CLINICAL PHARMACOLOGY
Orally administered erythromycin base and its salts are
readily absorbed in the microbiologically active form. Interindividual
variations in the absorption of erythromycin are, however, observed, and some patients
do not achieve optimal serum levels. Erythromycin is largely bound to plasma
proteins. After absorption, erythromycin diffuses readily into most body
fluids. In the absence of meningeal inflammation, low concentrations are
normally achieved in the spinal fluid but the passage of the drug across the
blood-brain barrier increases in meningitis. Erythromycin crosses the placental
barrier, but fetal plasma levels are low. The drug is excreted in human milk.
Erythromycin is not removed by peritoneal dialysis or hemodialysis.
In the presence of normal hepatic function, erythromycin
is concentrated in the liver and is excreted in the bile; the effect of hepatic
dysfunction on biliary excretion of erythromycin is not known. After oral administration,
less than 5% of the administered dose can be recovered in the active form in
the urine.
Orally administered ERYTHROCIN STEARATE tablets are
readily and reliably absorbed. Optimal serum levels of erythromycin are reached
when the drug is taken in the fasting state or immediately before meals.
Microbiology
Erythromycin acts by inhibition of protein synthesis by
binding 50 S ribosomal subunits of susceptible organisms. It does not affect
nucleic acid synthesis. Antagonism has been demonstrated in vitro between erythromycin
and clindamycin, lincomycin, and chloramphenicol.
Many strains of Haemophilus influenzae are
resistant to erythromycin alone, but are susceptible to erythromycin and
sulfonamides used concomitantly.
Staphylococci resistant to erythromycin may emerge during
a course of erythromycin therapy. Erythromycin has been shown to be active
against most strains of the following microorganisms, both in vitro and in
clinical infections as described in the INDICATIONS AND USAGE section.
Gram-positive Organisms
Corynebacterium diphtheriae
Corynebacterium minutissimum
Listeria monocytogenes
Staphylococcus aureus(resistant organisms may
emerge during treatment)
Streptococcus pneumoniae
Streptococcus pyogenes
Gram-negative Organisms
Bordetella pertussis
Legionella pneumophila
Neisseria gonorrhoeae
Other Microorganisms
Chlamydia trachomatis
Entamoeba histolytica
Mycoplasma pneumoniae
Treponema pallidum
Ureaplasma urealyticum
The following in vitro data are available, but their
clinical s ignificance is unknown.
Erythromycin exhibits in vitro minimal inhibitory
concentrations (MIC's) of 0.5 μg/mL or less against most ( ≥ 90%)
strains of the following microorganisms; however, the safety and effectiveness
of most ( ≥ 90%) strains of the following microorganisms; however, the
safety and effectiveness of erythromycin in treating clinical infections due to
these microorganisms have not been established in adequate and well-controlled
clinical trials.
Gram-positive Organisms
Viridans group streptococci
Gram-negative Organisms
Moraxella catarrhalis
Susceptibility Tests
Dilution Techniques
Quantitative methods are used to determine antimicrobial
minimum inhibitory concentrations (MIC's). These MIC's provide estimates of the
susceptibility of bacteria to antimicrobial compounds. The MIC's should be
determined using a standardized procedure. Standardized procedures are based on
a dilution method1 (broth or agar) or equivalent with standardized
inoculum concentrations and standardized concentrations of erythromycin powder.
The MIC values should be interpreted according to the following criteria:
MIC (pg/mL) |
Interpretation |
≤ 0.5 |
Susceptible (S) |
1-4 |
Intermediate (I) |
≥ 8 |
Resistant (R) |
A report of “Susceptible” indicates that the
pathogen is likely to be inhibited if the antimicrobial compound in the blood
reaches the concentrations usually achievable. A report of “Intermediate”
indicates that the result should be considered equivocal, and, if the
microorganism is not fully susceptible to alternative, clinically feasible
drugs, the test should be repeated. This category implies possible clinical
applicability in body sites where the drug is physiologically concentrated or
in situations where high dosage of drug can be used. This category also
provides a buffer zone which prevents small uncontrolled technical factors from
causing major discrepancies in interpretation. A report of
“Resistant” indicates that the pathogen is not likely to be inhibited
if the antimicrobial compound in the blood reaches the concentrations usually
achievable; other therapy should be selected.
Standardized susceptibility test procedures require the
use of laboratory control microorganisms to control the technical aspects of
the laboratory procedures. Standard erythromycin powder should provide the
following MIC values:
Microorganism |
MIC (pg/mL) |
S. aureus ATCC 29213 |
0.12-0.5 |
E. faecalis ATCC 29212 |
1-4 |
Diffusion Techniques
Quantitative methods that require measurement of zone diameters
also provide reproducible estimates of the susceptibility of bacteria to
antimicrobial compounds. One such standardized procedure2 requires the use of
standardized inoculum concentrations. This procedure uses paper disks
impregnated with 15-μg erythromycin to test the susceptibility of
microorganisms to erythromycin.
Reports from the laboratory providing results of the
standard single-disk susceptibility test with a 15-μg erythromycin disk
should be interpreted according to the following criteria:
Zone Diameter (mm) |
Interpretation |
≥ 23 |
Susceptible (S) |
14-22 |
Intermediate (I) |
≤ 13 |
Resistant (R) |
Interpretation should be as stated above for results
using dilution techniques. Interpretation involves correlation of the diameter
obtained in the disk test with the MIC for erythromycin.
As with standardized dilution techniques, diffusion
methods require the use of laboratory control microorganisms that are used to
control the technical aspects of the laboratory procedures. For the diffusion
technique, the 15-μg erythromycin disk should provide the following zone
diameters in these laboratory test quality control strains:
Microorganism |
Zone Diameter (mm) |
S. aureus ATCC 25923 |
22-30 |
REFERENCES
1. National Committee for Clinical Laboratory Standards. Methods
for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow
Aerobically, Third Edition. Approved Standard NCCLS Document M7-A3, Vol. 13,
No. 25 NCCLS, Villanova, PA, December 1993.
2. National Committee for Clinical Laboratory Standards, Performance
Standards for Antimicrobial Disk Susceptibility Tests, Fifth Edition. Approved
Standard NCCLS Document M2-A5, Vol. 13, No. 24 NCCLS, Villanova, PA, December
1993.