Recommended Topic Related To:

Pce

"The FDA suspended the food facility registration of Roos Foods Inc. of Kenton Delaware on March 11, 2014 after the FDA determined there was a reasonable probability of food manufactured, processed, packed, or held by Roos Foods causing seri"...

PCE

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.

The erythromycin particles in PCE tablets are coated with a polymer whose dissolution is pH dependent. This coating allows for minimal release of erythromycin in acidic environments, e.g., stomach. This delivery system is designed for optimal drug release and absorption in the small intestine. In multiple-dose, steady-state studies, PCE tablets have demonstrated rapid and generally adequate drug delivery in both fasting and nonfasting conditions. However, the presence of food results in lower blood levels, and optimal blood levels are obtained when PCE tablets are given in the fasting state (at least ½ hour and preferably 2 hours before meals). Bioavailability data are available from Arbor Pharmaceuticals.

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 influenza 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 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
aATCC 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

REFERENCES

1. Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, 7th ed. Approved Standard, CLSI Document M07-A7, Vol. 26(2). CLSI, Wayne, PA, Jan. 2006.

2. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing, 18th Informational Supplement, CLSI Document M100-S18, Vol 28(1). CLSI, Wayne, PA, Jan. 2008.

3. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Disk Susceptibility Tests, 9th ed. Approved Standard CLSI Document M02-A9, Vol. 26(1). CLSI, Wayne, PA, Jan. 2006.

Last reviewed on RxList: 2/24/2012
This monograph has been modified to include the generic and brand name in many instances.

A A A

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Women's Health

Find out what women really need.