Principles Of Antimicrobial Therapy

Appropriate management of mixed pulmonary aerobic and anaerobic infections requires the administration of antimicrobials that are effective against both the aerobic and anaerobic components of the infection (1,5,18). When such a therapy is not given, the infection may persist and more serious complications may occur (1,5,18).

The appropriate antimicrobial choice depends on the susceptibility of the organisms to antimicrobials. Unfortunately, the susceptibility of anaerobic bacteria to antimicrobial agents has become less predictable. Resistance to several antimicrobial agents by B. fragilis group and other AGNB has increased over the past three decades (19). Although routine susceptibility testing of all anaerobic isolates is unnecessary, it is important to perform susceptibility testing of isolates recovered from sterile body sites or those that are clinically important and have variable or unique susceptibility (20). Testing should be limited to those anaerobes isolated from blood cultures, pulmonary infections, and those isolated in pure culture. In addition to susceptibility testing, screening of AGNB for the production of the enzyme beta-lactamase may be helpful. Such screening can rapidly provide information regarding the organism's penicillin susceptibility. However, occasional bacterial strains may resist beta-lactam antibiotics through mechanisms other than the production of beta-lactamase.

When choosing antimicrobials for the therapy of polymicrobial pulmonary infections, their aerobic and anaerobic antibacterial spectrum should be considered. An attempt should be made to cover most or at least the most predominant organisms (with the heaviest growth in culture), with a single agent or a combination of agents. Some antimicrobials have a limited range of activity. Metronidazole is active only against anaerobes, and aminoglycosides and the "older"quinolones (i.e., ciprofloxacin) are mostly effective against Enterobacteriaceae. None of these agents can be administered as a single agent for the therapy of mixed infection. Others such as a penicillin plus a beta-lactamase inhibitor or a carbapenem have a wider spectrum of activity against Enterobacteriaceae and anaerobes.

Antimicrobial therapy may be guided by Gram stain of appropriate material but should not be withheld pending culture results in severely ill patients. Penicillin G may no longer be effective in the treatment of pleuropulmonary infections when BLPB are present. Two studies in adults showed clindamycin (which is more effective against anaerobic BLPB) to be more effective than penicillin in the treatment of lung abscesses in adults (21,22). A recent retrospective study illustrates the superiority of antimicrobials effective against penicillin-resistant anaerobic bacteria (ticarcillin-clavulanate or clindamycin) as compared to an antibiotic without such coverage (ceftriaxone) in the therapy of aspiration or tracheostomy-associated pneumonia in 57 children (23).

Antimicrobial therapy is directed at the major pathogens. Antimicrobials that are effective against penicillin-resistant anaerobic organisms are clindamycin, cefoxitin, chloramphenicol, metronidazole, the "newer" quinolones (i.e., moxifloxacin), a carbapenem (i.e., imipenem, meropenem, ertapenem), tigecycline or the combination of a penicillin plus a beta-lactamase inhibitor. Penicillin should be added to metronidazole to cover microaerophilic and anaerobic streptococci. Coverage against Enterobacteriaceae or P. aeruginosa may require the addition of an aminoglycoside, a quinolone, or a wide-spectrum cephalosporin (i.e., cefepime). When antistaphylococcal coverage is needed, a penicillinase-resistant penicillin (i.e., oxacillin), vancomycin, tigecycline, or linezolid should be administered. The last three agents are also effective against methicillin resistant staphylococci.

Therapy of community-acquired aspiration pneumonia is generally with clindamycin or combination of a penicillin plus a beta-lactamase inhibitor. In hospital-acquired aspiration pneumonia, coverage against Enterobacteriaceae or P. aeruginosa is also required by adding an effective agent or using a carbapenem.

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