Bacteroides species

Paul G. Auwaerter, M.D.

MICROBIOLOGY

  • Pleomorphic, Gram negative, anaerobic bacilli, easily cultivated.
  • Clinically important species: B. fragilis, B. thetaiotaomicron, B. vulgatus, B. distasonis, B. ovatus, B. uniformis, B. caccae.

CLINICAL

  • 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, carbapenems, beta-lactam/beta-lactamase inhibitor combinations, so speciation not usually important.
  • Culture only uncontaminated specimens: e.g., blood, peritoneal, pleural empyema or abscess aspirates.
  • Routine anaerobic culture of community-acquired intra-abdominal infections considered optional.
    • Consider susceptibility testing if persistent isolation, lack of therapeutic response or if considering prolonged therapy due to immunosuppression.
  • Recent emergence of multiply-drug resistant B. fragilis.

SITES OF INFECTION

TREATMENT

Antimicrobial agents

  • Recommendations assume polymicrobial infection (aerobic Gram negatives and Gram positives) and empiric treatment of Bacteroides species including B. fragilis.

Community-acquired intra-abdominal infections/Adults

Regimen

Mild-moderate severity (perforations/appendicitis)

High risk or severity/advanced age or immunocompromise

Single agent

ertapenem, moxifloxacin, tigecycline

imipenem/cilastatin, meropenem, doripenem, piperacillin/tazobactam

Combination therapy

cefazolin, cefuroxime, ceftriaxone, cefotaxime, ciprofloxacin or levofloxacin PLUS metronidazole

cefepime, ceftazidime, ciprofloxacin or levofloxacin PLUS metronidazole

  • Cefoxitin and cefotetan have increasing rates of resistance seen in Bacteroides species, would not use as monotherapy.

Adjunctive therapy

  • 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.

Surgical Prophylaxis

Selected Drug Comments

Drug

Recommendation

Ampicillin/sulbactam

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. May be adequate for community-acquired sepsis but rates of resistance among E. colirising and therefore no longer recommended for empiric therapy but could be used if cultures do not indicate resistance.

Cefotaxime

Cephalosporins other than cefoxitin and cefotetan are not good for anaerobes in general; in vitro activity variable, clinical experience nil as monotherapy.

Cefotetan

This drug is often thought as the equivalent of cefoxitin but with longer dosing intervals. Resistance among B. fragilis may be up to 35%.

Cefoxitin

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. Would not use as monotherapy in severe infections because many coliforms and all P. aeruginosa are resistant, along with rising rates of resistance among anaerobes.

Ciprofloxacin

No activity in vitro vs. B. fragilis.

Clindamycin

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.

Gatifloxacin

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.

Gentamicin

No activity against B. fragilis. Tobramycin or gentamicin is used in the media to promote growth of anaerobes.

Imipenem/cilastatin

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.

Levofloxacin

Anaerobic activity in vitro is variable—better than ciprofloxacin but inferior to gatifloxacin and moxifloxacin.

Metronidazole

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.

Moxifloxacin

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.

Piperacillin

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.
Drug is no longer manufactured routinely within the U.S.

Piperacillin/tazobactam

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.

Ticarcillin

No longer manufactured even as ticarcillin/clavulanatein U.S. In the beta-lactam/beta-lactamase form, this drug has better activity against anaerobes, most strep, most coliforms and some P. aeruginosa.

Ticarcillin/clavulanic Acid

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 longer available in the U.S.

Tobramycin

No activity against B. fragilis. Tobramycin or gentamicin is used in the media to promote growth of anaerobes.

Ertapenem

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.

Doripenem

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.

Meropenem

Usually same anaerobic spectrum as imipenem; however, the drug has been used less often in clinical trials for anaerobic processes.

OTHER INFORMATION

Basis for recommendation

  1. Solomkin JS, Mazuski JE, Bradley 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). 2010;11(1):79-109.  [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.

References

  1. Sadarangani SP, Cunningham SA, Jeraldo PR, et al. Metronidazole- and carbapenem-resistant bacteroides thetaiotaomicron isolated in Rochester, Minnesota, in 2014. Antimicrob Agents Chemother. 2015;59(7):4157-61.  [PMID:25941219]

    Comment: Although resistance has been described to both MTZ and carbapenems previously in B. thetaiotaomicron, this is the first report in which an isolate is resistant to both.

  2. Boyanova L, Kolarov R, Mitov I. Recent evolution of antibiotic resistance in the anaerobes as compared to previous decades. Anaerobe. 2015;31:4-10.  [PMID:24875330]

    Comment: Though still quite uncommon, rates of resistance to amox/clav, amp/sulbactam rising along with moxifloxacin for Bacteriodies/Parabacteroides spp. No resistance has yet been found to tigecycyline. SInce resistance testing not done routinely, we well may not have the full picture.

  3. Karlowsky JA, Walkty AJ, Adam HJ, et al. Prevalence of antimicrobial resistance among clinical isolates of Bacteroides fragilis group in Canada in 2010-2011: CANWARD surveillance study. Antimicrob Agents Chemother. 2012;56(3):1247-52.  [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).

  4. 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. 2008;52(12):4492-6.  [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.

  5. Lassmann B, Gustafson DR, Wood CM, et al. Reemergence of anaerobic bacteremia. Clin Infect Dis. 2007;44(7):895-900.  [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.
    Rating: Important

  6. Gal M, Brazier JS. Metronidazole resistance in Bacteroides spp. carrying nim genes and the selection of slow-growing metronidazole-resistant mutants. J Antimicrob Chemother. 2004;54(1):109-16.  [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.

  7. 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. 2003;52(2):308-11.  [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.

  8. Falagas ME, Siakavellas E. Bacteroides, Prevotella, and Porphyromonas species: a review of antibiotic resistance and therapeutic options. Int J Antimicrob Agents. 2000;15(1):1-9.  [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.
    Rating: Important

  9. Brook I, Frazier EH. Aerobic and anaerobic microbiology of infection after trauma. Am J Emerg Med. 1998;16(6):585-91.  [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.

  10. Rodrigues C, Siciliano RF, Zeigler R, et al. Bacteroides fragilis endocarditis: a case report and review of literature. Braz J Infect Dis. 2012;16(1):100-4.  [PMID:22358367]

    Comment: Review of the literature since 1980 for this rare entity.

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Last updated: January 30, 2016