CLINICAL PHARMACOLOGY
Orally administered erythromycin ethylsuccinate suspensions and Filmtab
tablets are readily and reliably absorbed. Comparable serum levels
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 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
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 method1,2 (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:
For Staphylococcus spp:
|
MIC (μg/mL)
|
Interpretation
|
| ≤ 0.5 |
Susceptible (S) |
| 1-4 |
Intermediate (I) |
| ≥ 8 |
Resistant (R) |
For Streptococcus spp. and Streptococcus pneumoniae:
|
MIC (µg/mL)
|
Interpretation
|
| ≤ 0.25 |
Susceptible (S) |
| 0.5 |
Intermediate (I) |
| ≥ 1 |
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 ATCCa 29213 |
0.25-1 |
|
E. faecalis ATCC 29212 |
1-4 |
|
S. pneumoniae ATCC 49619 |
0.03-0.12 |
a. ATCC is a registered trademark of the American Type Culture Collection
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 procedure2,3 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:
For Staphylococcus spp:
|
Zone Diameter (mm)
|
Interpretation
|
| ≥ 23 |
Susceptible (S) |
| 14-22 |
Intermediate (I) |
| ≤ 13 |
Resistant (R) |
For Streptococcus spp. and Streptococcus pneumoniae:
|
Zone Diameter (mm)
|
Interpretation
|
| ≥ 21 |
Susceptible (S) |
| 16-20 |
Intermediate (I) |
| ≤ 15 |
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 |
|
S. pneumoniae ATCC 49619 |
25-30 |
|
