Kingella kingae is a facultative anaerobic, β-hemolytic, Gram-negative coccobacillus of the Neisseriaceae family, difficult to detect in routine solid cultures of body fluids, particularly when blood culture vials are not used for the inoculation. In these cases, it can be isolated in <10% of truly positive cases.1 After colonization of the oropharyngeal mucosa of children, this microorganism is carried asymptomatically and spread by close interpersonal contact. The oropharynx is also the entry portal of the pathogen into the bloodstream from which it may cause system infections.2 The invasion of the oropharyngeal mucosa by the bacteria is almost always preceded or concomitant with a viral infection.1
The invasive disease due to K. kingae is mostly a disease of children under 4 years old or immunocompromised older children and adults. Its incidence has increased, although the global impact is not yet fully understood. It is the leading cause of osteoarticular infections between 6 and 48 months and a well-known cause of pediatric bacteremia and endocarditis, especially in children with known risk factors.2 It has very seldomly been reported as a cause of bacterial meningitis, and there are only 8 cases previously reported.3–10
We report a case of an acute meningitis caused by K. kingae in a healthy 10-year-old boy with no underlying condition that could predispose to this infection.
A previously healthy Portuguese 10-year-old boy was admitted to an emergency department with severe frontal headache, without improvement after oral paracetamol and ibuprofen, vomiting and prostration since the day before. He had no fever and no history of head injury. He had had aphthous stomatitis 1 week before the development of this symptoms. His vaccination schedule was complete according to the Portuguese Immunization Program. Physical examination revealed an afebrile, severely ill, prostrated and pale child, complaining of severe headaches. He presented neck stiffness and positive Kernig and Brudzinsky signs. His blood pressure was 120/74 mm Hg and the pulse rate was 110 beats/min. He did not have any focal neurologic signs neither papillary edema or any other signs of elevated intracranial pressure. Laboratory tests revealed white blood cell count of 12,260/mm3 with 82.8% neutrophils, C-reactive protein 8.26 mg/dL, procalcitonin 1.27 ng/mL and fibrinogen 467 mg/dL.
The computed tomography scan of the brain was normal and did not show any signs of elevated intracranial pressure. Lumbar puncture showed a turbid cerebrospinal fluid (CSF) with 276 white cells/mm3, hyperproteinorrachy (202 mg/dL) and hypoglycorrhachia (48 mg/dL, 45.7% of the serum glucose). Enterovirus RNA in CSF and stools was not detected.
Due to somnolence and persistent severe headaches, he was transferred to the Pediatric Intermediate Care Unit and treated with intravenous (IV) analgesics, ceftriaxone and vancomycin for presumptive bacterial meningitis.
The blood culture was negative. Kingella kingae, susceptible to penicillin, was isolated in the CSF (Fig. 1A) and vancomycin was suspended.
Two cardiac ultrasounds were performed, ruling out the presence of endocarditis. He had no osteoarticular complaints and his examination was unremarkable.
During the first 3 days of hospitalization, the patient complained of severe headache, requiring frequent analgesia with morphine. He underwent a magnetic resonance imaging of the brain that showed diffuse reinforcement of the cerebral and cerebellar meningeal signals (Fig. 1B).
During the hospitalization, he remained hemodynamically stable, nonfebrile and on day 4 of hospitalization showed clinical improvement and was transferred to the pediatric ward, being discharged on the eighth day of hospitalization, completing 14 days of IV ceftriaxone in an outpatient setting. At the end of the treatment, the patient had made a complete recovery. An underlying primary immunodeficiency that could explain this rare manifestation of K. kingae infection was excluded.
MATERIALS AND METHODS
Routine procedures were carried out for the laboratory diagnosis of bacterial meningitis, including cytochemical examination of the CSF, Gram stain and culture of the CSF sediment (blood agar, chocolate agar and brain heart infusion). After the detection of K. kingae in the CSF, an oropharyngeal swab was collected for molecular detection by PCR of this bacterium.
The Euroflow Primary Immunodeficiency Orientation Tube (Cytognos, Salamana, Spain) was used for the characterization of lymphocyte subsets and the innate immunity screening was performed with the functional CD62 ligand shedding assay, after stimulation with PMA, LPS and TLR7/8 ligands.
Immunoglobulins (IgG, IgA, IgM and IgE) were quantified in serum by immunoturbidimetry and specific responses to vaccines (diphtheria and tetanus) were evaluated by ELISA.
In the CSF Gram stain, no bacteria could be detected, but in the CSF culture β-hemolytic colonies were observed in the blood agar (Fig. 1A). This isolate was identified as K. kingae by the Matrix Assisted Laser Desorption Ionization Time-of-Flight methodology (MALDI-TOF.VITEKMS, bioMérieux), and it was found to be susceptible to penicillin (Minimum Inhibitory Concentration: 0.02 mg/L). Kingella kingae DNA was detected in the oropharyngeal swab.
The immunologic assessment of the patient was normal.
Kingella kingae is a common etiology of bacteremia and osteoarticular infections. It has also been associated with potentially life-threatening endocarditis and rarely to pneumonia and meningitis.1
The current report describes a rare case of a 10-year-old previously healthy child with K. kingae meningitis. Since 1983, only 8 pediatric cases of meningitis caused by K. kingae have been published (Table 1, Supplemental Digital Content 1, http://links.lww.com/INF/E341),3–10 7 of which occurred in children under the age of 5, 3 had endocarditis and only 1 case of isolated meningitis occurred in a previously healthy teenager (17 years old). Patients were treated with beta-lactam antibiotics (isolated or combined with chloramphenicol) or the third generation cephalosporins combined with glycopeptide or aminoglycosides. The duration of the therapy ranged from 10 days to 6 weeks, with prolonged therapy being used in those with concomitant endocarditis. All patients showed complete recovery within 24 hours of antibiotic treatment and 1 year of follow-up, except 1 patient who died (he presented infarction in the posterior cerebral arteries and endocarditis with mitral valve insufficiency). In these reports of K. kingae meningitis, an underlying immunodeficiency was not thoroughly excluded, but, in this case, an extensive workup allowed its exclusion.
Colonization of the oropharyngeal mucosa and carriage rate of this organism among pediatric patients is around 10%–12% until the end of the second year of life, and gradually declines to very low levels in older children and adults.1 In patients without endocarditis, meningitis due to K. kingae most probably results from hematogenous dissemination of the organism into the central nervous system after entering the bloodstream.
Previous studies have shown that K. kingae disease is almost always associated with a previous or concomitant viral infection, such as herpes simplex virus and enterovirus.1 We speculate that the preceding stomatitis that our patient presents a few days before was responsible for the bloodstream invasion of the pathogen with subsequent central nervous system infection.
The clinical presentation of this child, along with the CSF findings (pleocytosis, hyperproteinorrachy and low glucose), was highly suggestive of bacterial meningitis, despite the absence of fever. Therefore, he was treated with ceftriaxone and vancomycin and the latter was stopped upon identification of K. kingae. It is known that most of the K. kingae strains are susceptible to the second and third generation cephalosporins,1 and previous case reports of K. kingae meningitis showed a rapid recover after initiation of antibiotic therapy.3–5 This case was notable for the presence of very severe headaches, requiring treatment with morphine in the absence of intracranial complications or elevated intracranial pressure.
The Gram stain failed to identify any bacteria but, despite the low number of colonies in the blood agar, it was easy to detect and identify with the MALDI-TOF technology the K. kingae isolate. It is possible that a lower bacterial load in other situations, like synovial fluid or bone infections, can contribute to the low sensitivity of traditional culture methods.1
The duration of treatment is not well established in K. kingae meningitis, but previously published data suggest that at least 10 days of antibiotic therapy should be used.4
With the exception of endocarditis, most K. kingae infections follow a benign clinical course after administration of antibiotic therapy and the overall prognosis of meningitis caused by this pathogen is good.1
In summary, this article highlights that it is important to be aware that K. kingae is occasionally capable of causing serious invasive infections, including meningitis, that can arise in the absence of fever even in immunocompetent recipients.
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