Antimicrobials 1 Flashcards
Three broad types
Antibiotics
- bacterial
Antivirals
- viral
Antimicotics
- fungal
Prophylactic therapy
A sort of “pre-treatment” used in immunosuppressive patients that help increase resistance/treatment of an infection
Empiric vs definitive therapy
Empiric: agent is selected based on rational, often broad, judgements and experience
Definitive: agent is selected based on lab results and cultures with pathogen identity confirmed.
Difference is definitive is more narrow spectrum and reduces risk of resistance emerging against broad spectrum agents.
- also reduces super/opportunistic infections as well as community resistance
Most common gram negative rods
Enterobacters
E. coli
Haemophilus influenza
Proteus
Pseudomonas aeruginosa
Prophylactic therapy
Is a pre-treatment to prevent infections in immunocompromised patients
Empiric vs definitive therapy
Empiric (broad)= treatment of known or probable infection
Definitive (narrow)= pathogens identify and antibiotic susceptibility is 100% confirmed
- moving from an empiric to definitive therapy reduces risks of resistance development and reduces risk of superinfections/opportunistic infections*
Classes of antibiotics for bacterial infections
Inhibitors of cell wall synthesis
Inhibitors of protein synthesis
Inhibitors of DNA/RNA synthesis
General mechanisms of cell wall inhibitors that affect PBPs
All are bacterialcidal via 2 actions
- transpeptidase inhibition: cant synthesis new walls
- autolysin activation: break down cell walls too fast
Both autolysin and transpeptidase are penicillin binding proteins (PBPs) and are found on both gram positive and gram negative bacteria
penicillin has no effect on host cells since human cells do not possess cell walls or PBPs
Cell wall synthesis inhibitors broad mechanisms with respect to synthesis of peptidoglycan
Three main steps are possible
1) inhibition of synthesis of the Murein monomers
2) inhibition of polymerization of murein monomers into Glycan backbone
3) inhibition of glycan polymer cross-linking into peptidoglycan (transpeptidases)
* B-lactams prevents the cross linking, the rest of the cell wall synthesis inhibitors do everything else*
Peptidoglycan wall components
Primarily N-Ag and N-Am proteins
Why are cell wall synthesis inhibitors far more effective towards gram positive vs gram negative bacteria?
Gram positive possess more peptidoglycan than negative
Gram negative possess an additional outer membrane that blocks peptidoglycan
- cell wall inhibitors require gram negative bacteria to possess porin channels in order to infect them*
Mechanisms of resistance to cell wall inhibitors by bacteria
Altered PBPs
Expression of efflux pumps
development of B-lactamase enzymes that function to cleave B-lactam drugs
How all B-lactams are common
They all possess a common core structure
“active component” ring (3 carbons and 1 nitrogen)
These ring components acetylate PBPs and inactivates them in bacteria
B-lactamases
Defend bacteria against B-lactams
- primarily penicillins and cephalosporins
- B-lactamases inhibitors exist = clavulanic acid/clavulanate, sulbactam, tazobactam and avibactam*
Also some chemical modifications to B-lactams can make them more resistant to the B-lactamases (I.e methicillin)
DDIs for penicillin
Anti-gout medications (probalan specifically)
-blocks renal transporters
Aminopenicillins
Ampicillin (IV) and amoxicillin (PO)
- amoxicillin is drug of choice for upper respiratory infections*
- can develop resistance via B-lactamases*
What is the only antipseudomonal penicillin usable?
Piperacillin
- renally eliminated and specifically targets pseudomonas, kiebsiella pneumoniae
- do NOT co-administrate with vancomycin (increases acute intestinal nephritis risk)*
- high doses causes poor coagulation*
Cephalosporins
B-lactam drugs that are often used against bacteria that use penicillinase (cant use penicillin on them)
5 generations exist with varying spectrums
1st generation cephalosporins
Cefazolin (IV)
Cephalexin (PO)
Cefadroxil (PO)
Similar to anti-staph penicillins but are better tolerated
- great against MSSA, step species, staph species that have penicillinase
DONT USE AGAINST MRSA
Are renally excreted
Second gen cephalosporins
Cefactor (PO)
cefuroxime (PO)
Cefoxitin (IV)
Usually used against organisms that can be affected by 1st gen, but also includes more gram negative rods and cocci
- never inject via IM*
Are renally excreted
3rd gen cephalosporins
Cefotaxime (IV/IM)
Ceftazidime (IV/IM)
Ceftriaxone (IV/IM)
Often used against hamophilus and pneumococci infections and gonorrhoeae infections
- better against gram (-) than (+)
enter the CSF
Renal excretion except for ceftriaxone (liver excretion)
Why are there generations of cephalosporins
A lot of bacteria have grown resistance to previous generations
- also newer generations tend to have more gram(-) activity compared to gram (+) activity*
- exception is gen 5 ceftaroline (anti-MRSA)
Which 1st gen cephalosporin drug penetrates BBB?
Cefazolin (IV)
- drug of choice for surgical prophylaxis and bacteria staph infections
What drug combo is used for resistant intra-abdominal/urinary tract infections?
Ceftazidime and avibactam
4th gen cephalosporins
Cefepime (IV)
Only major drug and has similar uses to 3rd generation except for it also is indicated for the following
- enterobacter infections
- Lyme disease
- encephalopathy
- P. Aeruginosa
Renally cleared
distributes well into the CSF
5th gen cephalosporins
Ceftaroline (IV)
Binds to mutated PBP that confers resistance to almost all other b-lactams
can be used as an absolute final decision for almost all bacterial infections especially complicated ones, however it is used almost exclusively for only MRSA
Aztreonam
Primary used monobactams
- non penicillin; non cephalosporin
narrow spectrum that only works against gram negative bacteria
- similar spectrum to 3rd gen
- highly resistant to B-lactamases
Used primarily to treat serious gram (-) infections and for patients who are allergic to penicillin/ cephalosporins
can not be crossed with patients who are allergic to ceftazidime (can develop cross-allergenicity to aztreonam)
Can penetrate BBB
Carbapenems
Imipenem/cilastatin
Doripenem
Ertapenem
Meropenem
Renally excreted and all administered via IV
Broad spectrum agents used for patients who are experiencing resistant infections and are allergic to penicillin
- Urinary tract infections
- lower respiratory infections
- intra-abdominal and vaginal infections
- dont use for pseudomonas infections*
Why is imipenem always used with cilastatin clinically?
Imipenem by itself will be hydrolyzed to a toxic metabolite in the proximal tubular epithelium by renal dipeptidase
- cilastatin is an adjunct agent that prevents renal dipeptidase form doing this
Glycopeptides
Include primarily vancomycin and teicoplanin
MOA is to inhibit cell wall synthesis by preventing glycan strand polymerization
- also inhibit transpeptidase (PBP)
Primarily used for gram-positive infections (stap/strep) that are resistant to penicillin/cephalosporins.
- PO form is only used against c.diff infections*
Glycopeptides ADRs
Pretty widespread but are reversible
- phlebitis
- ototoxicity
- nephrotoxicity
- “red man syndrome” via hypersensitivity
- treat this with antihistamines and stop usage*
Worst misdiagnosis you can make as it pertains to antibiotics
Prescribing a patient who has a viral infection antibiotics.
(doesn’t do anything and increases chance of developing resistance, even higher chance if the antibiotic you prescribe is a broad/empiric agent)
