Haemophilus aphrophilus and Eikenella corrodens Coinfection of Brain: An Unusual Case from China.

Background: The HACEK group comprises Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae, are Gram-negative bacteria that are slow-growing and fastidious. These organisms are common causes of culture-negative endocarditis. However, brain abscesses caused by Haemophilus aphrophilus and E. corrodens have been rarely reported. The case we describe, which was promptly identified and successfully treated, will be meaningful for the diagnosis and treatment of such infectious diseases. Case Presentation: Herein, we report a case of brain abscess in a young man who was infected with Haemophilus aphrophilus and E. corrodens. The patient was admitted to the hospital with sudden onset of vomiting, coma, and fever. Magnetic resonance imaging (MRI) of the brain and cerebrospinal fluid cell counts suggested cerebral abscess, he underwent drainage of the abscess and empirical antimicrobial therapy of meropenem (2 g every 8 hours) and linezolid (0.6 g every 12 hours) for more than 10 days without significant improvement. Metagenomic next-generation sequencing (mNGS) of drainage fluid and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) detection for isolated bacteria from samples suggested the presence of H. aphrophilus and E. corrodens. After 7 weeks of ceftriaxone (2 g every 12 hours) and meropenem (2 g every 8 hours) intravenously, the patient was discharged with a normal temperature and brain MRI showed improvement of the lesion. Conclusion: Similar cases reported in previous studies were always associated with bacterial blood dissemination after dental surgery or myocarditis; however, the patient in our case had no any associated risk factors. As far as we know, this is the only case of central nervous system infection caused by H. aphrophilus and E. corrodens that has utilized combined mNGS and MALDI-TOF MS in the diagnosis.

Spatial ecology of Haemophilus and Aggregatibacter in the human oral cavity.

Haemophilus and Aggregatibacter are two of the most common bacterial genera in the human oral cavity, encompassing both commensals and pathogens of substantial ecological and medical significance. In this study, we conducted a metapangenomic analysis of oral Haemophilus and Aggregatibacter species to uncover genomic diversity, phylogenetic relationships, and habitat specialization within the human oral cavity. Using three metrics-pangenomic gene content, phylogenomics, and average nucleotide identity (ANI)-we first identified distinct species and sub-species groups among these genera. Mapping of metagenomic reads then revealed clear patterns of habitat specialization, such as Aggregatibacter species predominantly in dental plaque, a distinctive Haemophilus parainfluenzae sub-species group on the tongue dorsum, and H. sp. HMT-036 predominantly in keratinized gingiva and buccal mucosa. In addition, we found that supragingival plaque samples contained predominantly only one out of the three taxa, H. parainfluenzae, Aggregatibacter aphrophilus, and A. sp. HMT-458, suggesting independent niches or a competitive relationship. Functional analyses revealed the presence of key metabolic genes, such as oxaloacetate decarboxylase, correlated with habitat specialization, suggesting metabolic versatility as a driving force. Additionally, heme synthesis distinguishes H. sp. HMT-036 from closely related Haemophilus haemolyticus, suggesting that the availability of micronutrients, particularly iron, was important in the evolutionary ecology of these species. Overall, our study exemplifies the power of metapangenomics to identify factors that may affect ecological interactions within microbial communities, including genomic diversity, habitat specialization, and metabolic versatility. IMPORTANCE: Understanding the microbial ecology of the mouth is essential for comprehending human physiology. This study employs metapangenomics to reveal that various Haemophilus and Aggregatibacter species exhibit distinct ecological preferences within the oral cavity of healthy individuals, thereby supporting the site-specialist hypothesis. Additionally, it was observed that the gene pool of different Haemophilus species correlates with their ecological niches. These findings shed light on the significance of key metabolic functions in shaping microbial distribution patterns and interspecies interactions in the oral ecosystem.

Challenges and Insights in Aggregatibacter aphrophilus endocarditis: a review of literature.

Infective endocarditis is a serious disease associated with high mortality despite recent advances in diagnosis and treatment. Aggregatibacter aphrophilus is a fastidious Gram-negative member of the HACEK organisms (Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae). A. aphrophilus is associated with dental infections but has also been implicated in cases of infective endocarditis. We highlight the importance of a high index of suspicion in symptomatic patients with an initial negative blood culture, particularly in high-risk groups such as patients with congenital valve disease and prosthetic valve. The knowledge of this rare entity may lead to early diagnosis and appropriate management. We review the main characteristics of Aggregatibacter aphrophilus endocarditis reported in the medical literature.

La endocarditis infecciosa es una enfermedad grave que está asociada con una alta mortalidad a pesar de los avances recientes en el diagnóstico y tratamiento. Aggregatibacter aphrophilus es un miembro Gram-negativo de los organismos HACEK (Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens y Kingella kingae). A. aphrophilus está relacionado con infecciones dentales, pero también ha estado implicado en casos de endocarditis infecciosa. Se destaca la importancia de tener un alto índice de sospecha en pacientes sintomáticos con un cultivo sanguíneo inicial negativo, especialmente en grupos de alto riesgo como pacientes con enfermedad valvular congénita y válvula protésica. El conocimiento de esta entidad poco común puede llevar a un diagnóstico temprano y un manejo adecuado. Revisamos las principales características de la endocarditis por Aggregatibacter aphrophilus reportadas en la literatura médica.

Molecular basis for bacterial N-glycosylation by a soluble HMW1C-like N-glycosyltransferase.

Soluble HMW1C-like N-glycosyltransferases (NGTs) catalyze the glycosylation of Asn residues in proteins, a process fundamental for bacterial autoaggregation, adhesion and pathogenicity. However, our understanding of their molecular mechanisms is hindered by the lack of structures of enzymatic complexes. Here, we report structures of binary and ternary NGT complexes of Aggregatibacter aphrophilus NGT (AaNGT), revealing an essential dyad of basic/acidic residues located in the N-terminal all α-domain (AAD) that intimately recognizes the Thr residue within the conserved motif Asn0-X+1-Ser/Thr+2. Poor substrates and inhibitors such as UDP-galactose and UDP-glucose mimetics adopt non-productive conformations, decreasing or impeding catalysis. QM/MM simulations rationalize these results, showing that AaNGT follows a SN2 reaction mechanism in which the acceptor asparagine uses its imidic form for catalysis and the UDP-glucose phosphate group acts as a general base. These findings provide key insights into the mechanism of NGTs and will facilitate the design of structure-based inhibitors to treat diseases caused by non-typeable H. influenzae or other Gram-negative bacteria.

Aggregatibacter aphrophilus and Eikenella corrodens: a case of brain abscess.

We report a case of a 26-year-old female who developed a brain abscess that was strongly suspected to be caused by Staphylococcus epidermidis, A. aphrophilus, and E. corrodens species. In general, A. aphrophilus and E. corrodens, members of the HACEK group (Haemophilus spp., Aggregatibacter spp., C. hominis, E. corrodens, and K. kingae), have been associated with the development of endocarditis, meningitis, sinusitis, otitis media, pneumonia, osteomyelitis, peritonitis, and wound infections. Cerebral abscesses are a rare manifestation of these bacteria; only a few cases are described in the literature, generally related to the diffusion of these organisms through the bloodstream after a dental procedure or a heart disease. Our case is unique because the rarity of the infection site appeared apparently in absence of risk factors. The patient underwent surgery to drain the abscess and was subsequently put on intravenous antibiotic treatment with ceftriaxone, vancomycin, and metronidazole. After 6 months, brain imaging revealed that the lesion had disappeared. The patient achieved excellent results with this approach.

Aggregatibacter aphrophilus

A species of Gram-negative, facultatively anaerobic spherical or rod-shaped bacteria indigenous to oral cavity and pharynx. It is associated with BACTERIAL ENDOCARDITIS; and MENINGITIS.

Especie de bacterias Gramnegativas, facultativamente anaerobias esféricas o en forma de varas autóctonas en la cavidad oral y la faringe. Se asocia con la ENDOCARDITIS BACTERIANA y la MENINGITIS.

Espécie de bactérias esféricas ou bastonetes Gram negativos anaeróbias facultativos endêmicos da cavidade oral e faringe. Está associado a ENDOCARDITE BACTERIANA e MENINGITE.

Brain abscess due to Aggregatibacter aphrophilus in association with atrial septal defect：Case report and literature review.

BACKGROUND: Aggregatibacter aphrophilus（A. aphrophilus）is one of the organisms of the HACEK group. Previously reported cases of brain abscesses caused by A. aphrophilus infection have occurred in children with a basis for congenital heart disease, or in adults with a basis for dental disease. Rare cases of brain abscess caused by A. aphrophilus have been reported in adults with congenital heart disease or in patients without dental disease history. Herein we present a rare case of brain abscess caused by A. aphrophilus, who was in association with atrial septal defect for more than 20 years, and had no dental disease and did not develop infective endocarditis. CASE PRESENTATION: A 51-year-old female was admitted due to progressively worsening headache and left limb weakness for more than 10 days. She denied the history of chronic diseases such as hypertension and diabetes, and no periodontal disease. While she had a history of atrial septal defect, a form of congenital heart disease with severe pulmonary hypertension for more than 20 years. After admission, echocardiographic illustrated congenital heart disease with severe pulmonary hypertension. CT and MRI showed brain abscess. Cerebrospinal fluid (CSF) results also confirmed the presence of intracranial infection. Empirical therapy with vancomycin 1.0 g i.v q12h and meropenem 2.0 g i.v q8h was initiated from the day of admission. On the fourth day after admission, brain abscess resection and decompressive craniectomy were performed, and the pus drained on operation were cultured and Gram-negative bacilli grew, which was identified as A.aphrophilus. Vancomycin was discontinued and meropenem was continued（2.0 g i.v q8h）for 5 weeks, followed by oral levofloxacin 0.5 qd for 4 weeks of out-patient antibiotics. The patient recovered fully within 9 weeks of treatment. CONCLUSIONS: This is the first case of A. aphrophilus to cause brain abscess in adult with a history of congenital heart disease for more than 20 years, who had no dental disease and did not develop infective endocarditis. We also highlight the value of bacterial 16 S rDNA PCR amplification and sequencing in identifying bacteria in abscesses which are culture-negative, and prompt surgical treatment，choosing effective antibiotics and appropriate course of treatment will get better clinical effect.

The first case of cholecytitis caused by Aggregatibacter kilianii in Korea.

BACKGROUND: The bacterial genus Aggregatibacter was categorized in 2006 to accommodate the former Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, and H. segnis species. Aggregatibacter kilianii is a normal resident of the human upper respiratory tract but can also cause serious infections. A. kilianii is relatively newly identified and has been isolated from conjunctivitis, wounds, abdominal abscesses, and blood. CASE PRESENTATION: An 80-year-old female patient with distal common bile duct cancer was admitted to our hospital with sudden loss of consciousness and general weakness, fever, and abdominal pain for 3 days. Two colonial morphologies were isolated from both the blood and bile cultures; one was identified as Streptococcus constellatus subsp. pharyngis, but the other was not recognized by Vitek2 and MALDI-TOF. The 16 S rRNA sequences showed 99.73% similarity with the sequence of A. kilianii strains. CONCLUSION AND DISCUSSION: This article presents the first case of a clinical isolate of A. kilianii outside Europe. This case is also the first of the antimicrobial profile of this strain. This report highlights the importance of proper molecular identification for timely diagnosis and treatment of disease.

Exploration of Shoulder Abscess Association With Prompt Aggregatibacter aphrophilus Growth in Infective Endocarditis.

Aggregatibacter aphrophilus, formerly known as Haemophilus aphrophilus, is one member of a group of bacteria referred to as HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) organisms. Infections from any of the HACEK organisms typically lead to very poor outcomes and can be difficult to manage, especially when complicated by intracranial hemorrhage (ICH). HACEK organisms can also be difficult to grow on blood cultures, and A. aphrophilus is rarely seen, if at all. Traditionally, most laboratories follow an extended incubation protocol of 14 to 21 days to aid the growth of HACEK bacteria. Herein we report a case of infective endocarditis where A. aphrophilus resulted on blood culture in three days, in a patient with a right shoulder abscess, complicated by septic embolization leading to ICH. We explore a potential link between the prompt growth of A. aphrophilus on blood culture and the presence of the right shoulder abscess.

A case report of intracranial infection caused by Aggregatibacter aphrophilus / 中华神经科杂志

Aggregatibacter aphrophilus is a member of the normal flora of the human oral cavity and pharynx, a Gram-negative fastidous bacteria, belonging to agglomerates, which is a normal mixed oropharyngeal flora in humans, most commonly colonized on the surface of oral mucosa. This bacterial infection is rare in clinical practice, and it is difficult to culture and identify the bacteria, which is easy to be missed. A patient with intracranial infection was admitted to Huaihe Hospital, who showed fever and headache as the main clinical manifestations, and Aggregatibacter aphrophilus was detected by the metagenomic next-generation sequencing of cerebrospinal fluid. The patient′s symptoms were significantly improved after anti-infection treatment.

A rare case of voluminous brain abscess due to Actinomyces meyeri and Aggregatibacter aphrophilus: is there any evidence for a prolonged antibiotic oral relay?

We present the case of a patient with a voluminous cerebral abscess caused by Aggregatibacter aphrophilus and Actinomyces meyeri occurring a week post dental scaling. Both these bacteria are rarely involved in brain abscesses, and so far, cases of cerebral actinomyces have mostly been treated surgically and with intravenous (IV) antibiotics for 3-4 months, then put on oral antibiotic therapy with penicillin or amoxicillin for a further 3-12 months. Our patient underwent drainage through craniotomy and was subsequently put on intravenous ceftriaxone for 3 months accompanied by brain imaging control at the end of this period which showed complete regression of the abscess. Following parenteral treatment, no oral antibiotics were given since pharmacokinetic properties do not allow to attain high tissue concentration in the brain. This treatment gave excellent results.

An unusual case of multiple hepatic and pulmonary abscesses caused by Aggregatibacter aphrophilus in a young man: a case report.

BACKGROUND: Aggregatibacter aphrophilus, formerly known as Haemophilus aphrophilus, belongs to the HACEK organisms, a group of pathogens classically associated with infectious endocarditis. A. aphrophilus is a rarely found pathogen, though abscess formation in various organs has been described, typically due to spread from an infected heart valve. Here we describe the unusual case of multiple hepatic abscesses caused by A. aphrophilus. CASE PRESENTATION: A 33-year-old Caucasian man presented at our hospital with fever and malaise, elevated inflammatory markers, and liver enzymes. Imaging was compatible with multiple liver and pulmonary abscesses, without evidence of endocarditis. Cultures of blood and liver abscess material remained without growth. Polymerase chain reaction finally revealed Aggregatibacter aphrophilus in the liver tissue. The patient recovered fully within 6 weeks of doxycycline treatment. CONCLUSIONS: There are only a few case descriptions of liver abscesses caused by A. aphrophilus. As a ubiquitous organism in the gastrointestinal tract, A. aphrophilus may reach the liver via the portal venous system, as well as through hematogenous spread from the oropharynx. HACEK organisms are notoriously difficult to grow on culture, which highlights the diagnostic importance of eubacterial PCR.

Clinical characteristics of bacteremia caused by Haemophilus and Aggregatibacter species and antimicrobial susceptibilities of the isolates.

BACKGROUND/PURPOSE: This study aimed to investigate the clinical characteristics and outcomes of bacteremia caused by Haemophilus and Aggregatibacter species in patients who were treated at a medical center between 2006 and 2018. METHODS: Haemophilus and Aggregatibacter isolates were identified up to the species level using Bruker Biotyper MALDI-TOF analysis and ancillary 16S rRNA gene sequencing analysis (in case of ambiguity). Clinical characteristics and outcomes of patients with bacteremia caused by these organisms were evaluated. RESULTS: Sixty-five Haemophilus and Aggregatibacter species isolates causing bacteremia were identified from nonduplicated patients, including 51 (78.5%) Haemophilus influenzae, 6 (9.2%) Haemophilus parainfluenzae, 1 (1.5%) Haemophilus haemolyticus, 3 (4.6%) A. aphrophilus, and 4 (6.2%) A. segnis. Hospital mortality was observed in 18 (28.1%) of 64 patients with bacteremia caused by Haemophilus (n = 57) and Aggregatibacter species (n = 7). The majority of patients with bacteremia had community-acquired disease with low severity. The average Sequential Organ Failure Assessment (SOFA) score was low (4.4 ± 4.7). But, a higher SOFA score (adjusted odds ratio 2.5, 95% confidence interval 1.22-5.12; P = 0.01) was an independent factor predicting poor 7-day clinical outcomes in patients with community-acquired H. influenzae bacteremia (n = 39). CONCLUSIONS: The overall hospital mortality of 28.1% was observed among patients with bacteremia due to Haemophilus and Aggregatibacter species. A higher SOFA score was and independent predictor of poor 7-day clinical outcomes in patients with community-acquired H. influenzae bacteremia.

Aggregatibacter aphrophilus spinal epidural abscess.

A 76-year-old woman with a rare case of spinal epidural abscess (SEA) that had no risk factors for such type of infection, presented symptoms of back pain, progressive neurological deficit of the lower limb and loss of sphincter control. A gadolinium-enhanced MRI confirmed the diagnosis of an SEA. The patient underwent laminectomy with surgical drainage, where cultures showed the presence of Aggregatibacter aphrophilus, a bacterium of the HACEK group (Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species), rarely involved in SEA. Following surgery, the patient was treated with intravenous ceftriaxone for 6 weeks, and this gave excellent results.

Unique presentation of Aggregatibacter aphrophilus in a superficial left temporal abscess.

Aggregatibacter aphrophilus, previously Haemophilus aphrophilus, is an uncommon organism that historically has been associated with HACEK infective endocarditis and brain abscesses. This organism is most often isolated as part of normal oral flora, and patients with A. aphrophilus infection usually have an underlying periodontal infection or immunocompromised state allowing for infection. This case report outlines a unique presentation of left superficial temporal abscess due to A. aphrophilus infection in an immunocompetent individual.

The First Known Case of Liver Abscess Caused by Aggregatibacter aphrophilus in Japan.

A 48-year-old man presented with a sustained fever. Abdominal computed tomography revealed multilocular liver abscesses. He underwent percutaneous needle aspiration, yielding straw-colored pus. Gram staining revealed Gram-negative coccobacilli. The organism grew only on chocolate II agar in a 7% carbon dioxide atmosphere. Identification of Aggregatibacter aphrophilus was confirmed using mass spectrometry and 16S rRNA gene sequencing. He was successfully treated with antibiotics. Liver abscess caused by A. aphrophilus is extremely rare. We herein report the first such case in Japan. Even fastidious organisms, such as A. aphrophilus, should be correctly identified using mass spectrometry or 16S rRNA gene sequencing for adequate treatment.

Oropharyngeal microbiome of a college population following a meningococcal disease outbreak.

Asymptomatic oropharyngeal carriage of Neisseria meningitidis peaks in adolescence and young adulthood. Following a meningococcal disease outbreak at a U.S. college, we profiled the oropharyngeal microbiomes of 158 students to identify associations between bacterial community composition and meningococcal carriage or risk factors for carriage, including male gender, smoking, and frequent social mixing. Metagenomic shotgun sequencing identified 268 bacterial taxa at the genus or species level, with Streptococcus, Veillonella, and Rothia species being most abundant. Microbiome composition showed weak associations with meningococcal carriage and risk factors for carriage. N. meningitidis abundance was positively correlated with that of Fusobacterium nucleatum, consistent with hypothesized propionic acid cross-feeding. Additional species had positive abundance correlations with N. meningitidis, including Aggregatibacter aphrophilus, Campylobacter rectus, Catonella morbi, Haemophilus haemolyticus, and Parvimonas micra. N. meningitidis abundance was negatively correlated with unidentified Veillonella species. Several of these species are commonly found in dental plaque, while N. meningitidis is primarily found in the pharynx, suggesting that ecological interactions extend throughout the oral cavity. Although risk factors for meningococcal carriage do not strongly impact most bacterial species in the oropharynx, variation in the upper respiratory tract microbiome may create conditions that are more or less favorable for N. meningitidis carriage.

Polymicrobial Cerebral Abscess in a Child with Uncorrected Tetralogy of Fallot.

Aggregatibacter aphrophilus and Beta haemolytic Streptococci Lancefield group F are part of the normal oral flora and are known to cause endocarditis, sinusitis, empyema, meningitis and septic arthritis. They are now emerging as a cause of brain abscess particularly in patients with congenital heart diseases. We report a case of a 10-year-old boy with Tetralogy of Fallot (TOF), who presented with fever, headache and drowsiness. Culture yielded the growth of Aggregatibacter aphrophilus and Beta hemolytic streptococci Lancefield group F. He became clinically stable after treatment with ceftriaxone.