Lumbar Osteomyelitis and Epidural Abscess Caused by Cardiobacterium hominis—First Reported Case in the Pediatric Population: The Role of Universal 16S rRNA Gene PCR and Sequencing

Cardiobacterium hominis is a member of HACEK group (Haemophilus paraphrophilus, Haemophilus parainfluenzae, Aggregatibacter actinomycetemcomitans, Aggregatibacter aphrophilus, C. hominis, Eikenella corrodens, and Kingella kingae); it has low virulence and is known to be the cause of endocarditis and has been a notable cause of other infections such as septicemia, abdominal abscess, dacryocystitis, and joint infection.

This report details the first case of lumbar (L2–L3) epidural abscess and vertebral osteomyelitis caused by C. hominis in pediatric population. The diagnosis was made using universal 16S rRNA polymerase chain reaction (PCR).

CASE REPORT

A 14-year-old female patient, with no medical history, presented with 2-month history of worsening nonradiating back pain, and no preceding trauma was reported. She denied history of fever, chills, constitutional symptoms, ill contact, or recent travel. The physical examination demonstrated that the patient was afebrile with normal vital signs, and tenderness was noted over the lower lumbar vertebra without deformity, skin lesion, or focal neurological deficit. Her laboratory test results revealed that the white blood cell count was 7600/μL with normal differential. The level of C-reactive protein was 3.5 mg/L, and erythrocyte sedimentation ratio was 27 mm/h. The blood cultures remained negative at 10 days. Transthoracic echocardiogram showed no valvular vegetation, and the immunoglobulin serologic assay was negative.

The anteroposterior and lateral plain radiograph revealed thoracic lumbar scoliosis with curves of 23.9 and 7.6 degrees. In addition, the magnetic resonance imaging (MRI) of lumbar spine demonstrated lumbar (L2–L3) vertebral osteomyelitis, discitis, and an epidural abscess (Fig. 1)

F1FIGURE 1:

Lumbar MRI demonstrates destructive changes in the L2–L3 disc space with interosseous abscess with a small epidural abscess component extending into the left neuroforamen.

The patient underwent intraoperative washout, L2–L3 lumbar interbody fusion with placement of titanium mesh biomechanical crescent interbody cage along with posterior spinal instrumentation and bone graft. A deep aspiration of pocket site was sent to the microbiology laboratory for PCR amplification of the bacterial, mycobacterial, and fungal culture. Gram stain showed no organism; aerobic and anaerobic cultures remained negative at 10 days. Acid-fast bacillus smears and fungal culture came back negative. 16S rRNA detected C. hominis. The patient was treated with ceftriaxone 2 g for a duration of 6 weeks. At the 6 weeks follow-up, her back pain had resolved. Magnetic resonance imaging showed no residual infection.

DISCUSSION

Cardiobacterium hominis is a facultative anaerobic, fastidious, capnophilic, Gram-negative bacillus, and a member of the HACEK (Haemophilus, Aggregatibacter, Cardiobaterium, Eikenella, Kingella spp) group of organisms.1 There are only 2 species in the genus Cardiobacterium, and they are C. hominis and C. vivarium. These organisms are a rare cause of Gram-negative endocarditis, especially in the pediatric population.

Cardiobacterium hominis is a member of the normal oropharyngeal flora, but upon disturbance of mucosal integrity, it can become invasive and pathogenic leading to infection.2 Risk factors for Cardiobacterium infection include poor dentition, recent dental procedure, prior endocarditis, cardiac anatomical abnormalities, cardiac implantable electronic device, prosthetic heart disease, and recent endoscopy, none of which our patient had.

The presence of C. hominis in the blood is virtually diagnostic of endocarditis. It has also been reported to cause extracardiac infections such as septic arthritis, pericarditis, bacterial meningitis, osteomyelitis, neonatal sepsis peritonitis, abdominal abscess, septicemia, and lacrimal gland infection.3–6

Upon literature review, to date only, 3 cases of discitis and osteomyelitis caused by C. hominis have been reported in adult patients7–9 aged older than 60 years with a risk factor such as a bioprosthetic aortic valve or the presence of a cardiac device. They were found to have evidence of endocarditis and valve vegetations on echocardiogram, and the blood cultures were positive for C. hominis. To the best of our knowledge, in this report, we describe the first pediatric case of C. hominis osteomyelitis in a 14-year-old female patient with no risk factors, a normal transthoracic echocardiogram, and negative blood cultures at 10 days, thus making the diagnosis challenging.

The HACEK organisms are slow growing in standard blood culture media, and recovery may require prolonged incubation. Cardiobacterium hominis is oxidase-positive, catalase-negative, nitrate-negative, urease-negative, and indole-positive; however, these reactions may be weak. The production of indole is a feature useful in distinguishing C. hominis from other “HACEK” organisms.1 Modern advances in blood culture instrumentation and MALDI-TOF mass spectrometry have facilitated growth and identification.10 Although the growth of C. hominis in modern commercial media has been detectable within 5 days, incubation for 2 weeks is recommended before reporting a culture as negative. In addition, C. hominis has been cultured from an infected tissue sample. The first reported case of C. hominis vertebral osteomyelitis and discitis was the case of a 75-year-old woman, whose diagnosis was delayed as initial blood cultures were negative.8

In our patient, the blood cultures did not grow any bacteria at 10 days of incubation; the culture of intraoperative deep aspiration of the pocket site was negative. The diagnosis of C. hominis was made using a 16S rRNA broad-range PCR of the intraoperative sample of spinal abscess in 5 days.

The use of broad-range PCR is a highly sensitive technique that amplifies small quantities of bacterial or fungal DNA; moreover, if combined with sequencing, it can identify a specific organism. There are broad-range PCR techniques for amplifying 16S rDNA (for bacteria) or 18SrDNA (for fungi), which can then be sequenced for pathogen identification. This technique has previously been used as supplemental diagnostic tools in identification of culture negative infective endocarditis; however, its use to identify the causative agent for osteomyelitis and discitis has not been reported so far. Hence, this case emphasizes the importance of suspecting a fastidious organism when cultures are negative for patients with evidence of systemic infection and the usefulness of molecular testing as an important tool for the rapid detection of these organisms. In addition, this method can discriminate C. hominis from Cardiobacterium valvarum, which has recently been found to be responsible for endocarditis.

Previously, isolates of C. hominis were susceptible to penicillin and ampicillin. However, β-lactamase producing strains of C. hominis have been identified, and since antimicrobial susceptibility testing may be difficult to perform on HACEK microorganisms,11 the American Heart Association now recommends the use of third-generation cephalosporins as the treatment of choice. For patients who cannot tolerate β-lactams, fluoroquinolones are an appropriate alternative.12 Our patient received the recommended dose of ceftriaxone 2 g intravenously for 6 weeks. In comparison to other reported cased of C. hominis vertebral osteomyelitis, our patient underwent intraoperative washout, L2–L3 lumbar interbody fusion with the placement of titanium mesh biomechanical crescent interbody cage, posterior spinal instrumentation, and a bone graft. The follow-up MRI of the lumbar spine after the completion of antibiotic therapy demonstrated no residual infection.

In conclusion, vertebral osteomyelitis with C. hominis is a rare case and can be challenging to diagnose. This pathogen is difficult to identify with common culture methods, which can lead to incorrect diagnosis and treatment. Therefore, the broad-range PCR and gene sequencing with comparison to the DNA database is useful in these circumstances. This case demonstrates the importance of the 16S rRNA gene sequencing for diagnosing HACEK infection.

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