Anaerobic infections of the mouth, head, and neck
Anaerobic bacteria are commonly involved in infections of the mouth, head, and neck (Chap. 20). The predominant isolates are components of the normal microbiota of the upper airways—mainly the Bacteroides oralis group, pigmented Prevotella species, P. asaccharolytica, Fusobacterium species, peptostreptococci, and microaerophilic streptococci.
Soft tissue infections of the oral-facial area may or may not be odontogenic. Odontogenic infections—primarily dental caries and periodontal disease (gingivitis and periodontitis)—are common and have both local consequences (especially tooth loss) and the potential for life-threatening spread to the deep fascial spaces of the head and neck. Infections of the mouth can arise from either supragingival or subgingival dental plaque composed of bacteria colonizing the tooth surface. Supragingival plaque formation begins with the adherence of gram-positive bacteria to the tooth surface. This form of plaque is influenced by salivary and dietary components, oral hygiene, and local host factors. Supragingival plaque can lead to dental caries and, with further invasion, to pulpitis (endodontic infection) that can further perforate the alveolar bone, causing periapical abscess. Subgingival plaque is associated with periodontal infections (e.g., gingivitis, periodontitis, and periodontal abscess) that can further disseminate to adjacent structures such as the mandible, causing osteomyelitis of the maxillary sinuses. Periodontitis may also result in spreading infection that can involve adjacent bone or soft tissues. In the healthy periodontium, the sparse microbiota consists mainly of gram-positive organisms such as Streptococcus sanguinis and Actinomyces species. In the presence of gingivitis, there is a shift to a greater proportion of anaerobic gram-negative bacilli in the subgingival microbiota, with predominance of Prevotella intermedia. In well-established periodontitis, the complexity of the microbiota increases further. The predominant isolates are P. gingivalis, P. intermedia, Aggregatibacter actinomycetemcomitans, Treponema denticola, and Tannerella forsythensis.
Necrotizing ulcerative gingivitis
Gingivitis may become a necrotizing infection (trench mouth, Vincent’s stomatitis) (Chap. 20). The onset of disease is usually sudden and is associated with tender bleeding gums, foul breath, and a bad taste. The gingival mucosa, especially the papillae between the teeth, becomes ulcerated and may be covered by a gray exudate, which is removable with gentle pressure. Patients may become systemically ill, developing fever, cervical lymphadenopathy, and leukocytosis.
Noma (cancrum oris) is a necrotizing infection of the oral mucous membranes. It is characterized by destruction of soft tissue and bone and evolves rapidly from gingival inflammation to orofacial gangrene. Noma occurs most frequently in young children (1–4 years of age) with malnutrition or systemic disease. This infection occurs worldwide but is most common in sub-Saharan Africa.
Acute necrotizing infections of the pharynx
These infections usually occur in association with ulcerative gingivitis. Symptoms include an extremely sore throat, foul breath, and a bad taste accompanied by fever and a sensation of choking. Examination of the pharynx demonstrates that the tonsillar pillars are swollen, red, ulcerated, and covered with a grayish membrane that peels easily. Lymphadenopathy and leukocytosis are common. The disease may last for only a few days or, if not treated, may persist for weeks. Lesions begin unilaterally but may spread to the other side of the pharynx or the larynx. Aspiration of the infected material by the patient can result in lung abscesses.
Peripharyngeal space infections
These infections arise from the spread of organisms from the upper airways to potential spaces formed by the fascial planes of the head and neck. The etiology is typically polymicrobial and represents the normal microbiota of the mucosa of the originating site.
Peritonsillar abscess (quinsy) is a complication of acute tonsillitis caused mainly by a mixed flora containing anaerobes (e.g., F. necrophorum and Peptostreptococcus species) and the facultative anaerobe group A Streptococcus (Chap. 20). Of cases of submandibular space infection (Ludwig’s angina), 80% are caused by infection of the tissues surrounding the second and third molar teeth. This infection results in marked local swelling of tissues, with pain, trismus, and superior and posterior displacement of the tongue. Submandibular swelling of the neck can impair swallowing and cause respiratory obstruction. In some cases, tracheotomy is life-saving. Cervicofacial actinomycosis (Chap. 72) is caused by a branching, gram-positive, non-spore-forming, strict/facultative anaerobe that is a part of the normal oral microbiota. This chronic disease is characterized by abscesses, draining sinus tracts, fistula, bone destruction, and fibrosis. It can easily be mistaken for malignancy or granulomatous disease. Actinomycosis less frequently involves the thorax, abdomen, pelvis, and CNS.
Anaerobic bacteria have been implicated in chronic sinusitis but play little role in acute sinusitis. In several studies on chronic sinusitis, anaerobic bacteria were found in 0–52% of cases, depending on the method used to collect specimens. Polymicrobial infection is common, and the predominant anaerobic isolates are pigmented Prevotella, Fusobacterium, Peptostreptococcus, and P. acnes. Aerobic gram-negative bacilli and S. aureus have also been implicated in chronic sinusitis. Anaerobic bacteria have been isolated in a large percentage of cases of chronic suppurative otitis media in children. The role of anaerobes in acute otitis media is less clear.
Complications of anaerobic head and neck infections
Contiguous cranial spread of these infections can result in osteomyelitis of the skull or mandible or in intracranial infections such as brain abscess and subdural empyema. Caudal spread can produce mediastinitis or pleuropulmonary infection. Hematogenous complications can also result from anaerobic infections of the head and neck. Bacteremia, which occasionally is polymicrobial, can lead to endocarditis or other distant infections. Lemierre’s syndrome (Chap. 20), which has been uncommon in the antimicrobial era, is an acute oropharyngeal infection with secondary septic thrombophlebitis of the internal jugular vein and frequent metastasis, most commonly to the lung. F. necrophorum is the usual cause. This infection typically begins with pharyngitis, which is followed by local invasion in the lateral pharyngeal space, with resultant internal jugular vein thrombophlebitis. A typical clinical triad includes pharyngitis, a tender/swollen neck, and noncavitating pulmonary infiltrates.
CNS infections associated with anaerobic bacteria are brain abscess, epidural abscess, and subdural empyema. Anaerobic meningitis is rare and is usually related to parameningeal collection or shunt infection. If optimal bacteriologic techniques are used, as many as 85% of brain abscesses yield anaerobic bacteria. Most anaerobic brain abscesses arise by direct extension from a site of otorhinolaryngeal infection such as otitis, sinusitis, or tooth infection. Hematogenous dissemination from a distant infected site, usually intraabdominal or pelvic, can occur. Common isolates are Peptostreptococcus, Fusobacterium, Bacteroides, Prevotella, Propionibacterium, Eubacterium, Veillonella, and Actinomyces species. Facultative or microaerophilic streptococci and coliforms are often part of a mixed infecting flora in brain abscesses.
Anaerobic pleuropulmonary infections result from the aspiration of oropharyngeal contents by patients with predisposing conditions such as dysphagia due to neurologic or esophageal disorders or transiently impaired consciousness due to conditions such as alcohol or drug abuse, seizures, head trauma, and cerebrovascular accidents. Clinical syndromes that are associated with anaerobic pleuropulmonary infection produced by aspiration include aspiration pneumonitis, which can be complicated by necrotizing pneumonia, lung abscess, and empyema. Many of these infections have an indolent course that may serve as a clinical clue differentiating them, for example, from pneumococcal pneumonia, which often presents with abrupt onset, shaking chills, and rapid progression.
The anaerobes most common in pleuropulmonary infections are indigenous to the oral cavity, especially the gingival crevice, and include pigmented and nonpigmented Prevotella, Peptostreptococcus, and Bacteroides species and F. nucleatum. Many of these infections are of mixed aerobic-anaerobic etiology, and the predominant aerobes isolated from community-acquired aspiration pneumonias are microaerophilic streptococci such as Streptococcus milleri. Studies using in-depth culture techniques in patients with community-acquired lung abscess showed aerobic and microaerophilic streptococci to be the most common pathogens (60% of patients) and anaerobes to be the second most common (26%). In a study on aspiration pneumonia from a long-term care facility, the most common isolates were gram-negative bacilli (49%), anaerobes (16%), and S. aureus (12%). Nosocomial aspiration pneumonia commonly involves a mixture of anaerobes and gram-negative bacilli or S. aureus.
Bacterial aspiration pneumonitis must be distinguished from two other clinical syndromes associated with aspiration that are not of bacterial etiology. One syndrome results from aspiration of solids, usually food. Obstruction of major airways typically results in atelectasis and moderate nonspecific inflammation. Therapy consists of removal of the foreign body. The second aspiration syndrome is more easily confused with bacterial aspiration. Mendelson’s syndrome, a chemical pneumonitis, results from regurgitation of stomach contents and aspiration of chemical material, usually acidic gastric juices. Pulmonary inflammation—including the destruction of the alveolar lining, with transudation of fluid into the alveolar space—occurs with remarkable rapidity. Typically this syndrome develops within hours, often following anesthesia when the gag reflex is depressed. The patient becomes tachypneic, hypoxic, and febrile. The leukocyte count may rise, and the chest x-ray may evolve from normal to a complete bilateral “whiteout” within 8–24 h. Sputum production is minimal. The pulmonary signs and symptoms can resolve quickly with symptom-based therapy or can culminate in respiratory failure, with the subsequent development of bacterial superinfection over a period of days. Antibiotic therapy is not indicated unless bacterial infection supervenes.
In contrast to these syndromes, bacterial aspiration pneumonitis develops over a period of several days or weeks rather than hours. Patients who enter the hospital with this syndrome typically have been ill for several days and generally report low-grade fever, malaise, and sputum production. In some patients, weight loss and anemia reflect a more chronic process. Usually the history reveals factors predisposing to aspiration, such as alcohol overdose or residence in a nursing home. Examination sometimes yields evidence of periodontal disease. Sputum characteristically is not malodorous unless the process has been under way for at least a week. A mixed bacterial flora with many PMNs is evident on Gram’s staining of sputum. Expectorated sputum is unreliable for anaerobic cultures because of inevitable contamination by the normal oral microbiota. Reliable specimens for culture can be obtained by transtracheal or transthoracic aspiration—techniques that are rarely used at present. Culture of protected-brush specimens or bronchoalveolar lavage fluid obtained by bronchoscopy is controversial.
Chest x-rays show consolidation in dependent pulmonary segments: in the basilar segments of the lower lobes if the patient has aspirated while upright and in either the posterior segment of the upper lobe (usually on the right side) or the superior segment of the lower lobe if the patient has aspirated while supine.
This form of anaerobic pneumonitis is characterized by numerous small abscesses that spread to involve several pulmonary segments. The process can be indolent or fulminating. This syndrome is less common than either aspiration pneumonitis or lung abscess and includes features of both types of infection.
(See also Chap. 22) These abscesses result from subacute anaerobic pulmonary infection. The clinical syndrome typically involves a history of constitutional signs and symptoms (including malaise, weight loss, fever, night sweats, and foul-smelling sputum), perhaps over a period of weeks (Chap. 21). Patients who develop lung abscesses characteristically have dental infection and periodontitis, but lung abscesses in edentulous patients have been reported. Abscess cavities may be single or multiple and generally occur in dependent pulmonary segments (Fig. 73-1). Anaerobic abscesses must be distinguished from lesions associated with tuberculosis, neoplasia, and other conditions.
Chest radiograph of right-lower-lobe lung abscess in a 60-year-old alcoholic patient. (From GL Mandell [ed]: Atlas of Infectious Diseases, Vol VI. Philadelphia, Current Medicine Inc, Churchill Livingstone, 1996; with permission.)
Septic pulmonary emboli may originate from intraabdominal or female genital tract infections and can produce anaerobic pneumonia and abscess.
Empyema is a manifestation of long-standing anaerobic pulmonary infection complicated by bronchopleural fistula. The clinical presentation, which includes foul-smelling sputum, resembles that of other anaerobic pulmonary infections. Patients may report pleuritic chest pain and marked chest-wall tenderness.
Empyema may be masked by overlying pneumonitis and should be considered especially in cases of persistent fever despite antibiotic therapy. Diligent physical examination and the use of ultrasound to localize a loculated empyema are important diagnostic tools. The collection of a foul-smelling exudate by thoracentesis is typical. Cultures of infected pleural fluid yield an average of 3.5 anaerobic and 0.6 facultative or aerobic bacterial species. Drainage is required. Defervescence, a return to a feeling of well-being, and resolution of the process may require several months.
Extension from a subdiaphragmatic infection may also result in anaerobic empyema.
Intraabdominal infections—mainly peritonitis and abscesses—are usually polymicrobial and represent the normal intestinal (especially colonic) microbiota. These infections most often follow a breach in the mucosal barrier resulting from appendicitis, diverticulitis, neoplasm, inflammatory bowel disease, surgery, or trauma. On average, four to six bacterial species are isolated per specimen submitted to the microbiology laboratory, with a predominance of enteric aerobic/facultative gram-negative bacilli, anaerobes, and streptococci/enterococci. The most common isolates are Escherichia coli (found in ≥50% of patients) and B. fragilis (30–50%). Other anaerobes commonly isolated from this type of infection include Peptostreptococcus, Prevotella, and Fusobacterium species. The involvement of clostridia can lead to severe infections. The dominance of four to six bacterial species out of the more than 500 colonic mucosal species is related both to the virulence factors of these species and to the inability of clinical laboratories to culture many other species residing in the colonic mucosa.
Disease originating from proximal-bowel perforation reflects the microbiota of this site, with a predominance of aerobic and anaerobic gram-positive bacteria and Candida.
Neutropenic enterocolitis (typhlitis) has been associated with anaerobic infection of the cecum but—in the setting of neutropenia (Chap. 15)—may involve the entire bowel. Patients usually present with fever; abdominal pain, tenderness, and distention; and watery diarrhea. The bowel wall is edematous with hemorrhage and necrosis. The primary pathogen is thought by some authorities to be Clostridium septicum, but other clostridia and mixed anaerobes have also been implicated. More than 50% of patients developing early clinical signs can benefit from antibiotic therapy and bowel rest. Surgery is sometimes required to remove gangrenous bowel. See Chap. 29 for a complete discussion of intraabdominal infections.
Enterotoxigenic B. fragilis has been associated with watery diarrhea in a few young children and adults. In case–control studies of children with undiagnosed diarrheal disease, enterotoxigenic B. fragilis was isolated from significantly more children with diarrhea than children in the control group.
The vagina of a healthy woman is a major reservoir of anaerobic and aerobic bacteria. In the normal microbiota of the female genital tract, anaerobes outnumber aerobes by a ratio of ~10:1 and include anaerobic gram-positive cocci and Bacteroides species (Table 73-1). Anaerobes are isolated from most women with genital tract infections that are not caused by a sexually transmitted pathogen. The major anaerobic pathogens are B. fragilis, P. bivia, P. disiens, P. melaninogenica, anaerobic cocci, and Clostridium species. Anaerobes are frequently encountered in pelvic inflammatory disease, pelvic abscess, endometritis, tubo-ovarian abscess, septic abortion, and postoperative or postpartum infections. These infections are often of mixed etiology, involving both anaerobes and coliforms; pure anaerobic infections without coliform or other facultative bacterial species occur more often in pelvic than in intraabdominal sites. Septic pelvic thrombophlebitis may complicate the infections and lead to repeated episodes of septic pulmonary emboli. See Chap. 35 for a complete discussion of pelvic inflammatory disease.
Anaerobic bacteria have been thought to be contributing factors in the etiology of bacterial vaginosis. This syndrome of unknown etiology is characterized by a profuse malodorous discharge and a change in the bacterial ecology that results in replacement of the Lactobacillus-dominated normal microbiota with an overgrowth of bacterial species including Gardnerella vaginalis, Prevotella species, Mobiluncus species, peptostreptococci, and genital mycoplasmas. A study based on 16S rRNA identification found other anaerobes that were predominant in cases but not in controls: Atopobium, Leptotrichia, Megasphaera, and Eggerthella. Pelvic infections due to Actinomyces species have been associated with the use of intrauterine devices (Chap. 72).
Skin and soft tissue infections
Injury to skin, bone, or soft tissue by trauma, ischemia, or surgery creates a suitable environment for anaerobic infections. These infections are most frequently found in sites prone to contamination with feces or with upper airway secretions—e.g., wounds associated with intestinal surgery, decubitus ulcers, or human bites. Moreover, anaerobes have been isolated from cutaneous abscesses, rectal abscesses, and axillary sweat gland infections (hidradenitis suppurativa). Anaerobes also are often cultured from foot ulcers of diabetic patients. The deep soft-tissue infections associated with anaerobic bacteria are crepitant cellulitis, synergistic cellulitis, gangrene, and necrotizing fasciitis (Chaps. 26 and 51).
These soft tissue or skin infections are usually polymicrobial. A mean of 4.8 bacterial species are isolated, with an anaerobe-to-aerobe ratio of ~3:2. The most frequently isolated organisms include Bacteroides, Peptostreptococcus, Clostridium, Enterococcus, and Proteus species. The involvement of anaerobes in these types of infections is associated with a higher frequency of fever, foul-smelling lesions, gas in the tissues, and visible foot ulcer.
Anaerobic bacterial synergistic gangrene (Meleney’s gangrene), a rare infection of the superficial fascia, is characterized by exquisite pain, redness, and swelling followed by induration. Erythema surrounds a central zone of necrosis. A granulating ulcer forms at the original center as necrosis and erythema extend outward. Symptoms are limited to pain; fever is not typical. These infections usually involve a combination of Peptostreptococcus species and S. aureus; the usual site of infection is an abdominal surgical wound or the area surrounding an ulcer on an extremity. Treatment includes surgical removal of necrotic tissue and antimicrobial administration.
Necrotizing fasciitis, a rapidly spreading destructive disease of the fascia, is usually attributed to group A streptococci (Chap. 44) but can also be a mixed infection involving anaerobes and aerobes, usually occurring after surgeries and in patients with diabetes or peripheral vascular disease. The most frequently isolated anaerobes in these infections are Peptostreptococcus and Bacteroides species. Gas may be found in the tissues. Similarly, myonecrosis can be associated with mixed anaerobic infection. Fournier’s gangrene consists of cellulitis involving the scrotum, perineum, and anterior abdominal wall, with mixed anaerobic organisms spreading along deep external fascial planes and causing extensive loss of skin.
Bone and joint infections
Although actinomycosis (Chap. 72) accounts on a worldwide basis for most anaerobic infections in bone, organisms including peptostreptococci or microaerophilic cocci, Bacteroides species, Fusobacterium species, and Clostridium species can also be involved in osteomyelitis (Chap. 28). These infections frequently arise adjacent to soft tissue infections. Many patients with osteomyelitis due to anaerobic bacteria have evidence of an anaerobic infection elsewhere in the body; most commonly, infected adjacent soft-tissue sites are the source of the organisms involved. Examples are diabetic foot ulcers and decubitus ulcers that may be complicated by mixed aerobic-anaerobic osteomyelitis. Hematogenous seeding of bone is uncommon. Prevotella and Porphyromonas species are detected in infections involving the maxilla and mandible, whereas Clostridium species have been reported as anaerobic pathogens in cases of osteomyelitis of the long bones following fracture or trauma. Fusobacteria have been isolated in pure culture from sites of osteomyelitis adjacent to the perinasal sinuses. Peptostreptococci and microaerophilic cocci have been reported as significant pathogens in infections involving the skull, mastoid, and prosthetic implants placed in bone. In patients with osteomyelitis, the most reliable culture specimen is a bone biopsy sample free of normal uninfected skin and subcutaneous tissue.
In contrast to anaerobic osteomyelitis, most cases of anaerobic arthritis (Chap. 27) involve a single isolate, and most cases are secondary to hematogenous spread. The most common isolates are Fusobacterium species. Most of the patients involved have uncontrolled peritonsillar infections progressing to septic cervical venous thrombophlebitis (Lemierre’s syndrome) and resulting in hematogenous dissemination with a predilection for the joints. Unlike anaerobic osteomyelitis, anaerobic pyoarthritis in most cases is not polymicrobial and may be acquired hematogenously. Anaerobes are important pathogens in infections involving prosthetic joints; in these infections, the causative organisms (such as Peptostreptococcus species and P. acnes) are part of the normal skin microbiota.
Transient bacteremia is a well-known event in healthy individuals whose anatomic mucosal barriers have been injured (e.g., during dental extractions or dental scaling). These bacteremic episodes, which are often due to anaerobes, have no pathologic consequences. However, anaerobic bacteria are found in cultures of blood from clinically ill patients when proper culture techniques are used. Anaerobes have accounted for 5% (range at various institutions, 0.5–12%) of cases of clinically significant bacteremia. The incidence of anaerobic bacteremia decreased from the 1970s through the early 1990s. This change may have been related to the administration of antibiotic prophylaxis before intestinal surgery, the earlier recognition of localized infections, and the empirical use of broad-spectrum antibiotics for presumed infection. Recent reports present conflicting data regarding rates of anaerobic bacteremia. A study from the Mayo Clinic compared three periods (1993–1996, 1997–2000, and 2001–2004) and found a 74% increase in the mean incidence of anaerobic bacteremia; this finding contrasts with a 45% decrease in incidence from 1977 to 1988 at the same institution. In contrast, a report from Switzerland compared two periods (1997–2001 and 2002–2006) and found decreases in both the number of anaerobe-positive blood cultures and the proportion of all blood culture isolates that were anaerobes.
The majority of anaerobic bacteremias are due to gram-negative bacilli—mainly the B. fragilis group, with B. fragilis most commonly isolated (60–80% of cases). Other organisms causing bacteremia include Clostridium species (10%), Peptostreptococcus species (10%), and Fusobacterium species (5%).
Once the organism in the blood has been identified, both the portal of bloodstream entry and the underlying problem that probably led to seeding of the bloodstream can often be deduced from an understanding of the organism’s normal site of residence. For example, mixed anaerobic bacteremia including B. fragilis usually implies a colonic pathology with mucosal disruption from neoplasia, diverticulitis, or some other inflammatory lesion. Debilitating diseases such as malignancies, diabetes, organ transplantation, and abdominal and pelvic surgeries are among the predisposing factors for anaerobic bacteremia. In a retrospective nested case–control study, diabetes was identified as a risk factor for anaerobic bacteremia when the source of bacteremia was unknown. The initial manifestations are determined by the portal of entry and reflect the localized condition. When bloodstream invasion occurs, patients can become extremely ill, with rigors and hectic fevers. The clinical picture may be quite similar to that seen in sepsis involving aerobic gram-negative bacilli. Although complications of anaerobic bacteremia (e.g., septic thrombophlebitis and septic shock) have been reported, their incidence in association with anaerobic bacteremia is low. Anaerobic bacteremia is potentially fatal and requires rapid diagnosis and appropriate therapy. Reported case–fatality rates are high, ranging from 25% to 44%, and appear to increase with the age of the patient (with reported rates of >66% among patients >60 years old), with the isolation of multiple species from the bloodstream, and with the failure to surgically remove a focus of infection. The attributable mortality rate for bacteremia associated with the B. fragilis group was examined in a matched case–control study. Patients with B. fragilis–group bacteremia had a significantly higher mortality rate (28% vs 8%), with an attributable mortality rate of 19.3% and a mortality risk ratio of 3.2.
Endocarditis and pericarditis
(See also Chap. 24) Endocarditis due to anaerobes is uncommon. However, anaerobic streptococci, which are often classified incorrectly, are responsible for this disease more frequently than is generally appreciated. Gram-negative anaerobes are unusual causes of endocarditis. Signs and symptoms of anaerobic endocarditis are similar to those of endocarditis due to facultative organisms. Mortality rates of 21–43% have been reported for anaerobic endocarditis.
Anaerobes, particularly B. fragilis and Peptostreptococcus species, are uncommonly found in infected pericardial fluids. Anaerobic pericarditis is associated with a mortality rate of >50%. Anaerobes can reach the pericardial space by hematogenous spread, by spread from a contiguous site of infection (e.g., heart or esophagus), or by direct inoculation arising from trauma or surgery.