Medical Care
The patient's recovery from anaerobic infection depends on prompt and proper management according to the following 3 principles:
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Toxins produced by anaerobes must be neutralized.
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The environment must be changed to prevent local bacterial proliferation.
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The spread of bacteria must be limited.
The environment is controlled by debriding necrotic tissue, draining pus, improving circulation, alleviating obstruction, and increasing tissue oxygenation.
Certain types of adjunctive therapy, such as hyperbaric oxygen therapy, may be useful but remain unproven.
In many cases, antimicrobial therapy is the only form of therapy required, but it can also be used as an adjunct to a surgical approach.
Because anaerobic bacteria are generally recovered mixed with aerobic organisms, the appropriate choice for antimicrobial agents should provide adequate treatment of both groups of pathogens.
When choosing antimicrobials for the treatment of mixed infections, consider their aerobic and anaerobic antibacterial spectrum and their availability in oral or parenteral form.
Some antimicrobials have a limited range of activity. For example, metronidazole is active only against anaerobes and cannot be administered as a single agent in mixed infections. Others, such as imipenem, have wide spectra of activity against aerobes and anaerobes.
Because culture results are often not available, many patients are treated empirically. [1, 6]
Antimicrobial resistance patterns may vary. [33, 34] Some anaerobes have become, or may become, resistant to antimicrobials. Resistance rates vary among different geographic regions and institutions, and some antibiotic regimens that were used in the past are no longer considered adequate for empiric therapy. The major increase in antimicrobial resistance for AGNB is of clindamycin, cefoxitin, and cefotetan. The B fragilis group is almost uniformly susceptible to metronidazole, carbapenems, chloramphenicol, and combinations of a penicillin and beta-lactamase inhibitors. Resistance to other agents varies.
Multidrug antimicrobial resistance (MDR) in anaerobes including AGNB is increasing. [1, 35] Bacteroides fragilis group isolates have numerous resistance determinants such as multidrug efflux pumps and cfiA and nimB genes and activating insertion sequences; some isolates exhibited extensive drug-resistant patterns. MDR rates in B fragilis group were from 1.5 to >18% and up to >71% in cfiA and nimB positive isolates carrying insertion sequences. MDR was found in Prevotella spp. (in ≤10% of isolates), and Finegoldia magna. [35]
Recent reports of multidrug-resistant B fragilis [36, 37] underscore the need for improved antibiotic stewardship. Although B fragilis has long been considered reliably susceptible to a number of broad-spectrum antianaerobic drugs, [4] these cases suggest clinicians should no longer rely on cumulative susceptibility data from surveys alone to direct treatment and should consider requesting susceptibility testing when treating serious infections caused by B fragilis.
Aside from susceptibility patterns, other factors that influence the choice of antimicrobials include their pharmacokinetics, their toxicity, their effect on the normal florae, their bactericidal activity, and their ability to penetrate into sites of infection.
Although identification of organisms and their susceptibility is needed for optimal therapy, the clinical setting and the Gram stain results from the specimen are often helpful.
Antimicrobials useful in anaerobic infection are as follows [31] :
Penicillins
Penicillin G is still the drug of choice against most non–beta-lactamase–producing AGNB. However, in addition to the B fragilis group, which is resistant to penicillin, other AGNB show increased resistance. These include pigmented Prevotella and Porphyromonas species, P bivia, P disiens, Bilophila wadsworthia, and Bacteroides splanchnicus.
The combination of beta-lactamase inhibitors (eg, clavulanic acid, sulbactam, tazobactam) with a beta-lactam antibiotic (eg, ampicillin, amoxicillin, ticarcillin, piperacillin) can overcome these beta-lactamase–producing AGNB.
In high concentrations, ticarcillin, piperacillin, and mezlocillin have good activity against gram-negative enteric bacilli and most anaerobes; however, they are not completely resistant to beta-lactamase.
Anaerobes manifest 3 major mechanisms of resistance to beta-lactam antibiotics: inactivating enzymes, mainly beta-lactamases, which include penicillinases and cephalosporinases; low-affinity penicillin-binding proteins (PBPs); and decreased permeability through alterations in the porin channel. [4]
Cephalosporins
The B fragilis group, Prevotella species, and Porphyromonas species are resistant to first-generation cephalosporins by virtue of cephalosporinase production. [38]
Cefoxitin is the most effective cephalosporin against the B fragilis group, although 5-15% may be resistant. Cefoxitin is inactive against most clostridial organisms, except Clostridium perfringens. Other second-generation cephalosporins, such as cefotetan and cefmetazole, have a longer half-life than cefoxitin and are as effective as cefoxitin against B fragilis; however, they are less efficacious against other members of the B fragilis group.
Carbapenems
These agents, including imipenem, meropenem, doripenem, and ertapenem have excellent activity against a broad spectrum of aerobic and anaerobic bacteria. Two recent reports have noted the development of some carbapenem resistance among anaerobes, [31, 39] ranging from 1.1 to 2.5% in a multicenter US survey, but with a higher rate for a small number of isolates from Taiwan. [40]
Chloramphenicol
This agent shows excellent in vitro activity against most anaerobic bacteria, and resistance is rare; however, the development of less-toxic newer agents has limited their use. The drug has a somewhat unique property of lipid solubility to permit penetration across lipid barriers and achieves high concentrations in the CNS, even in the absence of inflammation.
Macrolides (erythromycin, azithromycin, and clarithromycin)
The macrolides have moderate-to-good in vitro activity against anaerobic bacteria other than the B fragilis group strains and fusobacteria. [4] Macrolides are active against pigmented Prevotella and Porphyromonas species and microaerophilic streptococci, gram-positive non–spore-forming anaerobic bacilli, and certain clostridia. They are less effective against Fusobacterium and Peptostreptococcus species. [41] They show relatively good activity against Clostridium perfringens and poor or inconsistent activity against AGNB. The emergence of erythromycin-resistant organisms during therapy has been documented and reached up to 50% in recent studies. [42, 43]
Clindamycin
This antimicrobial is effective against aerobic gram-positive cocci. Although the patterns differ by region, B fragilis resistance to clindamycin is increasing worldwide. Resistance of the B fragilis group in some centers in the United States and Europe recently reached about 40%. [44] Up to 10% resistance was noted for Prevotella,Fusobacterium, Porphyromonas, and Peptostreptococcus species, with higher rates for some Clostridium species (especially C difficile). [45] This agent therefore can not be used as empiric therapy. Antibiotic-associated colitis due to C difficile, although associated with most antimicrobials, was first described following clindamycin therapy.
Metronidazole
This has excellent activity against anaerobes, including AGNB; however, this efficacy is limited to anaerobes. Microaerophilic streptococci, P acnes, and Actinomyces species are often resistant; therefore; adding an antimicrobial that is effective against these organisms (eg, penicillin) often is necessary. Only 9 strains of the B fragilis group were ever reported to be clinically resistant and associated with therapeutic failure. [4, 46] Aerobic and facultative anaerobes, such as coliforms, are usually highly resistant.
Tetracyclines
Tetracycline, once the drug of choice for anaerobic infections, is presently of limited usefulness because of the development of resistance to it by virtually all types of anaerobes, including Bacteroides and Prevotella species. Resistance to P acnes has been related to previous use. [47] Only about 45% of all B fragilis strains are susceptible to this drug. [4] The newer tetracycline analogs doxycycline and minocycline are more active than the parent compound.
Because of the significant resistance to these drugs, they are useful only when susceptibility tests can be performed or in less severe infections in which a therapeutic trial is feasible. Doxycycline is effective against chlamydial and mycoplasmal infections and is added to most regimens when treating pelvic infections. The use of tetracycline is not recommended in patients younger than 8 years because of the adverse effect on teeth.
Tigecycline
This glycylcycline has effective in vitro activity against both gram-positive and gram-negative anaerobes, as well as against gram-positive aerobic strains such as methicillin-resistant staphylococci, streptococci, and enterococci. Resistance of members of the B fragilis group varied from 3.3% to 7.2%. [31] Tigecycline was approved by the FDA for the treatment of complicated skin and skin-structure infections and complicated intra-abdominal infections.
Quinolones
Trovafloxacin, moxifloxacin, and gatifloxacin yield low minimum inhibitory concentrations (MICs) against most groups of anaerobes. Moxifloxacin was approved by the FDA for the treatment of complicated skin and skin-structure infections and complicated intra-abdominal infections. However, up to 50% of Bacteroides isolates are resistant to moxifloxacin. [48, 49] The use of the quinolones is restricted in growing children and pregnancy because of their possible adverse effects on the cartilage.
Surgical Care
In most cases, surgical therapy is of critical importance. Surgical therapy includes draining abscesses, debriding necrotic tissues, decompressing closed-space infections, and relieving obstructions. [1, 18]
When surgical drainage is not used, the infection may persist and serious complications may develop.
