Antimicrobials Flashcards
MOA of penicillin
- bind penicillin binding proteins (transpeptidases) and block transpeptidase cross-linking of peptidoglycan
- activate autolytic enzymes
Penicillinase resistant penicillins
- Oxacillin, nafcillin, dicloxacillin
- use for S. aureus (except MRSA)
Aminopenicillins
- Ampicillin, amoxicillin
- combine with clavulanic acid to protect against beta-lactamase
Beta lactam antipesudomonals
- Ticarcillin, piperacillin
Beta-lactamase inhibitors
- CAST
- Clavulanic Acid, Sulbactam, Tazobactam
MOA of cephalosporins
- beta lactams that inhibit cell wall synthesis but are LESS susceptible to penicillinases
Organisms not covered by cephalosporins
- LAME
- Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci
Indications for 1st generation cephalosporins (cefazolin, cephalexin)
- gram positive cocci and PEcK
- Proteus, E. coli, Klebsiella
- cefazolin used prior to surgery to prevent S. aureus infections
Indications for 2nd generation cephalosporins (cefoxitin, cefaclor, cefuroxime)
- gram positive cocci and HEN PEcKS
- Haemophilius, Enterobacter, Neisseria, Proteus, E. coli, Klebsiella, Serratia
Indications for 3rd generation cephalosporins (ceftriaxone, cefotaxime, ceftazidime)
- serious gram negative infections resistant to other beta-lactams
- ceftriaxone: meningitis and gonorrhea
- ceftazidine: pseudomonas
Indications for 4th generation cephalosporins (cefepime)
- increased activity against pseudomonas and gram positive organisms
MOA of aztreonam
- monobactam resistant to beta-lactamases
- prevents peptidoglycan cross-linking by binding to PBP3
- synergistic with aminogycosides
Indications for aztreonam
- gram negative rods only
- penicillin allergic pts.
- pts. with renal insufficiency who cannot tolerate aminoglycosides
MOA of imipenem/cilastatin
- beta-lactamse resistant carbapenem
- always given with cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules
MOA of vancomycin
- inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors
- Bactericidal
Indications for vancomycin
- gram positive only: MRSA, enterococci, and C. difficile
Toxicity of vancomycin
- nephrotoxicity, ototoxicity, thrombophlebitis
- Red Man Syndrome: diffuse flushing (can be prevented by pretreatment with antihistamines and slow infusion rate)
Resistance to vancomycin
- amino acid change of D-ala D-ala to D-ala D-lac
Protein synthesis inhibitors
- Buy AT 30, CCEL at 50
- 30S inhibitors: aminoglycosides (bactericidal) and tetracyclines (bacteriostatic)
- 50S inhibitors: chloramphenicol, clindamycin (bacteriostatic), erythromycin (macrolide, bacteriostatic), and linezolid (variable)
MOA of aminoglycosides
- gentamicin, neomycin, amikacin, tobramycin, streptomycin
- bactericidal
- inhibit formation of initiation complex and cause misreading of mRNA
- also block translocation
Indications for aminoglycosides
- severe gram negative rod infections
- synergistic with beta-lactams
- ineffective against anaerobes because they require O2 for uptake
Toxicity of aminoglycosides
- nephrotoxicity (esp. when used with cephalosporins)
- ototoxicity (esp. when used with loop diuretics)
- neuromuscular blockade
- teratogen
Mechanism of resistance against aminoglycosides
- transferase enzymes that inactivate the drug by acetylation, phosphorylation or adenylation
MOA of tetracyclines
- tetracycline, doxycycline, demeclocycline, minocycline
- bacteriostatic
- bind to 30S and prevent attachment of aminoacyl-tRNA
- divalent cations inhibit its absorption in the gut (don’t take with milk, antacids, or iron-containing solutions)
5 indications of tetracyclines
- Borrelia burgdorferi
- M. pneumonia
- Rickettsia
- Chlamydia
- demeclocyline is also an ADH antagonist and used as a diuretic in SIADH
Toxicity of tetracyclines
- discoloration of teeth and inhibition of bone growth in children
- C.I. in pregnancy
Mechanism of resistance against tetracylines
- decreased uptake or increased efflux via transport pumps
- chemical modification and ribosomal protection
MOA of macrolides
- azithromycin, clarithromycin, erythromycin
- bacteriostatic
- block translocation by binding to the 23S rRNA of the 50S ribosomal subunit
Indications for macrolides
- atypical pneumonia
- STDs (Chlamydia)
- gram positive cocci
Toxicity of macrolides
- MACRO
- motility issues, arrhythmia, acute cholestatic hepatitis, rash, eosinophilia
- increases serum concentrations of theophyllines, oral anticoagulants (warfarin)
Mechanism of resistance against macrolides
- methylation of 23S rRNA binding site
MOA and indications of chloramphenicol
- MOA: blocks peptidyltransferase at 50S ribosomal subunit, bacteriostatic
- indication: meningitis (H. influenza, N. meningitidis, S. pneumoniae)
MOA and indications of clindamycin
- MOA: blocks peptide transfer (transpeptidation) at 50S ribosomal subunit, bacteriostatic
- indication: anaerobic infections (above the diaphragm compared to metronidazole which treats anaerobic infections below the diaphragm)
MOA of sulfonamides
- PABA antimetabolites inhibit dihydropteroate synthase
- bacteriostatic
Mechanism of resistance to sulfonamides
- altered enzyme (bacterial dihydropteroate synthase), decreased uptake, or increased PABA synthesis
MOA of trimethoprim
- inhibits bacterial dihydrofolate reductase
- bacteriostatic
Toxicity of trimethoprim and what drug can help prevent toxicity
- megaloblastic anemia, leukopenia, and granulocytopenia
- leucovorin is used for folinic acid rescue
MOA of fluoroquinolones
- inhibits DNA gyrase (topoisomerase II) and topoisomerase IV
- bactericidal
- topoisomerase II: more effective in gram negatives
- topoisomerase IV: more effective in gram positives
Toxicity of fluoroquinolones
- tendon rupture, prolonged QT interval
- C.I. during pregnancy
- must not be taken with antacids
MOA of metronidazole
- forms free radical toxic metabolites in the bacterial cell that damage DNA
- bactericidal, antiprotozoal
Indications for metronidazole
- GET GAP
- Giardia, Entamoeba, Trichomonas, Gardnerella, Anaerobes (Bacteroides, C. difficile), H. pylori
4 drug regimen of TB treatment
- RIPE
- rifampin, isoniazid, pyrazinamide, ethambutol