Antibiotics Flashcards
(27 cards)
Beta-lactams
penicillin, cephalosporin, and carbapenems, aztreonam (monocyclic beta-lactam)
bind to penicillin binding proteins (transpeptidases), inhibit bacterial cell wall synth –> leads to autolysis, bactericidal
seizures can result from high doses of beta-lactams
assume cross-allergenicity
renally excreted
Penicillin
spectrum: gram pos., few gram neg.
excreted by kidney, short half life (30 min)
-can be increased by simultaneous administration of probenecid (impairs renal secretion of weak acids)
Penicillin V (oral), penicillin G (IV form), benzanthine is longer acting (intramuscular administration, assoc. w/local pain and irritation
hypersensitivity: mild rash-anaphylaxis
side effects: nausea, diarrhea, seizure (drug can enter CNS, cross blood-brain barrier, can use for treating meningitis and other brain infections)
susceptible to penicillinase
antistaphylococcal penicillins
narrow spectrum (only used with staph infections)
nafcillin, dicloxacillin (methicillin no longer used)
-large R group, resistant to penicillinases
-methicillin sensitive Staphylococci aureus (MSSA)
-can still result in hypersensitivity reactions
penicillinases inhibitors
Clavulanate: combined with penicillin
-binds irreversibly to penicillinase allowing penicillin to be an effective drug
Sulbactam and Tazobactam are add’l beta-lactamase inhibitors
aminopenicillins
wider spectrum penicillinase-susceptible drugs (gram pos. and gram neg. bact.)
ampicillin and amoxicillin are more water soluble and can pass through porin channels gram neg. outer membrane
can still result in hypersensitivity runs
ampicillin can be combined with sulbactam
amoxicillin can be combined with clavulanate
(beta-lactamase [penicillinase] inhibitors)
ampicillin is assoc. with pseudomembranous colitis
antipseudomonals
wider spectrum penicillinase-susceptible drugs
broad activity against gram-neg. bacilli including Pseudomonas
ticarcillin, piperacillin
combine with penicillinase inhibitor (ticarcillin/clavulanate, piperacillin/tazobactam)
aztreonam
monobactam (monocyclic beta-lactam)
use if patient is allergic to penicillin
cell water inhibitor, binds to penicillin binding protein
spectrum: gram negative rods (Klebsiella, Pseudomonas, Serratia)
Inactivated by extended spectrum beta-lactamases (sensitive to penicillinases)
cephalosporins
beta-lactams, bactericidal
less susceptible to penicillinases, can e inactivated by extended-spectrum beta-lactamases
may be cross-sensitivity with penicillin (can try to use if patient has had minor penicillin allergy, don’t use if patient has severe penicillin allergy)
some available for oral use without food
excreted by kidney
(1st gen: cephalexin, 2nd gen: cefoxitin, 3rd gen: ceftriaxone, 4th gen: cefepime, 5th gen: ceftaroline)
1st gen cephalosporins
cephalexin
spectrum: gram + cocci
use: surgical prophylaxis
don’t use for CNS infections, doesn’t cross blood-brain barrier
2nd gen cephalosporins
cefoxitin
spectrum: more gram - activity and weaker gram + activity
use: immediately prior to surgery to prevent infection
- doesn’t cross blood brain barrier well
- can inhibit vitamin K production to prolong bleeding (vit. K promotes clotting)
- can cause a disulfiram-like rxn when coadministered with EtOH (get hangover symptoms)
3rd gen cephalosporins
ceftriaxone, cefotaxime, ceftazidime, cefdinir
use: streptococci and more serious gram - infections, resistant to other beta-lactams, meningitis treatment (can cross blood-brain barrier)
ceftriaxone interacts with calcium-containing medications to form crystals that precipitate in lungs and kidneys
4th gen cephalosporins
cefepime
broadest spectrum: gram neg, gram pos, including Pseudomonas
5th gen cephalosporins
ceftaroline
engineered to bind to penicillin-binding protein 2a present in MRSA that has low affinity for other beta-lactams
use: community acquired bacterial pneumonia (CABP, caused by MRSA) and acute bacterial skin and skin structure infections (ABSSSI)
beta-lactamases
many
penicillinases: more common in Staphylococci, prefer penicillin structure
cephalosporinases: prefer cephalosporin structure
extended spectrum beta-lactamases (NDM-1): recognize most beta-lactams and are more common in gram neg. bact.
carbapenems
imipenem/cilastatin, meropenem
mech: contain beta-lactam ring, bind to penicillin binding proteins
spectrum: broad, but MRSA is resistant
administration: parenterally (can’t administer orally, also secreted renally)
Toxicity: GI distress, cross allergic, check dose with renal dysfunction to prevent seizures
Imipenem is administered with cilastatin to decrease cleavage of beta-lactam ring by renal dehydropeptidase I and prevent formation of potentially toxic nephrotoxic metabolite
Resistance:
change in penicillin binding protein,
low susceptibility to beta-lactamases, but now Klebsiella pneumoniae carbapenemase which is transmitted through horizontal gene transfer
vancomycin
NOT beta-lactam
mech: binds w/high affinity to amino terminus of cell wall precursor, inhibits transglycosylase reaction of bact. cell wall (bactericidal)
spectrum: narrow; gram pos., esp. MRSA, C. difficile
added to empiric treatment
oral vanco is poorly absorbed (if treating C. diff, will administer orally b/c infection is in the gut)
side effects:
red man syndrome -hypersensitivity
nephrotoxicity -excreted by kidney
dosage adjusted in renal insufficiency
resistance in enterococci (replaces D-alanyl-D-alanine w/ D-alanyl-D-lactate or D-alanyl-D-serine to prevent vancomycin binding)
some staphylococci have learned vancomycin-resistance from enterococci
bacitracin
mech: prevents dephosphorylation of bactoprenol carrier needed for elongation of peptidoglycan cell wall (NOT a beta-lactam)
usage: poor bioavailability if taken orally,topical ophthalmic and dermatologic preparations, though weak evidence of benefit
side effect: nephrotoxic when given IM
resistance: rare
polymyxin B
mech: bind to LPS in membrane, creates holes, leads to release of cellular contents
spectrum: multidrug resistant gram neg. bacilli including Pseudomonas aeruginosa and Klebsiella pneumoniae
used in combination with other antibiotics to help facilitate entry
side effects: severe nephrotoxicity
resistance: infrequent and slow to develop, cross resistance doesn’t develop with any other presently used antibiotics
daptomycin
mech: binds to cell membrane, aggregates leading to depolarization of membrane (b/c drug is positively charged) and cell death, bactericidal
spectrum: only gram-pos. organisms (vanco-resistant, MRSA)
side effects: reversibile organizing pneumonia binds pulmonary surfactant accumulating in pulmonary spaces
resistance: add’n of positively charged lysine to cell surface which repels the positively charged drug
rifampin
(rifamycin)
mech: bactericidal- binds bact. RNA pol. at active center, blocking elongation of mRNA
spectrum: Myobacteria tuberculosis (treat w/4 antibiotics)
resistance:
intrinsic resistance- drug isn’t able to bind to the beta subunit of RNA pol
acquired resistance- strain requires mutations in rpoB gene preventing drug binding
adverse effects:
harmless metabolite turns body fluids orange-red and can stain contact lens
hepatitis, induction of cytochrome P450 enzyme CYP3A4 can induce metabolism of other medicines leading to organ rejection, loss of seizure control, and risk of pregnancy if on birth control
fidaxomicin
mech: bactericidal: inhibits RNA pol
spectrum: narrow, sparing many of gut flora
gram pos. anaerobes -treatment of C. diff
side effects: few due to low absorption, 92% of drug excreted in feces
resistance: pt mutation in RNA pol has been observed in vitro
fluoroquinolone
ciprofloxacin, levofloxacin, moxifloxacin
mech: bactericidal- inhibit DNA repl. by binding bact DNA topo II (gyrase, gram neg.) and topo IV (gram pos.)
spectrum: broad; gram +, gram -, atypical organisms like mycoplasma hospital acquired pneumonia and UTI
resistance: overprescribed
- active efflux of drug
- mutations in topoisomerases
adverse effects:
GI side effects
confusion (penetrates CNS)
clostridium difficile colitis, candida vaginitis
contraindicated in pregnant and breastfeeding women and children due to arthropathy
Important facts: chelate cations so don’t take with Calcium, iron, aluminum, and zinc, avoid dairy products or calcium-fortified juice
adjust for renal dysfunction
sulfanomides
sulfamethoxazole, sulfisoxazole
folate antagonists, indirect inhibition of DNA synth.
mech: bacteriostatic- drug is a para-aminobenzoic acid (PABA) analog, acts as competitive inhibitor of dihydropteroate synthetase (combine with trimethoprim –> bactericidal)
resistance: change in dihydropteroate synthetase, increased drug efflux, increased production of PABA
adverse effects:
hypersensitivity- rash, cross rxn w/other drugs containing sulfonamide moieties
crystalluria leading to acute renal failure
hemolysis if G-6-P dehydrogenase deficient
kernicterus- neurologic condition occuring in severely jaundiced newborns (compete for binding to albumin leading to free bilirubin that can build up in the brain, neonates high risk b/c no blood brain barrier)
trimethoprim
folate antagonist, combine with sulfamethoxazole
mech: bacteriostatic, inhibits bacterial dihydrofolate reductase, low affinity for mammalian enzyme
resistance: altered dihydrofolate reductase, increased amts of dihydrofolate reductase, alternative metabolic pathways
adverse effects: GI upset
