Molecular detection of Coxiella burnetii in heart valve tissue from patients with culture-negative infective endocarditis

Abstract

Coxiella burnetii is a common cause of blood culture-negative infective endocarditis (IE). Molecular detection of C burnetii DNA in clinical specimens is a promising method of diagnosing Q fever endocarditis. Here, we examined the diagnostic utility of Q fever polymerase chain reaction (PCR) of formalin-fixed heart valve tissue from patients with blood culture-negative IE who underwent heart valve surgery. Clinical and laboratory data of patients with blood culture-negative IE who underwent heart valve surgery during a 6-year period and for whom biopsy tissues were available were reviewed retrospectively. Blood culture-positive IE patients who underwent heart valve surgery within the last 3 years were used as controls. Heart valve samples were cultured and also subjected to histological examination and PCR for Q fever, brucellosis, and bartonellosis. Data from 20 patients with blood culture-negative IE and 20 with blood culture-positive IE were analyzed. Eight cases of blood culture-negative IE were PCR-positive for C burnetii (40%; 95% confidence interval, 19-64). No specimen was PCR-positive for brucellosis or bartonellosis. Histologically, 4 of 8 specimens with a positive Q fever PCR result were characterized by clusters of multinucleated giant cells without a fibrin ring. None of 20 patients with blood culture-negative IE received anti-Coxiella antibiotic therapy due to lack of clinical suspicion. Six-month mortality was higher in the Q fever PCR-positive group than in the Q fever PCR-negative group [38% (3/8) vs 0% (0/12), P = .049). Of the 20 patients with blood culture-positive IE, none yielded a positive Q fever PCR result for valve tissue. Approximately 40% of patients with culture-negative IE who received heart valve surgery were PCR-positive for Q fever; patients without clinical suspicion suffered high mortality. These data suggest that Q fever IE in patients with culture-negative IE is often missed in routine clinical practice.

Figure 1

Distribution of the 40 patients with suspected blood culture–negative infective endocarditis who underwent cardiac valve surgery from January 1, 2011 to July 31, 2016 (according to the Duke criteria and etiological diagnoses). IE = infective endocarditis.

Figure 2

Agarose gel electrophoresis of polymerase chain reaction (PCR) products derived from the Coxiella burnetii IS1111a gene. Amplification of bacterial DNA using Q fever-IS1111a primers to detect C burnetii. Gel electrophoresis of end-point PCR products (202 bp). M: 50 bp DNA size marker; 1–20: DNA samples from patients with culture-negative infective endocarditis (IE); 21–40: DNA samples from patients with culture-positive IE and the negative controls (N).