Choice of an Antimicrobial Agents- Drug Related Factors, B. Pharm

2. 1) SPECTRUM OF ACTIVITY:
For definitive therapy,
narrow-spectrum
drug:
For empirical therapy,
broad-spectrum drug:
 Selectively affect
concerned organism.
 More effective than a
broad-spectrum AMA.
 Less likely to disturb
normal microbial
flora.
 Cover all likely
pathogens.
 May disturb normal
microbial flora.

3. 2) TYPE OF ACTIVITY:
Infection in patients with normal host defence-
responds equally to both bacteriostatic & bactericidal
AMAs.
Acute infections resolves faster with bactericidal
drugs than bacteriostatic & also bactericidal are
superior to treating patients with impaired host
defence, life threatening infections, infections at less
accessible sites(SABE) or when carrier state is
possible(typhoid); because-

4. BACTERICIDAL: BACTERIOSTATIC:
 Reduces number of
bacteria at infectious
site by killing.
 Prolonged post
antibiotic effect so
maintaining drug level
continuously above
MIC is not essential.
 Only prevents increase
in number of the
bacteria.
 Bacteria multiplies
quickly if drug level fall
below MIC resulting in
relapse of infection.

5. 3) SENSITIVITY OF ORGANISM:
Assessed on basis of MIC value (if available) &
consideration of post antibiotic effect.
4) RELATIVE TOXICITY:
Less toxic AMA is preferred.
e.g. Preference: β lactam > amino glycosides,
Erythromycin > clindamycin.

6. 5) PHARMACOKINETIC PROFILE:
For optimum action antibiotic has to be present at
site of infection in sufficient concentration for
adequate length of time. This depends on their
pharmacokinetic characteristics. Most antibiotics are
given at 2-4 half-life intervals, thus attaining
therapeutic concentrations only intermittently. For
many organisms, amino glycosides &
fluoroquinolones produce “concentration dependent
inhibition” & inhibitory effect depends on ratio of
peak conc. to MIC; same daily dose of gentamicin
produces better action when given as a single dose
than if it is divided into 2-3 portions.

7. On other hand, β-lactams, glycopeptides & macrolides
produce “time dependent inhibition” & action
depends on length of time the conc. remains above
MIC; dividing daily dose has better effect. However,
doses should be so spaced that when the surviving
organisms again start multiplying, a cidal action is
exerted.
Penetration at infectious site also depends on
pharmacokinetic property of drug. Better drug
penetration & higher drug conc. at infectious site-
more effective.
e.g.-

8. Fluoroquinolones Excellent tissue penetration
& high conc. in soft tissue,
lungs, prostate, joints, etc.
Ciprofloxin & rifampin Good intracellular
penetration.
Cefuroxime, ceftriaxone,
chloramphenicol,
ciprofloxacin
High CSF conc.
Penicillins & amino glycosides Penetrates poorly in CSF
unless meninges are
inflamed.
Ampicillin, cephalosporins &
erythromycin
High biliary conc.

9. 6) ROUTE OF ADMINISTRATION:
Many AMAs can be given orally as well as
parenterally. Amino glycosides, penicillin-G,
carbenicillin, many cephalosporins, vancomycin, etc.
have to be given by injection only.
For less severe infections, an oral antibiotic is
preferable; but for serious infections, e.g. meningitis,
spreading cellulitis, septicaemias, a parenteral
antibiotic may be chosen.

10. 7) EVIDENCE OF CLINICAL EFFICACY:
Relative value of different AMAs to treat infection is
decided on basis of comparative clinical trials.
Optimum dosage regimens & duration of treatment
are also determined on the basis of such trials.
Reliable clinical data (if available) is the final guide for
choice of antibiotic.
8) COST:
Less expensive drugs are to be preferred.