20: Miscellaneous Antibiotics

Question 1

Name the miscellaneous antibiotics.

Answer 1

1. Quinolones/fluoroquinolones
2. Trimethoprim/Sulfamethoxazole (TMP-SMZ)
3. Daptomycin
4. Metronidazole
5. Polymyxin

Question 2

For quinolones:

1. Mechanism
2. Types
3. Resistance
4. Spectrum
5. Pharma
6. Indications
7. Toxicity

Answer 2

1. Bind topoisomerase II (DNA gyrase) or block topoisomerase IV, blocking DNA replication
2. Ciprofloxacin, levofloxacin, moxifloxacin
3. Increasing; single mutation in genes for topoisomerase II/IV, efflux system
4. GNs (Enterobac, Neisseria, Campylo, Pseudo), GPs (Pneumo, MSSA), respiratory (Myco, Legionella, Hemophilus), others (Mycobacterium tuberculosis [moxifloxacin], bacillus anthracis), limited anaerobic and enterococ
5. PO/parenterally; excellent distr., in kidney, prostate, lung and bile, usually > serum; in bone, CSF, < serum; high intracellular conc.; renal elimination, metal cations decrease oral absorption;
6. Empiric for CAP; complicated UTI/RTI, serious infx (osteomyelitis, pneumonia, soft tissue), STDs (gonorrhea, chancroid, chlamydial urethritis), ETEC (cipro), mutli-drug resistant TB (moxi), anthrax (cipro)
7. allergic rxn, photosensitivity, joint symptoms (ruptured tendon), QT prolongation

Question 3

For trimethoprim-sulfamethoxazole (TMP-SMZ):

1. Mechanism
2. Types
3. Resistance
4. Spectrum
5. Pharma
6. Indications
7. Toxicity

Answer 3

1. Sequential interference w/ folic acid synthesis –> synergism with bactericidal activity
2. Just TMP-SMZ (“Bactrim”)
3. TMP: decreased affinity, increased substrate; SMZ: decr. permeability, incr. substrate
4. Broad; GNs (E. coli, Kleb, proteus, salmonella, shigella, vibrio, burkholderia, h. infuenzae, neisseria), GPs (staph, strep, listeria; NOT enterococci), misc (pneumocystis, ocardia, chlamydia)
5. Combo abx with 1:5 ratio; PO/PE, will distr. in lungs, kidneys, biliary tree, CNS; hepatic metabolism; t.5 9-11 hrs, but prolonged in pts w/ renal insuff.
6. UTIs, prostatits, PCP pneumo, diarrhea due to salmonella, shigella, ETEC, U/L RTIs
7. Allergic, GI, nephrotoxicity, rare (hepatitis, megaloblastic anemia), Steven Johnson syndrome (toxic epidermal necrolysis) in AIDS subjects

Question 4

For daptomycin:

1. Mechanism
2. Types
3. Resistance
4. Spectrum
5. Pharma
6. Indications
7. Toxicity

Answer 4

1. Bactericidal; binds & inserts into GP membrane in calcium-dependent process; inserts lipophilic tail, oligomerizes forming channel allowing ion leakage.
2. Just dapto
3. Altered phospholipids in membrane
4. Abx-resist. GPs (VRE, MRSA, PCN-res. pneumococci)
5. PE only; renal clearance, inadequate conc. in lungs
6. VRE, MRSA, PCN-res. pneumo
7. Myopathy (must monitor CPK)

Question 5

For metronidazole:

1. Mechanism
2. Types
3. Resistance
4. Spectrum
5. Pharma
6. Indications
7. Toxicity

Answer 5

1. Release of short-lived free radicals that damage DNA/other molecules.
2. Just metro
3. Decreased ferrodoxin activity (reduced to produce radicals)
4. Broad anaerobes (clostridia, bacteroides), facultative anaerobes (helicobacter), anaerobic parasites (giardia, trichomonas, entamoeba)
5. PO/rect/vag/PE; renal metab., bactericidal well distr, even CSF
6. Anaerobic infx, including in CNS (brain abscess), pseudomembranous colitis, bacteroides
7. Disulfram effect w/ alcohol; do not use in pregnancy; interferes w/ coumadin metab.

Question 6

For polymyxin:

1. Mechanism
2. Types
3. Resistance
4. Spectrum
5. Pharma
6. Indications
7. Toxicity

Answer 6

1. Detergent; bind to LPS and disrupt membrane.
2. Colistin
3. Modified LPS w/ reduced surface charge
4. Mutli-drug resist. Enterobac, P. aerug, Acinetobacter
5. Final line agent
6. Often in ICU
7. Nephro, neuro