CLINICAL PHARMACOLOGY
Orally administered erythromycin ethylsuccinate suspensions and Filmtab tablets
are readily and reliably absorbed. Comparable serum levels (erythromycin ethylsuccinate) of erythromycin are
achieved in the fasting and nonfasting states.
Erythromycin diffuses readily into most body fluids. Only low concentrations
are normally achieved in the spinal fluid, but passage of the drug across the
blood-brain barrier increases in meningitis. In the presence of normal hepatic
function, erythromycin is concentrated in the liver and excreted in the bile;
the effect of hepatic dysfunction on excretion of erythromycin by the liver
into the bile is not known. Less than 5 percent of the orally administered dose
of erythromycin is excreted in active form in the urine.
Erythromycin crosses the placental barrier, but fetal plasma levels (erythromycin ethylsuccinate) are low.
The drug is excreted in human milk.
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.
Staphylocci resistant to erythromycin may emerge during a course of 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 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 (erythromycin ethylsuccinate) 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 25923 |
0.12-0.5 |
E. faecalis ATCC 29212 |
1-4 |
Diffusion Techniques
Quantitative methods that require measurement of zone diameters (erythromycin ethylsuccinate) 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 15Â 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 (erythromycin ethylsuccinate) 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.