Antimicrobials

Question 1

Penicillin G, Penicillin V

Answer 1

Prototype beta-lactam antibiodics

Bind (transpeptidases) to block cross-linking of peptidoglycan and subsequently activate autolytic enzymes

Mostly used for gram positive organisms, also used for N. meningitidis and T. pallidum

Bactericidal

Penicillinase sensitive

Cause hypersensitivity reactions, hemolytic anemia

Resistance caused by penicillinase in bacteria (beta-lactamase) cleaving beta-lactam ring

Question 2

Ampicillin, Amoxicillin

Answer 2

Same as penicillin mechanism,

Wider spectrum than penicillin: covers HIB, e. coli, listeria, salmonella, shigella, enteroccoci on top of gram-positives

Combine w/ clavulanic acid to protect against beta-lactamases

Causes hypersensitivity reactions, rashes, and possible pseudomembranous colitis

Resistance by beta-lactamases

Question 3

Oxacillin, nafcillin

Answer 3

Penicillinase resistant penicillins, bulky R group blocks access to beta lactamses to beta lactam ring

Same mechanism as penicillin

Narrow spectrum: S. aureus (except for MRSA)

Causes hypersensitivity reactions, interstitial neprhritis

Question 4

Ticarcillin, piperacillin

Answer 4

Same mechanism as penicillin

Extended spectrum: specifically covers pseudomonas, use w/ beta-lactamase inhibitors

Causes hypersensitivity reactions

Question 5

Cephalosporins

Answer 5

Beta-lactam drugs that are less susceptible to penicillinases

1st generation: cefazolin, cephalexin, covers gram positives, e.coli, klebsiella

2nd generation: cefoxitin, cefuroxime, covers gram positives, HIB, neisseria, e. coli, klebsiella

3rd generation: ceftriaxone, ceftazidime covers gram postives and gram negatives resistant to other beta lactams (meningitis, gonorrhea, pseudomonas)

4th generation: cefepime, increased activity against pseudomonas and gram positive organisms

5th generation: ceftaroline, broad gram-postive and gram negative coverage, including MRSA, but does not cover pseudomonas

Do not cover LAME: legionella, atypicals (mycoplasma, chlamydia), MRSA, enterococci

Can cause hypersensitivity reactions, vitamin K deficiency

Low cross-reactivity with penicillins

Question 6

Aztreonam

Answer 6

Monobactam, resistant to beta lactamses, similar mechanism as penicillin but no cross reactivity

Covers ONLY gram-negatives

Usually nontoxic, can cause occasional GI upset

Question 7

Cabapenems

Answer 7

Imipenem, meropenem

Similar mechanism as penicillin, beta-lactamse resistant

Always administered w/ cilastatin (inhibitor of dehydropeptidase) to decrease inactivation of drug in renal tubules

Covers gram-positives, gram negatives, and anaerobes

Significant side effects: GI distress, skin rash, CNS toxicity (seizures) at high plasma level

Question 8

Vancomycin

Answer 8

Inhibit cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors

Bactericidal

Covers gram positives only, including MRSA and C. diff (oral)

Well tolerated in general, but can cause nephrotoxicity, ototoxicity, thrombophlebitis, and diffuse flushing (red-man syndrome, can be prevented w/ anti-histamines and slower infusion rate)

Resistance occur when bacteria modifies D-ala D-ala to D-ala to D-ala D-lac

Question 9

Aminoglycosides

Answer 9

Buy AT 30, CCEL at 50

Gentamicin, neomycin

Bactericidal

Inhibit formation of initiation complex (30s) and cause misreading of mRNA. Also blocks translocation. Require O2 for uptake therefore ineffective against anaerobes

Used for severe gram-negative infections.
Synergistic w/ beta-lactam antibiotics

Cause nephrotoxicity (especially when used w/ cephalosporins), neuromuscular blockade, ototoxciity

Teratogen

Resistance caused by bacterial transferase enzymes inactivating drugs by acetylation, phosphorlyation or adenylation

Question 10

Tetracyclines

Answer 10

Tetracyline, doxycycline

Bacteriostatic

Binds to 30s and prevent attachment of amioacyl-tRNA
Limited CNS penetration
Fecally eliminated and can be used in pts w/ renal failure
Do not take w/ bivalent cations as they prevent drug absorption

Effective against Borrelia burgdorferi, M.pneumoniae, Rickesttsia, and Chlamydia

Cause GI distress, discoloration of teeth, and inhibition of bone growth in children

Contraindicated in pregnancy

Resistance caused by increase in efflux or decrease in uptake by plasmid-eoncdoed transport pumps

Question 11

Macrolides

Answer 11

Azithromycin, erythromycin, clarithromycin

Bacteriostatic

Inhibits protein synthesis by blocking translocation by binding to the 23S rRNA of the 50s unit

Used for treating atypical pneumonias (mycoplasma, chlamydia, legionella), STIs, gram-postivies (pt allergic to penicillin)

Cause gastrointestinal motility issues, arrhythmia associated w/ prolonged QT, acute cholestatic hepatitis, rash, and eosinophilila

Resistance caused by methylation of 23S rRNA binding site preventing binding of drug

Question 12

Chloramphenicol

Answer 12

Bacteriostatic

Blocks peptidyltransferase at 50s ribosomal subunit

Used rarely for meningitis (HIB, neisseria) and rocky mountain spotted fever (rickettsia)

Cause anemia, aplsatic anemia

Resistance caused by plasmid-coded acetyltransferases that inactivates the drug

Question 13

Clindamycin

Answer 13

Bacteriostatic

Blocks peptide transfer (translocation) at 50S

Used for anaerobic infections in aspiration pneumonia, lung abscesses, oral infections

Treats anaerobes above the diaphragm (metronidazole for anaerobes below diaphragm)

Causes specifically pseudomembraneous colitis (c.diff), fever, diarrhea

Question 14

Sulfonamides

Answer 14

Bacteriostatic

Sulfamethoxazole (SMX), sulfadiazine

Inhibit folate synthesis through inhibition of dihydropteroate synthase

Covers gram-positives, gram-negatives, norcadia, chlamydia

Causes hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity, and displaces other drugs from albumin (warfarin)

Resistance caused by altered enzyme

Question 15

Trimethoprim (TMP)

Answer 15

Bacteriostatic

Inhibits folate synthesis through inhibition of dihydrofolate reductase

Often used in combination w/ SMX (TMP-SMX), causing sequential blockade of folate synthesis. Used for UTIs, shigella, salmonella, PCP treatment/prophylaxis, toxo prophylaxis

Cause megaloblastic anemia, leukopenia, granulocytopenia (may alleviate w/ supplement of folinic acid)

Question 16

Fluoroquinolones

Answer 16

Ciprofloxacin, levofloxacin

Bactericidal

Inhibit DNA gyrase and topoisomerase IV

Covers gram-negatives (including psudomonas), Neisseria, and some gram positives

Can cause GI upset, skin rashes, less commonly tendonitis, tendon rupture

Contraindicated in pregnancy

Resistance caused by chromosome encoded mutation in DNA gyrase, or plasmid-mediated resistance such as efflux pumps

Question 17

Metronidazole

Answer 17

Bactericidal

Forms free radical toxic metabolites in the bacterial cell that damage DNA.

Antiprotozoal

Treats Giardia, Trichomonas, anaerobes (below the diaphragm)
Used w/ clarithromycin and PPI as triple therapy for H.pylor

Can cause disulfiram-like reaction with alcohol, headache, metallic taste

Question 18

Isoniazid (INH)

Answer 18

Antimycobacterial

Decrease synthesis of mycolic acids

Used for treatment of M.tuberculosis

The only agent that is used as solo prophylaxis for TB

Cause neurotoxicity, hepatoxicity. Pyridoxine (B6) can prevent neurotoxicity

Question 19

Rifampin

Answer 19

Antimyobacterial

Inhibits DNA-dependent RNA polymerase

4Rs:
RNA polyermase inhibitor
Ramp up microsomal cytochrome 450
Red/orange (benign) body fluids
Rapid resistance if used alone

Delays resistance of dapsone in treatment for leprosy

Can cause minor hepatotoxicity and drug interactions (increased cytochrome 450 activity)

Question 20

Pyrazinamide

Answer 20

Antimyobacterial

Acidify intracellular environment to make phagolysosomes in macrophages more effective against TB

Cause hyperuricemia and hepatotoxicity

Question 21

Ethambutol

Answer 21

Antimyobacterial

Decrease carbohydrate polymerization of mycobacterium cell wall

Cause optic neuropathy (red-green color blindness)