Chapter 20Anaerobic Gram-Negative Bacilli

Finegold SM.

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General Concepts

Clinical Manifestations

Anaerobic Gram-negative bacilli are common elements of the mucous membrane flora throughout the body; they often act as secondary pathogens. They are the most common anaerobes involved in infection and include some of the most antibiotic-resistant species.

Structure, Classification, and Antigenic Types

Some are pleomorphic, whereas others have distinctive morphology. Most are obligate anaerobes. The key characters for classification are motility, arrangement of flagella, organic and volatile fatty acid metabolic end products and cellular fatty acid patterns. Antigens are not useful.

Pathogenesis

They usually invade as opportunistic pathogens through a break in the mucosa. A low redox potential favors infection. Some types produce virulence factors or interfere with host defenses (e.g., by inhibiting phagocytosis).

Host Defenses

Antibodies, complement (via both classic and alternative pathways), and cell-mediated immunity (involving both polymorphonuclear leukocytes and T lymphocytes) are important.

Epidemiology

Infections arise endogenously from the mucosal flora.

Diagnosis

Clues suggesting anaerobic infection include foul-smelling discharge, proximity of infection to mucosal surfaces, abscess formation, necrosis and gas in tissues, septic thrombophlebitis, various distinctive clinical pictures (e.g., actinomycosis, gas gangrene), and results of a Gram stain of clinical specimens. Collection of clinical specimens should avoid the mucosal flora, and transport must be anaerobic.

Control

Control involves (1) surgical drainage of abscesses and debridement of necrotic tissue; and (2) use of antimicrobials (particularly metronidazole, imipenem, chloramphenicol, or combinations of amoxicillin, ticarcillin, ampicillin or piperacillin with β-lactamase inhibitors).

Introduction

At present there are over two dozen genera of Gram-negative anaerobic bacilli. In most clinical infections, only the genera Bacteroides, Prevotella, and Fusobacterium need be considered. These genera are prevalent in the body as members of the normal flora (Fig.20-1), constituting one-third of the total anaerobic isolates from clinical specimens, and may become involved in infections throughout the body (Fig.20-2). Within the Bacteroides group, B fragilis is the most common pathogen, followed by B thetaiotaomicron and other members of the B fragilis group. Among the bile-sensitive Prevotella species, the ones most commonly encountered clinically are P melaninogenica, P oris, and P buccae. Porphyromonas species seem to be much less pathogenic except in dental infections. Fusobacterium nucleatum is the Fusobacterium species most often found as a pathogen, but F necrophorum occasionally produces serious disease. These genera contain numerous other species that rarely or never infect humans.

Figure 20-1. Predominant sites colonized by Bacteroides and other anaerobic bacilli.

Figure 20-1

Predominant sites colonized by Bacteroides and other anaerobic bacilli.

Figure 20-2. Sites of anaerobic infections.

Figure 20-2

Sites of anaerobic infections.

Clinical Manifestations

Gram-negative anaerobic bacilli may cause infections anywhere in the body; the most common types are oral and dental, pleuropulmonary, intra-abdominal, female genital tract and skin, soft tissue and bone infections (Table 20-1). They may play a role in such diverse pathologic processes as periodontal disease and colon cancer. Bacteroides, Prevotella, Porphyromonas, and Fusobacterium produce enzymes (collagenase, neuraminidase, deoxyribonuclease, deoxyribonuclease [DNase], heparinase, and proteinases) that may play a role in pathogenesis by helping the organisms to penetrate tissues and to set up infection after surgery or other trauma. The incidence of infection by these organisms can best be reduced or eliminated by avoiding conditions that decrease the redox potential of tissues and by preventing introduction of the anaerobes into compromised host tissues.

Table 20-1. Common Syndromes of Anaerobic Infection.

Table 20-1

Common Syndromes of Anaerobic Infection.

Structure, Classification, and Antigenic Types

Bacteroides fragilis (Fig.20-3), the most important of all anaerobes because of its frequency of occurrence in clinical infection and its resistance to antimicrobial agents, is a Gram-negative bacillus with rounded ends 0.5 to 0.8 μm in diameter and 1.5 to 4.5 μm long. Most strains are encapsulated. Vacuolization or irregular staining is common, particularly in broth media. Some pleomorphism also may be seen. By electron microscopy, the ultrastructure of B fragilis is similar to that of other Gram-negative bacteria. The guanine-plus-cytosine content is 42 percent. Prevotella melaninogenica and Porphyromonas asaccharolytica are short to coccoid Gram- negative rods; they produce a distinctive pigment (brown to black), which is a heme derivative that colors the colony (Figs.20-4 and 20-5). Many strains of P melaninogenica require vitamin K, or similar compounds, as well as heme.

Figure 20-3. Microscopic morphology of B fragilis from broth culture.

Figure 20-3

Microscopic morphology of B fragilis from broth culture. Note the irregular staining, rounded ends of bacilli, and some pleomorphism.

Figure 20-4. Microscopic morphology of P melaninogenica.

Figure 20-4

Microscopic morphology of P melaninogenica. Organisms are tiny coccobacilli that stain regularly.

Figure 20-5. Colony morphology of P melaninogenica.

Figure 20-5

Colony morphology of P melaninogenica. Note the jet-black pigmented colonies.

Numerous studies of the endotoxin of Gram-negative anaerobic bacilli have determined that the B fragilis endotoxin contains little or no lipid A, 2-ketodeoxyoctanate, or heptose. It also lacks β-hydroxymyristic acid. This endotoxin exhibits little biologic activity in various test systems and little chemotactic activity; what activity there is is complement-mediated by the alternative pathway. Poor biologic activity of endotoxin also has been demonstrated for the closely related species B thetaiotaomicron, B ovatus, B vulgatus, and B distasonis. Prevotella melaninogenica endotoxin contains no heptose or 2-ketodeoxyoctanate, and it and the endotoxin of P oralis both show weak biologic activity. Serologic methods have not been reliable for characterizing Gram-negative anaerobic rods.

Members of the genus Fusobacterium (Figs.20-6 and 20-7) may be spindle shaped or may have parallel sides and rounded ends. The guanine-plus-cytosine content ranges from 26 to 34 percent. Cells of F necrophorum often are elongated or filamentous, are curved, and possess spherical enlargements and large, free, round bodies. Fusobacterium nucleatum, although not producing infections as serious as those caused by F necrophorum, is a virulent organism and is much more common clinically. The cells of this species are usually spindle shaped, are 5 to 10 μm long, and are often seen in pairs, end to end.

Figure 20-6. Microscopic morphology of F nucleatum from broth culture.

Figure 20-6

Microscopic morphology of F nucleatum from broth culture. Note the regular staining and thin, delicate bacilli with tapered ends. Organisms are sometimes found end to end.

Figure 20-7. Microscopic morphology of F mortiferum from broth culture.

Figure 20-7

Microscopic morphology of F mortiferum from broth culture. Note the filaments with swollen central portions, large round bodies, and irregular staining.

The lipopolysaccharide of F necrophorum is located in a multilayered external coat. The endotoxin varies from strain to strain in its content of 2-ketodeoxyoctanate and sugars. Although biologic activity varies also, many strains do show strong biologic activity, comparable to that of Salmonella enteritidis. The endotoxin of F nucleatum also is variable in its biologic activity, but often exhibits strong activity, comparable to that of S enteritidis.

Bacteriophages active against B fragilis are not uncommon. They are species specific and active against most strains. Bacteriocins also are produced by strains of B fragilis and B thetaiotaomicron. Plasmids have been found in about half the Bacteroides strains studied. For the most part, the biologic and clinical significance of these plasmids is not known; however, some code for resistance to such antimicrobial agents as clindamycin, erythromycin, tetracycline, chloramphenicol, ampicillin, and cephalothin. Plasmid-mediated antibiotic resistance has been transferred from strains of B fragilis to other strains of this species, to B thetaiotaomicron, and to Escherichia coli. Such resistance also has been transferred from B distasonis to B fragilis.

Most strains of the B fragilis group can deconjugate bile acids and are equally active whether the bile acid is conjugated with glycine or with taurine. Rarely, P melaninogenica may deconjugate bile acids, but in general this species, P oralis, and F nucleatum are inhibited by bile acids and do not deconjugate them. Fusobacterium necrophorum also is active in deconjugating bile acids but is active primarily on taurine conjugates. A few strains of Gram-negative anaerobic bacilli can convert primary bile acids to secondary bile acids. Bacteroides thetaiotaomicron can convert some lithocholic acid to its ethyl ester. Because lithocholic acid is toxic in humans and has been shown to exert tumor-promoting activity in animals, this reaction may be important. Bacteroides fragilis hydrolyzes the conjugated metabolites of benzpyrene. Glucuronidase produced by anaerobic Gram-negative bacilli may be of special significance in deconjugating compounds that had previously been detoxified in the liver by combination with glucuronide. There is speculation that this enzyme may be important in promoting bowel cancer. The activity of B thetaiotaomicron, B distasonis, and other members of the B fragilis group against plant polysaccharides, chondroitin, and mucin may be a factor in colon cancer and other disorders. Dietary fiber consists primarily of plant cell wall polysaccharides that are not digested in the stomach or small bowel.

Certain Bacteroides species possess distinguishing enzymes. Superoxide dismutase has been found in B fragilis, B thetaiotaomicron, B vulgatus, and B ovatus. In general, a good correlation exists between superoxide dismutase activity and oxygen tolerance. No consistent relationship has been found between catalase activity and oxygen tolerance, however. β-Lactamase activity has been demonstrated in several Bacteroides species, some Prevotella, and Bilophila; it accounts for most of the resistance to various β-lactam antibiotics, such as penicillins and cephalosporins, although other mechanisms are responsible occasionally. Urease is produced by Bilophila wadsworthia and by Bacteroides ureolyticus. The latter organism also produces an agarase, which accounts for pitting of the agar by the colonies. A related pitting organism, Sutterella wadsworthensis, is much more pathogenic and is relatively resistant to antimicrobial agents.

Pathogenesis

Bacteroides, Prevotella, Porphyromonas, and Fusobacterium species are prevalent in the indigenous flora on all mucosal surfaces. They may have an opportunity to penetrate tissues and then to set up infection under certain circumstances such as surgical or other trauma or when tumors arise at the mucosal surface (Table 20-2). In certain cases, such as aspiration pneumonia, anaerobic bacteria from a site of normal carriage may move into another area that is normally free of organisms and infect that site. Tissue necrosis and poor blood supply lower the oxidation-reduction potential, thus favoring the growth of anaerobes. Accordingly, vascular disease, cold, shock, trauma, surgery, foreign bodies, cancer, edema, and gas production by bacteria may significantly predispose individuals to infection with anaerobes, as may prior infection with aerobic or facultative bacteria. Antimicrobial agents such as aminoglycosides, trimethoprim/sulfamethoxazole, and quinolones, to which anaerobes are notably resistant, may facilitate anaerobic infection. Conditions predisposing persons to anaerobic infection are summarized in Table 20-2. The more aerotolerant anaerobes are more likely to survive after the normally protective mucosal barrier is broken and until conditions are satisfactory for their multiplication and invasion. Once anaerobes begin to multiply, they can maintain their own reduced environment by excreting end products of fermentative metabolism. Infections involving Gram-negative anaerobic bacilli often are characterized by abscess formation and tissue destruction.

Table 20-2. Conditions Predisposing to Anaerobic Infection.

Table 20-2

Conditions Predisposing to Anaerobic Infection.

Bacteroides, Prevotella, Porphyromonas, and Fusobacterium species produce enzymes that may play a role in pathogenesis. Prevotella melaninogenica is one of the few bacteria that produce collagenase, an enzyme of considerable importance. Cell extracts of P melaninogenica strains with collagenolytic activity, when given with a live Fusobacterium species, produce more severe lesions in rabbits than does the organism or the extract given alone. Porphyromonas gingivalis also produces collagenase and has trypsin-like activity. Neuraminidase may be important in the pathogenesis of Bacteroides infection. This enzyme alters neuraminic acid-containing glycoproteins of human plasma; Bacteroides strains isolated from clinical specimens have higher neuraminidase activity than do those isolated from stools, and strains of the B fragilis group have greater activity of this type than do strains of other Gram-negative anaerobic bacillary species. Hyaluronidase is produced by many strains of the B fragilis group and pigmented anaerobic Gram- negative rods. DNase is also produced by B fragilis and may be an important factor in infection. Many Gram-negative anaerobic bacilli produce phosphatase. A heparinase produced by B fragilis strains may contribute to intravascular clotting and hence increase the dosage of heparin needed to treat septic thrombophlebitis in infections caused by this organism. The lipopolysaccharides of B fragilis, B vulgatus, and F mortiferum activate the Hageman factor and thereby initiate the intrinsic pathway of coagulation. Fibrinolysin is produced by many P melaninogenica group strains and by a few B fragilis group strains. Porphyromonas asaccharolytica produces proteinases that render it capable of hydrolyzing gelatin, casein, coagulated protein, plasma protein, azacol, and collagen. Strains of Bacteroides and P gingivalis degrade complement factors and immunoglobulins G and M. A strain of P melaninogenica produces phospholipase A.

Fusobacteria necrophorum produces a leukocidin and hemolyses erythrocytes of humans, horses, rabbits, and, much less extensively, sheep and cattle. Certain F necrophorum cells hemagglutinate the erythrocytes of humans, chickens, and pigeons. A bovine isolate of F necrophorum demonstrates phospholipase A and lysophospholipase activity. Fusobacterium gonidiaformans produces an appreciable inflammatory reaction when inoculated into the skin of rabbits; when injected intraperitoneally into mice, it leads to liver abscesses and occasionally to death. A specific toxin has not yet been isolated.

Other factors may be involved in the continued growth and potential pathogenicity of certain anaerobes. For example, P melaninogenica can inhibit the growth of certain other organisms. Also, anaerobes such as P melaninogenica sometimes inhibit phagocytosis and killing of other organisms during mixed infection. Constituents of the cell envelope and cell surface may contribute to pathogenicity. The capsule of organisms such as B fragilis is an important virulence factor. Pili (fimbriae) and lectinlike adhesins may also be important in the adherence of Bacteroides cells to epithelial surfaces. Butyrate and succinate produced by Bacteroides show a cytotoxic effect.

Host Defenses

Polymorphonuclear leukocytes have oxygen-dependent and oxygen-independent microbicidal systems. Components of both systems might be important in phagocytic killing of anaerobes under conditions of varying oxygen tension. Specifically, polymorphonuclear leukocytes normally kill B fragilis under anaerobic and aerobic conditions. Random migration of polymorphonuclear leukocytes does not differ significantly under aerobic and anaerobic conditions. The same holds true for chemotaxis in response to factors generated by immune complexes in plasma; however, chemotaxis in response to factors generated by bacteria in plasma is markedly depressed under anaerobic conditions, and products of Gram-negative anaerobic bacilli may suppress neutrophil chemotaxis and phagocytic killing.

Studies of host defenses indicate that other interactions may occur between the bacteria and the host cells. Bacteroides fragilis, one organism used in the chemotaxis study described above, is more resistant to the normal bactericidal activity of serum than are other members of the B fragilis group. Fusobacterium mortiferum is killed by serum alone or by serum plus leukocytes under aerobic and anaerobic conditions. Under anaerobic conditions, B thetaiotaomicron and B fragilis are phagocytosed and killed intracellularly by human polymorphonuclear leukocytes only in the presence of normal human serum. Similar results are obtained in an aerobic environment, except that B fragilis is phagocytosed and killed intracellularly to some extent in the absence of serum. There is evidence that the capsule of certain strains interferes with their phagocytosis.

Immunoglobulin and components of the classic and alternative complement pathways participate in chemotaxis, bacteriolysis, and opsonophagocytic killing of various Gram-negative anaerobic bacilli. Antibody to the capsular polysaccharide of B fragilis can be induced in animals by infection with encapsulated strains or by implantation of the capsular material itself along with outer membrane components that stimulate an antibody response. Such immunization of animals confers significant protection against subsequent abscess development from B fragilis strains. Furthermore, a study of women with acute pelvic inflammatory disease demonstrated antibody to the capsular antigen of B fragilis in women whose infecting flora contained B fragilis; the antibody was quantified by precipitin analysis. Immunodiffusion techniques have also been used on trichloracetic acid extracts from B fragilis in detecting precipitating antibodies against this organism in sera of immune rabbits. Data indicate that more than one serotype exists.

Fusobacterium necrophorum persists for an extended period in the liver, where its proliferation in Küpffer cells impairs macrophage function.

T cells are involved in immunity of humans to B fragilis, specifically linked to early stages of abscess formation.

Epidemiology

All infections involving anaerobic Gram-negative bacilli arise endogenously when mucosal damage related to surgery, trauma, or disease permits tissue penetration by members of the indigenous flora. Knowledge of the composition of the indigenous flora at various sites under different circumstances permits the clinician to anticipate the likely infecting species in acute infections at different locations. The pathogenicity of various species also must be taken into account. Ecologic determinants include the oxygen sensitivity of various organisms, the ability of organisms to adhere (discussed in Chapter 7), and microbial interrelationships. These interrelationships permit one organism to supply growth factors needed by the other, to provide assistance with adherence or motility to another organism, and to facilitate the production of inhibitory substances.

At birth, an infant's oral cavity usually is sterile; but by 12 months of age, Fusobacterium species can be cultured from 50 percent of infants and other Gram-negative anaerobic bacilli species from a smaller percentage. In the human gingival crevice area, Gram-negative anaerobic rods account for 16 to 20 percent of the total cultivable flora. Prevotella melaninogenica is seldom isolated before the age of 6 years, but by the early teens this organism can be isolated from the gingival crevice area of most individuals. Gram-negative anaerobic rods usually constitute 8 to 17 percent of the cultivable flora of human dental plaque. Selective localization is illustrated by the fact that P melaninogenica is found routinely in the gingival crevice but is not found, or is only rarely found, on the tongue, cheek, or coronal tooth surface.

The stomach normally has few organisms and, as a rule, no anaerobic bacteria; however, in the presence of pathologic conditions such as duodenal ulcer with bleeding or obstruction, abnormal colonization with B fragilis may occur in the stomach. In the terminal ileum, approximately equal numbers of facultative aerobes and anaerobes are present, with Bacteroides being one of the major anaerobes. Bacteroides species are almost invariably found in the feces of adult subjects; the mean count is 1011/g. Fusobacterium species are found in the feces of 18 percent of adults; the mean count is 108/g. B thetaiotaomicron and B vulgatus are the dominant species of Bacteroides encountered, followed by B distasonis, B ovatus, and B fragilis. In animal studies, Bacteroides protects against infection with Salmonella or Shigella.

Bacteroides, Prevotella, and Fusobacterium species are common in the vaginal flora. In one quantitative study of the vaginal and cervical flora, Bacteroides and Prevotella species were recovered from half of the patients, with mean concentrations of 106/g of material. Species recovered from the normal cervical flora of healthy women include B fragilis, B capillosus, P oralis, P bivia, P disiens, P oris, P buccae, and B ureolyticus.

Studies of the normal urethral flora are relatively limited, but Fusobacterium and other Gram-negative anaerobic bacilli have been isolated. Fusiform bacilli and P melaninogenica have been found regularly on the external genitalia.

Bacteroides cells placed on the forearms of human volunteers may persist for a few hours; strains placed on laboratory benches may survive even 10 hours after exposure to air, and Bacteroides has been recovered from the hospital environment on occasion. Clearly, however, the source of infection with these organisms is the indigenous flora of the body, particularly of mucosal surfaces.

Diagnosis

The clinical characteristics of infection with Bacteroides, Prevotella or Fusobacterium are primarily those seen with anaerobes in general. These characteristics include foul-smelling discharge, location of infection in proximity to mucosal surfaces, tissue necrosis, gas in tissues or discharges, association of infection with cancer, infection related to the use of aminoglycosides or other agents with poor activity against anaerobes, septic thrombophlebitis, infection following human or animal bites, and certain distinctive clinical features. The clinical presentation of F necrophorum sepsis may be distinctive in that onset is characterized by sore throat and fever often accompanied by chills. A membranous tonsillitis with foul odor to the breath may be noted, and in the absence of effective therapy, bacteremia and widespread metastatic infection occurs. Black discoloration of blood-containing exudates or red fluorescence of such exudates under ultraviolet light indicates infection with pigmented anaerobic Gram-negative bacilli.

A definitive diagnosis requires demonstration or isolation of the organisms responsible for the infection. Even direct Gram stain may be helpful because of the frequently unique morphology of Gram-negative anaerobic bacilli. In general, these organisms are pale staining and they may stain erratically. Fusobacterium cells may exhibit classic tapered ends and filamentous forms, with or without swollen areas and large round bodies. Direct gas-liquid chromatography of clinical specimens occasionally provides important clues to the presence of certain Gram-negative anaerobic bacilli. A large amount of butyric acid in the absence of isobutyric or isovaleric acid indicates the presence of Fusobacterium. The presence of succinic acid and only Gram-negative rods seen on Gram stain, or of both succinic and isobutyric acid in the specimen, indicates that Bacteroides is present. Both direct and indirect fluorescent antibody techniques may be useful for rapid detection of Bacteroides, Prevotella, and Fusobacterium in clinical material. False-positive reactions are sometimes a problem. Reagents are available commercially; they will undoubtedly be improved. Collection of clinical specimens should avoid the mucosal flora, and transport must be anaerobic. Use of selective and differential media may facilitate isolation and identification of different Gram-negative anaerobic bacilli. Tests for antibody development in response to the infection are not practical.

Control

There are two primary guidelines in preventing anaerobic infections: avoiding conditions that reduce the redox potential of the tissues and preventing the introduction of anaerobes of the normal flora to wounds, closed cavities, or other sites prone to infection. Prophylactic antimicrobial therapy is effective in selected situations. Patients with acute leukemia who are to be treated intensively with antitumor chemotherapy may be managed with a diet low in bacterial count and with administration of an antimicrobial regimen designed to reduce significantly the total body flora, including anaerobes. Some workers have advocated using antibacterial regimens that are relatively inactive against anaerobes; as a result, anaerobes persist in the bowel and provide colonization resistance against potential aerobic or facultative pathogens. There is some disagreement on this point.

Anaerobic bacteremia following dental manipulation may be managed effectively by administering an antibacterial agent 1 hour before the manipulation and continuing for a limited period (12 to 24 hours) afterward. The effectiveness of prophylactic antimicrobial therapy before bowel surgery is now well established. The physician may use oral neomycin plus erythromycin, giving the agents for a limited time before surgery to prevent overgrowth of other organisms. Prophylaxis also is effective before certain types of gynecologic surgery. When infection already is established but surgery is indicated (appendectomy, cholecystectomy), antimicrobial therapy just before surgery again may be helpful. Appropriate therapy of established infections such as chronic otitis media and sinusitis may prevent subsequent spread of infection that could lead to intracranial abscess. Precautions to minimize aspiration are helpful in preventing anaerobic pulmonary infection. Care must be observed in feeding feeble or confused patients and those who have difficulty swallowing. Good surgical technique minimizes the risk of postoperative infection. Minimizing injury and devitalization of tissue during surgery protects against infection. The use of closed methods of bowel resection, when feasible, decreases the likelihood of infection with members of the bowel flora.

Table 20-3 indicates the relative effectiveness of a number of drugs against Gram-negative anaerobic bacilli. Aminoglycosides such as gentamicin and amikacin are inactive against most anaerobes as are trimethoprim/sulfamethoxazole and fluoroquinolones. The activity of erythromycin varies significantly according to the testing procedure. Most penicillins and cephalosporins are less active than penicillin G; unfortunately, increasing numbers of anaerobes are showing resistance to penicillin, usually on the basis of β-lactamase production. Ampicillin, carbenicillin, and penicillin V are roughly comparable to penicillin G on a weight basis, but the high blood levels safely achieved with carbenicillin and similar penicillins make them effective against 80 to 95 percent of B fragilis strains. Cefoxitin, which is resistant to penicillinase and cephalosporinase, used to be active against 95 percent of B fragilis strains, but now 25 percent of strains are resistant in some centers. Similarly, 20 percent of B fragilis strains are now resistant to clindamycin. The third-generation cephalosporins are usually less active than cefoxitin against the B fragilis group. Drugs active against essentially all Gram-negative (and other) anaerobes are metronidazole, imipenem, chloramphenicol, and combinations of β-lactam drugs plus a β-lactamase inhibitor.

Table 20-3. Antimicrobial Susceptibility of Gram-Negative Anaerobic Bacillia.

Table 20-3

Antimicrobial Susceptibility of Gram-Negative Anaerobic Bacillia.

In addition to antimicrobial therapy, surgery is important in treating anaerobic infection. This includes drainage of abscesses, excision of necrotic tissue, relief of obstruction, and ligation or resection of infected veins. Percutaneous nonsurgical drainage may be effective in certain patients. Lung abscess, which responds well to medical therapy, is the primary exception to the rule that abscesses require surgical drainage.

Hyperbaric oxygen therapy is not useful in Gram-negative anaerobic rod infections. General supportive measures are, of course, important in managing any type of serious infection. Anticoagulation may be useful in patients with septic thrombophlebitis, along with appropriate antimicrobial therapy.

As noted above, the B fragilis group is among the most resistant of all anaerobes to antimicrobial agents. In part, this is related to β-lactamase production by B fragilis and related strains, but other mechanisms of resistance exist as well. Sutterella wadsworthensis is often resistant to metronidazole and sometimes to penicillins (including piperacillin). Bilophila is also often resistant to penicillins by virtue of β-lactamase production. Plasmid-mediated transferable resistance to several antimicrobial agents has been demonstrated with B fragilis and related Bacteroides species. Numerous other anaerobic Gram-negative bacillary species also produce β-lactamases. Chloramphenicol acetyltransferase and nitroreductase have been demonstrated in Bacteroides but are not generally clinically significant. Among the fusobacteria, the primary organism manifesting resistance is F varium. Many strains of this species are resistant to clindamycin, and a number are resistant to penicillins and cephalosporins.

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