Here is a list of various macrolide antibiotics.
1. Erythromycin:
(i) This macrolide antibiotic was isolated from Streptomyces erythreus, a soil- born organism in 1952.
(ii) It consists of two sugars, desosamine and cladinose, which are attached to erythronolide, a macro cyclic lactone.
(iii) It is slightly water soluble.
(iv) The antibiotic remains more active, in alkaline medium than at neutrality and is unstable in acidic medium because the non-ionized (penetrable) form of the drug is favoured at higher pH.
Mechanism of Action:
Sensitive gram (+ ve) bacteria accumulate erythromycin which acts by inhibiting bacterial protein synthesis. After combination with 50S ribosome subunit, it interferes with ‘translocation’.
Following peptide bond formation between the newly attached amino acid and the nacent peptide chain at the acceptor site, the elongated peptide is translocate to the peptidyl site making the acceptor site available for next aminoacyl tRNA attachment.
Erythromycin prevents this process and the ribosome fails to move along the mRNA to expose the next codon. As a result protein synthesis specifically larger protein synthesis is suppressed.
Antimicrobial Spectrum:
Erythromycin is effective against streptococcus pyogenes, Streptococcus fecalis, Staphylococcus, Corynebacterium renale, C. pyogenes, Erysipelothrix rhusiopathiae Brucella suis and Ricketsiae are moderately sensitive whereas enterobacteriaceaes, other gram (- ve) bacilli and B. fragilis are not inhibited.
Resistance:
It develops mostly by mechanisms which decrease the permeability or acquiring the capacity to pump out the antibiotic. Plasmid mediated alteration in the ribosomal binding site is another way, while change in the 50S ribosome by mutation has also been reported. Cross resistance develops against oleandomycin, clindamycin and chloramphenicol.
Pharmacokinetics:
Erythromycin is readily absorbed from the small intestine after oral administration and is distributed throughout most tissues. Serum concentration declines sharply within 4-6 hrs. of oral administration. Following I/M administration at a dose of 15 mg/kg, erythromycin showed a half-life of 8-9 hrs.
Highest concentrations are detected in liver, sub-maxillary glands, lungs and kidneys after 2 hrs. of administration. It can cross the placenta and enter into the foetal circulations Erythromycin reaches prostatic fluid and semen and achieves one-third of the blood concentration.
Very little amounts are recovered from brain and CSF. Erythromycin is eliminated at a higher concentration through bile and therapeutically effective for many infections of biliary tract.
Clinical Use:
The oral does of erythromycin in non-herbivorous animals is 6.6-8.8 mg/kg/day administered in 3 to 4 divided does Erythomycin stearate can be administered orally using 4.4-6.6 mg/kg/day in 3 to 4 divided doses.
Erythromycin lactobionate may be administrated parenterally at a dose of 2.2-4.4 mg/kg at intervals of 8-12 hrs.
Local or topical use is not preferred because of skin sensitivities.
Oleandomycin and Troleandomycin:
Oleandomycin (used as phosphate salt), is an antibiotic derived from Streptomyces antibioticus. Troleandomycin is a derivative of oleandomycin used for oral administration due to its rapid and complete absorption. Antibacterial spectrum is like erythromycin but these are primarily anti-staphylococcal drug.
Dose:
1.1-2.2 mg/kg 4 times daily orally.
2. Newer Macrolides:
Roxithromycin:
1. It is a semisynthetic long acting acid stable macrolide whose antimicrobial spectrum resembles closely with erythromycin.
2. Its affinity for cytochrome P450 is lower.
3. It is an alternative to erythromycin for respiratory, ENT, skin soft tissue and genital tract infections.
Clarithromycin:
1. The antimicrobial spectrum resembles with erythromycin.
2. In addition, it is effective against Mycobacterium avium complex, other atypical mycobacteria, Mycobacterium leprae and some anaerobes but not Bact. fagilis.
3. But, bacteria that develop resistance against erythromycin, are also resistant to clarithromycin.
4. It is indicated in upper and lower respiratory tract infections, sinusitis, Otitis media, atypical pneumonia, skin infections due to streptococcus pyogenes and staphylococcus aureus.
Azithromycin:
1. A new azalide congener of erythromycin having extended spectrum.
2. It is more active against H. influenzae, but less active against gram (+ve) cocci than other macrolides.
3. Highly active against Mycoplasma and other respiratory pathogens.
4. Penicillinase producing staph, aureus are inhibited but not effective against methicillin resistant staphylococcus aureus.
5. Acid stable.
6. Marked intracellular penetration and tissue distribution.
7. High concentrations are attained in macrophages and fibroblasts.
8. It is indicated in pneumonia, urethritis, genital infections, pharyngitis, tonsilitis, sinusitis, otitis media, streptococcal and staphylococcal skin and soft tissue infections. Also used in typhoid & toxoplasmosis.
Lincosamides:
Lincosamide antibiotics are considered with macrolides due to similar antimicrobial spectra, therapeutic application and mechanism of action (inhibits protein synthesis by binding to 50S ribosome).
Lincomycin and Clindamycin:
Lincomycin is used as Lincomycin hydrochloride while clindamycin is used as clindamycin hydrochloride hydrate, clindamycin palmitate and clindamycin phosphate.
Antimicrobial Spectrum:
These are active against gram positive pathogens like penicillinase producing staphylococcus, streptococcus, Clostridium tetani, cl. diphtheriae, cl. welchii as well as several Actinomyces, some Nocardia and certain strains of Mycoplasma pneumoniae.
A distinctive feature of clindamycin is its high activity against anaerobes. Particularly the combination of lincomycin and spectinomycin in a 1: 2 ratio shows excellent activity against Mycoplasma gallisepticum and E. Coli infection in chicks. The combination also shows greater activity in controlling air sacculitis of turkey pouts.
Pharmacokinetics:
A single I/M injection of lincomycin (10 mg/kg) in dairy cow revealed a four to six times higher drug concentration in milk compared to blood plasma. Lincomycin persisted for 6-8 hrs. in milk of cows following single I/M injection. It is less bound to milk protein than that of plasma protein.
Concentration of clindamycin in milk also exceeded serum concentration at the peak serum concentration after I/M injection. Residue persisted in milk of the ewes after 11 hrs. of treatment. Both the drugs can be administered by Oral IM or IV route.
Clindamycin is semi-synthetically derived from Lincomycin by substitution of a chlorine atom for a hydroxyl group, which is responsible for its better absorption. Presence of food in the stomach does not interfere with absorption of clindamycin. Cross resistance may occur between lincomycin and clindamycin. It is also evidenced when used with erythromycin, oleandomycin and chloramphenicol.
Clinical Use:
Lincomycin 2-100 gm./900 kg of feed for broiler chickens may show a beneficial effect when birds are exposed to necrotic enteritis by clostridial infection.
40-100 gm. lincomycin/900 kg of feed for swine is used generally. But 200 mg lincomycin/kg swine feed has been reported as effective for controlling endemic enzootic pneumonia in pigs at 5-6 weeks of age.
Lincomycin is administered intramuscularly for treatment of arthritis and pneumonia involving Mycoplasma in pigs.
For treatment of infections caused by susceptible gram positive organisms in dogs and cats, lincomycin can be administered.
Dose:
11-22 mg/kg I/M twice daily for dogs and cats.
11 mg/kg I/M once daily for 5-6 days for swine.
The antibiotic must not be used within 48 hrs. of slaughter.
Undesirable Effects:
Pain, irritation and induration occur following I/M administration of both lincomycin and clindamycin.
In impaired renal function a dose reduction with an increased dosing interval for maintenance therapy is necessary.