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 and is excreted in breast 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. From 12 to 15 percent of intravenously administered erythromycin is excreted in active form in the urine.

Intravenous infusion of 500 mg of erythromycin lactobionate at a constant rate over 1 hour in fasting adults produced a mean serum erythromycin level of approximately 7 mcg/mL at 20 minutes, 10 mcg/mL at 1 hour, 2.6 mcg/mL at 2.5 hours, and 1 mcg/mL at 6 hours.

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 together.

Staphylococci resistant to erythromycin may emerge during a course of therapy. Culture and susceptibility testing should be performed.

Erythromycin is usually active against the following organisms in vitro (prior to use, refer to INDICATIONS AND USAGE)

Gram-positive Bacteria: Staphylococcus aureus (resistant organisms may emerge during treatment), Streptococcus pyogenes (Group A beta-hemolytic streptococcus), Alpha-hemolytic streptococcus (viridans group), Streptococcus (diplococcus) pneumoniae, Corynebacterium diphtheriae, Corynebacterium minutissimum.

Gram-negative Bacteria: Neisseria gonorrhoeae, Legionella pneumophila, Bordetella pertussis.

Mycoplasma: Mycoplasma pneumoniae, Ureaplasma urealyticum.

Other Microorganisms: Chlamydia trachomatis, Entamoeba histolytica, Treponema pallidum, Listeria monocytogenes.

Susceptibility Testing

Quantitative methods that require measurement of zone diameters give the most precise estimates of antibiotic susceptibility. One such standardized single-disc procedure has been recommended for use with discs to test susceptibility to erythromycin.¹ Interpretation involves correlation of the zone diameters obtained in the disc test with minimal inhibitory concentration (MIC) values for erythromycin.

Reports from the laboratory giving results of the standardized single-disc susceptibility test using a 15 mcg erythromycin disc should be interpreted according to the following criteria:

Susceptible organisms produce zones of 18 mm or greater, indicating that the tested organism is likely to respond to therapy.

Resistant organisms produce zones of 13 mm or less, indicating that other therapy should be selected.

Organisms of intermediate susceptibility produce zones of 14 to 17 mm. The “intermediate” category provides a “buffer zone” which should prevent small, uncontrolled technical factors from causing major discrepancies in interpretations; thus, when a zone diameter falls within the “intermediate” range, the results may be considered equivocal. If alternative drugs are not available, confirmation by dilution tests may be indicated.

Standardized procedures require the use of control organisms. The 15 mcg erythromycin disc should give zone diameters between 22 and 30 mm for the S. aureus ATCC 25923 control strain.

A bacterial isolate may be considered susceptible if the MIC value² for erythromycin is not more than 2 mcg/mL. Organisms are considered resistant if the MIC is 8 mcg/mL or higher. The MIC of erythromycin for S. aureus ATCC 29213 control strain should be between 0.12 and 0.5 mcg/mL.

REFERENCES

1. National Committee for Clinical Laboratory Standards, Approved Standard: Performance Standards for Antimicrobial Disk Susceptibility Tests, 3rd Edition, Vol. 4(16):m²-A3, Villanova, PA, December 1984.

2. Ericson, H.M., Sherris, J.C., Antibiotic Sensitivity Testing Report of an International Collaborative Study, Acta Pathologica et Microbiologica Scandinavica Section B Suppl. 217:1-90, 1971.

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