Chapter 205 Other Anaerobic Infections
Anaerobic bacteria are among the most numerous organisms colonizing humans. Anaerobes are present in soil and are normal inhabitants of all living animals, but infections caused by anaerobes are relatively uncommon. Anaerobes are relatively or entirely intolerant of exposure to oxygen. Most are facultative anaerobes, being able to survive in the presence of oxygen but growing better in reduced oxygen tensions. Obligate anaerobes cannot survive any exposure to oxygen.
Infections with anaerobes occur most commonly adjacent to mucosal surfaces, often as mixed infections with aerobes. Conditions of reduced oxygen tension provide the optimal conditions for proliferation of anaerobes. Traumatized areas, devascularized areas, and areas of crush injury are all ideal sites for anaerobic infection. Often both aerobic and anaerobic organisms are inoculated, with local extension and bacteremia most often caused by the more virulent aerobes. Abscess formation evolves over days to weeks and generally involves both aerobes and anaerobes. Examples of such infections include appendicitis and peri-appendiceal, pelvic, perirectal, peritonsillar, retropharyngeal, parapharyngeal, lung, and dental abscesses. Septic thrombophlebitis, which is a consequence of appendicitis, chronic sinusitis, pharyngitis, and otitis media, provides a route for spread of anaerobic infection to parenchymal organs such as the liver, brain, and lungs.
Anaerobic infection is usually caused by endogenous flora. Combinations of impaired physical barriers to infection, compromised tissue viability, alterations in normal flora, impaired host immunity, and anaerobic bacterial virulence factors contribute to infection with normal anaerobic inhabitants of mucous membranes. Virulence factors include capsules, toxins, enzymes, and fatty acids.
Anaerobic infections occur in a variety of sites throughout the body (Table 205-1). Anaerobes often coexist synergistically with aerobes. Infections with anaerobes are almost always polymicrobial and also include aerobes.
Table 205-1 INFECTIONS ASSOCIATED WITH ANAEROBIC BACTERIA
| SITE AND INFECTION | MAJOR RISK FACTORS | ANAEROBIC BACTERIA* |
|---|---|---|
| CENTRAL NERVOUS SYSTEM | ||
| Cerebral abscess | Cyanotic heart disease Cystic fibrosis Penetrating trauma |
Polymicrobial |
| Epidural and subdural empyemas | Direct extension from contiguous sinusitis, otitis media, mastoiditis | Bacteroides fragilis† Fusobacterium Peptostreptococcus Veillonella |
| UPPER RESPIRATORY TRACT | ||
| Dental abscess | Poor periodontal hygiene | Peptostreptococcus |
| Ludwig angina (cellulitis of sublingual-submandibular space) | Drugs that cause gum hypertrophy | Fusobacterium |
| Necrotizing gingivitis (Vincent stomatitis) | Prevotella melaninogenica | |
| Chronic otitis-mastoiditis-sinusitis | Tympanic perforation Tympanostomy tubes |
|
| Peritonsillar abscess | Streptococcal pharyngitis | |
| Retropharyngeal abscess | Penetrating injury | |
| LOWER RESPIRATORY TRACT | ||
| Aspiration pneumonia | Periodontal disease | Polymicrobial |
| Necrotizing pneumonitis | Bronchial obstruction | P. melaninogenica |
| Lung abscess | Altered gag or consciousness Aspirated foreign body Sequestered lobe Vascular anomaly |
Bacteroides intermedius Fusobacterium Peptostreptococcus, Eubacterium B. fragilis, Veillonella |
| Septic pulmonary emboli | Fusobacterium | |
| INTRA-ABDOMINAL | ||
| Abscess | Appendicitis | Polymicrobial |
| Secondary peritonitis | Penetrating trauma (especially of the colon) | Bacteroides spp. Clostridium Peptostreptococcus Eubacterium Fusobacterium |
| FEMALE GENITAL TRACT | ||
| Bartholin abscess | Vaginosis | B. fragilis |
| Tubo-ovarian abscess | Intrauterine device | Bacteroides bivius |
| Endometritis | Peptostreptococcus | |
| Pelvic thrombophlebitis | Clostridium | |
| Salpingitis | Mobiluncus | |
| Chorioamnionitis | Actinomyces | |
| Septic abortion | Clostridium | |
| SKIN AND SOFT TISSUE | ||
| Cellulitis | Decubitus ulcers | Varies with site and contamination with oral or enteric flora |
| Perirectal cellulitis | Abdominal wounds | Clostridium perfringens (myonecrosis) |
| Myonecrosis (gas gangrene) | Pilonidal sinus | Bacteroides Clostridia |
| Necrotizing fasciitis and synergistic gangrene | Trauma Human and animal bites Immunosuppressed or neutropenic patients Varicella |
Fusobacterium Clostridium tertium Clostridium septicum Anaerobic streptococci |
| BLOOD | ||
| Bacteremia | Intra-abdominal infection, abscesses, myonecrosis, necrotizing fasciitis | B. fragilis Clostridium Peptostreptococcus Fusobacterium |
* Infections may also be due to or may involve aerobic bacteria as the sole agent or as part of a mixed infection; brain abscess may contain microaerophilic streptococci; intra-abdominal infections may contain gram-negative enteric organisms and enterococci; and salpingitis may contain Neisseria gonorrhoeae and Chlamydia trachomatis.
† Bacteroides fragilis is usually isolated from infections below the diaphragm except for brain abscesses.
Anaerobes account for about 1% of bloodstream bacterial isolates in adults, but the rate is lower in children. Isolation of anaerobes from the blood is often an indication of a serious primary anaerobic infection elsewhere in the body. The most common blood isolates of anaerobic bacteria in children are Bacteroides fragilis, Peptostreptococcus spp, Clostridium spp, and Fusobacterium spp. The cell walls of gram-negative anaerobes may contain endotoxin and can be associated with the development of hypotension and shock when present in the circulatory system. Clostridia produce hemolysins, and the presence of these organisms in the blood can herald massive hemolysis and cardiovascular collapse.
Meningitis is rare, but it has occurred in neonates and as a complication of infections of the ear and neck. Brain abscess and subdural empyema are usually polymicrobial, with anaerobes commonly involved (Chapter 596). Brain abscess occurs most often as a result of spread of infection from sinuses, middle ear, or lung.
The respiratory tract is colonized by both aerobes and anaerobes. Anaerobic bacteria are involved in chronic sinusitis, chronic otitis media, peritonsillar infections, parapharyngeal and retropharyngeal abscesses, and periodontal infections. Anaerobic periodontal disease is most common in patients who have poor dental hygiene or who are receiving drugs that cause hypertrophy of the gums. Vincent angina, also known as acute necrotizing ulcerative gingivitis or trench mouth, is an acute, fulminating, mixed anaerobic bacterial-spirochetal infection of the gingival margin and floor of the mouth. It is characterized by gingival pain, foul breath, and pseudomembrane formation. Ludwig angina is an acute, life-threatening cellulitis of dental origin of the sublingual and submandibular spaces. Infection spreads rapidly in the neck and may cause sudden airway obstruction.
Lemierre syndrome, or postanginal sepsis, is a suppurative infection of the lateral pharyngeal space, of apparent increasing prevalence, that often begins as pharyngitis (Chapter 176). It may complicate Epstein Barr Virus or other infections of the pharynx. It usually manifests as a unilateral septic thrombophlebitis of the jugular venous system with septic pulmonary embolization. Clinical signs include unilateral painful neck swelling, trismus, and dysphagia culminating with signs of sepsis and respiratory distress. Fusobacterium necrophorum is the most commonly isolated organism, although polymicrobial infection may occur.
Anaerobic lung abscess, empyema, and anaerobic pneumonia are most common in children who have disordered swallowing or seizures or in whom an inhaled foreign body is occluding a bronchus. Most children and adults aspirate oral contents during sleep and periods of unconsciousness. In most cases, lung cilia and phagocytes clear particulate matter and microbes. If the aspiration is of increased volume or frequency or a foreign body blocks normal ciliary clearance, normal pulmonary clearance mechanisms are overcome and infection ensues. In unusual cases, particularly in patients with poor dental hygiene, aspirated mouth contents may contain the anaerobe Actinomyces israelii, resulting in pulmonary actinomycosis (Chapter 182). This anaerobic pneumonitis is remarkable for traversing tissues planes, and affected patients often have distinctive fistulas of the chest wall overlying the area intrathoracic infection.
The entire digestive tract is heavily colonized by anaerobes. The density of organisms is highest in the colon, where anaerobes outnumber aerobes 1,000 : 1. Perforation of the gut leads to leakage of gut flora into the peritoneum, resulting in peritonitis involving both aerobes and anaerobes. Secondary sepsis caused by aerobes often occurs early. As the peritoneal infection is walled off, an abscess composed of both aerobes and anaerobes often forms. Secondary hepatic abscesses may then develop as complications of appendicitis, intestinal perforation, inflammatory bowel disease, or biliary tract disease. In children with malignancies who are receiving chemotherapy, the intestinal mucosa is often damaged, leading to translocation of bacteria and focal invasion of bowel flora. Typhlitis is a mixed infection of the gut wall usually beginning in the ileocecum and characterized by abdominal pain, diarrhea, fever, and abdominal distention in neutropenic patients. Empirical antimicrobial therapy of fever and neutropenia may not be optimal against the anaerobes involved in typhlitis (Chapter 171). Similarly, a mixed aerobic/anaerobic infection of the intestinal wall and peritoneum may develop in a small infant as a complication of necrotizing enterocolitis, believed to be due to relative vascular insufficiency of the gut and hypoxia (Chapter 96.2).
Pelvic inflammatory disease and tubo-ovarian abscesses are frequently caused by mixed aerobic anaerobic infection. Vaginitis can be caused by overgrowth of anaerobic flora. Anaerobes frequently contribute to chorioamnionitis and premature labor and may result in anaerobic bacteremia of the newborn. Although these bacteremias are often transient, anaerobes occasionally cause invasive disease in the newborn, including central nervous system (CNS) infection.
Anaerobic skin infections occur in the setting of bites, foreign bodies, and skin and tissue ulceration due to pressure necrosis or lack of adequate blood supply. Animal bites and human bites inoculate oral and skin flora into damaged and hypoxic cutaneous tissue. The extent of the infection depends on the depth of the bite and the associated crush injury to the tissues. In immunocompromised patients, unusual oral anaerobes such as Capnocytophaga canimorsus can cause life-threatening infection.
Clostridial myonecrosis, or gas gangrene, is a rapidly progressive infection of deep soft tissues, primarily muscles, associated with Clostridium perfringens. Necrotizing fasciitis is a more superficial, polymicrobial infection of the subcutaneous space with acute onset and rapid progression that has significant morbidity and mortality (Chapter 657.2). Group A streptococcus, known in the popular press as “the flesh-eating bacteria,” and Staphylococcus aureus are occasionally the causative pathogens. Commonly, necrotizing fasciitis is produced by combined infection of S. aureus or gram-negative bacilli and anaerobic streptococci, termed synergistic gangrene. This infection is often seen as a complication of varicella following secondary infection of cutaneous vesicles. Diabetic patients may have a particularly aggressive and destructive synergistic gangrene of the inguinal area and adjacent scrotum or vulva known as Fournier gangrene. Early recognition with aggressive surgical debridement and antimicrobial therapy is necessary to limit disfiguring morbidity and mortality.
Occasionally, the bone adjacent to an anaerobic infection becomes infected by direct extension from a contiguous infection or by direct inoculation associated with trauma. Anaerobic infections of the kidneys (renal and perirenal abscesses) and heart (pericarditis) are rare. Enteritis necroticans (pigbel) is a rare but often fatal gastrointestinal infection that most commonly follows ingestion of a large meal in a previously starved child or adult. Anaerobic osteomyelitis, particularly of fingers and toes, can complicate any process capable of producing hypoxic necrosis, including diabetes, neuropathies, vasculopathies, and coagulopathies.
The diagnosis of anaerobic infection requires a high index of suspicion and the collection of appropriate and adequate specimens for anaerobic culture (Table 205-2). Culture specimens should be obtained in a manner that protects them from contamination with mucosal bacteria and from exposure to ambient oxygen. Swab samples from mucosal surfaces, nasal secretions, respiratory specimens, and stool should not be sent for anaerobic culture, because these sites normally harbor many anaerobes. Aspirates of infected sites, abscess material, and biopsy specimens are appropriate. Specimens must be protected from oxygen and transported to the laboratory immediately. An anaerobic transport medium is used to increase the likelihood of recovery of obligate anaerobes. Gram staining of abscess fluid from suspected anaerobic infections is useful because even if the organisms do not grow in culture, they can be seen on the smear. Methods for susceptibility testing exist but may not be routinely available. A rapid and easy screening test can be used to detect β-lactamase production and presumptive penicillin resistance.
Table 205-2 CLUES TO PRESUMPTIVE DIAGNOSIS OF ANAEROBIC INFECTIONS*
* Suspicion of anaerobic infection is critical before specimens are sample for culture, to ensure optimal microbiologic techniques and prompt, appropriate therapy.
Treatment of anaerobic infections requires adequate drainage and appropriate antimicrobial therapy. Antibiotic therapy varies depending on the suspected or proven anaerobe involved. Many oral anaerobic bacterial species are susceptible to penicillins, though some strains may produce a β-lactamase. Drugs that are active against such strains include metronidazole, penicillins combined with β-lactamase inhibitors (ampicillin-sulbactam, ticarcillin-clavulanate, and piperacillin-tazobactam), carbapenems (imipenem and meropenem), clindamycin, and cefoxitin. Penicillin and vancomycin are active against the gram-positive anaerobes.
Aerobes are usually present with the anaerobes, necessitating broad-spectrum antibiotic combinations for empirical therapy. Specific therapy is based on culture results and clinical course.
For soft tissue infections, providing adequate perfusion to the area is critical. At times, a muscle flap or skin flap procedure is needed to ensure that nutrients and antimicrobial agents are brought to the affected area and adequate oxygen tension is maintained. Drainage of infected areas is often necessary for cure. Bacteria may survive in abscesses because of high bacterial inoculum, lack of bactericidal activity, and local conditions that facilitate bacterial proliferation. Aspiration is sometimes effective for small collections, whereas incision and drainage may be required for larger abscesses. Extensive debridement and resection of all devitalized tissue are needed to control fasciitis and myonecrosis. The therapeutic benefit of hyperbaric oxygen therapy remains uncertain.
Strains of Clostridium cause disease by proliferation and often by production of toxins. Of the > 60 species that have been identified, only a few cause infections in humans. The most frequently implicated species are Clostridium difficile (Chapter 204), Clostridium perfringens, Clostridium botulinum (Chapter 202), Clostridium tetani (Chapter 203), Clostridium butyricum, Clostridium septicum, Clostridium sordellii, Clostridium tertium, and Clostridium histolyticus.
C. perfringens produces a variety of toxins and virulence factors. Strains of C. perfringens are designated A through E. Alpha toxin is a phospholipase that hydrolyzes sphingomyelin and lecithin and is produced by all strains. This toxin causes hemolysis, platelet lysis, increased capillary permeability, and hepatotoxicity. Beta toxin, produced by strains B and C, causes hemorrhagic necrosis of the small bowel. Epsilon toxin is produced by B and D strains and injures vascular endothelial cells, leading to increased vascular permeability, edema, and organ dysfunction. Iota toxin, produced by E strains, causes dermal edema. An enterotoxin is produced by type A and some type C and D strains. Hemolysins and a variety of enzymes are produced by many C. perfringens strains.
Clostridium species commonly invade the bloodstream shortly before, during, or just after death, leading to contamination of tissues that may be donated for transplantation. A large outbreak of Clostridium infections in tissue graft recipients was reported in 14 patients who received musculoskeletal grafts processed at a single tissue bank. As a result of this outbreak, recommendations for tissue processing now include a processing method that kills bacterial spores.
C. perfringens is the major etiologic cause of myonecrosis, a rapidly progressive anaerobic soft tissue infection. In immunocompromised persons, especially patients receiving cancer chemotherapy, C. septicum is a classic cause of rapidly fatal gas gangrene. A clue to the diagnosis is pain out of proportion to the clinical appearance of the wound. Infection progresses rapidly with edema, swelling, myonecrosis, and sometimes crepitation of soft tissues. Hypotension, mental confusion, shock, and renal failure are common. A characteristic sweet odor is present in the serosanguineous discharge. Gram staining of the exudate reveals gram-positive bacilli but few leukocytes. Early and complete debridement with excision of necrotic tissue is key to controlling the infection. Repeated, frequent assessment of tissue viability in the operating room is required. High-dose penicillin (250,000 U/kg/day divided every 4-6 hr IV) or clindamycin (25-40 mg/kg/day divided every 6-8 hr IV) should be started immediately. Amputation of affected limbs is often required. The role of hyperbaric oxygen remains unclear but has been reported to be beneficial in several studies. Unfortunately, the prognosis for patients with myonecrosis is poor, even with early, aggressive therapy.
C. perfringens type A produces an enterotoxin that causes food poisoning (Chapter 332). This intoxication results in the acute onset of watery diarrhea and crampy abdominal pain. The usual foods containing toxin are improperly prepared or stored meats and gravies. A specific etiologic diagnosis is rarely made in children with food poisoning. Therapy consists of rehydration and electrolyte replacement if necessary. The illness resolves spontaneously within 24 hr of onset. Prevention requires the maintenance of hot food at a temperature ≥ 74°C.
Bacteroides fragilis is 1 of the more virulent anaerobic pathogens and is most frequently recovered from blood cultures and cultures of tissue or pus. The most common B. fragilis infection in children occurs as a complication of appendicitis. The organism is part of normal colonic flora but is not common in the mouth or respiratory tract. B. fragilis is usually found as part of polymicrobial appendiceal and other intra-abdominal abscesses and is often involved in genital tract infections such as pelvic inflammatory disease and tubo-ovarian abscess. Prevotella organisms are normal oral flora, and infection with them typically involves gums, teeth, tonsils, and parapharyngeal spaces. Both B. fragilis and Prevotella may be involved in aspiration pneumonitis and lung abscess.
Strains of B. fragilis and Prevotella melaninogenica produce β-lactamase and are resistant to penicillins. Recommended treatment is with ticarcillin-clavulanate, piperacillin-tazobactam, cefoxitin, metronidazole, clindamycin, imipenem, or meropenem. Because infections involving these organisms are usually polymicrobial, therapy should include antimicrobial agents active against likely concomitant aerobic pathogens. Drainage of any abscesses and debridement of necrotic tissue are often required for control of these infections.
Fusobacterium organisms inhabit the intestine, respiratory tract, and female genital tracts. These organisms, which are more virulent than most of the normal anaerobic flora, cause bacteremia and a variety of rapidly progressive infections. Lemierre syndrome, bone and joint infections, and abdominal and genital tract infections are most common. Some strains produce a β-lactamase and are resistant to penicillins, requiring therapy with drugs like ampicillin-sulbactam and clindamycin.
Veillonella organisms are normal flora of the mouth, upper respiratory tract, intestine, and vagina. These anaerobes rarely cause infection. Strains are recovered as part of the polymicrobial flora causing abscess, chronic sinusitis, empyema, peritonitis, and wound infection. Veillonella organisms are susceptible to penicillins, cephalosporins, clindamycin, metronidazole, and carbapenems.
Peptostreptococcus species are normal flora of the skin, respiratory tract, and gut. These organisms are often present in brain abscesses, chronic sinusitis, chronic otitis, and lung abscesses. Such infections are often polymicrobial, and therapy is aimed at the accompanying aerobes as well as the anaerobes. Most of the gram-positive cocci are susceptible to penicillin, cephalosporins, carbapenems, and vancomycin.
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