Subject:

Preparatory Mindset

Antibiotics are classified by mechanism of action. The key is matching the drug class to its bacterial target: cell wall (β-lactams), protein synthesis (macrolides, aminoglycosides, tetracyclines), DNA synthesis (fluoroquinolones), folate synthesis (sulfonamides). Know the resistance mechanisms and spectrum of activity for each class.

Core Concepts

Ch07: Antibiotics

Antibiotic Classification by MOA

1. Inhibit Cell Wall Synthesis

| Class | Drug(s) | Spectrum | Key Features |
|------|---------|---------|-------------|
| Penicillins | Penicillin G | Narrow: GPC (strep, staph non-PNase), some GNC, spirochetes | Excreted via active tubular secretion (90%); Jarisch-Herxheimer with syphilis |
| Penicillinase-resistant | Methicillin, Oxacillin | GPC including β-lactamase-producing S. aureus | MRSA is resistant |
| Broad-spectrum | Amoxicillin, Ampicillin | GPC + some GNB | Combined with clavulanate (β-lactamase inhibitor) |
| Penicillin + β-lactamase inhibitor | Amoxicillin-clavulanate | Broader spectrum | Clavulanate inhibits β-lactamase (irreversible) |
| Cephalosporins | 1st-4th gen | Broader with each generation | Cross-allergenicity with penicillin (5-10%); ↓ nephrotoxicity in newer gens |
| Carbapenems | Imipenem | Very broad | Often with cilastatin (↓ renal metabolism) |
| Other | Vancomycin | GPC (MRSA, C. difficile) | Inhibits cell wall cross-linking; "Red man syndrome" on rapid infusion |

2. Inhibit Protein Synthesis

| Class | Drug(s) | Target | Key Features |
|------|---------|--------|-------------|
| Aminoglycosides | Gentamicin, Amikacin | 30S ribosome | Bactericidal; ototoxicity + nephrotoxicity; PAE; first-contact effect; poor oral absorption |
| Tetracyclines | Tetracycline, Doxycycline | 30S ribosome | Bacteriostatic; contraindicated in children <8 and pregnancy (bone/teeth); chelate Ca2+ |
| Macrolides | Erythromycin, Azithromycin | 50S ribosome | Bacteriostatic; GI side effects; PAE; azithromycin better tolerated |
| Chloramphenicol | Chloramphenicol | 50S ribosome | Aplastic anemia (dose-independent); gray baby syndrome |
| Clindamycin | Clindamycin | 50S ribosome | Pseudomembranous colitis (C. difficile) |
| Linezolid | Linezolid | 50S ribosome (early) | MRSA, VRE; myelosuppression |

3. Inhibit Nucleic Acid Synthesis

| Class | Drug(s) | Target | Key Features |
|------|---------|--------|-------------|
| Quinolones | Ciprofloxacin, Levofloxacin | DNA gyrase (topoisomerase II/IV) | Broad, oral; tendonitis in athletes, QT prolongation |
| Sulfonamides | Sulfamethoxazole | Dihydropteroate synthetase (PABA analog) | Often with TMP (co-trimoxazole); crystaluria, Stevens-Johnson syndrome |
| Rifampin | Rifampin | RNA polymerase | CYP450 inducer! (↓ effect of many drugs); red-orange body fluids |

Resistance Mechanisms (High-Yield)

| Mechanism | Example |
|-----------|---------|
| Enzymatic inactivation | β-lactamase (penicillin resistance) |
| Target modification | MRSA (altered PBP2a); Rifampin (RNA polymerase mutation) |
| Decreased accumulation | ↓ Porins (GNB resistance) or ↑ efflux pumps (tetracycline, macrolides) |
| Altered metabolic pathway | Sulfonamide resistance (↑ PABA production) |

Key Facts

Penicillin main resistance mechanism: β-lactamase (hydrolyzing enzyme)

First contact effect: Aminoglycosides

PAE (Post-Antibiotic Effect): Macrolides, Quinolones, Aminoglycosides

Superinfections: Broad-spectrum antibiotics → opportunistic pathogens (C. diff, Candida)

Combination therapy rationale: Synergy, mixed infection, life-threatening unidentified infection, delay resistance

INH + B6 (pyridoxine): Prevents peripheral neuropathy

Exam-Frequency Core Points (from exam notes)

I. Core Examination Points for General Principles of Antibacterial Drugs (Test Frequency ★★★, Basic Must-Know)Must-Know Details:

Definition of Chemotherapy: The general term for the treatment of diseases caused by pathogenic microorganisms, parasites, and tumor cells using drugs is collectively called chemotherapy. This is a high-frequency term for noun definition questions.

Core Evaluation Index: The Chemotherapeutic Index (CI = LD₅₀/ED₅₀) is the core index for evaluating the efficacy and safety of chemotherapeutic drugs. A larger numerical value indicates relatively higher safety for the drug; Penicillin is currently known to have the largest chemotherapeutic index among antibacterial drugs and has no effect on renal function.

Mechanisms of Action of Antibacterial Drugs (100% tested, common in both multiple-choice and short-answer questions):

- Inhibition of cell wall synthesis: β-lactams (penicillins, cephalosporins), Vancomycin class; among them, β-lactams act by inhibiting bacterial transpeptidase and preventing the cross-linking of peptidoglycan.
- Increasing cell membrane permeability: Polymyxins, Amphotericin B.
- Inhibition of protein synthesis:
- Initiation + elongation termination stages → Aminoglycosides.
- Peptide chain elongation stage → Tetracyclines (bind to the 30S ribosomal subunit), Macrolides, Chloramphenicol (bind to the 50S ribosomal subunit).
- Influence on nucleic acid / folate metabolism:
- Inhibition of DNA gyrase → Quinolones.
- Inhibition of DNA-dependent RNA polymerase → Rifampicin.
- Inhibition of dihydrofolate synthetase → Sulfonamides.
- Inhibition of dihydrofolate reductase → TMP.

Classification of Antibacterial Drug Activity (Basis for combination therapy knowledge):

- Class I (Cell wall inhibitors, bactericidal in the multiplication phase): Penicillins, Cephalosporins, Quinolones, Vancomycin class.
- Class II (Bactericidal in the resting phase): Aminoglycosides, Polymyxins.
- Class III (Rapid bacteriostatic agents): Tetracyclines, Macrolides, Chloramphenicol, Lincomycins.
- Class IV (Slow bacteriostatic agents): Sulfonamides, TMP.

Rules for Combination Therapy Effects: I + II → Synergistic; I + III → Antagonistic; II + III → Additive / Synergistic; III + IV → Additive.

II. Core Examination Points for β-Lactam Antibiotics (Test Frequency ★★★, Entire Chapter Must-Know)Must-Know Details:

Penicillins:

- Penicillin G: A narrow-spectrum bactericidal drug, highly effective against G⁺ cocci/bacilli, G⁻ cocci, and spirochetes, but weakly effective against G⁻ bacilli. It is the drug of choice for hemolytic streptococcal infections, pneumococcal infections, syphilis, leptospirosis, diphtheria, and tetanus. The most serious adverse reaction is anaphylactic shock, and the first-line rescue drug is epinephrine.
- Semi-synthetic penicillins: Ampicillin and Amoxicillin are broad-spectrum penicillins, available orally, and effective against both G⁺ and G⁻ bacilli. Amoxicillin has strong anti-*Helicobacter pylori* activity and is the core drug in the quadruple regimen for *H. pylori* eradication.

Cephalosporins (Characteristics of each generation 100% tested):

| Generation | Activity against G⁺ bacteria | Activity against G⁻ bacteria | Stability to β-lactamase | Nephrotoxicity | Core Clinical Applications |
| --- | --- | --- | --- | --- | --- |
| First | Strong | Weak | Unstable | Present | Mild to moderate respiratory tract, skin and soft tissue infections |
| Second | Slightly weaker | Enhanced | Relatively stable | Reduced | Abdominal and pelvic infections |
| Third | Weak | Strong | Highly stable | Essentially absent | Severe infections, sepsis, meningitis; Ceftazidime is the most potent cephalosporin against *Pseudomonas aeruginosa* |
| Fourth | Strong | Strong | Highly stable | Absent | Refractory severe drug-resistant bacterial infections |

III. Core Examination Points for Macrolides / Lincomycins / Polypeptide Antibiotics Must-Know Details:

Macrolides (Representatives: Erythromycin, Azithromycin):

- Mechanism of action: Binds to the 50S ribosomal subunit to inhibit protein synthesis, classified as a rapid bacteriostatic agent. Erythromycin is the drug of choice for mycoplasma pneumonia, legionnaires' disease, diphtheria carrier state, and campylobacter enteritis; it is also used as an alternative for patients allergic to penicillin. Azithromycin has a long half-life, strong activity against mycoplasma and chlamydia, and is administered only once daily.

Lincomycins (Representative: Clindamycin): Achieves high drug concentrations in bone tissue and is the drug of choice for osteomyelitis caused by *Staphylococcus aureus*; also highly effective against anaerobes.

Polypeptides:

- Vancomycin: Inhibits cell wall synthesis, highly potent only against G⁺ bacteria, and is the drug of choice for Methicillin-resistant *Staphylococcus aureus* (MRSA) infections. Adverse reactions include ototoxicity, nephrotoxicity, and Red Man Syndrome.
- Polymyxins: Increases bacterial cell membrane permeability, effective only against G⁻ bacilli (including *Pseudomonas aeruginosa*), with significant nephrotoxicity, used only for severe drug-resistant G⁻ bacillus infections.

IV. Core Examination Points for Aminoglycoside Antibiotics Must-Know Details:

Representatives: Streptomycin, Gentamicin, Amikacin. Mechanism of action involves inhibiting the initiation and termination stages of bacterial protein synthesis; classified as bactericidal agents in the resting phase, highly potent only against G⁻ bacilli.

Common Adverse Reactions (100% tested): Ototoxicity (vestibular + cochlear damage), Nephrotoxicity, Neuromuscular blockade, Allergic reactions.

Clinical Positioning: Gentamicin is a commonly used drug for G⁻ bacillus infections and can be combined with Penicillin synergistically for the treatment of Enterococcal endocarditis. Streptomycin is the drug of choice for plague and tularemia, and is also a first-line anti-tuberculosis drug. Amikacin is stable to inactivating enzymes and is used for G⁻ bacillus infections resistant to other aminoglycosides.

V. Core Examination Points for Tetracyclines and Chloramphenicol Must-Know Details:

Tetracyclines (Representative: Doxycycline):

- Mechanism of action: Binds to the 30S ribosomal subunit to inhibit protein synthesis; a broad-spectrum rapid bacteriostatic agent, highly effective against Rickettsia, Mycoplasma, and Chlamydia. It is the drug of choice for rickettsial diseases such as typhus and scrub typhus. Doxycycline is the preferred tetracycline for extra-renal infections in patients with renal insufficiency.
- Adverse reactions: Superinfection (dysbiosis), effects on bone and tooth development (tetracycline teeth). Contraindicated in pregnant women, nursing mothers, and children under 8 years of age.

Chloramphenicol: A broad-spectrum bacteriostatic agent that binds to the 50S ribosomal subunit to inhibit protein synthesis. Due to severe adverse reactions, it is used only as a backup drug for typhoid fever, paratyphoid fever, and bacterial meningitis. Core severe adverse reactions: Reversible bone marrow suppression, irreversible aplastic anemia, and Gray Baby Syndrome. Contraindicated in neonates and pregnant women.

VI. Core Examination Points for Synthetic Antibacterial Agents Must-Know Details:

Quinolones (Representatives: Levofloxacin, Moxifloxacin):

- Mechanism of action: Inhibits DNA gyrase, hindering bacterial DNA replication; classified as a bactericidal agent in the multiplication phase, broad-spectrum. Clinically commonly used for genitourinary, respiratory, and intestinal tract infections. Levofloxacin and Moxifloxacin are known as "Respiratory Quinolones", with strong activity against common respiratory pathogens.
- Adverse reactions: Cartilage damage; contraindicated in pregnant women, nursing mothers, and minors under 18 years of age. Photosensitivity reactions and central nervous system reactions may also occur.

Sulfonamides + TMP:

- Sulfonamides inhibit dihydrofolate synthetase, while TMP inhibits dihydrofolate reductase. The combination (Co-trimoxazole) provides a dual blockade of folate synthesis, producing a synergistic bactericidal effect. Sulfadiazine is one of the drugs of choice for epidemic cerebrospinal meningitis.
- Adverse reactions of Sulfonamides: Crystalluria and hematuria in the urinary tract. Patients should drink plenty of water and take sodium bicarbonate concurrently to alkalize the urine during treatment.

VII. Core Examination Points for Antifungal and Antiviral Agents Must-Know Details:

Antifungal Agents:

- Amphotericin B: A broad-spectrum antifungal agent, the drug of choice for deep fungal infections. Its mechanism involves increasing fungal cell membrane permeability. The most common adverse reactions are nephrotoxicity and infusion-related high fever with chills.
- Azoles (Fluconazole, Itraconazole): Inhibit the synthesis of ergosterol in the fungal cell membrane. Fluconazole has strong activity against cryptococcal meningitis, with mild adverse reactions, making it a commonly used clinical antifungal agent.
- Terbinafine: Used for the treatment of superficial fungal infections (tinea unguium, tinea pedis, tinea corporis).

Antiviral Agents:

- Anti-herpesvirus: Acyclovir is the drug of choice for Herpes simplex virus infections.
- Anti-influenza virus: Oseltamivir is the drug of choice for influenza A and B, with optimal efficacy when used within 48 hours of symptom onset.
- Anti-HIV: Zidovudine is a nucleoside reverse transcriptase inhibitor and a core drug in anti-HIV therapy, requiring combination use (HAART therapy).
- Anti-hepatitis virus: Entecavir and Tenofovir are the first-choice nucleoside analogs for chronic hepatitis B.

High-Yield Points

β-lactams (penicillins, cephalosporins): cell wall → bactericidal

Macrolides (erythromycin, azithromycin): 50S ribosome → bacteriostatic

Aminoglycosides (gentamicin): 30S ribosome → concentration-dependent bactericidal

Tetracyclines: 30S ribosome → contraindicated in children <8 and pregnancy (teeth/bone)

Fluoroquinolones (ciprofloxacin): DNA gyrase → broad spectrum

Sulfonamides: folate synthesis → bacteriostatic

Clindamycin: anaerobic coverage — risk of C. difficile colitis

Topic Summary

β-lactams (penicillins, cephalosporins) are cell wall synthesis inhibitors — bactericidal. Macrolides and tetracyclines inhibit protein synthesis — bacteriostatic. Aminoglycosides are concentration-dependent bactericidal. Fluoroquinolones inhibit DNA gyrase. Resistance mechanisms: β-lactamase, efflux pumps, target modification.

Pharmacology Notes