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.
Optimal blood levels are obtained when Erythromycin Base Filmtab (erythromycin tablets) tablets are given in the fasting state (at least 1/2 hour and preferably 2 hours before meals). Bioavailability data are available from Abbott Laboratories, Dept. 42W.
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 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 significance
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 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 (µg/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 (µg/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.