The macrolides are a group of antimicrobial drugs that work by preventing the formation of bacterial proteins. In most organisms this action inhibits bacterial growth; however, in high concentrations it can cause cell death.
First described in 1952, when McGuire and his team discovered erythromycin, they have become one of the most widely used groups of antibiotics in the world. Since the 1970s, the first synthetic macrolides - such as azithromycin and clarithromycin - were developed, mainly to be administered orally..
Erythromycin, like many other antibiotics, was isolated from a bacterium, the Saccharopolyspora erythraea. Formerly known as Streptomyces erythraeus, is a bacterium present in the soil whose cytocorome P450 is responsible for synthesizing the antibiotic through a partial hydroxylation process.
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Macrolides act at the ribosomal level, specifically on the 50S subunit, blocking its action. By doing this, they inhibit protein synthesis in sensitive microorganisms without affecting mammalian ribosomes. This effect prevents the growth of bacteria.
Due to their mechanism of action, macrolides are considered bacteriostatic antibiotics. However, depending on the dose and the sensitivity of the bacteria, they can become bactericidal. It is important to note that macrolides only have an effect on cells that are replicating or in the growth phase..
An important characteristic of macrolides is their ability to concentrate within macrophages and polymorphonuclear cells. It is for this reason that they are the antibiotics of choice for intracellular bacteria or atypical germs. In addition, they have a prolonged post-antibiotic effect, and can be used with comfortable dosages..
Many biological activities have been described for macrolides, including the ability to modulate inflammatory processes..
This fact has led them to also be indicated to treat neutrophil-mediated inflammations in many diseases of the respiratory sphere with diffuse bronchiolitis or cystic fibrosis..
These immunomodulatory actions appear to work in different ways. One of these is related to the inhibition of extracellular phosphorylation and the activation of the nuclear factor Kapa-B, both actions with anti-inflammatory results..
In addition, its intracellular presence has been linked to the regulation of the immune activity of the cell itself..
The main concern generated by the use of macrolides as immunomodulators is bacterial resistance. Researchers are currently working on the creation of a non-antibiotic macrolide to be used only as an immune modulator without the risk of antimicrobial resistance..
Due to its chemical structure, in which there is a common macrocyclic lactonic ring for all macrolides, there is a classification that considers the number of carbon atoms present in said ring.
- Erythromycin.
- Clarithromycin.
- Telithromycin.
- Dirithromycin.
- Azithromycin.
- Spiramycin.
- Midecamycin.
Certain publications offer another classification of macrolides based on their origin. Although not universally accepted, the information provided below is valuable:
- Erythromycin.
- Myocamycin.
- Spiramycin.
- Midecamycin.
- Clarithromycin.
- Azithromycin.
- Roxithromycin.
A third classification organizes the macrolides according to generations. It is based on the chemical structure and the pharmacodynamic and pharmacokinetic characteristics.
- Erythromycin.
- Josamycin.
- Spiramycin.
- Myocamycin.
- Azithromycin.
- Roxithromycin.
- Clarithromycin.
- Telithromycin.
- Cethromycin.
Some authors consider ketolides as a group apart from antibiotics, although the strictest ones assure that it is an important modification of macrolides, since it preserves the same original ring and mechanism of action..
The most important difference between the parent macrolides and ketolides is the spectrum of action. Macrolides up to the third generation have greater activity against Gram-positive; on the other hand, ketolides are effective against Gram-negative ones, especially Haemophilus influenzae Y Moraxella catarrhalis.
Most macrolides have the same side reactions, which, although rare, can be uncomfortable. The most important ones are described below:
They can present as nausea, vomiting, or abdominal pain. It is more frequent with the administration of erythromycin and is attributed to its prokinetic effects..
Some cases of pancreatitis have been described after the administration of erythromycin and roxithromycin, related to spastic effects on the sphincter of Oddi.
A rare but severe complication is hepatotoxicity, especially when ketolides are involved. The mechanism of liver damage is not well understood, but it subsides when the drug is withdrawn..
It has been described in pregnant women or young people and is accompanied by abdominal pain, nausea, vomiting, fever, and jaundice tint of the skin and mucous membranes..
It can manifest in different systems, such as the skin and blood, in the form of a rash or fever and eosinophilia. These effects subside when treatment is stopped.
It is not known exactly why they occur, but the immunological effects of macrolides may be involved..
QT prolongation is the most reported cardiac complication after macrolide administration. Cases of polymorphic ventricular tachycardia have also been described, but they are very rare..
In 2017, the FDA (drug regulatory body in the United States) reserved ketolides only for cases of community-acquired pneumonia due to cardiac complications and other adverse effects that it caused, ceasing to be indicated in cases of sinusopathy, pharyngotonsillitis or complicated bronchitis.
Although most macrolides are prescribed orally, existing intravenous forms can cause phlebitis. Its slow administration is recommended through a peripheral line of large caliber or a central line, and highly diluted in saline solution..
Although it does not occur commonly, cases of ototoxicity with tinnitus and even deafness have been described in patients who consume high doses of erythromycin, clarithromycin or azithromycin. This adverse effect is more frequent in the elderly and patients with chronic liver or kidney failure..
The administration of these medications by any route, especially oral, can cause a bad taste in the mouth..
Ketolides have been associated with transient visual disturbances. Its use should be avoided in pregnant women - since its action on the fetus is not known with certainty - and in patients with myasthenia gravis..
Caution is necessary when administered in conjunction with any other drug that is metabolized through the cytochrome P450, isoenzyme 3A4 system..
May raise serum digoxin levels and have an antagonistic effect when administered with chloramphenicol or lincosamines.
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