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Chapter 34: General Principles of Antimicrobial Therapy

A 43-year-old man is neutropenic and has developed a fever. After obtaining the appropriate cultures, you decide to start him on a broad-spectrum antibacterial and antifungal therapy. Your decision fits which of the following goals of antimicrobial therapy?

a. Prophylaxis

b. Definitive

c. Empirical

d. Preemptive

e. Post-treatment suppression

Answer is c. This is termed empiric therapy (see Figure 34-4). Neutropenic patients with fever have a high risk of mortality, and when febrile, they are presumed to have either a bacterial or fungal infection. Once the pathogen is identified and susceptibility determined the broad-spectrum therapy can be switched to a specific antimicrobial agent.


Figure 34-4. Antimicrobial therapy-disease progression timeline. Stages of disease progression are below the horizontal arrow; categories of antimicrobial therapy are above the arrow.

Typically the time when the antibiotic concentration is greater than the MIC is less with once-daily dosing than if the antibiotic were administered in 3 equally divided doses. However, aminoglycoside antibiotics are commonly administered once daily. The efficacy of once-daily dosing of aminoglycosides is due to

a. decreased toxicity.

b. increased renal excretion at higher doses.

c. less bacterial resistance to the antibiotic.

d. postantibiotic effect.

e. the rate of increase in the initial plasma concentration.

Answer is d. The peak antibiotic plasma concentration is what matters for some antimicrobial agents, such as aminoglycosides, and the persistence above MIC has less relevance. These drugs can be administered less frequently due to their long duration of postantibiotic effect. That is, their antibacterial effect continues long after antibiotic concentrations decline below the MIC.

Bacterial resistance to β-lactam antibiotics (eg, penicillin) is usually due to the bacterial production of β-lactamase. This results in

a. destruction of the antibiotic.

b. reduced affinity to a bacterial protein.

c. enhanced efflux of the antibiotic from the bacteria.

d. decreased entry of the antibiotic into the bacteria.

e. development of an alternative mechanism of bacterial survival in the presence of antibiotic.

Answer is a. β-lactamase is an enzyme that destroys antibiotics that contain a β-lactam in their chemical structure (see Chapter 39...

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