Micro FA p.187 - 204 Antimicrobials Flashcards
MoA of Penicillin
D-Ala-D-Ala structural analog
Bind penicillin-binding proteins (transpeptidases)
Block transpeptidase cross-linking of peptidoglycan in cell wall.
Clinical use of penicillins
gram ⊕ organisms (S pneumoniae, S pyogenes, Actinomyces).
Also used for gram ⊝ cocci (mainly N meningitidis) and spirochetes (mainly T pallidum).
(Bactericidal for gram ⊕ cocci, gram ⊕ rods, gram ⊝ cocci, and spirochetes. )
Adverse effects of penicillins
Hypersensitivity reactions, direct Coombs ⊕ hemolytic anemia, drug-induced interstitial nephritis
How do bact form resistence to penicillin?
β-lactamase cleaves the β-lactam ring. Mutations in PBPs.
Penicillinase sensitive penicillins ex.
Amoxicillin, ampicillin; aminopenicillins
MoA of Penicillinase sensitive penicillins, what do you combine it with
Same as penicillin. Wider spectrum; penicillinase sensitive. Also combine with clavulanic acid to protect against destruction by β-lactamase.
Amoxicillin has greater ____ ________than ampicillin.
AmOxicillin has greater Oral bioavailability than ampicillin.
Clinical use of penicillinase sensitive penicillins
Extended-spectrum penicillin—H influenzae, H pylori, E coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci.
Coverage: ampicillin/amoxicillin HHELPSS kill enterococci.
SE/ Penicillinase sensitive penicillins
Hypersensitivity reactions, rash, pseudomembranous colitis
How does bact form resistence vs amoxicillin (et al)
Penicillinase (a type of β-lactamase) cleaves β-lactam ring.
Ex of penicillinase resistant penicillins
Dicloxacillin, nafcillin, oxacillin.
MoA of penicillinase resistant penicillins
Same as penicillin. Narrow spectrum; penicillinase resistant because bulky R group blocks access of β-lactamase to β-lactam ring.
Clinical use of penicillinase resistant penicillins
S aureus (except MRSA).
“Use naf (nafcillin) for staph.”
SE/ of Dicloxacillin, Nafcillin, etc
Hypersensitivity reactions, interstitial nephritis.
Mech of resistance of penicillinase resistant penicillins
MRSA has altered penicillin-binding protein target site
Ex of antipseudomonal penicillins
Piperacillin, ticarcillin.
Clinical use of piperacillin
Pseudomonas spp. & G- rods
MoA of Cephalosporins
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal.
Organisms typically not covered by 1st–4th generation cephalosporins are
1.
2.
3.
4.
Organisms typically not covered by 1st–4th generation cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
1st gen cephalosporins used for?
ex/ of Rx
1st generation (cefazolin, cephalexin)—gram ⊕ cocci, Proteus mirabilis, E coli, Klebsiella pneumoniae.
1st generation—⊕ PEcK
_______ used prior to surgery to prevent S aureus wound infections.
Cefazolin used prior to surgery to prevent S aureus wound infections.
Clinical use of 2nd gen cephalosporins
ex/ of Rx?
2nd generation (cefaclor, cefoxitin, cefuroxime, cefotetan)—gram ⊕ cocci, H influenzae, Enterobacter aerogenes, Neisseria spp., Serratia marcescens, Proteus mirabilis, E coli, Klebsiella pneumoniae.
2nd graders wear fake fox fur to tea parties. 2nd generation—HENS PEcK.
Ex of 3rd gen cephalosporins?
ceftriaxone, cefotaxime, cefpodoxime, ceftazidim
Which gen of cephalosporins can cross brain barrier
3rd gen
Which cephalosporin is used for meningitis, gonorrhea, and disseminated Lyme disease?
Ceftriaxone
Which cephalosporin is used for Pseudomonas?
Ceftazidime—Pseudomonas
4th gen cephalosporins used for? ex?
—gram ⊝ organisms, with activity against Pseudomonas and gram ⊕ organisms.
ex/ cefepime
unlike 1st–4th generation cephalosporins, ceftaroline covers ____, and ______ ________
and does not cover ___________.
unlike 1st–4th generation cephalosporins, ceftaroline covers MRSA, and Enterococcus faecalis—does not cover Pseudomonas.
SE/ Cephalosporins
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency.
Cephalosporins increase what toxicity of aminoglycosides?
Inc nephrotoxicity of aminoglycosides.
Ex of β-lactamase inhibitors
Clavulanic acid, Avibactam, Sulbactam, Tazobactam
List antibiotic/B lactamase (-)’r combos (4)
amoxicillin-clavulanate, ceftazidime-avibactam, ampicillin-sulbactam, piperacillin-tazobactam)
List Carbapenems
Doripenem, Imipenem, Meropenem, Ertapenem (DIME antibiotics are given when there is a 10/10 [life-threatening] infection).
Imipenem is always administered with? MoA of that rx?
Imipenem always administered with cilastatin (inhibitor of renal dehydropeptidase I) to dec inactivation of drug in renal tubules.
Clinical use of carbapenems
Gram ⊕ cocci, gram ⊝ rods, and anaerobes.
Meropenem has a dec risk of _______ and is stable to ___________.
Meropenem has a dec risk of seizures and is stable to dehydropeptidase I.
SE// of Carbapenems
GI distress, rash, and CNS toxicity (seizures) at high plasma levels.
Carbapenems Cause a bad rash
C- CNS
CARBa-penems - GI
Mech of resistance of carbapenems?
Inactivated by carbapenemases produced by, eg, K pneumoniae, E coli, E aerogenes.
Which antibiotic is synergistic with aminoglycosides?
Aztreonam
MoA of monobactams?
Less susceptible to β-lactamases. Prevents peptidoglycan cross-linking by binding to penicillinbinding protein 3.
What are monobactam used for clinically?
Gram ⊝ rods only—no activity against gram ⊕ rods or anaerobes.
MoA of Vancomycin?
Inhibits cell wall peptidoglycan formation by binding D-Ala-D-Ala portion of cell wall precursors. Bactericidal against most bacteria
Clinical use of Vancomycin?
Gram ⊕ bugs only - for serious, multidrug-resistant organisms, including MRSA, S epidermidis, sensitive Enterococcus species, and Clostridium difficile (oral dose for pseudomembranous colitis).
SE/ of Vancomycin
Well tolerated in general—but NOT trouble free. Nephrotoxicity, Ototoxicity, Thrombophlebitis, diffuse flushing—red man syndrome A (largely preventable by pretreatment with antihistamines and slow infusion rate), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome).
Mech of resistance against Vanco?
Occurs in bacteria (eg, Enterococcus) via amino acid modification of D-Ala-D-Ala to D-Ala-D-Lac. “If you Lack a D-Ala (dollar), you can’t ride the van (vancomycin).”
All protein synthesis inhibitors are bacteriostatic, except ______ (bactericidal) and ______(variable).
All are bacteriostatic, except aminoglycosides (bactericidal) and linezolid (variable).
Give ex of aminoglycosides?
Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin
MoA of Aminoglycosides?
- Bactericidal; irreversible inhibition of initiation complex through binding of the 30S subunit.
- Can cause misreading of mRNA.
- Also block translocation.
Aminoglycosides require ___ for uptake; therefore ineffective against _____.
Aminoglycosides require O2 for uptake; therefore ineffective against anaerobes.
Clinical use of aminoglycosides
Severe gram ⊝ rod infections. Synergistic with β-lactam antibiotics
What aminoglycoside is used for bowel surgery?
Neomycin
SE of Aminoglycosides
Nephrotoxicity, Neuromuscular blockade (absolute contraindication with myasthenia gravis), Ototoxicity (especially with loop diuretics), Teratogenicity.
also dec Mg2+ in the body
Ex of tetracyclines
Tetracycline, doxycycline, minocycline
MoA of tetracyclins?
Bacteriostatic; bind to 30S and prevent attachment of aminoacyl-tRNA
Doxycycline is _____ eliminated and can be used in patients with ____ _______.
Doxycycline is fecally eliminated and can be used in patients with renal failure.
Can’t take tetracyclins with what?
Do not take tetracyclines with milk (Ca2+), antacids (eg, Ca2+ or Mg2+), or iron-containing preparations because divalent cations inhibit drugs’ absorption in the gut.
Clinical use of tetracyclins?
Borrelia burgdorferi, M pneumoniae. Drugs’ ability to accumulate intracellularly makes them very effective against Rickettsia and Chlamydia.
Doxycycline effective against community-acquired MRSA.
SE/ of Tetracyclins
GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity. Contraindicated in pregnancy.
Tetracyclin - severe nephrotox
TEETHracyclins
Mech of resistance of tetracyclins
Dec uptake or inc efflux out of bacterial cells by plasmid-encoded transport pumps.
MoA of Tigecyclin
Tetracycline derivative. Binds to 30S, inhibiting protein synthesis. Generally bacteriostatic.
Clinical use of Glycylcyclines?
Broad-spectrum anaerobic, gram ⊝, and gram ⊕ coverage.
Multidrug-resistant organisms (MRSA, VRE) or infections requiring deep tissue penetration.
MoA of Chloramphenicol
Blocks peptidyltransferase at 50S ribosomal subunit. Bacteriostatic
Clinical use of chloramphenicol?
Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae) and rickettsial diseases (eg, Rocky Mountain spotted fever [Rickettsia rickettsii]).
SE of Chloramphenicol
Anemia (dose dependent), aplastic anemia (dose independent), grey baby syndrome
Why does admin of chloramphenicol in premature infants lead to grey baby syndrome?
because they lack liver UDP-glucuronosyltransferase
Mech of resistance vs chloramphenicol
Plasmid-encoded acetyltransferase inactivates the drug
Clindamycin MoA
Blocks peptide transfer (translocation) at 50S ribosomal subunit. Bacteriostatic
Clinical use of clindamycin?
Anaerobic infections (eg, Bacteroides spp., Clostridium perfringens) in aspiration pneumonia, lung abscesses, and oral infections. Also effective against invasive group A streptococcal infection.
Treats anaerobic infections above the diaphragm, and Metronidazole below diaphragm
_______ treats anaerobic infections above the diaphragm vs ________ anaerobic infections below diaphragm.
Clindamycin treats anaerobic infections above the diaphragm vs metronidazole (anaerobic infections below diaphragm).
SE/ of Clindamycin
Pseudomembranous colitis (C difficile overgrowth), fever, diarrhea
MoA of Linezolid.
Inhibit protein synthesis by binding to 50S subunit and preventing formation of the initiation complex.
Use of Linezolid?
Gram ⊕ species including MRSA and VRE
SE/ of Linezolid
BOne marrow suppression (especially thrombocytopenia), peripheral NEuropathy, Serotonin syndrome (due to partial MAO inhibition).
Linezolid is bad for BONES
Mech of resistance of Linezolid
point mutation of ribosomal DNA
Macrolide MoA
Inhibit protein synthesis by blocking translocation (“macroslides”); bind to the 23S rRNA of the 50S ribosomal subunit. Bacteriostatic.
Clinical use of Macrolides
Atypical pneumonias (Mycoplasma, Chlamydia, Legionella), STIs (Chlamydia), gram ⊕ cocci (streptococcal infections in patients allergic to penicillin), and B pertussis.
SE of Macrolides
MACRO: Gastrointestinal Motility issues, Arrhythmia caused by prolonged QT interval, acute Cholestatic hepatitis, Rash, eOsinophilia
Macrolides Inc serum conc of ___________ & ____ _____________
Theophylline & oral anticoagulants
Which macrolides (-) Cyt p450?
Clarithromycin Erythromycin
Mech of resistance vs macrolides
Methylation of 23S rRNA-binding site prevents binding of drug.
MoA of Polymyxins
Cation polypeptides that bind to phospholipids on cell membrane of gram ⊝ bacteria. Disrupt cell membrane integrity –> leakage of cellular components–> cell death
Clinical use of Polymyxins
Salvage therapy for multidrug-resistant gram ⊝ bacteria (eg, P aeruginosa, E coli, K pneumoniae)
Polymyxins tox
Nephrotoxicity, neurotoxicity (eg, slurred speech, weakness, paresthesias), respiratory failure.