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MDR bacteria. Antimicrobial Stewardship Programs (ASPs)

have become widely popular in the United States and

Europe to address this unmet need (4). Such programs

aim to manage antimicrobial use in the acute care setting

through coordinated interventions designed to improve

and measure appropriate use. ASPs, therefore, promote

the selection of optimal antibiotic drug regimens including

dosing, duration of therapy, and route of administration

across the medical center. One component of ASPs is the

consideration and implementation of antibiotic regimens

based on pharmacodynamic concepts. Although the use of

pharmacodynamics to design antibiotic dosing regimens,

such as the continuous infusion of beta-lactams, has been

widely reported in the literature, the strategic design and

implementation of such programs as part of an ASP has been

more elusive.

Herein, a brief review of antimicrobial pharmacodynamics

is provided, followed by discussion of considerations and

strategy regarding where implementation of these dosing

strategies might provide the greatest benefits.

PHARMACODYNAMICS: WHAT’S THE RIGHT DOSE?

Inappropriate antibiotic therapy is most often a result

of delayed administration (i.e., waiting for culture or

susceptibility results before initiating antibiotics or

starting therapy as a result of a positive culture) or,

more often, an underestimation of current trends in

resistance. Regardless, the classification of an organism as

“Susceptible”, “Intermediate”, or “Resistant” does not inform

the prescriber of the ideal dose to use for the infection.

Instead, the term “optimal antibiotic therapy” should be

used and is meant to indicate that not only is the correct

antibiotic selected, but also that the dosage is sufficient

to obtain the maximal exposure threshold determined

from pharmacodynamic studies. An interesting observation

relevant to optimal antibiotic therapy is that the pathogen

need not be “Susceptible” to the drug in question, as long as

the exposure of the agent is sufficient to kill that organism.

Antimicrobial killing characteristics

are dependent on

both the concentration of drug in relation to the

minimum

inhibitory concentration (MIC)

and

the time that

this exposure is maintained

(Figure 1) (5). When the

effect of concentration predominates over that of time,

the antibiotic displays concentration-dependent effects

that are significantly associated with an optimal free drug

maximum concentration to MIC ratio (fC

max

/MIC). When

the effect of time is greater, the antibiotic displays time-

dependent effects, and bacterial outcomes are associated

with free drug concentrations remaining above the MIC for a

FIGURE 1. DEPICTION OF PHARMACODYNAMIC PARAMETERS OVER A CONCENTRATION TIME PROFILE

MIC: Minimum inhibitory concentration; Cmax/MIC: Maximum concentration to MIC ratio; AUC/MIC: Area under the curve to MIC ratio; T>MIC: Time

above the MIC.

Concentration (mg/L)

Time (hr)

Cmax/MIC

AUC/MIC

MIC

T>MIC

[REV. MED. CLIN. CONDES - 2016; 27(5) 615-624]