Anaerobes: Clostridium, Bacteroides, and Others
Anaerobes and Anaerobic Infections
Bacteriology of Anaerobiosis
Nature of Anaerobiosis
Anaerobes thrive in oxygen-depleted environments and require these conditions to initiate and sustain growth.
They fail to grow in the presence of 10% oxygen and some are sensitive to oxygen concentrations as low as 0.5%.
Oxygen tolerance varies among species; many can survive briefly in 2% to 8% oxygen.
Anaerobes lack cytochromes needed to use oxygen as a terminal electron acceptor, generating energy solely by fermentation.
Some anaerobes require extremely low oxidation-reduction potential (–300 mV) for enzyme activity; aerobic conditions create a metabolic block.
Many anaerobes lack catalase and superoxide dismutase, making them susceptible to toxic oxygen products like hydrogen peroxide and superoxide.
However, some virulent anaerobic pathogens produce antioxidant enzymes.
Classification of Anaerobes
Anaerobes indigenous to humans include diverse morphotypes and numerous species.
Classification relies on biochemical and culture-based tests, which are challenging due to specific growth requirements.
Characterization of cellular fatty acids and metabolic products via chromatography or mass spectrometry is valuable.
Nucleic acid base composition and homology have been used to revise taxonomy.
Common genera associated with disease include Peptoniphilus, Propionibacterium, Clostridium, Veillonella, Bacteroides fragilis group, Fusobacterium, Prevotella, and Porphyromonas.
Anaerobic Cocci
Medically important Gram-positive cocci include Peptoniphilus and Aerococcus.
Gram staining reveals long chains of tiny cocci.
Veillonella, a Gram-negative coccus, can be confused with Neisseria.
Clostridia
Clostridia are large, spore-forming, Gram-positive bacilli similar to Bacillus.
Spores are resistant to heat, desiccation, and disinfectants, allowing survival for decades.
Spores revert to vegetative form in favorable conditions.
Vegetative cell shape and spore location vary by species.
Some clostridial species rarely show spores in clinical specimens (e.g., Clostridium tetani with terminal “tennis racquet” spores).
Medically important clostridia produce potent protein exotoxins.
Histotoxic group (Clostridium perfringens) produces hemolysins with lytic effects on cells.
Neurotoxic group (Clostridium tetani, Clostridium botulinum) produces neurotoxins affecting distant neural sites.
Clostridioides difficile produces enterotoxins causing intestinal disease.
Nonsporulating Gram-positive Bacilli
Propionibacterium are small pleomorphic bacilli (anaerobic diphtheroids) common on the skin.
Eubacterium are long slender bacilli in the colonic flora, rarely causing disease alone.
Gram-negative Bacilli
Gram-negative, non-spore-forming bacilli are most common in anaerobic infections.
Key genera include Bacteroides, Fusobacterium, Porphyromonas, and Prevotella.
The Bacteroides fragilis group (B. fragilis, B. distasonis, B. ovatus, B. vulgatus, B. thetaiotaomicron) is virulent, producing β-lactamases and sometimes enterotoxin.
B. fragilis is a short Gram-negative bacillus with a polysaccharide capsule and is oxygen-tolerant.
Prevotella melaninogenica forms a black pigment in culture.
Fusobacterium is elongated with tapered ends.
Anaerobic Infections
Epidemiology
Anaerobes colonize oxygen-deficient microenvironments such as sebaceous glands, gingival crevices, lymphoid tissue, and intestinal and urogenital tracts.
These conditions are created by resident microbiota that reduce oxygen and lower oxidation-reduction potential.
Anaerobic infections are typically endogenous, originating from the patient's microbiota.
Specific anaerobes involved are linked to their prevalence in flora of relevant sites.
Spores of some anaerobes (e.g., Clostridia) from the intestinal tract can contaminate wounds from nonsterile objects or soil.
Pathogenesis
Anaerobic microbiota are normally commensal but can cause life-threatening infections if displaced into sterile tissues due to trauma, disease, or aspiration.
Host factors like malignancy or impaired blood supply increase infection risk.
The relation between microbiota and infection site may be indirect (e.g., oropharyngeal flora causing brain abscess).
Additional virulence factors are needed for anaerobes to produce infection.
Capsules and toxins are known virulence factors for some anaerobes.
Survival in oxidized conditions can be a virulence factor.
Mixed infections, involving two or more anaerobes and facultative bacteria like Escherichia coli, can synergize growth by providing growth factors or lowering oxidation-reduction potential.
These conditions may inhibit oxygen-dependent leukocyte bactericidal functions.
Anaerobic Infections: Clinical Aspects
Manifestations
Bacteroides, Fusobacterium, and anaerobic cocci cause localized abscesses in the cranium, thorax, peritoneum, liver, and female genital tract.
Species involved relate to pathogens in the adjacent mucosal surface microbiota.
Oral flora infections include dental infections and human bite infections.
Anaerobes play causal roles in chronic sinusitis, chronic otitis media, aspiration pneumonia, bronchiectasis, cholecystitis, septic arthritis, chronic osteomyelitis, decubitus ulcers, and soft tissue infections of diabetic patients.
Dissection of infection along fascial planes (necrotizing fasciitis) and thrombophlebitis are common complications.
Foul-smelling pus and crepitation (gas in tissues) are signs associated with anaerobic infections.
Infections may spread beyond the local site and enter the bloodstream.
Mortality rate of anaerobic bacteremias from nongenital sources is equivalent to staphylococci or Enterobacteriaceae bacteremias.
Diagnosis
A high-quality specimen (pus or fluid) is essential, taken directly from the infected site and protected from oxygen exposure.
Anaerobic transport tubes or air-free syringes should be used.
A generous pus collection serves as its transport medium unless transport is delayed.
A direct Gram-stained smear showing Gram-negative and/or Gram-positive bacteria of various morphologies suggests anaerobic infection.
Isolation requires an anaerobic incubation atmosphere and special media protected from oxygen exposure; an anaerobic jar is sufficient.
Media with reducing agents (cysteine, thioglycollate) and growth factors facilitate isolation.
Selective media are needed to protect slow-growing anaerobes from facultative bacteria.
Antibiotics, particularly aminoglycosides, are incorporated in culture media.
Identification procedures include morphology, biochemical characterization, and metabolic end-product detection by gas chromatography or mass spectrometry.
Treatment
Drainage of purulent material is the primary treatment, with appropriate chemotherapy.
Antimicrobial agents alone may be ineffective due to failure to penetrate the site of infection.
Selection is empiric due to slow growth and time required to distinguish species.
Antimicrobial susceptibility testing is slow and not generally available.
Selection is based on expected susceptibility of anaerobes known to produce infection at specific sites.
Anaerobes from oral flora are often susceptible to penicillin, but infections below the diaphragm are caused by fecal anaerobes including B. fragilis, which is resistant to many β-lactams.
Infections below the diaphragm are more likely to respond to metronidazole, imipenem, or cefotaxime.
Clostridium perfringens
Overview
Clostridium perfringens is a spore-forming Gram-positive rod commonly found in the intestine and environment.
It produces a range of wound and soft tissue infections, with gas gangrene being the most severe.
Food poisoning is characterized by diarrhea without fever or vomiting.
Bacteriology
C. perfringens is a large, Gram-positive, nonmotile rod with square ends.
It grows overnight under anaerobic conditions, producing hemolytic colonies on blood agar.
Growth in broth with fermentable carbohydrate produces large amounts of hydrogen and carbon dioxide gas.
It produces multiple exotoxins, classified into five types (A–E), with type A being most important in humans.
α-toxin: A phospholipase that hydrolyzes lecithin and sphingomyelin, disrupting cell membranes.
-toxin is a phospholipase that hydrolyzes lecithin and sphingomyelin disrupting cell membrane leading to cell lysis.θ-toxin: Alters capillary permeability and is toxic to heart muscle.
-toxin alters capillary permeability and is toxic to heart muscle.Enterotoxin: Inserts into enterocyte membranes to form pores leading to alterations in intracellular calcium, membrane permeability, and cell-to-cell tight junctions. Fluid and macromolecules are effluxed.
Enterotoxin that inserts into enterocyte membranes forming pores altering intracellular calcium, membrane permeability and integrity of cell junctions.
Disease
Gas Gangrene
Develops in traumatic wounds with avascular muscle necrosis contaminated with C. perfringens.
Clostridia come from the patient’s own intestinal flora or spores in the environment.
A delay between injury and surgical management is required for bacterial multiplication and toxin production.
Clostridial Food Poisoning
Caused by enterotoxin-producing strains contaminating food.
Outbreaks involve rich meat dishes kept warm for hours before consumption.
Spores convert to vegetative bacteria, which then multiply in the food.
It is common in developed countries, with over a million cases per year in the United States.
Pathogenesis
Gas Gangrene
C. perfringens spores germinate and then multiply, elaborating α-toxin when the oxidation-reduction potential in a wound is sufficiently low.
The process spreads along the muscle bundles, producing rapidly spreading edema and necrosis.
Increased vascular permeability and systemic absorption of the toxin lead to shock.
α-Toxin is the major cause of local destruction and shock.
θ-Toxin and oxygen deprivation due to the metabolic activities of C. perfringens contribute.
Clostridial Food Poisoning
Spores can withstand temperatures of for an hour or more.
Spores that survive initial cooking can convert to the vegetative form and multiply if food is not refrigerated properly or is not rewarmed. Vegetative cells produce enterotoxins.
Enterotoxin is released into the upper gastrointestinal tract after ingestion, causing a fluid outpouring in which the ileum is most severely involved.
Clinical Aspects
Gas Gangrene
Usually begins 1 to 4 days after the injury but may start within 10 hours.
The earliest finding is severe pain at the site of the wound accompanied by a sense of heaviness or pressure.
The disease then progresses rapidly with edema, tenderness, and pallor, followed by discoloration and hemorrhagic bullae.
The gas is apparent as crepitance in the tissue, but this is a late sign.
Systemic findings are those of shock with intravascular hemolysis, hypotension, and renal failure leading to coma and death.
Patients are often remarkably alert until the terminal stages.
Anaerobic Cellulitis
Clostridial infection of wounds and surrounding subcutaneous tissue in which there is marked gas formation (more than in gas gangrene).
Pain, swelling, and toxicity of gas gangrene are absent.
Less serious and can be controlled with antimicrobial therapy.
Endometritis
C. perfringens gains access to necrotic products of conception retained in the uterus, the bacterium multiply and thereby inject the endometrium.
Necrosis of uterine tissue and bacteremia with massive intravascular hemolysis due to α-toxin may then follow.
Common after an incomplete abortion with inadequately sterilized instruments.
Food Poisoning
The incubation period is 8 to 24 hours followed by nausea, abdominal pain, and diarrhea.
There is no fever, and vomiting is rare.
Spontaneous recovery usually occurs within 24 hours.
Diagnosis
Based substantially on clinical observations; bacteriologic studies are adjunctive.
C. perfringens is readily isolated in anaerobic cultures.
Isolation of high numbers of C. perfringens in the ingested food in the absence of any other cause is usually sufficient to confirm an etiology of a characteristic food poisoning outbreak.
Treatment and Prevention
Treatment of gas gangrene and endometritis must be initiated immediately because these conditions are almost always fatal if untreated.
Excision of all devitalized tissue is of paramount importance.
Administration of massive doses of penicillin is an important adjunctive procedure; broad-spectrum cephalosporins are often added.
Placement of patients in a hyperbaric oxygen chamber slows the spread of disease.
The most effective method of prevention of gas gangrene is the surgical debridement of traumatic injuries as soon as possible.
Prevention of food poisoning involves good cooking hygiene and adequate refrigeration.
Clostridium botulinum
Overview
Botulism is caused by ingestion of botulinum toxin preformed by C. botulinum contaminating foods inadequately sterilized and stored unrefrigerated for long periods.
The toxin acts at the neuromuscular junction blocking acetylcholine release leading to flaccid paralysis.
The disease begins with cranial nerve palsies and develops into descending symmetric motor paralysis, which may involve the respiratory muscles.
No fever or other signs of infection occur.
Bacteriology
C. botulinum is a large Gram-positive rod much like the rest of the clostridia.
Its spores resist boiling for long periods, and moist heat at is required for certain destruction.
Germination of spores and growth of C. botulinum can occur in a variety of alkaline or neutral foodstuffs when conditions are sufficiently anaerobic.
It elaborates a family of neurotoxins of extraordinary toxicity; a metalloproteinase that acts at neuromuscular junctions, blocking the release of the neurotransmitter acetylcholine from vesicles leading to flaccid paralysis.
C. botulinum is classified into multiple types (A–G) based on the antigenic specificity of the neurotoxins. All the toxins are heat-labile and destroyed rapidly at 100^\\circ C, but are resistant to the enzymes of the gastrointestinal tract.
Epidemiology
Spores of C. botulinum are found in soil, pond, and lake sediments in all parts of the world.
If spores contaminate food, they may convert to the vegetative state, multiply, and produce toxin in storage under certain conditions.
Botulism most often occurs after ingestion of home-canned products that have not been heated at temperatures sufficient to kill C. botulinum spores.
Infant and wound botulism result when the toxin is produced endogenously, beginning with spores that are either ingested in difficult to sterilize foods (honey) or contaminate wounds.
Pathogenesis
Foodborne botulism is an intoxication not an infection.
The ingested preformed toxin is absorbed in the intestinal tract and reaches its neuromuscular junction target via the bloodstream.
Its inhibition of acetylcholine release causes paralysis due to lack of neuromuscular transmission.
The damage to the synapse once the toxin has bound is permanent, and recovery requires growth of presynaptic axons and formation of new synapses.
Clinical Aspects
Manifestations
Usually starts 12 to 36 hours after ingestion of the toxin with nausea, dry mouth, and, in some cases, diarrhea.
Cranial nerve signs, including blurred vision, pupillary dilatation, and nystagmus, occur later.
Symmetric paralysis begins with the ocular, laryngeal, and respiratory muscles spreads to the trunk and extremities.
The most serious finding is complete respiratory paralysis.
Infant Botulism
Occurs in infants between the ages of 3 weeks and 8 months.
The organism is introduced on weaning or with dietary supplements, especially honey.
Ingested spores yield vegetative bacteria, which multiply and produce small amounts of toxin in the infant’s colon causing constipation, poor muscle tone, lethargy, and feeding problems.
Wound Botulism
Wounds infected with other organisms may allow C. botulinum to grow; contaminated wounds of drug users are sites of toxin production.
May begin with weakness localized to the injured extremity.
Diagnosis
The toxin can be demonstrated in blood, intestinal contents, or remaining food by immunoassay or nucleic acid amplification (NAA) methods.
C. botulinum may also be isolated from stool or from foodstuffs suspected of responsibility for botulism.
Treatment and Prevention
The availability of intensive supportive measures, particularly mechanical ventilation, is the single most important determinant of clinical outcome.
The administration of large doses of horse C. botulinum antitoxin is thought to be useful in neutralizing free toxin. Antimicrobial agents are given only to patients with wound botulism.
Adequate pressure cooking or autoclaving in the canning process kills spores, and heating food at for 10 minutes before eating destroys the toxin.
Clostridium tetani
Overview
Tetanus follows production of a neurotoxin in a wound infected by C. tetani; the tetanospasmin toxin blocks postsynaptic inhibition thus enhancing muscular contraction.
The striking feature of tetanus is severe muscle spasms (“lock-jaw” when the jaw muscles are involved.) despite minimal or no inflammation at the primary site of infection.
The disease is caused by in vivo production of a neurotoxin that acts centrally, not locally. Immunization with inactivated toxin prevents tetanus.
Bacteriology
C. tetani is a slim, Gram-positive rod, which forms spores readily in nature and in culture, yielding a round terminal spore that gives the organism a drumstick-like appearance.
C. tetani requires strict anaerobic conditions.
Its identity is suggested by culture-based as well as biochemical characteristics, but definite identification depends on demonstrating the neurotoxic exotoxin.
C. tetani spores remain viable in soil for many years and are resistant to most disinfectants and to boiling for several minutes.
The most important product of C. tetani is its neurotoxic exotoxin, tetanospasmin or tetanus toxin, a metalloproteinase that has structural and pharmacologic features similar to those of botulinum toxin.
Tetanus toxin degrades a protein required for neurotransmitter release from vesicles at the appropriate site on presynaptic membranes (Figure 29–3). The neurotransmitters; glycine and -aminobutyric acid (GABA), are the ones that affect inhibitory neurons resulting in
unopposed firing of the active motor neurons, generating spasms, and spastic paralysis, which are the opposite of the botulinum flaccid paralysis.The toxin is heat-labile, antigenic, readily neutralized by antitoxin, and rapidly destroyed by intestinal proteases. Treatment with formaldehyde yields a nontoxic product or toxoid that retains the antigenicity of toxin and thus stimulates the production of antitoxin.
Epidemiology
The spores of C. tetani exist in many soils, especially those that have been treated with manure, and the organism is sometimes found in the lower intestinal tract of humans and animals.
The spores are introduced into wounds contaminated with soil or foreign bodies.
In many developing countries, the majority of tetanus cases occur in recently delivered infants when the umbilical cord is severed or bandaged in a nonsterile manner.
Similarly, tetanus may follow an unskilled abortion, scarification rituals, female circumcision, and even surgery performed with nonsterile instruments or dressings.
Pathogenesis
The usual predisposing factor for tetanus is an area of very low oxidation–reduction potential in which tetanus spores can germinate.
Tetanus bacilli multiply locally and neither damage nor invade adjacent tissues.
Tetanospasmin is produced at the site of infection and enters the presynaptic terminals of lower motor neurons, reaching the central nervous system (CNS) mainly by exploiting the retrograde axonal transport system in the nerves.
In the spinal cord, it acts at the level of the anterior horn cells as well. Its blockage of postsynaptic inhibition of spinal motor reflexes produces spasmodic contractions of both protagonist and antagonist muscles.
Minor stimuli, such as a sound or a draft, can provoke generalized spasms.
Clinical Aspects
Manifestations
The incubation period of tetanus is from 4 days to several weeks.
The diagnosis is clinical; neither culture nor toxin testing is useful.
The masseter muscles are often the first to be affected, resulting in inability to open the mouth properly (trismus); this effect accounts for the term lock-jaw.
As other muscles become affected, intermittent spasms can become generalized to include muscles of respiration and swallowing. In extreme cases, massive contractions of the back muscles (opisthotonos) develop.
In fatal cases, death results from exhaustion and respiratory failure.
Respiratory failure leads to death.
Treatment
Specific treatment of tetanus involves neutralization of any unbound toxin with large doses of human tetanus immune globulin (HTIG).
Most important in treatment are nonspecific supportive measures, including maintenance of a quiet dark environment, sedation, and provision of an adequate airway.
The value of antimicrobials is not clear. Because toxin binding is irreversible, recovery requires the generation of new axonal terminals.
Prevention
Routine active immunization with tetanus toxoid, combined with diphtheria toxoid and pertussis vaccine (DTaP) for primary immunization in childhood and DT for adults, can completely prevent tetanus.
Unimmunized subjects with tetanus-prone wounds should be given passive immunity with a prophylactic dose of HTIG as soon as possible. Those who have had a full primary series of immunizations and appropriate boosters are given toxoid for tetanus-prone wounds if they have not been immunized within the previous 10 years in the case of clean minor wounds or 5 years for more contaminated wounds.
Penicillin therapy is a prophylactic adjunct in serious or neglected wounds, but in no way alters the need for specific prophylaxis.
Clostridioides difficile
Overview
Clostridioides difficile spores are either resident in the intestinal microbiota or ingested from the environment. When other members of the microbiota are suppressed by antibiotics these spores germinate and the vegetative cells produce powerful toxins.
C. difficile infection (CDI) is the most common and deadly cause of diarrhea that develops in association with the use of antimicrobial agents.
The diarrhea ranges from a few days of intestinal fluid loss to life-threatening toxic megacolon and pseudomembranous colitis (PMC). PMC is associated with intense inflammation and the formation of a pseudomembrane composed of inflammatory debris on the mucosal surface.
Bacteriology
Clostridioides difficile (formerly Clostridium difficile) is a Gram-positive rod that readily forms spores both in the environment and in vivo. The C. difficile germination mechanism differs from that of most other spore-forming bacteria in that it is triggered by bile salts.
In the vegetative form, C. difficile has a most important medical feature: its ability to produce toxins. In this species, two distinct large polypeptide toxins, Toxin A (TcdA) and Toxin B (TcdB), with similar structure
are released during late growth phases, perhaps at the time of cell lysis.
homology exist between Toxin A and Toxic B. Both toxins TcdA and TcdB are glucosyltransferases and act in the cytoplasm by inactivating signal transduction
proteins (Rho GTPases), particularly those that control the actin cytoskeleton.
This results in the disruption of intercellular tight junctions followed by altered membrane permeability and fluid secretion.A third toxin, C. difficile Binary toxin (CDT), has been discovered, which exerts an ADP-ribosylating action which inhibits actin cytoskeleton polymerization within the enterocyte.
Epidemiology
C. difficile is present in the stool of 2% to 15% of the general population, sometimes at higher rates among hospitalized persons and infants. Although CDI is endogenous in most cases, hospital outbreaks have clearly established that the environment can be the source as well; spores are excreted into the surrounding and remain there.
More than two decades of the antibiotic era had elapsed before the medical importance of C. difficile was recognized through its association with antibiotic-associated diarrhea (AAD). C. difficile is not the only cause of AAD, but it is the most common identifiable cause.
CDI is clearly on the rise worldwide and is now the leading cause of death due to an acute diarrheal illness. New strains combining more potent A and B toxins, along with the CDT toxin, have been particularly virulent. Although CDI is primarily an endogenous infection, the generation of spores from excretions provides the prospect for person-to-person spread.
Pathogenesis
When C. difficile becomes established in the colon of individuals with normal gut microbiota, few, if any, direct consequences result, probably because its numbers are dwarfed by the other flora.
Alteration of the colonic flora with antimicrobials (particularly ampicillin, cephalosporins, and clindamycin) favors
C. difficile in two ways. First, strains resistant to the antimicrobial agent can grow in its presence and assume a larger if not dominant position in the flora. Second, in an antimicrobial milieu, the readiness with which C. difficile forms spores may favor its survival over non-spore-forming bacteria.A distinctive feature of C. difficile spores is that their germination is triggered by taurocholate, a bile salt, through a receptor in the spore itself.
Clinical Aspects
Manifestations
Diarrhea is a common side effect of antimicrobial treatment. In C. difficile-caused diarrhea, the onset is usually 5 to 10 days into the antibiotic treatment, but the range is from the first day to weeks after cessation.
The diarrhea may be mild and watery or bloody and accompanied by abdominal cramping, leukocytosis, and fever. In PMC, it progresses to a severe, occasionally lethal inflammation of the colon that can be demonstrated by endoscopic examination. Systemic signs of inflammation are common and WBC counts of more than 15,000 per cubic millimeter are considered ominous. Toxic megacolon is the most serious complication leading to colectomy or death.
Diagnosis
Although selective media have been developed for isolation of C. difficile, direct detection of toxins in the stool has largely replaced culture for diagnostic purposes.
Stool toxin is detected by immunoassays, which reveal TcdA and/or TcdB in the stool. These tests are now being superseded by NAA (nucleic acid amplification) as well as mass spectrometric methods with improved sensitivity and specificity.
Treatment
In AAD, discontinuing the implicated antimicrobial often results in the resolution of clinical symptoms. Once C. difficile toxins are detected in the stools, treatment with metronidazole, vancomycin, or fidaxomicin is indicated. Vancomycin is not absorbed orally which is an advantage in this situation because the toxin production is taking place in the bowel lumen. Metronidazole is only used for mild to moderate CDI. Fidaxomicin is a narrower-spectrum antimicrobial, so is employed when intestinal dysbiosis control is expediently required.
C. difficile is susceptible to penicillins and cephalosporins in vitro, but these drugs are ineffective because of access in the intestinal lumen and the hazard of destruction by β-lactamases produced by other bacteria.
Treatments under investigation include probiotics, and molecules that bind the toxin(s) or its intestinal toxin receptor. These approaches are usually combined with antimicrobial therapy. The emergence of PMC with toxic megacolon requires a high-risk colectomy.
Prevention
Strategies to prevent recurrences of CDI have generated some highly creative approaches. In pulsed-treatment, a single dose of vancomycin is given once every few days rather than multiple times a day as in standard treatment. The idea is to allow time for the vegetative bacteria to emerge from the inert spore and then block their cell wall synthesis as they start to multiply.
The most recent and sensational approach has been the infusion of donor feces into the intestine in an effort to reestablish an effective competitive flora. This “fecal microbiota transplant” (FMT) has now moved from anecdotal relapse cures to greater than 90% success in controlled trials including the use of standardized preparations in capsules.
Finally, another strategy is aimed at preventing germination of C. difficile spores by administration of competitive inhibitors of the bile salts known to trigger germination.
Bacteroides fragilis
Overview
Bacteroides fragilis, a minor component of the intestinal microbiota, is a leading cause of intraabdominal abscess. When displaced beyond mucosal barriers, oxygen tolerance and a polysaccharide capsule allow this anaerobic Gram-negative rod to cause local injury. Deep pain and tenderness anywhere below the diaphragm are typical of the onset of B. fragilis infection.
Production of β-lactamases, unusual for anaerobes, complicates treatment.
Bacteriology
The B. fragilis group constitutes the most common opportunistic pathogens of the genus Bacteroides.
These slim, pale-staining, capsulated, Gram-negative rods form colonies overnight on blood agar medium incubated anaerobically.
Most strains produce superoxide dismutase and are relatively tolerant to atmospheric oxygen.
B. fragilis has adhesive surface pili and a capsule composed of a polymer of two polysaccharides. The LPS endotoxin in the B. fragilis outer membrane is less toxic than that of most other Gram-negative bacteria, possibly owing to modification or absence of the lipid A portion.
Epidemiology
Like the other Gram-negative anaerobes, B. fragilis infections are endogenous, originating in the patient’s own intestinal microbiota. Given the mass and diversity of intestinal anaerobes, the frequent presence of B. fragilis in clinically significant infections is striking. It is typically mixed with other anaerobes and facultative bacteria. Human-to-human transmission is not known and seems unlikely.
Pathogenesis
The relative oxygen tolerance of B. fragilis probably plays a role in its virulence by aiding its survival in oxygenated tissues in the period between its displacement from the intestinal flora and the establishment of a reduced local microenvironment. Oxygen tolerance mediated by oxidative stress response
The polysaccharide capsule confers resistance to phagocytosis, inhibits macrophage migration, and mediates binding to the peritoneum. Experimentally, the B. fragilis capsular polysaccharide stimulates abscess formation, even in the absence of live cells, a property not found in the capsules of bacteria like Streptococcus pneumoniae or Neisseria meningitidis. Some strains of B. fragilis produce an enterotoxin that causes enteric disease in animals, and in some studies they have been associated with a self-limited, watery diarrhea in children.
Clinical Aspects
Manifestations
Requires displacing B. fragilis along with other members of the intestinal flora is required to initiate infection.
The local effects of the developing abscess include abdominal pain and tenderness, often with a low-grade fever.
The course of illness is strongly influenced by the other bacteria in the abscess, particularly members of the Enterobacteriaceae. Spread to the bloodstream is more common with B. fragilis than any other anaerobe.
Treatment
Drainage of abscesses and debridement of necrotic tissue are the mainstays of the treatment of B. fragilis infections, as with anaerobic infections in general.
The accompanying antimicrobial therapy is complicated by the fact that abdominal B. fragilis isolates almost always produce a β-lactamase, which not only inactivates penicillin but other β-lactams, including many cephalosporins. Resistance to tetracycline is also common, but most strains are susceptible to clindamycin, and metronidazole.