Arcanobacterium Haemolyticum

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]

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]

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]

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]

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 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]

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

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.

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.