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THE MERCK MANUAL MEDICAL LIBRARY: The Merck Manual of Diagnosis and Therapy
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Mixed Anaerobic Infections

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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 infections. Organisms in the Prevotella group and Fusobacterium sp are part of the normal oral flora.

Pathophysiology

Anaerobic infections can usually be characterized as follows:

  • They tend to occur as localized collections of pus or abscesses.
  • The reduced O2 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. 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 The Manual and Table 2: Anaerobic Bacteria: Disorders Often Caused by Mixed* Anaerobic OrganismsTables. Anaerobes are rare in UTI, septic arthritis, and infective endocarditis.

Table 2

Disorders Often Caused by Mixed* Anaerobic Organisms

Anaerobic cellulitis

Aspiration pneumonia

Bartholin's 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's 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's glands infection

Vincent's 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. 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 all 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 closed or drained. 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.

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 Some Trade Names
CLEOCIN
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or a β-lactam/β-lactamase combination such as amoxicillin/clavulanate Some Trade Names
AUGMENTIN
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. In patients allergic to penicillin, clindamycin Some Trade Names
CLEOCIN
Click for Drug Monograph
or metronidazole Some Trade Names
FLAGYL
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(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 Some Trade Names
FLAGYL
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, carbapenems (eg, imipenem/cilastatin Some Trade Names
PRIMAXIN
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, meropenem Some Trade Names
MERREM
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, ertapenem Some Trade Names
INVANZ
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), β-lactam/β-lactamase combinations (eg, piperacillin/tazobactam Some Trade Names
ZOSYN
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, ampicillin/sulbactam Some Trade Names
UNASYN
Click for Drug Monograph
, amoxicillin/clavulanate Some Trade Names
AUGMENTIN
Click for Drug Monograph
, ticarcillin Some Trade Names
TICAR

/clavulanate), tigecycline, and moxifloxacin Some Trade Names
AVELOX
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. No single regimen appears to be superior. Drugs that are somewhat less predictably active in vitro against B. fragilis but are usually effective include clindamycin Some Trade Names
CLEOCIN
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, cefoxitin Some Trade Names
MEFOXIN
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, and cefotetan Some Trade Names
CEFOTAN
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. All except clindamycin Some Trade Names
CLEOCIN
Click for Drug Monograph
and metronidazole Some Trade Names
FLAGYL
Click for Drug Monograph
can be used as monotherapy because these drugs also have good activity against facultative anaerobic gram-negative bacilli.

Metronidazole Some Trade Names
FLAGYL
Click for Drug Monograph
is active against clindamycin Some Trade Names
CLEOCIN
Click for Drug Monograph
-resistant B. fragilis, has unique anaerobic bactericidal activity, and usually avoids the pseudomembranous colitis sometimes associated with clindamycin Some Trade Names
CLEOCIN
Click for Drug Monograph
. Concerns about its potential mutagenicity have not been of clinical consequence.

Because many regimens are available to treat GI or female pelvic anaerobic infections, 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 Some Trade Names
NEO-FRADIN
NEO-RX
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plus erythromycin Some Trade Names
ERY-TAB
ERYTHROCIN
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or neomycin Some Trade Names
NEO-FRADIN
NEO-RX
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plus metronidazole Some Trade Names
FLAGYL
Click for Drug Monograph
; these drugs are given no more than 18 to 24 h before the procedure. Examples of parenteral preoperative regimens are cefotetan Some Trade Names
CEFOTAN
Click for Drug Monograph
, cefoxitin Some Trade Names
MEFOXIN
Click for Drug Monograph
, or cefazolin Some Trade Names
ANCEF
KEFZOL
Click for Drug Monograph
plus metronidazole Some Trade Names
FLAGYL
Click for Drug Monograph
. 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 Some Trade Names
CLEOCIN
Click for Drug Monograph
plus gentamicin Some Trade Names
GARAMYCIN
Click for Drug Monograph
, aztreonam Some Trade Names
AZACTAM
Click for Drug Monograph
, or ciprofloxacin Some Trade Names
CILOXAN
CIPRO
Click for Drug Monograph
; or metronidazole Some Trade Names
FLAGYL
Click for Drug Monograph
plus gentamicin Some Trade Names
GARAMYCIN
Click for Drug Monograph
or ciprofloxacin Some Trade Names
CILOXAN
CIPRO
Click for Drug Monograph
.

Last full review/revision August 2009 by Joseph R. Lentino, MD, PhD

Content last modified August 2009

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