Exam 8: Miscellaneous Antibiotics Flashcards
What drug is not in the lecture notes that we need to know?
Fosfomycin
How is Vancomycin usually administered?
IV
Can be given orally for GI infections (it is poorly absorbed through the GI tract)
What is the tissue distribution of Vancomycin?
Widely distributed
Can penetrate BBB (good for meningitis)
How is Vancomycin eliminated?
though the kidneys
Adjust dose with renal failure
What is the mechanism of action of Vancomycin? Static or cidal?
-cidal
Inhibits bacterial cell wall synthesis
Binds to the D-alanyl-D-alanine portion of the peptidoglycan pentapeptide (same result as drugs that bind to PBP)
What is the general spectrum of Vancomycin?
Really good at killing gram positive bacteria (staph, strep, clostridium)
Worthless against gram negatives (too big to fit through gram negative porin channels)
What bugs have concerning resistance to Vancomycin? Mechanism?
Enterococci Bacterial enzymes (encoded by Van genes, plasmid) replace the D-alanyl-D-alanine end of the polypeptide, which don't permit adequate binding to the target.
What are 3 types of Van phenotypes?
Van A- inducible resistance to Vanco and teicoplanin
Van B- lower resistance, to Vanco only
Van C- Constitutive resistance to Vanco
What causes intermediate vanco resistance in Staph. aureus?
Thick walls and false drug targets
What causes high level resistance to vanco in Staph. aureus?
Van A transposon form Enterococcus faecalis
What are clinical uses of Vancomycin? (5)
- Serious MRSA staph infections (also pneumonia with MRSA)
- Gram positive infections in patients allergic to Penicillins and Cephalosporins
- C. diff (orally administered)
- Staph. meningitis
- Included with 3rd gen Cephalosporin to treat Strep pneumo meningitis
Adverse effects of Vancomycin
Ototoxicity (especially with coadministration of aminoglycosides)
Nephrotoxicity (especially with coadministration of ahminoglycosides or cephalosporins)
Red Neck Syndrome- Rapid infusion can cause flushing due to histamine release (not a true allergic reaction)
Where does Clindamycin penetrate well? Not well?
Penetrates most tissues well
Penetrates abscessed well
Does not penetrate BBB (can still treat cerebral toxoplasmosis somehow)
how is clindamycin excreted?
metabolized by liver (adjust dose for liver failure)
What is the mechanism of Clindamycin?
Binds 50S ribosomal subunit
Bacteriostatic
What mechanisms underlie resistance to Clindamycin?
- Modified 50S subunit (mutations)
2. Enzymatic methylation of 50S subunit (as seen with macrolides)
What if you get a positive D test?
Dont use Clindamycin for a serious infection.
What are 3 types of bugs Clindamycin is good at treating?
- Staph
- Strep
- ANAEROBES!
What are uses of Clindamycin?
- Anaerobic infections (abscesses outside the CNS)
- In combo with other drugs in penetrating wounds of the abdomen
- Prophylaxis for endocarditis in high risk patients getting dental procedures (alternative to Amoxicillin due to allergy)
- Alternative agent for gram positive and anaerobic infections in patients allergic to penicillins and cephalosporins
What is a major complication associated with Clindamycin?
C. diff (pseudomembranous colitis)
How is Nitrofurantoin excreted?
Super rapidly in the urine (so fast that you don’t see it systemically)
Causes brown urine
What is a contraindication for Nitrofurantoin?
Renal failure
What is the mechanism of Nitrofurantoin?
Bacteriostatic or -cidal depending on the dose (-cidal >100micro grams/mL)
Mechanism: Reduced forms of the drug bind to and damage bacterial DNA
What is Nitrofurantoin used to treat?
UTIs (acute treatment and chronic prophylaxis)
What is the most common adverse effect of Nitrofurantoin?
GI Upset
Fosfomycin
Taken orally in water solution
Excreted by kidneys
Inhibits bacterial cell wall synthesis (-cidal)
Used to treat UTIs
Adverse effects: Headaches, diarrhea, vaginitis
Polymyxins B and E Administration and Mechanism
E is parenteral only, B can be topical, otic, ophthalmic or parenteral
Parenteral admin is a last resort
They are Cationic Detergents that interact with phospholipids and disrupt bacterial cell walls (killing effect)
What bugs are Polymyxins good at treating?
Gram negatives
Uses of Polymyxins
Topical use with neomycin/bacitracin (Neosporin) in skin infections
Urinary bladder irrigation to prevent infections with indwelling catheters
Parenteral admin is last resort in some bad gram negative infections
Adverse effects of Polymyxins
Nephrotoxicity
Neurotoxicity
What are methods of Metronidazole administration?
Oral, IV, rectal, Vaginal gel
Where can Metronidazole penetrate?
CNS (brain abscess)
What can Metronidazole do to the urine?
Turn it red/brown
Metronidazole mechanism
Nitro group is reduced, it then binds to bacterial DNA and inhibits synthesis
What kinds of bugs can Metronidazole treat well?
Anaerobic powerhouse antibiotic
Metronidazole Uses
anaerobic brain abscesses
B. fragilis
C. diff
Adverse effects of Metronidazole
Carcinogenic… avoid in breast milk/pregnancy
Peripheral neuropathy
Disulfiram like reaction with alcohol
How can Bacitracin NOT be administered? Why?
Parenterally
Nephrotoxic
Bacitracin mechanism
Inhibits bacterial cell wall synthesis
Inhibits transpoty of peptidoglycan subunits
Uses of Bacitracin
Mostly topical
Open wounds
Eye infections
Oral for C. diff (alternative therapy)
Adverse effects of Bacitracin?
Nephrotoxicity- renal failure and glomerular necrosis
Quinupristin+Dalfopristin
Combo used by IV
Quinupristin+Dalfopristin (synercid) elimination?
Metabolized mostly by liver, biliary excretion
Mechanism of action of Quinupristin+Dalfopristin (Synrecid)
Binds to 50S subunit (-cidal)
They each bind to a different part of the subunit
What are 3 modes of resistance for Quinupristin+Dalfopristin ?
- Methylation of binding site
- Acetylation inactivation of dalfopristin
- Efflux pumps
Uses for Quinupristin+Dalfopristin
Complicated skin infections by staph and strep
MDR serious infections
Bacteremia by Vanco resistant bugs
Linezolid Mechanism
Binds to 50S subunit
What bugs can Linezolid treat?
Gram positives (not anaerobes)
Uses of Linezolid
Infections caused by Vanco resistance enterococcus
Nosocomial pneumonia from Staph aureus/MRSA*
CAP
Complicated and uncomplicated skin infections
Use of Linezolid for enterococcus
Not first line because it is bacteriostatic for Enterococcus
Adverse effects of Linezolid
Thrombocytopenia
GI, Headache, Peripheral Neuropathy
Inhibits MAO (don’t give it with SSRIs or Tyramine rich foods or you may cause serotonin syndrome)
Daptomycin Mechanism
Binds to plasma membrane and causes depolarization leading to cell death
Daptomycin elimination
mostly renal (adjust dose for renal failure)
Used of Daptomycin
Complicated skin infections by Staph and Strep
Bacteremia
Endocarditis
When don’t we use Daptomycin? Why?
Pulmonary infections
Surfactant antagonizes the drug
