Antimicrobial Therapy

Appropriate management of mixed aerobic and anaerobic infections requires the administration of antimicrobials that are effective against both aerobic and anaerobic components of the infection (7) in addition to surgical correction and drainage of pus. When such therapy is not given, the infection may persist, and more serious complications may occur (8,9).

A number of factors should be considered when choosing appropriate antimicrobial agents. They should be effective against all target organism(s), induce little or no resistance, achieve sufficient levels in the infected site, have minimal toxicity, and have maximum stability and longevity.

Antimicrobials often fail to cure the infection. Some of the reasons they do not work are the development of bacterial resistance, achievement of insufficient tissue levels, incompatible drug interaction, and the development of an abscess. The environment of an abscess is detrimental for many antimicrobials. The abscess fibrotic capsule interferes with the penetration of antimicrobial agents, and the low pH and the presence of binding proteins or inactivating enzymes (i.e., beta-lactamases) may impair the activity of many antimicrobials. The low pH and the anaerobic environment within the abscess are especially deleterious toward the aminoglycosides (10). It should be remembered that an acidic environment, high osmolarity, and presence of an anaerobic environment can develop in an infection site without the presence of an abscess (11).

When choosing antimicrobials for the therapy of mixed infections, the physician should consider their aerobic and anaerobic antibacterial spectrum and their availability in oral or parenteral form (Table 1). Some antimicrobials have a limited range of activity. Metronidazole is active against only anaerobes and therefore cannot be administered as a single agent for the therapy of mixed infections. Other antimicrobials, such as cefoxitin and the carbapenem

TABLE 1 Antimicrobial Agents Effective Against Mixed Infection

Anaerobic bacteria Aerobic bacteria

Anaerobic bacteria Aerobic bacteria

TABLE 1 Antimicrobial Agents Effective Against Mixed Infection

Antimicrobial agent

Beta-lactamase-producing bacteroides

Other anaerobes

Gram-positive cocci

Enterobac-teriacea

Penicillin3

0

+ + +

+

0

Chloramphenicol3

+ + +

+ + +

+

+

Cephalothin

0

+

+ +

+/-

Cefoxitin

+ +

+ + +

+ +

+ +

Imipenem/meropenem/

+ + +

+ + +

+ + +

+ + +

ertapenem

Clindamycin3

+ +

+ + +

+ + +

0

Ticarcillin

+

+ + +

+

+ +

Amoxicillin + clavulanic

+ + +

+ + +

+ +

+ +

acid3

Piperacillin + tazobactam

+ + +

+ + +

+ +

+ +

Metronidazole3

+ + +

+ + +

0

0

Moxifloxacin3

+ +

+ +

+ +

+ + +

Tigecycline

+ +

+ + +

+ + +

+ +

Degrees of activity: 0 to + + +. 3 Available also in oral form.

Degrees of activity: 0 to + + +. 3 Available also in oral form.

(i.e., imipenem, meropenem), have a wider spectrum of activity against Enterobacteriaceae and anaerobes.

Selecting antimicrobial agents is simplified when a reliable culture result is available. However, this may be particularly difficult in anaerobic infections because of the problems in obtaining appropriate specimens. For this reason, many patients are treated empirically on the basis of suspected, rather than established, pathogens. Fortunately, the types of anaerobes involved in many anaerobic infections and their antimicrobial susceptibility patterns tend to be predictable (12,13). However, some anaerobic bacteria have become resistant to antimicrobial agents, and many can become resistant while a patient is receiving therapy (14,15).

The susceptibility of the Bacteroides fragilis group, the most commonly recovered group of anaerobes, to the commonly used antimicrobial drugs was studied systemically over the past several years by collecting strains each year from several medical centers across the U.S.A. (16) and Canada (17). Similar surveys are also available from other countries (Table 2) (18-20). These surveys have shown no resistant strains to chloramphenicol and metronidazole, and resistance to other agents varies. Resistance differs among the contributing centers and generally increases with the extensive use of some of the antimicrobial agents such as penicillins, cephalosporins, and clindamycin.

The results of a multicenter USA survey using the National Committee for Clinical Laboratory Standards evaluated the in vitro susceptibility of 2673 isolates of B. fragilis group species from 1997 to 2000 (16). Declines in the geometric mean minimum inhibitory concentrations (MICs) were seen with imipenem, meropenem, ampicillin-sulbactam, and cephamycins. Increased geometric means were observed with the fluoroquinolones and were usually accompanied by an increase in resistance rates. Bacteroides distasonis shows the highest resistance rates among beta-lactam antibiotics, whereas Bacteroides vulgatus shows the highest resistance levels among fluoroquinolones. B. fragilis shows the lowest resistance rates for all antibiotics. All strains were susceptible to chloramphenicol and metronidazole concentrations less than 8 ng/mL (Table 2). The data underscore the need for species identification and continued surveillance to monitor resistance patterns.

Aside from susceptibility patterns, other factors influencing the choice of antimicrobial therapy include the pharmacologic characteristics of the various drugs, their toxicity, their effect on the normal flora, and bactericidal activity (21). Although identification of the infecting organisms and their antimicrobial susceptibility may be needed for selection of optimal therapy, the clinical setting and Gram stain preparation of the specimen may indicate the types of anaerobes present in the infection as well as the nature of the infectious process.

TABLE 2 Percentage of Antimicrobial Resistance In a National Susceptibility Testing of 589 Bacteroides fragilis Group Isolates in 2000 (in parenthesis—number of tested strains)

Antibiotic

Imipenem

Meropenem

Ertapenem

Piperacillin/tazobactam

Ampicillin/sulbactam

Ticarcillin/clavulanate

Cefoxitin

Cefotetan

Cefmetazole

Clindamycin

Trovafloxacin

Clinafloxacin

TABLE 2 Percentage of Antimicrobial Resistance In a National Susceptibility Testing of 589 Bacteroides fragilis Group Isolates in 2000 (in parenthesis—number of tested strains)

Bacteroides fragilis (288)

Bacteroides distasonis (36)

Bacteroides thetaiotaomicron (136)

Bacteroides ovatus (61)

Bacteroides vulgatus (35)

Bacteroides uniformis (11)

Other3 (22)

Bacteroides fragilis group (589)

0.0

2.8

0.0

0.0

0.0

0.0

0.0

0.2

0.0

2.8

0.0

0.0

0.0

0.0

0.0

0.2

1.0

2.8

0.7

0.0

0.0

0.0

0.0

0.9

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

1.4

5.6

2.2

0.0

2.9

0.0

0.0

1.7

0.4

2.8

1.5

0.0

0.0

0.0

0.0

0.7

3.5

25.0

18.4

14.8

8.6

0.0

13.6

10.0

13.2

66.7

75.7

77.0

28.6

27.3

59.1

40.4

6.6

55.6

69.1

59.0

14.3

18.2

31.8

31.1

16.3

38.9

33.1

44.3

37.1

36.4

18.2

26.1

20.1

33.3

23.5

14.8

62.9

54.5

18.2

24.3

7.6

27.8

16.2

14.8

45.7

18.2

27.3

14.8

a Includes Bacteroides caccae, Bacteroides eggerthii, Bacteroides merdae, and Bacteroides tercoris. Source: From Ret. 16.

Because anaerobic bacteria generally are recovered mixed with aerobic organisms, selection of proper therapy becomes more complicated. In the treatment of mixed infection, the choice of the appropriate antimicrobial agents should provide for adequate coverage of most of the pathogens. Some broad-spectrum antibacterial agents possess such qualities, while for some organisms additional agents should be added to the therapeutic regimen.

Antimicrobial therapy for anaerobic infections usually should be given for prolonged periods because of their tendency to relapse.

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