Since the 1970s, PLIVA's research team, led by Dr Slobodan Dokic, had been working in the area of macrolide antibiotics. In 1981, his team of researchers, Gabrijela Kobrehel, Zrinka Tamburasev and Gorjana Radobolja-Lazarevski, synthesised a novel antibiotic named azithromycin, the first member of a new class of macrolide antibiotics, termed azalides. The newly formed molecule, azithromycin dihydrate, was obtained from the erythromycin molecule and demonstrated properties superior to those of the original molecule. Because of its exceptional therapeutic properties, azithromycin revolutionised antibiotic treatment and became one of the most successful drugs worldwide. From its early trials, it proved to be an extremely efficient antibiotic with expanded and enhanced antibacterial activity (particularly against gram-negative pathogens), prolonged and higher tissue concentration and a low incidence of gastrointestinal side effects compared to other similar antibiotics.

Azithromycin has a number of principal applications: the treatment of respiratory tract infections, skin and soft tissue infections, gastric and duodenal infections caused by Helicobacter pylori and sexually transmitted diseases. Its competitive advantages over other known antibiotics are its short dosing period (3 days as opposed to 10) and low potential for adverse drug reactions.

On 20 August 2000 in Washington D.C., USA, the American Chemical Society (ACS), a non-profit association of American chemists and chemical engineers and the largest association of scientists in the world organised the "Heroes of Chemistry 2000" ceremony. For their discovery of azithromycin, PLIVA scientists Slobodan Dokic and Gabrijela Kobrehel were named "Heroes of Chemistry", together with representatives from US-based Pfizer which had also contributed to the success of azithromycin, today marketed worldwide as Sumamed and Zithromax. The "Heroes of Chemistry 2000" award is one of numerous awards presented over the years to PLIVA scientists for their long-term contribution to global science, medicine and the improvement of quality of life. This latest recognition is additional confirmation of the value and achievements of PLIVA's entire team of researchers who worked on the discovery of azithromycin. The discovery of azithromycin was the greatest event in history of PLIVA's research and a milestone for the Croatian pharmaceuticals industry. That success has put PLIVA among those few pharmaceutical companies in the world that have developed their own drug.

Many years of research led PLIVA to the development of a valuable drug with huge therapeutic and marketing potential. In 1981, PLIVA filed a patent application for azithromycin in the former Yugoslavia, which was followed by further applications worldwide, including in the United States. PLIVA's first patent for azithromycin was granted in Belgium. In 1988 PLIVA registered azithromycin under the brand name Sumamed.
PLIVA chose Pfizer as its strategic and licensing partner because of Pfizer's overall capabilities and track record and because its international presence and sales force complemented PLIVA's presence in Central and Eastern Europe. Additionally, Pfizer had developed additional understanding of azithromycin as a result of its own research in this area. For PLIVA, the licensing agreement meant a huge breakthrough in terms of annual revenues and the expansion of research activities.

Azithromycin acts by interfering with bacterial protein synthesis. Although this mechanism is considered bacteriostatic, concentrations several times higher than minimum inhibitory concentrations (MIC) contribute to the bactericidal activity of azithromycin.
Azithromycin is rapidly absorbed and distributed throughout body tissues, reaching high and sustained tissue concentrations that result in sustained antimicrobial activity. Since azithromycin is a weak base, it easily penetrates the cell membrane and stays within the cell, mainly in lysosomes. High concentrations of azithromycin are found in infected tissues since phagocytes, polymorphonuclear leukocytes and macrophages deliver azithromycin to the infection site and release it there in the presence of bacteria.
Those pharmacokinetic properties of azithromycin in combination with wide antimicrobial activity give the drug wide therapeutic applications. For the majority of infections, azithromycin is administered once daily for three days. In the treatment of sexually transmitted diseases, azithromycin is administered as a single dose and in the treatment of erythema migrans once daily over 5 days. Azithromycin's short dosing regimen is convenient for the patients and improves patient compliance.
In clinical trials, azithromycin showed itself to be either better or equally well tolerated, compared to other antibiotics. The tolerability and safety profile of azithromycin (Sumamed) have been assessed in 4,727 patients enrolled in clinical trials carried out in Croatia, the Czech Republic, Hungary, Macedonia, Poland, the Slovak Republic, Slovenia, Russia and the former Yugoslavia. In addition, azithromycin, unlike the majority of macrolides, does not bind to cytochrome P-450 in the liver, resulting in low potential for drug to drug interaction.

Numerous clinical trials have confirmed azithromycin's efficacy for many different indications. At present, azithromycin is used in the treatment of upper respiratory tract infections (bacterial pharyngitis/tonsillitis, bacterial sinusitis, bacterial otitis media), lower respiratory tract infections (bacterial bronchitis, acute exacerbation of chronic bronchitis, community acquired pneumonia), sexually transmitted diseases (uncomplicated urethritis, uncomplicated cervicitis), pelvic inflammatory disease, gastric and duodenal infections caused by Helicobacter pylori, skin and soft tissue infections (erysipelas, impetigo, secondary pyoderma, erythema migrans) and prevention of disseminated Mycobacterium avium complex in persons with advanced HIV infection.
Azithromycin's advantage is its activity against gram-negative organisms, particularly Haemophilus influenzae, and intracellular and other organisms (Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia trachomatis and Legionella pneumophila). Since azithromycin shows a good activity against the most common pathogens it is used as a choice for empirical therapy.

Clinical investigation into new indications is lead by the in vitro activity of azithromycin on one hand and unmet medical needs on the other. Potential prospects for azithromycin in clinical usage belong to field of infectious diseases and chronic "non-infectious" diseases. Among infectious diseases, azithromycin may have potential uses in the treatment of acute infectious diarrhoea, inclusion conjunctivitis, dental infections, acne, pertussis, prostatitis, trachoma, toxoplasmosis, syphilis, rickettsiosis, leptospirosis and typhoid fever. In field of chronic "non-infectious" diseases, the strongest indication extensively investigated so far is atherosclerosis.