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Antibacterial & Antimicrobial Drugs

Key Terminology

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Sources of Antimicrobial Agents

1. Natural antibiotics — produced by molds (Penicillium → penicillin) or soil bacteria (Streptomyces → streptomycin, tetracyclines, chloramphenicol, erythromycin)
2. Chemically synthesized agents — discovered via screening (e.g., sulfonamides from aniline dyes) or structure-based drug design (e.g., trimethoprim)
3. Semi-synthetic modifications — chemical manipulation of natural antibiotics to broaden spectrum, improve pharmacokinetics, or overcome resistance (e.g., extended-spectrum penicillins, newer cephalosporins)

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Classification by Mechanism of Action

1. 🔵 Inhibitors of Cell Wall Synthesis

• Inhibit transpeptidase enzymes (Penicillin-Binding Proteins, PBPs) → prevent cross-linking of peptidoglycan → weakened cell wall → osmotic lysis
• Bactericidal; selective toxicity because human cells lack cell walls
• Resistance mechanisms: β-lactamase production (e.g., ampC); altered PBPs (e.g., PBP-2A in MRSA)
• Countermeasures: β-lactamase inhibitors (clavulanate + amoxicillin); PBP-targeting new agents (ceftaroline for MRSA)
• Mycoplasma (no cell wall) is intrinsically resistant

• Binds D-Ala-D-Ala terminus of peptidoglycan precursors → blocks transglycosylation and transpeptidation
• Active only against Gram-positive organisms (too large to penetrate Gram-negative outer membrane)
• Key uses: MRSA, C. difficile (oral)

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2. 🟡 Inhibitors of Protein Synthesis

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3. 🟢 Inhibitors of Nucleic Acid Synthesis

• Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV → prevent DNA supercoiling and replication
• Bactericidal; broad Gram-negative coverage; newer agents cover Gram-positives and atypicals

• Structural analogs of PABA → competitively inhibit dihydropteroate synthase → block folate synthesis
• Bacteriostatic; humans obtain folate from diet (selective toxicity)

• Inhibits bacterial dihydrofolate reductase → prevents conversion of dihydrofolate to tetrahydrofolate
• Used with sulfamethoxazole (TMP-SMX / co-trimoxazole) for sequential blockade of folate pathway → synergistic bactericidal effect

• Nitro group is reduced under anaerobic conditions → toxic intermediates cause DNA strand breaks
• Active against a wide range of anaerobes including Bacteroides fragilis; also active against parasites (Trichomonas, Giardia, Entamoeba)
• Used for GI anaerobic infections (often combined with a β-lactam for polymicrobial coverage)
• Side effects: nausea, metallic taste, peripheral neuropathy; disulfiram-like reaction with alcohol

• Bind the β-subunit of DNA-dependent RNA polymerase → prevent initiation of RNA synthesis
• Active against Gram-positives, Neisseria, Haemophilus, and mycobacteria (cornerstone of TB therapy)
• Always combined with other drugs for active infections (rapid resistance develops by polymerase mutation)
• Solo use: chemoprophylaxis for N. meningitidis and H. influenzae contacts; latent TB
• Drug interactions: potent inducer of hepatic cytochrome P450 enzymes
• Rifaximin: non-absorbed oral form; used for bacterial diarrhea (E. coli)

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4. 🔴 Disruptors of Cell Membrane Integrity

• Mimics phospholipid bilayer; inserts into Gram-positive bacterial membranes → forms pores → ion efflux → cell death
• Spectrum: Gram-positive only (including multidrug-resistant Enterococcus and S. aureus)
• Limitation: inactivated by pulmonary surfactant — cannot treat pneumonia

• Cationic detergent-like effect; bind and disrupt Gram-negative outer membranes → cytoplasmic contents leak out
• Spectrum: Gram-negative rods including P. aeruginosa
• Toxicity: nephrotoxicity, neurotoxicity — historically topical use only; now IV for multidrug-resistant Gram-negatives

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Summary Table: Drug Classes at a Glance

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Antimicrobial Resistance — Key Mechanisms

1. Enzymatic inactivation — β-lactamases hydrolyze the β-lactam ring
2. Target modification — altered PBPs (MRSA), altered ribosomal subunits
3. Efflux pumps — active drug expulsion from the cell
4. Reduced permeability — porin channel mutations (Gram-negatives)
5. Bypass pathways — altered metabolic pathway that doesn't require the drug target

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Antibacterial & Antimicrobial Drugs — Names & Explanation

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1. 🔵 PENICILLINS — Cell Wall Synthesis Inhibitors

• Amoxicillin/Clavulanate (Augmentin)
• Ticarcillin/Clavulanate
• Ampicillin/Sulbactam
• Piperacillin/Tazobactam (Pip-Tazo)

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2. 🔵 CEPHALOSPORINS — Cell Wall Synthesis Inhibitors

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3. 🔵 CARBAPENEMS — Cell Wall Synthesis Inhibitors (Broadest Spectrum)

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4. 🔵 GLYCOPEPTIDES — Cell Wall Synthesis Inhibitors

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5. 🟡 AMINOGLYCOSIDES — Protein Synthesis Inhibitors (30S + 50S)

• Inactive against anaerobes (no oxygen-dependent transport)
• Inactive against intracellular organisms (Rickettsia, Chlamydia)

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6. 🟡 TETRACYCLINES — Protein Synthesis Inhibitors (30S)

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7. 🟡 MACROLIDES — Protein Synthesis Inhibitors (50S)

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8. 🟡 CLINDAMYCIN (Lincosamide) — Protein Synthesis Inhibitor (50S)

• Drug: Clindamycin
• Spectrum: Gram-positive organisms + anaerobes (B. fragilis); MRSA (skin infections)
• Side effects: ⚠️ Risk of Clostridioides difficile colitis (pseudomembranous colitis)

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9. 🟡 OXAZOLIDINONES — Protein Synthesis Inhibitors (50S)

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10. 🟢 FLUOROQUINOLONES — DNA Synthesis Inhibitors

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11. 🟢 SULFONAMIDES + TRIMETHOPRIM — Folate Synthesis Inhibitors

• Sulfonamides → inhibit dihydropteroate synthase (compete with PABA) → block folate production
• Trimethoprim → inhibit dihydrofolate reductase → block folate conversion
• Together (TMP-SMX / Co-trimoxazole) = sequential double blockade → synergistic, bactericidal

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12. 🟢 RIFAMYCINS — RNA Synthesis Inhibitors

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13. 🟢 METRONIDAZOLE (Nitroimidazole) — DNA Disruptor

• Drug: Metronidazole (Flagyl)
• Spectrum: Anaerobes (B. fragilis, C. difficile), protozoa (Giardia, Trichomonas, Entamoeba)
• Side effects: Nausea, metallic taste, peripheral neuropathy; disulfiram-like reaction with alcohol (avoid alcohol during treatment)

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14. 🔴 CELL MEMBRANE DISRUPTORS

Daptomycin (Lipopeptide)

• Mechanism: Inserts into Gram-positive bacterial membrane → forms ion pores → cell death → bactericidal
• Spectrum: Gram-positive ONLY — including MRSA and VRE
• ⚠️ Cannot treat pneumonia — inactivated by pulmonary surfactant
• Side effects: Myopathy (monitor CK)

Polymyxins

• Mechanism: Cationic detergent action → disrupt Gram-negative outer membrane → contents leak → bactericidal
• Side effects: ⚠️ Nephrotoxicity + Neurotoxicity

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Quick Visual Summary

CELL WALL          → Penicillins, Cephalosporins, Carbapenems, Glycopeptides
PROTEIN (30S)      → Aminoglycosides, Tetracyclines
PROTEIN (50S)      → Macrolides, Clindamycin, Linezolid, Chloramphenicol
DNA/RNA SYNTHESIS  → Fluoroquinolones, Rifamycins, Metronidazole
FOLATE PATHWAY     → Sulfonamides, Trimethoprim
CELL MEMBRANE      → Daptomycin, Polymyxins

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Classification of Antibacterial & Antimicrobial Drugs

"The broad classification of antibiotics follows the classification of microorganisms closely, so that we have antibacterial, antiviral, antifungal, and antiparasitic agents." — Goodman & Gilman's The Pharmacological Basis of Therapeutics

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LEVEL 1 — Broadest Classification: By Target Microorganism

ANTIMICROBIAL DRUGS
├── 1. ANTIBACTERIAL (act on bacteria)
├── 2. ANTIVIRAL (act on viruses)
├── 3. ANTIFUNGAL (act on fungi)
└── 4. ANTIPARASITIC (act on parasites)

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LEVEL 2 — Classification of ANTIBACTERIAL Drugs

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A. BY MECHANISM OF ACTION (most important classification)

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🔵 1. CELL WALL SYNTHESIS INHIBITORS

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🟡 2. PROTEIN SYNTHESIS INHIBITORS

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🟢 3. NUCLEIC ACID SYNTHESIS INHIBITORS

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🟠 4. FOLATE SYNTHESIS INHIBITORS (antimetabolites)

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🔴 5. CELL MEMBRANE DISRUPTORS

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B. BY SPECTRUM OF ACTIVITY

NARROW SPECTRUM
├── Gram-positive only:  Penicillin G/V, Vancomycin, Daptomycin
├── Gram-negative only:  Aztreonam, Colistin/Polymyxins
└── Specific organisms:  Metronidazole (anaerobes), Rifampin (mycobacteria)

BROAD SPECTRUM (Gram-positive + Gram-negative)
├── Moderate broad:     Ampicillin, Amoxicillin
├── True broad:         Tetracyclines, Fluoroquinolones, TMP-SMX
└── Very broad:         Carbapenems, Piperacillin-Tazobactam, Tigecycline

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C. BY EFFECT ON BACTERIA

⚠️ This distinction is not absolute — some drugs are cidal at high concentrations and static at low concentrations.

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D. BY CHEMICAL STRUCTURE / SOURCE

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LEVEL 3 — Classification by Type of Infection / Clinical Use

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LEVEL 4 — Full Antimicrobial Classification (Beyond Antibacterials)

ALL ANTIMICROBIAL DRUGS
│
├── ANTIBACTERIAL ──── (all classes above)
│
├── ANTIFUNGAL
│   ├── Polyenes:         Amphotericin B, Nystatin
│   ├── Azoles:           Fluconazole, Itraconazole, Voriconazole
│   ├── Echinocandins:    Caspofungin, Micafungin, Anidulafungin
│   └── Pyrimidines:      Flucytosine (5-FC)
│
├── ANTIVIRAL
│   ├── Anti-Herpes:      Acyclovir, Valacyclovir, Ganciclovir
│   ├── Anti-Influenza:   Oseltamivir, Zanamivir
│   ├── Anti-HIV (ARVs):  NRTIs, NNRTIs, PIs, INSTIs, Fusion inhibitors
│   └── Anti-HCV/HBV:     Sofosbuvir, Tenofovir, Entecavir
│
└── ANTIPARASITIC
    ├── Antiprotozoals:   Metronidazole, Chloroquine, Quinine
    ├── Antihelminthics:  Albendazole, Mebendazole, Ivermectin
    └── Ectoparasiticides: Permethrin, Lindane

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Master Summary Diagram

ANTIBACTERIAL CLASSIFICATION
│
├── BY MECHANISM
│   ├── 1. Cell Wall → Penicillins, Cephalosporins, Carbapenems, Glycopeptides
│   ├── 2. Protein (30S) → Aminoglycosides, Tetracyclines
│   ├── 3. Protein (50S) → Macrolides, Clindamycin, Chloramphenicol, Linezolid
│   ├── 4. DNA/RNA → Fluoroquinolones, Rifamycins, Metronidazole
│   ├── 5. Folate → Sulfonamides, Trimethoprim
│   └── 6. Membrane → Daptomycin (G+), Polymyxins (G-)
│
├── BY SPECTRUM
│   ├── Narrow-spectrum
│   └── Broad-spectrum
│
├── BY EFFECT
│   ├── Bactericidal
│   └── Bacteriostatic
│
└── BY SOURCE
    ├── Natural (from Penicillium / Streptomyces)
    ├── Semi-synthetic
    └── Fully synthetic

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Clinical Case Analysis — Patient K., 42 years old

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🔍 CLINICAL DATA SUMMARY

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✅ DIAGNOSIS

ICD-10: J18.9 — Pneumonia, unspecified

Justification:

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⚠️ KEY CLINICAL CONSTRAINTS THAT DRIVE TREATMENT

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💊 TREATMENT PLAN

🔴 Drugs to AVOID in this patient:

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✅ RECOMMENDED ANTIBIOTIC REGIMEN

⚠️ Cross-reactivity between penicillins and cephalosporins is very low (~1–2%). Ceftriaxone is considered safe in penicillin-allergic patients unless they had anaphylaxis to penicillin. Since the allergy is documented but severity is not specified as anaphylaxis, ceftriaxone can be used with monitoring.

• Excellent coverage of Streptococcus pneumoniae (most common CAP pathogen)
• Covers H. influenzae, Gram-negative pathogens
• Does NOT prolong QT
• No dose adjustment needed in renal failure (hepatically excreted — safe in hemodialysis)
• Not a penicillin (different β-lactam ring side chain)

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Atypical Coverage (if clinical features suggest atypical pneumonia):

Doxycycline is preferred over azithromycin here because it does not prolong QT.

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Antipyretic / Symptomatic Treatment:

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⚠️ Drugs Taken by Patient (Aspirin + Analgin):

• Aspirin — acceptable for fever, but NSAIDs worsen renal function in CKD; switch to paracetamol
• Analgin (Metamizole) — avoid; risk of agranulocytosis and nephrotoxicity

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📋 SHORT TREATMENT SUMMARY

DIAGNOSIS:
Community-Acquired Pneumonia (CAP), right-sided, moderate severity
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ANTIBIOTICS:
1. Ceftriaxone 1–2 g IV once daily × 7–10 days
   (No QT prolongation | No renal dose adjustment | 
    Safe with penicillin allergy)

2. Doxycycline 100 mg PO twice daily × 5–7 days
   (Add if atypical coverage needed | Does NOT prolong QT)
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SUPPORTIVE:
• Paracetamol 500–1000 mg q6–8h (replace Aspirin + Analgin)
• Ambroxol 30 mg 3× daily (mucolytic)
• O₂ therapy if SpO₂ < 94%
• Careful IV fluids (dialysis patient)
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MONITORING:
• Daily ECG (QT interval — already prolonged!)
• Renal function / dialysis schedule
• WBC, CRP, temperature trend
• Chest X-ray at 7–10 days to assess resolution
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AVOID:
✗ Fluoroquinolones (QT prolongation)
✗ Azithromycin (QT prolongation)
✗ Aminoglycosides (nephrotoxic)
✗ Ampicillin/Amoxicillin (allergy)
✗ NSAIDs (worsen renal function)

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Patient K., 42 y/o — Short Summary

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DIAGNOSIS

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3 KEY CONSTRAINTS

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TREATMENT

• Ceftriaxone 1–2 g IV once daily × 7–10 days (Safe: no QT effect, no renal dose adjustment, low cross-reactivity with penicillin)

• Paracetamol 500–1000 mg q6–8h (replace Aspirin/Analgin)
• Ambroxol 30 mg × 3/day (mucolytic)
• O₂ if SpO₂ < 94%

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AVOID

• ❌ Fluoroquinolones (levofloxacin) — QT prolongation
• ❌ Azithromycin — QT prolongation
• ❌ Aminoglycosides — nephrotoxic
• ❌ Ampicillin/Amoxicillin — allergy
• ❌ NSAIDs — worsen renal function