Classification of antibiotics and all examples
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Classification of Antibiotics
Antibiotics are classified along several dimensions: mechanism of action, chemical structure, and spectrum of activity. The primary classification by mechanism is the most clinically useful.
1. INHIBITORS OF CELL WALL SYNTHESIS
A. Beta-Lactams
All share a beta-lactam ring; bind penicillin-binding proteins (PBPs) and block peptidoglycan crosslinking.
i. Natural Penicillins
| Drug | Route | Notes |
|---|---|---|
| Penicillin G (benzylpenicillin) | IV/IM | Acid-labile; narrow spectrum |
| Penicillin V (phenoxymethylpenicillin) | Oral | Acid-stable oral form |
Spectrum: Beta-hemolytic streptococci, meningococci, most gram-positive anaerobes. Poor against gram-negatives.
ii. Penicillinase-Resistant Penicillins (Anti-staphylococcal)
| Drug |
|---|
| Methicillin |
| Nafcillin |
| Oxacillin |
| Cloxacillin / Dicloxacillin / Flucloxacillin |
Spectrum: Active against penicillinase-producing Staphylococcus aureus (MSSA). Useless against MRSA.
iii. Broad-Spectrum (Aminopenicillins)
| Drug |
|---|
| Ampicillin |
| Amoxicillin |
Spectrum: Gram-positive cocci + some gram-negatives (E. coli, Proteus, Haemophilus).
iv. Extended-Spectrum (Antipseudomonal) Penicillins
| Drug |
|---|
| Piperacillin |
| Ticarcillin |
| Carbenicillin |
Spectrum: Broad, including Pseudomonas aeruginosa.
v. Beta-Lactam + Beta-Lactamase Inhibitor Combinations
| Combination |
|---|
| Ampicillin-sulbactam (Unasyn) |
| Amoxicillin-clavulanate (Augmentin) |
| Ticarcillin-clavulanate (Timentin) |
| Piperacillin-tazobactam (Zosyn) |
| Ceftazidime-avibactam |
| Ceftolozane-tazobactam |
| Meropenem-vaborbactam |
Beta-lactamase inhibitors (clavulanic acid, sulbactam, tazobactam, avibactam) are relatively inactive alone but irreversibly inhibit beta-lactamases, restoring activity of the companion drug.
B. Cephalosporins
Derived from 7-aminocephalosporanic acid; same mechanism as penicillins but wider spectrum and more stable to many beta-lactamases. Classified by "generations":
| Generation | Key Drugs | Spectrum |
|---|---|---|
| 1st | Cephalexin, Cefazolin, Cephalothin, Cefadroxil | Gram-positive cocci (MSSA), limited gram-negatives |
| 2nd | Cefuroxime, Cefaclor, Cefprozil, Cefoxitin (cephamycin), Cefotetan | Broader gram-negative coverage (H. influenzae, Moraxella); cephamycins cover anaerobes |
| 3rd | Cefotaxime, Ceftriaxone, Ceftazidime, Cefixime, Cefdinir, Cefpodoxime | Extended gram-negative coverage including Enterobacteriaceae; ceftazidime covers Pseudomonas |
| 4th | Cefepime | Broad spectrum; Pseudomonas + gram-positives |
| 5th | Ceftaroline, Ceftobiprole | Active against MRSA (binds PBP2a) |
C. Carbapenems
Broadest spectrum beta-lactams; stable to most beta-lactamases including ESBLs. Not active against MRSA.
| Drug |
|---|
| Imipenem-cilastatin (cilastatin prevents renal inactivation) |
| Meropenem |
| Ertapenem (no Pseudomonas coverage) |
| Doripenem |
| Biapenem |
D. Monobactams
Monocyclic beta-lactam ring; active only against aerobic gram-negatives (including Pseudomonas). Safe in penicillin allergy (minimal cross-reactivity).
| Drug |
|---|
| Aztreonam |
E. Glycopeptides
Inhibit cell wall synthesis by binding D-Ala-D-Ala terminus of peptidoglycan precursors. Active against gram-positives only (including MRSA).
| Drug | Notes |
|---|---|
| Vancomycin | First-line for MRSA |
| Teicoplanin | Longer half-life |
| Dalbavancin | Long-acting (weekly dosing) |
| Oritavancin | Single-dose therapy |
| Televancin | Active against MRSA, VRE |
F. Other Cell Wall Inhibitors
| Drug | Class | Notes |
|---|---|---|
| Bacitracin | Polypeptide | Topical use; gram-positives |
| Fosfomycin | Phosphonic acid | Inhibits MurA; UTI treatment |
| Cycloserine | D-amino acid analog | Anti-TB (2nd line) |
| Isoniazid (INH) | Nicotinic acid analog | Anti-TB; inhibits mycolic acid synthesis |
| Ethambutol | Synthetic | Anti-TB; inhibits arabinogalactan synthesis |
| Ethionamide | Thioamide | Anti-TB (2nd line) |
2. INHIBITORS OF PROTEIN SYNTHESIS (30S Ribosome)
A. Aminoglycosides
Bind 30S ribosomal subunit; cause misreading of mRNA. Bactericidal. Concentration-dependent killing.
| Drug |
|---|
| Gentamicin |
| Amikacin |
| Tobramycin |
| Streptomycin (also anti-TB) |
| Neomycin (topical) |
| Kanamycin |
| Netilmicin |
| Spectinomycin |
Spectrum: Aerobic gram-negatives; synergistic with beta-lactams against enterococci.
B. Tetracyclines
Bind 30S subunit; reversibly block aminoacyl-tRNA binding. Bacteriostatic. Broad spectrum.
| Generation | Drugs |
|---|---|
| Classic | Tetracycline, Oxytetracycline, Chlortetracycline |
| Long-acting | Doxycycline, Minocycline |
| Glycylcycline | Tigecycline (overcomes tetracycline resistance) |
| New | Omadacycline, Eravacycline |
Uses: Atypicals (Chlamydia, Mycoplasma, Rickettsia), Brucella, acne, community-acquired pneumonia.
3. INHIBITORS OF PROTEIN SYNTHESIS (50S Ribosome)
A. Macrolides
Bind 50S subunit; block translocation. Bacteriostatic (bactericidal at high concentrations). Excellent intracellular penetration.
| Drug |
|---|
| Erythromycin (prototype) |
| Azithromycin (Z-pack) |
| Clarithromycin |
| Roxithromycin |
| Spiramycin |
| Fidaxomicin (GI-restricted; C. difficile) |
B. Ketolides
Structural derivatives of macrolides; overcome macrolide resistance.
| Drug |
|---|
| Telithromycin |
| Solithromycin |
C. Lincosamides
Bind 50S; similar spectrum to macrolides but excellent anaerobic coverage.
| Drug |
|---|
| Clindamycin |
| Lincomycin |
D. Chloramphenicol
Binds 50S; inhibits peptidyl transferase. Broad spectrum but reserved due to bone marrow toxicity (aplastic anemia).
| Drug |
|---|
| Chloramphenicol |
E. Oxazolidinones
Bind 50S; prevent formation of initiation complex. Active against MRSA, VRE, drug-resistant gram-positives.
| Drug |
|---|
| Linezolid |
| Tedizolid |
F. Streptogramins
Bind 50S in two sequential steps (synergistic combination). Active against MRSA and VRE (vanA-negative).
| Drug |
|---|
| Quinupristin-dalfopristin (Synercid) |
G. Pleuromutilins
Bind 50S (peptidyl transferase center).
| Drug |
|---|
| Lefamulin (systemic) |
| Retapamulin (topical) |
4. INHIBITORS OF DNA SYNTHESIS / REPLICATION
A. Fluoroquinolones (Quinolones)
Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV; bactericidal.
| Generation | Drugs | Coverage |
|---|---|---|
| 1st (Quinolones) | Nalidixic acid, Cinoxacin | Gram-negative (urinary only) |
| 2nd | Ciprofloxacin, Ofloxacin, Norfloxacin, Enoxacin | Broad gram-negative + Pseudomonas |
| 3rd | Levofloxacin, Sparfloxacin | Adds improved gram-positive + atypicals |
| 4th | Moxifloxacin, Gatifloxacin, Gemifloxacin | Broadest including anaerobes; "respiratory fluoroquinolones" |
B. Nitroimidazoles
Reduced to toxic radicals inside anaerobic organisms; damage DNA. Active against strict anaerobes and certain protozoa.
| Drug |
|---|
| Metronidazole (Flagyl) |
| Tinidazole |
| Ornidazole |
| Secnidazole |
C. Nitrofurans
Reductive activation; multiple mechanisms including DNA damage. Used only for urinary tract infections.
| Drug |
|---|
| Nitrofurantoin |
| Furazolidone |
5. INHIBITORS OF RNA SYNTHESIS
Rifamycins
Inhibit DNA-dependent RNA polymerase (beta subunit). Bactericidal; excellent intracellular penetration.
| Drug |
|---|
| Rifampicin (Rifampin) - anti-TB |
| Rifabutin - anti-TB (MAC) |
| Rifaximin - non-absorbable (traveler's diarrhea, hepatic encephalopathy) |
| Rifapentine - anti-TB (once-weekly) |
6. INHIBITORS OF CELL MEMBRANE FUNCTION
A. Polymyxins
Disrupt gram-negative outer membrane by acting like detergents. Last-resort agents for MDR gram-negatives.
| Drug |
|---|
| Polymyxin B |
| Colistin (Polymyxin E) |
B. Lipopeptides
Depolarize gram-positive bacterial membrane; rapidly bactericidal.
| Drug |
|---|
| Daptomycin |
Spectrum: Gram-positives including MRSA, VRE. Inactivated by pulmonary surfactant (not for pneumonia).
7. ANTIMETABOLITES (Inhibitors of Folate Synthesis)
Sulfonamides and trimethoprim act at sequential steps in folate synthesis - powerful synergy when combined.
| Drug | Target |
|---|---|
| Sulfonamides: Sulfamethoxazole, Sulfadiazine, Sulfisoxazole, Sulfadoxine, Mafenide, Silver sulfadiazine | Inhibit dihydropteroate synthase (DHPS) - block PABA incorporation |
| Trimethoprim | Inhibits dihydrofolate reductase (DHFR) |
| Co-trimoxazole (TMP-SMX) | Sequential blockade - synergistic |
| Dapsone | Inhibits DHPS (anti-leprosy, PCP prophylaxis) |
| Para-aminosalicylic acid (PAS) | Anti-TB; inhibits folate/salicylate synthesis |
| Pyrimethamine | Inhibits DHFR (antiprotozoal) |
8. ANTI-MYCOBACTERIAL AGENTS (Special Group)
| Drug | Class | Primary Use |
|---|---|---|
| Isoniazid (INH) | Isonicotinic acid | TB (1st line) |
| Rifampicin | Rifamycin | TB (1st line) |
| Pyrazinamide | Nicotinic acid amide | TB (1st line) |
| Ethambutol | Synthetic | TB (1st line) |
| Streptomycin | Aminoglycoside | TB (2nd line) |
| Amikacin | Aminoglycoside | MDR-TB |
| Capreomycin | Cyclic peptide | MDR-TB |
| Cycloserine | D-amino acid | MDR-TB |
| Ethionamide / Prothionamide | Thioamide | MDR-TB |
| Bedaquiline | Diarylquinoline (ATP synthase inhibitor) | MDR-TB |
| Delamanid | Nitroimidazole | MDR-TB |
| Clofazimine | Phenazine | Leprosy, MDR-TB |
| Dapsone | Sulfone | Leprosy |
Summary Table by Mechanism
| Mechanism | Classes | Bactericidal / Static |
|---|---|---|
| Cell wall synthesis | Beta-lactams, Glycopeptides, Bacitracin, Fosfomycin | Cidal |
| 30S ribosome | Aminoglycosides, Tetracyclines | Cidal (AG), Static (Tet) |
| 50S ribosome | Macrolides, Clindamycin, Chloramphenicol, Linezolid, Quinupristin-dalfopristin | Static (mostly), Cidal (Linezolid variable) |
| DNA gyrase / Topoisomerase | Fluoroquinolones | Cidal |
| DNA damage | Metronidazole, Nitrofurantoin | Cidal |
| RNA polymerase | Rifamycins | Cidal |
| Cell membrane | Polymyxins, Daptomycin | Cidal |
| Folate synthesis | Sulfonamides, Trimethoprim | Static |
Sources: Medical Microbiology 9e (Murray et al.), Tables 17.2-17.3; Goodman & Gilman's Pharmacological Basis of Therapeutics, Ch. 56 - "Antimicrobial Chemotherapy: Classes and Actions"
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