FA - Micro - Antimicrobials (2016) Flashcards
Carbapenems - Mechanism of imipenem:
- Broad-spectrum, β-lactamase-resistant carbapenem.
- ALWAYS administered with cilastatin (inhibitor of renal dihydropeptidase I) to DECREASE inactivation of drug in renal tubules.
Newer carbapenems include:
- Ertapenem –> LIMITED PSEUDOMONAS coverage.
2. Doripenem.
Carbapenems - Clinical use:
- Gram (+) cocci.
- Gram (-) rods.
- Anaerobes.
Carbapenems - Clinical use limited to …?
Life-threatening infections or after other drugs have failed.
–> Significant side effects.
Meropenem has …?
Decr. risk for SEIZURES and is STABLE to dehydropeptidase I.
Carbapenems - Adverse effects:
- GI distress.
- Skin rash.
- CNS toxicity (seizures).
At high plasma levels.
Vancomycin - Mechanism:
Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors.
Vancomycin - Bacteriostatic/cidal?
Bactericidal against MOST bacteria.
- -> Bacteriostatic against C.difficile.
- -> Not susceptible to beta-lactamases.
Vancomycin - Clinical use:
Gram (+) bugs ONLY –> Serious multidrug-resistant organisms, including:
- MRSA.
- S.epidermidis.
- Sensitive Enterococcus species.
- C.difficile (ORAL dose).
Vancomycin - Adverse effects:
- Well tolerated in general - But NOT trouble free.
- Nephrotoxicity.
- Ototoxicity.
- Thrombophlebitis.
- Diffuse flushing - Red man syndrome (pretreat with antihistamines + slow infusion rate).
Vancomycin - Mechanism of resistance:
Occurs in bacteria via amino acid modification of D-ala D-ala to D-ala D-lac.
Oxazolidinones:
Linezolid.
Linezolid - Mechanism:
- Inhibits protein synthesis by binding to 50S.
2. Prevents formation of the initiation complex.
Linezolid - Clinical use:
Gram (+) species including MRSA + VRE.
Linezolid - Adverse effects:
- Bone marrow suppression (esp. thrombocytopenia).
- Peripheral neuropathy.
- Serotonin syndrome.
Linezolid - Mechanism of resistance:
Point mutation of ribosomal RNA.
Dapsone - Mechanism:
Similar to sulfonamides, but structurally distinct agent.
Dapsone - Clinical use:
- Leprosy (lepromatous and tuberculoid).
2. PCP proph.
Dapsone - Side effects:
Hemolysis if G6PD deficient.
Daptomycin - Mechanism:
LIPOPEPTIDE that disrupts cell membrane of gram (+) cocci.
Daptomycin - Clinical use:
- S.aureus skin infections (esp. MRSA).
- Bacteremia.
- Endocarditis.
- VRE.
Daptomycin - Side effects:
- Myopathy.
2. Rhabdomyolysis.
Daptomycin - NOT used for …?
PNEUMONIA!!!
AVIDLY BINDS AND INACTIVATES SURFACTANT!!!
Rifamycins - Mechanism of resistance:
Mutations reduce drug binding to RNA polymerase.
–> Monotherapy rapidly leads to resistance.
Streptomycin - Mechanism:
Interferes with 30S.
Streptomycin - Clinical use:
Mycobacterium tuberculosis (2nd line).
Streptomycin - Adverse effects:
- Tinnitus.
- Vertigo.
- Ataxia.
- Nephrotoxicity.
Treatment of highly-resistant bacteria - Multidrug-resistant P.aeruginosa, multidrug-resistant Acinetobacter baumannii:
- Polymyxin B.
2. Polymyxin E (colistin).
Azoles inhibit which CYP450 enzyme involved in ergosterol synthesis?
14-alpha-demethylase.
Anti-mite/louse therapy:
- Permethrin (blocks Na channels –> Neurotoxicity).
- Malathion (AChE inhibitor).
- Lindane (Blocks GABA –> Neurotoxicity).
- -> Used to treat scabies (Sarcoptes scabiei) + Lice (Pediculus and Pthirus).
Hep C therapy:
- Ribavirin.
- Sofosbuvir.
- Simeprevir.
Sofosbuvir - Mechanism:
Inhibits HCV RNA-dependent RNA polymerase –> Acts as a chain terminator.
Sofosbuvir - Clinical use:
- Chronic HCV in combination with ribavirin, +/- Peg-IFN.
2. DO NOT use as MONOTHERAPY.
Sofosbuvir - Adverse effects:
- Fatigue.
- Headache.
- Nausea.
Simeprevir - Clinical use:
- Chronic HCV in combination with LEDIPASVIR.
2. DO NOT USE AS MONOTHERAPY.
Simeprevir - Adverse effects:
- Photosensitivity.
2. Rash.
Ledipasvir:
NS5A INHIBITOR.
5 infection control techniques:
- Autoclave.
- Alcohols.
- Chlorhexidine.
- Hydrogen peroxide.
- Iodine and iodophors.
Infection control techniques - Goals include:
- Disinfection.
2. Sterilization.
Disinfection:
Reduction of pathogenic organism counts to safe levels.
Sterilization:
Inactivation of self-propagating biological entities.
Autoclave:
Pressurized steam at >120C - May be sporicidal.
Alcohols:
Denature proteins and disrupt cell membranes. Not sporicidal.
Chlorhexidine:
Denatures proteins and disrupts cell membranes. NOT sporicidal.
Hydrogen peroxide:
Free radical oxidation - Sporicidal.
Iodine and iodophors:
Halogenation of DNA, RNA, and proteins - May be sporicidal.
Cephalosporins (I-V) - Mechanism of resistance:
Structural change in penicillin-binding proteins (transpeptidases).