Antibiotics

Vivian Imbriotis | July 8, 2026

Here antibiotics are classified by broad mechanism. For each group, their exact mechanism and mode of elimination is noted.

Cell wall synthesis inhibitors

  • Typically more effective against gram positive bacteria, which lack an outer cell membrane
  • Beta-lactams (penicillins, cephalosporins, carbapenems): bind to penicillin-binding protein \(\to\) prevent peptidoglycan crosslinking \(\to\) weaken cell wall; all renally cleared except ceftriaxone (dual renal/biliary).
  • Glycopeptides (vancomycin, teicoplanin): bind to peptidoglycan directly \(\to\) prevent crosslinking \(\to\) weaken cell wall; renally cleared
  • Isoniazid: prevents mycolic acid synthesis \(\to\) kills mycobacteria. Hepatically metabolized \(\to\) inactive.

Plasma membrane alteration

  • Daptomycin; "fancy vancomycin"; forms K-permiable pores in cells \(\to\) K efflux and cell death. Renally cleared. Kills gram positives.
  • Polymixins: form large pores in gram-negative outer membrane \(\to\) cell death by osmotic lysis. Good gram negative and poor gram positive coverage (because their positive charge attracts them to the gram negative outer membrane). Dual renal/biliary clearance.

Prevent protein synthesis (mostly gram positive coverage, as penetration of gram negatives is more difficult with 2 membranes):

  • Aminoglycosides (gentamycin, tobramycin, amikacin): inhibit 30s ribosomal subunit. Renally cleared. Atypically, have good gram negative and poor gram positive coverage (because their positive charge attracts them to the gram negative outer membrane). When paired with a beta-lactam they are synergists at killing gram positives.
  • Tetracyclines (doxycycline): inhibit 30s ribosomal subunit; doxycycline is excreted in bile (others have some urinary excretion). Active against atypical gram negatives.
  • Macrolides (azithromycin): inhibit 50s ribosomal subunit; excreted in bile. Some gram negative coverage.
  • Clindamycin: technically not a macrolide. Inhibits 50s ribosomal subunit; dual renal/biliary excretion
  • Linezolid: binds to 50s ribosomal subunit; renally excreted

Interfere with DNA synthesis

  • NB normally in bacteria, PABA \(\to\) dihydrofolate \(\to\) tetrahydrofolate \(\to\) purines \(\to\) DNA. Cover gram positives and negatives.
  • Fluroquinolones (ciprofloxacin): inhibit DNA gyrase \(\to\) promotes DNA breakage. Dual biliary/renal excretion
  • Trimethoprim; prevents dihydrofolate \(\to\) tetrahydrofolate; renal excretion
  • Sulfonamides (sulfamethoxazole) and dapsone; prevents PABA \(\to\) dihydrofolate; renal excretion


Pharmaceutics - IV only.

PK

  • A poor orally
  • D minimally protein bound
  • M not metabolized
  • E Renally cleared T1/2=1 hour

PD

  • Binds to PBP \(\to\) inhibits peptigoglycan crosslinking \(\to\) cell lysis by osmosis
  • Killing determined by time over MIC
  • Kills gram positives (except MRSA, MRSE, VRE; MRSA has a modified PBP \(\to\) low affinity). Kill most gram negatives (including most pseudomonas). Kills obligate anaerobes. Kills ESCAPPMs (not degraded by inducible beta-lactamase). Cannot kill treponema pallidum or mycobacteria.

AEs

  • Minimal direct adverse effects
  • Dysbiosis, bacterial overgrowth, C diff colitis

Pharmaceutics - IV only.

PK

  • A poor orally
  • D Vd ~0.1L/kg; crosses BBB
  • M not metabolized
  • E Mixed billiary and renal excretion (only beta-lactam in routine use with biliary clearance); T1/2=8 hours

PD

  • Binds to PBP \(\to\) inhibits peptigoglycan crosslinking \(\to\) cell lysis by osmosis
  • Killing determined by time over MIC
  • Kills gram positives (except MRSA, MRSE, VRE; MRSA has a modified PBP \(\to\) low affinity). Kill most gram negatives (not pseudomonas). Does not kill obligate anaerobes. Does not kill ESCAPPMs. Cannot kill mycobacteria. Does kill treponema pallidum.

AEs

  • Cephalosporin-induced neurotoxicity (rare)
  • Allergy (~1% crossreactivity with penicillin allergy)
  • Interstitial nephritis


Pharmaceutics - IV only.

PK

  • A poor orally
  • D minimally protein bound
  • M minimally metabolized
  • E Renally cleared T1/2=1 hour

PD

  • Binds to PBP \(\to\) inhibits peptigoglycan crosslinking \(\to\) cell lysis by osmosis
  • Tazocin inhibits beta-lactamases \(\to\) impairs resistance
  • Killing determined by time over MIC
  • Kills gram positives (except MRSA, MRSE, VRE; MRSA has a modified PBP \(\to\) low affinity). Kill most gram negatives (including most pseudomonas). Kills obligate anaerobes. Does not cover ESCAPPMs. Cannot kill treponema pallidum or mycobacteria.

AEs

  • Penicillin anaphylaxis
  • SJS-TEN
  • Dysbiosis, bacterial overgrowth, C diff colitis


Pharmaceutics - IV only.

PK

  • A poor orally
  • D not protein bound
  • M not metabolized
  • E Renally cleared T1/2=1 hour

PD

  • Irreversibly bind to and inactivate 30s ribosomal subunit \(\to\) inhibits protein synthesis \(\to\) cell death
  • Killing determined by Cmax/MIC
  • Because binding is irreversible, exhibit post-antibiotic effect (killing continues after plasma levels reach 0).
  • No gram positive activity (as a single agent). Syngergistic gram positive killing when administered with a beta-lactam (as they can then cross the cell wall \(\to\) bind ribosomes). Kill most gram negatives (including most pseudomonas).

AEs

  • Nephrotoxicity
  • Vestibular and auditory toxicity
  • Adverse effects are related to AUC \(\to\) minimized by a single large dose


Pharmaceutics - IV only.

PK

  • A - poor oral absorption. Oral administration \(\to\) local effect against enteral C. diff
  • D - ~0.5L/kg
  • M - Minimal
  • E - renal, T1/2=6 hours

PD

  • Binds to peptidoglycan and prevents it being enzymatically cross-linked by penicillin binding protein \(\to\) weakens cell wall \(\to\) lysis
  • Killing determined by AUC/MIC
  • Covers essentially all gram positives - including C. Diff and MRSA


AEs

  • "Red man syndrome" - histamine release during infusion \(\to\) flushing, vasodilation, hypotension
  • Nephrotoxicity
  • Vestibular and auditory toxicity

Pharmaceutics - IV or oral

PK

  • A - 70% OBA
  • D - 5L/kg
  • M - Minimal
  • E - dual biliary/renal excretion, T1/2=4 hours

PD

  • inhibit DNA gyrase \(\to\) promotes DNA breakage. Dual biliary/renal excretion
  • covers most gram-negatives (including some pseudomonas)
  • covers some gram-positives (including MRSA, but not pneumococcus)
  • Killing characteristic is AUC/MIC


AEs

  • Weaken connective tissue \(\to\) tendon rupture, aortic dissection
  • Qtc prolongation
  • Neuropathy
  • Dysbiosis, bacterial overgrowth, C diff colitis