Aa is a slow-growing capnophilic Gram-negative coccobacillus which was first isolated by Klinger in 1912, member of HACEK group of gram-negative bacteria [2]. Its name derived from the frequent association with Actinomyces israleii in actinomycosis. It is part of the normal human oral flora. It is associated with periodontal infection, dental disease, as well as for systemic infections, endocarditis, soft tissue abscesses; brain abscesses, osteomyelitis and pneumonia are less common [7].
We conducted a Medline-type bibliographic search to identify documented cases of pediatric infections caused by Aa, excluding those involving only the oral cavity (dental caries, periodontal disease) and including systemic infections, remote infections and those with local regional involvement (even in the facial district). Key search terms were ‘Aggregatibacter actinomycetemcomitans infection’ or ‘Case report of Aggregatibacter actinomycetemcomitans associated disease’, using filter for age (Child: birth-18 years) (Table 1).
The main limitations of our case report are that current literature is poor of pediatric cases of infections by Aa and the manuscripts are often old. The strength of our manuscript is related to the uniqueness of the clinical presentation and the localization of infection in a pediatric patient, treated in a III level pediatric hospital.
Until January 2021, 20 cases of Aa infection were reported in the literature (including in the search patients aged 0 to 18), 11 females and 8 males, the age of the patients ranged from 1.5 to 18 years: in some cases it was the only isolated pathogen (15/20 cases), in 5 cases it was associated with other bacteria including Actinomyces israelii, Bacteroides ureolyticus (B. corrodens), Eikenella corrodens and Haemophilus. aphrophiIus, capnocytophaga species [8–21].
Aa infections may have different locations in children. There were described different pediatric cases with pulmonary involvement: 1 patients with pneumonia [8], 1 with empyema [14], 2 patients with pneumonia associated with chest wall mass [8, 14], 6 cases of lung consolidation with chest wall mass and a bony involvement (especially lytic lesions of the ribs), associated in 3 cases with a pleural effusion and in 1 case with a mediastinal and pulmonary abscesses [9, 14, 15, 16, 17], 3 cases of pneumonia associated with empyema [8, 10, 12].
Our case is different from the others, the most similar is a case of a girl of 14 years old with lung consolidation, pleural infection extending to the chest wall and subphrenic area, but in our case there’s not concurrent pneumonia [8]. There are two cases described with brain involvement [14, 21]: one patient with a brain abscess after surgery, one case with subdural empyema.
Besides, one case of osteomyelitis [13], one with septic arthritis [18], one with endocarditis after valvuloplasty [19] and a one case of a soft tissue mass over mandibular area [20] are reported.
In our case, the Aa infection involved the visceral and parietal pleura, causing empyema, extending to the chest wall and subphrenic area.
All patients are immunocompetent, no specific immunological deficit were associated with infections, but in some cases there are underlying conditions associated with a major risk of Aa infections according to the related pathogenic mechanism, for example pulmonary infection by Aa is described in patients with an increased risk of aspiration: two cases of cerebral palsy [8, 14], one with residual tracheal–cutaneous fistula and tracheostomy with pulmonary infection by Aa [10]. In two patients Aa infection has been reported after heart and brain surgery [14, 19]. In one case Aa infection occurred in a patient with diabetes mellitus [14].
Clinical manifestations depends from localization, typically, the course of the infection is subacute, with fever, anorexia, weight loss, and night sweats, malaise, or bulging mass and local pain. In our case patient presented with a right abdominal mass with occasional dry cough and marked asthenia, without fever, weight loss or recent history of trauma were reported.
As the presentation is nonspecific for an infectious process, a differential diagnosis may be necessary, especially with malignancy, Mycobacterium tuberculosis infection and trauma [9].
Duration of symptoms ranged from 4 days to 365 days, in this case they lasted 7 days. The precise pathogenesis of Aa infections is unknown. Because the Aa is a mouth commensal, presumably its invasive extension occurs via the mucous membrane resulting in haematogenous dissemination to the skin, joints, bones and disc spaces (due to enzymes in saliva that may modify mucosal surfaces to promote adhesion and colonization), or as a result of aspiration during dental procedure [22, 23].
In our case, we found that the Aa infection may have spread perpendicular to the chest wall, invading and breaking through the visceral and parietal pleura, extending to the chest wall and subphrenic area, without involvement of the pulmonary parenchyma. This behaviour suggests a collagenolytic activity, similar to the Actinomyces israelii.
Our patient didn’t have a periodontal disease but presented dental caries, in our search 12/20 patients had periodontal disease or dental caries, in one patient was not mentioned.
The diagnosis of Aa depends on bacterial culture, the major number of cases have been diagnosed by culture of biopsy specimen or aspirate from the involved tissue, isolation and identification of this organism may require prolonged incubation (72– 96 h) [24]. The use of modern molecular diagnostic methods may be more rapid and accurate.
Aa is generally susceptible to main classes of antibiotics (cephalosporins, aminoglycosides, chloramphenicol, rifampicin and tetracycline). Resistance to ampicillin and penicillin is common. In addition to antimicrobial therapy, dental medication will be needed to avoid recurrence.
The optimal duration of therapy is not known, but a long period of antibiotic therapy is needed. Duration depends on the clinical response of the patient, on the extent of tissue involvement, and on resolution of the infective process on follow-up.
In the pediatric cases reviewed here, the range of duration of treatment was between 21 days to 365 days in survived children, in our patient it lasted 180 days. The major number of children survived (18/20), without sequelae. Two patients died as a result of a compromise of the general conditions induced by the underlying disease (cerebral palsy) [8, 14].
In conclusion extra-oral infections caused by Aa are extremely rare and not yet well described in current literature, especially in pediatric patients. Our patient represents the only pediatric case described in literature presenting with subphrenic abscess and pulmonary empyema without involvement of lung parenchyma. Aa pulmonary involvement is quite rare in children and can mimic tuberculosis or malignancy. Patients are usually immuno-competent and most of them have an underlying periodontal disease or dental caries. Diagnosis is not prompt and requires tissue biopsy and prolonged bacterial culture. Duration of antibiotic treatment is usually prolonged and based on clinical and radiological response. Our case report reminds us the importance of an accurate inspection of the oral cavity during the examination of pediatric patients and of considering HACEK group infections among differential diagnosis in children with suggestive clinical signs.