Kingella kingae is a leading agent of osteomyelitis, septic arthritis and bacteremia in children 6–36 months of age in different countries. This Gram-negative bacterium, which is carried asymptomatically in the oropharynx, can penetrate the bloodstream and disseminate to distant sites.1 Because of the difficulties in recovering K. kingae in cultures, real-time polymerase chain reaction (PCR) in joint fluid is usually used. Current knowledge of the pathogenesis of invasive K. kingae suggests interaction with respiratory viruses.
We describe a case of K. kingae recurrent septic arthritis of left then right knee probably caused by the same strain in a 16-month-old boy.
CASE REPORT
A 16-month-old boy without underlying medical condition was hospitalized in the Department of Paediatric Orthopaedics of Trousseau Hospital, in Paris, France, with recurrent acute septic arthritis of left then right knee.
On March 14, 2018, the boy was seen at the Emergency Department, for a 24-hour hyperthermia up to 38.5°C, asthenia, limping and refusal to walk. A viral infection of the upper respiratory tract had occurred in the previous 3 weeks, treated by symptomatic therapy. There was no history of trauma. He was in contact with other children in day-care centers.
Upon admission, the temperature was 38.3°C and clinical examination revealed upper respiratory tract infection and inflammatory symptoms of the left knee, analgesic gait and joint effusion. He had no mouth ulcers or stomatitis. Blood analysis showed an increase of C-reactive protein level at 17.7 mg/L, normal white blood cell counts of 11.220 G/L and platelet count of 248.000 G/L. Conventional knee radiographs were normal. Joint puncture was performed and showed purulent joint fluid; joint debridement by arthrotomy was then done. Intravenous empiric antibiotic therapy with cefazolin (150 mg/kg/d in 4 divided doses) was immediately initiated. Articular liquid was sown in a blood culture flask and sent to the Microbiology Department of Saint Antoine Hospital in Paris. Direct examination and Gram stain of joint fluid revealed Gram-negative bacilli, and cultures yielded K. kingae susceptible to amoxicillin. After 3 days, oral amoxicillin (150 mg/kg/d in 3 divided doses) was administered and continued for a duration of 3 weeks in total.
On April 13, 2018, one week after the end of antibiotic therapy, the boy was seen again for 24 hours of fever up to 40°C, asthenia and inability to weightbear. He had gone back to day-care centers after the first infection and also had a recent history of rhinopharyngitis. Clinical examination revealed joint effusion of right knee. Blood results showed increase of C-reactive protein level at 30 mg/L with normal whole blood cell count. Left knee was investigated by joint puncture then arthrotomy. Joint fluid was analyzed by the Microbiology Department of Saint Antoine Hospital, and cultures were negative. The laboratory diagnosis of viruses used real-time reverse-transcription PCR assays on nasopharyngeal aspiration for viral detection and revealed a viral infection with parainfluenzae 3. Intravenous cefazolin was introduced for 3 days and then changed to oral amoxicillin adapted to a positive PCR for K. kingae in joint fluid.
The outcome was good with normal range of motion of both knees at the 1-month follow-up. The results of immunologic investigations (whole blood cell count with smear) and determination of immunoglobulins (total IgG, IgA and IgM antibodies levels) were normal.
MOLECULAR RESULTS
Joint fluid samples of left and right knees were sent to the Microbiology Department of Robert Debre Hospital in Paris to perform PCR for K. kingae. Molecular analysis revealed the presence of K. kingae DNA in both samples, and multilocus sequence typing was directly performed. Multilocus sequence typing used the sequence of 6 housekeeping genes, abcZ, adk, aroE, cpn60, gdh and recA. The PCR of rtxA which encodes the RTX toxin, a virulent factor as previously described,2 was also found to be positive in both samples. It was possible to successfully sequence 5 of these 6 genes but gdh failed to amplify; however, the allele combination indicated that both isolates belong to the sequence type complex 14 (1 of the 3 major ones in France).2 Both rtxA sequences were of allele 14. For both samples, capsular PCR performed as previously described3 indicated that both isolates harbored a capsule type “a.” Together these molecular findings strongly suggest that both episodes of acute septic arthritis were the same strain.
DISCUSSION
To the best of our knowledge, we report the first case of 2 consecutive episodes of septic arthritis (left then right knee) caused by the same strain of K. kingae in a context of 2 concomitant respiratory viral infections in a child. We did not observe any immunodeficiency, and we eliminate an endocarditis because of a normal echocardiography. Compliance with antibiotic therapy given for 3 weeks on each occasion was correct.
This is an interesting case considering the physiopathology, transmission and treatment of K. kingae infections in young children.
K. kingae is known as a major pathogen of bone and joint infections (BJI) in children <4 years of age in several countries. These infections are frequently preceded by clinical symptoms such as rhinitis, pharyngitis and stomatitis, suggesting viral upper respiratory tract infections.4 In a recent study between October 2009 and September 2016, the authors observed that weekly distributions of K. kingae BJI and human rhinovirus were significantly correlated.5 They showed a temporal association between viral and bacterial infections. Basmaci et al6 also found that at least 1 virus was significantly higher in the group with K. kingae BJI compared with control group with BJI not K. kingae. Human rhinovirus was the most frequent virus.6 In our case, we found that both episodes of septic arthritis were preceded by viral respiratory infections. The second one was due to parainfluenzae 3. These results suggest the important role of a viral coinfection in breaching the integrity of the pharyngeal epithelium and facilitating the invasion of the bloodstream by colonizing K. kingae organisms.
In our case, we describe a recurrent septic arthritis probably caused by the same K. kingae strain after antibiotic therapy. This observation suggests either that the oropharyngeal carriage of K. kingae has not been eradicated despite effective antibiotic therapy for K. kingae BJI or that there has been a recolonization of the bacterium in a day-care center. Indeed, K. kingae is carried asymptomatically in the human oropharynx.1 In a childcare center, the colonization rate based on PCR was 85% among healthy contacts. Also, in several studies, carriage eradication of K. kingae was unsuccessful despite the sensitivity of the isolates to rifampin the dosage used for Neisseria meningitidis prophylaxis.7 In a study in Marseille, 75% (3/4) of index cases still carried the organism 13–23 days after the start of rifampin.4 So carriage of K. kingae is difficult to eradicate, especially in studies where rifampin or amoxicillin was used.
Different studies suggest that only some K. kingae strains are able to cause invasive diseases.8 Analyses have shown that isolates of K. kingae produce a polysaccharide capsule which is a virulent factor. Indeed, the capsule can protect the bacterium against the immune system. In an international collection of 150 invasive and carriage isolates from 10 countries, Porsch et al9 described 4 capsule type isolates using PCR: “a,” “b,” “c” and “d.” They found that 95% of invasive isolates were related to capsule type “a” or “b.” In a French study, from July 2013 to April 2018, the authors described, among 105 patients, 71 (61.6%) capsules “a,” 33 (31.4%) capsules “b,” 1 (0.9%) capsule “c” and no capsule “d.”3 Our patient had a K. kingae strain with capsule type “a.”
In our case, the boy returned to a day-care center after the first infection. In day-care centers, where contact between children is close, K. kingae and viruses are easily transmitted from child-to-child, increasing the risk of transmission and recontamination. In a study between May 2015 and June 2016 among healthy children, results showed that healthy carriers were more frequently cared for out-of-home, especially in day-care centers, than noncarriers.10
To conclude, we describe for the first time a recurrent acute septic arthritis in the same child, probably caused by the same virulent strain of K. kingae and occurring consecutively after 2 viral infections of the upper respiratory tract. With close contacts between children in day-care centers, both bacteria and respiratory viruses can be simultaneously passed on to new hosts. In addition, viral disruption of the respiratory epithelial layer, known as the first line of defense against bacterial infection, can lead to ineffective bacterial clearance. A better understanding of physiopathology could lead to the identification of host factors which can promote the transition between asymptomatic carriage and invasive disease.
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