Antimicrobials III Flashcards
mechanism of vancomycin
binds to D-Ala-D-Ala terminus of nascent peptidoglycan pentapeptide –> inhibition of transglycosylase –> inhibiting further elongation of peptidoglycan and cross-linking –> peptidoglycan and cell wall synthesis inhibition –> cell lysis
pay back 2 D-ALAs for VANdalizing
how are enterococci resistant against vancomycin
terminal D-Ala is replaced with D-lactate hence vancomycin not being able to bind to its target
clinical use of vancomycin
- against serious gram positive bacteria only – especially those that are beta lactam resistant or allergic
- ex: C. difficile pseudomembrane colitis and staph enterocolitis
when is vancomycin used to treat enterococci
it is used together with aminoglycosides against E. faecalis or E. faecium in enterococcal endorcarditis
adverse effect of vancomycin
PORN
- Phlebitis
- Red man or Red neck syndrome: flushing of the face or upper torso due to release of histamine
- Ototoxicity and Nephrotoxicity: esp if renal insufficiency or given with aminoglycosides
mechanism of daptomycin
binds to cell membrane of bacteria via calcium dependent insertion of lipid tail –> depolarization of cell membrane and potassium efflux –> rapid cell death
clinical applications of daptomycin
- vancomycin resistant enterococci and staph aureus
- MRSA, MSSA, VRE
what do you not use daptomycin to treat and why
not used to treat pneumonia because pulmonary surfactant antagonizes daptomycin
adverse effects of daptomycin
constipation, nausea, headache, insomnia
-myopathy and possible increase in creatinine phosphokinase
mechanism of bacitracin
interferes with dephosphorylation in cycling of the lipid carrier that transfers peptidoglycan subunits to growing cell wall –> cell wall synthesis inhibition
clinical application of bacitracin
topical treatment of mixed bacterial infections of skin, wounds, or mucous membrane
adverse effect of bacitracin
nephrotoxic if administered systemically hence why used topically
mechanism of fosfomycin
inhibits enolypyruvate transferase which is a cytoplasmic enzyme used in early stages of cell wall synthesis
clinical application of fosfomycin
uncomplicated lower urinary tract infections
what are the protein synthesis inhibitors
TAMGOS [CC FML]
Tetracyclines
Aminoglycosides
Macrolides
Glycylcylines
Other: Chloramphenicol, Clindamycin, Fidaxomicin, Mupirocin, Linezolid
Streptogramins: Dalfopristin/Quinupristin
what part of the bacteria do protein synthesis inhibitors work on and why is there still adverse effects?
- they work on ribosome 70S found only in bacteria (compare to 80S found in mammalians)
- adverse effects seen because mammalian ribosome closely resembles bacterial ribosome
what are the tetracyclines
Tetracycline
Doxycycline
Minocycline
mnemonic for protein synthesis inhibitors for what does what part of the 70s ribosome
Buy AT 30, CCEL at 50
30S:
Aminoglycosides (bactericidal)
Tetracyclines (bacteriostatic) (glycylcylines as well since it is derived from tetracyclines)
50S: Chloramphenicol (bacteriostatic) Clindamycin (bacteriostatic) Erythromycin (all macrolides) (bacteriostatic) Linezolid (variable)
mechanism of tetracyclines
binds to 30S and prevents attachment of aminoacyl-tRNA –> inhibition of AA to growing peptide
clinical application of tetracyclines (name them)
tetracycline, doxycycline, minocycline
- most common: severe acne and rosacea (flushed appearance of cheeks and nose)
- Chlamydia, Cholera, Anthrax, Rickettsia, Lyme diseases, Mycoplasma
what cations impair absorption of tetracyclines
Ca2+, Mg2+, Fe2+
adverse effects of tetracyclines (name them)
Tetracycline, Doxycycline, Minocycline
- Discoloration and Hyperplasia of teeth and stunting of growth (affects fetus and kids less than 8)
- Dizziness and Vertigo
- Photosensitization
- Nephrotoxicity
- Hepatotoxicity
- GI disturbances (most common)
first three are more testable
what is the glycylcylines
Tigecycline
mechanism of glycylcyline (name it)
Tigecycline
binds to 30S but more tightly than tetracyclines and overcome resistance associate with acquired efflux pumps and ribosomal protection
what is intrinsically resistant to glycylcyline (name it)
tigecycline
Proteus
P. aeruginosa
clinical application of glycylcylines (name it)
tigecycline
complicated skin, soft tissue, and intra abdominal infections
-MRSA, VISA, VRE
adverse effects of glycylcylines (name it)
tigecycline
- same as tetracyclines
- Discoloration and hyperplasia of teeth and stunting of growth
- Photosensitization
- Dizziness and Vertigo
- Nephrotoxicity and Hepatotoxicity
- GI disturbances (also most common here as well)
who are glycylcylines and tetracyclines contraindicated in and why
pregnant women and children under 8 due to discoloration and hyperplasia of teeth and stunting of growth
what are the aminoglycosides
Mean (aMINoglycosides) GNATS caNNOT kill anaerobes – all bactericidal
Gentamicin Neomycin Amikacin Tobramycin Streptomycin
NNOT are the adverse effects - Nephrotoxicity, Neuromuscular blockade, Ototoxicity (esp with loop diuretics), and Teratogen
mechanism of aminoglycosides (name them)
GNATS - gentamicin, neomycin, amikacin, tobramycin, streptomycin
irreversible inhibition of initiation complex via binding the 30S subunit –> protein wall synthesis inhibition
aminoglycosides initially cross the outer membrane of the bacteria via passive diffusion. how can this step be inhibited
divalent cations
anaerobic environment
acidic pH
increased osmolality
how can resistance to aminoglycosides occur (name them)
GNATS: gentamicin, neomycin, amikacin, tobramycin, streptomycin
- inactivating drug by phosphorylation, adenylylation, and acetylation
- receptor protein on 30S can be altered or deleted due to mutation
- decreased accumulation of drug by impaired entry into cell or increased efflux
pharmacodynamic property of aminoglycosides (name them)
GNATS: gentamicin, neomycin, amikacin, tobramycin, streptomycin
post antibiotic effect (PAE): suppression of bacterial growth even after drug has been removed
concentration dependent killing: higher conc induces more rapid and complete killing of organism hence why a larger, single dose is more effective than smaller, multiple doses
clinical application of aminoglycosides (name them)
GNATS: gentamicin, neomycin, amikacin, tobramycin, streptomycin
- severe gram neg rod infections
- gentamicin plus penicillin/vancomycin for infective endocarditis
- streptomycin for plague caused by yersinia pestis
- neomycin for hepatic encephalopathy (lactulose is first line though)
adverse effects of aminoglycosides (name them)
Mean (aMEANoglycosides) GNATS caNNOT kill anaerobes
GNATS: gentamicin, neomycin, amikacin, tobramycin, streptomycin
NNOT Nephrotoxicity Neuromuscular blockade Ototoxicity (esp if taken with loop diuretics) Teratogen
contraindication of aminoglycosides
pregnant women (teratogen) myasthenia gravis (due to neuromuscular blockade)
what are the macrolides
Macrolides CEAT
Clarithromycin
Erythromycin
Azithromycin
Telithromycin
mechanism of macrolides (name them)
Macrolides CEAT: clarithromycin, erythromycin, azithromycin, telithromycin
bind to 50S –> inhibition of transpeptidation, translocation, chain elongation, and protein synthesis
mechanism of resistance in macrolides (name them)
Macrolides CEAT: clarithromycin, erythromycin, azithromycin, telithromycin
- reduced membrane permeability or active efflux
- makes esterase –> hyrolyzation of drug
- modification of ribosomal binding site via chromosomal mutation or methylase
clinical application macrolides (name them)
Macrolides CEAT: clarithromycin, erythromycin, azithromycin, telithromycin
- erythromycin: whooping cough
- infection by by Hemophilus, Strep pneumo, staph, enterococci
of all the macrolides, which one is only one available as an IV
azithromycin
safest macrolide for pregnancy
erythromycin
drug interactions of macrolides
- CET (clarithromycin, erythromycin, telithromycin) leads to increase in plasma conc of drugs that are metabolized by CYP3A4, theophylline, anticoagulants, carbamazepine
- erythromycin increases plasma levels of digoxin
adverse effects of macrolides (name them)
Macrolide CEAT: clarithromycin, erythromycin, azithromycin, telithromycin
MACRO Motility issues Arrhythmias due to long QT interval Cholestatic hepatitis Rash eOsinophilia
Steven Johnson Syndrome
