Abiotrophia defectiva is a facultative anaerobic gram-positive streptococcus (1–3) which is a normal flora of human oral, upper respiratory, urogenital, and intestinal tracts. In 1961, Frenkel and Hirsch (4) defined a virulent streptococcus with “satellite” growth around other bacterial colonies as nutritionally variant Streptococci. In 2000, Collins and Lawson (3) classified nutritionally variant Streptococci into Abiotrophia and Granulicatella by 16S rRNA gene sequence, while Abiotrophia has only one species, A. defectiva.

When the body is immunocompromised, it becomes an opportunistic pathogen and may cause infective endocarditis (IE) (4), an inflammatory endocardial lesion caused by a variety of pathogens, usually streptococcal and staphylococcal infections (5). IE caused by A. defectiva is clinically uncommon, accounting for 5–6% of all patients with IE (5), but it has a high mortality rate and many complications. With the progression of the disease, complications such as septic arthritis are observed.

Only a few pediatric cases have been reported internationally (6), and there are no clinical studies with large sample sizes. A search of PubMed, China National Knowledge Infrastructure, Wanfang Medical Online, and other databases revealed that one pediatric case of IE caused by A. defectiva was reported in Taiwan in 2002 (7). As far as we know, the first pediatric case of IE caused by A. defectiva in mainland China is reported as follows.

An 8-year-old girl was admitted on July 6th, 2021. Four days before admission, the child had a body temperature of 39.2°C with headache and malaise. Three days before admission, she had symptoms of right-sided slanting of the mouth, slurred speech, right-sided limb weakness, and unstable holding. A head CT performed at another hospital showed a hypodense shadow next to the posterior horn of the right lateral ventricle (Figure 1A). She was given ceftriaxone anti-infective treatment for 2 days, but the symptoms did not improve. Therefore, she was transferred to our department.

Physical examination showed mild anemia, pharyngeal congestion, enlarged type II tonsils with yellowish-white secretions adhering to the surface, a heart rate of 116 beats per minute, and a class II/6 systolic murmur audible in the precordial region, neck stiffness, right-sided angle of the mouth, tongue extension to the right, grade IV muscle strength in the right limb, grade V muscle strength in the left limb, hyperalgesia on the right side, and positive Barthel’s sign on the right side. Auxiliary examination showed a routine blood count of 6.88 × 10⁹/L (reference range 5–12), neutrophils of 3.35 × 10⁹/L (reference range 2–7.7), and lymphocyte of 2.72 × 10⁹/L (reference range 0.8–4). Erythrocyte sedimentation rate was 100 mm/h (reference range 0–20), C-reactive protein of 40.67 mg/L (reference range 0–3), and procalcitonin of 0.05 ng/ml (reference range 0–0.05). Gram-negative bacteria lipopolysaccharide was negative. Tests of the cerebrospinal fluid (CSF) sample showed a white blood cell count of 17 × 10⁶/L (reference range 0–15), Mononuclear cell (MNC) of 16 × 10⁶/L, polymorphonuclear (PMN) of 1 × 10⁶/L, Cl of 126.1 mmol/L (reference range 117–127), glucose (GLU) of 2.37 mmol/L (synchronous peripheral blood glucose: 6.5 mmol/L), and protein quantification of 384.7 mg/L (reference range 100–200). CSF culture was negative. Transthoracic echocardiography showed thickening of the anterior mitral valve leaflet with vegetation attachment and vegetation formation at the entrance to the pulmonary veins in the lateral posterior wall of the left atrium (Figure 2). Contrast-enhanced MRI + magnetic resonance angiography of the head showed aneurysm formation in the right middle temporal artery, distal right posterior cerebral artery and apical region of the basilar artery, cerebral bridge infarction, and stenosis of the left middle cerebral artery with multiple collateral vessel formation (Figure 3).

PACEseq metagenomic next-generation sequencing (mNGS) (Hugobiotech, Beijing, China) of blood detected A. defectiva with a specific sequence number of 161. mNGS of CSF also detected A. defectiva with the specific sequence number of 165. The results were also confirmed by blood culture.

Multiple pathogen detection tools detected A. defectiva, but no drug sensitivity tests were performed because our hospital does not have criteria for drug sensitivity for this organism. Meropenem (20 mg/kg, once every 8 h) combined with vancomycin (10 mg/kg, once every 6 h) was given empirically as anti-infective treatment, and the body temperature returned to normal. Half a month after the combination anti-infective treatment, the child showed no positive neurological signs. The repeated blood culture was negative, the blood and CSF mNGS were negative, and the antibiotics were adjusted to ceftriaxone combined with vancomycin for anti-infective treatment.

On the 36th day after hospitalization, the child developed a severe headache and slurred speech, which recovered with anti-infective treatment. A CT head examination was completed, which showed a right parietal hematoma and a falciform herniation of the brain (Figure 1B). A pseudoaneurysm hemorrhage was considered. She then immediately underwent right temporo-occipital hematoma removal, cerebral vascular malformation resection, and cranial decompression. After the surgery, she gradually regained her speech. After a total of 60 days of hospitalization, her family requested to be discharged. At this point, the child was conscious, her speech ability had returned to normal, only the right upper limb muscle strength was grade III (may be related to the posterior cone crossover damage in the child), the rest of the limb muscle strength was normal, and there was still valve redundancy on cardiac ultrasonography, which was unchanged from before.

Infective endocarditis (IE) caused by A. defectiva usually occurs in children with congenital heart disease or a history of previous cardiac surgery (7), but some patients have no underlying disease (6). However, oral surgery related to dentistry is the most common cause (8–10). In this case, the child had no congenital heart disease and no history of cardiac-related surgery, but had septic tonsillitis at the time of presentation, which may have contributed to this child’s IE.

Abiotrophia defectiva is slow-growing and nutritionally demanding, usually growing only on media containing L-cysteine or vitamin B6 (11). Gram staining results are variable and morphologically diverse, making culture and identification difficult and diagnosis easily missed or delayed (12), which may explain the negative blood cultures in pediatric patients with IE (8, 13). Compared to conventional culture, mNGS is more sensitive (14, 15) and is particularly suitable for the detection of mixed and rare infections (4, 16). mNGS has been widely used in the diagnosis of clinical infectious diseases (7, 17), and has been reported for the clinical diagnosis of IE (14, 18). In this case, A. defectiva was detected in blood and CSF specimens by mNGS within 48 h of admission, but only one blood culture at admission was positive, while other blood cultures and CSF cultures were negative, indicating that the sensitivity of mNGS is much higher than that of traditional culture methods and can be used as an important means for identification of pathogens in patients with IE. Although it needs to be acknowledged that the pathogen was also detected by culture, and that the isolated strain could be used for the assessment of the antibiotic susceptibility tests.

Previous studies have shown that A. defectiva-associated IE may be resistant to penicillin but sensitive to a variety of antibiotics, such as third-generation cephalosporins, meropenem, vancomycin, gentamicin, and linezolid (11, 19). Specifically, it has been suggested (14) that A. defectiva is 94.6% susceptible to ceftriaxone, 91.9% susceptible to clindamycin, and 100% susceptible to meropenem, imipenem, vancomycin, and levofloxacin. Others (20) suggested that A. defectiva is 8, 92, and 83% susceptible to penicillin, amoxicillin, and ceftriaxone, and 100% susceptible to meropenem, clindamycin, rifampicin, levofloxacin, ofloxacin, and vancomycin, respectively. A combination of drugs is recommended. Due to the fact that there was no previous experience in the anti-infective treatment of this organism in our hospital, we chose meropenem combined with vancomycin based on the literature. As the child’s condition improved, we replaced meropenem with ceftriaxone to prevent bacterial resistance and secondary infection by other pathogens caused by prolonged use of broad-spectrum antibiotics. Because ceftriaxone can also cross the blood–brain barrier, it is also useful for central nervous system infections.

Compared to IE caused by other pathogens, A. defectiva-associated IE is more likely to form valvular vegetation and produce extracardiac organ embolic complications (21, 22), with poor prognosis and high mortality. The most common complication of the heart in IE is the formation of valvular redundancy, with mitral valve involvement being the most common, followed by aortic valve, and in rare patients, aortic, tricuspid, and pulmonary valves (8, 12, 14, 23), which can even be complicated by valve perforation in some cases (24). Extracardiac organ embolism can cause cerebral infarction, intracranial aneurysms, splenic infarction, infectious pneumonia, limb arterial embolism, aneurysms, etc. (12, 21, 25). On admission, the child was found to have vegetation on the mitral valve. The subsequent review revealed that vegetation was also observed at the entrance to the pulmonary veins of the left atrial and combined with multiple intracranial pseudoaneurysm formation, which is rare in clinical practice. Such a child usually requires surgical intervention. However, this child had both heart valve vegetation and multiple intracranial pseudoaneurysms, which are extremely risky for clinical procedures and may lead to an incurable and very poor prognosis.

In summary, A. defectiva is a rare pathogen causing IE, and the possibility of this disease should be considered especially in patients with IE having negative blood cultures. Because of the harsh culture conditions and low positivity rate of A. defectiva, mNGS is worthy of clinical application.

The original contributions presented in this study are included in this article/supplementary material, further inquiries can be directed to the corresponding author.

YD and YW conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. ZZ, CC, HZ, and ZG collected data, carried out the initial analyses, and reviewed and revised the manuscript. HX designed the data collection instruments, coordinated and supervised data collection, and critically reviewed the manuscript. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

HX was employed by Hugobiotech Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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