Antibiotics Classes

Why This Matters

Antibiotics don't just "kill bacteria"—they target specific cellular machinery, and understanding which machinery determines everything from spectrum of activity to resistance patterns. You're being tested on your ability to connect mechanism of action to clinical application: Why does vancomycin work against MRSA when penicillin doesn't? Why do we combine certain antibiotics for synergy? These questions require you to think beyond memorization.

The antibiotic classes below demonstrate core principles of selective toxicity, ribosomal targeting, cell wall architecture, and resistance evolution. When you encounter exam questions about treatment choices or resistance mechanisms, you need to instantly recall which cellular target each class hits—and why that matters for Gram-positive versus Gram-negative coverage. Don't just memorize drug names; know what each class teaches you about bacterial vulnerability.

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Cell Wall Synthesis Inhibitors

The bacterial cell wall is a unique target because human cells lack this structure entirely—making these antibiotics highly selective. Beta-lactams and glycopeptides both disrupt peptidoglycan synthesis, but they bind to different molecular targets, explaining their different resistance profiles.

Beta-Lactams (Penicillins, Cephalosporins, Carbapenems)

• Inhibit transpeptidase enzymes (PBPs)—prevents cross-linking of peptidoglycan, causing osmotic lysis and cell death
• Spectrum varies by generation: penicillins target Gram-positives; cephalosporins broaden coverage; carbapenems are reserved for multi-drug resistant (MDR) infections
• Beta-lactamase production is the primary resistance mechanism—bacteria literally destroy the drug's beta-lactam ring

Glycopeptides (Vancomycin)

• Binds D-alanyl-D-alanine precursors—physically blocks cell wall building blocks rather than inhibiting enzymes
• Gram-positive only: the large molecule cannot penetrate the outer membrane of Gram-negatives, making it the go-to for MRSA
• "Red man syndrome" occurs with rapid infusion—a histamine release reaction, not a true allergy

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Protein Synthesis Inhibitors: 30S Ribosomal Subunit

Bacterial ribosomes (70S) differ structurally from human ribosomes (80S), allowing selective targeting. Drugs binding the 30S subunit interfere with the initiation complex or cause mRNA misreading.

Aminoglycosides

• Bind 30S subunit irreversibly—causes misreading of mRNA and production of faulty proteins that damage the cell membrane
• Aerobic Gram-negative coverage: require oxygen-dependent uptake, so they're ineffective against anaerobes
• Nephrotoxicity and ototoxicity limit use—often combined with beta-lactams for synergistic killing against serious infections

Tetracyclines

• Bind 30S subunit reversibly—blocks aminoacyl-tRNA from entering the A site, halting elongation (bacteriostatic)
• Broad-spectrum including atypicals: effective against Chlamydia, Mycoplasma, and Rickettsia due to intracellular penetration
• Contraindicated in pregnancy and children—deposits in developing bones and teeth; resistance via efflux pumps is widespread

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Protein Synthesis Inhibitors: 50S Ribosomal Subunit

Drugs targeting the 50S subunit block later steps in translation—either peptide bond formation or translocation. These tend to be bacteriostatic and cover atypical pathogens well.

Macrolides

• Bind 50S subunit—blocks translocation, preventing the ribosome from moving along mRNA (bacteriostatic)
• Respiratory infection workhorses: cover Streptococcus pneumoniae plus atypicals like Mycoplasma and Legionella
• Penicillin allergy alternative—commonly prescribed for community-acquired pneumonia when beta-lactams are contraindicated

Oxazolidinones (Linezolid)

• Bind 50S subunit uniquely—prevents formation of the 70S initiation complex, blocking translation before it starts
• Reserved for resistant Gram-positives: effective against MRSA and VRE when vancomycin fails
• Myelosuppression with prolonged use—monitor blood counts; also interacts with MAOIs causing serotonin syndrome

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DNA Targeting Antibiotics

These classes attack bacterial DNA directly—either by disrupting replication machinery or damaging the DNA itself. Because DNA processes are fundamental, resistance often requires mutations in essential enzymes.

Fluoroquinolones

• Inhibit DNA gyrase and topoisomerase IV—prevents DNA unwinding and segregation, halting replication (bactericidal)
• Broad-spectrum oral option: covers both Gram-positives and Gram-negatives; excellent bioavailability
• Black box warning for tendon rupture—particularly in older adults and those on corticosteroids; resistance via target mutations is increasing

Nitroimidazoles (Metronidazole)

• Forms toxic free radicals inside anaerobes—damages DNA in organisms with low redox potential (requires anaerobic activation)
• Anaerobe and protozoa specialist: drug of choice for Clostridioides difficile, Bacteroides, and Giardia
• Disulfiram-like reaction with alcohol—patients must avoid alcohol during treatment; relatively low resistance rates

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Membrane and Metabolic Pathway Disruptors

These classes don't fit the classic "cell wall or ribosome" categories—they target the cell membrane directly or block essential metabolic pathways.

Polymyxins

• Disrupt outer membrane integrity—bind LPS and insert into the membrane like detergents, causing leakage and death
• Last-resort Gram-negative coverage: effective against MDR Pseudomonas and Acinetobacter when nothing else works
• Significant nephro- and neurotoxicity—reserved for desperate situations; emerging resistance threatens this final option

Sulfonamides

• Block dihydropteroate synthase—inhibits folic acid synthesis, which bacteria must make de novo (humans obtain folate from diet)
• Synergistic with trimethoprim: TMP-SMX (Bactrim) blocks two sequential steps in folate pathway, creating sequential blockade
• Allergic reactions common—sulfa allergies are frequently reported; also watch for hematological effects

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Quick Reference Table

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Self-Check Questions

1. Both aminoglycosides and tetracyclines bind the 30S ribosomal subunit—why is one bactericidal and the other bacteriostatic?

2. A patient with a severe penicillin allergy presents with community-acquired pneumonia. Which antibiotic class would you choose, and what mechanism makes it effective against atypical respiratory pathogens?

3. Compare and contrast beta-lactam resistance (via beta-lactamases) with vancomycin resistance (via D-ala-D-lac modification). How do these different mechanisms reflect each drug's binding target?

4. Why is metronidazole ineffective against aerobic bacteria, and what does this tell you about its mechanism of action?

5. If an FRQ asks you to design a combination therapy for a serious Gram-positive infection, which two classes would you pair for synergy, and what cellular targets would you be hitting simultaneously?