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129 Cards in this Set
- Front
- Back
What drugs are useful against mycobacterial infections?
|
Streptomycin
Amikacin Clarithromycin Azithromycin Rifampin |
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Drugs against MSSA?
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PRPs (methicillin, nafcillin, oxacillin, dicloxacillin)
Beta-lactam/Beta-lactamase inhibitors 1st generation cephalosporins (cephalexin and cefazolin) Cefepime |
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Drugs against ESBL (extended-spectrum beta-lactamases)
|
DOC is ertapenem (group 1 carbapenem)
Dori, imi, and mero-penem good from gram-negatives Tigecycline |
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Drugs against MRSA?
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Vancomycin
Daptomycin Linezolid Tetracyclines (doxycycline and minocycline) Tigecycline Lincosamides - clindamycin TMP/SMX Rifampin |
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Drugs against VRE?
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DOC is linezolid
Daptomycin Quinupristin/dalfopristin (Synercid) Tigecyclin |
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Antipseudomonal agents?
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Piperacillin (Piperacillin/tazobactum)
Ceftazadime Cefepime Carbapenems (except ertapenem) Aztreonam Aminoglycosides FQs (Cipro > Levo) Polymixins |
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Drugs with anaerobic coverage?
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Metronidazole
Penicillin B-lactam/B-lactamase inhibitors - ampicillin/sulbactam - piperacillin/tazobactum Clindamycin Cephamycins (2B Cephalosporins) Carbapenems Moxifloxacin Tetracyclins (Some) |
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Antimicrobials effective against enterococci?
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Penicillin
Aminopenicillins Piperacillin - (only if enterococcus is also susceptible to ampicillin) Carbapenems - Imipenem the best - Ertapenem NO activity Aminoglycosides - Amikacin - Gentamycin - Streptomycin Vancomycin Daptomycin Linezolid |
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What antimicrobials target protein synthesis?
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Aminoglycosides
Tetracyclines Tigecycline Linezolid Quinupristin/Dalfopristin Macrolides Lincosamides Chloroamphenicol |
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What drugs target the 30S ribosome?
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Aminoglycosides
Tetracyclines |
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What drugs target the 50S ribosome?
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Chloroamphenicol
Macrolides Lincosamides Linezolid Quinupristin/Dalfopristin |
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What are the CAPs (community-acquired pathogens)?
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S. pneumoniae
M. catarrhalis H. influenzae |
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What drugs can be used to treat Community Acquired Pneumonia (CAP)?
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3rd generation cephalosporins
Fluroquinolones (except Ciprofloxacin) Macrolides (namely azithromycin - 1st line) Tetracyclines (doxycycline and minocycline) |
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What are considered the respiratory fluroquinolones?
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Levofloxacin and Moxifloxacin (and gemifloxacin)
|
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What is the DOC for CAP/meningitis?
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Ceftriaxone (3rd generation cephalosporins)
|
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What are considered the "nasty" gram-negative bacteria?
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A. baumannii
P. aeruginosa |
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What classes or particular drugs disrupt cell wall synthesis?
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beta-lactams
vancomycin daptomycin |
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Folic acid inhibitors?
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SMX/TMP (sulfa drugs)
Trimethoprim inhibits DHF-reductase SMX is a antagonist of PABA |
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Drugs that inhibit DNA synthesis?
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Fluoroquinolones via inhibition of DNA gyrase and topoisomerase IV
|
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What drugs are protein synthesis inhibitors?
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Aminoglycosides
Tetracylcines Chloroamphenicol Lincosamides Linezolid Macrolides Streptogramins |
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What is MOA of beta-lactams?
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Bind to PBPs and prevent transpeptidation thereby disrupting cell wall synthesis
|
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What are beta-lactamases?
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Beta-lactamases are enzymes secreted by the targeted organism that hydrolyze the beta-lactam antibiotics
- penicillinases - cephalosporinases - carbapenemases |
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What are the remaining clinical uses of penicillin?
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Syphillis
Mouth anaerobes (dental procedures) Necrotizing fascitis |
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What are the drugs of choice for MSSA?
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Nafcillin and oxacillin (both administered IV)
|
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What advantage does piperacillin give over ampicillin?
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It expands the coverage of ampicillan to include p. aeruginosa
|
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What class of drugs were created to overcome beta-lactamases produced by gram-negs and anaerobes?
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Beta-lactam/Beta-lactamase inhibitors
- Amoxicillin/clavulanic acid - Ampicillin/sulbactam - Ticaracillin/clavulanic acid - Piperacillin/tazobactum |
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What are the common adverse effects involved with penicillin?
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Allergic reaction (rash vs anaphylaxis)
Acute interstitial nephritis Bone marrow suppression (rare) Seizures - (high, non-renally adjusted doses) Gastrointestinal symptoms - common with ampicillin Contact dermatitis - common with ampicillin |
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Penicillin drug interactions?
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Minimal but potential for additive toxicites with other agents
- Probenecid (gout medication) - Increases half-life - Block renal excretion |
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Clinical pearl of the cephalosporin class?
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Good gram-positive coverage but no activity against enterococcus
|
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What are the first generation cephalosporins?
-Uses? |
Cephalexin and cefazolin
- Good vs MSSA (s. aureus) and most streptococcus - Good skin coverage if not worried about MRSA |
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What are second generation cephalosporins?
|
-2A
- Cefaclor and cefuroxime - Use in respiratory tract infecions -2B - Cefotetan and cefoxitin - EXCELLENT anaerobic activity |
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What are the cephamycins?
What is the clinical utility? |
The cephamycins are the 2B generation cephalosporins:
- Cefotetan - Cefoxitin Their utility: - Excellent anerobic activity - Used for surgical prophylaxis and community acquired intraabdominal infections |
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What are the 3rd generation cephalosporins?
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Cetriaxone
Cefotaxime Cefixime Cefpodoxime (PO) |
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Clinical utility of 3rd generation cephs?
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Excellent s. pneumoniae - drug of choice for CAP
Excellent in vitro activity vs. most nosocomial gram-neg bacilli |
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What is the utility of ceftazadime?
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Adds p. aeruginosa
|
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Clinical pearls of 3rd generation cephs?
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- Meningits
- Treatment of choice for CNS infections - Ceftriaxone and ceftazadime can penetrate well into the meninges - Ceftriaxone is DOC for community acquired meningitis |
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What is the drug of choice for community acquired meningitis?
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Ceftriaxone
|
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Coverage of Cefepime?
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Excellent staph and strep (MSSA)
Good against: - Nosocomial agents - P. aeruginosa - SPICE Organisms |
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What is a side effect of ceftriaxone?
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Biliary sludging in neonates
Avoid in this population |
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What cephalosporins have a MTT group and what are the implications of this?
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- Cefotetan (2B), Cefetazole and cefoparazone
- Hypothrombinemia and disulfram-like reactions with alcohol |
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What are the carbapenems?
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Imipenem (2)
Doripenem (2) Meropenem (2) Ertapenem (1) |
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What coverage do the group 2 carbapenems provide?
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- imipenem, meropenem, doripenem
- Great gram-negative coverage - ESBL - P. aeruginosa (dori/mero > imi) - A. baumannii (imi > dori/mero) |
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What do carbapenems NOT cover?
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MRSA
Entercoccus resistant to ampicillin KPC S. maltophilia C. difficile Fungi and viruses |
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What side effect is of biggest concern when treating with carbapenems?
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Seizures
|
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What is the coverage and clinical use of Aztreonam?
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- Gram-negative activity only
- P. aeruginosa - NO ESBL, SPICE Place in therapy: - Empiric gram-negative nosocomial coverage in patients with penicillin allergy |
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What beta-lactams DO NOT require renal dosing?
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- Ceftriaxone
- Penicillinase-resistant penicillins - Nafcillin, methicillin, oxacillin, dicloxacillin |
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What are the aminoglycosides?
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- Tobramycin
- Gentamicin - Amikacin - Streptomycin - Neomycin (PO/topical) |
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What class of organisms do aminoglycosides not work against and why?
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- Anaerobes
- They require active transport (oxygen dependent) to get into the bacterial cell to exert its action |
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Spectrum of activity for aminoglycosides?
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- Gram (+)
- Activity against strep and staph - Only used in this respect with synergy for serious infections - Gram (-) - Many gram (-) bacilli - Pseudomonas - Amikacin > tobramycin > gentamycin |
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What are the fluoroquinolones? (5)
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- Levofloxacin
- Moxifloxacin - Cirpofloxacin - Gemifloxacin - Norfloxacin |
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What fluroquinolones have the best bioavailability?
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- Levofloxacin and moxifloxacin (100%)
- Ciprofloxacin (80%) - NOT norfloxacin (used for UTI) |
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What fluroquinolone has anaerobic coverage?
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Moxifloxacin
|
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What class of organisms do aminoglycosides not work against and why?
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- Anaerobes
- They require active transport (oxygen dependent) to get into the bacterial cell to exert its action |
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Spectrum of activity for aminoglycosides?
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- Gram (+)
- Activity against strep and staph - Only used in this respect with synergy for serious infections - Gram (-) - Many gram (-) bacilli - Pseudomonas - Amikacin > tobramycin > gentamycin |
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Clinical use of tobramycin/amikacin?
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Used for empirical coverage of nosocomial infections
|
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Aminoglycoside PK
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- Poor oral absoprtion --> PO not used for systemic infections
- Concentration-dependent killing - Hydrophilic (poor concentration in tissues) - High concentration in the urine which makes them good for UTI |
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What are the adverse side effects associated with aminoglycosides (3 main ones)?
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- Nephrotoxicity
- associated with duration and trough levels - Vestibular/Oto-toxicity - associated with peak levels - Neuromuscular blockade |
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Fluroquinolone: spectrum of activity
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Gram (+)
- Levofloxacin > Moxifloxacin > Ciprofloxacin Gram (-) - Cirpofloxacin > Levofloxacin > Moxifloxacin |
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What two fluroquinolones have anti-pseudomonas activity?
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Ciprofloxacin and levofloxacin (C > L)
|
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What fluoroquinolone has anaerobic coverage?
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Moxifloxacin
|
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Fluroquinolone PK
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- Highly lipophilic, good to treat infections in a number of sites (CSF, lungs, skin, bone, joint, blood)
- Renally eliminated and therefore needs renal adjustment (except for moxifloxacin) |
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What are the side effects associated with fluroquinolones?
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- CNS toxicity
- Ruptured tendon - Damage to growing cartilage - Dysglycemia - Cardiac arrhythmias and possible torsades |
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Drug interactions with FQs
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Reduced absorption when taken with divalent cations (Ca, Mg, and Fe) due to chelation
|
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Which of the following would not be expected to have activity versus e. faecalis:
- Piperacillin - Ampicillin - Ceftazadime - Ampicillin/Sulbactam |
Ceftazadime
As a whole, the entire cephalosporin class lacks enterococcal activity |
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Which cephalosporin would you expect to have the greatest gram-negative activity:
- Cefuroxime - Cephalexin - Ceftriaxone |
Ceftriaxone
|
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What is the SOA for vancomycin?
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Gram positives ONLY!
aerobes > anaerobes |
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MOA of vancomycin?
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Binds to d-ala d-ala termpinal portion of peptidoglycan precursors and prevents further cross-linking
|
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What is the clinical application of vancomycin?
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-Used empirically to cover for MRSA
-Patient with beta-lactam allergy - Vanco has activity against strep and enterococcus, as well as MSSA, but is inferior to beta-lactams in this respect |
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Beta-lactams vs vancomycin
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Vancomycin is able to cover for MSSA, streptococcus and enterococcus but not with the same efficacy as beta-lactams
- Vancomycins niche is in the treatment of MRSA |
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What is MRSA?
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MRSA is the result of a PBP alteration that confers resistance to beta-lactams -- antibiotics that utilize PBPs to exert their function
|
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What are the AE of Vancomycin?
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- Nephrotoxicity
- Ototoxicity - Rash - Red Man's Syndrome |
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MOA of daptomycin
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In a calcium-dependent manner, inserts into the cell wall of the bacteria and forms a pore that results in potassium efflux and death
|
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Spectrum and uses of Daptomycin
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- IV use only
-Gram-positives ONLY! - staph, strep, enterococcus -Used clinically to treat: - MRSA and VRE bloodstream infections, endocarditis, and soft tissue infections |
|
AE associated with daptomycin
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- CPK elevations and rhabdomyolysis
- Irreversible binding to pulmonary surfactant -- AVOID in pneumonia |
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Spectrum of activity of Linezolid
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Gram-positive ONLY (staph and enterococcus)
|
|
Clinical use of Linezolid
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- DOC for VRE infections
- Some use for MRSA (pneumonia +/- elevated vancomycin MIC) |
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AE of linezolid
|
- Thrombocytopenia with long courses of linezolid (~14 days)
- Rare peripheral/optic neuropathy |
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Drug interactions assoc. with Linezolid
|
-Linezolid is a weak MAOI
- May lead to serotonin syndrome with drugs such as SSRIs |
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What is the mechanism associated with resistance in VRE?
|
Vanco binds to the D-ala D-ala terminal portion of peptidoglycan precursors to prevent cross-linking
In VRE, one of the D-ala subunits is changed to either D-ser or D-lac. This single amino acid change results in an inability for Vanco to bind and work. |
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Why has quinupristin/dalfopristin (streptogramin, synercid) fallen out of favor as a treatment for VRE?
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Due to the high rates of infusion reactions, arthralgias, and myalgias
|
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How do macrolides exert their function?
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They bind to the 50S subunit of bacterial ribosomes to inhibit bacterial protein synthesis
|
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What are the macrolides?
|
Erythromycin (IV/PO)
Clarithromycin (PO) Azithromycin (IV/PO) |
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What is the SOA of the macrolides?
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- Respiratory pathogens
- C. trachomatis - Mycobacterial avium complex - azithromycin and clarithromycin - H. pylori - clarithromycin |
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What are the AEs assoc. with Macrolides? (3)
|
- Greatest concern: N/V/D (worst with erthromycin)
- Hepatotoxicity - QT prolongation |
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What are the PKs of the Macrolides?
|
- Azithromycin has excellent bioavailability (the best in its class) and a long half life
- The macrolides are in general inhibitors and substrates of CYP3A4 liver enzymes - Many DDIs - Worst with erythromycin and clarithromycin - Not so bad with azithromycin |
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Clinical uses of Macrolides
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- Azithromycin is the 1st line treatment for respiratory tract infections with CAP
- Clarithromycin is standard treatment for H. pylori - Often used as part of mycobacterial regimens |
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What is telithromycin and why has its use been restricted?
|
- Derivative of macrolides with a similar spectrum to azithromycin but with enhanced streptococcus pneumoniae coverage
- Limited due to its serious hepatotoxicity |
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What are the tetracyclins?
|
- Tetracyclin
- Doxycycline - Minocycline - Demeclocycline |
|
SOA for doxycycline and minocycline
|
- Gram (+)
- S. pneumoniae - S. aureus - Enterococcus -Gram (-) - H. influenzae and m. catarrhalis - Some activity against enterobacteraciae |
|
Tetracyclin PK
|
- Highly lipophilic
- Penetrates many sites well but does not stay in the blood |
|
AE associated with the tetracylcines
|
- N/V/D
- Photosensitization - Binding into growing teeth and bones (therefore avoid in < 8 yo) - Chelate with divalent and trivalent cations |
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What are the two drugs that are capable of chelating with ions?
|
- Tetracyclin (trivalent and divalent)
- Fluoroquinolones (divalent only) |
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Clinical uses of tetracyclines
|
Doxycycline and minocycline used for:
- Respiratory tract infections, CAP - UTIs - Skin and soft tissue infections |
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What is the advantage of tigecycline over tetracyclines?
|
Different structure allows it to avoid or overcome resistance mechanisms:
- Target-side modifications - Efflux pumps |
|
SOA of tigecycline
|
- Gram (+)
- Broad, include MRSA and VRE - Gram (-) - Similar to tetracyclines but includes resistant Gram (-) organisms - acinetobacter, ESBL |
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Place in therapy of tigecycline
|
Last line option for the nasty gram-neg bacterial organisms
- carbapenem resistant acinetobacter, klebsiella Polymicrobial wounds including MRSA and VRE |
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What are the lincosamides?
|
Lincomycin, clindamycin
Clindamycin has completely replaced lincomycin due to enhanced activity |
|
What is MOA of lincosamides?
|
- Binds to the 50S subunit of the bacterial ribosome
|
|
SOA of Clindamycin
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- Gram (+)
- S. aureus (including MRSA) - Streptococcus (usually) - NO GRAM NEGATIVE ACTIVITY - Good anaerobic activity but used to primarily treat oral anaerobes |
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What are the AEs of clindamycin?
|
- Diarrhea
- Nausea - C. difficile diarrhea |
|
Clinical applications of clindamycin
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- Skin infections (staph (and MRSA) and strep coverage)
- Aspiration pneumonia |
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What is MOA of sulfonamides?
|
- Structural analogs of PABA that blocks the production of DHF acid
|
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What is the MOA of Trimethoprim?
|
Trimethoprim inhibits DHF reductase, which is the next step in the eventual productions of purines and DNA
|
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SOA for TMP/SMX
|
- Gram (+)
- Good for staphylococcus including MRSA - Some activity vs. strep but lacks GBS - NO ENTEROCOCCAL COVERAGE - Gram (-) - Activity against enteric gram-negs is variable - No pseudomonas coverage - SPICE but clinical experience |
|
AE associated with TMP/SMX
|
- Sulfa drugs are most commonly associated with hypersensitivity reactions
- High concentrations can crystallize in the urine -Trimethoprim can lead to bone marrow suppression (anemia, leukopenia, graulocytopenia) - Trimethoprim and HYPERkalemia - Increased INR when given with warfarin |
|
TMP/SMX clinical uses
|
- Most common agent for UTIs
- Used for skin infections when MRSA is a concern (but not Group B Staph) - Drug of choice for nasty infections - s. maltophilia, PCP pneumonia, nocardia |
|
What is the SOA of metronidazole?
|
- ANAEROBES ONLY
- Better for lower GI anaerobes than mouth anaerobes - DOC for c. difficile |
|
What is the drug of choice for c. difficile?
|
Metronidazole
|
|
AE of metronidazole
|
- Nausea and vomitting
- Disulfram reaction with alcohol - Peripheral neuropathies |
|
PK and DDIs of metroinidazole
|
- 100% bioavailability and minimal renal elimination
- Increased INR when given warfarin |
|
What are the clinical applictions of metronidazole?
|
- Anaerobic coverage for nosocomial agents
- DOC for c. difficile - T. vaginalis |
|
What is MOA of rifampin?
|
Binds to the b-subunit of DNA-dependent RNA polymerase and blocks RNA synthesis
|
|
SOA of Rifampin
|
- Gram (+)
- S. aureus; including MRSA and streptococcus - Only used in synergy - Gram (-) - Not effective as monotheraphy - Use with beta-lactams for synergy - Mycobacterial infections |
|
Side effects and DIs with Rifampin
|
- Hepatotoxicity
- Discolored fluids - Strong inducer of CYP 450 isoenzymes - contraindicated with HIV meds - Significant interaction with many antifungal agents, anti-hypertensives, statins |
|
Clinical application of Rifampin
|
Synergy
- Severe staph. infections - Multi-drug resistant gram (-) bacilli Part of standard regimen for TB infections due to mycobacterial coverage |
|
What is the MOA of the polymixins?
|
- Cationic detergent that damages the cell membrane leading to leakage of intracellular substances and rapid cell-death
|
|
Polymixin SOA
|
- NO GRAM POSITIVE COVERAGE
- Gram (-) - P. aeruginosa, A. baumannii, K. pneumoniae, E. coli No activity against: serratia, proteus and a few others |
|
Adverse events assoc. with Polymixins
|
- Nephrotoxicity
- Neurotoxicity |
|
Clinical applications of Rifampin
|
Synergy
- Severe staphylococcal infections - Multi-drug resistant Gram (-) bacilli Mycobacterial infections - Part of standard TB regimen |
|
Chloramphenicol AEs
|
Not clinically used anymore:
- Bone marrow suppression - Aplastic anemia - Gray baby syndrome |
|
Nitrofurantoin
-SOA -MOA -Use -Side effects |
- Urinary tract organisms
- Inhibits a variety of bacterial enzyme systems needed for metabolism - Only used to treat lower UTIs - Rare inflammatory lung process |
|
Dapsone
-MOA -Use -Side effect |
- Antagonist of PABA
- Prevention and treatment of PCP pneumonia when TMP/SMX cannot be used - Hemolysis (much more prevalent in patient with G6PD) |
|
What antibacterials are cidal? (BAFVDSP)
|
Beta-lactams
Aminoglycosides Fluroquinolones Vancomycin Daptomycin SMX/TMP Polymixins |
|
What anitbacterials are static?
|
Aminopenicillins
Tetracyclines Macrolides Lincosamides Sulfamethoxazone Trimethaprim |
|
Time-dependent drugs?
|
Beta-lactams
|
|
Concentration-dependent drugs?
|
Aminoglycosides
Fluroquinolones |
|
Drugs that only have gram-positive activity
|
Vancomycin
Daptomycin Linezolid Lincosamides |
|
What antibiotics are primarily renally eliminated?
|
Aminoglycosides
Beta-lactams Vancomycin |
|
What antibiotics are primarily hepatically eliminated?
|
Macrolides
Clindamycin Metronidazole Nafcillin Ceftiraxone |