Macrolidelike

Macrolidelike refers to a group of antibiotics that share a macrocyclic lactone ring and a mechanism of inhibiting bacterial protein synthesis by binding to the 50S ribosomal subunit. The term encompasses macrolides and related compounds that have similar structure and pharmacodynamic properties.

Most macrolidelike agents are bacteriostatic in typical therapeutic concentrations. They act by binding to the 23S rRNA portion of the 50S subunit, inhibiting translocation of the peptidyl-tRNA and blocking protein elongation. The macrocyclic ring is typically 14 to 16 members in size, with various substituents shaping pharmacokinetics and spectrum.

Major subgroups include macrolides (erythromycin, clarithromycin, azithromycin), azalides (azithromycin), and ketolides (telithromycin). All share activity against many Gram-positive cocci and atypical pathogens such as Mycoplasma and Chlamydophila, with varying activity against Gram-negatives. Azalides and ketolides were developed to improve pharmacokinetic properties and activity, including coverage of some macrolide-resistant strains.

Pharmacokinetics and clinical use: macrolidelike agents generally have good oral bioavailability and tissue penetration, with varying half-lives. Erythromycin and clarithromycin can inhibit cytochrome P450 enzymes, whereas azithromycin has fewer interactions. Clinically, they are used for respiratory tract infections, skin and soft tissue infections, and sexually transmitted infections caused by atypical pathogens, and as alternatives for patients with penicillin allergy.

Resistance and safety: common resistance mechanisms include methylation of the 23S rRNA (MLS_B) and efflux pumps, reducing binding or intracellular concentrations. Safety considerations include gastrointestinal upset, QT interval prolongation (notably with some macrolides), and potential drug interactions; ketolides have raised safety concerns in some contexts.