Streptococcus mitis infective endocarditis in a patient with ventricular septal defect and orthodontic appliances

Background

The potential of the normal oral flora to cause infective endocarditis in the setting of orthodontic appliances is not addressed in the current guidelines.

Streptococcus mitis belongs to the group of the oral streptococci (previously known as the Viridans group Streptococci). Oral streptococci are the dominant species comprising more than 50% of the oral microbiota in healthy individuals. They are commensals with generally low pathogenic potential, but they can invade the bloodstream and cause serious infections.1 Among the oral streptococci, S. mitis is a leading cause of infective endocarditis and bacteraemia.2

S. mitis is a pioneer coloniser of the neonatal human oropharynx and remains a significant commensal throughout life. The origin of S. mitis colonisation of the neonatal oropharynx is the primary caregiver of the neonate and the external environment. The successful colonisation of the oropharynx is facilitated by various factors. The most important of them is the ability of S. mitis to produce adhesins that promote attachment to host tissues and IgA1 proteases to overcome the local host defences. Moreover, S. mitis is remarkably tolerant to various human antimicrobial peptides and can also modulate the expression of the proinflammatory chemokine interleukin-8. The latter, along with other not well-investigated mechanisms, appears to dampen the inflammatory immune response. The pathogenesis of S. mitis infective endocarditis is probably promoted by the very same factors that make S. mitis a successful oral commensal. The ability of S. mitis to produce adhesins and bind directly to human platelets is key in the pathogenesis of infective endocarditis. S. mitis can also produce a toxin similar to the Streptococcus pneumoniae pneumolysin.2

Health Protection Agency in the UK reported increasing rates of bacteraemia caused by S. mitis exceeding that of group A or Group B streptococci. S. mitis bacteraemia increased from 1.9 cases per 100 000 in the period 2002–2004 to 2.4 cases per 100 000 in 2008. S. mitis strains isolated from bacteraemic patients were also routinely resistant to commonly used antibiotics. Patients tend to become infected with their own commensal strains and the mortality rate from S. mitis bacteraemia ranges from 6% to 30%.2

Infective endocarditis is a rare infection of the endocardium with a global incidence rate estimated between 1.5 cases and 11.6 cases per 100 000 individuals per year. The mortality rate remains high—up to 22% in hospital, and up to 40% on 5-year follow-up. The higher mortality rates were reported in developing countries. The overall mean proportion of Infective Endocarditis (IE) patients that underwent valve surgery was 0.324±0.188.3

Right-sided infective endocarditis accounts for 5%–10% of infective endocarditis cases. It is more frequent in intravenous drug users, but can also affect patients with pacemakers, Implantable Cardioverter Defibrillator (ICD), central venous catheters or congenital heart disease. S. aureus is the predominant microorganism (60%–90% of cases) and the tricuspid valve is the most frequently affected right heart structure. The usual manifestations of right-sided IE are persistent fever, bacteraemia and multiple septic pulmonary emboli, which may manifest as chest pain, cough or haemoptysis. In-hospital mortality is approximately 7%.4

In a study from 2009, oral streptococci were the second the most common cause worldwide for infective endocarditis (17%) after the Staphylococcus group (42%), with higher incidence rate seen in South America (26%) and lowest incidence in North America (9%).5 In a more recent review from 2016 oral streptococci remained the second most commonly reported micro-organisms, but they were the leading cause for infective endocarditis in Asia and also in patients with congenital heart defects.6

Case presentation

A 17-year-old girl presented to the emergency department in a remote and rural hospital in March 2020, with recent onset of mild, left-sided, pleuritic chest pain. She reported 8 weeks’ history of malaise, lethargy, night sweats, increasing dyspnoea and lately—light-headedness on exertion. Her illness started in January 2020 with tiredness, chills, body aches and night sweats. The symptoms were attributed initially to a viral infection and the stress around her school exams. She felt better for a while in January 2020 and then her symptoms worsened again. She denied fever, cough or substantial weight loss.

She lives with her mother and sister and reported no COVID-19 contacts, animal exposure, or insect bites. There was no history of intravenous drug use, blood transfusions, high-risk sexual contacts or recent foreign travel.

She was fitted orthodontic appliances (self-ligating Damon Q brackets) in November 2017 and had regular follow-ups and adjustments in the Dental Clinic since. Two years later, in late November 2019, a routine adjustment of the appliances resulted in a protruding arch wire causing ongoing buccal abrasion and mild intermittent bleeding in the following days. She requested an urgent dental review, but there was no visiting dentist available. She was given an appointment several days later in December 2019 at which time the arch wire was trimmed and stopped further buccal abrasion.

Her medical history was notable for a restrictive perimembranous ventricular septal defect under follow-up in the cardiology clinic, lactose intolerance, acne and moderate thoracolumbar scoliosis with convex to the right.

Medication history included the use of contraceptive patch and adapalene cream for acne.

On presentation to the emergency department, her temperature was 37.5°C, the heart rate was 117 beats per minute, the blood pressure—122/74 mm Hg, the respiratory rate—16 /min and the oxygen saturation—100% in room air.

The physical examination revealed a slender, teenage girl of Caucasian origin, with pale complexion, without clubbing, cyanosis or peripheral stigmata of infective endocarditis. The cardiovascular examination revealed regular heart sounds with a harsh ejection systolic murmur loudest at the left sternal edge in keeping with the known ventricular septal defect. Neurological, pulmonary, gastrointestinal and skin examinations were normal, and there was no evidence of organomegaly, lymphadenopathy or rash. Musculoskeletal examination revealed the known scoliosis.

Investigations

The full blood count revealed anaemia (haemoglobin—82 g/L) and mild neutrophilia (white cell count—11.1×10⁹/L, neutrophils—8220/mm³). There was significant rise in C reactive protein—129.6 mg/L (normal range: 0–8 mg/L) and erythrocyte sedimentation rate—130 mm/hour (normal range: 0–10 mm/hour).

There was also mild rise in prothrombin time—16.9 s (normal range: 9.8–13.5 s), international normalised ratio—1.5 (normal range: 0.8–1.2), D-dimer—394 ug/L (normal range: 0–230 ug/L) and lactate dehydrogenase—231 U/L (normal range: 100–200 U/L). Three blood cultures were sent in the following hours separated in time and site, but the first reports were available after 24 hours.

The ECG showed sinus tachycardia.

The chest X-ray was unremarkable, apart from the known scoliosis.

Differential diagnosis

During her assessment in the emergency department, a strong suspicion was raised for subacute infective endocarditis of the right heart, complicated with septic lung emboli causing the reported pleuritic chest pain, given the known ventricular septum defect and the traumatic adjustment of the orthodontic appliances in late November 2019.

However, due to the presentation with pleuritic chest pain and concomitant use of the contraceptive patches, the protracted constitutional symptoms in the previous several weeks, anaemia and the significantly raised Erythrocyte Sedimentation Rate (ESR) we felt we should also exclude pulmonary thromboembolism and other underlying systemic illnesses, like malignancy.

A CT angiography of the pulmonary artery (CTPA) was requested and revealed small wedge-shaped areas in the lungs suspicious for mycotic emboli (figure 1).

The patient was admitted to the hospital for treatment with intravenous antibiotics for a working diagnosis of right-sided infective endocarditis, complicated with septic lung emboli.

The results of the blood cultures were available in the following 24 hours and all revealed bacteraemia from S. mitis sensitive to penicillin (Minimum Inhibitory Concentration (MIC): 0.094).

The following day, the transthoracic echocardiography confirmed the working diagnosis by revealing a vegetation on the septal leaflet of the tricuspid valve (figure 2) in relation to the ventricular septal defect. The peak velocity through the ventricular septal defect was 5 m/s. The heart chambers were non-dilated and there was trivial regurgitation of the aortic, mitral and tricuspid valves.

Outcome and follow-up

Postoperatively, the patient had further 3 days treatment with intravenous benzylpenicillin, followed by oral erythromycin for a week. She made a smooth recovery and was discharged home 10 days later. A culture taken from the tricuspid area intraoperatively was sterile.

The septic lung emboli responded nicely to the extended treatment with antibiotics and required no additional management. The patient reported quick resolution of the pleurisy and dyspnoea and remained asymptomatic after the discontinuation of the antibiotics.

She continued shielding in the community due to the COVID-19 pandemic and she was followed up in the local outpatient cardiology clinic. After 8 weeks from the surgery, a routine blood test revealed mildly raised C reactive protein (26 mg/L) without any infective symptoms. Serial blood investigations revealed normalisation of the C reactive protein without the use of antibiotics and serial blood cultures were sterile.

At 3 months’ review, she remained well and symptom-free. The transthoracic echocardiography showed non-dilated heart chambers and trivial mitral, tricuspid and aortic regurgitations. The C reactive protein was normal. She was scheduled for a follow-up transthoracic echocardiography and clinic review after 1 year.