Package Insert and Label Information: Erythrocin Lactobionate

By Hospira, Inc. | Last revised: 9 February 2012

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ERYTHROCIN LACTOBIONATE- erythromycin lactobionate injection, powder, lyophilized, for solution
Hospira, Inc.

Sterile Erythromycin Lactobionate, USP

INTRAVENOUS USE ONLY

Vials

Rx only

To reduce the development of drug-resistant bacteria and maintain the effectiveness of erythromycin and other antibacterial drugs, erythromycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

DESCRIPTION

Erythromycin is produced by a strain of Streptomyces erythraeus and belongs to the macrolide group of antibiotics. It is basic and readily forms salts with acids.

Erythrocin Lactobionate (Sterile Erythromycin Lactobionate, USP), is a soluble salt of erythromycin suitable for intravenous administration. It is available as a sterile, lyophilized powder in vials containing the equivalent of 500 mg of erythromycin activity. It is prepared as a solution and lyophilized in its final container.

Erythromycin lactobionate is chemically known as erythromycin mono (4-0-β-D-galactopyranosyl-D-gluconate) (salt). The structural formula is:

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CLINICAL PHARMACOLOGY

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 S. aureus may emerge during therapy.

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
Pathogen	Susceptibility Interpretive Criteria
	Minimum Inhibitory Concentration (mcg/mL)			Disk Diffusion (zone diameter in mm)
	S	I	R	S	I	R
Staphylococcus spp .	≤0.5	1 — 4	≥8	≥23	14 — 22	≤13
Enterococcus spp.	≤0.5	1 — 4	≥8	≥23	14 — 22	≤13
Streptococcus pneumoniae ^a,b	≤0.25	0.5	≥1	≥21	16 — 20	≤15
Streptococcus spp. (β-hemolytic group)^a,b	≤0.25	0.5	≥1	≥21	16 — 20	≤15
Streptococcus spp. (Viridans group)^a,b	≤0.25	0.5	≥1	≥21	16 — 20	≤15
^a The MIC interpretive criteria for Streptococcus pneumoniae, Streptococcus spp. (β-hemolytic group), and Streptococcus spp. (Viridans group) are applicable only to tests performed by broth microdilution using cation-adjusted Mueller-Hinton broth supplemented with 2-5% lysed horse blood inoculated with a direct colony suspension and incubated in ambient air at 35 ± 2°C for 20 to 24 hours. ^b The zone diameter interpretive criteria for Streptococcus pneumoniae, Streptococcus spp. (β‑hemolytic group), and Streptococcus spp. (Viridans group) are applicable only to tests performed using Mueller-Hinton agar supplemented with 5% defibrinated sheep blood inoculated with a direct colony suspension and incubated in 5% CO₂ at 35 ± 2°C for 20 to 24 hours.

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
QC Strain	Acceptable Quality Control Ranges
QC Strain	Minimum Inhibitory Concentration (mcg/mL)	Disk Diffusion (zone diameter in mm)
Enterococcus faecalis ATCC 29212	1 — 4	NA^a
Staphylococcus aureus ATCC 29213	0.25 — 1	NA
Staphylococcus aureus ATCC 25923	NA	22 — 30
Streptococcus pneumoniae ATCC 49619^b	0.03 — 0.12^c	25 — 30^d
^a not applicable ^b This organism may be used for validation of susceptibility test results when testing Streptococcus spp. other than S. pneumoniae. ^c This quality control range for S. pneumoniae is applicable only to tests performed by broth microdilution using cation-adjusted Mueller-Hinton broth supplemented with 2-5% lysed horse blood inoculated with a direct colony suspension and incubated in ambient air at 35 ± 2°C for 20 to 24 hours. ^d This quality control zone diameter range is applicable only to tests performed using Mueller-Hinton agar supplemented with 5% defibrinated sheep blood inoculated with a direct colony suspension and incubated in 5% CO₂ at 35 ± 2°C for 20 to 24 hours.