Community-acquired intra-abdominal infections/Adults
Mild-moderate severity (perforations/appendicitis)
High risk or severity/advanced age or immunocompromise
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.
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%.
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.
No activity in vitro vs. B. fragilis.
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.
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.
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.
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.
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.
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.
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.
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.
Usually same anaerobic spectrum as imipenem; however, the drug has been used less often in clinical trials for anaerobic processes.
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).
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
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.
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.
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.
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.
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).
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.
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.
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.
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.
Comment: Review of the literature since 1980 for this rare entity.
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.