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, 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.
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. 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 many report declining rates of susceptibility 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 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 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 as monotherapy for the 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. The drug is no longer manufactured routinely 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.
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.
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 the treatment of intra-abdominal sepsis of community-onset or low severity. No longer available in the U.S.
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.
Usually same anaerobic spectrum as imipenem; however, the drug has been used less often in clinical trials for anaerobic processes.
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.
Comment: The first described resistance, the nim gene, in Bacteroides now with 11 nim genes known (nimA to nimK). Mostly 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 described to both MTZ and carbapenems previously in B. thetaiotaomicron, this is the first report in which an isolate is resistant to both.
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 tigecycline. Since resistance testing not done routinely, we well may not have the full picture.
Comment: A 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).
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.
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.
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.
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.
Comment: Review of the literature since 1980 for this rare entity.
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