All about antibiotics
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All About Antibiotics
Antibiotics are chemical agents that kill or inhibit the growth of bacteria. The word technically refers to substances derived from microorganisms (like penicillin from Penicillium mold), though the term is now used broadly for all antibacterial drugs, whether natural, semi-synthetic, or fully synthetic.
1. How Antibiotics Are Classified
There are two main ways to classify antibiotics: by mechanism of action and by spectrum of activity.
By Mechanism of Action
| Class | Mechanism | Key Agents |
|---|---|---|
| Beta-lactams | Inhibit peptidoglycan cross-linking (cell wall synthesis) | Penicillins, cephalosporins, carbapenems, aztreonam |
| Glycopeptides | Disrupt cell wall synthesis via steric hindrance of backbone glycan formation | Vancomycin, teicoplanin |
| Aminoglycosides | Bind 30S ribosomal subunit - inhibit protein synthesis | Gentamicin, tobramycin, amikacin |
| Macrolides | Bind 50S ribosomal subunit - inhibit protein synthesis | Azithromycin, clarithromycin, erythromycin |
| Tetracyclines | Bind 30S ribosomal subunit - block tRNA binding | Doxycycline, minocycline |
| Fluoroquinolones | Inhibit DNA gyrase and topoisomerase IV - disrupt DNA replication | Ciprofloxacin, levofloxacin, moxifloxacin |
| Sulfonamides/Trimethoprim | Inhibit folate synthesis (different steps) | TMP-SMX (co-trimoxazole) |
| Polymyxins | Disrupt bacterial cell membrane | Colistin (polymyxin E), polymyxin B |
| Oxazolidinones | Bind 50S subunit - inhibit protein synthesis initiation | Linezolid |
| Nitroimidazoles | Disrupt DNA by free radical formation (anaerobes) | Metronidazole, tinidazole |
| Rifamycins | Inhibit bacterial RNA polymerase | Rifampin, rifabutin |
| Lincosamides | Bind 50S ribosomal subunit | Clindamycin |
| Streptogramins | Bind 50S ribosomal subunit - two components act synergistically | Quinupristin-dalfopristin |
| Daptomycin | Disrupts cell membrane (calcium-dependent) | Daptomycin |
Source: Textbook of Family Medicine 9e, Table 15-2; Katzung's Basic and Clinical Pharmacology, 16th Ed.
By Spectrum of Activity
- Narrow-spectrum: Active against a limited range of organisms. Example: penicillin G (mainly gram-positives).
- Broad-spectrum: Active against both gram-positive and gram-negative bacteria. Examples: fluoroquinolones, carbapenems, tetracyclines.
- Extended-spectrum: Includes atypical organisms (Mycoplasma, Chlamydia, Legionella) in addition to typical bacteria.
2. The Beta-Lactam Family (Most Prescribed Class)
Beta-lactams are the largest and most widely used antibiotic class. They all share a core beta-lactam ring and work by binding penicillin-binding proteins (PBPs), blocking peptidoglycan cross-linking and causing bacterial cell lysis.
| Subclass | Generations/Types | Examples |
|---|---|---|
| Penicillins | Natural, aminopenicillins, antistaphylococcal, antipseudomonal | Penicillin G/V, amoxicillin, oxacillin, piperacillin |
| Beta-lactam + inhibitor | Combined with clavulanate, sulbactam, tazobactam | Amoxicillin-clavulanate, piperacillin-tazobactam |
| Cephalosporins | 1st - 5th generation (broader spectrum with each generation) | Cefazolin (1st), cefoxitin (2nd), ceftriaxone (3rd), cefepime (4th), ceftaroline (5th) |
| Carbapenems | Broadest spectrum, stable against most beta-lactamases | Meropenem, imipenem-cilastatin, ertapenem |
| Monobactams | Gram-negatives only, safe in penicillin allergy | Aztreonam |
Source: Tietz Textbook of Laboratory Medicine, 7th Ed.; Textbook of Family Medicine 9e
3. Bactericidal vs. Bacteriostatic
This is clinically important - particularly in immunocompromised patients and serious infections like endocarditis.
| Bactericidal (kill bacteria) | Bacteriostatic (inhibit growth) |
|---|---|
| Aminoglycosides | Chloramphenicol |
| Beta-lactam antibiotics | Clindamycin |
| Glycopeptides (vancomycin) | Macrolides |
| Fluoroquinolones | Tetracyclines |
| Daptomycin | Sulfonamides |
| Rifampin | Oxazolidinones |
| Metronidazole | Trimethoprim |
| Polymyxins | Tigecycline |
Clinical rule: Bactericidal agents are required for endocarditis, meningitis, and infections in neutropenic patients - situations where the host immune system cannot finish off merely-inhibited bacteria. For immunocompetent patients with most infections, bacteriostatic agents are equally effective.
Source: Katzung's Basic and Clinical Pharmacology, 16th Ed.
4. Pharmacokinetics and Pharmacodynamics (PK/PD)
Understanding PK/PD drives how antibiotics are dosed.
Killing Patterns
There are two fundamental killing patterns - and they dictate dosing schedules:
1. Time-Dependent Killing
- Efficacy correlates with the time the drug concentration stays above the MIC (minimum inhibitory concentration)
- Examples: Beta-lactams, vancomycin
- Strategy: Dose frequently or use continuous infusions to maximize "time above MIC"
2. Concentration-Dependent Killing
- Efficacy correlates with the peak drug concentration relative to MIC (Cmax:MIC ratio)
- Examples: Aminoglycosides, fluoroquinolones
- Strategy: Give large, infrequent doses (even once-daily aminoglycosides) to maximize peak
- This is the pharmacodynamic basis for once-daily aminoglycoside dosing
3. AUC-Dependent Killing
- Efficacy correlates with overall drug area under the concentration curve (AUC)
- Example: Vancomycin - AUC:MIC ratio is the key target parameter
Source: Goldman-Cecil Medicine, International Edition; Katzung's Basic and Clinical Pharmacology, 16th Ed.
Post-Antibiotic Effect (PAE)
Persistent suppression of bacterial growth after drug is removed. Mathematically: PAE = T - C (where T = time for 10-fold regrowth in treated culture, C = same in untreated culture). Aminoglycosides and fluoroquinolones have long PAEs, supporting less frequent dosing. Beta-lactams generally have short PAEs.
5. Types of Antibiotic Therapy
There are three clinical approaches:
-
Empiric (Presumptive) Therapy: Started before culture results, based on the most likely pathogens for a given syndrome. Severity of illness and immune status determine how broad the coverage should be.
-
Targeted (Definitive) Therapy: Adjusted once culture and sensitivity results return (typically 48-72 hours). "De-escalation" - narrowing to the most specific effective drug - is strongly recommended to limit resistance development and adverse effects.
-
Prophylactic Therapy: Given before a procedure or in defined high-risk situations. Most effective when given within 1 hour of a surgical incision. Examples: surgical prophylaxis with cefazolin, PCP prophylaxis (TMP-SMX) in HIV/AIDS, CMV prophylaxis in transplant recipients.
Source: Textbook of Family Medicine 9e
6. Antibiotic Resistance
This is the most pressing global challenge in infectious disease.
How Resistance Develops
Two driving forces:
- Innate (intrinsic) resistance: Genetically encoded in the species - e.g., gram-negative bacteria naturally lack the penicillin-binding proteins that penicillin targets, making them inherently resistant.
- Acquired resistance: From natural selection under antibiotic pressure. Can be:
- Mutational (chromosomal changes)
- Horizontal gene transfer via plasmids or transposons - this is how resistance spreads across species
Cellular Resistance Mechanisms (4 main types)
| Mechanism | How It Works | Example |
|---|---|---|
| Enzymatic inactivation | Bacteria produce enzymes that destroy the antibiotic | Beta-lactamases hydrolyze the beta-lactam ring |
| Target site modification | Drug binding site is altered so the antibiotic cannot bind | Altered PBPs in MRSA (methicillin-resistant S. aureus) |
| Reduced permeability | Bacteria downregulate porins (membrane channels) so antibiotic cannot enter | Carbapenem resistance in gram-negatives |
| Efflux pumps | Active pumps expel the antibiotic before it can act | Multi-drug resistance pumps in Pseudomonas |
Source: Schwartz's Principles of Surgery, 11th Ed.; Goldman-Cecil Medicine, International Edition
Notable Resistant Organisms
- MRSA - methicillin-resistant Staphylococcus aureus: altered PBP2a (encoded by mecA gene); treated with vancomycin, daptomycin, or linezolid. Community-acquired MRSA strains produce Panton-Valentine leukocidin toxin.
- ESBL-producing Enterobacteriaceae (typically Klebsiella, E. coli): produce plasmid-mediated beta-lactamases. Laboratory sensitivity to cephalosporins is misleading - use leads to treatment failure. Carbapenems are the drug of choice.
- CRE (carbapenem-resistant Enterobacterales): major threat worldwide, options are very limited (polymyxins, ceftazidime-avibactam, meropenem-vaborbactam).
- VRE (vancomycin-resistant enterococci): treat with linezolid or daptomycin.
7. Important Adverse Effects
| Antibiotic Class | Key Adverse Effects |
|---|---|
| Beta-lactams | Hypersensitivity (penicillin allergy - rash, anaphylaxis), C. diff (broad-spectrum) |
| Aminoglycosides | Nephrotoxicity, ototoxicity (both cochlear and vestibular) - dose-related |
| Fluoroquinolones | Tendon rupture (Achilles), QT prolongation, CNS effects, cartilage concerns in children |
| Macrolides | QT prolongation, GI upset, drug-drug interactions (CYP3A4 inhibition) |
| Tetracyclines | Photosensitivity, teeth discoloration and bone effects in children, GI upset |
| Glycopeptides (vancomycin) | Nephrotoxicity, "red man syndrome" (infusion-related), ototoxicity |
| Metronidazole | Metallic taste, peripheral neuropathy with prolonged use, disulfiram-like reaction with alcohol |
| Clindamycin | C. difficile colitis (notably high risk) |
| Linezolid | Serotonin syndrome risk, myelosuppression with prolonged use |
| Polymyxins | Nephrotoxicity, neurotoxicity |
8. Antimicrobial Stewardship
Stewardship programs aim to:
- Use antibiotics only when indicated
- Choose the narrowest-spectrum agent that covers the likely pathogen
- Use the shortest effective duration
- De-escalate from empiric broad-spectrum to targeted therapy as soon as possible
Evidence supports shorter antibiotic courses for most infections: community-acquired pneumonia can be treated in 3-5 days; ventilator-associated pneumonia in 7-8 days vs. the traditional 14-day course. Shorter courses perform equally well with fewer adverse events. A 2025 systematic review and meta-analysis in Clinical Infectious Diseases confirmed that audit and feedback interventions for antibiotic prescribing in primary care significantly reduce inappropriate prescribing.
The WHO AWaRe (Access, Watch, Reserve) classification categorizes antibiotics to guide rational use:
- Access group: first-line drugs for common infections (e.g., amoxicillin, TMP-SMX)
- Watch group: broader spectrum, higher resistance potential, use when Access fails (e.g., fluoroquinolones, carbapenems)
- Reserve group: last-resort antibiotics for multi-drug resistant infections (e.g., colistin, linezolid, ceftazidime-avibactam)
9. High-Bioavailability Oral Antibiotics (IV-equivalent by mouth)
Some oral antibiotics achieve near-100% bioavailability, making them as effective as IV:
- TMP-SMX
- Fluoroquinolones (e.g., levofloxacin)
- Metronidazole
- Clindamycin
- Linezolid
This matters clinically - patients can often be stepped down from IV to oral without losing efficacy, reducing hospitalization costs and catheter-related complications.
10. Quick Reference: Antibiotic Coverage by Organism
| Target | Drug of Choice | Alternative |
|---|---|---|
| Strep throat (S. pyogenes) | Penicillin/amoxicillin | Azithromycin, cephalexin |
| MSSA | Nafcillin/oxacillin | Cefazolin |
| MRSA | Vancomycin, daptomycin | Linezolid, TMP-SMX (mild) |
| Pneumococcus (pneumonia) | Amoxicillin, penicillin | Azithromycin, levofloxacin |
| H. pylori | Triple/quad therapy (PPI + clarithromycin + amoxicillin ± bismuth) | Bismuth quadruple |
| E. coli UTI (uncomplicated) | Nitrofurantoin, TMP-SMX | Fosfomycin |
| Pseudomonas | Piperacillin-tazobactam, cefepime | Meropenem, ciprofloxacin |
| Anaerobes | Metronidazole | Clindamycin, amoxicillin-clavulanate |
| Atypicals (Legionella, Mycoplasma) | Azithromycin, doxycycline | Levofloxacin |
| TB | Isoniazid + rifampin + pyrazinamide + ethambutol | (based on sensitivity) |
Sources: Textbook of Family Medicine 9e - Katzung's Basic and Clinical Pharmacology 16th Ed. - Schwartz's Principles of Surgery 11th Ed. - Goldman-Cecil Medicine International Edition - Lippincott Illustrated Reviews: Pharmacology
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