A class of drugs prescribed for treating bacterial infections, antibiotics either destroy bacteria or inhibit their growth. This HealthHearty write-up provides information on the side effects of macrolide antibiotics.
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Erythromycin was the first macrolide antibiotic that was isolated from a bacterium called Streptomyces erythreus, in 1952. It breaks down into a motilin-receptor agonist in the acidic environment of the stomach, which in turn stimulates contractions. Azithromycin and clarithromycin, which are semi-synthetic derivatives of erythromycin, are less likely to cause the gastrointestinal effects that are linked to the use of erythromycin.
In the field of medicine, the term ‘antibiotic’ was first used by Selman Waksman, a Ukrainian-American microbiologist who is credited with the discovery of streptomycin. Antibiotics, which are drugs that are used for treating infections caused by bacteria, are classified on the basis of their spectrum (number of organisms affected by the same drug) and type of activity. Broad-spectrum antibiotics are drugs that can work on several types of bacteria, whereas, narrow-spectrum antibiotics are effective against specific bacteria. Therefore, broad-spectrum antibiotics are prescribed when the causal bacterium for an infection or medical condition is not known. Macrolide antibiotics are placed under the category of broad-spectrum antibiotics.
Antibiotics are also classified into bactericidal and bacteriostatic drugs. While the former works by destroying bacteria, the latter works by preventing bacteria from multiplying. In severe cases, where the affected individual has a compromised immune system, healthcare providers often recommend the use of bactericidal drugs. However, it must be noted that when taken in large doses, certain bacteriostatic antibiotics might act as bactericidal drugs for certain types of bacteria, and vice versa. In regular doses, macrolide antibiotics prevent the bacterium from reproducing. However, these drugs might act as bactericidal drugs at high doses.
Macrolides get their name from their chemical structure. Depending on the number of carbon atoms in the macrocyclic lactone ring, these are divided into 14-membered (erythromycin, roxithromycin, clarithromycin), 15-membered (azithromycin), and 16-membered (midecamycin, spiramycin, josamycin) ring. It must be noted that only azithromycin, clarithromycin, erythromycin, and telithromycin have been approved by the Food and Drug Administration of the United States (FDA).
Macrolides are often recommended in place of penicillin, when the patient is allergic to penicillin. They might also be given along with other antibiotics. These drugs can have a bactericidal effect on beta-hemolytic streptococcus group A, pneumococcus, and the causative agents of whooping cough and diphtheria. Macrolides exhibit antibacterial effect against Gram-positive bacteria, such as:
✦ Streptococcus aureus
✦ Streptococcus pneumoniae
✦ Streptococcus pyogenes
These are also effective against other pathogens such as mycoplasma, chlamydia, campylobacter, legionella, etc. They might also be recommended for treating infections caused by:
✦ Haemophilus influenzae
✦ Chlamydia pneumoniae
✦ Helicobacter pylori
✦ Staphylococcus aureus (with the exception of MRSA)
✦ Mycoplasma pneumoniae
✦ Chlamydia trachomatis
✦ Chlamydophila pneumoniae
✦ Legionella sp
✦ Corynebacterium diphtheriae
✦ Campylobacter sp
✦ Treponema pallidum
✦ Propionibacterium acnes
✦ Borrelia burgdorferi
Macrolides inhibit the RNA-dependent protein synthesis by reversibly binding to the 50S ribosomal subunits of the susceptible bacteria or pathogens. They cause the disassociation of peptidyl transfer RNA (tRNA) from the ribosome during the elongation phase of transcription. These drugs work by inhibiting the bacterial protein biosynthesis in the ribosomes of the microbial cells, which in turn prevents the causal bacterium from multiplying, thereby inhibiting bacterial growth.
Some macrolide antibiotics also possess immunomodulatory and moderate anti-inflammatory activity, which in turn is dependent on their ability to prevent the production of cytokines3 and proinflammatory mediators. The anti-inflammatory activity can vary. For instance, roxithromycin has stronger anti-inflammatory properties as compared to clarithromycin and azithromycin.
It must be noted that among the macrolide antibiotics, azithromycin, clarithromycin, and roxithromycin are better tolerated than erythromycin. Though their mechanism of action is quite similar, they differ in terms of bioavailability (amount of drug that reaches the physiological site of activity after administration). The bioavailability of clarithromycin is more than twice than that of erythromycin, whereas, the bioavailability of azithromycin is 1.5 times than that of erythromycin. The better absorption rate is responsible for acid stability.
The reason behind the development of gastrointestinal symptoms after the ingestion of erythromycin is the breakdown of erythromycin into a motilin-receptor agonist, which stimulates a G-protein coupled pathway in the smooth cells of the gastrointestinal tract. This leads to contractions, which causes abdominal cramps and pain. The other gastrointestinal effects that are associated with the use of erythromycin include:
✦ Nausea
✦ Vomiting
✦ Abdominal discomfort
✦ Diarrhea
✦ Loss of appetite
In rare cases, the use of macrolide antibiotics could cause an allergic reaction. Seek medical help at the earliest if you experience anaphylaxis. It is a life-threatening allergic reaction, that is characterized by the following symptoms:
✦ Hives
✦ Swelling of the mouth, lips, tongue, and throat
✦ Shortness of breath
✦ Difficulty breathing and/or swallowing
✦ Palpitations
✦ Wheezing
✦ Lightheadedness
Other uncommon side effects include headaches, taste disturbance, and hepatotoxicity. Medical help must be sought if one experiences symptoms that are indicative of an increase in serum aminotransferase levels or hepatoxicity. It is believed that these drugs could cause cholestatic hepatitis, which could give rise to the following symptoms:
✦ Jaundice (yellowing of the eyes or skin)
✦ Fever
✦ Malaise
✦ Weakness
✦ Abdominal pain
✦ Nausea
✦ Vomiting
Thus, adverse effects can occur in case of individuals affected by liver failure, or those who are allergic to antibiotics or other ingredients used in the drug.
Another cause of concern has been the link between macrolide antibiotics and the risk of cardiac arrhythmias. As per the FDA, the use of azithromycin (Zithromax or Zmax) could give rise to abnormal changes in the electrical activity of the heart, which in turn might lead to a potentially fatal irregular heart rhythm. Large doses of some of these drugs could cause QT interval (a measure of the time between the start of the Q wave and the end of the T wave in the heart’s electrical cycle) prolongation, which could be indicative of ventricular tachyarrhythmias. Thus, caution must be exercised while prescribing these drugs, especially in case of individuals with an existing QT interval prolongation, or those who are being treated for abnormal heart rhythms.
Erythromycin can be used by pregnant women and nursing mothers, but there’s a lack of evidence regarding the safety of azithromycin during pregnancy. Therefore, azithromycin is prescribed for pregnant women and nursing mothers only if the benefits outweigh the risks. Roxithromycin and clarithromycin can be used by nursing mothers. Erythromycin (and to a lesser extent clarithromycin) could inhibit certain enzymes, which can increase the effect of several drugs. Macrolides are not given to those who are taking statins (drugs used for lowering cholesterol, including simvastatin and pravastatin), as this combination can cause untoward symptoms such as muscular spasms, weakness, and stiffness. Thus, it is advisable to inform your healthcare provider about the drugs that you are taking currently, so as to avoid adverse drug interactions. Also, make sure you follow the guidelines regarding dosage.
On a concluding note, some of the newer macrolides are better tolerated than erythromycin, which is why they are commonly used to treat bacterial infections. Clarithromycin and azithromycin are less likely to cause gastrointestinal side effects than erythromycin. Since erythromycin has a shorter elimination half-life (1 – 1.5 hours) than azithromycin and clarithromycin, more number of doses are required. Studies have shown that therapy with erythromycin is more likely to be stopped prematurely due to side effects in comparison to antibiotic therapy involving the use of azithromycin or clarithromycin.
Disclaimer: The information provided in this article is solely for educating the reader. It is not intended to be a substitute for the advice of a medical expert.
