标准差）为3.44±1.06mg/L]，并接受了增加剂量的多西环素治疗。增加剂量治疗1年后，血清多西环素平均（±标准差）浓度增至4.86±1.14mg/L（P<0.05），I相抗体稀释度平均（±标准差）下降增至3.42±1.78（P<0.05）。
在Q热心内膜炎治疗期间，应同时监测多西环素的血清浓度和I相抗体，以便调整多西环素剂量，使血清学演变缓慢的患者达到更高浓度。
