Antibiotics: Inhibitors of Protein Synthesis Flashcards
Fluoroquinolones
• Synthetic fluorinated analogs of the quinolone nalidixic acid
- Ciprofloxacin
- Levofloxacin
- Moxifloxacin
- Newer class of antibiotics but widely used - broad spectrum of activity
- Resistance emerging
Fluoroquinolones MOA
Fluoroquinolones - Pharmacokinetics
- Oral bioavailability is excellent but is reduced by divalent cations (e.g. antacids)
- Good distribution to tissues; little experience in treating meningitis
- Most eliminated through the kidney
Fluoroquinolones – Spectrum and Clinical Use
- Gram-neg bacilli
- Traveler’s diarrhea
- Salmonella
- UTI (E. coli)
- Pseudomonas
– Ciprofloxacin > others
– Only PO drugs that cover Pseudomonas
• S. pneumoniae, Haemophilus
– “respiratory”
– Cipro ineffective
- Atypicals (e.g. Mycoplasma)
- Second-line as part of TB regimen
- Prophylaxis for N. meningitidis (not for treatment)
Fluoroquinolones FDA Black Box Warning
- Risks outweigh benefits for:
- Bacterial sinusitis
- Acute-on-chronic bronchitis
- Uncomplicated UTI
- Benefits outweigh risks for:
- Bacterial pneumonia
- Anthrax
- Plague
- Others
Fluoroquinolones - Adverse Reactions
Metronidazole MOA
• Activated in bacterial cell by reduction via endogenous nitroreductase
- Only anaerobic bacteria produce nitroreductase
- Aerobic bacteria lack nitroreductase
• Intermediate free radical metabolites disrupt DNA and inhibit DNA synthesis
Metronidazole Pharmacokinetics and Pharmacodynamics
- Well absorbed from the GI tract
- Large volume of distribution, including brain / CSF
- Metabolized in liver; excreted in urine
- Nausea and vomiting
- Disulfiram-like effect
- Peripheral neuropathy (rare)
Metronidazole – Clinical Use
• Anaerobic infections
- Broadest anaerobic drug
- Intra-abdominal abscesses
- CNS polymicrobial infections
• Clostridial infections
- C. difficile
- C. tetani
• Protozoal infections
- Entamoeba histolytica
Rifampin
- Oral and IV formulations
- Inhibits bacterial DNA-dependent RNA polymerase
- Penetrates all tissues, including CNS
- Hepatic metabolism, biliary excretion
- Significant drug interactions (azoles, warfarin, immunosupressives, etc)
- Adverse effects:
- Turns urine and tears orange, stains contact lenses • Hepatitis
- Cholestasis (elevated direct bilirubin)
• Clinic use:
- Adjunctive therapy for S. aureus – never given alone for MSSA/MRSA due to rapid development of resistance
- Latent tuberculosis (monotherapy)
- Active tuberculosis (as part of a combination)
- Non-TB mycobacteria (as part of a combination) Classification by Mech
Antifolates
- Mammalian cells use exogenous preformed folate
- Bacteria must synthesize folate from PABA
Sulfonamides
• Sensitive organisms
- those that must synthesize own folate
• Acquired resistance
– Altered DHPS
– Increased PABA producti
Sulfonamides Adverse Reactions
- Highly allergenic
- Hypersensitivity reactions, especially patients with HIV
- Stevens-Johnson Syndrome
- Toxic epidermal necrolysis
- Life-threatening
Trimethoprim
Trimethoprim / Sulfamethoxazole
- 20-100 X greater activity than sulfa alone
- Both excreted unchanged by kidney
- “Co-trimoxazole” (Bactrim, Septra)
- Spectrum of activity
- MSSA/MRSA are susceptible
- GAS are resistant
- Listeria (2nd-line)
- GNRs – E. coli, Salmonella, etc
- Stenotrophomonas maltophilia
- Nocardia
- Pneumocystis jiroveci
- Toxoplasma gondii
