Antibiotic Mechanisms
Antibiotic targets: CWMPR — Cell Wall, cell Membrane, Metabolites, Protein synthesis, RNA/DNA
Cell Wall · Membrane · Metabolites · Protein synthesis · RNA/DNA synthesis
Five bacterial targets that antibiotics exploit — humans lack most of them
Cell wall synthesis (beta-lactams, vancomycin): bacteria have it, humans don't — excellent selective toxicity. Cell membrane (polymyxins): disrupt Gram- outer membrane. Folate synthesis (sulfonamides, trimethoprim): bacteria make folate, humans get it from diet. Protein synthesis (tetracyclines, macrolides, aminoglycosides, chloramphenicol): target bacterial 30S/50S ribosome. DNA/RNA synthesis (fluoroquinolones, rifampin): target bacterial gyrase or RNA polymerase.
► Show full breakdown Cell Wall
Beta-lactams, vancomycin, glycopeptides
Membrane
Polymyxins — disrupt outer membrane
Metabolites
Sulfonamides, TMP — folate pathway
Protein
30S: aminoglycosides, tetracyclines. 50S: macrolides, chloramphenicol
DNA/RNA
Fluoroquinolones (gyrase), rifampin (RNA pol)
Beta-Lactams
Beta-lactam ring binds penicillin-binding protein (transpeptidase) → blocks cell wall cross-linking → lysis
Beta-Lactam Antibiotics
The largest and most widely used antibiotic class
Penicillins: narrow spectrum (amoxicillin, ampicillin) or extended (piperacillin). Cephalosporins: generations 1–5, increasingly broad. Carbapenems (imipenem, meropenem): broadest — last resort. Monobactams (aztreonam): Gram- only. Beta-lactamase inhibitors (clavulanate, tazobactam): added to overcome resistance. Allergy: true IgE allergy in ~1%.
Antibiotic Resistance Mechanisms
Resistance: BET — Beta-lactamase, Efflux pumps, Target modification
Beta-lactamase · Efflux · Target modification
Three main ways bacteria resist antibiotics
Beta-lactamase: enzyme breaks beta-lactam ring (MRSA: altered PBP2a instead). Efflux pumps: actively pump drug out of cell (tetracycline, fluoroquinolone resistance). Target modification: MRSA altered PBP; VRE altered vancomycin binding site (D-Ala-D-Lac). Decreased permeability: loss of porins in Gram- bacteria. Enzymatic inactivation: aminoglycoside-modifying enzymes.
► Show full breakdown B
Beta-lactamase — destroys beta-lactam ring
E
Efflux pumps — export drug from cell
T
Target modification — drug can't bind
Protein Synthesis Inhibitors
30S inhibitors: "TAME" — Tetracyclines, Aminoglycosides. 50S: "MAC" — Macrolides, chlorAmphenicol, Clindamycin
Ribosome Targeting Antibiotics
Antibiotics that block bacterial protein synthesis at 30S or 50S
30S inhibitors: tetracyclines (block tRNA entry), aminoglycosides (misreading, bactericidal). 50S inhibitors: macrolides (erythromycin — block translocation), chloramphenicol (peptidyl transferase inhibitor — aplastic anemia risk), clindamycin (blocks translocation), linezolid (MRSA/VRE). Bacteriostatic: tetracycline, macrolides, clindamycin. Bactericidal: aminoglycosides.
Fluoroquinolones
Fluoroquinolones: inhibit DNA gyrase (Gram-) and topoisomerase IV (Gram+). Broad spectrum. "-floxacin" ending.
Fluoroquinolone Antibiotics
Fluoroquinolones — the broad-spectrum DNA-targeting antibiotic class
Ciprofloxacin: excellent Gram- coverage (Pseudomonas, E. coli, Salmonella). Levofloxacin/moxifloxacin: respiratory fluoroquinolones — add Gram+ (S. pneumoniae). Mechanism: inhibit DNA gyrase (topoisomerase II) and topoisomerase IV → prevent DNA unwinding → bactericidal. Adverse effects: tendon rupture (Achilles), QT prolongation, avoid in children and pregnancy.
Vancomycin
Vancomycin: glycopeptide — binds D-Ala-D-Ala of peptidoglycan. MRSA drug of choice. "Red man syndrome" from fast infusion.
Vancomycin
The go-to antibiotic for MRSA and other resistant Gram-positive infections
Mechanism: binds D-Ala-D-Ala terminus of peptidoglycan precursors → blocks cell wall synthesis without beta-lactam ring → not affected by beta-lactamase. MRSA treatment: IV vancomycin is standard. VRE (vancomycin-resistant Enterococcus): altered target (D-Ala-D-Lac) → use linezolid or daptomycin. Red man syndrome: histamine release from rapid infusion — not true allergy. Monitor renal function (nephrotoxic).
Antifungal Mechanisms
Antifungals target: ergosterol (azoles, amphotericin B), cell wall glucan (echinocandins), nucleic acid (flucytosine)
Antifungal Drug Targets
Why fungal infections are harder to treat than bacterial infections
Fungi are eukaryotes (like us) — fewer unique targets. Ergosterol (fungal membrane sterol, humans use cholesterol): azoles (fluconazole, itraconazole) block ergosterol synthesis. Amphotericin B: binds ergosterol directly → pores → cell death (very toxic — nephrotoxic). Echinocandins (caspofungin): block beta-glucan synthase → weak cell wall. Flucytosine: converted to 5-FU in fungi → inhibits DNA synthesis.
Bacteriostatic vs Bactericidal
Bacteriostatic = stops growth (immune system finishes). Bactericidal = kills directly. Critical distinction for immunocompromised patients.
Bacteriostatic vs Bactericidal
Why this distinction matters most in immunocompromised patients
Bacteriostatic (tetracyclines, macrolides, clindamycin, TMP-SMX, chloramphenicol): stop bacterial replication — rely on immune system to clear remaining bacteria. Bactericidal (beta-lactams, aminoglycosides, fluoroquinolones, vancomycin, metronidazole): directly kill. In immunocompromised patients (HIV, transplant, neutropenia): must use bactericidal drugs — no immune backup available.
Metronidazole
Metronidazole: "Metro kills what has no O₂" — anaerobes and protozoa. Works by DNA strand breakage.
Metronidazole (Flagyl)
The antibiotic of choice for anaerobic bacteria and certain parasites
Mechanism: reduced by anaerobic organisms → toxic metabolite → DNA strand breaks → bactericidal. Coverage: anaerobes (Bacteroides fragilis, Clostridium difficile), protozoa (Giardia, Trichomonas, Entamoeba). Uses: C. diff colitis (oral), bacterial vaginosis, intraabdominal infections (with cefazolin). Adverse: disulfiram-like reaction with alcohol — warn patients. Metallic taste.
Sulfonamides and TMP
TMP-SMX: blocks folate synthesis at 2 steps — "double block." First-line for Pneumocystis and UTIs.
Trimethoprim-Sulfamethoxazole
Sequential folate pathway blockade — why combination is synergistic
Sulfonamides block PABA → dihydropteroate synthase. Trimethoprim blocks dihydrofolate reductase. Combined: sequential blockade → synergistic killing, prevents resistance. Humans eat folate; bacteria must make it → selective toxicity. Uses: UTIs, Pneumocystis jirovecii pneumonia (PCP), Toxoplasma prophylaxis, MRSA skin infections. Adverse: rash (Stevens-Johnson), kernicterus in neonates, hemolysis in G6PD deficiency.
MRSA Treatment
MRSA = Methicillin-Resistant S. aureus. Hospital: IV vancomycin. Community (skin): TMP-SMX or doxycycline.
MRSA Management
Treatment depends on severity and whether it's hospital-acquired or community-acquired
MRSA resistance: mecA gene encodes altered PBP2a — low affinity for all beta-lactams. Hospital-acquired MRSA (HA-MRSA): bacteremia, pneumonia, endocarditis → IV vancomycin or daptomycin. Community-acquired MRSA (CA-MRSA): skin and soft tissue infections → TMP-SMX, doxycycline, or clindamycin (check D-zone test for inducible resistance). Linezolid: oral option, 100% bioavailability.
Antiparasitic Drugs
Malaria: chloroquine (sensitive) or artemisinin (resistant). Helminthes: albendazole/mebendazole. Protozoa: metronidazole.
Antiparasitic Drugs
Key drugs for the most clinically important parasitic infections
Malaria: chloroquine (P. vivax/ovale/malariae), artemisinin-based combinations (resistant P. falciparum), primaquine (liver stage/hypnozoites). Toxoplasma: pyrimethamine + sulfadiazine. Giardia/Trichomonas/C. diff: metronidazole. Roundworms/hookworms/pinworms: albendazole or mebendazole (block tubulin polymerization). Schistosomiasis: praziquantel. Ivermectin: onchocerciasis, strongyloidiasis, lice, scabies.