Antimicrobial agents are described using two key suffixes: -cidal agents such as bactericidal drugs directly kill the organism, whereas -static agents such as bacteriostatic drugs inhibit growth and rely on the host immune system to clear the infection. Different antibiotic classes target distinct bacterial processes. Beta-lactams including penicillins and cephalosporins inhibit peptidoglycan cross-linking by binding penicillin-binding proteins, weakening the cell wall and causing lysis. Vancomycin binds the D-Ala-D-Ala terminus of peptidoglycan precursors, blocking cell wall synthesis, and is effective mainly against Gram-positives. Aminoglycosides such as gentamicin irreversibly bind the 30S ribosomal subunit, causing mRNA misreading and inhibiting protein synthesis. Tetracyclines also bind the 30S subunit, blocking aminoacyl-tRNA attachment, while macrolides like erythromycin and azithromycin bind the 50S subunit to block translocation.
Other antibiotics target nucleic acid and metabolic pathways. Fluoroquinolones such as ciprofloxacin inhibit DNA gyrase and topoisomerase IV, blocking DNA replication. Rifampin inhibits bacterial DNA-dependent RNA polymerase, halting transcription. Sulfonamides competitively inhibit dihydropteroate synthase, blocking folic acid synthesis required for nucleotide production. Metronidazole forms toxic free radicals in anaerobic and microaerophilic organisms, damaging their DNA and making it useful against anaerobes and certain protozoa. Two drugs that act on the same pathway can produce antibiotic synergy, an effect greater than the sum of individual contributions, as exemplified by trimethoprim-sulfamethoxazole, which sequentially blocks two steps of folate synthesis.
Four general mechanisms underlie antibiotic resistance: enzymatic drug inactivation, altered target sites, decreased drug uptake or permeability, and increased efflux pump activity. Beta-lactamase (penicillinase) hydrolyzes the beta-lactam ring, inactivating penicillins; beta-lactamase inhibitors such as clavulanic acid are combined with penicillins, as in Augmentin (amoxicillin-clavulanate), to protect the antibiotic. Extended-spectrum beta-lactamases (ESBLs) confer resistance to a broad range of beta-lactams including cephalosporins. Methicillin-resistant Staphylococcus aureus (MRSA) arises from altered penicillin-binding protein PBP2a, encoded by the mecA gene. Vancomycin-resistant Enterococcus (VRE) replaces the D-Ala-D-Ala terminus of peptidoglycan precursors with D-Ala-D-Lac, which vancomycin cannot bind. Resistance genes spread readily through horizontal gene transfer, commonly mediated by plasmids (R factors), transposons, and integrons transferred via conjugation.