Other Antibiotics Flashcards
Trimethoprime/sulphamethoxazole
Trimethoprim/sulphamethoxazole: Drugs: - Oral or IV cotrimoxazole (TMP/SMX) = trimethoprim (TMP) + sulfamethoxazole (SMX) - Oral sulfisoxazole - Oral sulfadiazine + pyrimethamine
Mechanism of action:
- Sulfonamides inhibit bacterial folic acid synthesis.
- TMP inhibits dihydrofolate reductase (DHFR), a key enzyme in purine synthesis
- DHFR reduces dihydrofolic acid to tetrahydrofolic acid (THF), using NADPH
- THF can subsequently be converted to methylene-THF
- Methylene-THF is an important cofactor for thymidylate synthetase, which catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP)
- Both SMX and TMP are bacteriostatic, but become bactericidal when combined.
CNS penetration:
- Good
Route of elimination:
- Primarily renal
Clinical use: SMX - Gram-positive bacteria - Gram-negative bacteria - Simple urinary tract infections (UTIs) - Nocardia - Chlamydia TMP/SMX - Shigella - Salmonella - Recurring UTIs - Prophylaxis and treatment of P. jirovecii - Prophylaxis of toxoplasmosis
Adverse effects:
SMX
- Hyperkalemia
- Exanthem
- Gastrointestinal distress
- Photosensitivity
- Nephrotoxicity (especially tubulointerstitial nephritis)
- Kernicterus in infancy
- Triggers hemolytic anemia in G6PD-deficient patients
- Displaces albumin-binding drugs (e.g., warfarin)
TMP:
- May be alleviated by leucovorin rescue
- Megaloblastic anemia
- Leukopenia/granulocytopenia
- Hyperkalemia, particularly in HIV-positive patients
- Artificially increased creatinine (despite unchanged GFR)
Contraindications:
- Last trimester of pregnancy
- Lactating women
**Trimethoprim (TMP) Treats Marrow Poorly.
Flurquinolones
Drugs:
- Oral: norfloxacin, moxifloxacin, gemifloxacin
- Oral or IV: ciprofloxacin, ofloxacin, levofloxacin
Mechanism of action:
- Inhibition of prokaryotic topoisomerase II (DNA gyrase) and topoisomerase IV
- Bactericidal
CNS penetration:
- Good
Route of elimination:
- Primarily renal
- Moxifloxacin undergoes biliary excretion
- Absorption is reduced when coadministered with polyvalent cations (e.g. magnesium, calcium, or iron)
Clinical use:
- Gram-negative bacilli causing urinary and GI infections
- Genital pathogens Neisseria gonorrhoeae, Chlamydia trachomatis, Ureaplasma urealyticum
- Ciprofloxacin is effective against Pseudomonas
- Pneumonia
- Certain forms of atypical pneumonia (e.g., Legionella, Mycoplasma, and Chlamydophila pneumoniae)
- Also affective against anaerobes
- Gemifloxacin is highly potent against penicillin-resistant pneumococci.
Adverse effects:
- In children: potential damage to growing cartilage; reversible arthropathy
- Muscle ache, tendinitis, tendon-rupture (especially the Achilles tendon)
- Hyperglycemia/hypoglycemia
- Peripheral neuropathy
- Can lower the seizure threshold
- QT prolongation
- Photosensitivity
Contraindications:
- < 18 years
- Pregnancy
- Lactating women
- Epilepsy, stroke, CNS lesions/inflammation
- QT prolongation
- Renal failure (relative contraindication)
- Hepatic failure (relative contraindication)
Mechanisms of resistance:
- Bacterial mutations can occur in genes that mediate:
- -DNA gyrase and topoisomerase IV enzymes
- Cell wall permeability
- Efflux pumps
Nitroimidazoles
Drugs:
- Oral or IV metronidazole
Mechanism of action:
- Creates free radicals within the cell, which leads to DNA-strand breaks
- Bactericidal
CNS penetration:
- Good
Route of elimination:
- Renal
Clinical use:
- Certain protozoa (Giardia, Entamoeba histolytica, Trichomonas)
- Anaerobes (e.g., Clostridium, Bacteroides)
- Facultative anaerobes
- Gardnerella vaginalis
- Helicobacter pylori as part of a triple therapy regimen
Adverse effects:
- Neurotoxicity (e.g., headache)
- Disulfiram-like reaction when consumed with alcohol (flushing, tachycardia, hypotension)
- Nitroimidazoles inhibit acetaldehyde dehydrogenase → accumulation of acetaldehyde → immediate hangover-like symptoms
- Metallic taste
Contraindications:
- Lactating women
- Hepatic failure (relative contraindication)
** GET GAP on the Metro! (Giardia, Entamoeba, Trichomonas, Gardnerella, Anaerobes (Clostridium, Bacteroides), H. Pylori → Metronidazole)
** Clindamycin is indicated for anaerobes above the diaphragm and metronidazole treats anaerobes below it!
