Discussion

A. urinae is an emerging alpha-haemolytic, gram-positive coccus increasingly recognised as a pathogen in invasive infections, including infective endocarditis. ^{Reference Banerjee, Murali, Azhar, Pathmanathan and Chaudhuri1,Reference Ahmed, Bardia, Judge, Ahmad, Malozzi and Calderon2} Its identification is often hindered by phenotypic similarities to Staphylococcus and Enterococcus, leading to underdiagnosis. ^{Reference Ahmed, Bardia, Judge, Ahmad, Malozzi and Calderon2} While 16S rRNA gene sequencing remains the gold standard for species identification, its cost and limited availability restrict routine use. ^{Reference Ahmed, Bardia, Judge, Ahmad, Malozzi and Calderon2,Reference Ludhwani, Li, Huang, Sikora and Thomas4} Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry offers a faster, more accessible alternative by matching bacterial protein mass spectra to reference libraries. ^{Reference Sugaya, Muraoka, Doi and Kawahito3} Additionally, fluorescence in situ hybridisation has shown promise in identifying A. urinae in culture-negative infective endocarditis cases and visualising biofilm activity. ^{Reference Yaban, Kikhney and Musci5}

The pathogenesis of A. urinae involves biofilm formation and platelet activation on infected tissues, contributing to immune evasion and embolic complications. Infective endocarditis due to A. urinae carries a high mortality rate, approaching 50%, underscoring the importance of early recognition and targeted therapy. ^{Reference Sugaya, Muraoka, Doi and Kawahito3}

Risk factors include advanced age, male gender, structural cardiac anomalies, and urinary tract abnormalities. Although paediatric cases are rare, three have been reported, including our case. All involved congenital heart defects and urinary tract issues. Our patient, a 15-year-old female with atrioventricular septal defect and neurogenic bladder, presented with embolic stroke secondary to mitral valve infective endocarditis.

Our patient received a 4-week course of ceftriaxone and metronidazole, followed by mitral valve replacement and a 6-week postoperative regimen of gentamicin and penicillin. The two previously reported paediatric cases also underwent surgical management and combination antibiotic therapy, resulting in favourable outcomes. ^{Reference Sous, Piwoz, Baer and Bhavsar7,Reference Qureshi and Patel8} These cases highlight the need for heightened clinical suspicion, timely diagnosis, and a multidisciplinary approach to improve prognosis in paediatric A. urinae endocarditis.

A. urinae is an alpha-haemolytic, gram-positive coccus that is an emerging pathogen for invasive infections. ^{Reference Banerjee, Murali, Azhar, Pathmanathan and Chaudhuri1,Reference Ahmed, Bardia, Judge, Ahmad, Malozzi and Calderon2} A. urinae is often misidentified as Staphylococcus as they both display semi-transparent colonies and appear in pairs, tetrads, or clusters on blood agar plates. ^{Reference Ahmed, Bardia, Judge, Ahmad, Malozzi and Calderon2} As a consequence of these diagnostic barriers, the role of A. urinae in the development of invasive infections, such as endocarditis, is underappreciated, and the present body of literature is fairly limited. We present the third reported case of A. urinae infective endocarditis in the paediatric population.

The mortality rate of infective endocarditis caused by A. urinae can reach approximately 50%. ^{Reference Sugaya, Muraoka, Doi and Kawahito3} Prompt diagnosis of A. urinae as the causative pathogen of infective endocarditis and establishing appropriate treatment can crucially improve the mortality outcome. While the gold standard for identification of Aerococcus species is 16S ribosomal RNA gene sequencing, this method is rarely used due to its high cost and limited availability. ^{Reference Ahmed, Bardia, Judge, Ahmad, Malozzi and Calderon2,Reference Ludhwani, Li, Huang, Sikora and Thomas4} Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry is a faster, more accessible method of A. urinae identification, which is divided into two processes: a laser is used to ionise the sample (matrix-assisted laser desorption ionisation), then the ions are detected through time-of-flight mass spectrometry. Bacterial identification is then based on pattern matching between the protein mass spectrum of the tested bacteria and the mass spectrum data of the bacteria in the library. ^{Reference Sugaya, Muraoka, Doi and Kawahito3} Another unique feature of A. urinae is its ability to produce biofilms by activating platelets on infected structures, which contributes to pathogenesis and results in suboptimal host defence. ^{Reference Yaban, Kikhney and Musci5} Fluorescence in situ hybridisation, an emerging molecular biological method, can help identify pathogens that may have been missed in routine culture studies and help visualise the infection’s state of activity. In one study, two heart valve samples from two different patients with infective endocarditis were collected. Both were screened using the fluorescence in situ hybridisation technique, and the positive sections of tissue were sent for PCR amplification. This resulted in a 99.6% and 100% homology to A. urinae. From there, a fluorescently labelled probe AURI specific to A. urinae was designed. ^{Reference Yaban, Kikhney and Musci5} This developing technique has the potential to significantly expedite the diagnosis of A. urinae infection.

Predisposing risk factors for A. urinae infective endocarditis include advanced age, male gender, urinary tract abnormalities, and cardiac abnormalities. Beyond advanced age, these risk factors warrant careful consideration even in the paediatric population. There are two other reported cases of A. urinae infective endocarditis in paediatrics aside from our case. One being an 11-year-old male with a history of unrepaired ventricular septal defect and imperforate anus, which is associated with an increased risk of urinary tract infections, largely due to recto urinary fistulas, coexisting urinary tract abnormalities, and potential bladder dysfunction. ^{Reference Sous, Piwoz, Baer and Bhavsar7} The other reported paediatric case is a 17-year-old male with a native bicuspid aortic valve and an uncircumcised penis. ^{Reference Qureshi and Patel8} Uncircumcised males have a 4–20 times higher risk of developing a urinary tract infection. ^{Reference Morris and Wiswell9} This, combined with the presence of cardiac abnormalities, increases the patient’s susceptibility to A. urinae infective endocarditis. Our patient is a 15-year-old female with a history of atrioventricular septal defect and neurogenic bladder with vesicostomy. All three reported paediatric cases of A. urinae infective endocarditis occurred in patients with structural heart disease and additional risk factors for urinary tract infection.

A formal antibiotic treatment guideline for A. urinae infective endocarditis has not been established. ^{Reference Sugaya, Muraoka, Doi and Kawahito3} Multiple regimens have reported efficacy. Penicillin is the first-line antibiotic reported in literature. ^{Reference Meyer and Hug6} It is also reported that gentamicin has a synergistic effect in combination with penicillin and is distinctly beneficial if a biofilm has already formed. ^{Reference Sugaya, Muraoka, Doi and Kawahito3,Reference Meyer and Hug6} Benzylpenicillin, ampicillin, meropenem, rifampicin, nitrofurantoin and vancomycin consist of the known susceptibility pattern of A. urinae. ^{Reference Meyer and Hug6} Ciprofloxacin resistance has been reported. In addition to antibiotic therapy, surgical management was reported in 36.6% of all cases. ^{Reference Meyer and Hug6}

Our patient was initially treated with a 4-week ceftriaxone and metronidazole regimen, followed by mitral valve replacement operation, and a 6-week post-op gentamicin and penicillin treatment. In the reported case of the 11-year-old male with ventricular septal defect, the patient was initially treated with ceftriaxone and vancomycin after blood cultures grew gram-positive cocci in clusters for four consecutive days. Matrix-assisted laser desorption ionisation time-of-flight confirmed A. urinae as the causative pathogen. The antibiotic treatment then changed to penicillin G (MIC 0.047 mg/L). A notable complication in this patient’s course was the development of large mycotic pulmonary artery aneurysms secondary to septic emboli. This was repaired in surgery via right lower lobectomy and removal of the aneurysmal pulmonary artery segment that had perforated from the embolus. The patient received IV penicillin G for 6 weeks post operatively and had a successful recovery. ^{Reference Sous, Piwoz, Baer and Bhavsar7} In the case of the 17-year-old male, the patient received a total of 6 weeks of penicillin and 3 weeks of gentamicin for synergy. The patient underwent an aortic valve replacement and a patch reconstruction of the noncoronary sinus and mitral valve anterior leaflet after resection of the mitral valve vegetation with no postoperative complications. A combination of penicillin and gentamicin therapy with surgical intervention resulted in successful clinical outcomes for the reported cases in the paediatric population.