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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 is a macrolide antibiotic with activity against Gram-positive and Gram-negative bacteria.

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.

Interactions with Other Antibiotics

Antagonism has been demonstrated in vitro between erythromycin and clindamycin, lincomycin and chloramphenicol.

Many strains of Haemophilus influenzae are resistant to erythromycin, but are susceptible to erythromycin and sulfonamides used concomitantly.

Development of Resistance

Resistance to erythromycin in Staphylococcus aureus may emerge during therapy. Culture and susceptibility testing should be performed.

Erythromycin has been shown to be active against most strains of the following organisms both in vitro and in clinical infections [see INDICATIONS AND USAGE]:

Aerobic and facultative Gram-positive microorganisms

Corynebacterium diphtheriae
Corynebacterium minutissimum
Staphylococcus aureus (methicillin-susceptible strains only)
Streptococcus pneumoniae
Streptococcus pyogenes

Aerobic and facultative Gram-negative microorganisms

Legionella pneumophila
Neisseria gonorrhoeae

Other Microorganisms

Mycoplasma pneumoniae

At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for erythromycin. However, the efficacy of erythromycin in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled trials.

Aerobic and facultative Gram-negative microorganisms

Moraxella catarrhalis

Susceptibility Testing

When available, the clinical microbiology laboratory should provide cumulative results of the 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 the most effective antimicrobial.

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 procedure. Standardized procedures are based on a dilution method (broth or agar)¹ or equivalent with standardized inoculum concentrations and standardized concentrations of erythromycin powder. The MIC values should be interpreted according to the criteria provided in Table 1.

Diffusion technique: Quantitative methods that require measurement of zone diameters 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 mcg of erythromycin to test the susceptibility of microorganisms to erythromycin. The disk diffusion interpretive criteria are provided in Table 1.

Table 1: Susceptibility Interpretive Criteria for Erythromycin

A report of Susceptible indicates that the antimicrobial is likely to inhibit growth of the pathogen 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 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 in the blood reaches the concentrations usually achievable and other therapy should be selected. Quality Control: Standardized susceptibility test procedures require the use of quality control microorganisms to control the technical aspects of the test procedures³. Standard Erythromycin powder should provide the following range of values noted in Table 2.

Table 2: Acceptable Quality Control Ranges for Erythromycin

REFERENCES

1. Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Seventh Edition. Clinical and Laboratory Standards Institute document M7-A7 [ISBN 1-56238-5879]. Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2006.

2. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard—Ninth Edition. Clinical and Laboratory Standards Institute document M2-A9 [ISBN 1-56238-586-0]. Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2006.

3. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Eighteenth Informational Supplement. CLSI document M100-S18 [ISBN 1-56238-653-0]. Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2008.

Last reviewed on RxList: 6/23/2011
This monograph has been modified to include the generic and brand name in many instances.