Other Gram-Negative Coccobacilli

Aggregati Bacter Species

Aggregatibacter (formerly Actinobacillus ) actinomycetemcomitans , a small, fastidious gram-negative coccobacillus, is a cause of endocarditis, of periodontal infection, and of pneumonia and soft-tissue abscesses, often in conjunction with Actinomyces israelii (see Chapter 187, Chapter 195 ). The other species of this genus within the family Pasteurellaceae are Aggregatibacter aphrophilus (formerly Haemophilus aphrophilus and Haemophilus paraphrophilus ), which can cause bone and joint infections, spondylodiscitis, brain abscess, and endocarditis; and Aggregatibacter (formerly Haemophilus ) segnis , which can cause endocarditis. The other Actinobacillus species— A. equuli subsp. equuli , A. equuli subsp. haemolyticus , A. lignieresii , A. ureae , and A. hominis— occasionally are associated with human disease; the first three primarily infect animals.

A. actinomycetemcomitans commonly is part of the normal flora of the mouth of humans, especially in gingival and supragingival crevices and also of various animal species. The incidence of carriage is markedly higher in individuals with refractory periodontitis and in people with juvenile periodontal disease. The organism can be transmitted among household members.

A. actinomycetemcomitans contributes to the HACEK organisms, an acronym for a group of fastidious gram-negative coccobacilli that also include Haemophilus parainfluenzae , Aggregatibacter (formerly Haemophilus ) aphrophilus , Cardiobacterium hominis , Eikenella corrodens , and Kingella kingae that cause endocarditis. Poor dentition or recent dental manipulation is a risk factor for A. actinomycetemcomitans endocarditis, and most patients are adults with underlying valvular heart disease. Infection manifests subacutely with a mean interval from onset of symptoms to diagnosis of 3 months. Symptoms include fever, chills, malaise, anorexia, and weight loss. Hepatosplenomegaly and peripheral stigmata, including petechiae, are common clinical findings. The incidence of embolic phenomena is similar to that in persons with endocarditis from other causes. Anemia and an elevated erythrocyte sedimentation rate are common laboratory findings.

The most common illness associated with A. actinomycetemcomitans is juvenile and adult periodontal disease. A. actinomycetemcomitans also causes soft tissue abscesses, particularly of the chest wall or mandibular area, often as a coinfection with A. israelii . Chest wall lesions often are associated with pulmonary or pleural lesions, and lesions of the mandibular area typically are associated with dental caries or periodontal disease. Cases of pneumonia, empyema, osteomyelitis, septic arthritis, brain abscess, cervical lymphadenitis, intra-abdominal abscess, and urinary tract infection have been reported with A. actinomycetemcomitans as a sole pathogen or copathogen.

Isolation of the organism is hampered by slow and fastidious growth; a carbon dioxide−enriched environment improves growth. Growth in nutrient broth, such as trypticase soy or Schaedler, can occur without turbidity in blood culture bottles, including radiometric blood culture bottles, or can appear as tiny puffballs growing in the blood cell layer or as granules that adhere to the sides or bottom of the bottle. A. actinomycetemcomitans grows on blood or chocolate agar, forming small colonies after up to 7 days of incubation, but grows poorly on MacConkey agar. A. aphrophlius and A. segnis can require V factor for growth. Identification of isolates can be difficult and misidentified as Haemophilus ; speciation may be facilitated by PCR, VITEK 2 ID-NH (bioMérieus, Marcy l’Etoile, France), or matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Nucleic acid amplification of 16S rRNA has been used to identify A. actinomycetemcomitans directly from biopsy material.

Although penicillin or ampicillin has been used commonly to treat infections caused by A. actinomycetemcomitans , resistance can occur occasionally. A test for β-lactamase should be performed on isolates. Strains are uniformly susceptible to the third-generation cephalosporin antibiotic ceftriaxone that can be considered the drug of choice pending results of susceptibility testing. Isolates usually are susceptible to aminoglycosides, rifampin, metronidazole, tetracycline, trimethoprim-sulfamethoxazole, fluoroquinolones, azithromycin, imipenem, and chloramphenicol and generally are resistant to antistaphylococcal penicillins, clindamycin, vancomycin, and erythromycin. ^{, , ,}

Clinical experience suggests that treatment of endocarditis with penicillin and gentamicin usually is successful. Ceftriaxone with or without an aminoglycoside or rifampin may be optimal therapy for endocarditis. Oral ciprofloxacin also has been used successfully. Severe periodontal disease usually is treated with mechanical debridement in combination with tetracycline, a fluoroquinolone, or with the combination of metronidazole and amoxicillin.