Peritonsillar abscess associated with Helicobacter cinaedi bacteremia: A case report.

Helicobacter cinaedi, a gram-negative spiral bacterium, has historically been associated with infections primarily in immunocompromised patients. Recently, however, its potential to cause infections in immunocompetent individuals has been recognized. We report a unique case of a man in his 20 s who reported having sex with men. He presented with symptoms of fever and throat discomfort and was diagnosed with a peritonsillar abscess. While the rapid antigen test for Group A Streptococcus was positive and antibiotics were administered, a puncture fluid from the peritonsillar abscess taken the day after antibiotic treatment revealed the presence of Group C Streptococcus. By the fifth day, the blood culture taken on the first day detected a gram-negative spirochete, which was subsequently identified H. cinaedi. The patient had engaged in oral sex with his male partner, suggesting a potential transmission route. This is significant as H. cinaedi was initially identified from rectal cultures in men who have sex with men (MSM), raising the possibility of pharyngeal transmission through oral sex. In our patient, although H. cinaedi was not isolated from the aspirate of the peritonsillar abscess, its presence in the blood culture and lack of other potential sources of bacteremia make the abscess a likely primary site of infection. This case highlights the importance of considering H. cinaedi as a potential pathogen in immunocompetent patients, particularly in cases of MSM. The potential for H. cinaedi transmission through oral sex and its role in the development of peritonsillar abscesses, a previously unreported association, requires further investigation.

Helicobacter cinaedi bacterium association with atherosclerosis and other diseases.

Helicobacter is a genus of spiral-shaped Gram-negative enterohepatic bacteria whose members are capable of causing bacteremia in humans. One of the poorly studied members of this genus is the bacterium Helicobacter cinaedi. This microorganism was first isolated from human fecal samples in 1984. Although it was long considered to be associated with only immunocompromised patients, more evidence in recent years has implicated H. cinaedi in causing serious pathologies in immunocompetent populations. In addition, H. cinaedi is also reported to be associated with a few chronic or severe illnesses, such as atherosclerosis, which in turn can lead to the development of other cardiovascular pathologies: one of the leading causes of mortality worldwide. Helicobacter cinaedi often goes unnoticed in standard diagnostic methods due to its slow growth under microaerobic conditions. This often leads to significant underdetection and hence undermines the role of this bacterium in the pathogenesis of various diseases and the extent of its spread in humans. In this review, we have compiled information on pathologies associated with H. cinaedi, the occurrence of the bacterium in humans and animals, and the latest developments in diagnosing the bacterium and treating associated diseases.

Characterization of HcaA, a novel autotransporter protein in Helicobacter cinaedi, and its role in host cell adhesion.

IMPORTANCE: Helicobacter species are classified as gastric or enterohepatic according to their habitat. Among enterohepatic Helicobacter species, which inhabit the intestine, colon, and liver, Helicobacter cinaedi has been most frequently isolated from humans. H. cinaedi often causes bacteremia and cellulitis in immunocompromised hosts. Here, we focused on the H. cinaedi autotransporter protein A (HcaA), a novel virulence factor in H. cinaedi. We discovered that HcaA contributes to cell adhesion via its Arg-Gly-Asp motif. Furthermore, in animal experiments, bacterial colonization was reduced in mice infected with HcaA-knockout strains, supporting the hypothesis that HcaA contributes to H. cinaedi adhesion to host cells. Our study provides a novel mechanism for the establishment of H. cinaedi infections and provides new insights into the role of autotransporter proteins in the establishment of Helicobacter infection.

Helicobacter cinaedi Infections in Emergency Departments: A Descriptive Study.

AIM: Helicobacter cinaedi, a Gram-negative spiral bacterium, is a rare cause of bacteremia in humans. Unfortunately, little is known about H. cinaedi infections in emergency departments (EDs). We aimed to describe the clinical features of H. cinaedi infections in the ED. METHODS: We conducted a descriptive study at the ED of Kobe City General Hospital (KCGH) in Japan between November 2011 and December 2020. We included all ED patients with H. cinaedi infections. We retrospectively obtained the patient data from electronic medical records and described the patient characteristics, clinical course, and management of H. cinaedi infections. RESULTS: A total of 22 patients in the ED were diagnosed with H. cinaedi infections, and all of them were detected through blood cultures. The chief complaints were vague: fever (18/22, 81.8%), chills (10/22, 45.5%), and localized pain or tenderness (8/22, 36.4%). Patients with complicated cases were also reported in the ED; three patients had vertebral osteomyelitis, two had infected aortic aneurysms, and another two had infected cysts (renal cyst and pancreatic cyst with concomitant empyema). Tetracycline (minocycline) was primarily prescribed and administered intravenously in five of 15 (33.3%) and orally in nine of 20 (45.0%) patients. Only one (4.5%) patient required surgical interventions. None of the patients died in the hospital. CONCLUSIONS: We reported the clinical features of H. cinaedi infections in the ED. Although some patients developed complicated infections, the prognosis was not poor under appropriate treatment, and most of them were successfully treated with antibiotics, primarily tetracycline.

Metagenomics assists in the diagnosis of a refractory, culture-negative pyoderma gangrenosum-like ulcer caused by Helicobacter cinaedi in a patient with primary agammaglobulinemia.

Helicobacter cinaedi is known to cause various infections in immunocompromised hosts ranging from skin lesions to disseminated septicemia. Identification of H. cinaedi is difficult through conventional identification methods due to its fastidious nature. We reported a refractory and culture-negative pyoderma gangrenosum-like ulcer caused by H. cinaedi in a patient with primary agammaglobulinemia. Metagenomic next-generation sequencing (mNGS) was applied for the identification of H. cinaedi and prolonged minocycline and amoxicillin-clavulanate potassium was used to eradicate the infection. Given the difficulties in culturing this organism, it's highly possible that H cinaedi infections have been overlooked. We suggest that early consideration of H. cinaedi infection should be suspected in immunocompromised patients presenting with unexplained skin lesions as the appropriate antibiotic choice plus a prolonged treatment course is essential for the prognosis. Application of mNGS could contribute to the early identification of rare and cryptogenic pathogens.

Presence of Helicobacter cinaedi in Atherosclerotic Abdominal Aortic Aneurysmal Wall.

Recently, the relationship between Helicobacter cinaedi (H. cinaedi) infection and several diseases, including cardiovascular and central nervous system disorders, bone and soft tissue disorders, and infectious abdominal aortic aneurysms (AAAs), has been reported. Moreover, H. cinaedi may be associated with arteriosclerosis. In the present study, we investigated the association between H. cinaedi infection and clinically uninfected AAAs. Genetic detection of H. cinaedi in the abdominal aneurysm wall was attempted in 39 patients with AAA undergoing elective open surgery between June 2019 and June 2020. DNA samples extracted from the arterial wall obtained during surgery were analyzed using nested polymerase chain reaction (PCR). The target gene region was the H. cinaedi-specific cytolethal distending toxin subunit B (cdtB). Nine (23.1%) of 39 patients showed positive bands corresponding to H. cinaedi, and further sequencing analyses demonstrated the presence of H. cinaedi DNAs in their aneurysm walls. In contrast, all the non-aneurysm arterial walls in our patients were negative for H. cinaedi. In conclusion, this is the first report of the detection of H. cinaedi in the walls of a clinically non-infectious AAA.

Recurrent Cellulitis Revealing Helicobacter cinaedi in Patient on Ibrutinib Therapy, France.

Helicobacter cinaedi bacteremia caused recurring multifocal cellulitis in a patient in France who had chronic lymphocytic leukemia treated with ibrutinib. Diagnosis required extended blood culture incubation and sequencing of the entire 16S ribosomal RNA gene from single bacterial colonies. Clinicians should consider H. cinaedi infection in cases of recurrent cellulitis.

Pan-Genome-Assisted Computational Design of a Multi-Epitopes-Based Vaccine Candidate against Helicobacter cinaedi.

Helicobacter cinaedi is a Gram-negative bacterium from the family Helicobacteraceae and genus Helicobacter. The pathogen is a causative agent of gastroenteritis, cellulitis, and bacteremia. The increasing antibiotic resistance pattern of the pathogen prompts the efforts to develop a vaccine to prevent dissemination of the bacteria and stop the spread of antibiotic resistance (AR) determinants. Herein, a pan-genome analysis of the pathogen strains was performed to shed light on its core genome and its exploration for potential vaccine targets. In total, four vaccine candidates (TonB dependent receptor, flagellar hook protein FlgE, Hcp family type VI secretion system effector, flagellar motor protein MotB) were identified as promising vaccine candidates and subsequently subjected to an epitopes' mapping phase. These vaccine candidates are part of the pathogen core genome: they are essential, localized at the pathogen surface, and are antigenic. Immunoinformatics was further applied on the selected vaccine proteins to predict potential antigenic, non-allergic, non-toxic, virulent, and DRB*0101 epitopes. The selected epitopes were then fused using linkers to structure a multi-epitopes' vaccine construct. Molecular docking simulations were conducted to determine a designed vaccine binding stability with TLR5 innate immune receptor. Further, binding free energy by MMGB/PBSA and WaterSwap was employed to examine atomic level interaction energies. The designed vaccine also stimulated strong humoral and cellular immune responses as well as interferon and cytokines' production. In a nutshell, the designed vaccine is promising in terms of immune responses' stimulation and could be an ideal candidate for experimental analysis due to favorable physicochemical properties.

Determining Infected Aortic Aneurysm Treatment Using Focused Detection of Helicobacter cinaedi.

We detected Helicobacter cinaedi in 4 of 10 patients with infected aortic aneurysms diagnosed using blood or tissue culture in Aichi, Japan, during September 2017-January 2021. Infected aortic aneurysms caused by H. cinaedi had a higher detection rate and better results after treatment than previously reported, without recurrent infection.

Helicobacter cinaedi is a human-adapted lineage in the Helicobacter cinaedi/canicola/'magdeburgensis' complex.

Helicobacter cinaedi is an enterohepatic Helicobacter that causes bacteremia and other diseases in humans. While H. cinaedi-like strains are isolated from animals, including dog isolates belonging to a recently proposed H. canicola, little is known about the genetic differences between H. cinaedi and these animal isolates. Here, we sequenced 43 H. cinaedi- or H. canicola-like strains isolated from humans, hamsters, rats and dogs and collected 81 genome sequences of H. cinaedi, H. canicola and other enterohepatic Helicobacter strains from public databases. Genomic comparison of these strains identified four distinct clades (clades I-IV) in H. cinaedi/canicola/'magderbugensis' (HCCM) complex. Among these, clade I corresponds to H. cinaedi sensu stricto and represents a human-adapted lineage in the complex. We identified several genomic features unique to clade I. They include the accumulation of antimicrobial resistance-related mutations that reflects the human association of clade I and the larger genome size and the presence of a CRISPR-Cas system and multiple toxin-antitoxin and restriction-modification systems, both of which indicate the contribution of horizontal gene transfer to the evolution of clade I. In addition, nearly all clade I strains but only a few strains belonging to one minor clade contained a highly variable genomic region encoding a type VI secretion system (T6SS), which could play important roles in gut colonization by killing competitors or inhibiting their growth. We also developed a method to systematically search for H. cinaedi sequences in large metagenome data sets based on the results of genome comparison. Using this method, we successfully identified multiple HCCM complex-containing human faecal metagenome samples and obtained the sequence information covering almost the entire genome of each strain. Importantly, all were clade I strains, supporting our conclusion that H. cinaedi sensu stricto is a human-adapted lineage in the HCCM complex.

Bacteremia caused by Helicobacter cinaedi: a case report.

Objectives: Helicobacter cinaedi is a Gram-negative, spiral-shaped bacterium that primarily affects immunosuppressed patients. Case presentation: A 49-year-old patient with ulcerative colitis diagnosed in 1992, who presented to the ED of our hospital with fever and testicular complaints. The patient was discharged with a diagnosis of left-sided acute epididymitis, which was probably sexually transmitted. At the ED, he was administered intravenous Ceftriaxone and discharged with a prescription of doxycycline for 10 days, with a good progress. Aerobic cultures were positive at three days from collection. Gram staining showed Gram-negative, corkscrew-shaped bacteria. The analysis of the blood culture bottles, and the colonies grown in Campylosel agar incubated in microaerophilic conditions at 42 °C were identified as H. cinaedi on the Maldi-TOF Biotyper 3.0 system (Bruker Diagnostics Inc.). Conclusions: Direct analysis of the blood culture bottle on the Maldi-TOF system allowed for the identification of the etiology of the bacteremia since H. cinaedi could not have been grown in standard culture conditions. The treatment of this infection is a matter of debate; however, the combination of ceftriaxone with doxycycline can be ineffective for bacteremia caused by H. cinaedi infection since it occurs by the translocation of the bacteria from the gastrointestinal tract. This type of bacteremia is associated with intestinal mucosal damage secondary to ulcerative colitis, and it primarily affects immunosuppressed patients.

Recurrent Fever due to Helicobacter cinaedi Infection during R-CHOP Chemotherapy in Diffuse Large B-Cell Lymphoma: Case Report and Literature Review.

Fever due to Helicobacter cinaedi bacteremia under chemotherapy has not been widely recognized among clinicians. We experienced a 72-year-old man with diffuse large B-cell lymphoma, who was complicated with H. cinaedi bacteremia-induced fever under R-CHOP chemotherapy. We summarized 6 cases including ours, suggesting that fever without neutropenia developing around day 6 from starting chemotherapy is a possible symptom caused by H. cinaedi bacteremia. We should discriminate fever due to H. cinaedi bacteremia if fever emerged before myelosuppression in the course of chemotherapy.

Bacteremia Caused by Both Legionella pneumophila Serogroup 2 and Helicobacter cinaedi.

A 74-year-old woman with a history of pure red cell aplasia and hypogammaglobulinemia developed pneumonia. A urine antigen test and sputum subculture on buffered charcoal yeast extract (BCYE)α agar were positive for Legionella pneumophila. Serological testing identified L. pneumophila serogroup 2. An aerobic blood culture also became positive on day 5; its subculture on BCYEα agar revealed the same pathogen, but that on blood agar revealed Helicobacter cinaedi. We thus diagnosed her with bacteremia caused by both pathogens. Hence, in cases of H. cinaedi bacteremia along with pneumonia, the screening of other pathogens including L. pneumophila is needed.

Helicobacter cinaedi-infected chronic subdural hematoma mimicking an expanding hematoma: A case report.

BACKGROUND: We present the rare case of a spontaneous intracranial subdural empyema caused by Helicobacter cinaedi in a preexisting chronic subdural hematoma (CSDH). CASE DESCRIPTION: A 72-year-old man with a history of the right CSDH that remained radiologically unchanged for the past 2 years with conservative management was transferred to our hospital because of fever and convulsive seizure. Systemic sources of infection were not identified. Fever and extremely high levels of serum C-reactive protein (CRP) spontaneously improved without antibacterial therapy. One month after the fever disappeared, brain computed tomography (CT) showed an increase in CSDH size. Mildly elevated CRP levels persisted without fever. Interval changes in shape on CT and hyperintense signals on diffusion-weighted magnetic resonance imaging (DWI) within the CSDH were observed with no neurological deficits. Five months later, the patient underwent craniotomy for a progressively enlarged CSDH. An infected organized hematoma was found, and copious pus was evacuated. Subsequently, an infected subdural hematoma (ISH) was diagnosed. Although bacterial cultures of the purulent specimen were negative, H. cinaedi was identified by gene sequencing analysis. Six months post antibiotic therapy, the ISH was under control, and abnormal DWI signals disappeared. CONCLUSION: To the best of our knowledge, this is the first report of ISH caused by H. cinaedi. This case suggests that ISH can follow a chronic course, mimicking the progressive expansion of subdural hematoma, and that H. cinaedi should be considered as a causative organism of ISH especially when conventional cultures are negative.

Acquired Hemophilia A Presenting with Infectious Aortic Aneurysms Due to an Underlying Helicobacter cinaedi Infection.

Acquired hemophilia A (AHA) is a bleeding disorder caused by the acquired appearance of inhibitor for factor VIII. Approximately half of all patients with AHA have some type of underlying disease. We herein report the case of a 72-year-old Japanese man with AHA who presented with infectious aortic aneurysms due to an underlying Helicobacter cinaedi infection. To our knowledge, this is the first report of AHA triggered by a bacterial infection; however, there may be similar cases that remain undiagnosed because this pathogen is difficult to identify. Clinicians should consider the possibility of H. cinaedi as a causative pathogen in patients presenting with a fever of unknown origin.

Helicobacter cinaedi bacteraemia secondary to enterocolitis in an immunocompetent patient.

BACKGROUND: Helicobacter cinaedi are motile, gram-negative spiral rods with a natural reservoir in the intestinal tract of hamsters and rhesus monkeys. In humans, H. cinaedi has been reported in different human infections like fever, abdominal pain, gastroenteritis, proctitis, diarrhoea, erysipelas, cellulitis, arthritis, and neonatal meningitis typically diagnosed by positive blood cultures. Even though H. cinaedi has been detected from human blood and stool the entry of H. cinaedi into the blood stream was undocumented until quite recently. The use of pulse-field gel electrophoresis (PFGE) demonstrated that stool- and blood-derived H. cinaedi strains were consistent. CASE PRESENTATION: Here, we describe a rare Danish case of H. cinaedi bacteraemia in an immunocompetent 44-year-old male with diarrhoea. We isolated H. cinaedi from a blood culture taken at admission, and from a FecalSwab taken at day six despite ongoing antibiotic therapy. Next, we made a genetic comparison of both isolates by use of Multi-locus sequence typing (MLST)- and Single nucleotide polymorphism (SNP)-analysis. The two isolates were identical with zero SNPs and by use of MLST the isolate was identified as a novel ST20, confirming previous data of the intestinal tract as a route of H. cinaedi bacteraemia. The results of our AST showed a resistance pattern with higher MICs for ciprofloxacin and clarithromycin than for ampicillin, amoxicillin, gentamicin, and imipenem. The patient was cured with targeted therapy with pivampicillin; however, the primary source of transmission was unknown. CONCLUSIONS: In conclusion, this case of H. cinaedi bacteraemia secondary to enterocolitis in an immunocompetent patient provide clear evidence that one route of infection occurs through translocation from the intestinal tract to the bloodstream. Helicobacter cinaedi from blood and faeces were identical with a novel ST20, resistant to ciprofloxacin and clarithromycin however, the patient was cured with oral pivampicillin.

Spiral-shaped bacteremia: Difference in the duration of blood cultures between Helicobacter spp. and Campylobacter spp. using the BACTEC system.

Although spiral bacteria are uncommon, they cause bacteremia. We evaluated their characteristics, in particular, the time from the start of blood culture to the first report of a positive result to physicians, using the BACTEC blood culture system. In cases of spiral bacteremia, an extended treatment period should be considered.

Infected aortic aneurysm caused by Helicobacter cinaedi: case series and systematic review of the literature.

BACKGROUND: Helicobacter cinaedi is rarely identified as a cause of infected aneurysms; however, the number of reported cases has been increasing over several decades, especially in Japan. We report three cases of aortic aneurysm infected by H. cinaedi that were successfully treated using meropenem plus surgical stent graft replacement or intravascular stenting. Furthermore, we performed a systematic review of the literature regarding aortic aneurysm infected by H. cinaedi. CASE PRESENTATION: We present three rare cases of infected aneurysm caused by H. cinaedi in adults. Blood and tissue cultures and 16S rRNA gene sequencing were used for diagnosis. Two patients underwent urgent surgical stent graft replacement, and the other patient underwent intravascular stenting. All three cases were treated successfully with intravenous meropenem for 4 to 6 weeks. CONCLUSIONS: These cases suggest that although aneurysms infected by H. cinaedi are rare, clinicians should be aware of H. cinaedi as a potential causative pathogen, even in immunocompetent patients. Prolonged incubation periods for blood cultures are necessary for the accurate detection of H. cinaedi.

Helicobacter cinaedi-Associated Refractory Cellulitis in Patients with X-Linked Agammaglobulinemia.

X-linked agammaglobulinemia (XLA) is characterized by severe or recurrent infections, hypogammaglobulinemia, and circulating B cell deficiency. The frequent pathogens seen in patients with XLA include Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and enterovirus as well as Campylobacter and Helicobacter species. Here, we describe two patients with XLA who developed cellulitis and bacteremia caused by Helicobacter cinaedi even when administered an appropriate immunoglobulin replacement therapy. H. cinaedi may be difficult to isolate using a conventional blood culture system and could be identified by sequence analysis and mass spectrometry. H. cinaedi infection causes recurrent symptoms frequently, and patients require a long course of antibiotic treatment. Recently, the case of non-H. pylori Helicobacter (NHPH) infection such as H. cinaedi and H. bilis infection is increasing in number in patients with XLA. Systemic NHPH infection should be suspected, and extensive microbiological analysis should be performed to appropriately treat patients with XLA who present with fever and skin lesions.