and methylase production are by far the most important resistance mechanisms in gram-positive organisms.Cross-resistance is complete between erythromycin and the other macrolides.Constitutive methylase production also confers resistance to structurally unrelated but mechanistically similar compounds such as clindamycin and streptogramin B(so-called macrolide-lincosamide-streptogramin,or MLS-type B, resistance),which share the same ribosomal binding site.Because nonmacrolides are poor inducers of the methylase,strains expressing an inducible methylase will appear susceptible in vitro.However,constitutive mutants that are resistant can be selected out and emerge during therapy with clindamycin. Pharmacokinetics Erythromycin base is destroyed by stomach acid and must be administered with enteric coating.Food interferes with absorption.Stearates and esters are fairly acid-resistant and somewhat better absorbed.The lauryl salt of the propionyl ester of erythromycin (erythromycin estolate)is the best-absorbed oral preparation.Oral dosage of 2 g/d results in serum erythromycin base and ester concentrations of approximately 2 mg/mL.However,only the base is microbiologically active,and its concentration tends to be similar regardless of the formulation.A 500-mg intravenous dose of erythromycin lactobionate produces serum concentrations of 10 mg/mL 1 hour after dosing.The serum half-life is approximately 1.5 hours normally and 5 hours in patients with anuria.Adjustment for renal failure is not necessary. Erythromycin is not removed by dialysis.Large amounts of an administered dose are excreted in the bile and lost in feces,and only 5%is excreted in the urine.Absorbed drug is distributed widely except to the brain and cerebrospinal fluid.Erythromycin is taken up by polymorphonuclear leukocytes and macrophages.It traverses the placenta and reaches the fetus. Clinical Uses An erythromycin is a drug of choice in corynebacterial infections (diphtheria. corynebacterial sepsis,erythrasma);in respiratory,neonatal,ocular,or genital chlamydial infections;and in treatment of community-acquired pneumonia because its spectrum of activity includes pneumococcus,mycoplasma,and legionella. Erythromycin is also useful as a penicillin substitute in penicillin-allergic individuals with infections caused by staphylococci (assuming that the isolate is susceptible), streptococci,or pneumococci.Emergence of erythromycin resistance in strains of group A streptococci and pneumococci(penicillin-resistant pneumococci in particular) has made macrolides less attractive as first-line agents for treatment of pharyngitis, skin and soft tissue infections,and pneumonia.Erythromycin has been recommended as prophylaxis against endocarditis during dental procedures in individuals with valvular heart disease,although clindamycin,which is better tolerated,has largely replaced it.Although erythromycin estolate is the best-absorbed salt,it imposes the greatest risk of adverse reactions.Therefore,the stearate or succinate salt may beand methylase production are by far the most important resistance mechanisms in gram-positive organisms. Cross-resistance is complete between erythromycin and the other macrolides. Constitutive methylase production also confers resistance to structurally unrelated but mechanistically similar compounds such as clindamycin and streptogramin B (so-called macrolide-lincosamide-streptogramin, or MLS-type B, resistance), which share the same ribosomal binding site. Because nonmacrolides are poor inducers of the methylase, strains expressing an inducible methylase will appear susceptible in vitro. However, constitutive mutants that are resistant can be selected out and emerge during therapy with clindamycin. Pharmacokinetics Erythromycin base is destroyed by stomach acid and must be administered with enteric coating. Food interferes with absorption. Stearates and esters are fairly acid-resistant and somewhat better absorbed. The lauryl salt of the propionyl ester of erythromycin (erythromycin estolate) is the best-absorbed oral preparation. Oral dosage of 2 g/d results in serum erythromycin base and ester concentrations of approximately 2 mg/mL. However, only the base is microbiologically active, and its concentration tends to be similar regardless of the formulation. A 500-mg intravenous dose of erythromycin lactobionate produces serum concentrations of 10 mg/mL 1 hour after dosing. The serum half-life is approximately 1.5 hours normally and 5 hours in patients with anuria. Adjustment for renal failure is not necessary. Erythromycin is not removed by dialysis. Large amounts of an administered dose are excreted in the bile and lost in feces, and only 5% is excreted in the urine. Absorbed drug is distributed widely except to the brain and cerebrospinal fluid. Erythromycin is taken up by polymorphonuclear leukocytes and macrophages. It traverses the placenta and reaches the fetus. Clinical Uses An erythromycin is a drug of choice in corynebacterial infections (diphtheria, corynebacterial sepsis, erythrasma); in respiratory, neonatal, ocular, or genital chlamydial infections; and in treatment of community-acquired pneumonia because its spectrum of activity includes pneumococcus, mycoplasma, and legionella. Erythromycin is also useful as a penicillin substitute in penicillin-allergic individuals with infections caused by staphylococci (assuming that the isolate is susceptible), streptococci, or pneumococci. Emergence of erythromycin resistance in strains of group A streptococci and pneumococci (penicillin-resistant pneumococci in particular) has made macrolides less attractive as first-line agents for treatment of pharyngitis, skin and soft tissue infections, and pneumonia. Erythromycin has been recommended as prophylaxis against endocarditis during dental procedures in individuals with valvular heart disease, although clindamycin, which is better tolerated, has largely replaced it. Although erythromycin estolate is the best-absorbed salt, it imposes the greatest risk of adverse reactions. Therefore, the stearate or succinate salt may be