topic 12 Flashcards
What are the two macrolides in use today? What is their mechanism of action?
Clarithromycin and Azithromycin
Work on the 50S subunit of the ribosome to prevent transfer of peptidyl tRNA and thus blocks protein synthesis.
What is the administration, distribution, and metabolism of clarithromycin? What affect does renal function have on it?
Administered oral/IV
Wide distribution besides to CNS
P450 metabolism in live
Must adjust dose based on renal function.
What are the side effects of clarithromycin?
Occasional: Nausea, GI intolerance, diarrhea
What is the spectrum of clarithromycin?
Effective against G (+) cocci such as Streptococcus Group A,B,C,F,G and Streptococcus Pneumoniae.
Not activity against Entercoccus sp Staphlyococcus sp (MRSA, VRSA)
Not active against anaerobes.
Active against some aerobic G(-)bacilli
CAP-Community Acquired Pneumonia Streptococcus pneumoniae Haemophilus influenzae Bordetella sp Mycobacterium avium intracellulare complex (MAC)
What is the administration, distribution, and metabolism of Azithromycin? What affect does renal function have on it?
Administered oral/IV
Wide distribution but to CNS
No P450 metabolism
Don’t need to adjust dose based on renal function?
What are the side effects of azithromycin
Occasional: Nausea, GI intolerance, diarrhea
What is the spectrum of azithromycin?
Effective against Gram (+)but less than Clarithromycin.
Exception: Not activity against Entercoccus sp or
Staphlyococcus sp
(20%-30% of Streptococcus pneumoniae strains resistant to azithromycin)
Not active against anaerobes. Active against some aerobic G(-)bacilli Hemophilus influenzae Bordetella sp Mycobacterium avium intracellulare complex
What is the mechanism of clindamycin? What cross resistance occurs.
Same as macrolides (50S).
Microbes resistant to macrolides will be resistant to clindamycin.
Bacteriostatic
What is the admin, absorp, distrib, and excret of clindamycin?
Admin: oral/IV/topical
absorp:90% GI absorption
Distribution: Widely distributed, not to CNS
Excretion: Hepatic, must look at dosage in hepatic failure.
What is the spectrum of clindamycin?
Active against most G(+) cocci and bacilli (aerobic and anaerobic)
In contrast to macrolides it is active against Staphlyococcus aureus (MSSA/MRSA)
NOT Enterococcus sp
Effective against most Gram negative anaerobes
All aerobic gram negative bacilli are resistant-
Anaerobic bacteria
Bacteroides fragilis and Clostridium perfringens, Lactobacillus sp, Bifidobacterium sp
Does not kill Clostridium difficile
What are the adverse effects of clindamycin? What do you do when it occurs?
Clindamycin therapy has been associated with Clostridium difficile colitis also known as antibiotic associated pseudomembranous colitis (AAPMC)
Symptoms: Diarrhea, fever, Abdominal pain.
This occurs in 3-5% of patients and can be fatal. : clindamycin is discontinued and replaced it with vancomycin or metronidazole.
Neuromuscular blockade (drug interaction with muscle relaxants)
How is clindamycin usually used in treatment?
Used as a treatment for renal abscess due to
S. aureus.
Clindamycin is valuable for the treatment of serious anaerobic bacterial infection due B. fragilis.
Used in combination with an aminoglycoside
is used to treatment of infection arising from fecal spillage due to a hole or tear in the gastrointestinal or biliary tracts
What is the mechanism of quinopristin/dalfopristin? Cidal or static?
Both bind to 50S ribosome
Quinupristin-binds same site as macrolides
Dalfopristin-binds nearby site.
Synergistic action
Cidal
What is the admin, distribution, metab. of quinopristin/dalfopristin?
admin: only IV
Distrib: Little CNS
Metab: can inhibit P450 enzymes
What are the side effects of quinopristin/dalfopristin?
phlebitis (vein swelling) at injection site (should be injected by a central vein a large vein in the neck (internal jugular vein), chest (subclavian vein) or groin (femoral vein).
Severe arthalgias (joint pain) and myalgias (muscle pain) are common.
How is quinopristin/dalfopristin typically used?
Gram positive aerobic bacteria
Reserved for use treatment of infections
caused by drug resistant organisms.
Bone infections due to
methicillin resistant S. aureus (MRSA)
Endocarditis due vancomycin resistant Enterococcus faecium (VRE)
NOT active against Enterococcus faecalis
what is the mech of action of linezolid? cross resistance?
Binds to 50S, prevents binding with 30S to form 70S. No cross resistance with other drugs.
What is the admin, distrib, excretion of linezolid?
Orally, IV
Distribution:
Widely distributed with good CNS penetration (70%)
Excretion-80% of dose appears in urine. 30% renal excretion as active metabolite and remaining as oxidized metabolite.
What are the side effects of linezolid?
reversible thrombocytopenia, anemia,
leukopenia
What is linezolid’s spectrum? How is it used?
Active against gram positive bacteria.
It has poor activity against gram negative bacteria (aerobic and anaerobic gram negative bacteria).
Can be used in Vancomycin resistant
Enterococcus faecium (VRE)
Reserved for use as agent of last resort for treatment of infections caused by multi-drug resistant strains.
What is a drug interaction of linezolid?
It is a nonselective inhibitor of monoamine oxidase.
If given with antidepressants (SSRI) increased risk of serotonin syndrome.
What is the mechanism of polymyxin B?
Polymyxin B acts like a cationic detergent that
binds to the lipids of the bacterial cytoplasmic
membrane which results in alteration of osmotic barrier of the membrane and causes leakage of essential intracellular metabolites and nucleosides.
what is the admin/absorption/distribution of polymyxin B?
Admin: topical for skin, mucous membranes, eye and ear infections; or IV in severe infections
Absorption: poor
Distrib: poor CNS
What are the adverse effects of polymyxin B?
severe nephrotoxicities if given IV. Therefore, only given IV for serious multi drug resistant strains (Pseudomonas aeruginosa and Actinobacter baumanii infections)
Must change dosage based on renal function
What are the drug interactions of polymyxin B?
Enhance neuromuscular blockade by
non-depolarizing muscle relaxants
e.g. tubocurarine
What is the mechanism of action of daptomycin?
It is cyclic lipopeptide antibiotic which functions by depolarizing the bacterial cell membrane.
The loss of membrane potential stops oxidative phosphorylation and production of ATP
What is the absorption, distib, admin, elimin of daptomycin?
Given IV, poorly absorbed orally, never given IM
Primary mode of elimination is renal with ~ 80% of the drug being excreted unchanged in the urine.
No P450
Dosage adjustments are required in patients with impaired renal function.
It is widely distributed except in the CNS (<5%) where therapeutic levels are not reached.
92% bound to plasma proteins
What are the side effects of daptomycin?
Constipation, nausea and headache.
Infrequently:
2. Can cause dose dependent muscle damage.
Monitor serum creatine phosphokinase levels to detect potential muscle damage (don’t use with statins)
How is daptomycin used clinically?
- It is effective against a variety of aerobic Positive bacteria including S. aureus (MRSA) and E. faecalis/faecium including VRE. Not effective against gram negative or anaerobes.
- Not effective in treating pneumonia as it is inactivated by binding pulmonry surfactant
- Used to treat skin infections, acute bacterial endocarditis and bacteremias due MRSA.
What is the mechanism of action of bacitracin?
Bactericidal drug which inhibits bacterial cell-wall synthesis by preventing the incorporation of peptidoglycans.
It does this by inhibiting a pyrophosphatase which is required for recycling of lipid carrier
How is bacitracin admin, absorb, distrib?
Given IM (rapidly and completely absorbed when given IM); given topically (prevent infection in minor cuts, scrapes, and burns. Also used to treat conjunctivitis and infected corneal ulcers)
Do not admin IV (severe thrombophloebitis)
Not absorbed in GI (no oral)
Distributed to all body organs
What are the side effects of bacitracin?
Frequent: nephrotoxicity and pain with IM.
Rarely used systemically.
With topical use
hypersensitivity reactions can occur
but are rare.
What is the spectrum of bacitracin?
Mainly gram positives.
What are drug interactions of bacitracin?
Enhance neuromuscular blockade by
non-depolarizing muscle relaxants
e.g. tubocurarine
What is the mechanism of vancomycin?
inhibition of cell wall synthesis.
Functions by binding to the peptidoglycan at d-alanine-d-alanine residue and prevents elongation of peptidoglycan backbone and transpeptidation.
What is the spectrum of vancomycin?
similar to penicillin, i.e. mainly effective against G(+) organisms including Staph. Aureus resistant to methicillin. C. Diff if given orally.
Bacterocidal against most
gram- positive bacteria
Bacterostatic against Enterococcus spp
unless given with an aminoglycoside e.g gentamicin
Can be used with Enterococcus faecalis
and faecium but increased resistance seen
with Enterococcus faecium (VRE)
Not effective with gram negative bacteria as it cannot penetrate outer membrane
What is the admin, absorp, distrib, excret, of vancomycin?
Poorly absorbed from GI tract.
After IV administration, distributes well to all compartments except CSF (0%) unless the meninges are inflamed (15%) (intrathecal dose (IT dose) might be needed). .
Excreted in urine-renal function affects dosage
What are the side effects of vancomycin?
Hypersensitivity reactions:vary from skin rash to anaphylactic reaction.
Red neck syndrome (extreme flushing on face and chest) Phlebitis and pain at the site of injection.
What situations is vancomycin reserved for clinically?
- methicillin-resistant Staphylococcus aureus (MRSA) and multi-drug resistant Staphylococcus epidermidis (MRSE).
- individuals with serious allergy to penicillins
What are the drug interactions of vancomycin?
Increases nephrotoxicity of aminoglycosides
and polymxin B.
