eMedicine Specialties > Infectious Diseases > Bacterial Infections

Bacteroides Infection

Itzhak Brook, MD, MSc, Professor, Department of Pediatrics, Georgetown University School of Medicine

Updated: Oct 29, 2009

Introduction

Background

This article describes infections caused by the Bacteroides fragilis group and other anaerobic gram-negative bacilli (AGNB) that were previously included in the Bacteroides genus but are now included in the Prevotella and Porphyromonas genera. Infections due to AGNB are common, yet the specific identification of AGNB in these infections is difficult.

Bacteroides species are anaerobic bacteria that are predominant components of the bacterial florae of mucous membranes¹ and are therefore a common cause of endogenous infections. Bacteroides infections can develop in all body sites, including the CNS, the head, the neck, the chest, the abdomen, the pelvis, the skin, and the soft tissues. Inadequate therapy against these anaerobic bacteria may lead to clinical failure.

Because of their fastidiousness, they are difficult to isolate and are often overlooked. Their isolation requires appropriate methods of collection, transportation, and cultivation of specimens.² Treatment is complicated by 3 factors: slow growth, increasing resistance to antimicrobial agents,³ and the polymicrobial synergistic nature of the infection.⁴

The B fragilis group, a member of the Bacteroidaceae family, includes B fragilis (causes the most clinical infections), Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, and Bacteroides vulgatus. These bacteria are resistant to penicillins, mostly through the production of beta-lactamase. They are part of the normal GI florae¹ and predominate in intra-abdominal infections and infections that originate from those florae (eg, perirectal abscesses, decubitus ulcers). Enterotoxigenic B fragilis (ETBF) is also a potential cause of diarrhea.⁵

Pigmented Prevotella, such as Prevotella melaninogenica and Prevotella intermedia (which were previously called the Bacteroides melaninogenicus group), Porphyromonas (eg, Porphyromonas asaccharolytica), and nonpigmented Prevotella (eg, Prevotella oralis, Prevotella oris) are part of the normal oral and vaginal florae and are the predominant AGNB isolated from respiratory tract infections and their complications, including aspiration pneumonia, lung abscess, chronic otitis media, chronic sinusitis, abscesses around the oral cavity, human bites, paronychia, brain abscesses, and osteomyelitis. Prevotella bivia and Prevotella disiens (previously called Bacteroides) are important in obstetric and gynecologic infections.

Pathophysiology

Most infections due to AGNB originate from the endogenous mucosal membrane florae. Knowledge of the common mode of distribution allows for a logical choice of antimicrobial therapy for infections in these sites.

AGNB infections are generally polymicrobial. The number of isolates can reach 5-10 organisms. The type of copathogens depends on the infection site and the circumstances of the infection. Antimicrobial therapy should be directed at all major aerobic and anaerobic pathogens. AGNB promote infection through synergy with their aerobic and anaerobic counterparts and with each other.

An indirect pathogenic role of AGNB is their ability to produce the enzyme beta-lactamase, which allows them to protect themselves and other penicillin-susceptible organisms from the activity of penicillins.

Frequency

United States

The exact frequency of AGNB infection is difficult to calculate because of inappropriate methods of collection, transportation, and cultivation of specimens. AGNB are more commonly found in chronic infections. Their rate of recovery in blood cultures is 2-5% and higher with patients who have predisposing conditions.

International

The frequency of these infections appears to be higher in developing countries, where therapy is often inadequate or delayed.

Mortality/Morbidity

The mortality rate has decreased over the past 3 decades because of early recognition and initiation of proper prophylactic and therapeutic antimicrobial therapies.

Age

AGNB infections can occur in patients of all ages; however, the frequency of head and neck infections is higher in pediatric patients than in other patients.

Clinical

History

AGNB infections occur more often in chronic infections and in association with the predisposing conditions discussed below. However, they can also cause acute infections (ie, maxillary sinusitis associated with dental infections, intra-abdominal infections following perforation).^6,7

CNS infections
- AGNB can cause various intracranial infections, including brain abscess, subdural empyema, epidural abscess, and meningitis (usually from contiguous spread from adjacent foci of infection). Brain abscesses are commonly caused by chronic infections in the ears, the mastoids, the sinuses, the oropharynx, the teeth, or the lungs.
- Hematogenous spread can occur after dental, oropharyngeal, pulmonary, or intra-abdominal infection. Rarely, bacteremia of another origin or endocarditis leads to such infection.⁸
Head and neck infections: Anaerobes, including AGNB, are recovered from various infections, especially in their chronic form. Head and neck infections include chronic otitis media⁹; sinusitis¹⁰; mastoiditis; tonsillar,¹⁰ peritonsillar, and retropharyngeal abscesses; cervical lymphadenitis; all deep neck space infections; thyroiditis; odontogenic infections; and postsurgical and nonsurgical head and neck wounds and abscesses.¹¹
- Sinusitis is complicated by anaerobes, including AGNB, when it becomes chronic and oxygen levels decline. Anaerobes are isolated from 10% of patients with acute maxillary sinusitis (mostly secondary to odontogenic infection), but they are found in as many as 67% of chronic infections of the maxillary, ethmoid, frontal, and sphenoid sinuses.^12,10 The infection may spread via anastomosing veins or contiguously to the CNS. Complications include orbital cellulitis, meningitis, cavernous sinus thrombosis, and epidural and subdural brain abscesses.
- Tonsillitis, whether acute or chronic, may have AGNB involvement.^13,10 AGNB can also be involved with tonsillitis complications, including internal jugular vein thrombophlebitis, which often causes postanginal sepsis. Prevotella species and other anaerobes are recovered from tonsillar or retropharyngeal abscesses without any aerobic bacteria, and they are isolated in cases of Vincent angina.
Pleuropulmonary infections: Aspiration of oropharyngeal or gastric secretions and periodontal or gingival disease are risk factors for anaerobic pleuropulmonary infection due to AGNB and to other anaerobes. The infection can progress from pneumonitis to necrotizing pneumonia and lung abscess, with or without empyema.¹⁴
Intra-abdominal infections¹⁵
- Secondary peritonitis and abdominal abscesses generally occur after entry of enteric organisms into the peritoneal cavity through perforation of the intestine or other viscus as a result of obstruction, infarction, or trauma.
- The more distal the perforation, the more numerous the types and number of organisms that gain access into the peritoneal cavity (ie, perforations in the descending colon are associated with spillage of more organisms than perforations in proximal parts of the colon).
- Enterotoxigenic B fragilis are considered an emerging enteropathogen-causing diarrhea.
Female genital tract infection: These infections include bacterial vaginosis; soft tissue perineal, vulvar, and Bartholin gland abscesses; endometritis; pyometra; salpingitis; tubo-ovarian abscesses; adnexal abscess; pelvic inflammatory disease, which may include pelvic cellulitis and abscess; amnionitis; septic pelvic thrombophlebitis; intrauterine device–associated infection; septic abortion; and postsurgical obstetric and gynecologic infections.
Skin and soft tissue infections
- Infections involving AGNB include superficial infections, such as infected cutaneous ulcers, cellulitis, secondary diaper rash, gastrostomy or tracheostomy site wounds, infected subcutaneous sebaceous or inclusion cysts, eczema, scabies or kerion infections, paronychia, hidradenitis suppurativa, and pyoderma.
- Subcutaneous tissue infections and postsurgical wound infections that may also involve the skin include cutaneous and subcutaneous abscesses, decubitus ulcers, infected diabetic (vascular or trophic) ulcers, breast abscesses, bite wounds,¹⁶ anaerobic cellulitis and gas gangrene, bacterial synergistic gangrene, infected pilonidal cyst or sinus, Meleney ulcer, and burn wound infection.
- Deeper anaerobic soft tissue infections include necrotizing fasciitis, necrotizing synergistic cellulitis, gas gangrene, and crepitus cellulitis. These infections can involve the fascia alone or also the muscle surrounded by the fascia, inducing myositis and myonecrosis.
- Anaerobic infections, such as decubitus ulcers or diabetic foot ulcers, are generally polymicrobial and are often complicated by osteomyelitis or bacteremia.
- Deep tissue infections, such as necrotizing cellulitis, fasciitis, and myositis, often involve clostridial organisms and Staphylococcus pyogenes. They may be polymicrobic; may contain gas and gray, thin, putrid pus; and are associated with bacteremia and mortality.¹⁷
Osteomyelitis and septic arthritis: Osteomyelitis in the long bones and the cranial and facial bones is frequently polymicrobic and may be associated with anaerobes in patients with peripheral vascular disease and decubitus ulcers.¹⁸
Bacteremia
- The prevalence of anaerobes, including AGNB, in bacteremia was once 5-15%. However, rates declined to 2-6% in the 1990s. Increased awareness of the importance of anaerobes and enhanced recognition of the types of clinical infection caused by these organisms, along with appropriate prophylaxis and treatment, have been proposed as explanations for the decreased incidence of anaerobic bacteremia from 1974–1988.¹⁹ However, recent studies have reported a resurgence in anaerobic bacteremia. A study from the Mayo Clinic (Rochester, MN) has reported that the mean incidence of anaerobic bacteremia increased from 53 cases per year during 1993–1996 to 75 cases per year during 1997–2000 to 91 cases per year during 2001–2004 (an overall increase of 74%).²⁰
- The authors concluded that the sources of anaerobic bacteremia are now more varied than they once were, especially among immunosuppressed individuals and persons with complex underlying disease.
- Which organisms are involved depends on their portal of entry and the underlying disease. The common isolates are the B fragilis group (60-75% of isolates).⁸ The B fragilis group and clostridial organisms are associated with a GI source.
- Pigmented Prevotella, Porphyromonas, and Fusobacterium are associated with the oropharynx and a pulmonary source.
- Fusobacterium species involve the female genital tract.
- Propionibacterium acnes is associated with a foreign body.
- Peptostreptococcus species are associated with all sources but especially with oropharyngeal, pulmonary, and female genital tract sources.
- Predisposing factors include neoplasms; hematologic disorders; organ transplant; intestinal obstruction; decubitus ulcers; dental extraction; diabetes mellitus; postsplenectomy; use of cytotoxic agents or corticosteroids; total-body irradiation; and recent GI, obstetric, or gynecologic surgery.
- Features typical of anaerobic bacteremia include metastatic lesions, hyperbilirubinemia, and suppurative thrombophlebitis.
- The risk of mortality is 15-30% and improves with early appropriate antimicrobial therapy and resolution of the primary infection.

Causes

Conditions that predispose to AGNB infections include the exposure of sterile sites to a high inoculum of indigenous mucous membrane florae; use of antibiotics that are ineffective against AGNB; reduced blood supply; and tissue necrosis, which lowers the oxidation-reduction potential and favors the growth of anaerobes. Conditions that lower the blood supply include trauma, foreign body, malignancy, surgery, edema, shock, colitis, and vascular disease.^6,7
Infection with aerobic bacteria can make the local tissue conditions more favorable for the growth of anaerobes. The host defenses can become impaired by anaerobic conditions and anaerobic bacteria.
Anaerobic infection often manifests as suppuration, thrombophlebitis, abscess formation, and gangrenous destruction of tissue associated with gas.
Anaerobes, including AGNB, are common in chronic infections. Therapy with antimicrobials, such as aminoglycosides, trimethoprim-sulfamethazine, and older quinolones, frequently fails to eradicate anaerobes.
Certain infections that often involve anaerobes include brain abscess, oral or dental infections, human or animal bites, aspiration pneumonia, lung abscesses, amnionitis, endometritis, septic abortions, pelvic inflammatory disease, tubo-ovarian abscess, peritonitis following viscus perforation, abscesses in and around the oral and rectal areas, and pus-forming necrotizing infections of soft tissue or muscle.^6,7
Some tumors, such as colonic, uterine, and bronchogenic carcinomas and necrotic tumors of the head and the neck, can become infected with anaerobes.

Workup

Laboratory Studies

Collection of specimens of anaerobic bacteria is important because documentation of an anaerobic infection is through culture of organisms from the infected site. Appropriate documentation of anaerobic infection requires proper collection of appropriate specimens, expeditious transportation, and careful laboratory processing.
- Specimens must be obtained free of contamination. Inadequate techniques or media can lead to missing the presence of anaerobic bacteria or the assumption that only aerobic organisms are present in a mixed infection.
- Because anaerobes are present on skin and mucous membranes, even minimal contamination with normal florae can be misleading.
- Unacceptable or inappropriate specimens can yield normal florae and, therefore, have no or little diagnostic value.
Appropriate materials should be obtained by using techniques that bypass the normal florae.
- Direct-needle aspiration is the best method of obtaining a culture; the use of swabs is much less desirable.
  - Specimens obtained from normally sterile sites, such as blood or spinal, joint, or peritoneal fluids, are collected after thorough skin decontamination.
  - Two approaches are used to culture the maxillary sinus following sterilization of the canine fossa or the nasal vestibule, via either the canine fossa or the inferior meatus.
  - Urine is collected by percutaneous suprapubic bladder aspiration.
  - Other specimens can be collected from abscess contents, from deep aspirates of wounds, and via special techniques, such as transtracheal aspirates or direct lung puncture.
  - Specimens of the lower respiratory tract are difficult to obtain without contamination with indigenous florae. Double-lumen catheter bronchial brushing and bronchoalveolar lavage, cultured quantitatively, can be useful.
  - Culdocentesis fluid obtained after decontamination of the vagina is acceptable.
- Transportation of specimens should be prompt unless transport devices are available. Transport devices generally contain oxygen-free environments provided by a mixture of carbon dioxide, hydrogen, and nitrogen, plus an aerobic condition indicator. Specimens should be placed into an anaerobic transporter as soon as possible.
Liquid or tissue specimens are always preferred to swabs.
- Liquid specimens are inoculated into an anaerobic transport vial or a syringe and a needle.
- All air bubbles are expelled from the syringe. Insertion of the needle tip into a sterile rubber stopper is no longer recommended. Because air gradually diffuses through the plastic syringe wall, specimens should be processed in less than 30 minutes.
Swabs are placed in sterilized tubes that contain carbon dioxide or prereduced anaerobically sterile Carey and Blair semisolid media.
Tissue specimens can be transported in an anaerobic jar or in a sealed plastic bag rendered anaerobic.
Gram stain of a smear of the specimen provides important preliminary information regarding the types of organisms present, helps determine appropriate initial therapy, and serves as a quality control.
Cultures should be immediately placed under anaerobic conditions and should be incubated for 48 hours or longer. An additional 36-48 hours is generally required for species- or genus-level identification by using biochemical tests. Kits that contain these tests are commercially available.²
A rapid enzymatic test enables identification after only 4 hours of aerobic incubation.
Gas-liquid chromatography of metabolites is often used.
Nucleic acid probers and polymerase chain reaction methods are also being developed for rapid identification.
Detailed procedures of laboratory methods can be found in microbiology manuals.²
Antimicrobial susceptibility testing of AGNB has become less predictable because their resistance to several antimicrobials has increased.²¹ Screening of AGNB isolates for beta-lactamase activity may be helpful.^13,22 However, occasional strains may resist beta-lactam antibiotics through other mechanisms.
Routine susceptibility testing is time-consuming and often unnecessary. However, testing the susceptibility of isolates recovered from sterile body sites and/or those that are clinically important (ie, blood cultures, bone, CNS, serious infections) and have variable susceptibilities, especially those isolated in pure culture from properly collected specimens, is important.³
- Antibiotics that should be tested include penicillin, a broad-spectrum penicillin, a penicillin plus a beta-lactamase inhibitor, clindamycin, chloramphenicol, a second-generation cephalosporin (eg, cefoxitin), tigecycline, newer quinolones, metronidazole, and a carbapenem.
- The recommended methods include agar microbroth and macrobroth dilution.
- Newer methods include the E-test and the spiral gradient end point system.

Imaging Studies

Radiologic or imaging studies are helpful. Abscesses are a common complication of Bacteroides infections. The presence of gas in the infected site is highly suggestive of anaerobic infection.

Treatment

Medical Care

The patient's recovery from anaerobic infection depends on prompt and proper management according to the following 3 principles:
- Toxins produced by anaerobes must be neutralized.
- The environment must be changed to prevent local bacterial proliferation.
- The spread of bacteria must be limited.
The environment is controlled by debriding necrotic tissue, draining pus, improving circulation, alleviating obstruction, and increasing tissue oxygenation.
Certain types of adjunctive therapy, such as hyperbaric oxygen therapy, may be useful but remain unproven.
In many cases, antimicrobial therapy is the only form of therapy required, but it can also be used as an adjunct to a surgical approach.
- Because anaerobic bacteria are generally recovered mixed with aerobic organisms, the appropriate choice for antimicrobial agents should provide adequate treatment of both groups of pathogens.
- When choosing antimicrobials for the treatment of mixed infections, consider their aerobic and anaerobic antibacterial spectrum and their availability in oral or parenteral form.
- Some antimicrobials have a limited range of activity. For example, metronidazole is active only against anaerobes and cannot be administered as a single agent in mixed infections. Others, such as imipenem, have wide spectra of activity against aerobes and anaerobes.
Because culture results are often not available, many patients are treated empirically.
- Antimicrobial resistance patterns may vary. Some anaerobes have become, or may become, resistant to antimicrobials.
- The B fragilis group is almost uniformly susceptible to metronidazole, carbapenems, chloramphenicol, and combinations of a penicillin and beta-lactamase inhibitors. Resistance to other agents varies.
Aside from susceptibility patterns, other factors that influence the choice of antimicrobials include their pharmacokinetics, their toxicity, their effect on the normal florae, their bactericidal activity, and their ability to penetrate into sites of infection.
Although identification of organisms and their susceptibility is needed for optimal therapy, the clinical setting and the Gram stain results from the specimen are often helpful.
Antimicrobials useful in anaerobic infection are as follows:^21,23
- Penicillins
  - Penicillin G is still the drug of choice against most non–beta-lactamase–producing AGNB. However, in addition to the B fragilis group, which is resistant to penicillin, other AGNB show increased resistance. These include pigmented Prevotella and Porphyromonas species, P bivia, P disiens, Bilophila wadsworthia, and Bacteroides splanchnicus.
  - The combination of beta-lactamase inhibitors (eg, clavulanic acid, sulbactam, tazobactam) with a beta-lactam antibiotic (eg, ampicillin, amoxicillin, ticarcillin, piperacillin) can overcome these beta-lactamase–producing AGNB.
  - In high concentrations, carbenicillin, ticarcillin, piperacillin, and mezlocillin have good activity against gram-negative enterics and most anaerobes; however, they are not completely resistant to beta-lactamase.
- Cephalosporins
  - The B fragilis group, Prevotella species, and Porphyromonas species are resistant to first-generation cephalosporins by virtue of cephalosporinase production.
  - Cefoxitin is the most effective cephalosporin against the B fragilis group, although 5-15% may be resistant. Cefoxitin is inactive against most clostridial organisms, except Clostridium perfringens. Other second-generation cephalosporins, such as cefotetan and cefmetazole, have a longer half-life than cefoxitin and are as effective as cefoxitin against B fragilis; however, they are less efficacious against other members of the B fragilis group.
- Carbapenems: These agents, including imipenem, meropenem, doripenem (recently approved by the FDA for the treatment of complicated intra-abdominal infections), and ertapenem have excellent activity against a broad spectrum of aerobic and anaerobic bacteria.
- Chloramphenicol: This agent shows excellent in vitro activity against most anaerobic bacteria, and resistance is rare; however, the development of less-toxic newer agents has limited their use.
- Clindamycin: This antimicrobial is effective against anaerobes and has good activity against aerobic gram-positive cocci. Resistance of the B fragilis group is 5-25%. Antibiotic-associated colitis due to Clostridium difficile, although associated with most antimicrobials, was first described following clindamycin therapy.
- Metronidazole: This has excellent activity against anaerobes, including AGNB; however, this efficacy is limited to anaerobes. Microaerophilic streptococci, P acnes, and Actinomyces species are often resistant; therefore; adding an antimicrobial that is effective against these organisms (eg, penicillin) is often necessary.
- Tigecycline: This glycylcycline has effective in vitro activity against both gram-positive and gram-negative anaerobes, as well as against gram-positive aerobic strains such as methicillin-resistant staphylococci, streptococci, and enterococci. Tigecycline was recently approved by the FDA for the treatment of complicated skin and skin-structure infections and complicated intra-abdominal infections.
- Quinolones: Trovafloxacin, moxifloxacin, and gatifloxacin yield low minimum inhibitory concentrations (MICs) against most groups of anaerobes. Moxifloxacin was recently approved by the FDA for the treatment of complicated skin and skin-structure infections and complicated intra-abdominal infections. However, up to 40% of Bacteroides infections are resistant to moxifloxacin. The use of the quinolones is restricted in growing children and pregnancy because of their possible adverse effects on the cartilage.

Surgical Care

In most cases, surgical therapy is of critical importance. Surgical therapy includes draining abscesses, debriding necrotic tissues, decompressing closed-space infections, and relieving obstructions.
When surgical drainage is not used, the infection may persist and serious complications may develop.

Medication

Clinical judgment, personal experience, safety, and patient compliance should direct the physician in the choice of the appropriate antimicrobial agents. When choosing antimicrobials for the therapy of mixed infections, their aerobic and anaerobic antibacterial spectrum and their availability in oral or parenteral form should be considered. Some antimicrobials have a limited range of activity. For example, metronidazole is active only against anaerobes and therefore cannot be administered as a single agent for the therapy of mixed infections. Others (ie, carbapenems) have wide spectra of activity against aerobes and anaerobes.

Aside from susceptibility patterns, other factors that influence the choice of antimicrobial therapy include the pharmacologic characteristics of the various drugs, their toxicity, their effect on the normal florae, and their bactericidal activity. Although identification of the infecting organisms and their antimicrobial susceptibility may be needed for selection of optimal therapy, the clinical setting and Gram-stain preparation of the specimen may indicate the types of anaerobes present in the infection and the nature of the infectious process.

Although the duration of therapy for anaerobic infections is generally longer than for aerobes and facultative infections, the duration of treatment must be individualized, depending on the response. In some cases, treatment may require 6-8 weeks, but therapy may be shortened with proper surgical drainage. An anti–gram-negative enteric agent is generally added to treat Enterobacteriaceae when treating intra-abdominal infections.

The available parenteral antimicrobials for most infections include clindamycin, metronidazole, chloramphenicol, cefoxitin, a penicillin (ie, ticarcillin, ampicillin, piperacillin) and a beta-lactamase inhibitor (ie, clavulanic acid, sulbactam, tazobactam), tigecycline, and the carbapenems (eg, imipenem, meropenem, doripenem, ertapenem).²³

An agent effective against gram-negative enteric bacilli (ie, aminoglycoside) or an antipseudomonal cephalosporin (ie, cefepime) is generally added to clindamycin, metronidazole, and, occasionally, cefoxitin when treating intra-abdominal infections to provide coverage for these bacteria.

Penicillin can be added to metronidazole in the therapy of intracranial, pulmonary, or dental infections to cover microaerophilic streptococci and Actinomyces species.

A macrolide (ie, erythromycin) is added to metronidazole for upper respiratory tract infections to treat Staphylococcus aureus and aerobic streptococci.

Penicillin is added to clindamycin to supplement its coverage against Peptostreptococcus species and other gram-positive anaerobic organisms.

Penicillin is still the drug of choice for bacteremia caused by non–beta-lactamase producers. However, other agents should be used for the therapy of bacteremia caused by beta-lactamase producers.

For Chlamydia and Mycoplasma species, doxycycline is added to most regimens when treating pelvic infections.

Oral therapy is often substituted for parenteral therapy. The agents available for oral therapy include clindamycin, amoxicillin and clavulanate, and metronidazole.

Antimicrobials

Empiric antimicrobial therapy must cover all likely pathogens in the context of this clinical setting.

Penicillin G (Pfizerpen)

Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms (beta-lactam).

Dosing

Adult

10-28 million U/d IV

Pediatric

50,000-100,000 U/d IV

Interactions

Probenecid can increase effects; coadministration of tetracyclines can decrease effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Caution in impaired renal function

Cefoxitin (Mefoxin)

Second-generation cephalosporin indicated for gram-positive cocci and gram-negative rod infections. Infections caused by cephalosporin- or penicillin-resistant gram-negative bacteria may respond.

Dosing

Adult

1-2 g IV q6h

Pediatric

40 mg/kg/d IV q6h

Interactions

Probenecid may increase effects; coadministration with aminoglycosides or furosemide may increase nephrotoxicity (closely monitor renal function)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Bacterial or fungal overgrowth of nonsusceptible organisms may occur with prolonged use or repeated treatment; caution in patients with previously diagnosed colitis

Cefotetan (Cefotan)

Second-generation cephalosporin indicated for infections caused by susceptible gram-positive cocci and gram-negative rods. Dosage and route of administration depend on condition of patient, severity of infection, and susceptibility of causative organism.

Dosing

Adult

1-2 g IV q12h; not to exceed 4 g/d

Pediatric

20-40 mg/kg/dose IV q12h for 5-10 d

Interactions

Consumption of alcohol within 72 h of administration may produce disulfiramlike reactions; may increase hypoprothrombinemic effects of anticoagulants; coadministration with potent diuretics (eg, loop diuretics) or aminoglycosides may increase nephrotoxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Reduce dosage by half if CrCl <10-30 mL/min and by one fourth if CrCl <10 mL/min; bacterial or fungal overgrowth of nonsusceptible organisms may occur with prolonged or repeated therapy

Clindamycin (Cleocin)

Lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes causing RNA-dependent protein synthesis to arrest.

Dosing

Adult

150-450 mg PO q6h
450-900 mg IV q8h

Pediatric

20-30 mg/kg/d PO divided q6h
25-40 mg/kg/d PO divided q6-8h

Interactions

Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects; antidiarrheals may delay absorption

Contraindications

Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis

Amoxicillin and clavulanate (Augmentin)

Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins. Addition of clavulanate inhibits beta-lactamase–producing bacteria.
Good alternative antibiotic for patients allergic to or intolerant to macrolides. Usually is well tolerated and provides good coverage for most infectious agents. Not effective against Mycoplasma and Legionella species. Half-life of oral dosage form is 1-1.3 h. Has good tissue penetration but does not enter cerebrospinal fluid.
For children >3 mo, base dosing protocol on amoxicillin content. Because of different ratios of amoxicillin to clavulanic acid in 250-mg tab (250/125) vs 250-mg chewable tab (250/62.5), do not use 250-mg tab until child weighs >40 kg.

Dosing

Adult

500 mg PO q8h or 875 mg PO q12h

Pediatric

<3 months: 125 mg/5 mL PO susp based on amoxicillin; 30 mg/kg/d divided bid
>3 months: If using 200 mg/5 mL or 400 mg/5 mL susp, 45 mg/kg/d PO q12h; if using 125 mg/5 mL or 250 mg/5 mL susp, 40 mg/kg/d PO q8h
>40 kg: Administer as in adults

Interactions

Coadministration with warfarin or heparin increases risk of bleeding

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Administer for a minimum of 10 d to eliminate organism and to prevent sequelae (eg, endocarditis, rheumatic fever); following treatment, perform cultures to confirm eradication of streptococci

Ticarcillin and clavulanate potassium (Timentin)

Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active growth. Antipseudomonal penicillin plus beta-lactamase inhibitor that provides coverage against most gram-positive organisms, most gram-negative organisms, and most anaerobes. Contains 4.7-5.0 mEq of Na⁺/g.

Dosing

Adult

3.1 g IV q4-6h

Pediatric

200-300 mg/kg/d IV q4-6h

Interactions

Tetracyclines may decrease effects; high concentrations may physically inactivate aminoglycosides if administered in same IV line; effects are synergistic when administered concurrently with aminoglycosides; probenecid may increase levels

Contraindications

Documented hypersensitivity; severe pneumonia, bacteremia, pericarditis, emphysema, meningitis, and purulent or septic arthritis should not be treated with oral penicillin during acute stage

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Perform CBC counts prior to initiation of therapy and at least weekly during therapy; monitor for liver function abnormalities by measuring AST and ALT during therapy; exercise caution in patients with hepatic insufficiencies; perform urinalysis and BUN/creatinine determinations during therapy, and adjust dose if values become elevated; monitor blood levels to avoid possible neurotoxic reactions

Chloramphenicol (Chloromycetin)

Binds to 50S bacterial ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria.

Dosing

Adult

0.25-1 g IV q6h; not to exceed 4 g/d

Pediatric

80-100 mg/kg/d IV

Interactions

Concurrently with barbiturates, chloramphenicol serum levels may decrease while barbiturate levels may increase, causing toxicity; manifestations of hypoglycemia may occur with sulfonylureas; rifampin may reduce serum levels, presumably through hepatic enzyme induction; may increase effects of anticoagulants; may increase serum hydantoin levels, possibly resulting in toxicity; levels may be increased or decreased

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Use only for indicated infections or as prophylaxis for bacterial infections; serious and fatal blood dyscrasias (eg, aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) can occur; evaluate baseline, and perform periodic blood studies approximately every 2 d while in therapy; discontinue upon appearance of reticulocytopenia, leukopenia, thrombocytopenia, or anemia or upon findings attributable to chloramphenicol; adjust dose in liver or kidney dysfunction; caution in pregnancy at term or during labor because of potential toxic effects on fetus (gray syndrome)

Imipenem and cilastatin (Primaxin)

Carbapenem used for treatment of multiple organism infections in which other agents do not have wide-spectrum therapeutic activity or are contraindicated because of potential toxicity.

Dosing

Adult

500-750 mg IV q6h; not to exceed 3 g/d IV

Pediatric

<12 years: Not established; 15-25 mg/kg/d IV suggested
>12 years: 15-25 mg/kg/d IV

Interactions

Coadministration with cyclosporine may increase CNS adverse effects of both agents; coadministration with ganciclovir may result in generalized seizures

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adjust dose in impaired renal function; high doses can cause seizures and renal failure, especially in elderly persons and in those with prior seizure disorder; adverse effects include phlebitis, transitory hypotension, hepatotoxicity, vomiting, and diarrhea

Meropenem (Merrem)

Broad-spectrum carbapenem antibiotic that inhibits cell wall synthesis and has bactericidal activity. Effective against most gram-positive and gram-negative bacteria. Has slightly increased activity against gram-negative bacteria and slightly decreased activity against staphylococci and streptococci compared with imipenem. Also less likely to cause seizures compared with imipenem.

Dosing

Adult

1 g IV q8h

Pediatric

40 mg/kg IV q8h

Interactions

Probenecid may inhibit renal excretion, increasing levels

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Pseudomembranous colitis and thrombocytopenia may occur, requiring immediate discontinuation

Metronidazole (Flagyl)

Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Used in combination with other antimicrobial agents (except for C difficile enterocolitis).

Dosing

Adult

375-750 mg IV q8h

Pediatric

30 mg/kg/d IV q6h

Interactions

Cimetidine may increase toxicity; may increase effects of anticoagulants; may increase toxicity of lithium and phenytoin; disulfiramlike reaction may occur with orally ingested ethanol

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

X - Contraindicated; benefit does not outweigh risk

Precautions

Has shown mutagenicity in Ames test; tumorigenicity shown in animals but not in humans; adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy

Ertapenem (Invanz)

Bactericidal activity results from inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin-binding proteins. Stable against hydrolysis by a variety of beta-lactamases, including penicillinases, cephalosporinases, and extended-spectrum beta-lactamases. Hydrolyzed by metallo-beta-lactamases.

Dosing

Adult

1 g/d for 14 d if given IV and for 7 d if given IM; infuse over 30 min if given IV

Pediatric

Not established

Interactions

Probenecid may reduce renal clearance and increase half-life but benefit is minimal and does not justify coadministration

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Pseudomembranous colitis may occur; seizures and adverse CNS reactions may occur; when using with lidocaine to administer IM, avoid inadvertent injection into blood vessel

Moxifloxacin (Avelox)

Inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription.

Dosing

Adult

400 mg PO/IV qd

Pediatric

<18 years: Not recommended
>18 years: Administer as in adults

Interactions

Antacids and electrolyte supplements reduce absorption; loop diuretics, probenecid, and cimetidine increase serum levels; NSAIDs enhance CNS stimulating effect
May increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT); ferrous sulfate decreases bioavailability (administer moxifloxacin 4 h prior or 8 h following ferrous sulfate); coadministration with drugs that prolong QTc interval (quinidine, procainamide, amiodarone, sotalol, erythromycin, tricyclic antidepressants) increase risk of life-threatening arrhythmia

Contraindications

Documented hypersensitivity; known QT prolongation, concurrent administration of drugs that cause QT prolongation

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

In prolonged therapy, periodically evaluate organ system functions (eg, renal, hepatic, hematopoietic); superinfections may occur with prolonged or repeated antibiotic therapy; fluoroquinolones have induced seizures in CNS disorders and caused tendinitis or tendon rupture

Tigecycline (Tygacil)

A glycylcycline antibiotic that is structurally similar to tetracycline antibiotics. Inhibits bacterial protein translation by binding to 30S ribosomal subunit and blocks entry of amino-acyl tRNA molecules in ribosome A site. Indicated for complicated skin and skin structure infections caused by E coli, E faecalis (vancomycin-susceptible isolates only), S aureus (methicillin-susceptible and -resistant isolates), S agalactiae, S anginosus group (includes S anginosus, S intermedius, and S constellatus), S pyogenes, and B fragilis.

Dosing

Adult

Infuse each dose over 30-60 min
100 mg IV once, then 50 mg IV q12h
Severe hepatic impairment (ie, Child Pugh class C): 100 mg IV once, then 25 mg IV q12h

Pediatric

<18 years: Not established
>18 years: Administer as in adults

Interactions

Coadministration decreases warfarin clearance and increases warfarin C_max and AUC (monitor aPTT and INR); coadministration of antibiotics with oral contraceptives may decrease contraceptive effect

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in severe hepatic impairment (reduce dose); may adversely effect tooth development; may permit clostridia overgrowth, resulting in antibiotic-associated colitis; may have adverse effects similar to tetracyclines (eg, photosensitivity, pseudotumor cerebri, pancreatitis, antianabolic action)

Follow-up

Deterrence/Prevention

In areas where AGNB and other anaerobes predominate, early and aggressive treatment of acute infection can prevent them from becoming chronic.
When the risk of anaerobic infections (eg, intra-abdominal and wound infection following surgery) is high, proper antimicrobial prophylaxis may reduce the risk.
Preventing oral florae aspiration by improving neurologic status, suctioning oral secretions, improving oral hygiene, and maintaining lower stomach pH can reduce the risk of aspiration pneumonia and its complications.
Irrigation and debridement of wounds and necrotic tissue, drainage of pus, and improvement of the blood supply help prevent skin and soft tissue infections.

Patient Education

For excellent patient education resources, visit eMedicine's Bites and Stings Center and Ear, Nose, and Throat Center. Also, see eMedicine's patient education articles Human Bites and Tonsillitis.

Miscellaneous

Medicolegal Pitfalls

Failure to promptly and properly institute the following 3 principles:
- Neutralization of toxins produced by anaerobes
- Prevention of local bacterial proliferation by changing the environment
- Limitation of bacterial spread

References

Brook I. Indigenous microbial flora of humans. In: Surgical Infectious Diseases. 3^rd ed. Norwalk, Conn: Appleton & Lange; 1995:37.
Jousime-Somers H, Summanen P, Citron DM. Belmont, Calif. Wadsworth-KTL Anaerobic Bacteriology Manual. 6^th ed. Star Publishing; 2002.
Wexler HM, Finegold SM. Current susceptibility patterns of anaerobic bacteria. Yonsei Med J. Dec 1998;39(6):495-501. [Medline].
Brook I. Enhancement of growth of aerobic and facultative bacteria in mixed infections with Bacteroides species. Infect Immun. Dec 1985;50(3):929-31. [Medline].
Durmaz B, Dalgalar M, Durmaz R. Prevalence of enterotoxigenic Bacteroides fragilis in patients with diarrhea: a controlled study. Anaerobe. Dec 2005;11(6):318-21. [Medline].
Brook I. Treatment of anaerobic infection. Expert Rev Anti Infect Ther. Dec 2007;5(6):991-1006. [Medline].
Finegold SM. Anaerobic Bacteria in Human Disease. Orlando, Fla: Academic Press; 1977.
Brook I. Anaerobic bacterial bacteremia: 12-year experience in two military hospitals. J Infect Dis. Dec 1989;160(6):1071-5. [Medline].
Brook I. Prevalence of beta-lactamase-producing bacteria in chronic suppurative otitis media. Am J Dis Child. Mar 1985;139(3):280-3. [Medline].
Nord CE. The role of anaerobic bacteria in recurrent episodes of sinusitis and tonsillitis. Clin Infect Dis. Jun 1995;20(6):1512-24. [Medline].
Brook I. The role of anaerobic bacteria in upper respiratory tract and other head and neck infections. Curr Infect Dis Rep. May 2007;9(3):208-17. [Medline].
Brook I, Thompson DH, Frazier EH. Microbiology and management of chronic maxillary sinusitis. Arch Otolaryngol Head Neck Surg. Dec 1994;120(12):1317-20. [Medline].
Brook I. The role of beta-lactamase-producing bacteria in the persistence of streptococcal tonsillar infection. Rev Infect Dis. Sep-Oct 1984;6(5):601-7. [Medline].
Bartlett JG. Anaerobic bacterial infections of the lung and pleural space. Clin Infect Dis. Jun 1993;16 Suppl 4:S248-55. [Medline].
Bohnen JM. Antibiotic therapy for abdominal infection. World J Surg. Feb 1998;22(2):152-7. [Medline].
Goldstein EJ. Current concepts on animal bites: bacteriology and therapy. Curr Clin Top Infect Dis. 1999;19:99-111. [Medline].
Brook I, Frazier EH. Clinical and microbiological features of necrotizing fasciitis. J Clin Microbiol. Sep 1995;33(9):2382-7. [Medline].
Lewis RP, Sutter VL, Finegold SM. Bone infections involving anaerobic bacteria. Medicine (Baltimore). Jul 1978;57(4):279-305. [Medline].
Dorsher CW, Rosenblatt JE, Wilson WR, Ilstrup DM. Anaerobic bacteremia: decreasing rate over a 15-year period. Rev Infect Dis. Jul-Aug 1991;13(4):633-6. [Medline].
Lassmann B, Gustafson DR, Wood CM, Rosenblatt JE. Reemergence of anaerobic bacteremia. Clin Infect Dis. Apr 1 2007;44(7):895-900. [Medline].
Snydman DR, Jacobus NV, McDermott LA, Ruthazer R, Golan Y, Goldstein EJ, et al. National survey on the susceptibility of Bacteroides fragilis group: report and analysis of trends in the United States from 1997 to 2004. Antimicrob Agents Chemother. May 2007;51(5):1649-55. [Medline].
Nakano V, Padilla G, do Valle Marques M, Avila-Campos MJ. Plasmid-related beta-lactamase production in Bacteroides fragilis strains. Res Microbiol. Dec 2004;155(10):843-6. [Medline].
Brook I. Treatment of anaerobic infection. Expert Rev Anti Infect Ther. Dec 2007;5(6):991-1006. [Medline].
Brook I. Anaerobic Infections. Diagnosis and Management. In: Informa Healthcare USA, Inc. 4th Ed. New York, NY: 2007.

Keywords

anaerobic gram-negative bacilli, AGNB, Bacteroides fragilis, B fragilis, Prevotella species, Porphyromonas species, Bacteroides distasonis, B distasonis, Bacteroides ovatus, B ovatus, Bacteroides thetaiotaomicron, B thetaiotaomicron, Bacteroides vulgatus, B vulgatus, Prevotella melaninogenica, P melaninogenica, Prevotella intermedia, P intermedia, Porphyromonas asaccharolytica, P asaccharolytica, Prevotella oralis, P oralis, Prevotella oris, P oris, Prevotella bivia, P bivia, Bacteroides bivia, B bivia, Prevotella disiens, P disiens, Bacteroides disiens, Bacteroides melaninogenicus group, B melaninogenicus group, perirectal abscess, decubitus ulcer, bedsore, bed sore, pressure sore, intra-abdominal abscess, intraabdominal abscess, aspiration pneumonia, lung abscess, chronic otitis media, chronic sinusitis, oral cavity abscess, abscesses around the oral cavity, human bites, paronychia, brain abscesses, osteomyelitis, Bacteroidaceae

Contributor Information and Disclosures

Author

Itzhak Brook, MD, MSc, Professor, Department of Pediatrics, Georgetown University School of Medicine
Itzhak Brook, MD, MSc is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Armed Forces Infectious Diseases Society, Association of Military Surgeons of the US, Infectious Diseases Society of America, International Immunocompromised Host Society, International Society for Infectious Diseases, Medical Society of the District of Columbia, New York Academy of Sciences, Pediatric Infectious Diseases Society, Society for Ear, Nose and Throat Advances in Children, Society for Experimental Biology and Medicine, Society for Pediatric Research, Southern Medical Association, and Surgical Infection Society
Disclosure: Nothing to disclose.

Medical Editor

Jeffrey D Band, MD, Clinical Professor of Medicine, Wayne State University School of Medicine; Director, Division of Infectious Diseases and International Medicine, William Beaumont Hospital Corporation
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Ronald A Greenfield, MD, Professor, Department of Internal Medicine, Section of Infectious Diseases, University of Oklahoma College of Medicine
Ronald A Greenfield, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Central Society for Clinical Research, Infectious Diseases Society of America, Medical Mycology Society of the Americas, Phi Beta Kappa, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology
Disclosure: Pfizer Honoraria Speaking and teaching; Gilead Honoraria Speaking and teaching; Ortho McNeil Honoraria Speaking and teaching; Wyeth Honoraria Speaking and teaching; Abbott Honoraria Speaking and teaching; Astellas Honoraria Speaking and teaching; Cubist Speaking and teaching

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Further Reading