Nonbetalactams

Nonbetalactams, or non-beta-lactam antibiotics, constitute a broad and diverse group of antimicrobial agents that do not contain the beta-lactam ring found in penicillins, cephalosporins, monobactams, and carbapenems. They are used to treat bacterial infections through mechanisms distinct from those of beta-lactams, and are often chosen when beta-lactams are ineffective, contraindicated, or when resistance diminishes beta-lactam utility.

Nonbetalactams act on a variety of bacterial targets. Inhibitors of protein synthesis include macrolides (such as azithromycin and erythromycin), lincosamides (clindamycin), tetracyclines (doxycycline), aminoglycosides (gentamicin), and oxazolidinones (linezolid). Agents that interfere with nucleic acid synthesis include fluoroquinolones (ciprofloxacin, levofloxacin), rifamycins (rifampin), and metronidazole. Compounds that disrupt cell membranes or cell wall synthesis without a beta-lactam mechanism include glycopeptides (vancomycin, teicoplanin), polymyxins (colistin), and daptomycin. Antimetabolites such as sulfonamides and trimethoprim inhibit folate synthesis. The nonbetalactams encompass many drug classes used across clinical settings, often with specific spectra and toxicity profiles.

Clinical use and considerations: Nonbetalactams are employed for a wide range of infections, including skin and soft tissue, respiratory, intra‑abdominal, and gynecologic infections, particularly when beta-lactams are contraindicated or resistance limits beta-lactam utility. Resistance arises through target modification, reduced uptake, efflux, or enzymatic inactivation, and cross-resistance with beta-lactams varies by drug class. Safety profiles differ by agent; for example, aminoglycosides can cause nephrotoxicity and ototoxicity, tetracyclines have restrictions in children and pregnant patients, macrolides may affect cardiac conduction, and metronidazole has a disulfiram-like potential with alcohol use.