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Mixed Anaerobic Infections

by Joseph R. Lentino, MD, PhD

Anaerobes can infect normal hosts and hosts with compromised resistance or damaged tissues. Symptoms depend on site of infection. Anaerobes are often accompanied by aerobic organisms. Diagnosis is clinical combined with Gram stain and anaerobic cultures. Treatment is with antibiotics and surgical drainage and debridement.

Hundreds of species of nonsporulating anaerobes are part of the normal flora of the skin, mouth, GI tract, and vagina. If this commensal relationship is disrupted (eg, by surgery, other trauma, poor blood supply, or tissue necrosis), a few of these species can cause infections with high morbidity and mortality. After becoming established in a primary site, organisms can spread hematogenously to distant sites. Because aerobic and anaerobic bacteria are frequently present in the same infected site, appropriate procedures for isolation and culture are necessary to keep from overlooking the anaerobes. Anaerobes can be the main cause of infection in the pleural spaces and lungs; in intra-abdominal, gynecologic, CNS, upper respiratory tract, and cutaneous diseases; and in bacteremia.

Etiology

The principal anaerobic gram-positive cocci that cause disease are peptococci and peptostreptococci, which are part of the normal flora of the mouth, upper respiratory tract, and large intestine. The principal anaerobic gram-negative bacilli include Bacteroides fragilis, Prevotella melaninogenica, and Fusobacterium sp. The B. fragilis group is part of the normal bowel flora and includes the anaerobic pathogens most frequently isolated from intra-abdominal and pelvic infections. Organisms in the Prevotella group and Fusobacterium sp are part of the normal oral and large-bowel flora.

Pathophysiology

Anaerobic infections can usually be characterized as follows:

  • They tend to occur as localized collections of pus or abscesses.

  • The reduced O 2 tension and low oxidation-reduction potential that prevail in avascular and necrotic tissues are critical for their survival.

  • When bacteremia occurs, it usually does not lead to disseminated intravascular coagulation (DIC) and purpura.

Some anaerobic bacteria possess distinct virulence factors. The virulence factors of B. fragilis probably account for its frequent isolation from clinical specimens despite its relative rarity in normal flora compared with other Bacteroides sp. This organism has a polysaccharide capsule that apparently stimulates abscess formation. An experimental model of intra-abdominal sepsis has shown that B. fragilis alone can cause abscesses, whereas other Bacteroides sp require the synergistic effect of another organism. Another virulence factor, a potent endotoxin, is implicated in septic shock associated with severe Fusobacterium pharyngitis.

Morbidity and mortality rates for anaerobic and mixed bacterial sepsis are as high as those for sepsis caused by a single aerobic organism. Anaerobic infections are often complicated by deep-seated tissue necrosis. The overall mortality rate for severe intra-abdominal sepsis and mixed anaerobic pneumonias tends to be high. B. fragilis bacteremia has a high mortality rate, especially in the elderly and in patients with cancer.

Symptoms and Signs

Patients usually have fever, rigors, and critical illness; shock may develop. DIC may occur in Fusobacterium sepsis.

For specific infections (and symptoms) caused by mixed anaerobic organisms, see elsewhere in T he M anual and Disorders Often Caused by Mixed* Anaerobic Organisms. Anaerobes are rare in UTI, septic arthritis, and infective endocarditis.

Disorders Often Caused by Mixed* Anaerobic Organisms

Anaerobic cellulitis

Aspiration pneumonia

Bartholin gland infections

Brain abscesses

Chronic otitis media

Chronic sinusitis

Decubitus or ischemic ulcer infections

Dental abscesses

Endometritis

Epidural and subdural empyema

Human bite infections

Intra-abdominal abscess

Liver abscess

Ludwig angina

Lung abscess

Mandibular osteomyelitis

Necrotizing gingivitis

Necrotizing ulcerative mucositis (cancrum oris)

Nongonococcal tubo-ovarian abscess

Parametrial abscess

Pelvic peritonitis

Periodontitis

Peritonitis

Septic thrombophlebitis

Skene glands infection

Vincent angina

*With aerobes or other anaerobes.

Diagnosis

  • Clinical suspicion

  • Gram stain and culture

Clinical clues to the presence of anaerobic organisms include

  • Infection adjacent to mucosal surfaces that bear anaerobic flora

  • Ischemia, tumor, penetrating trauma, foreign body, or perforated viscus

  • Spreading gangrene involving skin, subcutaneous tissue, fascia, and muscle

  • Feculent odor in pus or infected tissues

  • Abscess formation

  • Gas in tissues

  • Septic thrombophlebitis

  • Failure to respond to antibiotics that do not have significant anaerobic activity

Anaerobic infection should be suspected when any wound smells foul or when a Gram stain of pus from an infected site shows mixed pleomorphic bacteria but aerobic cultures show no growth. Only specimens from normally sterile sites should be cultured because commensal contaminants may easily be mistaken for pathogens.

Gram stains and aerobic cultures should be obtained for all specimens. Gram stain, particularly in Bacteroides infection, and cultures for anaerobes may be falsely negative. Antibiotic sensitivity testing of anaerobes is exacting, and data may not be available for 1 wk after initial culture. However, if the species is known, sensitivity patterns can usually be predicted. Therefore, many laboratories do not routinely test anaerobic organisms for sensitivity.

Treatment

  • Drainage and debridement

  • Antibiotic choice varying by site of infection

In established infection, pus is drained, and devitalized tissue, foreign bodies, and necrotic tissue are removed. Organ perforations must be treated by closure or drainage. Whenever possible, blood supply should be reestablished. Septic thrombophlebitis may require vein ligation as well as antibiotics.

Because anaerobic culture results may not be available for 3 to 5 days, antibiotics are started. Antibiotics sometimes work even when some of the bacterial species in a mixed infection are resistant to the antibiotic, especially if surgical debridement and drainage are adequate. Antibiotics are chosen based on infection site and thus likely organisms.

Oropharyngeal anaerobic infections may not respond to penicillin and thus require a drug effective against penicillin-resistant anaerobes (see below). Oropharyngeal infections and lung abscesses should be treated with clindamycin or a β-lactam/β-lactamase combination such as amoxicillin/clavulanate. In patients allergic to penicillin, clindamycin or metronidazole (plus a drug active against aerobes) is useful.

GI or female pelvic anaerobic infections are likely to contain obligate anaerobic gram-negative bacilli such as B. fragilis plus facultative gram-negative bacilli such as Escherichia coli; antibiotic regimens must be active against both. Resistance of B. fragilis and other obligate anaerobic gram-negative bacilli to penicillins and 3rd- and 4th-generation cephalosporins occurs. However, the following drugs have excellent in vitro activity against B. fragilis and are effective: metronidazole, carbapenems (eg, imipenem/cilastatin, meropenem, ertapenem), β-lactam/β-lactamase combinations (eg, piperacillin/tazobactam, ampicillin/sulbactam, amoxicillin/clavulanate, ticarcillin/clavulanate), tigecycline, and moxifloxacin. No single regimen appears to be superior. Drugs that are less predictably active in vitro against B. fragilis include clindamycin, cefoxitin, and cefotetan. All except clindamycin and metronidazole can be used as monotherapy because these drugs also have good activity against facultative anaerobic gram-negative bacilli.

Metronidazole is active against clindamycin-resistant B. fragilis, has unique anaerobic bactericidal activity, and usually avoids the pseudomembranous colitis sometimes associated with clindamycin. Concerns about metronidazole's potential mutagenicity have not been of clinical consequence.

Because many regimens currently used to treat GI or female pelvic anaerobic infections are also effective against gram-negative bacilli, use of a potentially nephrotoxic aminoglycoside (to cover enteric gram-negative bacilli) plus an antibiotic active against B. fragilis is no longer warranted.

Prevention

Before elective colorectal surgery, patients should have bowel preparation consisting of

  • Cathartics

  • Enemas

  • Antibiotics

Most surgeons give both oral and parenteral antibiotics. For emergency colorectal surgery, parenteral antibiotics are used alone. Examples of oral regimens are neomycin plus erythromycin or neomycin plus metronidazole; these drugs are given no more than 18 to 24 h before the procedure. Examples of parenteral preoperative regimens are cefotetan, cefoxitin, or cefazolin plus metronidazole; these drugs are given within 1 h before the procedure. Preoperative parenteral antibiotics control bacteremia, reduce secondary or metastatic suppurative complications, and prevent local spread of infection around the surgical site.

For patients with confirmed allergy or adverse reaction to β-lactams, one of the following regimens is recommended: clindamycin plus gentamicin, aztreonam, or ciprofloxacin; or metronidazole plus gentamicin or ciprofloxacin.

Key Points

  • Mixed anaerobic infections occur when the normal commensal relationship among the normal flora of mucosal surfaces (eg, skin, mouth, GI tract, vagina) is disrupted (eg, by surgery, injury, ischemia, or tissue necrosis).

  • Infections tend to occur as localized collections of pus or abscesses.

  • Base clinical suspicion on the clinical setting and the presence of gangrene, pus, abscess, tissue gas, and/or feculent odor.

  • Draining and debride the infected area, and give antibiotics selected based on the infection location (and thus likely organisms).

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • AVELOX
  • No US brand name
  • FLAGYL
  • TYGACIL
  • MEFOXIN
  • MERREM
  • AMOXIL
  • CLEOCIN
  • INVANZ
  • ERY-TAB, ERYTHROCIN
  • NEO-FRADIN
  • GENOPTIC
  • CILOXAN, CIPRO
  • ANCEF, KEFZOL
  • AZACTAM

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