- Pleomorphic, gram negative, anaerobic bacilli, easily cultivated.
- Clinically important species: B. fragilis, B. thetaiotaomicron, B. vulgatus, B. distasonis, B. ovatus, B. uniformis, B. caccae.
- See separate B. fragilis module for information on that species.
- Normal component of intestinal, oral, vaginal flora.
- Most significant in polymicrobial infections, abscesses.
- Virtually all members of genus sensitive to metronidazole, most carbapenems (imipenem/cilastatin best), beta-lactam/beta-lactamase inhibitor combinations (piperacillin/tazobactam best), so speciation not usually important.
- Culture only uncontaminated specimens: blood, peritoneal, pleural empyema, or other abscess aspirates.
- Routine anaerobic culture of community-acquired intra-abdominal infections considered optional.
- Consider susceptibility testing if persistent isolation or if considering prolonged therapy due to immunosuppression.
- Recent emergence of multiply-drug resistant B. fragilis.
SITES OF INFECTION
- Intra-abdominal: abscess (often polymicrobial) associated with ruptured viscus, intestinal surgery (especially B. fragilis); liver abscess (especially with abnormal anatomy or stone); infected pancreatic pseudocyst.
- CNS: brain abscess often in association with other bacteria, and as consequence of chronic sinusitis, chronic otitis media; subdural empyema; epidural abscess.
- Oral cavity, upper respiratory tract: tooth abscess, periodontitis, peritonsillar abscess (in association with other bacteria), sinusitis (chronic), parotiditis (unusual).
- Lung: aspiration pneumonia or necrotizing pneumonia, lung abscess, empyema.
- GU: Bartholin’s cyst abscess, PID, tuboovarian abscess, endometritis, chorioamnionitis, post-ob/gyn surgical wound infections.
- Bloodstream: common isolate, often indicates a primary source (intra-abdominal in one-half to two-thirds of cases).
- Skin/soft tissue: human/animal bites, post-surgical, necrotizing fasciitis; decubitus and diabetic ulcers.
- Bone: osteomyelitis especially polymicrobial in association with decubitus ulcer, other local contamination.
- Recommendations assume polymicrobial infection and empiric treatment of Bacteroides species including B. fragilis.
Community-acquired intra-abdominal infections/Adults
Mild-moderate severity (perforations/appendicitis)
High risk or severity/advanced age or immunocompromise
ertapenem, moxifloxacin, tigecycline, ticarcillin/clavulanate
imipenem/cilastatin, meropenem, doripenem, piperacillin/tazobactam
cefazolin, cefuroxime, ceftriaxone, cefotaxime, ciprofloxacin or levofloxacin PLUS metronidazole
cefepime, ceftazidime, ciprofloxacin or levofloxacin PLUS metronidazole
- Healthcare-associated intra-abdominal infections:
- Cefoxitin and cefotetan have increasing rates of resistance seen in Bacteroides species, would not use as monotherapy.
- Surgical or percutaneous catheter drainage of abscess.
- Exception: most tubo-ovarian abscesses, some brain (multiple or ≤ 2cm) and liver abscesses respond to abx alone.
- Hyperbaric oxygen not demonstrated to be useful in clinical trials, and is of only theoretical benefit.
Selected Drug Comments
Active against many clinical infections by Bacteroides species, although B. fragilis susceptibility may only be 86%. Also active against streptococci, methicillin-sensitive S. aureus, many coliforms; activity vs. Enterobacteriaceae less than ticarcillin/clavulanate and piperacillin/tazobactam. It has no against Pseudomonas or many nosocomial Enterococcus infections. Good for community-acquired sepsis but rates of resistance among E. colirising.
Cephalosporins other than cefoxitin and cefotetan are not good for anaerobes in general; in vitro activity variable, clinical experience nil as monotherapy.
This drug is often thought as the equivalent of cefoxitin but with longer dosing intervals. Resistance among B. fragilis may be up to 35%.
The best cephalosporin for B. fragilis and most other anaerobes. In vitro activity vs. B. fragilis is not as predictable as that of imipenem or beta-lactam/beta-lactamase inhibitors, but the clinical experience is extensive and good historically although resistance is rising. It may be risky as monotherapy in severe infections because many coliforms and all P. aeruginosa are resistant.
No activity in vitro vs. B. fragilis.
This is the first major B. fragilis drug with extensive trials in the 1970’s. It still performs, but many report declining rates of susceptibility by B. fragilis and other anaerobes in recent years compared to the 70’s & 80’s. The clinical significance of this in vitro resistance is less clear but many now do not depend on this drug for significant anaerobic infections with potential for B. fragilis. Clindamycin is no longer recommended for routine use in intra-abdominal sepsis.
The in vitro data for activity vs. B. fragilis is somewhat similar to moxifloxacin but the published clinical experience is less. No longer available in U.S. market.
No activity against B. fragilis. Tobramycin or gentamicin is used in the media to promote growth of anaerobes.
Active against nearly all B. fragilis, anaerobes and most other components of a mixed flora except MRSA, S. epidermidis and some P. aeruginosa/Enterobacteriaceae. The track record in intra-abdominal sepsis as a single agent is excellent, and no other carbapenem performs better against anaerobes.
Anaerobic activity in vitro is variable—better than ciprofloxacin but inferior to gatifloxacin and moxifloxacin.
Most potent antibiotic available for anaerobic bacterial infection. Virtually all strains of B. fragilis are susceptible. It is unlikely that there will be any new agent in another class in the foreseeable future that can challenge metronidazole in terms of in vitro activity, bacteriocidal activity, or in vivo results. BUT it is active only against anaerobes so it is commonly combined with an additional agent for coliforms and strep that are commonly part of a mixed flora.
In vitro data show rising resistance profiles, though the FDA approved as monotherapy for treatment of complicated intra-abdominal infections. Would only consider in mild-moderate infections with adequate drainage/surgical intervention.
This is a reasonably good drug for B. fragilis. The usual mechanism of resistance is beta-lactamase production so piperacillin/tazobactam is better in vitro. However, the high dose used for piperacillin apparently overcomes this resistance that has made penicillin passé for B. fragilis.
Active against nearly all B. fragilis, anaerobes and most other components of a mixed flora except MRSA, S. epidermidis and some P. aeruginosa/Enterobacteriaceae. The track record in intra-abdominal sepsis as a single agent is excellent.
Only available as ticarcillin/clavulanate (Timentin) in U.S. In the beta-lactam/beta-lactamase form, this drug has better activity against anaerobes, most strep, most coliforms and some P. aeruginosa.
Active against many all anaerobes, most streptococci, and coliforms but resistance rising and has less than optimal activity against many P. aeruginosa. This is a rational single agent for treatment of intra-abdominal sepsis of community-onset or low severity.
No activity against B. fragilis. Tobramycin or gentamicin is used in the media to promote growth of anaerobes.
May have a bit less anaerobic activity then imipenem but significantly lacks anti-pseudomonal activity, so would only use for community-onset or mild-moderate infections, empirically.
In vitro sensitivity testing indicates may be more active for some B. fragilis than ertapenem, ampicillin/sulbactam, but some studies have shown it to be slightly less (in terms of MICs) to imipenem.
Usually same anaerobic spectrum as imipenem; however, the drug has been used less often in clinical trials for anaerobic processes.
Basis for recommendation
- Solomkin JS et al: Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt) 11:79, 2010 [PMID:20163262]
Comment: Since Bacteriodes spp. most often associated with an intra-abdominal infection, main recommendations for treatment of a polymicrobial infection are referenced within this module.
- Dubreuil L, Odou MF: Anaerobic bacteria and antibiotics: What kind of unexpected resistance could I find in my laboratory tomorrow? Anaerobe 16:555, 2010 [PMID:20971200]
Comment: Article summarizes literature going back to the 1990s examining antibiotic resistance in anaerobes. For B. fragilis, porin loss when added to chromosomal cephalosporinase hyperproduction, is the origin of resistance to the β-lactams–β-lactamase inhibitor combinations.
"Nim genes, responsible for metronidazole resistance, are spreading worldwide. Originally limited to the B. fragilis group, they are nowadays also seen in Prevotella species and in gram-positive cocci.
Considering the decreased susceptibility to metronidazole, the detection of nim genes by PCR does not necessarily point to resistance. Therefore detection remains problematic and has been associated with therapeutic failures. This phenomenon is increasing in several European countries."
Authors argue that for clinical practice, anaerobes should undergo antibiotic susceptibility testing.
- Sullivan A, Barkholt L, Nord CE: Lactobacillus acidophilus, Bifidobacterium lactis and Lactobacillus F19 prevent antibiotic-associated ecological disturbances of Bacteroides fragilis in the intestine. J Antimicrob Chemother 52:308, 2003 [PMID:12865387]
Comment: In a study of 24 healthy adults given clindamycin with probiotic yogurt with or without the above-described bacteria, the probiotic preparation prevented outgrowth of Bacteroides spp. despite a rise in the MIC of these bacteria to clindamycin.
- Karlowsky JA et al: Prevalence of antimicrobial resistance among clinical isolates of Bacteroides fragilis group in Canada in 2010-2011: CANWARD surveillance study. Antimicrob Agents Chemother 56:1247, 2012 [PMID:22203594]
Comment: Canadian study of Bacteroides fragilis group (n = 387) collected in 2010-2011 tested by CLSI broth microdilution method. B. fragilis (59.9%), Bacteroides ovatus (16.3%), and Bacteroides thetaiotaomicron (12.7%) accounted for ~90% of isolates collected. Overall rates of percent susceptibility were as follows: 99.7%, metronidazole; 99.5%, piperacillin-tazobactam; 99.2%, imipenem; 97.7%, ertapenem; 92.0%, doripenem; 87.3%, amoxicillin-clavulanate; 80.9%, tigecycline; 65.9%, cefoxitin; 55.6%, moxifloxacin; and 52.2%, clindamycin. Percent susceptibility to cefoxitin, clindamycin, and moxifloxacin was lowest for B. thetaiotaomicron (n = 49, 24.5%), Parabacteroides distasonis/P. merdae (n = 11, 9.1%), and B. ovatus (n = 63, 31.8%), respectively. One isolate (B. thetaiotaomicron) was resistant to metronidazole, and two isolates (both B. fragilis) were resistant to both piperacillin-tazobactam and imipenem. Since the last published surveillance study describing Canadian isolates of B. fragilis group almost 20 years ago (A.-M. Bourgault et al., Antimicrob. Agents Chemother. 36:343-347, 1992), rates of resistance have increased for amoxicillin-clavulanate, from 0.8% (1992) to 6.2% (2010-2011), and for clindamycin, from 9% (1992) to 34.1% (2010-2011).
- Rodrigues C et al: Bacteroides fragilis endocarditis: a case report and review of literature. Braz J Infect Dis 16:100, 2012 Jan-Feb [PMID:22358367]
Comment: Review of the literature since 1980 for this rare entity.
- Snydman DR, Jacobus NV, McDermott LA: In vitro activities of doripenem, a new broad-spectrum carbapenem, against recently collected clinical anaerobic isolates, with emphasis on the Bacteroides fragilis group. Antimicrob Agents Chemother 52:4492, 2008 [PMID:18838581]
Comment: Observation of in vitro sensitivities of multiple strains of clinical anaerobic isolates including B. fragilisand other Bacteroides spp. to doripenem and standard agents. Three of ~400 B. fragilis isolates were resistant; all were multiply resistant.
- Brook I, Frazier EH: Aerobic and anaerobic microbiology of infection after trauma. Am J Emerg Med 16:585, 1998 [PMID:9786544]
Comment: The microbiology of hundreds of trauma patients was examined. The predominant anaerobic bacteria included Bacteroides spp., Peptostreptococcus spp, Clostridium spp), Prevotella spp, and Fusobacterium spp. Types of infections included abscesses, bacteremia, bites, pleural empyema, osteomyelitis, peritonitis, thrombophlebitis, and wounds (including posttraumatic wounds, cellulitis, stump wound, decubitus ulcers, myositis, and fasciitis). Oropharyngeal flora predominated in infections originating from head and neck wounds, abscesses; bites);GI flora in peritonitis, intra-abd abscesses, decubiti.
- Lassmann B et al: Reemergence of anaerobic bacteremia. Clin Infect Dis 44:895, 2007 [PMID:17342637]
Comment: These authors provide a comprehensive analysis of anaerobic bacteremia, include those infections due to Bacteroides species. The major reason for this observation is complexity and severity of illness in their hospitalized patient population. This is an important issue because some have advocated for eliminating routine anaerobic cultures of adults as a cost-saving measure.
- Falagas ME, Siakavellas E: Bacteroides, Prevotella, and Porphyromonas species: a review of antibiotic resistance and therapeutic options. Int J Antimicrob Agents 15:1, 2000 [PMID:10856670]
Comment: This article discusses recent basic and clinical research on the taxonomy, microbiology, epidemiology, antimicrobial susceptibility and treatment of infections due to Bacteroides and other anaerobes. To the present, agents active against >99% of clinical isolates of Bacteroides are metronidazole, chloramphenicol and carbapenems. Agents active against 95-99% of Bacteroides fragilis isolates are the beta-lactam/beta-lactamase inhibitor combinations.
- Gal M, Brazier JS: Metronidazole resistance in Bacteroides spp. carrying nim genes and the selection of slow-growing metronidazole-resistant mutants. J Antimicrob Chemother 54:109, 2004 [PMID:15190033]
Comment: This article shows that metronidazole resistance can occur in a novel way in Bacteroides spp., manifesting in vitro as slow growing bacteria with a variably reversible phenotype. The bacteria studied were obtained from humans, so that clinical resistance mechanisms observed here may be applicable in the future. The molecular basis of the resistance was not determined.
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