Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2016 Publisher: PANPHARMA, ZI DU CLAIRAY, 35133 LUITRE, FRANCE
Pharmacotherapeutic group: ANTIBACTERIAL FOR SYSTEMIC USE
ATC code: J01FA01
Erythromycin is a semi-synthetic macrolide with a 14-membered lactone ring.
Erythromycin exerts its antimicrobial action by binding to the 50S ribosomal sub-unit of susceptible microorganisms and suppresses protein synthesis.
Erythromycin does not bind to cytoplasmic membranes of the host cells. This is a possible explanation of its low toxicity and safety record.
Erythromycin is bacteriostatic and bactericidal depending on its concentration and the type of organism. It inhibits protein synthesis by binding to ribosmal subunits, inhibiting translocation of aminocyl transfer RNA and inhibiting polypeptide synthesis without causing any alteration in the nucleic acid cycle.
Erythromycin is usually active against most strains of the following organisms both in vitro and in clinical infections.
Known resistance mechanisms in pathogens relevant to the indications:
There is complete cross-resistance in the “M”-phenotype of erythromycin with clarithromycin, roxithromycin or azithromycin. In the “MLSs”-phenotype, there is additional cross-resistance to clindamycin and Group B Strep gram positive bacteria. There is a partial cross resistance to the 16-membered macrolide, spiramycin.
The testing of erythromycin is made using the usual dilution series for erythromycin. As a result, minimal inhibitory concentrations (MIC) for susceptible and resistant bacteria were identified. The recommended EUCAST (European Committee on Antimicrobial Susceptibility Testing) MIC breakpoints for erythromycin are presented below in the table for MIC testing (mg/L):
EUCAST clinical MIC breakpoints for erythromycin (version 2.0, valid from 2014-01-01):
| Pathogen | Susceptible (mg/L) | Resistant (mg/L) |
|---|---|---|
| Staphylococcus spp. | ≤1 | >2 |
| Streptococcus groups A,B,C,G | ≤0.25 | >0.5 |
| Streptococcus pneumoniae | ≤0.25 | >0.5 |
| Haemophilus influenzae | ≤0.5 | >16 |
| Moraxella catarrhalis | ≤0.25 | >0.5 |
| Campylobacter jejuni | 4 | 4 |
| Campylobacter coli | 8 | 8 |
| Non species related breakpoints | IE* | IE* |
* “IE” indicates that there is insufficient evidence that the species in question is a good target for therapy with the drug. A MIC with a comment but without an accompanying S, I or R categorisation may be reported.
The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is known and the utility of the agent in at least some types of infections is questionable.
Aerobic Gram-positive bacteria:
Corynebacterium diphtheriae
Corynebacterium minutissimum
Streptococcus pyogenes
Aerobic Gram-negative bacteria:
Bordetella pertussis
Campylobacter jejuni
Moraxella catarrhalis
Other bacteria:
Chlamydia trachomatis
Chlamydia pneumoniae
Chlamydia psittaci
Legionella pneumophila
Mycoplasma pneumoniae
Aerobic Gram-positive bacteria:
Staphylococcus aureus (Methicillin-susceptibility)
Streptococcus pneumoniae
Aerobic Gram-negative bacteria:
Haemophilus influenzae
Other bacteria:
Treponema pallidum
Aerobic Gram-negative bacteria:
Escherichia coli
Klebsiella spp.
Pseudomonas aeruginosa
Aerobic Gram-positive bacteria:
Staphylococcus aureus (Methicillin-resistant)+
The apparent volume of distribution of erythromycin is around 45% of body weight in normal subjects. This large distribution volume is consistent with the extensive tissue penetration of erythromycin.
Erythromycin diffuses readily into most body fluids, except the cerebrospinal fluid. However, in cases of meningeal inflammation, higher concentrations are apparent.
In studies using rabbit microsomes it has been shown that erythromycin is demethylated to des-N-methyl erythromycin and formaldehyde.
In the presence of normal hepatic function, erythromycin is concentrated in the liver and excreted in the bile; the effect of hepatic dysfunction on excretion of erythromycin by the liver is not known.
From 12% to 15% of intravenously administered erythromycin is excreted in active form in the urine.
The drug is also excreted in the faeces.
The plasma elimination half-life in patients with normal renal function is about 2 hours. In severe renal impairment the half-life may be prolonged to between 4 and 7 hours.
The acute and chronic oral toxicity of erythromycin is low.
No evidence has been verified of teratogenicity or any other adverse reaction in the reproduction of female rats, who received oral tube administration of 350 mg/kg/day (7 times the human dose) of Erythromycin base prior to or during mating, pregnancy and during weaning.
No evidence was observed of teratogenicity or embryo toxicity when erythromycin base was administered by oral tube to pregnant female rats and mice at a dose of 700 mg/kg/day (14 times the human dose), and to pregnant female rabbits at a dose of 125 mg/kg/day (2.5 times the human dose).
A slight reduction was detected in birth weights when female rats were treated prior to mating, during mating, pregnancy and breastfeeding, with a high oral dose of 700 mg/kg/day of erythromycin base; the weights of the litter were comparable to those of the controls by the time of weaning. No evidence of teratogenicity or effects on reproduction were observed at this dose. When administered during the final stage of pregnancy and breastfeeding, this dose of 700 mg/kg/day (14 times the human dose) did not result in any adverse effects in birth weight, growth or survival of the litter.
Long-term studies (2 years) with the oral formulation of erythromycin stearate, conducted in rats up to almost 400 mg/kg/day and in mice up to almost 500 mg/kg/day, did not reveal any evidence of tumorigenicity.
The mutagenicity studies conducted did not reveal any genotoxic potential, and no evident effects were observed on the fertility of male or female rats treated with 700 mg/kg/day of erythromycin base via oral tube.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
