Classification of antibiotics
Antibacterial agents are divided into bactericidal (kill microorganisms) and bacteriostatic (halt growth). To memorize the main groups, a mnemonic combining key classes is used:
- Tetracyclines — tetracycline, doxycycline, tigecycline;
- Quinolones/fluoroquinolones — levofloxacin, moxifloxacin, gemifloxacin;
- Glycopeptides — vancomycin, teicoplanin;
- Cephalosporins of five generations — cefazolin, cefoxitin, ceftriaxone, ceftazidime, cefepime, ceftaroline;
- Sulfonamides — sulfamethoxazole;
- Aminoglycosides — gentamicin, streptomycin;
- Carbapenems — meropenem, imipenem, doripenem, ertapenem;
- Penicillins — penicillin G and V, antistaphylococcal penicillins (nafcillin, oxacillin, dicloxacillin), aminopenicillins (amoxicillin, ampicillin), antipseudomonal penicillins (piperacillin);
- Macrolides — azithromycin, clarithromycin, erythromycin;
- Rifampin, metronidazole, monobactams (aztreonam), oxazolidinones (linezolid).
Mechanisms of action
Antibiotics target five key components of the bacterial cell.
Inhibition of cell wall synthesis
Vancomycin, teicoplanin and cycloserine bind to the D-alanine residue, blocking transpeptidase and peptidoglycan formation. Fosfomycin inhibits the MurA enzyme at the precursor synthesis stage. Beta-lactams (penicillins, cephalosporins, carbapenems, monobactams), due to their four-membered beta-lactam ring, bind to penicillin-binding proteins (PBPs) and disrupt cross-linking. Bacteria produce beta-lactamases that cleave this ring; clavulanic acid, sulbactam, and tazobactam are used to inhibit them.
Damage to the cell membrane
Daptomycin forms a channel through which potassium ions exit, disrupting the membrane potential and ATP synthesis; it is inactivated by pulmonary surfactant. Polymyxins act as cationic detergents, disrupting the membrane — they are highly toxic and used as reserve drugs.
Disruption of nucleotide synthesis
Sulfamethoxazole blocks dihydropteroate synthase, and trimethoprim blocks dihydrofolate reductase. Their combination (co-trimoxazole, bactrim) provides a bactericidal effect.
Effects on DNA and RNA
Metronidazole and nitrofurantoin form free radicals under anaerobic conditions that damage DNA. Rifampin inhibits DNA-dependent RNA polymerase. Fluoroquinolones block DNA gyrase and topoisomerase IV.
Inhibition of protein synthesis
The bacterial ribosome (70S) consists of 30S and 50S subunits. Aminoglycosides (bactericidal) and tetracyclines (bacteriostatic) act on the 30S subunit. Macrolides, clindamycin, chloramphenicol, and linezolid act on the 50S subunit.
Spectrum of activity
Gram-positive bacteria
Against methicillin-susceptible S. aureus (MSSA), penicillins, antistaphylococcal penicillins, first-generation cephalosporins, and fluoroquinolones are used. Against MRSA — vancomycin, daptomycin (except for pneumonia), ceftaroline, co-trimoxazole, linezolid. S. pneumoniae and S. pyogenes are susceptible to penicillins, aminopenicillins, cephalosporins, macrolides, and clindamycin. Enterococci are resistant to most beta-lactams; aminopenicillins and nitrofurantoin (for cystitis) are effective, while linezolid is used against vancomycin-resistant E. faecium. Listeria requires intracellular-penetrating drugs: aminopenicillins and co-trimoxazole.
Gram-negative bacteria
HENS PEcKS mnemonic: Haemophilus, Enterobacter, Neisseria, Serratia, Proteus, E. coli, Klebsiella, Pseudomonas. P. aeruginosa and Acinetobacter require antipseudomonal penicillins, third- and fourth-generation cephalosporins, carbapenems, and aminoglycosides. ESBL producers are treated with carbapenems, aminoglycosides, or the ceftazidime/avibactam combination. Stenotrophomonas maltophilia is primarily susceptible to co-trimoxazole.
Anaerobes and atypical pathogens
Anaerobes above the diaphragm — clindamycin; below the diaphragm — metronidazole. For C. difficile colitis — oral vancomycin or metronidazole. Atypical pathogens (Mycoplasma, Chlamydia, Legionella) — macrolides, respiratory fluoroquinolones, tetracyclines. Spirochetes (Borrelia, Treponema) — doxycycline, penicillin G.
Empirical antibiotic therapy
- Community-acquired pneumonia: azithromycin, doxycycline, or amoxicillin/clavulanate; for hospitalized patients — ceftriaxone + azithromycin.
- Hospital-acquired pneumonia: vancomycin + piperacillin/tazobactam or cefepime (covering MRSA and Pseudomonas).
- Pyelonephritis: intravenous ceftriaxone; complicated cases — addition of vancomycin and antipseudomonal drugs.
- Uncomplicated cystitis: nitrofurantoin or fosfomycin.
- Community-acquired meningitis: ceftriaxone + vancomycin; listerial meningitis — ampicillin.
- Sepsis, osteomyelitis: drug of choice is vancomycin (often in combination regimens).
Side effects and interactions
Neurotoxicity: penicillins, cephalosporins, carbapenems, polymyxins, linezolid (serotonin syndrome when combined with antidepressants). Hematological disorders: cytopenias with penicillins, cephalosporins, co-trimoxazole, chloramphenicol, linezolid. Ototoxicity and nephrotoxicity: aminoglycosides and vancomycin. Pulmonary fibrosis: nitrofurantoin. Tendinitis and Achilles tendon rupture: fluoroquinolones. QT prolongation: fluoroquinolones, macrolides. Disulfiram-like reaction with alcohol — metronidazole, ceftriaxone. Hemolytic anemia in G6PD deficiency: sulfonamides, fluoroquinolones, nitrofurantoin. Photosensitization: doxycycline, co-trimoxazole. Broad-spectrum agents (clindamycin, carbapenems, third- and fourth-generation cephalosporins) increase the risk of C. difficile colitis.
Fluoroquinolones, tetracyclines, co-trimoxazole, and chloramphenicol are contraindicated in pregnancy. Dangerous combinations: cephalosporins + aminoglycosides (nephrotoxicity), aminoglycosides + loop diuretics, tetracyclines with dairy products (impaired absorption), macrolides and co-trimoxazole with warfarin (elevated INR).
Key points
- Five mechanisms of action: cell wall inhibition, membrane damage, disruption of DNA, RNA, nucleotide, and protein synthesis.
- Beta-lactams bind to PBPs; the primary mechanism of resistance is beta-lactamases, which are neutralized by clavulanate, sulbactam, or tazobactam.
- MRSA requires vancomycin, linezolid, or ceftaroline; daptomycin is ineffective for pneumonia.
- Anaerobes above the diaphragm — clindamycin; below the diaphragm — metronidazole.
- Atypical pneumonias are treated with macrolides, respiratory fluoroquinolones, or doxycycline.
- Aminoglycosides and vancomycin exhibit oto- and nephrotoxicity; their combination with cephalosporins or loop diuretics is hazardous.
- Fluoroquinolones and macrolides prolong the QT interval and can provoke torsades de pointes.
- Broad-spectrum agents are the main risk factor for pseudomembranous colitis caused by C. difficile.