Occult bacteremia due to Kingella kingae associated with herpetic gingivostomatitis

Dear Editor,

We present the case of a previously healthy 18-month-old female infant who was brought to our hospital's emergency department with a clinical picture of fever during 48 h, lethargy and lesions of the oral mucosa. On examination she presented an axillary temperature of 38.5 °C, normal cardiopulmonary auscultation, no visceromegaly, normal acute phase reactants, no signs of exanthema and no signs of neurological alterations. A urine culture was ordered, which was negative, and also a blood culture. A lumbar puncture was performed, and cytochemical and microbiological analyses of the cerebrospinal fluid were normal. No culture of the oral lesions was performed. The patient was hospitalised with a diagnosis compatible with herpetic gingivostomatitis and treatment was initiated with cefotaxime and aciclovir. At 48 h, the blood culture came back positive, with growth observed of a gram-negative coccobacillus that was identified as Kingella kingae. The child did not present signs of osteoarticular or cardiological infection, and the control blood culture at four days was negative. After five days, the IV cefotaxime treatment was suspended, and treatment was continued for a further week with oral amoxicillin-clavulanic acid at home for five days. There was no recurrence of the process in the following six months.

Currently, K. kingae is the pathogen that most commonly causes septic arthritis in children under 2 years of age.¹ In this group, it has been reported that 10% of children are oropharyngeal carriers of this bacteria.² In these carrier children, invasion of the respiratory mucosa and access to the skeletal tissue via the circulatory system would appear to be facilitated by the destruction of the epithelial barrier caused by viral infections.³ El Houmami et al.⁴ studied nine outbreaks caused by K. kingae in 27 children, 24 of whom suffered osteoarticular infections, with associated viral infections causing mouth ulcers being identified in the majority of patients.

The taking of blood cultures for the diagnosis of bacteraemia without focus in these patients with damage to the oral mucosa would enable us to pre-empt the severe pathologies that result from this microorganism's tropism for osteoarticular and endocardial tissue. In fact, bacteraemia without focus is the second most common presentation of K. kingae in paediatric patients.⁵ However, suspicion of this pathology on the part of clinicians is complex, as the clinical picture is often mild.⁶ Dubnov-Raz et al.⁷ studied a total of 322 infections with 140 cases of occult bacteraemia (43.6%) in children under 36 months. The patients studied did not have fever, leukocytosis or elevated acute phase reactants.

The relevance that this microorganism has taken on may be related to a reduction in skeletal infections caused by Haemophilus influenzae due to generalised vaccination,⁸ improved culture techniques such as inoculation of blood culture vials with samples of synovial fluid,⁹ and the development of several commercial methods to identify this microorganism, such as the Vitek2 NH card and mass spectrometry.⁶ Moreover, the use of nucleic acid amplification techniques on direct samples of synovial fluid has been a big advance.¹⁰ Nonetheless, these techniques are expensive, often laborious and are not available in all laboratories, and there is very little data on their use on positive blood cultures.

The Clinical and Laboratory Standards Institute (CLSI)¹¹ includes K. kingae in the HACEK group and recommends the same cut-off points for sensitivity to antimicrobial agents for difficult-to-grow microorganisms, including K. kingae. In 2020, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) established specific cut-off points for K. kingae,¹² so in the case in question the strain was resistant to penicillin, since it presented an MIC of 0.064 µg/mL.

Our study is focused on the convenience of protocolising the taking of blood cultures in paediatric patients with oral involvement in order to rule out occult bacteraemia due to K. kingae, in view of the colonisation rate in children under 2 years of age and the benign clinical picture of this type of infection. The current diagnostic tool in positive blood cultures is still primarily identification of growth in conventional culture. For this, the microbiologist needs to be particularly aware of this type of microorganism to avoid deeming it a contaminant and thus to provide information for decision-making that will avoid complicated infections such as endocarditis and septic arthritis. EUCAST and CLSI differ on their cut-off points for sensitivity to penicillin for this microorganism. Given the relevance that K. kingae has acquired as an invasive pathogen in recent years, we consider the use of the European criterion to be justified as it is tailored to this species.