Continuing Education Activity

Arcanobacterium haemolyticum is a rare infectious pathogen that principally causes pharyngitis in adolescents and soft-tissue infections in immunocompromised elderly patients. Its treatment consists of supportive care and antibiotics, resulting in a good prognosis without any long-term sequelae when recognized and treated promptly. This activity reviews the role of the interprofessional team in the evaluation and management of patients afflicted by Arcanobacterium haemolyticum.

Objectives:

• Describe the epidemiology of Arcanobacterium haemolyticum in various populations.
• Outline the evaluation of Arcanobacterium haemolyticum.
• Review the management of patients with Arcanobacterium haemolyticum.

Introduction

Arcanobacterium haemolyticum is a gram-positive, facultative anaerobic, branching bacillus.[1] The first cases ascribed to this pathogen were described in 1946 and caused ulcerative skin lesions among American soldiers in the Pacific Islands. Today, infections by A. haemolyticum are rare but most commonly cause pharyngitis in adolescents and young adults or skin and soft-tissue infections in immunocompromised populations.

Though cases of systemic infections such as meningitis or bacteremia are uncommon, A. haemolyticum should remain on the differential to enable the early recognition, management, and treatment of disease associated with the pathogen.[2] 

The classic presentation of pharyngeal disease may commonly be mistaken for streptococcal infections. Patients present with a sore throat, pharyngeal erythema, fever, exanthema, and swollen lymph nodes. The natural history of the disease may be self-limiting or require antibiotic treatment.[3]

Etiology

Cultures of A. haemolyticum can be detected as a part of normal skin flora and pharynx of healthy individuals. This causes difficulty in early detection of the pathogen since the organism is often overlooked as the cause of symptoms during an infection. In symptomatic patients, A. haemolyticum has been cultured as the sole pathogen or as a part of a polymicrobial infection.[4] 

There are two biotypes of A. haemolyticum: smooth and rough. The smooth-type form, even colonies on a growth medium, are beta-hemolytic, beta-glucuronidase negative, and ferment sucrose and trehalose. Smooth-type colonies are more commonly associated with soft-tissue infections. The rough-type form uneven colonies on a growth medium, are non-hemolytic, beta-glucuronidase positive, and does not ferment sucrose and trehalose. Rough-type colonies are more commonly associated with pharyngitis.[5] 

Epidemiology

Among adolescents, A. haemolyticum is responsible for 0.5% - 2.5% of all bacterial pharyngitis with another study by Mackenzie et al. reporting the group with the highest incidence being 15 to 18-year-olds.[6] It has been noted that men are at a higher risk of being infected by A. haemolyticum than women.[7] While in the elderly population, especially those with diabetes mellitus or are immunocompromised, A. haemolyticum is more likely to cause soft-tissue infections.[1] Tan et al. report that 72% of patients with soft tissue infections had diabetes mellitus. [8] 

Special populations such as those with diabetes mellitus or lymphoma have also been recognized to be at a higher risk of bacteremia.[9] A recent report indicates that A. haemolyticum may be a major factor in patients who are suffering from complications of chronic wound care.[10]

History and Physical

The severity of illness may range from a mild respiratory tract infection to a diphtheria-like illness. Pharyngitis and pharyngeal erythema are present in nearly all patients. About half of patients will also experience fever, tender bilateral anterior cervical or submandibular adenopathy, and an erythematous rash. The rash appears as diffuse erythematous blanching papules often described as “sandpaper-like.” It begins on the distal extremities then spreads centrally, affecting mostly the neck, chest, and back while sparing the face, palms, and soles. The pharyngitis usually presents 1 to 4 days before the rash, and the rash persists between 2 to 5 days. Clinically, symptoms resemble Scarlet Fever due to Streptococcus pyogenes; however, there is no strawberry tongue.[3][6] Some cases of A. haemolyticum can have complications such as Lemierre disease.[11]

In patients with cutaneous symptoms, A. haemolyticum infections present as chronic skin ulcers, infection, abscess, or cellulitis. They are often found co-infected most commonly with other gram-positive bacteria such as Staphylococcus aureus, Corynebacterium diphtheria, or Streptococci.[12] Cases of osteomyelitis have also been reported to originate from cutaneous A. haemolyticum infections. [8]

Though less common, reports of A. haemolyticum infections may be complicated and have been reported to cause brain abscesses, pneumonia, infective endocarditis, pyothorax, and bacteremia.[4][13][8][14][15] An immunosuppressed or immunocompromised state of health such as cancer, HIV, or diabetes mellitus may increase the risk of systemic infections like meningitis and bacteremia.[1][2][9]

Evaluation

This rod-shaped bacterium is a gram-positive, weakly acid-fast, non-facultative anaerobe that grows optimally in blood or serum-enriched medium at 37 degrees C with 5-10% carbon dioxide. Chemically, A. haemolyticum is catalase-negative, oxidase-negative, indole-negative, and urease-negative. Clinical microbiology labs can often miss the diagnosis of A. haemolyticum because streptococci undergo beta-hemolysis quickly on sheep agar, within 24 hours, while A. haemolyticum hemolyze slowly between 48 to 72 hours, therefore, plates are often discarded before an appropriate amount of incubation has occurred.[1][16]

Additionally, many clinicians rely on rapid streptococcal antigen tests from the pharynx which, if negative, could be a clue that A. haemolyticum may be involved.  Therefore, clinicians must coordinate with their laboratory if there is a concern that A. haemolyticum is the cause of pharyngitis.  It has been proposed that a selective medium enhanced with mupirocin can improve the isolation of A. haemolyticum but this technique has not been employed in most clinical settings.[17]

With advancements in technology, biochemical and spectroscopy tests are performed for diagnosis as well. A Reverse Christie-Atkins-Munch-Peterson (CAMP) test will be positive in A. haemolyticum patients.[8] Additionally,  Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) of the bacterium 16sRNA can allow for quick diagnosis of the bacterium if this technology is available in the laboratory being utilized.[18]

Treatment / Management

In vitro, mean-inhibitory concentration (MIC) studies have reported A. haemolyticum is sensitive essentially to all classes of antibiotics utilized to treat respiratory tract infections with the exception of trimethoprim/sulfamethazine.[7] It should be noted that there have been reports of penicillin tolerance requiring higher concentrations of penicillin. Therriault et al. published a review of the literature that suggests first-line therapy for deep soft-tissue infections should be intravenous penicillin or cephalosporins.[1] In cases of treatment failure or beta-lactam allergies, macrolides are a good alternative.

Additionally, for patients with beta-lactam allergies, antibiotics such as vancomycin, fluoroquinolones, clindamycin, and doxycycline should be considered. In addition to medical management with antibiotics, patients with systemic infections may require vasopressors, fluid resuscitation, and surgical intervention as needed.[4][19]

Differential Diagnosis

Acute pharyngitis is a common infection and can be caused by a wide variety of organisms such as Streptococcus pyogenes, Mycoplasma pneumoniae, Neisseria gonorrhea, and many others to include viral pathogens such as influenza. The presence of a maculopapular or scarlatiniform rash may make the infection appear like scarlet fever.  A. haemolyticum can be differentiated from S. pyogenes in the laboratory by a negative strep and catalase test and a positive reverse CAMP test. Severe upper respiratory infections may also cause diphtheria-like symptoms where a gray membrane overlying the tonsil or epiglottis can be seen.[20] Failure to grow A. haemolyticum on tellurite enables differentiation from Corynebacterium diphtheria.[21]

Prognosis

Like most pharyngitis, A. haemolyticum typically resolves within 7 to 10 days. In more severe and persistent cases, airway obstruction via membranous pharyngitis similar to diphtheria may be present. Complications have rarely been reported.  Infections treated with appropriate antibiotics will lead to the resolution of symptoms.[11]

Complications

Complications of A. haemolyticum pharyngitis include Lemierre syndrome, brain abscesses, endocarditis, and bacteremia. Rarely have long-term sequelae of A. haemolyticum infection has been reported. Persistent infection due to the delayed recognition of the organism as the causative agent may lead to a poor outcome and mortality due to sepsis especially in patients with serious co-morbidities.[4][8][9][15][22]

Consultations

Consultation with an infectious disease specialist may be useful in order to try to coordinate care with the clinical microbiology lab.

Deterrence and Patient Education

Droplet contact precaution can reduce the risk of spreading the disease. Patients should be educated on symptoms and methods of prevention such as hand washing, covering mouth when coughing, sharing utensils, social distance, and etc. from others when symptomatic. Symptoms by A. haemolyticum can be very easily managed through aggressive fluid hydration, rest, and the use of non-steroidal anti-inflammatory drugs. Early detection and treatment using a variety of antibiotics, with the exception of TMP-SMX, will promptly treat infection and result in the resolution of symptoms.

Enhancing Healthcare Team Outcomes

The key areas of interprofessional communication for treating patients with A. haemolyticum is the coordination between physicians, clinical laboratory microbiologists, and pharmacists. Physicians need to communicate with the laboratory if they are considering this diagnosis in order to make sure that pharyngeal culture specimens are handled properly.  Infectious diseases consultation may be useful. Coordination with the laboratory and pharmacy may be necessary in cases where non-beta lactam antibiotics may be needed for the treatment of patients with known allergy or intolerance.  This coordination will ensure that patients who have pharyngitis that is not caused by S. pyogenes have the best clinical outcomes.

Evidence for the findings discussed in this article is all from historical cohort or case-control studies and case Series, studies with no controls, and expert opinion.