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Combinations of antimicrobials

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Combinations of antimicrobials are generally used to broaden the spectrum of coverage for empiric therapy, achieve synergistic activity against the infecting organism, and prevent the emergence of resistance. Increasing the coverage of antimicrobial therapy is generally necessary in mixed infections in which multiple organisms are likely to be present, such as intraabdominal and female pelvic infections in which a variety of aerobic and anaerobic bacteria may produce disease. Another clinical situation in which increased spectrum of activity is desirable is with nosocomial infection.

Synergism

The achievement of synergistic antimicrobial activity is advantageous for infections caused by gram-negative bacilli in immunosuppressed patients. Traditionally, combinations of aminoglycosides and β-lactams have been used because these drugs together generally act synergistically against a wide variety of bacteria. However, the data supporting superior efficacy of synergistic over nonsynergistic combinations are weak.


Synergistic combinations may produce better results in infections caused by Pseudomonas aeruginosa, as well as in certain infections caused by Enterococcus spp. The use of combinations to prevent the emergence of resistance is widely applied but not often realized. The only circumstance in which this has been clearly effective is in the treatment of tuberculosis.

Disadvantages of Combination Therapy

Although there are potentially beneficial effects from combining drugs, there are also potential disadvantages, including increased cost, greater risk of drug toxicity, and superinfection with even more resistant bacteria.




Some combinations of antimicrobials are potentially antagonistic. For example, agents that are capable of inducing β-lactamase production in bacteria (eg, cefoxitin) may antagonize the effects of enzyme-labile drugs such as penicillins or imipenem.

MONITORING THERAPEUTIC RESPONSE

After antimicrobial therapy has been instituted, the patient must be monitored carefully for a therapeutic response. Culture and sensitivity reports from specimens collected must be reviewed. Use of agents with the narrowest spectrum of activity against identified pathogens is recommended.

Patient monitoring should include a variety of parameters, including WBC count, temperature, signs and symptoms of infection, appetite, radiologic studies as appropriate, and determination of antimicrobial concentrations in body fluids.

As the patient improves, the route of antibiotic administration should be reevaluated.
Switching to oral therapy is an accepted practice for many infections. Criteria favoring the switch to oral therapy include the following:
Over all clinical improvement
Lack of fever for 8 to 24 hours
Decreased WBC
A functioning gastrointestinal (GI) tract

Combinations of antimicrobials Combinations of antimicrobials Reviewed by gafacom on June 23, 2019 Rating: 5

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