USMLE Step 1 Antibiotics

Penicillin mechanism

binds to penicillin binding proteins in peptidoglycan (blocks transpeptidase crosslinking); activates autolytic enzymes

penicillin use

gram positives and syphilis

penicillin toxicity

hypersensitivity reactions, hemolytic anemia

penicillinase resistant penicillins

methicillin, nafcillin, dicloxacillin

penicillinase resistant penicillin use

Staph aureus

penicillin resistant penicillin toxicity

hypersensitivity; methicillin: interstitial nephritis

aminopenicillins

ampicillin, amoxacillin

aminopenicillin mechanism

same as penicillin but wider spectrum

aminopenicillin use

select gram positive and negative bacteria--H flu, E coli, Listeria, Proteus, Salmonella, enterococci

aminopenicillin toxicity

hypersensitivity, ampicillin rash, pseudomembranous colitis

antipseudomonal drugs

ticarcillin, piperacillin, carbenicillin

antipseudomonal mechanism

same as penicillin; wider spectrum

antipseudomonal use

Pseudomonas and gram negative rods

antipsuedomonal toxicity

hypersensitivity reaction

beta lactamase inhibitor mechanism

inhibit beta lactamase (protects penicillins from destruction)

beta lacatamase drugs

clavulanic acid, sulbactam, tazobactam

bacteriostatic antibiotics

erythromycin, clindamycin, sulfamethoxazole, trimethoprim, tetracycline, chloramphenicol

bactericidal antibiotics

vancomycin, fluoroquinolones, penicillin, aminoglycosides, cephalosporins, metronidazole

1st generation cephalosporins

cefazolin, cephalexin

1st generation cephalosporin coverage

gram positive cocci, Proteus, E coli, Klebsiella

cephalosporin mechanism

beta lactams; inhibit cell wall synthesis but less susceptible to penicillinases

2nd generation cephalosporins

cefoxitin, cefaclor, cefuroxime

2nd generation cephalosporin coverage

same as 1st plus H flu, enterobacter, Neisseria, Srratia

3rd generation cephalosporins

ceftriaxone, ceftazidime, cefotaxime

3rd generation cephalosporin coverage

serious gram negative infections; ceftriaxone: Neisseria, ceftazidime: pseudomonas

4th generation cephalosporins

cefepime

cephalosporin toxicity

hypersensitivity, vitamin K deficiency, cross-hypersensitivity with penicillins, increase nephrotoxicity of aminoglycosides, reaction with alcohol

aztreonam mechanism

beta lactamase resistant monobactam; binds penicillin binding protein

aztreonam use

gram negative rods only

aztreonam toxicity

occasional GI upset

imipenem/cilastin mechanism

beta-lactamase resistant carbapenem; cilastin is a renal dihydropeptidase 1 (to decrease renal inactivation)

imipenem use

broad spectrum; gram + cocci, gram - rods and anaerobes

(use limited to life-threatening or refractory infections because of side effects)

imipenem toxicity

GI distress, skin rash, CNS toxicity (seizures) at high plasma levels

vancomycin mechanism

inhibits cell wall mucopeptide formation by binding D ala D ala portion of cell wall precursors

vancomycin use

gram + only; use reserved for resistant infections--Staph aureus, enterococci, C diff

vancomycin toxicity

nephrotoxicity, ototoxicity, thrombophlebitis, red man syndrome, but well-tolerated in general

resistance to vancomycin

amino acid change from D-ala D-ala to D-ala D-lac

30s ribosomal inhibitors

tetracyclins, aminoglycosides

50s ribosomal inhibitors

clindamycin, chloramphenicol, erythromycin, linezolid, lincomycin

aminoglycoside drugs

gentamicin, neomycin, amikacin, tobramycin, streptomycin

aminoglycoside mechanism

inhibit formation of the initiation complex and cause misreading of mRNA; require O2 for uptake

aminoglycoside use

no anaerobe coverage; severe gram - rod infections; synergistic with beta lactams; neomycin for bowel surgery

aminoglycoside toxicity

nephrotoxicity (esp with cephalosporins), ototoxicity (esp with loop diuretics), teratogen

aminoglycoside resistance

drug modification via transferases

tetracycline mechanism

binds to 30s and prevents attachment of amino-acyl tRNA; limited CNS penetration

tetracycline use

borrelia burgdorferi, H. pylori, Mycoplasma. Rickettsia, Chlamydia (accumulates intercellularly); demeclocycline is ADH antagonist so used in SIADH

tetracycline administration consideration

absorption inhibited by milk, antacids, iron preparations; can be used in patients with renal failure because fecally eliminated

tetracycline toxicity

GI distress, teeth discoloration, inhibition of bone growth in children, photosensitivity

tetracycline resistance

decreased uptake or increased efflux

macrolide drugs

erythromycin, azithromycin, clarithromycin

macrolide mechanism

binds to 50s subunit and blocks translocation (binds to 23s RNA)

macrolide use

atypical pneumonias (mycoplasma, chlamydia, legionella), URIs, STDs, gram positive cocci (in pts allergic to penicillin), Neisseria

macrolide toxicity

prolonged QT, GI discomfort, acute cholestatic hepatitis, eosinophilia, skin rashes, increases serum concentration of theophyllines and oral anticoagulants

macrolide resistance

methylation of 23s binding site

chloramphenicol mechanism

binds to 50s ribosome, inhibits peptidyltransferase activity

chloramphenicol use

meningitis (H flu, Neisseria meningitis, Strep pneumo)

clindamycin mechanism

binds to the 50 S ribosome, blocks peptide bond formation (bacteriostatic)

clindamycin use

anaerobic infections in aspiration pneumonia or lung abscesses

clindamycin toxicity

psuedomembranous colitis, fever, diarrhea

sulfonamide mechanism

PABA antimetabolites inhibit dihydropteroate synthetase; inhibit bacterial folic acid production (bacteriostatic)

sulfonamide use

gram positive, gram negative, Nocardia, chlamydia, simple UTI, also opportunistic infection prophylaxis in HIV patients

sulfonamide toxicity

hypersensitivity reactions, hemolysis in G6PD deficiency, nephrotoxicity, photosensitivity, kernicterus in infants, displaces warfarin and other drugs from albumin binding

sulfonamide resistance

altered bacterial dihydropteroate synthetase, decreased uptake or increased PABA synthesis

trimethoprim mechanism

inhibits bacterial dihydrofolate reductase (bacteriostatic)

trimethoprim use

used in combo with sulfamethoxazole for recurrent UTI's, Shigella. Salmonella, pneumocystis

trimethoprim toxicity

megaloblastic anemia, leukopenia, granulocytopenia; lurcovorin rescue to supplement with folinic acid

fluoroquinolone mechanism

inhibit bacterial DNA gyrase (bactericidal)

sulfonamide drugs

sulfamethoxazole, sulfisoxazole, sulfadiazine

fluoroquinolone drugs

ciprofloxacin, norfloxacin, ofloxacin, sparfloxacin, moxifloxacin, gatifloxacin, enxoxacin, nalidixic acid (a quinolone)

fluoroquinolone use

gram negative rods of urinary and GI tracts, Neisseria, some gram positive, also has action vs. psuedomonas

fluoroquinolone toxicity

GI upset, rash, superinfection, headache, dizziness; contraindicated in pregnant women because of risk or cartilage damage, tendonitis and tendon rupture in adults, legs cramps and myalgias in kids; do not take with antacids

fluoroquinolone resistance

chromosomal DNA gyrase mutation

metronidazole mechanism

forms free radical toxic metabolites in bacterial cell that damages DNA; bactericidal and anti-protozoal

metronidazole use

anaerobes, giardia, entamoeba histolytica, trichomonas, gardnerella vaginalis; used in H. pylori triple therapy

metronidazole toxicity

disulfuram like reaction with alcohol; headache; metallic taste

polymixin drugs

polymixin B, colistimethate

polymixin mechanism

bind to cell membranes of bacteria and disrupt osmotic properties; catatonic and basic proteins that act as detergents

polymixin toxicity

neurotoxicity, acute renal tubular necrosis

polymixin use

resistant gram - infections

TB treatments

rifampin, isoniazide, ethambutol, pyrazinamide (isoniazid is prophylaxis)

Mycobacterium avium treatment

azithromycin, rifampin, ethambutol, streptomycin

mycobacterium leprae treatment

rifampin, dapsone, clofazimine

ethambutol toxicity

optic neuropathy

pyrazinamide toxicity

hepatotoxicity

ethambutol mechanism

blocks arabinosyltransferase to decrease carbohydrate polymerization of cell wall

isoniazid mechanism

decreases synthesis of mycolic acids; need bacterial catalase peroxidase to convert isoniazid to active metabolite

clinical use of isoniazid

TB

isoniazid toxicity

neurotoxicity, hepatotoxicity, lupus, pyradoxime (B6) deficiency--supplementation can prevent neurotoxicity and maybe lupus

rifampin mechanism

inhibits DNA-dependent RNA polymerase

rifampin use

TB, delays dapsone resistance in leprosy, Neisseria and H.flu prophylaxis

rifampin toxicity

minor hepatotoxicity, P450 inducer, orange body fluids

rifampin resistance

mutation in RNA polymerase

meningococcal prophylaxis

rifampin, minocycline

gonorrhea prophylaxis

ceftriaxone

syphylis prophylaxis

penicillin G

recurrent UTI prophylaxis

TMP-SMX

pneumocystis prophylaxis

TMP-SMX, aerosolized pentamidine

endocarditis prophylaxis in surgical/dental procedures

penicillins

mycobacterium avium prophylaxis

azithromycin

amphotericin B mechanism

binds ergosterol in fungal membrane and forms pores that allow leakage of electrolytes; does not cross BBB