Invasive Kingella Kingae Infection Associated With Stomatitis in Children

Kingella kingae, a Gram-negative bacillus normally found in the respiratory tract,1 is increasingly recognized as a cause of bacteremia, skeletal infections and endocarditis in young children.2-5 The pathogenesis of invasive K. kingae infections has not been adequately explained. The incidence of the disease increases during the fall and winter months, and a substantial fraction of patients with arthritis or bacteremia present with upper respiratory tract symptoms, suggesting concomitant viral infections that might facilitate entry of K. kingae into the blood stream.3, 5 During the past 10 years 16 children with stomatitis and bacteremia or septic arthritis caused by K. kingae were diagnosed at 2 medical centers in Israel. In this study we describe the clinical course of these patients and discuss the possible role played by ulceration of the oral mucosa in the pathogenesis of invasive K. kingae infections. Methods. The patients included in the study were referred during 1988 to 1997 to two medical centers in Israel [Schneider Children's Medical Center of Israel (SCMCI), Petah Tikvah, and the Soroka Medical Center (SMC) in Beer Sheva] and underwent blood cultures at the physician's discretion, using the BACTEC blood culture system (Becton Dickinson, Cockeyville, MD). From December, 1993, to December, 1995, children with suspected primary herpetic gingivostomatitis were enrolled at the SCMCI for studies on the administration of acyclovir6 and the evaluation of a rapid assay for the detection of a herpes simplex virus antigen.7 As part of the diagnostic protocols viral cultures of the vesicles were obtained from all patients and bacteriologic blood cultures were drawn from patients evaluated in the emergency room. In addition synovial fluid specimens of children with arthritis treated at the SMC were routinely inoculated into aerobic blood culture bottles. Inoculated bottles were processed according to the manufacturer's recommendations. Organisms were identified as K. kingae on the basis of a typical Gram stain appearance as Gram-negative square bacilli in pairs or short chains. Colonies produced beta-hemolysis, had no growth on MacConkey agar, gave positive oxidase and negative catalase tests, showed negative motility and urease tests and produced acid from glucose and maltose but not from other sugars.8 Medical records of all patients in whom K. kingae organisms were isolated from blood and/or synovial fluid cultures and concomitant stomatitis diagnosed in both medical centers were reviewed. Demographic, clinical and laboratory data were gathered. Results. A total of 52 children with invasive K. kingae infections were diagnosed at the SMC and 13 at the SCMCI. Sixteen of the 65 (24.6%) had erosions in the buccal, gingival and/or glossal surfaces. Clinical and laboratory data of these patients are summarized in Table 1. Duration of the stomatitis before blood sampling was 2 to 6 days. K. kingae was isolated from the blood in 14 children and from the joint fluid in 3 (1 child had positive cultures of both specimens). Six children had leukocytosis (>15 000 white blood cells/mm3).TABLE 1: Invasive Kingella kingae infections associated with stomatitis In most cases no attempt was made to identify the cause of the stomatitis. In 4 children with gingivostomatitis, herpes simplex virus was isolated from oral lesions, and in an additional 4 patients the clinical data suggested herpetic gingivostomatitis (involvement of oral mucosa, gums and lesions around the mouth). In one varicella-zoster virus infection was clinically diagnosed. All patients were treated with antibiotic agents and completely recovered without complications. Overall K. kingae was isolated from 4 (13.8%) of 29 children with culture-proved primary herpetic gingivostomatitis in whom blood cultures were obtained. Discussion. Members of the flora that colonize human body surfaces comprise a wide spectrum of organisms with various degrees of potential pathogenicity. The anatomical integrity of mucosal and skin surfaces is a critical first line defense against invasion of blood and tissues by these bacteria. Studies conducted in recent years have shown that K. kingae is a normal component of the respiratory flora of infants and toddlers and may be recovered from the tonsils in up to one-third of asymptomatic day-care center attendees.1 The prevalence of the organism in the pharynx of children parallels the occurrence of invasive disease among the different age groups.3 The 52 children with K. kingae bacteremia or skeletal infections diagnosed at the SMC in southern Israel during the last decade were 6 to 40 months old. The prevalence of K. kingae in the pharynx of healthy children of this age was 10%, 6% among older children, and the organism was not isolated in infants 2 to 4 months old.1 The results of the present study suggest that occurrence of diffuse stomatitis in young children may be associated with a risk to develop bacteremia or focal K. kingae infections. Review of the relevant literature revealed other cases of K. kingae bacteremia, septic arthritis or meningitis associated with stomatitis in children9-11 andK. kingae endocarditis associated with stomatitis in adults.12, 13 Although the etiology of stomatitis in our patients was not thoroughly investigated in most cases, a few infections by herpes viruses such as herpes simplex and varicella-zoster were identified. Conversely a substantial fraction with culture-proved herpes simplex infection had concomitant K. kingae bacteremia (13.8%). This association does not seem to be coincidental. The peak attack rate of primary herpetic gingivostomatitis occurs in children between the ages of 6 and 48 months, coinciding with the age of maximal carriage rate of K. kingae. It is postulated that a breach of the mucosal continuity caused by viral infection provides a portal of entry to K. kingae organisms, which colonize the tonsillar surfaces. The immunosuppressive effect of the systemic viral infection may contribute to the process as well. Penetration of the organism into the bloodstream may be followed by hematogenous seeding of K. kingae to remote sites and especially to the skeletal system to which the organism shows a striking and still unexplained affinity.3, 4 Jacob Amir, M.D. Pablo Yagupsky, M.D. Department of Pediatrics C; Schneider Children's Medical Center of Israel; Petah Tikva (JA) Sackler School of Medicine; Tel Aviv University; Tel Aviv (JA) Clinical Microbiology Laboratory; Soroka Medical Center; Ben Gurion University of the Negev Medical School; Beer Sheva (PY) Israel