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MIC) can be comfortably exceeded by doses tolerated by the patient.Most agents are bound to some extent to serum albumin, and the protein-bound form is usually unavailable for antimicrobial action.Because the influence of antimicrobials on the natural history of different categories of infection (eg, pneumonia, meningitis, diarrhea) varies, clinical trials may include both a range of bacterial species and different infected sites (eg, lung, bone, CSF).Other characteristics include whether the agents are absorbed from the upper gastrointestinal tract, whether they are excreted and concentrated in active form in the urine, whether they can pass into cells, whether and how rapidly they are metabolized, and the duration of effective antimicrobial levels in blood and tissues.Furthermore, in urinary infections, urine levels of some antimicrobial agents may be very high (eg, fluo- roquinolones), and organisms that are resistant in vitro may be eliminated in the patient.With regard to organisms, use of the term susceptible (sensitive) implies that their MIC is at a concentration attainable in the blood or other appropriate body fluid (eg, urine) using recommended doses.For example, less toxic antibiotics such as the penicillins and cephalosporins can be administered in massive amounts and may thereby inhibit some pathogens that would normally be considered resistant in vitro.

MIC) can be comfortably exceeded by doses tolerated by the patient. Use of the antimicro-
bial in animal models and then human infections must also have demonstrated a thera-
peutic response. Because the influence of antimicrobials on the natural history of different
categories of infection (eg, pneumonia, meningitis, diarrhea) varies, clinical trials may
include both a range of bacterial species and different infected sites (eg, lung, bone, CSF).
These clinical studies are important to determine whether what should work actually does
work and, if so, to define the parameters of success and failure. Physicians must decide
whether the evidence used to earn FDA approval for a new antimicrobial applies to the
particular circumstances of the case before them.
Once these factors are established, the routine selection of therapy can be based on
known or expected characteristics of organisms and pharmacologic features of antimicro-
bial agents. With regard to organisms, use of the term susceptible (sensitive) implies that
their MIC is at a concentration attainable in the blood or other appropriate body fluid (eg,
urine) using recommended doses. Resistant, the converse of susceptible, implies that the
MIC is not exceeded by normally attainable levels. As in all biological systems, the MIC
of some organisms lies in between the susceptible and resistant levels. Borderline strains
are called intermediately sensitive. The antimicrobial in question may still be used to treat
these organisms, but at increased doses. For example, less toxic antibiotics such as the
penicillins and cephalosporins can be administered in massive amounts and may thereby
inhibit some pathogens that would normally be considered resistant in vitro. Furthermore,
in urinary infections, urine levels of some antimicrobial agents may be very high (eg, fluo-
roquinolones), and organisms that are resistant in vitro may be eliminated in the patient.
Important pharmacologic characteristics of antimicrobial agents include dosage as well
as the routes and frequency of administration. Other characteristics include whether the
agents are absorbed from the upper gastrointestinal tract, whether they are excreted and
concentrated in active form in the urine, whether they can pass into cells, whether and how
rapidly they are metabolized, and the duration of effective antimicrobial levels in blood and
tissues. Most agents are bound to some extent to serum albumin, and the protein-bound
form is usually unavailable for antimicrobial action. The amount of free to bound antibi-
otic can be expressed as an equilibrium constant, which varies for different antibiotics. In
general, high degrees of binding lead to more prolonged but lower serum levels of an active
antimicrobial after a single dose.