Updated: Jun 20, 2008
This article describes infections caused by the Bacteroides fragilis group and other anaerobic gram-negative bacilli (AGNB) that were previously included in the Bacteroides genus but are now included in the Prevotella and Porphyromonas genera. Infections due to AGNB are common, yet the specific identification of AGNB in these infections is difficult.
Bacteroides species are anaerobic bacteria that are predominant components of the bacterial florae of mucous membranes1 and are therefore a common cause of endogenous infections. Bacteroides infections can develop in all body sites, including the CNS, the head, the neck, the chest, the abdomen, the pelvis, the skin, and the soft tissues. Inadequate therapy against these anaerobic bacteria may lead to clinical failure.
Because of their fastidiousness, they are difficult to isolate and are often overlooked. Their isolation requires appropriate methods of collection, transportation, and cultivation of specimens.2 Treatment is complicated by 3 factors: slow growth, increasing resistance to antimicrobial agents,3 and the polymicrobial synergistic nature of the infection.4
The B fragilis group, a member of the Bacteroidaceae family, includes B fragilis (causes the most clinical infections), Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, and Bacteroides vulgatus. These bacteria are resistant to penicillins, mostly through the production of beta-lactamase. They are part of the normal GI florae1 and predominate in intra-abdominal infections and infections that originate from those florae (eg, perirectal abscesses, decubitus ulcers). Enterotoxigenic B fragilis (ETBF) is also a potential cause of diarrhea.5
Pigmented Prevotella, such as Prevotella melaninogenica and Prevotella intermedia (which were previously called the Bacteroides melaninogenicus group), Porphyromonas (eg, Porphyromonas asaccharolytica), and nonpigmented Prevotella (eg, Prevotella oralis, Prevotella oris) are part of the normal oral and vaginal florae and are the predominant AGNB isolated from respiratory tract infections and their complications, including aspiration pneumonia, lung abscess, chronic otitis media, chronic sinusitis, abscesses around the oral cavity, human bites, paronychia, brain abscesses, and osteomyelitis. Prevotella bivia and Prevotella disiens (previously called Bacteroides) are important in obstetric and gynecologic infections.
Most infections due to AGNB originate from the endogenous mucosal membrane florae. Knowledge of the common mode of distribution allows for a logical choice of antimicrobial therapy for infections in these sites.
AGNB infections are generally polymicrobial. The number of isolates can reach 5-10 organisms. The type of copathogens depends on the infection site and the circumstances of the infection. Antimicrobial therapy should be directed at all major aerobic and anaerobic pathogens. AGNB promote infection through synergy with their aerobic and anaerobic counterparts and with each other.
An indirect pathogenic role of AGNB is their ability to produce the enzyme beta-lactamase, which allows them to protect themselves and other penicillin-susceptible organisms from the activity of penicillins.
The exact frequency of AGNB infection is difficult to calculate because of inappropriate methods of collection, transportation, and cultivation of specimens. AGNB are more commonly found in chronic infections. Their rate of recovery in blood cultures is 2-5% and higher with patients who have predisposing conditions.
The frequency of these infections appears to be higher in developing countries, where therapy is often inadequate or delayed.
The mortality rate has decreased over the past 3 decades because of early recognition and initiation of proper prophylactic and therapeutic antimicrobial therapies.
AGNB infections can occur in patients of all ages; however, the frequency of head and neck infections is higher in pediatric patients than in other patients.
AGNB infections occur more often in chronic infections and in association with the predisposing conditions discussed below. However, they can also cause acute infections (ie, maxillary sinusitis associated with dental infections, intra-abdominal infections following perforation).6, 7
- CNS infections
- AGNB can cause various intracranial infections, including brain abscess, subdural empyema, epidural abscess, and meningitis (usually from contiguous spread from adjacent foci of infection). Brain abscesses are commonly caused by chronic infections in the ears, the mastoids, the sinuses, the oropharynx, the teeth, or the lungs.
- Hematogenous spread can occur after dental, oropharyngeal, pulmonary, or intra-abdominal infection. Rarely, bacteremia of another origin or endocarditis leads to such infection.8
- Head and neck infections: Anaerobes, including AGNB, are recovered from various infections, especially in their chronic form. Head and neck infections include chronic otitis media9; sinusitis10; mastoiditis; tonsillar,10 peritonsillar, and retropharyngeal abscesses; cervical lymphadenitis; all deep neck space infections; thyroiditis; odontogenic infections; and postsurgical and nonsurgical head and neck wounds and abscesses.11
- Sinusitis is complicated by anaerobes, including AGNB, when it becomes chronic and oxygen levels decline. Anaerobes are isolated from 10% of patients with acute maxillary sinusitis (mostly secondary to odontogenic infection), but they are found in as many as 67% of chronic infections of the maxillary, ethmoid, frontal, and sphenoid sinuses.12, 10 The infection may spread via anastomosing veins or contiguously to the CNS. Complications include orbital cellulitis, meningitis, cavernous sinus thrombosis, and epidural and subdural brain abscesses.
- Tonsillitis, whether acute or chronic, may have AGNB involvement.13, 10 AGNB can also be involved with tonsillitis complications, including internal jugular vein thrombophlebitis, which often causes postanginal sepsis. Prevotella species and other anaerobes are recovered from tonsillar or retropharyngeal abscesses without any aerobic bacteria, and they are isolated in cases of Vincent angina.
- Pleuropulmonary infections: Aspiration of oropharyngeal or gastric secretions and periodontal or gingival disease are risk factors for anaerobic pleuropulmonary infection due to AGNB and to other anaerobes. The infection can progress from pneumonitis to necrotizing pneumonia and lung abscess, with or without empyema.14
- Intra-abdominal infections15
- Secondary peritonitis and abdominal abscesses generally occur after entry of enteric organisms into the peritoneal cavity through perforation of the intestine or other viscus as a result of obstruction, infarction, or trauma.
- The more distal the perforation, the more numerous the types and number of organisms that gain access into the peritoneal cavity (ie, perforations in the descending colon are associated with spillage of more organisms than perforations in proximal parts of the colon).
- Enterotoxigenic B fragilis are considered an emerging enteropathogen-causing diarrhea.
- Female genital tract infection: These infections include bacterial vaginosis; soft tissue perineal, vulvar, and Bartholin gland abscesses; endometritis; pyometra; salpingitis; tubo-ovarian abscesses; adnexal abscess; pelvic inflammatory disease, which may include pelvic cellulitis and abscess; amnionitis; septic pelvic thrombophlebitis; intrauterine device–associated infection; septic abortion; and postsurgical obstetric and gynecologic infections.
- Skin and soft tissue infections
- Infections involving AGNB include superficial infections, such as infected cutaneous ulcers, cellulitis, secondary diaper rash, gastrostomy or tracheostomy site wounds, infected subcutaneous sebaceous or inclusion cysts, eczema, scabies or kerion infections, paronychia, hidradenitis suppurativa, and pyoderma.
- Subcutaneous tissue infections and postsurgical wound infections that may also involve the skin include cutaneous and subcutaneous abscesses, decubitus ulcers, infected diabetic (vascular or trophic) ulcers, breast abscesses, bite wounds,16 anaerobic cellulitis and gas gangrene, bacterial synergistic gangrene, infected pilonidal cyst or sinus, Meleney ulcer, and burn wound infection.
- Deeper anaerobic soft tissue infections include necrotizing fasciitis, necrotizing synergistic cellulitis, gas gangrene, and crepitus cellulitis. These infections can involve the fascia alone or also the muscle surrounded by the fascia, inducing myositis and myonecrosis.
- Anaerobic infections, such as decubitus ulcers or diabetic foot ulcers, are generally polymicrobial and are often complicated by osteomyelitis or bacteremia.
- Deep tissue infections, such as necrotizing cellulitis, fasciitis, and myositis, often involve clostridial organisms and Staphylococcus pyogenes. They may be polymicrobic; may contain gas and gray, thin, putrid pus; and are associated with bacteremia and mortality.17
- Osteomyelitis and septic arthritis: Osteomyelitis in the long bones and the cranial and facial bones is frequently polymicrobic and may be associated with anaerobes in patients with peripheral vascular disease and decubitus ulcers.18
- The prevalence of anaerobes, including AGNB, in bacteremia was once 5-15%. However, rates declined to 2-6% in the 1990s. Increased awareness of the importance of anaerobes and enhanced recognition of the types of clinical infection caused by these organisms, along with appropriate prophylaxis and treatment, have been proposed as explanations for the decreased incidence of anaerobic bacteremia from 1974–1988.19 However, recent studies have reported a resurgence in anaerobic bacteremia. A study from the Mayo Clinic (Rochester, MN) has reported that the mean incidence of anaerobic bacteremia increased from 53 cases per year during 1993–1996 to 75 cases per year during 1997–2000 to 91 cases per year during 2001–2004 (an overall increase of 74%).20
- The authors concluded that the sources of anaerobic bacteremia are now more varied than they once were, especially among immunosuppressed individuals and persons with complex underlying disease.
- Which organisms are involved depends on their portal of entry and the underlying disease. The common isolates are the B fragilis group (60-75% of isolates).8 The B fragilis group and clostridial organisms are associated with a GI source.
- Pigmented Prevotella, Porphyromonas, and Fusobacterium are associated with the oropharynx and a pulmonary source.
- Fusobacterium species involve the female genital tract.
- Propionibacterium acnes is associated with a foreign body.
- Peptostreptococcus species are associated with all sources but especially with oropharyngeal, pulmonary, and female genital tract sources.
- Predisposing factors include neoplasms; hematologic disorders; organ transplant; intestinal obstruction; decubitus ulcers; dental extraction; diabetes mellitus; postsplenectomy; use of cytotoxic agents or corticosteroids; total-body irradiation; and recent GI, obstetric, or gynecologic surgery.
- Features typical of anaerobic bacteremia include metastatic lesions, hyperbilirubinemia, and suppurative thrombophlebitis.
- The risk of mortality is 15-30% and improves with early appropriate antimicrobial therapy and resolution of the primary infection.
- Conditions that predispose to AGNB infections include the exposure of sterile sites to a high inoculum of indigenous mucous membrane florae; use of antibiotics that are ineffective against AGNB; reduced blood supply; and tissue necrosis, which lowers the oxidation-reduction potential and favors the growth of anaerobes. Conditions that lower the blood supply include trauma, foreign body, malignancy, surgery, edema, shock, colitis, and vascular disease.6, 7
- Infection with aerobic bacteria can make the local tissue conditions more favorable for the growth of anaerobes. The host defenses can become impaired by anaerobic conditions and anaerobic bacteria.
- Anaerobic infection often manifests as suppuration, thrombophlebitis, abscess formation, and gangrenous destruction of tissue associated with gas.
- Anaerobes, including AGNB, are common in chronic infections. Therapy with antimicrobials, such as aminoglycosides, trimethoprim-sulfamethazine, and older quinolones, frequently fails to eradicate anaerobes.
- Certain infections that often involve anaerobes include brain abscess, oral or dental infections, human or animal bites, aspiration pneumonia, lung abscesses, amnionitis, endometritis, septic abortions, pelvic inflammatory disease, tubo-ovarian abscess, peritonitis following viscus perforation, abscesses in and around the oral and rectal areas, and pus-forming necrotizing infections of soft tissue or muscle.6, 7
- Some tumors, such as colonic, uterine, and bronchogenic carcinomas and necrotic tumors of the head and the neck, can become infected with anaerobes.
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anaerobic gram-negative bacilli, AGNB, Bacteroides fragilis, B fragilis, Prevotella species, Porphyromonas species, Bacteroides distasonis, B distasonis, Bacteroides ovatus, B ovatus, Bacteroides thetaiotaomicron, B thetaiotaomicron, Bacteroides vulgatus, B vulgatus, Prevotella melaninogenica, P melaninogenica, Prevotella intermedia, P intermedia, Porphyromonas asaccharolytica, P asaccharolytica, Prevotella oralis, P oralis, Prevotella oris, P oris, Prevotella bivia, P bivia, Bacteroides bivia, B bivia, Prevotella disiens, P disiens, Bacteroides disiens, Bacteroides melaninogenicus group, B melaninogenicus group, perirectal abscess, decubitus ulcer, bedsore, bed sore, pressure sore, intra-abdominal abscess, intraabdominal abscess, aspiration pneumonia, lung abscess, chronic otitis media, chronic sinusitis, oral cavity abscess, abscesses around the oral cavity, human bites, paronychia, brain abscesses, osteomyelitis, Bacteroidaceae