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130 Cards in this Set
- Front
- Back
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4 major antibiotic targets
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cell wall
cell membrane protein synthesis DNA |
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minimum inhibitory concentration (MIC)
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minimum concentration of an abx necessary to prevent growth at 24 hours
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bioavailability
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amt of drug absorbed orally compared to an IV dose
oral doses account for bioavailability |
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3 beta lactams
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PCNs
cephalosporins carbapenems cell wall active agents |
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bacterial cell wall composed of 3 things and 2 key constituents
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alternating polysaccharides, polypeptides, peptidoglycan
NAGA, NAMA |
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PCN-binding proteins use what to crosslink cell wall section
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D-ALA, D- ALA tail (cap of NAMA)
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beta-lactam pharmacology
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irreversibly bint to PCN-binding protein (suicide inhibition)
breakdown of cell wall continues unopposed most active against dividing bacteria bacterial killing profile is characterized by TIME > MIC |
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resistance to PCN identified in
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staphylococcus aureus
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now resistance comes in 4 main flavors:
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beta-lactamases
porins active efflux pumps altered PCN-binding protein structure |
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PCN distribution into tissues/fluids
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CNS penetration is variable
poor penetration into prostate, brain, eye |
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PCN- high concentrations where?
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urine
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PCN: long or short half-lives?
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short
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PCN active against
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only Gram-pos infections
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PCN drug of choice for:
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streptococcal infections: Groups A,B,C,G
syphylis (drug of choice) dental propylaxis |
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Amoxicillin (PO) and Ampicillin (IV) treat what
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gram-positive
gram-neg |
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2 examples of beta-lactamase inhibitors
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-extends spectrum of amoxicillin, ampicillin
amoxicillin/clavulanate (PO) ampicilin/sulbactam (IV) |
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beta-lactamase inhibitors- same as amoxicillin/ampicillin plus:
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some anaerobes
more gram-negative (resistance sill a problem) |
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beta lactamase inhibitors used for:
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head/neck infections, aspiration pneumonia
animal bites diabetic foot infections (not pseudomonas, MRSA, VRE) |
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aminoPCN rash
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pseudo-allergic rxn caused by aminoPCN rx in a pt infected with EBV
asymptomatic, harmless not documented as allergy |
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3 antistaphylococcal PCNS:
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oxacillin (IV), nafcillin (IV), dicloxacillin (PO)
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antistaphylococcal PCNS: drug of choice agains:
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methicillin-sensitive S. aureus
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antistaphylococcal PCNS still active against:
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Streptococcus species
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antistaphylococcal PCNS can cause:
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renal dysfunction or neutropenia with prolonged use
managed by dose reduction |
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2 antipsuedomonal PCNs
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Piperacillin/tazobactam (IV)
Ticarcillin/clavulanate (IV) |
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Piperacillin/tazobactam (IV) works against which types of bacteria
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gram-positives: not MRSA
anaerobes |
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Piperacillin/tazobactam (IV) useful for variety of:
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hospital-acquired infections
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PCNs: adverse rxns
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GI upset with oral admin- more common with amoxicillin/clavulanate
hypersensitivity reactions may occur -rash more common with aminoPCNs -serum sickness, not common anymore CNS disturbances- high dose PCN G in renal dysfunction |
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cephalosporins excreted how?
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renally
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cephalosporins with excellent CSF penetration
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ceftotaxime
ceftriaxone cefepime |
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cephalosporins penetrate three other protected sites:
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aqueous humor
placenta biliary tract |
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cephalosporins not clinically useful activity againts:
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enterococcus
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3 first generation cephalosporins
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cefazolin (IV, IM), cefadroxil (PO), cephalexin (PO)
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1st generation cephalosporins work against which types of bacteria:
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gram-pos: S.aureus (not methicillin-resistant stratins)
gram-neg |
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1st generation cephalosporins useful for:
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skin/soft tissue infections,
URIs surgical prophylaxis |
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3 2nd generation cephalosporins
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cefuroxime (IV, PO), cefoxitin (IV), cefotetan (IV)
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cefuroxime used for
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commonly acquired pneumonia
disseminated gonococcal infections (2nd line) |
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cefoxitin (IV), cefotetan (IV)- unique side chains adds __ coverage at the cost of gram-positive activity
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Bacteroides
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4 3rd generation cephalosporins
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ceftriaxone (IV, IM), cefotaime (IV)
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3rd generation cephalosporins active against
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extended gram-neg coverage, Gram-neg with broad-spectrum beta-lactamases
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3rd generation cephalosporins used for
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commonly acquire pneumonia (with atypical coverage)
UTIs empiric rx foc meningitis (drug of choice, incombination) intraabdominal infections (in combo with anti-anaerobic coverage gonorrhea (uncomplicated or disseminated) Lyme disease |
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Cefixime (PO) preferred for:
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gonorrhea, although resistance is a problem
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Cefpodoxime (PO) used for
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not much clinical utility
not an oral version of ceftrixone, cefotaxime |
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2 anti-psuedomonal cephalosporins
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ceftazidime (IV)
cefepime (IV) |
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ceftazime (IV) works against
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extended gram-neg coverage
lacks any clinically useful gram-pos coverage |
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ceftazidimine (IV) used for
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healthcare-associate pneumonia, UTIs
febrile neutropenia cystic fibrosis |
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cefepime (IV) coverage:
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extremely broad coverage, including gram-pos and gram-neg (Pseudomonas included)
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cefepime: good penetration into:
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CSF
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cefepime used for
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healthcare-associate pneumonia, UTIs
febrile neutropenia cystic fibrosis |
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cephalosporins ARs
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cross-reactivity with PCNs
-incidince dec as generation inc -can safely be used in almost all situations, other than anaphylaxis to PCNs disulfiram-like reaction, hypoprothombinemia -associated with N-methylthiotetrazole side chain on certain drugs ceftriaxone may cause kernicterus in neonates by displacing bilirubin from circulating albumin -use cefotaxime if less than 30 days old |
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only drug marketed against disulfiram-like rxn
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cefotetan
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carbapenems- general principles
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as broad as abx come
should be reserved for serious infections with no alternative agents available. indiscriminate use can lead to development of bact that are untreatable -use is restricted for this reason excellent penetration into almost all tissue sites should NOT be used as empiric rx of pancreatitis/cholecystitis, despite what they tell you. other beta-lactams work just fine |
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4 carbapenems
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Ertapenem (IV, IM), Doripenem (IV), meropenem (IV), imipenem/cilastatin (IV)
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Ertapenem (IV, IM) covers:
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gram-pos: enterococcus faecalis (amp-sensitive), not MRSA
gram-neg: including extended-spectrum beta-lactamase producing organisms; not active against Psudomonas or Acinetobacter anaerobes |
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Ertapenem used for:
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ESBL-producing Gram-neg infections without alternatives
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Doripenem, meropenem, imipenem/cilastatin covers:
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gram-pos: not MRSA
gram-neg |
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What does ciastatin component oc imioenem/cilastatin do?
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prevents degradation of imipenem by dehydropeptidase in renal tubules
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Doripenem, meropenem, imipenem/cilastatin used for:
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cystic fibrosis with no alternative agents available
febrile neutropenia in an institution with high rates or resistance to alternatives |
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carbapenems- ARs
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hypersensitivity: cross-reactivity rate in pts with reported ally to PCN
seizures: pts with renal dysfunction are at highest risk. imipenem > meropenem = doripenem > ertapenem |
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carbapenems: significant drug interaction:
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valproic acid
rduction in valproate levels when used together alternaive anti-epilectics should be added if a carbapenem must be used with valproate |
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only commercially available monobactam
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aztreonam
low (none?) cross-reactivity in pn-allergic pts |
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aztreonam covers:
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no gram-pos coverage
gram-neg coverage |
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aztreonam used for
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the same situations you would use ceftazidime, if pcn allergic
healthcare-associate pneumonia, UTIs febrile neutropenia cystic fibrosis pseudomonas resistant to other options |
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3 cell wall active agents
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vancomycin, telavancin, fosfomycin
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vancomycin pharm
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Binds to D-ALA, D-ALA terminus of NAMA, preventing growth of cell wall
bacteriostatic optimal bacterial killing is characterized by AUC/MIC ratio |
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resistance to vancomycin
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fairly common in enterococcus
-D-ALA, D-ALA section is replaced by D ALA, D-LAC, preventing effective binding of vancomycin to target site extremely rare in MRSA, but has been described heteroresistant MRSA (hVISA) -elevated MIC to vancomycin that may develop on therapy, clinical significance is still debated |
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vanco: general principles
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drug of last resort for MRSA infections
excellent distribution into most sites of infection oral vanco not used for anything except C.Dif Vanco does not penetrate into colon |
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vanco: most aggressive dosing in 5 dz states:
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pneumonia
meningitis endocarditis osteomyelitis MRSA with elevated MIC |
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vanco spectrum of activity
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Gram-pos only
-Staphylococcus (including MRSA) -enterococcus (not vanco-resistant strains) -sterptococcus Clostridium difficile- must be given orally |
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vanco used for:
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suspected MRSA infections
gram-pos infections if allergic to PCNS/cephalosporins febrile neutopenia severe/ recurrent C. Dif |
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Vanco trough levels
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10-15 for most infections
15-20 for pneumonia, endocarditis, meningitis, osteomyelitis, hVISA |
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Vancomycin toxicity
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Red-man syndrome- anaphylactoid reaction associated with histamine release, can be prevented by dec infusion rate
nephrotoxicity- directly associated with inc trough concentrations, may be transient, may be permanent, absolutely, positively must adjust for renal dysfunction thrombocytopenia |
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telavancin pharmacology
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binds to same D-ALA, D-ALA site as vancomycin
bactericidal lipophilic tail also inserts into cell membrane and causes cellular depolarization |
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telavancin: genearl info:
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approx. twice as active ag. MRSA as vanco- not a clinically relevant diff for most part, identical spectrum otherwise
also causes nehrotoxicity teratogenic- should not be used in women of chile bearing age causes false elevations in INR, aPTT |
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telavancin used for
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infections that have failed therapy with vancomycin
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fosfomycin pharmacology
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inhibits the MurA enzyme, preventing a critical step in peptidoglycan synthesis
raidly bactericidal |
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fosfomycin (PO) used for which type of bacteria:
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broad spectrum
most urinary gram-negatives enterococcus (including vancomycin-resistant strains only useful for treatment of UTIs |
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fosfomycin (PO) used for:
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UTIs caused by VRE or Gram-neg resistant to other options
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4 protein synthesis inhibitors
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aminoglycosides
lincosamides macrolides linezolid |
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pharm of aminoglycosides
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bind to 30s subunit, preventing formation of 70s ribosome and preventing protein synthesis initiation or altering protein structure
rapidly bactericidal prolonged post-abx effect bacterial killing characterized by "peak/mic ratio" |
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aminoglycosides basics
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not orally absorbed
distribution: mainly intravascular not useful for meningitis rapidly and completely renally excreted passage into bact cell is pH dependent. cannot be used in anaerobic conditions such as abscesses resistance is mediated by altered penetration, dec ribosomal binding, or enzymatic modification of structure resistanct to one aminoglycoside may not mean resistance to another |
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5 aminoglycosides
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amikacin, gentamicin, tobramycin commonly used
streptomycin and kanamycin are used in limited situations |
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aminoglycosides spectrum of activity
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broad gram-neg coverage
synergistic ag. gram-pos- cannot be used as a single agent ag gram-pos infection; commonly used in combo with beta-lactam or vanco mycobacteria |
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aminoglycoside toxicity
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nephrotoxicity- frequently in pts with existing renal dz or pts taking other nephrotoxic meds, but can happen to anyone. once daily admin limits this
ototoxicity/ vestibular dysfunction- associated with prolonged, elevated trough concentrations, irreversible and absolutely devastating to the pt, more common with older aminoglycosides and before monitoring, now rare neuromuscular blockade |
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clindamycin pharm
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binds to 50s ribosomal subunit and terminates peptide elongation
bacteriostatic drug cross-resistance bwn clindamycin and macrolides is common |
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clindamycin-basics
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distributes well into most tissues
CNS concentrations are too low to treat most infections |
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clindamycin spectrum
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mainly gram-pos and anaerobes
most methicillin-resistant Staphylcocci are resistant to clindamycin (even if susceptible on a test panel) 20% of clostridia are resistant |
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clindamycin used for
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dental prophylaxis when PCN allergy
adjunctive therapy for nectrotizing fasciitis salvage therapy for some AIDS opportunistic infections |
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clindamycin AEs
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GI distress
C Dif- abx most commonly associated with development of C. dif injection site irritation |
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macrolides- pharm
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binds to 50s ribosome and prevent peptide elongation
bacteriostatic agents cross-resistance within the class is complete azithromycin accumulates in macrophages, creating prolonged effect from brief dosing azithromycin also has unrelated anti-inflammatory effects erythromycin strongly binds to GI motilin receptor |
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macrolides: used for:
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atypical coverage in community acquired pneumonia, chlamydia, pertussis + diphteria
H. pylori, antiinflammatory infections in COPD and cystic fibrosis (azithromycin only) GI motility (erythromycin only) MAI prophylaxis or treatment |
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macrolides: AEs
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GI upset
hepatic toxicity from erythormycin was due to d/ced formulation, not drug itself significant drug interactions due to inhibition of CYP3A4: erythromycin > clarithromycin >>> azithromycin |
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3 macrolides
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azithromycin, clarithromycin, erythromycin
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tetracyclines: pharm
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bind to 30s ribosome and prevent initiation of protein synthesis
bacteriostatic resistance is mediated by enzymatic modification, drug efflux pump, or ribosomal alterations degrade into toxic byproducts |
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tetracycline basics
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distributes effectively throughout all tissue spaces, including CNS and bone
widespread resistance and low blood concentrations have limited clinical use. general rule: not be used for bloodstream infections |
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tetracycline uses
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doxycycline: Tickborne illness: Lyme dz, rickettsia, atypical coverage in community acquired pneumonia, acne
minocycline: same as doxycycline plus certain resistant Gram-negs |
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3 tetracyclines
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doxycyxline
minocycline tigercycline (technically not a tetracycline) |
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tetracycline SEs
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N/V
photsensitivity deposition in teeth/bones -may permanently discolor teeth in young children may alter bone growth if used in preg women generally not used in pregnancy or <5 y/o vestibular toxicity- minocycline only, goes away pancreatitis- rate, tigecycline only |
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linezolid pharm
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binds to 23s ribosomal subunit, preventing formation of 50s ribosome and initiation of protein synthesis
bacteriostatic resistance requires two mutations in 23s ribosome |
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linezolid spectrum
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most clinically relevant gram-pos infections incl. MRSA, VRE
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linezolid SEs
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Short-term use: MAO inhibition
Long-term: neuropathy, myelosuppression, blindness |
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linezolid used for
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resistant infections with no other options
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4 miscellaneous agents
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Fluoroquinlones, trimethoprim/sulfamethoxazole, daptomycin, nitrofurantoin
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fluoroquinolones pharm
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bind to DNA gyrase or topoisomerase IV, inhibiting formation of DNA superstructure
bactericidal distribute broadly throughout the body optimal killing defined by AUC/MIC ratio |
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3 fluroquinolones
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cipro, moxifloxacin, levofloxacin
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Fluoroquinolone uses
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cipro: CTIs, intra-abd infections (in combo with anaerobic coverage), gram-neg pneumonia, cystic fibrosis
moxifloaxcin- community-acquired pneumonia levofloxacin- same as cipro and moxifloxacin |
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Fluoroquinolone toxicity
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GI disturbances- incl C. Dif colitis
tendon rupture/ arthropathy -higher risk when used concurrently with corticosteroids or in end-stage renal dz, generally avoided in children myasthenia -can actually worsen, cause myastenic crisis QTc prolongation -most common with moxifloxacin and older quinolones photosensitivity |
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Trimethoprim-sulfamethoxazole pharm
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2-drug combo that inhibits 2 sequential steps bacterial folate synthesis
-dihydropteroate synthetase -dihydrofolate reductase ratio of TMP : SMX in commercially available preparations achieves optimal pharm activity distribute broadly throughout the body resistance is created by acquisition of altered dihydrofolate reductase |
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Trimethoprim-sulfamethoxazole coverage
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gram-neg, pos coverage
includes MRSA |
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Trimethoprim-sulfamethoxazole used for:
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skin/soft tissue infections caused by S. aureus
UTIs pneumocystis pneumonia (rx and prophylaxis) |
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Trimethoprim-sulfamethoxazole ARs
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hypersensitivity
derm reactions- including S-J syndrome myelosuppression -worse if already folate-deficient or myelosuppressed -can cause drug0induced pancytopenia |
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daptomycin pharm
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cyclic lipopeptide that disrupts bacterial cell membrane and leads to cellular rupture
do not use for pneumonia inactivated by pulmonary surfactant bactericidal distributes widely throughout the body, except CNS killing is characterized by AUC/MIC ratio |
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daptomycin spectrum
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gram-pos only
includes MRSA, VRE |
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daptomycin ARs
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elevation in CPK
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daptomycin uses
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infections resistant to alternative agents
not pneumonia |
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nitrofurantoin pharm
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interferes with multiple bacterial metabolic pathways
concentrates in urine, does not have nay efficacy for systemic infections |
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nitrofurantoin spectrum
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most urinary pathogens
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nitrofurantoin efficacy dependent on:
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adequate renal function, completely useless if CrCl < 50
watch for elderly no point in dose-adjusting for renal dysfunction |
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nitrofurantoin AEs
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generally only occur if used at high doses with poor renal function (neurotoxicity)
GI upset |
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triazole antifungals pharm
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inhibit fungal cytochrome P450, preventing synthesis of ergosterol (fungal equivalent of cholesterol),inhibiting cell membrane formation
-major drug interactions -hepatotoxicity with prolonged use -drug levels should be monitored for long-term use of voriconazole voriconazole may cause hallucinations at high doses |
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triazole uses
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fluconazole- vaginal yeast infections, oral candidiasis, candida esophagitis
voriconazole- Aspergillus |
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echinocandins pharm
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inhibit synthesis of 1,3-beta-D-glucan (an essential cell wall polysaccharid), leading to fungal cell wall rupture
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echinocandins uses
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triazole-resistant Candida infections
Aspergillus if intolerant of alternatives |
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2 echinocandins
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Micafungin
anidulafungin |
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Nystatin/Amphotericin pharm
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bind to ergosterol, disrupting fungal cell membrane stability leading to cellular rupture
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Nystatin info
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not absorbed, usually topical for Candida infections, oral thrust
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Amphotericin info
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"amphoterrible"- nephrotoxic, electrolyte wasting
used for serious fungal infections with absoultely no other choice lipid formulations may reduce toxicity |
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Acyclovir / Valacyclovir / Famciclovir pharm
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nucleoside analogue, incorporates into viral DNA and prevents viral replication
active only against herpes viruses Valacyclovir improves bioavailability and allows for less frequent dosing |
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Acyclovir / Valacyclovir / Famciclovir uses
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Herpes simplex rx, herpes zoster rx, herpes simplex prophylaxis
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Oseltamivir / Zanamivir pharm
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inhibits the influenza virus neuraminidase, preventing viral release from infected cells
generally well tolderated, may cause neuropsychiatric s/s |
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Oseltamivir / Zanamivir used for
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rx or prophylaxis of flu if used within 48 hours of onset of symptoms
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