Quiz____?
Trimethoprim -
Answer✓✓
*MOA:*
Inhibits bacterial dihydrofolate reductase
*Clinical use:*
BacterioSTATIC used in combination with sulfonamides (trimethoprim-sulfamethoxazole [TMP-
SMX]), causing sequential block of folate synthesis. Combination used for UTIs, Shigella,
Salmonella, Pneumocystis jirovecii pneumonia treatment and prophylaxis, toxoplasmosis
prophylaxis.
*Toxicity:*
Megaloblastic anemia, leukopenia, granulocytopenia. (may alleviate with supplement
leucovorin/folinic acid rescue)
Quiz____?
1
, Ciprofloxacin
Norfloxacin
Levofloxacin
Ofloxacin
Moxifloxacin
Gemifloxacin
Enoxacin -
Answer✓✓
Fluoroquinolones
*MOA*:
Inhibition of *topoisomerase II (DNA gyrase)* and topoisomerase IV, the prokaryotic enzymes
that removes the buildup of supercoils that form at the site opposite the DNA replication fork
on the circular bacterial DNA so the DNA can be unwound during replication. Bactericidal.
*Clinical use*:
*Gram-⊖ bacilli of urinary and GI tracts,* including some hospital strains like Pseudomonas
(not moxifloxacin) and S. typhi
Gram-⊖ cocci (Neisseria spp)
Levofloxacin and moxifloxacin are also active against Gram-⊕ cocci (Staph and Strep) and
*atypical respiratory pathogens* (Legionella pneumophila, Mycoplasma pneumoniae, and
Chlamydophila pneumoniae)
*Cannot be taken with anti-acids*
2
, *Toxicity*:
Minor severity but frequent occurrence: nausea, vomiting, pain, headache
*Cartilage damage* seen in experimental dogs, rupture of Achilles' tendon in humans without
trauma (Contraindicated in pregnant women, nursing mothers, and children < 18 yo, *except in
children with CF°)
QTc interval prolongation (precursor to *torsade de pointes*)
Trovafloxacin linked to acute hepatic failure
Gatifloxacin caused hypo- and hyperglycemia
*MOR*:
Chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.
Quiz____?
Daptomycin -
Answer✓✓
*MOA*:
Lipopetide that disrupts cell membrane of Gram-⊕ cocci (not effective for gram-negatives)
*Clinical Use:*
S. aureus skin infections (especially MRSA), bacteremia, endocarditis, VRE.
*Not used for pneumonia* because inactivated by surfactant
3
, *Toxicity*:
Myopathy, rhabdomylosis (↑ CPK)
Quiz____?
Metronidazole -
Answer✓✓
*MOA:*
Forms *toxic free radical metabolites* in the bacterial cell that damage DNA. Bactericidal,
antiprotozoal.
*Clinical use:*
Anaerobes below the diaphragm.
Treats *G*iardia, *E*ntamoeba, *T*richomonas, *G*ardnerella vaginalis, *A*naerobes
(Bacteroides, C. difficile). Used with a proton pump inhibitor and clarithromycin for "triple
therapy" against H. *P*ylori.
("*GET GAP* on the *Metro* with *metr*onidazole!)
*Toxicity:*
*Disulfiram-like reaction* (severe flushing, tachycardia, hypotension) with alcohol; headache,
metallic taste.
4
Trimethoprim -
Answer✓✓
*MOA:*
Inhibits bacterial dihydrofolate reductase
*Clinical use:*
BacterioSTATIC used in combination with sulfonamides (trimethoprim-sulfamethoxazole [TMP-
SMX]), causing sequential block of folate synthesis. Combination used for UTIs, Shigella,
Salmonella, Pneumocystis jirovecii pneumonia treatment and prophylaxis, toxoplasmosis
prophylaxis.
*Toxicity:*
Megaloblastic anemia, leukopenia, granulocytopenia. (may alleviate with supplement
leucovorin/folinic acid rescue)
Quiz____?
1
, Ciprofloxacin
Norfloxacin
Levofloxacin
Ofloxacin
Moxifloxacin
Gemifloxacin
Enoxacin -
Answer✓✓
Fluoroquinolones
*MOA*:
Inhibition of *topoisomerase II (DNA gyrase)* and topoisomerase IV, the prokaryotic enzymes
that removes the buildup of supercoils that form at the site opposite the DNA replication fork
on the circular bacterial DNA so the DNA can be unwound during replication. Bactericidal.
*Clinical use*:
*Gram-⊖ bacilli of urinary and GI tracts,* including some hospital strains like Pseudomonas
(not moxifloxacin) and S. typhi
Gram-⊖ cocci (Neisseria spp)
Levofloxacin and moxifloxacin are also active against Gram-⊕ cocci (Staph and Strep) and
*atypical respiratory pathogens* (Legionella pneumophila, Mycoplasma pneumoniae, and
Chlamydophila pneumoniae)
*Cannot be taken with anti-acids*
2
, *Toxicity*:
Minor severity but frequent occurrence: nausea, vomiting, pain, headache
*Cartilage damage* seen in experimental dogs, rupture of Achilles' tendon in humans without
trauma (Contraindicated in pregnant women, nursing mothers, and children < 18 yo, *except in
children with CF°)
QTc interval prolongation (precursor to *torsade de pointes*)
Trovafloxacin linked to acute hepatic failure
Gatifloxacin caused hypo- and hyperglycemia
*MOR*:
Chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.
Quiz____?
Daptomycin -
Answer✓✓
*MOA*:
Lipopetide that disrupts cell membrane of Gram-⊕ cocci (not effective for gram-negatives)
*Clinical Use:*
S. aureus skin infections (especially MRSA), bacteremia, endocarditis, VRE.
*Not used for pneumonia* because inactivated by surfactant
3
, *Toxicity*:
Myopathy, rhabdomylosis (↑ CPK)
Quiz____?
Metronidazole -
Answer✓✓
*MOA:*
Forms *toxic free radical metabolites* in the bacterial cell that damage DNA. Bactericidal,
antiprotozoal.
*Clinical use:*
Anaerobes below the diaphragm.
Treats *G*iardia, *E*ntamoeba, *T*richomonas, *G*ardnerella vaginalis, *A*naerobes
(Bacteroides, C. difficile). Used with a proton pump inhibitor and clarithromycin for "triple
therapy" against H. *P*ylori.
("*GET GAP* on the *Metro* with *metr*onidazole!)
*Toxicity:*
*Disulfiram-like reaction* (severe flushing, tachycardia, hypotension) with alcohol; headache,
metallic taste.
4
