antibiotics 1 Flashcards
4 classes of beta-lactams
what do they all target?
penicillins
cephalosporins
carbecephams
monobactams
–all target cell wall biosynthesis
what two types of drugs target cell wall biosynthesis?
beta lactams and glycopeptides
what class of drugs target membrane potential?
lipopeptides
what class of drugs target cell membrane disruption?
polymyxins
sulfonamides target…?
nucleic acid biosynthesis
trimethoprim targets…?
nucleic acid biosynthesis
What do fluoroquinolones target?
DNA replication/transcription
bacteriostatic
inhibits bacterial growth without causing cell death
MIC vs MBC
MIC - lowest {} that inhibits growth after 18-24 hrs in vitro
MBC - lowest [] at which 99.9% of culture is killed after 18-24 hours in vitro
PAE
post antibiotic effect
suppression of bacterial growth continues after [ ] falls below MIC
gram + stains ___?
gram negative stains ____?
+ blue
- pink
3 aerobic gram + cocci
staphylococci
streptococcus
enterococcus
3 aerobic gram + bacilli
bacillus
cornyebacterium
listeria monocytogenes
3 aerobic gram - cocci
acinetobacter
moraxella catarhallis
neisseria
aerobic gram - bacilli
acinetobacter citrobacter enterobacter helicobacter e coli H. influenzae klebsiella proteus pseudomonas salmonella shigella
gram - spirochetes
borrelia burgdorfera
treponema pallidum
above diaphragm anaerobe
peptostreptocuccus
below diaphragm anaerobes
gram + clostridium perfringens, tetani, and dificile
gram - bacterioides and fusobacterium
acid fast bacteria
mycobacterium and nocardia species that produce myolic acid = stain purple
do human cells have cell walls?
no…this is why we can target them
B lactams mechanism
inhibit peptidoglycan layer of cell wall synthesis
- inhibits crosslinks between disaccharide units
- can inhibit transpeptidase or PBPs
how to overcome penicillinase resistance?
combine penicillin with an inhibitor of B lactamase
side effects of beta lactams except monobactams
diarrhea
CV overload due to increased salts (v overload)
in renal failure –> hallucinations/convulsions
coagulation defects d/t inhibition of platelet activation and conversion of fibrinogen to fibrin
are penicillins and cephalosporins antigenic?
no, but their polymers and metabolites can react with bacterial or tissue proteins to form antigenic conjugates –> causing allergic reactions
penicillins structure
3 roles of the beta lactam ring
beta lactam ring + thiazolide ring = 6 aminopenicillanic acid
beta-lactam ring: 1) the active center of abx, 2) site of action for bacterial enzymes, and 3) site of formation of antigenic determinants
B lactamases and penicillinases
bacterial enzymes that allow resistance against penicillins
do penicillins have good solubility?
no; they are ionized free acids at physiological pH so to improve solubility they are given as Na or K salts
do peniciliins enter csf?
no, only during inflammation
penicillin G and penicillin V
natural penicillins - made from the fungus penicillium
broad gram + bacteria (non penicillinase)
penicillin G
acid labile (not stable in acid) only a third of dose is absorbed
penicillin V
acid stable form
better oral absorption than penicillin G
broad spectrum gram +
penicilin G vs V coverage
G is more active against neisseria and some anaerobes
two ways to prolong penicillin G blood levels?
1) delay absorption by adding organic base like procaine or benzathine –> poorly soluble form
2) delay elimination by adding probenacid (blocks tubular secretion)
penicillinase resistant penicillins (5)
use when bacteria are resistant to penicillin
"i met nasty oxen" methicillin nafcillin oxacillin cloxacilin dicloxacillin
i met nasty oxen (penicillinase resistant penicillins) are not active against
NOT active against gram -
MRSA
methicillin resistant related to failure to bind penicillin binding proteins (PBPs)
first line treatment for B lactamase producing staph?
penicillinase resistant penicillins
- methacillin
- nafcillin
- oacillin, cloxacillin, dicloxacillin
extended range penicillins
ampicillin
amoxicillin
“am” extended
first penicillins effective against gram - (better penetration of outer membrane)
less susceptibility to to gram - penicillinases but more suseptibility to gram + penicillinases
amoxicillin or ampicillin: which extended penicillin is more completely absorbed orally?
amoxicillin
amoxicillin and ampicillin are active against which specific 6 orgs?
e coli p mirabilis h influenzae salmonella shigella neisseria
anti pseudomonal penicillins
–carboxylated derivatives (ticarcillin)
extend the range of ampicillin to P aeruginosa, indole-positive proteus and enterobacter
ticarcillin
used with pulmonary infections
extends ampicillin range from 6 gram - (epnssh)
and adds p aeruginosa
proteus
and enterobacter
cephalosporins
similar structure and mechanism as penicillins
wider activity range
4 generations
side effects of cephalosporins
GI issues and
BLEEDING
1st gen cephalosporins
cephalexin
cefazolin
- narrow spectrum (staph and strep) (gram + >gram -)
- use for SURG prophylaxis; -NOT for active infection
- dont penetrate CNS
- not effective against MRSA
what is recommended for mild foot infections in diabetics?
first gen cephalosporin –> cephalexin
second gen cephalosporin
cefoxitin
used for B fragilis and other anerobics
prophylaxis for abdominal surgery
prophylaxis for abdominal surgery?
cefoxitin (2G cephalosporin)
3rd gen cephalosporins
ceftriaxone and ceftazidime
broad; penetrates CNS
highly active against gram - enteric orgs
ceftriaxone used for what 3 bacteria?
–> N gonorrheae, N meningitis, and B burgdorferi
ceftazidime used for what?
–> multidrug resistant gram - infections (like P aeruginosa)
what is the first B lactam approved for MRSA infections?
ceftaroline fosamil
a 3G cephalosporin
cefepime
4G cephalosporin
similar to ceftazidime against P aeruginosa and other gram -
better than 3g against gram + due to resistant to chromosomally encoded B lactamases
ertapenem
a carbapenem
resistant to B lactamases, but
NOT resistant to metallo B lactamases
BROAD ( +, -, and anaerobics)
CNS and renal toxicity
aztreonam
a monobactam
gram -
can be inhaled; little cross allergenicity with other B lactam abx
vancomycin
a glycopeptide abx that prevents d-ala attachment to cell wall (binds substrate)
must give by IV; no cross-allergenicity!
bactericidal against gram + rods (including penicillinase producers and MRSA)
LAST resort for c dificile
when can vancomycin be given orally?
abx-resistant pseudomembranous colitis and staph enterocolitis
what resistance canbe developed against vancomycin?
van HAX genes
replaces D-ala with D lactate
vancomycin side effects
“Red man syndrome” – hypersensitivity skin flushing or rash
tissue necrosis if given IM
neutropenia and nephrotoxicity
daptomycin
lipopeptide; inhibits cell membrane potential by forming ca-dep membrane channels
used for skin infections and endocarditis by aerobic, gram +
works against resistant strains (VRSA, MRSA)
vancomycin and daptomycin: can they be given IM?
no –> they cause tissue necrosis!
polymyxins
polymyxins A and B (colistin)
cationic detergents that disrupt cell membrane
used topically or in eye/ear drops
NEPHROTOXIC
what drug is used for acinetobacter from middle east
polymyxins (colistin)
