Antibiotics Flashcards
What are the major antibiotic categories?
beta-lactams (penicillin, cephalosporins, carbapenens)
macrolides and clindamycin
tetracyclines/glycylcyclines
glycopeptides
aminoglycosides
quinolones
sulfonamides and trimethoprim
metronidazole
linezolid
How do penicillin’s exhibit their action?
bind to penicillin binding protein (PBP) resulting in inhibition of peptidoglycan synthesis and activation of autolytic enzymes in cell wall
True or false: penicillins are bacteriostatic
false
they are bactericidal
How does resistance develop to penicillins?
production of beta-lactamases
lack of PBP or altered PBP
efflux of drug out of cell
failure to synthesize peptidoglycans such as mycoplasmas or metabolically inactive bacteria
What is the structure of penicillins?
6-aminopenicillanic acid (thiazolidine ring attached to beta-lactam ring)
What are the natural penicillins?
penicillin G
penicillin V
Which bacteria is penicillin G highly active against?
gram positive and spirochetes
Describe penicillin G.
highly active against gram + and spirochetes
destroyed by beta-lactamases
acid labile (not used orally)
What are the available forms of penicillin G?
aqueous Pen G
procaine Pen G (IM)
benzathine Pen G (IM)
What is the difference between penicillin G and penicillin V?
penicillin V is an oral formulation that is more acid stable
What are the special instructions for use of penicillin V?
taken on an empty stomach
What are the uses of the natural penicillins?
DOC for:
-streptococci
-pneumococci
-meningcocci
-spirochetes
-clostridia
-anaerobic gp rods
-actinomyces
-enterococci
Which penicillins are designed for Staph aureus?
cloxacillin
methicillin
flucloxacillin
dicloxacillin
What are the “anti-staphylococcal” penicillins relatively resistant to?
beta-lactmases
When should the pencillins such as cloxacillin or methicillin not be used?
should not be used for MRSA
-methicillin resistant staph aureus
What is the spectrum of activity for aminopenicillins?
active against both gp and gn
-streptococci, enterococci, neiserria, non-blp H influenzae, e.
coli, p. mirabilis, salmonella, etc
What can destroy the aminopenicillins?
beta-lactamases
What are the aminopenicillins? Describe each.
ampicillin
-IV
-more acid stable than the natural pencillins
-poor bioavailability
amoxicillin
-oral
-better absorption than ampicillin
-can be combined with clavulanic acid
What is clavulanic acid?
beta-lactamase inhibitor
What does beta-lactamase do?
opens the beta-lactam ring of penicillins and cephalosporins
no longer active
What are ESBLs?
extended spectrum beta-lactamases
-found in E.coli and Klebsiella pneumoniae
What is NDM BL?
New Delhi metallo-beta-lactamase
-found in Acteinobacter baumannii
What is the ureidopenicillin presented in class?
piperacillin
Which penicillin has increased activity against Pseudomonas aeruginosa?
piperacillin (great against gn rods)
-parenteral only
Which drug is piperacillin availably combined with?
tazobactam (beta-lactamase inhibitor)
Describe the pharmacokinetics of penicillins.
oral bioavailability varies
wide tissue distribution including CNS
most are excreted by the kidneys
short half-life
concentration independent PD
all taken on empty stomach but one
safe in pregnancy
distributed to breast milk
Which pencillin should be taken with food?
amoxicillin
Why are penicillins frequently dosed?
short half-lifes
What is a drug interaction that must be kept in mind with penicillins?
oral contraceptives
-penicillins can destroy the estrogen
-explain it to the woman
What are the adverse effects of penicillins?
allergic reactions
anaphylactic shock
serum sickness (fever, joint stiffness, rash)
skin rashes
fever, nephritis, eosinophilia
electrolyte imbalance
neutropenia, thrombocytopenia
diarrhea, GI upset (most common)
What is the structure of cephalosporins?
7-aminocephalosporanic acid
Why are cephamycins not considered to be a true cephalosporin?
they have an oxygen where the sulfur is
What is the MOA of cephalosporins?
same as penicillins (PBP to decrease peptidoglycan synthesis)
bactericidal
In terms of resistance, how do cephalosporins differ from penicillins?
cephalosporins are resistant to beta-lactamases produced by Staph aureus and common gnb (increased spectrum)
How does resistance develop to cephalosporins?
lack of PBP or altered PBP
beta-lactamase
efflux
inability to penetrate
What are the first generation cephalosporins?
oral: cephalexin and cefadroxil
IV/IM: cefazolin
What is the activity of first generation cephalosporins?
gram positive cocci, NOT enterococci or MRSA
some gram negative bacilli (E.coli, Proteus, Klebsiella)
True or false: first generation cephalosporins penetrate the CNS
false
What situations are first generation cephalosporins the DOC?
not the DOC for any infection except cefazolin for surgical prophylaxis
What are the second generation cephalosporins?
oral: cefuroxime axetil, cefprozil
IV/IM: cefuroxime
What is the activity of second generation cephalosporins?
organisms covered by 1st gen cephalosporins
greater coverage of gram negative bacilli (not Pseudomonas aeruginosa)
What are the third generation cephalosporins?
cefotaxime, ceftriaxone, ceftadizime (IV)
cefixime (oral)
What is ceftadizime reserved for?
Ps. aeruginosa
What is the activity of third generation antibiotics?
decreased activity against gram positive cocci (except Strep pneumoniae)
enhanced activity against gram negative bacilli
What is the difference in tissue distribution between 1st gen and 3rd gen cephalosporins?
3rd gen can penetrate the CNS
What are the fourth generation cephalosporins?
cefepime (enterobacter and citrobacter, Ps. aeruginosa)
ceftaroline and ceftobiprole (MRSA, ampicillin sensitvive E. faecalis, penicillin resistant S. pneumoniae)
What are the adverse effects of cephalosporins?
hypersensitivity
diarrhea and skin rash=most common
other: fever, granulocytopenia, hemolytic anemia
What is a unique side effect of ceftriaxone?
biliary pseudolithiasis
What are the carbapenems?
imipenem
meropenem
ertapenem
What is imipenem always given with?
cilastatin
-protects from dehydropeptidase and prolongs antibacterial
effects
What is the activity of imipenem and meropenem?
gram positive
gram negative (including Pseudomonas)
anaerobic organisms
What is the activity of ertapenem?
poor activity against enterococcus and P. aeruginosa
Which carbapenem is given once daily?
ertapenem (long half-life)
Describe monobactams.
monocyclic beta-lactam ring
resistant to beta-lactamases
active against gnb including P. aeruginosa
not active against ESBL or AmpC producers
What is a monobactam discussed in class, not available in Canada?
aztreonam
What are the macrolides?
erythromycin
clarithromycin
azithromycin
What is the MOA of macrolides?
attach to the 23S rRNA on the 50S subunit of bacterial ribosome resulting in inhibition of protein synthesis
bacteriostatic; time dependent killing (conc independent)
How does resistance develop to macrolides?
methylation of the rRNA receptor
inactivating enzymes
efflux
What is the spectrum of activity of macrolides?
gram positive: pneumococci, streptococci, corynbacteria
M pneumoniae
Chlamydia trachomatis
C. pneumophilia
Bordatella pertussis
Campylobacter jejuni
Helicobacter pylori
What are the available forms of erythromycin?
base
stearate (succinate)
estolate
Why is erythromycin avoided IV?
can cause severe phlebitis
What are the adverse effects of erythromycin?
GI (macrolides known to have significant GI effects)
increased liver function tests (LFTs)
cholestatic hepatitis (increased with estolate and pregnancy)
QT prolongation/cardiac arrhythmias (especially with CYP 3A inhibitors)
What is the activity of clarithromycin and azithromycin?
active against staph and strep
useful for some MRSA
enhanced activity against variety of organisms
If an organisms is resistant to erythromycin, then which other drugs would we suspect this organism to be resistant to?
clarithromycin and azithromycin
How do clarithromycin and azithromycin compare to erythromycin in dosing and adverse effects?
less frequent dosing
lower rate of GI effects
What is the concern with a 5 day therapy of azithromycin?
azithromycin has long half-life
5 days of azithromycin=10 days of therapy
may lead to more resistance
What are the uses of the macrolides?
URTIs
STIs
acne
What are the drug interactions for macrolides?
erythromycin and clarithromycin are substrates+inhibitors of CYP 3A4, so many drugs that are metabolized by CYP 3A4
antiarrythmias
antidepressants
anticonvulsants
statins
fewer with azithromycin
What is the MOA of clindamycin?
same as macrolides
-has different structure
When is clindamycin the DOC?
never
What is the spectrum of clindamycin?
anaerobes
S.aureus
some MRSA
streptococci
When is clindamycin typically used?
penicillin allergy
resistant organism
What are the adverse effects of clindamycin?
nausea, vomitting, diarrhea
rash
elevated LFTs
esophageal irritation
ASSOCIATED WITH C. DIFFICILE DIARRHEA
What are the tetracyclines?
tetracycline
minocycline
doxycycline
What is the MOA of tetracyclines?
inhibit binding of aminoacyl-tRNA to the 30S unit of ribosome therby inhibiting protein synthesis
bacteriostatic
What is the spectrum of activity of tetracyclines?
many gp and gp
-high rates of resistance
When are tetracyclines the DOC?
rickettsiae
bartonella
chlamydia
M. pneumoniae
What are the adverse effects of tetracyclines?
GI upset
skin rashes
photosensitivity
yeast overgrowth
deposited in bones and teeth
hepatitis
vestibular toxicity (dizziness, vertigo, ataxia)
Which group are tetracyclines contraindicated in?
children <8
Which tetracycline is associated with hypersensitivity reactions?
minocycline
What are some drug interactions with tetracyclines?
some anticonvulsants
divalent and trivalent cations reduce absorption
-iron, bismuth, calcium, magnesium, aluminum
increased INR and bleeding with warfarin
What are the synthetic analogues of tetracyclines?
glycylcyclines:
-tigecycline
What is the spectrum of activity of glycylcyclines?
many gp and gn
-MRSA
-S. pneumoniae
-enterococci
-salmonella
-shigella
-actinobacter
-anaerobes
How are glycylcyclines eliminated?
biliary tract or feces
What is the reserved usage of glycylcyclines?
resistant organisms
What is the glycopeptides studied in class?
vancomycin
What is the MOA of glycopeptides?
inhibits cell wall peptidoglycan synthesis
bactericidal
Which organisms are resistant to vancomycin?
VRE
S. aureus
What is the spectrum of activity of vancomycin?
gpc in particular enterococci
PRSP
MRSA
clostridia
some bacilli
When is vancomycin given orally? What about IV?
orally: C. difficile only (not orally absorbed)
IV for serious infection
What are the adverse reactions of vancomycin?
nephrotoxicity (especially in combo with nephrotoxins)
ototoxicity (hearing impairment, messes with balance)
red-man syndrome
granulocytopenia
True or false: therapeutic drug monitoring is not commonly performed with vancomycin
false
commonly performed
What are the aminoglycosides?
streptomycin
gentamicin
tobramycin
amikacin
What is the MOA of aminoglycosides?
inhibit protein synthesis by inhibiting 30S subunit of bacterial ribosome
How does resistance develop to aminoglycosides?
mutation or methylation of 16S rRNA-binding site
enzymatic destruction of drug
lack of permeability to the drug molecule
active efflux
What is the spectrum of aminoglycosides?
aerobic gnb
synergistic with penicillins for enterococci and streptococci
streptomycin for TB
What is the route of administration for aminoglycosides?
IV/IM (not orally absorbed)
How good is the penetration of aminoglycosides? How are they eliminated?
poor tissue penetration, not CNS
renal elimination
True or false: therapeutic drug monitoring is commonly performed with aminoglycosides
true
What are the adverse effects of aminoglycosides?
nephrotoxicity
ototoxicity
neuromuscular blockade
allergies rare
What are the fluoroquinolones?
ciprofloxacin
levofloxacin
moxifloxacin
What is the MOA of fluoroquinolones?
inhibit DNA gyrase or topoisomerase II & IV
bacteriocidal
How does resistance develop to fluoroquinolones?
alteration of the A or B subunit of DNA gyrase
mutation in ParC or ParE of topoisomerase IV
change in outer membrane permeability
efflux
What is the spectrum of fluoroquinolones?
highly active against gnb, haemophilus, neisseriae, chlamydiae
ciprofloxacin-P.aeruginosa
levofloxacin-S.pneumoniae
moxifloxacin-anaerobes
What are the uses of fluoroquinolones?
UTIs
STIs
lower respiratory tract infections
enteritis/travellers diarrhea
drug resistant mycobacterial infections
Describe the pharmacokinetics of fluoroquinolones.
excellent oral bioavailability
available IV or po but parenteral use not commonly needed
ciprofloxacin and levofloxacin-renal elimination
moxifloxacin-biliary pathway
What are the adverse effects of fluoroquinolones?
nausea, vomiting, diarrhea
insomnia, headache, dizziness
other CNS effects including seizures
skin rashes
impaired liver function
tendinitis/tendon rupture
prolongation of QTc interval
hypo/hyperglycemia
C. difficile
peripheral neuropathy
What are the drug interactions associated with fluoroquinolones?
di and trivalent cations
QTc prolongation
CYP 1A2 inhibitors
increased INR with warfarin
What are the reserved situations for fluoroquinolones?
resistant organisms or when you cant use the DOC
not used in children <18
What is the MOA of sulfamethoxazole?
structural analogue of PABA; competitively inhibits dihydrofolate acid synthesis
What is the MOA of trimethoprim?
binds to dihydrofolate reductase therefore inhibiting the reduction of dihydrofolic acid to tetrahydrofolic acid
How does resistance develop to SMX and TMP?
ability of cell to use preformed folic acid
What is the spectrum of SMX and TMP?
wide spectrum of gp, gn, chlamydiae, nocardiae, protozoa
staphylococci-including MRSA
S. pneumoniae (not group A strep)
S. maltophilia
moraxella
H. influenza
enterobacteriaciae
brucella
pneumocystis jirovecii
What are the uses of SMX and TMP?
UTIs
skin and soft tissue infections-MRSA
PJP
many others
What are the adverse effects of sulfonamides and trimethoprim?
skin rashes (can be severe)
hypersensitivity
headache
GI
bone marrow suppression
hyperkalemia & hyponatremia
photosensitivity
What is CI of SMX/TMP? What is a caution with SMX/TMP?
CI: first and third trimester of pregnancy
caution: renal dysfunction
What is the MOA of metronidazole?
unknown but possible inhibition of nucleic acid synthesis and disruption of DNA
What is the spectrum of metronidazole?
anaerobes including C.difficile
protozoa-trichomonas, giardia
Which organism is resistant to metronidazole?
propionibacterium
What are the adverse effects of metronidazole?
GI
metallic taste
headache
dark urine
peripheral neuropathy
disulfiram-like reaction with alcohol
insomnia
stomatitis
What are the drug interactions of metronidazole?
alcohol
increased INR and bleeding with warfarin
What is the MOA of linezolid?
inhibits protein synthesis
usually bacteriostatic
bactericidal against Streptococci
What is the spectrum of linezolid?
streptococci
enterococci (including VRE)
staphylococci (including MRSA)
What is the reserved use of linezolid?
multi-drug resistant organisms
an alternative to vancomycin
What are the adverse effects of linezolid?
headache
nausea, vomiting, diarrhea
rash
increased LFTs
myelosuppression
optic/peripheral neuropathy
lactic acidosis
decreased seizure threshold
What are the drug interactions for linezolid?
increased serotonin syndrome risk with SSRIs and MAOs
rifampin decreases linezolid levels
