ERYTHROMYCIN RATIONAL USE (*ONLY FOR THE REFERENCE OF MEDICAL /HEALTH CARE PROFESSIONAL).

DRUG NAME : ERYTHROMYCIN

BACTERIAL RESISTANCE

CLASS OF DRUG :MACROLIDES.

FOUNDED YEAR : 1952

ISOLATED FROM: STREPTOMYCES ERYTHREUS.

MECHANISM OF ACTION: BLOCKS 50S RIBOSOMES -INHIBITS THE PROTEIN SYNTHESIS -BACTERICIDAL ACTIVITY.

Macrolide antibiotics are bacteriostatic agents that

inhibit protein synthesis by binding reversibly to the 50S ribosomal subunits

of sensitive organisms. Erythromycin appears to inhibit the translocation step

such that the nascent peptide chain temporarily residing at the A site fails to

move to the P, or donor, site. Alternatively, macrolides may bind and cause a

conformational change that terminates protein synthesis by indirectly interfering

with transpeptidation and translocation

 

ANTIMICROBIAL SPECTRUM:

streptococcus pyogenes

streptococcus pneumoniae

niseria gonorrhoeae

clodtridia

clostridium diphtheria

clostridium listera

campylobacter

legionella

branhamella catarrhalis

gardnerella vaginallis

mycoplasma

Helicobacter ducreyi

Helicobacter influenza

branhamella pertussis

ANTIMICROBIAL RESISTANCE 

penicillin resistance staphylococcus 

all cocci bacteria  now developed resistance against the erythromycin

t1/2 = 90min

FORMULATION

tablet=250mg(BID),500mg(MID)

dry syrup = 100mg/5ml calculate using BMI

pediatric drops = 100mg/ml calculate using Youngs formula

ointment = 30% used for boils,carbuncles and skin infection but( not much effective in this formulation). 

ADR

epigastric pain

diarrohea occasionaly

alters the bacterial flora in gi track

high dose = hearing impairment

hyper sensitivity = rashes and fever

DETAILED ADR

GI Toxicity. Oral or intravenous administration of erythromycin frequently

is accompanied by moderate-to-severe epigastric distress. Erythromycin

stimulates GI motility by acting on motilin receptors  indeed, erythromycin is used off label as a prokinetic agent

in the intensive care setting and in patients with diabetic gastroparesis.

Clarithromycin, azithromycin, and telithromycin also may cause GI distress,

but to a lesser degree than erythromycin.

Cardiac Toxicity. Erythromycin, clarithromycin, azithromycin, and

telithromycin have been reported to cause cardiac arrhythmias, including

QT prolongation with ventricular tachycardia. A large cohort study found

a small but statistically significant increase in the risk of sudden cardiac

death with azithromycin compared to no antibiotic treatment or to amoxicillin.

Risk factors for clinically significant cardiac toxicity include receipt

of concomitant antiarrhythmic drugs or other agents that prolong QTc.

Hepatotoxicity. Cholestatic hepatitis is associated with long-term

treatment with erythromycin. The illness starts after 10–20 days of treatment

and is characterized initially by nausea, vomiting, and abdominal

cramps. These symptoms are followed shortly thereafter by jaundice,

which may be accompanied by fever, leukocytosis, eosinophilia, and elevated

transaminases in plasma. Findings usually resolve within a few days

after cessation of drug therapy. Hepatotoxicity has also been observed

with clarithromycin and azithromycin, although at a lower rate than

with erythromycin. Telithromycin may induce severe hepatotoxicity and

should only be used if it represents a clear advantage over alternative

agents (Brinker et al., 2009).

Other Toxic and Irritative Effects. Allergic reactions observed are fever,

eosinophilia, and skin eruptions, which disappear shortly after therapy

is stopped. Auditory impairment and tinnitus have been observed with

macrolides, especially at higher doses. Visual disturbances due to slowed

accommodation have been reported following telithromycin. Telithromycin

is contraindicated in patients with myasthenia gravis due to exacerbation

of neurological symptoms.

INTERACTION 

PENICILLIN RESISTANCE INFLUENZA AND PNEUMONEA

DIPHTHERIA TREATED BY PENICILLIN 

TETANUS - ANTITOXINS,TOXOID THERAPY 

SYPHILIS AND GONORRHEA CANNOT BE USED WHEN REPULSIVE RATE ARE HIGH

LEPTOSPIROSIS:250MG 6 HOURLY TREATMENT

IN PATIENT ALLERGIC TO  PENICILLINS

Erythromycin inhibits hepatic oxidation

of many drugs. The clinically significant

interactions are—rise in plasma levels of theophylline,

carbamazepine, valproate, ergotamine

and warfarin.

Several cases of Q-T prolongation, serious

ventricular arrhythmias and death have been

reported due to inhibition of CYP3A4 by erythromycin/

clarithromycin resulting in high blood

levels of concurrently administered terfenadine/

astemizole/cisapride

FIRST CHOICE OF DRUG:

mycoplasma pneumonia

whopping cough :1-2 week course 

B.pertussis from upper respiratory tract infection

chancroid : 2g/day divided dose for 7 days 

SECOND CHOICE OF DRUG

Campylobacter enteritis: duration of diarrhoea and presence

of organisms in stools is reduced. However, fluoroquinolones

are superior.

 Legionnaires’ pneumonia: 3 week erythromycin treatment

is effective, but azithromycin/ciprofloxacin are preferred.

 Chlamydia trachomatis infection of urogenital tract:

erythromycin 500 mg 6 hourly for 7 days is an effective

alternative to single dose azithromycin.

 Penicillin-resistant Staphylococcal infections: its value has

reduced due to emergence of erythromycin resistance as

well. It is not effective against MRSA.

THERAPEUTIC USE AND DOAGE:

The usual oral dose of erythromycin (erythromycin base) for adults ranges

from 1 to 2 g/d, in divided doses, usually given every 6 h. Food should not

be taken concurrently, if possible, with erythromycin base or the stearate

formulations, but this is not necessary with erythromycin estolate. The

oral dose of erythromycin for children is 30–50 mg/kg/d, divided into

four portions; this dose may be doubled for severe infections. Intravenous

administration is generally reserved for the therapy of severe infections

and is now used uncommonly; the usual dose is 0.5–1 g every 6 h.

 prophylaxis of MAI infection in HIV-infected patients requires higher

doses: 500–600 mg daily in combination with one or more other agents for

treatment or 1200 mg once weekly for primary prevention. 

Respiratory Tract Infections. Macrolides are suitable drugs for the

treatment of a number of respiratory tract infections. Azithromycin and

clarithromycin are suitable choices for treatment of mild-to-moderate community-

acquired pneumonia among ambulatory patients. In hospitalized

patients, a macrolide is commonly added to an antipneumococcal β-lactam

for coverage of atypical respiratory pathogens. Because of excellent in vitro

activity, superior tissue concentration, the ease of administration as a single

daily dose, and better tolerability compared to erythromycin, azithromycin

(or a fluoroquinolone) has supplanted erythromycin as the first-line agent

for treatment of legionellosis. Macrolides are also appropriate alternative

agents for the treatment of acute exacerbations of chronic bronchitis, acute

otitis media, acute streptococcal pharyngitis, and acute bacterial sinusitis.

Azithromycin or clarithromycin are generally preferred to erythromycin

due to their broader spectrum and superior tolerability.

Telithromycin is effective in the treatment of community-acquired

pneumonia, acute exacerbations of chronic bronchitis, and acute bacterial

sinusitis and has a potential advantage where macrolide-resistant strains

are common. Due to a number of cases of severe hepatotoxicity, the drug’s

FDA approval is limited to community-acquired pneumonia; telithromycin

should be used only in circumstances where it provides a substantial

advantage over less-toxic therapies.

Skin and Soft-Tissue Infections. Macrolides are alternatives for treatment

of erysipelas and cellulitis among patients who have a serious allergy

to penicillin (Stevens et al., 2014). Erythromycin has been an alternative

agent for the treatment of relatively minor skin and soft-tissue infections

caused by either penicillin-sensitive or penicillin-resistant S. aureus. However,

many strains of S. aureus are resistant to macrolides.

Chlamydial Infections. Chlamydial infections can be treated effectively

with any of the macrolides. A single 1-g dose of azithromycin is recommended

for patients with uncomplicated urethral, endocervical, rectal, or

epididymal infections because of the ease of compliance. Erythromycin

base is preferred for chlamydial pneumonia of infancy and ophthalmia

neonatorum (50 mg/kg/d in four divided doses for 14 days). Azithromycin,

1 g/week for 3 weeks, may be effective for lymphogranuloma

venereum.

Diphtheria. Erythromycin for 7 days is very effective for acute infections

or for eradicating the diphtheria carrier state. Other macrolides are not

FDA-approved for this indication. Antibiotics do not alter the course of

an acute infection with diphtheria or decrease the risk of complications.

Antitoxin is indicated in the treatment of acute infection.

Pertussis. Erythromycin is the drug of choice for treating persons with

B. pertussis disease and for postexposure prophylaxis of household members

and close contacts. Clarithromycin and azithromycin also are effective.

If administered early in the course of whooping cough, erythromycin

may shorten the duration of illness; it has little influence on the disease

once the paroxysmal stage is reached. Nasopharyngeal cultures should be

obtained from people with pertussis who do not improve with erythromycin

therapy because resistance has been reported.

Helicobacter pylori Infection. Clarithromycin, 500 mg, in combination

with omeprazole, 20 mg, and amoxicillin, 1 g, each administered twice

daily for 10–14 days, is effective for treatment of peptic ulcer disease

caused by H. pylori.

Mycobacterial Infections. Clarithromycin or azithromycin is recommended

as first-line therapy for prophylaxis and treatment of disseminated

infection caused by MAI in patients with HIV infection and for

treatment of pulmonary disease in patients not infected with HIV (Masur

et al., 2014). Clarithromycin (500 mg twice daily) plus ethambutol

(15 mg/kg once daily) with or without rifabutin is an effective combination

regimen. Clarithromycin also has been used with minocycline for the

treatment of M. leprae in lepromatous leprosy.

Prophylactic Uses. Azithromycin or clarithromycin is recommended for

primary prevention of infection due to MAI among patients with HIV

infection and less than 50 CD4 cells/mm3. Single-agent therapy should

not be used for treatment of active disease or for secondary prevention

in patients with HIV. Erythromycin is an effective alternative for the prophylaxis

of recurrences of rheumatic fever in individuals who are allergic

to penicillin.