What Is Azithromycin?

Azithromycin is a broad spectrum antibiotic. It was one of the best-selling drugs in the US after its commercialization.

Azithromycin is a broad-spectrum antibiotic drug used for different infections. This active principle, in addition to being sold under this name, is marketed under the name of other brands such as Zithromax, Acimut, or Koptin.

Azithromycin belongs to the group of macrolide antibiotics and, within them, to the subclass azolides. It’s a semisynthetic antibiotic that, despite having the same mechanism of action as macrolides, has some peculiarities that differentiate it from conventional macrolides.

History of azithromycin

It was the Croatian pharmaceutical company Pliva that discovered this antibiotic in the late 1970s. However, it wasn’t until 1981 that they submitted the application, despite the fact that the drug was still in the experimental stage.

Patenting the antibiotic proved to be the key to its commercial success. When scientists from the large multinational Pfizer searched the database of the United States Patent and Trademark Office, they found Plival’s patent and offered an ideal channel for its commercialization.

In 1986, talks between the two pharmaceutical companies culminated in a licensing agreement, thanks to which both companies and the general public were able to benefit from the commercialization of this antibiotic.

Under the agreement, Pfizer acquired the right to sell azithromycin worldwide. However, Pliva retained the right to sell the product in Central and Eastern Europe.

Zithromax, the name under which Pfizer markets azithromycin, was one of the best-selling antibiotics in the US and around the world. Next, we’ll see the following characteristics of this drug, which is so well-known worldwide:

• Mechanism of action
• Pharmacokinetics
• Indications and dosage
• Adverse reactions and contraindications
• Antibiotic resistance

Mechanism of action

Azithromycin, belonging to the group of macrolide antibiotics, owes its antibacterial action to its ability to inhibit the synthesis of proteins in the bacteria.

The drug penetrates the cell wall of the bacteria and binds to the 50S subunit of the ribosome. In other words, it binds to a part of a cellular structure responsible for protein synthesis. By being inhibited, it blocks the functioning of this structure known as the ribosome and, therefore, protein synthesis is not allowed.

By inhibiting this process, azithromycin works as a bacteriostatic, that is, it prevents the growth of the bacteria, because, without proteins, the bacteria can’t grow. In addition, at higher doses, it can have a bactericidal action (it kills the bacteria) on some germs such as S.pneumoniae, S.pyogenes, and H. influenzae.

Broad spectrum antibiotic?

We commented at the beginning of the article that this antibiotic is broad-spectrum, but what exactly is that? Antibiotics can either be broad-spectrum or narrow-spectrum. The former are those that show their action against gram-positive and gram-negative bacteria, while those with a reduced spectrum are only effective against one type of bacteria.

However, gram-positive and gram-negative bacteria are differentiated by the characteristics of their cell membranes. The former have a cell membrane composed of peptidoglycan and an internal cytoplasmic membrane formed by a double layer of lipids.

On the other hand, gram-negative ones, in addition to the inner cytoplasmic membrane, have another lipid bilayer in the outermost membrane. Between both membranes there is a space called the periplasmic space.

This space in gram-negative bacteria is made up of peptidoglycan, which is much larger and wider than in gram-positive bacteria. As we can see, the cell membrane of gram-negative ones is more complex than that of the positive ones.

To know if it’s one type or another, a series of tests must be carried out in the laboratory that allow us to classify the bacteria. The best-known technique is the Gram stain.

Pharmacokinetics

Within the topic of pharmacokinetics (the different processes through which the drug passes within the body) we’ll see the following points: absorption, distribution, metabolism and elimination.

Absorption

Azithromycin is administered orally. After that, the bioavailability, that is, the amount of drug that actually has the capacity to perform the effect, is approximately 37%. This bioavailability is so low because absorption is incomplete.

Furthermore, absorption is further compromised if the tablet is taken with food. It also decreases significantly if it’s administered simultaneously with an antacid containing aluminum or magnesium. The time to reach peak plasma concentrations is 2-3 hours.

Distribution

When administered orally, the drug is widely distributed throughout the body. Some studies on the pharmacokinetics of this drug have shown higher concentrations of azithromycin in tissues than in plasma.

This result indicates that the drug is highly tissue bound, a parameter to take into account for toxicity. However, at therapeutic doses, there’s no accumulation in the tissues.

Azithromycin is concentrated within cells, especially within phagocytes. These cells are a type of immune system cell that can surround and destroy microorganisms, ingest foreign material, and kill dead cells.

Metabolism

By metabolism or biotransformation we understand the chemical reactions that a drug undergoes in the body in order to make it more soluble and favor its elimination. Thus, concentrations of up to 237 mg/ml of azithromycin have been found in human bile along with 10 other metabolites.

Metabolites are the molecules resulting from the chemical reactions of the parent drug. None of these 10 metabolites have shown an important role in the microbiological activity of the macrolide. However, most of them are eliminated without having undergone transformations.

Elimination

Approximately 12% of an intravenously administered dose is excreted unchanged in the urine over a period of 3 days – the highest proportion in the first 24 hours.

However, most are eliminated in the feces without having undergone any transformation. The mean mean plasma elimination is 68 hours, while the tissue half-life varies between 1 and 4 days. This data indicates the capacity of azithromycin to accumulate in tissues.

Indications and dosage

Azithromycin is indicated for the following infections caused by sensitive microorganisms. Within these infections we find:

• Chest infections such as worsening chronic bronchitis and pneumonia.
• Infection of the sinuses, throat, tonsils or ears.
• Mild to moderate skin and soft tissue infections. For example, folliculitis, cellulitis, or erysipelas (skin infection with swelling and bright red color).
• Erythrema migrans (first stage of Lyme disease), when other antibiotics cannot be used.
• Chlamydia trachomatis, Mycoplasma pneumoniae, Treponema pallidum, and Mycobacterium avium complex infection.

The dose of the drug varies according to the indication. Most of the cases (in the pediatric population of more than 45 kg of weight and adults) a total dose of 1.5 g is required, distributed in 500 mg every day for 3 days. Another option is to give 500 mg the first day and then 250 mg daily for 4 days. Other presentations are available for different dosage regimens.

Some groups require dose adjustment. These are:

• Children weighing less than 45 kg: The tablets are not recommended for this group of patients. Other dosage forms such as suspensions can be used.
• Elderly patients: They can take the same dose as other adults. Those who are arrhythmic, special caution is recommended due to the risk of developing cardiac arrhythmia and torsades.
• Patients with renal and hepatic insufficiency: If it’s mild to moderate, a dose adjustment isn’t necessary.

Adverse reactions and contraindications

The vast majority of adverse effects are mild or moderate. In addition, by suppressing the treatment they disappear. The most frequent occur at the gastrointestinal level and include:

• Sickness
• Vomiting
• Diarrhea
• Abdominal pain

Its frequency is higher when higher doses are used and its gastrointestinal tolerability can improve if the drug is administered with meals.

On the other hand, there may also be other adverse effects such as rashes, hives, or itching. However, they occur in between 1 and 5% of cases. Some serious dermatological problems such as Stevens-Johnson syndrome, erythema multiforme, or toxic epidermal necrolysis have been described very rarely. Some cases of allergic problems have also been seen.

We haven’t mentioned all the adverse reactions as there are many despite their low occurrence levels. We have simply mentioned some of the most common.

We should also point out that azithromycin, like any other macrolide antibiotic or any of the excipients included in the formulation, is contraindicated in allergic patients.

Antibiotic resistance

Antibiotics such as azithromycin don’t work for colds, flu, and other viral infections. Using antibiotics when they aren’t needed increases the risk of getting an infection later that will resist antibiotic treatment.

A big problem we have today in the field of health is resistance to antibiotics. The fact that the strains are resistant to antibiotics means that this antibiotic is no longer effective against that bacterium, but how can this happen? Well, there are various mechanisms that these microorganisms develop to defend themselves from the effects of the drug.

Generally, the resistance of different bacterial species to macrolides occurs through mechanisms associated with:

• Changes in its location of action
• Modification of the antibiotic
• Changes in the transportation of the antibiotic

On the other hand, one may think that if that drug is no longer effective against that bacteria, we can use another and the problem ends. This is the solution we have today, but the problem is that we abuse the use of antibiotics and the bacteria that are being treated with the other antibiotic can also become resistant to it.

Because of this, there are fewer and fewer antibiotics that we can use against pathogenic bacteria and we could be left without a cure. The development of new drugs is a complex, long, and very expensive process, so you must avoid self-medicating or overusing these drugs.