Limitations of Oropharyngeal Molecular Testing for Diagnosing Invasive Kingella kingae Infections

To the Editors: I read the recent PIDJ manuscript by Nielsen et al.1 assessing the value of a species-specific nucleic acid amplification test (NAAT) performed on an oropharyngeal swab for the diagnosis of Kingella kingae skeletal system infections. Because K. kingae frequently invades joints and bones that are too small or difficult to reach, as well as intervertebral disks, source samples such as synovial fluid or tissue from the bone and intervertebral disc are seldom available for analysis. The bacteriological diagnosis of these infections, particularly that of spondylodiscitis and sacroiliitis, is highly problematic in an uncooperative young child. Physicians are frequently hesitant to perform joint aspirations or take biopsies in pediatric patients because these invasive procedures require sedation and imaging guidance. Obtaining an intervertebral disc biopsy is considered potentially risky, and an animal experimental model has demonstrated that even the negligible damage caused by a needle puncture may result in progressive disc degeneration.2 In a retrospective study involving 124 children with spondylodiscitis, a spinal biopsy was performed in only 2 patients, and no pathogens were isolated.3 The alternative noninvasive diagnostic strategy evaluated in Nielsen et al.1 study demonstrated complete agreement in the positive detection of the bacterium in joint and bone specimens, as well as in oropharyngeal specimens. This finding supports the concept that the colonized mucosal surface serves as the portal of entry for the organism into the bloodstream, allowing for its dissemination and invasion of the skeletal system. However, the oropharyngeal swab was also positive in 33 of 112 (29.5%) of patients with unproven K. kingae disease.1 This finding is consistent with the significant prevalence of oropharyngeal carriage in the preschool population (10%) and higher among children attending daycare facilities (28%), which reduces the diagnostic usefulness of a positive test result.4 A second caveat is that NAATs targeting the rtx operon also detect the repeat-in-toxin A (RTXA)-producing Kingella negevensis.5 This recently identified species of uncertain clinical significance is also carried asymptomatically in the oropharynx by the pediatric population. Thus, oropharyngeal colonization by K. negevensis may contribute to joint or bone infections being attributed to K. kingae, further decreasing the specificity of the test. Although the positive predictive value of the oropharyngeal NAAT approach is suboptimal, as convincingly shown by Nielsen’s study, its negative predictive value is high. The failure of a sensitive molecular test to detect K. kingae DNA sequences in the oropharynx of a young child effectively rules out the bacterium as the etiology of the skeletal disease.