Macrolides

Macrolides are relatively poorly absorbed orally. Fidaxomicin is minimally absorbed and active only locally in the gastrointestinal tract. Food has the following effects on macrolide absorption:

• For immediate-release clarithromycin tablet or suspension, no effect

Once absorbed, macrolides diffuse well into body fluids, except cerebrospinal fluid, and are concentrated in phagocytes. Excretion is mainly in bile.

Macrolides (except fidaxomicin) are active against

• Aerobic and anaerobic gram-positive cocci, except for most enterococci, many Staphylococcus aureus strains (especially methicillin-resistant strains), and some Streptococcus pneumoniae and S. pyogenes strains

• Mycoplasma pneumoniae

• Chlamydia trachomatis

• Chlamydophila pneumoniae

• Legionella species

• Corynebacterium diphtheriae

• Campylobacter species

• Treponema pallidum

• Cutibacterium acnes (formerly Propionibacterium acnes)

• Borrelia burgdorferi

Bacteroides fragilisHaemophilus influenzae and activity against Mycobacterium avium complex.

Macrolides have been considered the antibiotics of choice for group A streptococcal and pneumococcal infections when penicillin cannot be used. However, pneumococci with reduced penicillin sensitivity are often resistant to macrolides, and macrolide resistance among S. pyogenes varies globally. Because macrolides are active against atypical respiratory pathogens, they are often used empirically for lower respiratory tract infections, but another antibiotic is often necessary to cover macrolide-resistant pneumococci. Macrolides have other clinical uses (see table Some Clinical Uses of Macrolides). Macrolides are not used to treat meningitis.

Clostridioides difficile (formerly Clostridium difficile). It is used exclusively for C. difficile infection because there is minimal systemic absorption.

Macrolides are contraindicated in patients who have had an allergic reaction to them.

erythromycin and clarithromycin.

erythromycin during early pregnancy than after exposure to penicillin exposure; however, in other studies this increased risk was not observed. Erythromycin is considered safer than azithromycin because clinical use has been much more extensive.

Clarithromycin should not be used in pregnant women except when there is no alternative therapy.

Fidaxomicin has minimal systemic absorption, therefore risk of adverse effect to a fetus or breastfeeding infant should be relatively low.

Main concerns with macrolides include

• Gastrointestinal (GI) disturbances (mainly with erythromycin)

• QT-interval prolongation

• Inhibition of hepatic metabolism, leading to numerous drug interactions

Erythromycinerythromycin has been given previously. Erythromycin is not given IM because it causes severe pain; when given IV, it may cause phlebitis or pain. Hypersensitivity reactions are rare.

hypertrophic pyloric stenosis. This risk is less with other macrolides.

Azithromycin is the least likely to interact with other medications.

Interactions may occur when erythromycin or clarithromycin is taken with the following: