BACKGROUND: Arcanobacterium haemolyticum causes pharyngotonsillitis in children and young adults. It is rarely isolated in pharyngeal swabs as testing for it is not routine. Data on complications, management, and antibiotic susceptibility testing is limited. We sought to review the available literature on the presentation and management of A. haemolyticum pharyngotonsillitis in this age group.
METHODS: A systematic review of eligible studies reporting pharyngotonsillitis and related complications in children and young adults caused by A. haemolyticum was conducted. Literature from case reports, case series, and available cohorts was compiled. Data were analyzed using descriptive statistics.
RESULTS: The initial database search yielded 63 articles, after applying exclusion criteria 17 studies were included. 191 patients were identified with a median age of 16.5 years. The most common presentation was throat pain reported in 93.7% of patients. Tonsillar exudates, fever at presentation and rash were present in more than half of the reviewed cases. The diagnosis was established by a positive culture on a pharyngeal swab in 98.8% of swabs collected. Complications described included peritonsillar abscesses, Lemierre\'s syndrome, pneumonia, and sepsis. Penicillin was the first line antibiotic in 81% of patients followed by macrolides in 19 patients (18%).
CONCLUSIONS: A. haemolyticum occurs in children and young adults and may result in complications. Our review supports its susceptibility to penicillin. We suggest a diagnostic and management algorithm to guide clinicians in targeted testing and aid with decision making regarding timely and appropriate antibiotic therapy, in an effort to reduce the burden of its complications.

A 57-year-old man with untreated diabetes mellitus was admitted to our hospital due to an intrathoracic mass lesion infiltrating the vertebral body and mediastinum. The mass was suspected to be invasive lung cancer; however, percutaneous needle biopsy revealed that the mass was inflammatory granulation tissue caused by an Arcanobacterium haemolyticum infection. To the best of our knowledge, this is the first report of an intrathoracic mass lesion caused by an A. haemolyticum infection. When an intrathoracic mass lesion is suspected, clinicians should consider possible infections that cause granulation tissue, such as A. haemolyticum. This is particularly important in immunocompromized hosts such as patients with diabetes.

BACKGROUND: Aging and comorbidities such as diabetes and vascular problems contribute to the increasing occurrence of chronic wounds. From the beginning of 2016, a marked increase in Arcanobacterium haemolyticum (ARH) in chronic wound cultures was noted among patients visiting a wound expertise centre in The Netherlands.
OBJECTIVE: To report the outbreak investigation of ARH cultured from chronic wounds and describe the implemented infection prevention measures.
METHODS: In total, 50 ARH isolates were sent to a reference laboratory for molecular typing. Samples for bacterial culture and ARH polymerase chain reaction were taken from care workers, the environment and items used for wound care. Infection prevention measures were implemented in a bundled approach, involving education, better aseptic wound care conditions and hygienic precautions. Before and after the implementation of infection prevention measures, two screening rounds of ARH testing were performed among all patients receiving home care.
RESULTS: ARH isolates from wound care patients were found to be identical by core genome multi-locus sequence typing. No definite outbreak source could be determined by culture. However, three pairs of forceps, used by two nurses on multiple patients, were found to be ARH positive by polymerase chain reaction. In the two screening rounds before and after the implementation of infection prevention measures, the proportion of ARH-positive patients decreased significantly from 20% (20/99) to 3% (3/104). Subsequently, no new cases occurred.
CONCLUSIONS: This first ARH outbreak was likely caused by re-using contaminated instruments. Through the implementation of improved infection prevention measures and re-education of all employees involved, the outbreak was controlled. With the current trend of care transition, infection control must be a major concern.

We report the case of a twenty-year-old immunocompetent male patient presenting to the emergency room with pharyngitis and fever. Blood cultures were drawn and Arcanobacterium haemolyticum (rough biotype) was recovered. The presence of the arcanolysin gene was investigated at the molecular level and the upstream region was amplified and sequenced in order to correlate it with the smooth or rough biotype. Although the isolate was susceptible to penicillin, vancomycin and gentamicin, empirical treatments first with amoxicillin/clavulanic acid (1g/12h) and then with ceftriaxone (1g/12h) failed and the infection evolved to sepsis. Finally, treatment with vancomycin (1g/12h) plus piperacillin/tazobactam (4.5g/8h) was effective. Lemierre\'s syndrome was ruled out. To the best of our knowledge, this is the first case of bacteremia by A. haemolyticum reported in Argentina.

An 81-year-old Japanese man with no history of diabetes mellitus was admitted to our hospital for a fever with a new ulcerative lesion on the left heel. Blood cultures on admission grew Arcanobacterium haemolyticum in aerobic bottles. He was therefore diagnosed with A. haemolyticum bacteremia and osteomyelitis complicated with foot decubitus ulcer. He was successfully treated with intravenous antibiotic therapy and debridement of the left heel. Our case and literature review show that it is important to recognize that A. haemolyticum is a systemic causative pathogen in immunocompetent patients in primary care practice.

Arcanolysin, produced by the human pathogen Arcanobacterium haemolyticum, is a cholesterol-dependent cytolysin. To mediate the pore-formation process, arcanolysin is secreted by A. haemolyticum and then must interact with cholesterol embedded within a host membrane. However, arcanolysin must compete with membrane components, such as the phospholipid sphingomyelin, to interact with cholesterol and form pores. Cholesterol forms transient hydrogen bonds with the extracellular portion of sphingomyelin, shielding cholesterol from extracellular factors, including arcanolysin. A. haemolyticum also produces a sphingomyelin-specific phospholipase D, which removes the choline head from sphingomyelin, leaving cyclic-ceramide phosphate and eliminating the potential for cholesterol sequestration. We hypothesized that the enzymatic activity of phospholipase D decreases sphingomyelin-mediated cholesterol sequestration and increases cholesterol accessibility for arcanolysin. Using purified arcanolysin and phospholipase D, we demonstrate that the enzymatic activity of phospholipase D is necessary to promote arcanolysin-mediated hemolysis in both time- and concentration-dependent manners. Phospholipase D promotion of arcanolysin-mediated cytotoxicity was confirmed in Detroit 562 epithelial cells. Furthermore, we determined that incubating phospholipase D with erythrocytes corresponds with an increase in the amount of arcanolysin bound to host membranes. This observation suggests that phospholipase D promotes arcanolysin-mediated cytotoxicity by increasing the ability of arcanolysin to bind to a host membrane.

Arcanobacterium hemolyticum (A.haemolyticum) is a gram-positive bacillus. Man is the primary environmental reservoir. It is essentially an opportunistic pathogen in immunocompromised patients and may be responsible for infections of the skin and pharynx in healthy subjects, especially in children and adolescents. It can cause superinfections of chronic ulcers, but occasionally it causes invasive infections. Its isolation from culture samples is always difficult because it simulates many bacteria to which it is often associated in pathological products. There are not recommendations concerning the study of its antibiotics sensitivity. Arcanobacterium Bacteremia are rare to our knowledge, only sixteen case reports have been described in the literature. We here report another case of a patient with A.haemolyticum bacteremia secondary to superinfection of gluteal eschars.

Phospholipase D (PLD) toxins from sicariid spiders, which cause disease in mammals, were recently found to convert their primary substrates, sphingomyelin and lysophosphatidylcholine, to cyclic phospholipids. Here we show that two PLD toxins from pathogenic actinobacteria and ascomycete fungi, which share distant homology with the spider toxins, also generate cyclic phospholipids. This shared function supports divergent evolution of the PLD toxins from a common ancestor and suggests the importance of cyclic phospholipids in pathogenicity.