VANCOUVER, BRITISH COLUMBIA–Azithromycin (Zithromax), the first of a new generation of antibiotics, appears to boost compliance with its highly abbreviated regimen, reported Godfrey Harding, MD, at the Dermatology Update here.

“Azithromycin’s spectrum is quite broad and includes both gram-negative and gram-positive organisms. Because the standard regimen is 5 days, most patients will take all their medication. In Europe the regimen is only 3 days,” said Dr. Harding, professor, departments of medicine and medical microbiology, the University of Manitoba, Winnipeg, Manitoba.

The reason it is recommended for 3 days in Europe and 5 days in North America is that the US studies that provided supporting data were all 5 days long, he said.

A major distinguishing feature of the drug is not the range of its activity, which is comparable with that of clarithromycin(Biaxin), but its pharmacokinetics. Azithromycin does not have high serum levels. Instead, it is taken up by macrophages and polymorphonuclear leukocytes and is concentrated in phagosomes and lysosomes. The cells containing the agent deliver it to the infection site. Because it is concentrated in cells at the infection site rather than in serum, it remains effective for a longer time, explained Dr. Harding.

“Even though it doesn’t staylong in the serum and serum levels are low, you get higher ‘levels in tissues. It stays there for a long time. This is why it works so well against nongono-coccal urethritis and chlamydia cervicitis. It can stay in tissues for as long as 4 to 7 days after the last dose,” he said.
High Levels in Tissues

It also is important to note that any gram-positive organism that is resistant to erythromycin, such as Staphylococcus aureus, may be resistant to azithromycin. Cloxacillin (Cloxapen, Tegopen) should be considered for S aureus in patients not allergic to penicillin, he said. Because of its lower cost, penicillin also remains the drug of choice for streptococcal impetigo and pharyngitis. It also is still used for syphilis and some strep-tococcal skin infections such as erysipelas, he added.

“On the other hand, azithromycin works better against Hae-mophilus influenzae than clarithromycin. This is because of azithromycin’s structure,” said the doctor.

Whereas clarithromycin is a second-generation macrolide, azithromycin is an azalide, a prototype for an entirely new generation of antibiotics, he explained. It has nitrogen and a methyl group central to its structure. The addition of the nitrogen makes it an azalide, therefore, changing its properties.

Azithromycin is recommended as a single-dose, first-line therapy for Chlamydia trachomatis (nongonococcal urethritis and mucopurulent cervicitis).
Single Dose a Plus

“A patient can take the drug in the office and does not have to take doxycycline for 7 days. Single-dose azithromycin and a 7-day course of doxycycline were compared in some studies and they were found to be equally effective,” said Dr. Harding.

The single-dose treatment is especially important when treating contacts of the infected patient, he explained. In contacts, the disease may be asymptomatic. If they are given a twice-a-day, 7-day course of doxycycline, they may take it for 2 or 3 days, but because there are no symptoms, they may forget about it, he said.

Although it is recommended only for chlamydia cervicitis and nongonococcal urethritis, a single dose also appears to work well against Haemophilus ducreyi and chancroid, Dr. Harding added.

Other indications for the new agent may follow. Studies have shown that it has significant in vitro activity against Group A streptococci (Streptococcus pyogenes), Group B streptococci (Sagalactiae), Staphylococcus aureus, Moraxella catarrhalis, Haemophilus influenzae, Hae-mophilus ducreyi (chancroid), Chlamydia trachomatis, C pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae, and Mycobacterium avium complex. It also appears effective against bacillary angiomatosis due to Bartonella (Rochalimaea) henseleae and Borrelia burgdorferi, the organism responsible for Lyme disease.

The macrolides were a major advance when erythromycin was introduced in the 1950s but they were not without shortcomings. Among these were a relatively low bioavailability, which required frequent dosing and caused gastrointestinal side effects. The azalide class of drugs was discovered as part of the quest to improve on the macrolides, said Dr. Harding.
Resistance Likely

The doctor said he knows of no documented development of resistance to the drug but does not doubt that it will appear sooner or later. “It will appear eventually. Everything becomes resistant in time,” he cautioned.

Though the agent appears to be better tolerated than others of its class, it is not without side effects. Studies have compared azithromycin with amoxicillin/clavulanic acid, amoxicillin, penicillin V, erythromycin, di-cloxacillin, and flucloxacillin as therapies for otitis media, pharyngitis, and skin infections in children. The most frequently seen side effects were gastrointestinal, which appeared in 7.6% of the azitbromycin-treated patients compared with 13.8% of the patients given the other agents.

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By Mac Overmeyer, Contributing Editor