DRUG
MECHANISM
USES
TOXICITY · NOTES
Sulfonamides (SMX, sulfadiazine)
PABA analog → inhibit dihydropteroate synthase
Sulfadiazine + pyrimethamine for Toxoplasma; silver sulfadiazine for burns
Hypersensitivity, SJS/TEN, photosensitivity, G6PD hemolysis, crystalluria, kernicterus, interstitial nephritis
Inhibits bacterial dihydrofolate reductase
Combined with SMX
Hyperkalemia (ENaC block), ↑ creatinine (blocks secretion), megaloblastic anemia, leukopenia (give leucovorin)
Sequential blockade → cidal
Cystitis, Pneumocystis, Toxoplasma prophylaxis, Nocardia, MRSA skin, Shigella, Listeria (alternative), Cyclospora, Stenotrophomonas
Potentiates warfarin, phenytoin (CYP2C9)
Inhibits DNA gyrase (gram ⁻) and topoisomerase IV (gram ⁺) → DNA breaks; cidal
UTI, pyelonephritis, Pseudomonas, traveler's diarrhea, anthrax, meningococcal prophylaxis
Weak gram ⁺ coverage
Levofloxacin · moxifloxacin
"Respiratory" FQs; better gram ⁺ and atypicals
Community pneumonia, MDR TB (moxi, levo); moxi covers anaerobes
Moxi poor urine levels
Collagen and cartilage effects; hERG block
Tendinitis/Achilles rupture (age > 60, steroids, transplant), QT prolongation, aortic aneurysm/dissection, CNS (seizures, delirium), peripheral neuropathy, dysglycemia, C difficile
Avoid in children and pregnancy (cartilage) · chelated by antacids, iron, calcium
Mutations in gyrase (gyrA) and topo IV; efflux
Gonorrhea now resistant
—
Reduced in anaerobes → free radicals damage DNA
Anaerobes below the diaphragm, C difficile (mild, alternative), BV, Trichomonas, Giardia, Entamoeba, H pylori
Disulfiram-like reaction with alcohol, metallic taste, peripheral neuropathy
Reactive intermediates damage DNA, ribosomes; concentrates in urine
Uncomplicated cystitis, prophylaxis; safe in most of pregnancy
Pulmonary fibrosis/pneumonitis, hemolysis in G6PD, peripheral neuropathy · avoid in pyelonephritis and low GFR
Inhibit DNA-dependent RNA polymerase
TB, meningococcal/Hib prophylaxis, staph biofilm adjunct
Human vs bacterial targets
Humans take up folate (no dihydropteroate synthase); bacterial DHFR differs from human
Selective toxicity
Methotrexate hits human DHFR; pyrimethamine hits protozoal