EXAM 1 Antimicrobials I Flashcards
what are the main antimicrobial targets of cell wall synthesis?
- beta lactams
- vancomycin
- bacitracin
- cell membrane
what are the 4 steps beta-lactam antimicrobials must take in order to be effective?
- evade bacterial defenses
- penetrate outer cell layers to reach inner cytoplasmic membrane
- keep their beta-lactam ring structure intact
- bind to the transpeptidase enzyme (penicillin-binding protein, PBP) on the bacteria’s cytoplasmic membrane
the beta-lactam region structurally resembles the D-Ala-D-Ala end of the peptide that serves as a substrate for ____
transpeptidase enzymes
what is the role of transpeptidase PBP in new bacterial cell wall synthesis?
- clips off the terminal D-Ala residue and crosslink adjacent glycan chains
- covalently bonded chains form rigid cell walls that prevent osmotic forces from rupturing bacterial cell walls
- beta-lactam drugs bind to the transpeptidase PBP and prevent transpeptidation
what are the 3 characteristics common to all beta-lactam drugs?
- require actively proliferating microorganisms to be maximally effective
- inactive against organisms devoid of peptidoglycans
- should be dosed to achieve serum concentrations (T) > MIC for at least 50% of the dosing interval (type II time-dependent PD)
what are the 2 forms of natural penicillins?
penicillin G and penicillin V
natural penicillins, aminopenicillins, penicillinase-resistant penicillins, anti-pseudonomal penicillins, cephalosporins, and carbapenems are all ___ antimicrobials
beta-lactam
what are the two forms of aminopenicillins?
ampicillin and amoxicillin
*aminopenicillins = extended spectrum penicillins
what are the 4 forms of penicillinase-resistant penicillins?
methicillin, nafcillin, oxacillin, and dicloxacicillin
which penicillinase-resistant penicillin is the first-line treatment of choise for staphylococcal endocarditis?
nafcillin
what are the 3 forms of anti-pseudomonoal penicillins, and what are examples of each?
- monobactams (ex. aztreonam)
- ureidopenicillins (ex. piperacillin)
- carboxypenicillins (ex. ticarcillin, indanyl carbenicillum)
of all the anti-pseudomonal penicillins, ___ and then ___ have the broadest spectrums of activity
ticarcillin, piperacillin
describe the mechanism of cephalosporins
- analogous to penicillin
- bactericidal, so long as T > MIC maintained appropriately
what is the most important carbapenem, and why is it important?
- impenem
- it is the broadest antibacterial available
other than imipenem, what are two other forms of carbapenems?
meropenem and ertapenem
___ is the only true naturally occurring penicillin
penicillin G
penicillin is rapidly hydrolyzed by ___
penicillinase enzymes (beta-lactamase enzymes)
how is penicillin G usually administered?
IM or IV (sodium pen G injected every 6-12h)
is penicillin G a broad or narrow spectrum antimicrobial? describe
- narrow
- very active against gram +, but less active against gram -
- 5-10x more active against gram - neisseria species and anaerobes than pen VK
describe penicillin V
- acid stable
- orally active
- same spectrum as pen G, but less active
why are aminopenicillins considered “extended spectrum penecillins”?
better gram - coverage than either pen G or pen V; still sensitive to beta-lactamases
what class of drugs is the drug of choice for listeria monocytogenes, prophylaxis of infective endocarditis, and treatment of UTIs caused by susceptible enterococci?
aminopenicillins (ampicillin and amoxicillin)
aminopenicillins are usually administered with a ___
- beta-lactamase inhibitor
- ex. clavulanate, sulbactam, or tazobactam
what 2 drugs make up augmentin?
amoxicillin and clavulanate
___ has higher oral absorption, higher CPmax, longer 1/2 life, and less likely to cause adverse GI effects than ___.
amoxicillin, ampicillin
what is the interaction warning for amoxicillin?
it dose-dependently inhibits renal tubular excretion of methotrexate, resulting in prolonged/high serum levels of methotrexate
what is the drug of choice for standard prophylactic prevention of bacterial endocarditis?
amoxicillin (PO)
as an alternative to amoxicillin, in the case of non-anaphylactic allergy, what drug can be given for prophylactic prevention of bacterial endocarditis?
cephalexin - 1st generation cephalosporin
as an alternative to amoxicillin, in cases of serious allergy requiring non-beta-lactams, what 2 drugs can be given for prophylaxis for the prevention of bacterial endocarditis?
- clindamycin
- lincosamide protein synthesis inhibitor
- azithromycin or clarithromycin
- macrolide protein synthesis inhibitors
what drug is active against all organisms sensitive to pen G, plus many gram - bacilli?
ampicillin
amoxicillin is better absorbed through which route? why is this important
orally
it is not influenced by food consumption, and thus produces higher plasma concentrations
describe the parenteral use of ampicillin
drug of choice in pateints unable to take oral medications so long as they are not allergic to penicillin
what are the adverse effects of ampicillin?
- diarrhea
- pseudomembranous colitis (c. dificile overgrowth)
- rashes
- hypersensitivity
___ inactivates ampicillin if mixed in IV solution
hydrocortisone
what can occur if probenecid (given for gout) is taken with ampicillin?
slows renal excretion of ampicillin
describe how penicillinase-resistant penicillins are “anti-staphylococcal penicillins”
active against staphylococci and streptococci but not enterococci, anaerobic bacteria, or gram - cocci and rods
penicillnase-resistant penicillins are less potent than ___, but are agents of first choice for treatment of which 2 penicillinase-producing bacteria that are not methicillin-resistant?
- pen G
- s. aureus and s. epidermidis
which 2 penicillinase-resistant penicillins have activity similar to methacillin and beta-lactamase resistance, but are acid stable with reduced risk of interstitial nephritis?
oxacillin and dicloxacillin
what is the drug of choice for serious s. aureus infections (non-MRSA), such as in cellulitis, endocarditis, and sepsis? why?
- nafcillin
- think “use naf for staph”
- they are resistant to staphylococcal beta-lactamases
why does probenecid not interact with nafcillin, oxacillin, and dicloxacillin?
they are lipophilic and undergo biliary excretion (not renal excretion)
describe probenecid
it is a uric acid reducer used to treat gout and to increase plasma levels of some antibiotics
___ inhibits organic anion transporter’s (OAT) in the renal proximal tubule, reducing clearance, and thus increasing plasma levels of drugs normally secreted by this mechanism
probenacid
since most beta-lactams are renally excreted, their ___ levels are increase, and ___ are prolonged if given with probenecid
- serum levels
- half-lives
anti-pseudomonal penicillins are clinically used for treating serious bacteremias, pneumonias, post-burn infections, and UTIs, due to what?
bacteria resistant to pen G and ampicillin
how are anti-pseudomonal penicillins administered?
IM or IV
not PO
the recent emergence of ___ is threatening the utility of anti-pseudonomal penicillins
broad-spectrum beta-lactamases
carboxypenicillins (indanyl carbenicillin and ticarcillin) are more or less active than piperacillin against pseudonomas?
less
which carboxypenicillin is orally active and is used clinically for management of UTIs caused by p. aerugenosa or proteus sp?
indanyl carbenicillin
___ is 2-4x more active than indanyl carbenicillin
ticarcillin
what is the main cilinical use of ticarcillin?
- injectable agent against gram - bacteria, particularly p. aeruginosa
- it is one of the few antibiotics capable of treating stenotrophomonas maltophilia infections in/on indwelling mechanical devices
ticarcilin is no longer available in the US. what was it replaced with?
timentin (ticarcillin/clavulanate combination)
piperacillin retains all the activity of ampicillin against gram + cocci and l. monocytogenes, plus has excellent activity against what?
pseudomonas, klebsiella, and other gram - microorganisms
___ is the broadest spectrum of the antipseudomonal penicillins
piperacillin
what is preferred over piperacillin to combat beta-lactamases?
zosyn (piperacillin/tazobactam)
___ is great for patients with IgE-mediated penicillin allergy
aztreonam (IV)
aztreonam is resistant to some ___, but not ___
- beta-lactamases
- extended-spectrum lactamases
describe the toxicity of aztreonam
- pseudomonas colitis (c. dificile overgrowth)
- cellulitis
- hematologic disorders
describe the common side effects of penicillins
- hypersensitivity/anaphylaxis
- local effects
- large doses of pen G may produce lethargy, confusion, twitching, seizures, kidney failure, and coma
- low superinfection risk for narrower spectrum drugs
cephalosporins are resistant to what?
many older penicillinases (beta-lactamases)
like most penicillins, cephalosporins are ___ excreted, and may cause toxicity in patients with ___
- renally
- renal insufficiency
cephalosporin cross allergy with penicillins is ___%. patients with mild, delayed penicillin allergy can often tolerate cephalosporins, but patients with history of ___ cannot.
- 5%
- anaphylaxis
name the 1st-5th generation cephalosporins
- 1st generation - cephalexin, cefazolin
- 2nd generation - cefaclor, cefuroxime, cefoxitin
- 3rd generation - cefdinir, cefotaxime, ceftazidime, ceftriaxone
- 4th generation - cefepime
- 5th generation - ceftaroline
describe the spectrum of activity of 1st generation cephalosporins
- moderate spectrum
- active against gram +, modest gram - activity
- most active against s. aureus, streptococci, and pneumococcus
describe the spectrum of activity of 2nd generation cephalosporins
- moderate/broad spectrum
- not as active against gram + organisms as 1st generation, but also possess good activity against e. coli, h. influenzae, and klebsiella
- not active against pseudomonas
describe the spectrum of activity of 3rd generation cephalosporins
- have broadest spectrum of all the cephalosporins and are extremely effective against gram - organisms
- most can cross the blood brain barrier (exception is cefoperazone)
- important for the treatment of meningitis
describe the spectrum of activity of 4th generation cephalosporins
broad spectrum, less gram +, but more gram - activity and resistance to beta-lactamase
describe the spectrum of activity of 5th generation cephalosporins
broad spectrum, same as 4th generation plus active against MRSA
because 2nd, 3rd, and 4th generation cephalosporins have reduced gram + activity, ___ with these may occur
superinfection
___ has the broadest spectrum coverage (IV or IM) available to man
imipenem
___ is a non-beta-lactam antibacterial, blycopeptide, bactericidal, covers all gram + bacteria (not gram -), and is used to treat endocarditis in penicillin-allergic patients (IV)
vancomycin (IV)
none of the 1st generation cephalosporins penetrate the ___
CNS
___ generation cephalosporins are not the first drug of choice for any active infections
1st
___ is a ___ generation cephalosporin used for prophylaxis prior to surgery
cefazolin, 1st
___ is a ___ generation cephalosporin used to treat oral sinusitis and otitis media caused by H. influenzae
cefaclor, 2nd
___ is a ___ generation cephalosporin that has enhanced anaerobe activity and extended beta-lactamase resistance
cefoxitin, 2nd
why is cefuroxime a unique 2nd generation cephalosporin?
it can cross the blood brain barrier
___ or ___ are both ___ generation cephalosporins (both IV) used for gram - bacterial sepsis and meningitis
- cefotaxime or ceftriaxone
- 3rd
___ is a ___ generation cephalosporin that is active against pseudomonas aeruginosa
- ceftazidime
- 3rd
___ is a ___ generation cephalosporin, the highest selling cephalosporin, and is used for the treatment of otitis, soft tissue infections, respiratory tract infections, including sinitis, strep throat, CAP, and acute bronchitis.
- cefdinir
- 3rd
___ is a ___ generation cephalosporin that has activity greater than ceftazidime against streptococci and methicillin-susceptible staph, and has comparable activity to ceftazidime against pseudomonas aeruginosa
- cefepime
- 4th
___ is a ___ generation cephalosporin that is active against MRSA, gram + bacteria, and gram - bacteria
- ceftaroline
- 5th
___ is a carbapenem that is active against gram + organisms, gram - rods, and anaerobes
imipenem
___ and ___ are both resistant to imipenem
MRSA and mycoplasma
carbapenems are very stable in the presence of beta-lactamases, including ___ and ___ that are resistant to most beta-lactam antibiotics
penicillinase and cephalosporinase
what are the adverse effects of carbapenems?
- similar to penicillins
- renal clearance is critical
- levels in patients with renal insufficiency is known to cause seizures
why is impenem always coadministered with cilistatin (renal dehydropeptidase 1 inhibitor)?
imipenem is rapidly degraded by the renal enzyme dehydropeptidase-1, so it is always coadministered with cilistatin, the inhibitor of this enzyme
name 2 newer carbapenems that are not inactivated by renal dipeptidases so do not require silistatin coadministration
meropenem and ertapenem
what are the 4 non-beta-lactam antibacterials?
- bacitracin (topical)
- vancomycin (IV)
- polymyxins
- daptomycin (IV)
___ is a non-beta-lactam antibacterial, polypeptide from bacillus subtillus, bactericidal, disrupts both gram + and gram - bacteria, and can cause kidney damage when used internally?
bacitracin
___ inhibits cell wall synthesis in gram + bacteria at an earlier stage of the peptidoglycan synthetic pathway than beta-lactams, and is not active against most gram - bacteria
vancomycin
___ is the first line IV treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by MRSA
vancomycin
why should vancomycin not be used to treat methicillin-sensitive s. aureus?
vancomycin is inferior to nafcillin
vancomycin is poorly absorbed PO. how can this be advantageous?
for the treatment of clostridium difficile colitis
vancomycin is a good alternative for the treatment of infections caused by gram + microorganisms in patients with ___
serious allergies to beta-lactam antimicrobials
what are 3 adverse effects of vancomycin?
thrombophlebitis, skin rashes, leukopenia
vancomycin has traditionally been considered a ___ and ___ drug, especially when given in patients on aminoglycosides
nephrotoxic and ototoxic drug
what is red man syndrome?
- can be an adverse effect of vancomycin
- rapid infusion induced non-immunological release of histamine
___ are non-beta-lactam antibacterials that are bactericidal against gram - bacteria, used clinically against multidrug resistant gram - bacteria, and are associated with neurotoxicity and acute renal tubular necrosis
polymyxins
___ is a non-beta-lactam antibacterial that is a cyclic lipopeptide, bactericidal against gram + bacteria, is inactivated by pulmonary surfactants (so it is not indicated for pneumonia), and has adverse effects that include myopathy, arthralgia, and eosinophylic pneumonia
daptomycin (IV)
describe immediate/acute onset allergic reactions to penicillins/beta-lactams
- reactions within 30 minutes (anaphylaxis)
- IgE mediated - life-threatening
describe accelerated onset allergic reactions to penicillins/beta-lactams
- arise 30min to 48hr after administration
- urticaria, pruitis, wheezing, local inflammatory response
describe delayed onset allergic reactions to penicillins/beta-lactams
- reactions that take longer than 2 days to develop
- 80-90% of penicillin reactions are of this type
