Bacteroides species

Paul G. Auwaerter, M.D.

MICROBIOLOGY

  • Pleomorphic, Gram-negative bacilli
    • Obligate anaerobes, but among the most aerotolerant
    • Easily cultivated
  • Clinically significant species: B. fragilis, B. thetaiotaomicron, B. vulgatus, B. distasonis, B. ovatus, B. uniformis, B. caccae.
  • Antimicrobial susceptibilities:
    • B. fragilis is the most commonly resistant organism, with low rates of resistance (1-2% range) in the U.S. and Europe.
      • Reports of higher carbapenem resistance rates reported from Taiwan (7-12%), Germany (4.9-5.3%) and Canada (2.3-12.7%)
      • Multidrug-resistant B. fragilis with simultaneous resistance to carbapenems and metronidazole have also been identified.[12][5]

CLINICAL

  • See the separate B. fragilis module for information on that species as the most commonly pathogenic of the Bacteriodes species.
  • Bacteroides are typical components of intestinal, oral and vaginal flora.
  • Most clinically significant in polymicrobial infections, abscesses.
  • Virtually all members of the genus are sensitive to metronidazole, carbapenems, and beta-lactam/beta-lactamase inhibitor combinations, so speciation is not usually necessary.
  • Diagnosis:
    • Culture only uncontaminated specimens: e.g., blood, peritoneal or pleural fluid, or abscess aspirates.
    • Routine anaerobic culture of community-acquired intra-abdominal infections is considered optional.
      • Consider susceptibility testing if persistent isolation, lack of therapeutic response or if considering prolonged therapy due to immunosuppression.

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, 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

Adjunctive therapy

  • Critical to consider surgical or percutaneous catheter drainage of abscess or devitalized tissue.
  • Exception: most tuboovarian abscesses, some brain (multiple or ≤ 2cm) and smaller liver abscesses respond sufficiently to abx alone.
  • Hyperbaric oxygen has not been demonstrated to be helpful 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, and many coliforms; activity vs. Enterobacteriaceae less than ticarcillin/clavulanate and piperacillin/tazobactam. It has no against Pseudomonas or many nosocomial Enterococcus infections. It may be adequate for community-acquired sepsis, but rates of resistance among E. coliis rising, and no longer recommended for empiric therapy unless local antibiograms dictate. It could be used if cultures do not indicate resistance.

Cefotaxime

Cephalosporins other than cefoxitin and cefotetan are unsuitable for anaerobes in general; in vitro activity variable, clinical experience is nil as monotherapy.

Cefotetan

This drug is often thought of 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 imipenem or beta-lactam/beta-lactamase inhibitors, but the clinical experience is extensive and good historically, although resistance is rising. It 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 1970s. It still performs, but reports are now routine for lower susceptibility rates by B. fragilis and other anaerobes in recent years compared to the ’70s & ’80s. 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 the 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 similar to moxifloxacin, but the published clinical experience is less. No longer available in the U.S. market.

Gentamicin

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

The nitroimidazole class is the most potent antibiotic available for anaerobic bacterial infection. Virtually all strains of B. fragilis are susceptible though some countries now describe rising resistance, especially among B. fragilis or B. thetaiotaomicron isolates. 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, bactericidal 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 now show substantial resistance, though the FDA approved it as monotherapy for treating complicated intra-abdominal infections. I would only consider mild-moderate infections with adequate drainage/surgical intervention or mild community infections, e.g., diverticulitis.

Piperacillin

This is a reasonably good drug for B. fragilis. The usual resistance mechanism is beta-lactamase production, so piperacillin/tazobactam is better in vitro. However, the high dose of piperacillin overcomes this resistance that has made penicillin passé for B. fragilis. The drug is no longer manufactured 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/clavulanate 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 treating 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 the growth of anaerobes.

Ertapenem

It may have a bit less anaerobic activity than imipenem but significantly lacks anti-pseudomonal activity, so it would only use empirically for community-onset or mild-moderate infections.

Doripenem

In vitro sensitivity testing may be more active for some B. fragilis than ertapenem, ampicillin/sulbactam. Still, some studies have shown it 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

  • Usually unnecessary to offer empiric double-coverage for anaerobic Bacteroides (e.g., metronidazole + carbapenem [such as ertapenem or meropenem]).
  • Due to increasing resistance rates, do not use the following drugs for severe infections where B. fragilis is suspected: most resistance is due to beta-lactamase production.
  • For intra-abdominal sepsis—treat B. fragilis and E. coli; this covers everything common and essential.
  • B. fragilis is the most common species causing anaerobic bacteremia.
  • B. melaninogenicus is a common species in lung abscess, oto/odontogenic infection.
  • Variable in vitro susceptibilities for non-fragilis Bacteroides (maybe as low as 50-65%): clindamycin, cefoxitin, cefotetan, moxifloxacin, especially, but also seen for beta-lactamase inhibitor combinations and tigecycline (see recent UK study[2]).
    • Metronidazole remains the best performer.
    • Consider anaerobic susceptibility testing for any isolate in a severely ill patient.
  • Research in the intestinal microbiome and also the potential association with malignancies is very active.

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 Bacteroides spp. most often associated with intra-abdominal infection, the main recommendations for treatment of a polymicrobial infection are referenced within this module. This outdated guideline is undergoing revision (2022).

References

  1. Copsey-Mawer S, Hughes H, Scotford S, et al. UK Bacteroides species surveillance survey: Change in antimicrobial resistance over 16 years (2000-2016). Anaerobe. 2021;72:102447.  [PMID:34560274]

    Comment: Authors now state that in the UK, anaerobic susceptibility testing should be routine. Among 224 isolates from 2000 to 168 in 2016, Bacteroides fragilis was the most common species. B. thetaiotaomicron (10% in 2000; 9% in 2016), B. ovatus (6%; 4%) and B. vulgatus (6%; 3%). B. uniformis, B. xylanisolvens, B. dorei, B. stercoris, B. caccae, B. faecis and B. cellulosilyticus were isolated in < 2% specimens. There was an overall increase in the rates of non-susceptible isolates between the cohorts. Clindamycin was the worst performer in the non-B. fragilis groups at 25.4% resistance. Metronidazole remained effective with only 2.4% resistance by the nim gene in the B. fragilis cohort, but this represented a 6x increase and the most remarkable rise of any antimicrobial tested. For the non-fragilis Bacteroides group tested against amox/clav reduced susceptibility was seen at 12.7% in 2000, rising to 31.5% in 2016. Meropenem resistance was seen in this non-B. fragilis group was moving up to 2.6% of these isolates. Moxifloxacin was 9.9% in 2000 to 26.3% in 2016. Tigecycline 3.9 to 14.6%. The non-fragilis group had higher levels of MDR (15.8%), including five isolates resistant to four classes of antimicrobials

  2. Kouhsari E, Mohammadzadeh N, Kashanizadeh MG, et al. Antimicrobial resistance, prevalence of resistance genes, and molecular characterization in intestinal Bacteroides fragilis group isolates. APMIS. 2019;127(6):454-461.  [PMID:30803024]

    Comment: A study from India found that MTZ-resistant strains were found in 3 non-B. fragilis of total Bacteroides spp. isolates (n=475): one each for B. thetaiotaomicron, B. vulgates, and B. ovatus.

  3. Alauzet C, Lozniewski A, Marchandin H. Metronidazole resistance and nim genes in anaerobes: A review. Anaerobe. 2019;55:40-53.  [PMID:30316817]

    Comment: The first described resistance, the nim gene, in Bacteroides now with 11 nim genes known (nimA to nimK). Most are reported in Bacteroides fragilis group. Resistance rates in Bacteroides described with reduced susceptibilities in Greece (11.7%) and Pakistan (16%) among the highest yet described. That said, resistance is not wholly related to the nim genes, so other factors likely.

  4. 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 previously described to both MTZ and carbapenems in B. thetaiotaomicron, this is the first report in which an isolate is resistant to both.

  5. 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 relatively uncommon, rates of resistance to amoxicillin/clavulanate, ampicillin/sulbactam rising along with moxifloxacin for Bacteriodies/Parabacteroides spp. No resistance has yet been found to tigecycline. Since resistance testing is not done routinely, we may not have the complete picture.

  6. 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: A Canadian study of the Bacteroides fragilis group (n = 387) collected in 2010-2011 was tested by the 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 piperacillin-tazobactam and imipenem. Since the last published surveillance study describing Canadian isolates of the 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).

  7. 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, including those infections due to Bacteroides species. The primary reason for this observation is the 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

  8. 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 the clinical resistance mechanisms observed here may be applicable in the future. The molecular basis of the resistance was not determined.

  9. 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 the outgrowth of Bacteroides spp. despite a rise in the MIC of these bacteria to clindamycin.

  10. 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 had 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.

  11. 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.

  12. Zafar H, Saier MH. Gut Bacteroides species in health and disease. Gut Microbes. 2021;13(1):1-20.  [PMID:33535896]

    Comment: Many complex interactions between these organisms and the gut are known in science; however, their ramifications have yet to be anywhere close to fully elucidated to understand issues related to metabolism, immunity or malignancy.

Bacteroides species is a sample topic from the Johns Hopkins ABX Guide.

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Last updated: December 11, 2022