Chapter 252. Arcanobacterium

Arcanobacterium haemolyticum is a bacterium responsible for cases of both pharyngitis and cutaneous infections but has also been identified infrequently as a cause of various types of invasive disease.

This pleomorphic, nonsporulating, hemolytic gram-positive (sometimes gram variable) bacillus grows like Corynebacterium diphtheriae on Loeffler medium but grows poorly on tellurite media. Optimal growth is achieved on either human or rabbit blood agar, but the organism will slowly grow on standard blood agar plates. This organism was formerly classified as Corynebacterium haemolyticum. The bacterium typically has a black opaque dot in the center of each colony. A haemolyticum can liberate toxins, including a dermonecrotic toxin, using a mechanism similar to that for the production of erythrogenic toxin by group A streptococci (GAS).1

Humans are the primary reservoir of A haemolyticum,2,3 but the organism is rarely recovered from healthy individuals.4 Peak age of illness is in the second decade of life,5 whereas GAS, which may cause a similar presentation, peaks in the first decade of life. No seasonal variation occurs. A haemolyticum is responsible for 0.5% to 2.5% of bacterial pharyngitis cases in the United States.3,6Disease is spread from person to person presumably by respiratory droplet, although the mechanism of spread has yet to be completely determined. The incubation period is unknown.

The mechanism for adherence of this organism to pharyngeal mucosa is unknown. Experimentally, Arcanobacterium can invade certain types of cells and survive.7 Similar to group A streptococci, an exotoxin is likely the cause of rash with this organism.

Clinical Manifestations

Presentation of disease caused by A haemolyticum is similar to GAS pharyngitis with fever, pharyngeal exudate, and lymphadenopathy, but palatal petechiae and a strawberry tongue are usually absent.1,3,8 In up to 50% of cases, a rash is present; usually maculopapular, but may be scarlatiniform.3 The rash begins peripherally on extensor surfaces of the extremities and spreads centrally sparing the face, palms, and soles. The rash typically starts 1 to 4 days after symptoms of the sore throat begin. Occasionally pruritic, the rash persists for over 2 days in the majority of patients.

Skin infections, especially chronic ulceration, caused by A haemolyticum occur mainly in tropical countries. Invasive infections, including sepsis, brain abscess, meningitis, osteomyelitis, and pneumonia have been reported.3,9,10

Diagnosis

Adolescents and young adults complaining of sore throat and found to have a rash should be suspect. Isolation of A haemolyticum from a clinical specimen is diagnostic. Growth of the Arcanobacterium is facilitated by culture using human or rabbit blood-agar and incubating the plates for 24 to 48 hours at 37°C with 5% carbon dioxide.1Microbiology kits designed to help identify A haemolyticum have been developed11 but are not generally available in most clinical laboratories. Colonies seen at 48 hours of incubation are small (1 mm) and nonpigmented with a 3- to 5-mm zone of hemolysis.1 Coinfection with GAS and A haemolyticum as well as Epstein-Barr virus and A haemolyticum have been reported. Skin biopsy of the exanthema will typically show edema and a mixed cell perivascular infiltrate. Organisms are not typically observed.8

Treatment and Prevention

No prospective randomized study has established efficacy of antimicrobial treatment for A haemolyticum infection.1,3 In infected patients without antibiotic therapy, symptoms can last for a few days to more than 1 week. However, in antibiotic-treated patients, symptoms last, on average, 3 days.8 In vitro A haemolyticum is sensitive to erythromycin, clindamycin, azithromycin, and vancomycin.2,3,12 The organism has sensitivity to penicillin but some tolerance has been demonstrated. A haemolyticum has shown some resistance (30%) to tetracycline13,14 and is usually resistant to sulfonamides and trimethoprim-sulfamethoxazole. Resistance to ciprofloxacin was recently described in a case of brain abscess.10 Erythromycin is the drug of choice.1,3,4,8 Bacteriologic failure has occurred when penicillin was given to treat pharyngitis from which A haemolyticum was cultured. Whereas pharyngitis due to A haemolyticum has resolved in the untreated patient, invasive disease caused by A haemolyticum can be fatal. For invasive disease, intravenous beta-lactams (ie, penicillin, ampicillin, cefotaxime) are recommended, but susceptibility testing should be performed. Vancomycin should be effective; however, a strain carrying the van A gene, and resistant to vancomycin, has been identified.15 In disseminated disease, penicillin plus an aminoglycoside given by parenteral route should be considered empirically.3

Because the exact mechanism for human-to-human spread is unknown, judicious hand washing and avoidance of sharing food and utensils may be of benefit in limiting disease transmission.