Streptococcus intermedius Brain Abscess with Lung Abscess and Aortic Valve Endocarditis. A Case Report and Literature Review

1. Introduction

Streptococcus intermedius is a gram positive, catalase-negative coccus belonging to the Streptococcus anginosus group (SAG), which is often referred to as the Streptococcus milleri group, including S. intermedius, S. anginosus, and S. constellatus. SAG bacteria have been detected in the mouth, the gastrointestinal and upper respiratory tract, and the vagina [1,2].

Streptococcus intermedius is frequently associated with brain and liver abscesses, while pleuropulmonary infections are considered rarer [3]. Even less frequent is the association of lung and brain abscess due to this agent with left heart endocarditis. We describe the case of a 40-year-old man with a brain abscess due to S. intermedius and concomitant lung abscess and aortic native valve endocarditis.

2. Case presentation

The patient was a 40-year-old male of Egyptian origin, residing in Italy for about 15 years. He denied allergies, previous hospitalizations, or surgical interventions. For about 20 days he experienced persistent cough, asthenia, intermittent fever, intense headache, and worsening back and lumbar pain partially responsive to therapy with paracetamol and non-steroidal anti-inflammatory drugs. Due to the worsening of these symptoms, he went to the Emergency Department (ED) of a peripheral Hospital, where his vital signs were as follows: blood pressure 140/80 mmHg, heart rate 105 bpm, respiratory rate 17 breaths per minute, oxygen saturation 97% in room air, body temperature 38°C, and Glasgow Coma Scale 15. There were no focal neurological deficits, no meningeal signs, no positive covid antigen tests. Blood tests showed neutrophilic leukocytosis (white blood cells 12,900/mmc; neutrophils 77.7%) and a slight increase in C-reactive protein (1.2 mg/dL). A non-contrast cranial computed tomography (CT) scan revealed a necrotic-colliquative expansive lesion measuring 36 mm in diameter in the left subcortical occipital area, with an associated perilesional oedema. The patient started treatment with ceftriaxone 2 g intravenously (IV) and methylprednisolone 4 mg.

He was then transferred to the ED of a second level Center with Neurosurgical facilities, where a contrast-enhanced chest CT scan showed a pleural-based consolidative lesion in the left lung lower lobe measuring 63 mm in diameter, associated with a 16 mm internal cavity (Figure 1). The patient was admitted to the Oncologic Pneumology department. After an Infectious Diseases consultation, the antibiotic therapy was modified to include meropenem 2 g three times/day (TID) and vancomycin 500 mg four times/day. QuantiFERON-TB (QTF) Gold Plus and blood cultures resulted negative. A nuclear magnetic resonance (NMR) scan (Figure 2) confirmed the abscess nature of the brain lesion and revealed its communication with the trigone of the left lateral ventricle, along with perilesional oedema.

He was then transferred to the Neurosurgery department, where a bronchial aspiration was performed for direct microscopic examination, culture and DNA testing for Mycobacterium tuberculosis complex, non-tuberculous mycobacteria, and Aspergillus. A full spine NMR scan was also conducted but resulted negative for focal lesions. Pending microbiologic results, considering the possible tubercolar etiology of the disease, empirical combination therapy with linezolid 600 mg two times/daily, meropenem 2 g TID, rifampicin 600 mg once daily (QD), isoniazid 300 mg QD, ethambutol 1200 mg QD, levofloxacin 750 mg QD, and dexamethasone 6 mg TID was initiated.

Subsequently, a left occipital parasagittal craniotomy procedure was performed, resulting in drainage of the abscess and partial removal of the abscess capsule, along with sampling of biological material. The culture of the cerebral abscess samples resulted positive for Streptococcus intermedius sensitive to ampicillin, ceftriaxone, clindamycin, teicoplanin, and vancomycin. Thus, the patient started targeted therapy with ceftriaxone 2 g IV BID and dexamethasone 12 mg IV BID. Following the QTF and PCR results, which tested negative for mycobacteria and fungi, the previous anti-tubercular therapy was discontinued.

The patient was then transferred to our Infectious Diseases Center in stable conditions and afebrile. During the hospitalization, a transesophageal color Doppler echocardiography revealed aortic valve thickening with a prolapsing attitude of the right cusp, and a nodular hyperechogenic image between the right and left cusps, along with mild valve insufficiency. Due to the presence of multiple carious lesions, a dental CT scan was performed, showing periapical bone resorption at tooth 14 in the upper arch and a large carious lesion of tooth 36, accompanied by an inflammatory periapical bone resorption area.

The patient received a four-week course of ceftriaxone 2 g IV BID, resulting in progressive improvement of his clinical, laboratory, and radiological findings (Figure 3). He was discharged in good general conditions, with instructions to continue oral therapy with amoxicillin/clavulanate 875 mg TID for further 10 days and a program of cardiological, neurosurgical and dental outpatient visits. After a three-month follow-up the patient is still in good health with no signs of infection relapse.

3. Discussion

Pleuropulmonary infections due to Streptococcus intermedius are considered uncommon [4]; however, in recent years their importance has been increasingly recognized. We reviewed the available medical literature by PubMed with the keywords “Streptococcus intermedius” AND “lung abscess”, “pleural effusion”, “pleural empyema” from 1993 to 2023, published in English. We found 34 articles meeting the inclusion criteria (Table 1), of which 4 described concomitant brain and lung abscesses, but none reported the presence of lung and brain abscess due to S. intermedius associated with left heart endocarditis [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34]. Only one paper [14] described the case of lung and brain abscess associated with Chiari network endocarditis in the right heart.

Streptococcus intermedius is a Gram-positive, catalase-negative, nonmotile and facultative anaerobe coccus that colonize the mouth and the upper respiratory tract [2,26]. SAG streptococci are oral bacteria and may be unable to grow significantly on ordinary aerobic cultures; as a consequence, conventional cultivation may underestimate the role of these pathogens [25] in respiratory infections. The significance of anaerobes and oral bacteria in patients with community-acquired pneumonia and pleuritis has previously been reported [35,36]. In some cases, a 16S rRNA gene sequencing analysis of bronchoalveolar or pleural effusion specimens was able to identify pathogens that are generally difficult to isolate using ordinary cultivation methods [25].

Risk factors for S. intermedius pleuropulmonary disease include smoking, alcoholism, dental diseases, chronic obstructive pulmonary disease, malignant neoplasms, liver cirrhosis, and diabetes [3]. Our patient had dental lesions that could have caused bacteremia and aortic valve endocarditis with brain abscess as a haematogenous spread complication. The lung abscess could have been caused by aspiration or haematogenous spread. Teramoto et al. [37] reported that aspiration may contribute to the pathogenesis of pneumonia in elderly patients, and that an increased age is associated with the risk of developing aspiration pneumonia. Given the young age of our patient, the aspiration in this case is less likely, whereas the haematogenous spread could have caused the lung abscess. Bacteraemic venous blood following the venous draining system to the right ventricle of the heart is pumped into the pulmonary arteries, until the capillary network of alveoli and parts of the visceral pleura. Indeed, several works described the simultaneous occurrence of brain abscess and lung abscess or pleural empyema [22]. In their recent work, Dyrhovden and coll. suggest that facultative and anaerobic oral bacteria, able to spread by deoxygenated venous blood to establish purulent infections in brain tissue, could also be able to reach and establish pyogenic infections in the lung parenchyma or pleural cavity [22].

S. intermedius is reported as a causative pathogen in only 2-5% of cases of bacterial pneumonia, but in 13-44% of pulmonary abscesses/empyema [21]. S. intermedius infections are commonly associated with abscess development. Virulence factors contributing to tissue invasion and abscess formation by this agent have recently been described by Issa and coll. [38] and include antigens I/II surface proteins; hydrolytic enzymes such as hyaluronidase, chondroitin sulfatase, and deoxyribonuclease; biofilm formation and defensive genes to oppose the human immune system, such as superantigens that cause lymphocyte apoptosis; the polysaccharidic capsule formation; the genes of the Streptococcus Invasion locus system; the intermedilysin, which initiates pore complex formation in host cell membranes, and the sialidase A that contributes to pathogenicity by controlling interbacterial communication and host-bacterial interactions. Abscess drainage and surgery should be considered, on a case by case basis, in order to successfully achieve an adequate source control of the infection.

4. Conclusions

In summary, we described a case of brain abscess caused by S. intermedius, associated with lung abscess and aortic valve endocarditis, in a young patient with dental disorders. In addition to being a well known cause of brain abscess, S. intermedius is increasingly recognised as a causative agent of pleuropulmonary disease.