Erythromycin Capsules

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 acceptable serum levels. Erythromycin is largely bound to plasma proteins, and the freely dissociating bound fraction after administration of erythromycin base represents 90% of the total erythromycin absorbed. 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. The drug is excreted in human milk. The drug crosses the placental barrier, but fetal plasma levels are low. 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 enteric coating of pellets in Erythromycin Delayed release Capsules protects the erythromycin base from inactivation by gastric acidity. Because of their small size and enteric coating, the pellets readily pass intact from the stomach to the small intestine and dissolve efficiently to allow absorption of erythromycin in a uniform manner. After administration of a single dose of a 250 mg Erythromycin Delayed-release Capsule, peak serum levels in the range of 1.13 to 1.68 mcg/mL are attained in approximately 3 hours and decline to 0.30 to 0.42 mcg/mL in 6 hours. Optimal conditions for stability in the presence of gastric secretion and for complete absorption are attained when erythromycin is taken on an empty stomach.

Microbiology

Mechanism of Action

Erythromycin acts by inhibition of protein synthesis by binding 50 S ribosomal subunits of susceptible organisms. It does not affect nucleic acid synthesis.

Mechanism of Resistance

The major route of resistance is modification of the 23S rRNA in the 50S ribosomal subunit to insensitivity, while efflux can also be significant.

Interaction with other Antimicrobials

Antagonism exists in vitro between erythromycin and clindamycin, lincomycin, and chloramphenicol. Erythromycin has been shown to be active against most isolates of the following bacteria both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Gram-positive bacteria:

  Corynebacterium diphtheriae   Corynebacterium minutissimum   Listeria monocytogenes   Staphylococcus aureus   Streptococcus pneumoniae   Streptococcus pyogenes

Gram-negative bacteria:

  Bordetella pertussis   Haemophilus influenzae   Legionella pneumophila   Neisseria gonorrhoeae

Other Microorganisms:

  Chlamydia trachomatis   Entamoeba histolytica   Mycoplasma pneumoniae   Treponema pallidum   Ureaplasma urealyticum

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drugs used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug for treatment.

Dilution techniques

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method1,2 (broth and/or agar). The MIC values should be interpreted according to criteria provided in Table 1.

Diffusion techniques

Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method.2,3 This procedure uses paper disks impregnated with 15 mcg erythromycin to test the susceptibility of microorganisms to erythromycin. The disc diffusion interpretive criteria are provided in Table 1.

Table 1. In vitro Susceptibility Test Interpretive Criteria for Erythromycin

	Minimum Inhibitory Concentration (mcg/mL)			Disk Diffusion (zone diameter in mm)
Pathogen	S	I	R	S	I	R
Staphylococcus aureus	≤0.5	1-4	≥8	≥23	14-22	≤13
Streptococcus pneumoniae	≤0.25	0.5	≥1	≥21	16-20	≤15
Streptococcus pyogenes	≤0.25	0.5	≥1	≥21	16-20	≤15

A report of Susceptible indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations at the site of infection necessary to inhibit growth of the pathogen. 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 a 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 antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations usually achievable at the infection site; other therapy should be selected.

Quality Control

Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individuals performing the test.1,2,3,4 Standard erythromycin powder should provide the following range of MIC values noted in Table 2. For the diffusion technique using the erythromycin 15 mcg disk the criteria in Table 2 should be achieved.

Table 2. Acceptable Quality Control Ranges for Erythromycin

QC Strain	Minimum Inhibitory Concentration (mcg/mL)	Disk diffusion (Zone Diameter in mm)
Staphylococcus aureus ATCC 29213	0.25-1	N/A
Enterococcus faecalis ATCC 29212	1-4	N/A
Staphylococcus aureus ATCC 25923	N/A	22-30
Streptococcus pneumoniae ATCC 49619	0.03-0.12	25-30