149.1 🎓 醫孞生版

149.1.0.1 📌 䞀頁重點

  • Bactericidal vs Bacteriostatic: kill vs inhibit. 嚎重 / immunocompromised → bactericidal 優先
  • PK/PD:
    • Time-dependent (β-lactam, vancomycin): T > MIC; 倚次 dose / continuous infusion
    • Concentration-dependent (aminoglycoside, fluoroquinolone): Cmax/MIC; once-daily dosing
    • AUC/MIC (vancomycin newer, fluoroquinolone, linezolid)
  • 抗生玠䞻芁分類:
    • Cell wall: β-lactams (penicillin, cephalosporin, carbapenem, monobactam), vancomycin, daptomycin, fosfomycin
    • Protein synthesis 30S: aminoglycoside, tetracycline
    • Protein synthesis 50S: macrolide, lincosamide (clindamycin), chloramphenicol, oxazolidinone (linezolid)
    • DNA: fluoroquinolone (gyrase/topo IV), metronidazole, rifampin (RNA polymerase)
    • Folate: TMP-SMX (sulfa + DHF reductase)
  • Prophylaxis 重芁 indications:
    • Endocarditis prophy: high-risk + dental/respiratory invasive
    • Surgical antibiotic prophy (Ch 147)
    • PCP prophy: HIV / transplant
    • Splenectomy: PCV20 + Hib + Men ACWY + Men B + daily amox or pen V
    • Sickle cell: pen V daily 0-5 yr (age)
    • Meningococcal contact: cipro / rifampin / ceftri
    • Lyme (high-risk tick bite): doxy 200 single
    • Anti-tetanus post-injury

149.1.0.2 1⃣ 䞻芁抗生玠 by Mechanism

149.1.0.2.1 Cell Wall Inhibitors
149.1.0.2.1.1 β-Lactams
  • Mechanism: inhibit penicillin-binding proteins (PBPs) → cell wall synthesis ↓ → lysis
  • Time-dependent killing
  • Resistance: β-lactamase (TEM, SHV, CTX-M, KPC, NDM), PBP alteration (MRSA mecA)

Penicillins: - Natural PCN: Pen G (IV), Pen V (PO) — Strep, Treponema - Anti-staph PCN: Methicillin (historical), Nafcillin, Oxacillin, Dicloxacillin — MSSA - Aminopenicillin: Ampicillin, Amoxicillin — Strep, Enterococcus, Listeria, gram-negative (limited) - Extended spectrum: Ticarcillin, Piperacillin — Pseudomonas (need β-lactamase inhibitor) - Combination (β-lactamase inhibitor): Amoxicillin-clavulanate, Ampicillin-sulbactam, Piperacillin-tazobactam (workhorse)

Cephalosporins (generation by spectrum): - 1st gen (cefazolin, cephalexin): GP (Staph, Strep) - 2nd gen (cefuroxime, cefotetan, cefoxitin): + some GN; cefoxitin/cefotetan anaerobic - 3rd gen (ceftriaxone, cefotaxime, ceftazidime): broad GN; ceftazidime + Pseudomonas - 4th gen (cefepime): broad GN + Pseudomonas + Staph - 5th gen (ceftaroline): + MRSA; ceftolozane-tazo + MDR Pseudomonas - New (anti-resistance): Ceftazidime-avibactam, Meropenem-vaborbactam, Imipenem-relebactam, Cefiderocol, Sulbactam-durlobactam — MDR / CRE

Carbapenems: Meropenem, Imipenem, Doripenem, Ertapenem — broadest β-lactam; ESBL coverage - Ertapenem: no Pseudomonas, no Acinetobacter, no Enterococcus

Monobactam: Aztreonam — GN only (no GP, no anaerobic); good for severe PCN allergy

149.1.0.2.1.2 Vancomycin
  • Mechanism: bind D-Ala-D-Ala → inhibit cell wall (different site from PBP)
  • Time-dependent + AUC/MIC dependent
  • Spectrum: GP only (MRSA, CoNS, Enterococcus — VRE resistant), C. difficile (oral only)
  • Toxicities: nephrotoxic, red-man syndrome (infusion), ototoxic (high)
  • Targets: AUC 400-600 (replaced “trough 15-20”)
149.1.0.2.1.3 Daptomycin
  • Mechanism: depolarize cell membrane via Ca-dependent insertion
  • Concentration-dependent
  • Spectrum: GP (MRSA, VRE, Strep)
  • Inactivated by surfactant → not for pneumonia!
  • Toxicity: myopathy (monitor CK), eosinophilic pneumonia
149.1.0.2.1.4 Fosfomycin
  • Mechanism: inhibit MurA (early cell wall synthesis)
  • Single dose PO for cystitis; IV for MDR (CRE, ESBL) systemic
149.1.0.2.2 Protein Synthesis
149.1.0.2.2.1 Aminoglycosides
  • Mechanism: bind 30S ribosome → misreading → cell death
  • Concentration-dependent, once-daily dosing
  • Spectrum: aerobic GN (E. coli, Pseudomonas, Klebsiella, Acinetobacter), synergy with β-lactam for Enterococcus
  • Toxicities: nephrotoxic, ototoxic, neuromuscular blockade
  • Examples: Gentamicin, Tobramycin, Amikacin, Streptomycin, Plazomicin (CRE)
149.1.0.2.2.2 Tetracyclines / Glycylcyclines
  • Mechanism: bind 30S ribosome → block aminoacyl-tRNA
  • Bacteriostatic
  • Spectrum: broad — Strep, MRSA (limited), atypical (Mycoplasma, Chlamydia, Legionella), rickettsia, spirochete, anaerobes, Pasteurella
  • Toxicities: GI, photosensitivity, tooth discoloration (< 8 yr), pseudotumor cerebri
  • Examples: Doxycycline, Minocycline, Tigecycline (broad MDR), Omadacycline, Eravacycline
149.1.0.2.2.3 Macrolides
  • Mechanism: bind 50S ribosome → block translocation
  • Bacteriostatic
  • Spectrum: GP (Strep), atypical (Mycoplasma, Chlamydia, Legionella, Bordetella), MAC
  • QT prolongation! drug interaction (CYP3A4)
  • Examples: Azithromycin, Clarithromycin, Erythromycin, Fidaxomicin (C. diff)
149.1.0.2.2.4 Clindamycin (Lincosamide)
  • Mechanism: bind 50S ribosome
  • Bacteriostatic
  • Spectrum: GP, anaerobes (above diaphragm — oral); inhibits toxin synthesis (Strep TSS, necrotizing fasciitis)
  • C. diff risk (highest among antibiotics)
  • Penetrates well into bone, abscess
149.1.0.2.2.5 Oxazolidinones
  • Mechanism: bind 23S rRNA of 50S subunit
  • Spectrum: GP (MRSA, VRE)
  • Examples: Linezolid, Tedizolid
  • Toxicities: thrombocytopenia (long-term), serotonin syndrome (with SSRI), peripheral / optic neuropathy, lactic acidosis
149.1.0.2.3 DNA / RNA Inhibitors
149.1.0.2.3.1 Fluoroquinolones
  • Mechanism: inhibit DNA gyrase (GN) and topoisomerase IV (GP)
  • Concentration-dependent
  • Spectrum: broad GN (Pseudomonas), atypical (Legionella, mycoplasma, chlamydia), some GP (levofloxacin, moxifloxacin = “respiratory FQ”)
  • FDA black box: aortic aneurysm/dissection, tendinopathy, QT, hypoglycemia, mental health, peripheral neuropathy
  • C. diff risk (highest!)
  • Examples: Ciprofloxacin, Levofloxacin, Moxifloxacin, Delafloxacin
149.1.0.2.3.2 Rifampin
  • Mechanism: inhibit bacterial RNA polymerase
  • Spectrum: TB, MRSA biofilm (add-on), N. meningitidis prophylaxis, Legionella, Brucella
  • Many drug interactions (CYP3A4 inducer — warfarin, OCP, ART, immunosuppressants)
  • Resistance develops rapidly if monotherapy → combo only
  • Color change: orange urine, tears, secretion
149.1.0.2.3.3 Metronidazole
  • Mechanism: nitroimidazole → reduced in anaerobes → DNA damage
  • Spectrum: anaerobes (Bacteroides, Fusobacterium), Trichomonas, Giardia, Entamoeba, H. pylori, C. difficile (no longer first-line)
  • Disulfiram reaction with alcohol
149.1.0.2.4 Folate Inhibitors
149.1.0.2.4.1 TMP-SMX (Bactrim)
  • Mechanism: TMP inhibits DHF reductase + SMX inhibits PABA → folate synthesis ↓
  • Bactericidal (synergistic)
  • Spectrum: many GN (UTI), MRSA, PJP, Nocardia, Stenotrophomonas, Toxoplasma
  • Toxicities: rash (SJS/TEN), hyperkalemia, AKI (false Cr rise), bone marrow suppression, hyponatremia

149.1.0.3 2⃣ Prophylaxis Indications

適應症 Regimen
Endocarditis (high-risk) Amoxicillin 2g PO 30-60 min pre-dental; ampicillin/cefazolin IV if can’t PO
Surgical site (clean) Cefazolin 1-2g IV within 60 min
Surgical (colorectal) Cefazolin + Metronidazole; + oral neomycin/erythromycin bowel prep
PJP (HIV CD4 < 200, transplant, chronic steroid) TMP-SMX 1 SS daily OR 1 DS 3x/wk
MAC (HIV CD4 < 50) Azithromycin 1200 mg weekly
Splenectomy PCV20 + Hib + Men ACWY + Men B; daily pen V (children) or amox/eryth
Sickle cell (children) Pen V 125-250 mg BID 0-5 yr
Meningococcal contacts Cipro 500 mg ×1 OR Rifampin 600 BID × 2 d OR Ceftri 250 IM ×1
Lyme (high-risk tick attached > 36h) Doxycycline 200 mg single
Post-exposure rabies HRIG + vaccine 4-dose
Pertussis exposure Azithromycin 5d
Recurrent UTI TMP-SMX 1/2 DS daily or postcoital
Tuberculosis (LTBI) INH 9 mo OR INH+RPT 3 mo (3HP) OR Rifampin 4 mo