of the extended release formulation once daily.Clarithromycin penetrates most tissues well,with concentrations equal to or exceeding serum concentrations. Clarithromycin is metabolized in the liver.The major metabolite is 14-hydroxyclarithromycin,which also has antibacterial activity.A portion of active drug and this major metabolite is eliminated in the urine,and dosage reduction (eg,a 500-mg loading dose,then 250 mg once or twice daily)is recommended for patients with creatinine clearances less than 30 mL/min.Clarithromycin has drug interactions similar to those described for erythromycin. The advantages of clarithromycin compared with erythromycin are lower incidence of gastrointestinal intolerance and less frequent dosing.Except for the specific organisms noted above,the two drugs are otherwise therapeutically very similar,and the choice of one over the other usually turns out to be cost and tolerability AZITHROMYCIN Azithromycin,a 15-atom lactone macrolide ring compound,is derived from erythromycin by addition of a methylated nitrogen into the lactone ring.Its spectrum of activity and clinical uses are virtually identical to those of clarithromycin. Azithromycin is active against M avium complex and T gondii.Azithromycin is slightly less active than erythromycin and clarithromycin against staphylococci and streptococci and slightly more active against H influenzae.Azithromycin is highly active against chlamydia. Azithromycin differs from erythromycin and clarithromycin mainly in pharmacokinetic properties.A 500-mg dose of azithromycin produces relatively low serum concentrations of approximately 0.4 mcg/mL.However,azithromycin penetrates into most tissues (except cerebrospinal fluid)and phagocytic cells extremely well,with tissue concentrations exceeding serum concentrations by 10-to 100-fold.The drug is slowly released from tissues (tissue half-life of 2-4 days)to produce an elimination half-life approaching 3 days.These unique properties permit once-daily dosing and shortening of the duration of treatment in many cases.For example,a single 1-g dose of azithromycin is as effective as a 7-day course of doxycycline for chlamydial cervicitis and urethritis.Community-acquired pneumonia can be treated with azithromycin given as a 500-mg loading dose,followed by a 250-mg single daily dose for the next 4 days. Azithromycin is rapidly absorbed and well tolerated orally.It should be administered 1 hour before or 2 hours after meals.Aluminum and magnesium antacids do not alter bioavailability but delay absorption and reduce peak serum concentrations.Because it has a 15-member (not 14-member)lactone ring,azithromycin does not inactivate cytochrome P450 enzymes and therefore is free of the drug interactions that occur with erythromycin and clarithromycin.of the extended release formulation once daily. Clarithromycin penetrates most tissues well, with concentrations equal to or exceeding serum concentrations. Clarithromycin is metabolized in the liver. The major metabolite is 14-hydroxyclarithromycin, which also has antibacterial activity. A portion of active drug and this major metabolite is eliminated in the urine, and dosage reduction (eg, a 500-mg loading dose, then 250 mg once or twice daily) is recommended for patients with creatinine clearances less than 30 mL/min. Clarithromycin has drug interactions similar to those described for erythromycin. The advantages of clarithromycin compared with erythromycin are lower incidence of gastrointestinal intolerance and less frequent dosing. Except for the specific organisms noted above, the two drugs are otherwise therapeutically very similar, and the choice of one over the other usually turns out to be cost and tolerability. AZITHROMYCIN Azithromycin, a 15-atom lactone macrolide ring compound, is derived from erythromycin by addition of a methylated nitrogen into the lactone ring. Its spectrum of activity and clinical uses are virtually identical to those of clarithromycin. Azithromycin is active against M avium complex and T gondii. Azithromycin is slightly less active than erythromycin and clarithromycin against staphylococci and streptococci and slightly more active against H influenzae. Azithromycin is highly active against chlamydia. Azithromycin differs from erythromycin and clarithromycin mainly in pharmacokinetic properties. A 500-mg dose of azithromycin produces relatively low serum concentrations of approximately 0.4 mcg/mL. However, azithromycin penetrates into most tissues (except cerebrospinal fluid) and phagocytic cells extremely well, with tissue concentrations exceeding serum concentrations by 10- to 100-fold. The drug is slowly released from tissues (tissue half-life of 2-4 days) to produce an elimination half-life approaching 3 days. These unique properties permit once-daily dosing and shortening of the duration of treatment in many cases. For example, a single 1-g dose of azithromycin is as effective as a 7-day course of doxycycline for chlamydial cervicitis and urethritis. Community-acquired pneumonia can be treated with azithromycin given as a 500-mg loading dose, followed by a 250-mg single daily dose for the next 4 days. Azithromycin is rapidly absorbed and well tolerated orally. It should be administered 1 hour before or 2 hours after meals. Aluminum and magnesium antacids do not alter bioavailability but delay absorption and reduce peak serum concentrations. Because it has a 15-member (not 14-member) lactone ring, azithromycin does not inactivate cytochrome P450 enzymes and therefore is free of the drug interactions that occur with erythromycin and clarithromycin