Antimicrobials Flashcards
What are the 5 classes of drugs that inhibit cell-wall synthesis and are all bactericidal?
[all beta lactams] Penicillin Cephalosporin Carbapenem Monobactam
Glycopeptides [only non-lactam]
What is one positive and one negative effect of an antibiotic target unique to microbials (not normally found in humans)?
- Positive: wide therapeutic index (can give high doses)
- Negative: more likely to cause allergic reaction
What are 3 modes of resistance to penicillins/cephalosporins?
- Penicillinases (beta-lactamases)-cleave lactam ring structure
- Structural changes in PBP (i.e MRSA)
- Change in porin structure (Abx can’t cross cell wall in gram(-) i.e pseudomonas)
Which 2 microbes would penicillin G and V be ineffective against?
Staph aureus & B. Fragilis
Both have 100% penicillinase activity and Penicillin G & V are narrow spectrum, beta-lactamase sensitive
What are 2 narrow spectrum, beta-lactamase sensitive anti-microbials and what are they used to treat?
Penicillin G (IV) & Penicillin V (oral) --> useful for streptococci, pneumococci, meningococci and Treponema pallidum
What are 3 very narrow spectrum, beta-lactamase resistant anti-microbials? What are they used to treat?
Oxacillin (IV), Dicloxacillin (oral), Methacillin
Only have activity against S. aureus (but NOT MRSA)
What is the mechanism of action of ampicillin and those in its class?
(Penicillin)
Interacts with cytoplasmic PBP to inhibit transpeptidation and cross-linking of cell wall (final steps of synthesis) –> lack of cell wall rigidity causes organism to lyse
What is an extended spectrum, beta-lactamase sensitive agent that is primarily used IV in the hospital? Used to treat?
Piperacillin
–> increased activity against gram- rods (pseudomonas)
(Usually given with suicide inhibitor)
What are 2 broad spectrum, aminopenicillin, beta-lactamase sensitive anti-microbials? Used to treat?
Ampicillin (IV) & Amoxicillin (oral)
Gram+ cocci (not staph) E.coli H. Influenzae Listeria monocytogenes (ampicillin) Borrelia burgdorferi (amoxicillin) H. Pylori (amoxicillin)
PBP 2b is the binding site for…?
PBP 2x is the binding site for…?
2b: all penicillins and 1st generation cephalosporins
2x: all other cephalosporins, carbapenems & monobactams
What is the purpose of suicide inhibitors? Name 2.
Beta-lactamase inhibitor –> enhance activity of penicillins
- Augmentin: combination of amoxicillin (broad spectrum, lactamase sensitive) and clavulanic acid (suicide inhibitor)
- Zosyn: pipercillin (extended spectrum, lactamase sensitive) with tazobactam
Which 2 microbes confer resistance by altering PBP?
Pneumococcus- 30% PBP 2b mutation (resistance to all penicillins and 1st generation cephalosporins)
MRSA- PBP 2b and 2x (resistance to all lactam drugs)
What is the cross-reactivity of penicillins? What is the difference between an IgE and IgM mediated response?
- penicillins will cross-react with other penicillins and 1st generation cephalosporins
- no cross reaction with monobactam or aztreonam (due to lack of ring adjacent to lactam structure)
- IgE: anaphylaxis (hives, angioedema, stridor, hypotension)
- IgM: maculopapular rash (no cross-reactivity with other penicillins)
What is the mechanism of action of cefpodoxime and those in its class?
(cephalosporins)
identical to penicillins- Interacts with cytoplasmic PBP to inhibit transpeptidation and cross-linking of cell wall (final steps of synthesis) –> lack of cell wall rigidity causes organism to lyse
Name 2 1st generation cephalosporins. spectrum? common use?
Cefazolin (IV) & Cephalexin (oral)
–> gram+ cocci (not MRSA), E. coli, Klebsiella pneumoniae
-commonly used in surgical prophylaxis
Name a 2nd generation cephalosporin. spectrum?
Cefuroxime (IV, oral)
–> gram+ cocci (except MRSA), increased gram_ coverage- H. flu, anaerobes
Name three 3rd generation cephalosporins. spectrum? use?
Ceftriaxone (IV), Ceftazidime (IV) & Cefpodoxime (oral)
- -> broad spectrum: gram+ cocci, gram- cocci, gram- rods
- used in empiric management of meningitis and sepsis
Name a 4th generation cephalosporin. spectrum?
Cefepime (IV)
–> very broad spectrum (gram+ cocci and rods, gram- rods)
Name a carbapenem. Mechanism? Spectrum and use?
Imipenem (IV)
- -> binds to PBP to prevent cell wall cross-linking but is also resistant to beta-lactamases
- -> very broad spectrum (gram+ cocci, gram- rods, anaerobes)
- -> in-hospital agent for severe, life-threatening infections (sepsis)
What drug is given with Imipenem? why?
Cilastatin (renal dehydropeptidase inhibitor)
–> inhibits kidney from metabolizing impinenem to its nephrotoxic metabolite too quickly
What is aztreonam? Mechanism, use, cross-allergenicity?
- monobactam, given IV
- -> binds PBP to prevent cell wall cross-linking and is beta-lactamase resistant
- -> only active against gram- rods
- -> NO cross-allergenicity with penicillins/cephalosporins
Describe the class, mechanism, and use of vancomycin
glycopeptide used IV or oral
- ->binds D-ala-D-ala muramyl pentapeptide and sterically hinders transglycosylation/peptide elongation of cell wall [slower onset (hrs) than lactams]
- -> used for MRSA, enterococci and metronidazole-resistant C. difficile (oral)
What is the acronym/orgranisms not covered by cephalosporins?
LAME Listeria monocytogenes (amoxicillin) Atypicals- Chlamydia, Mycoplasma MRSA (vancomycin) Enterococci (ampicillin + aminoglycosides)
What is the mode of resistance to vancomycin?
- enterococci: change in muramyl pentapeptide such that the terminal D-ala is readily replaced by D-lactate and vancomycin can’t bind
- increased cell wall thickness
Other than typical allergic side effects, what are 3 other adverse effects of vancomycin?
- “red man syndrome” (flushing, tachycardia, hypotension from histamine/vasodilatory effect)
- ototoxicity
- nephrotoxicity (mild)
Which lactam agents can enter the CNS?
- Cefuroxime (only 2nd generation)
- most 3rd generation cephalosporins
- 4th generation cephalosporins
- imipenem
What drug may be given for vancomycin resistant enterococci (VRE) and vancomycin resistant S. aureus (VRSA)? Class, mechnism, use, adverse effects?
Daptomycin (cell membrane toxin)
- Mechanism: inserts into cell membrane forming a channel that allows leakage of intracellular ions
- Use: Gram+ ONLY, serious infections that are otherwise resistant
- SE: allergy, rhabdomyolysis (use >7days)
What is Colistin? Mechanism, use and adverse effects?
(polymixin- cell membrane toxin)
- -> binds LPS disrupting outer cell membrane of gram- and leakage of intracellular ions
- Use: gram- ONLY that are otherwise resistant (mainly Pseudomonas)
- SE: highly nephrotoxic
What are 3 classes that inhibit bacterial nucleic acid synthesis? General descriptor of each?
- Floroquinolones- inhibit DNA gyrase (top. II) and topoisomerase IV
- Rifampin- inhibits DNA-dependent RNA polymerase
- Metronidazole- unknown (free radicals?)
What is the action of DNA gyrase? What are the 1st and 2nd generation floroquinolones that inhibit its action? Contraindications?
- DNA gyrase- negative supercoiling that orients DNA for replication [not present in humans]
- Ciprofloxacin (1st generation)
- Levofloxacin (2nd generation)
- ->contraindicated in pregnancy/children
What agent may be used for lactam-resistant pneumococci? What is a potential adverse effect?
levofloxacin (floroquinolone)
–>may cause QT prolongation and v. tach (torsades de points)
What is the mechanism of action, spectrum and adverse effects of Metronidazole?
- Mech: prodrug activated in an ANAEROBIC environment that is toxic to nucleic acids
- Spectrum: DOC pseudomembranous colitis (C. difficile), works for most anaerobic gram- species; DOC as antiprotozoal for Giardia, Trichomonas, Entamoeba
- SE: inhibits aldehyde dehydrogenase (dont use EtOH)
What are the 5 classes of bacteria protein synthesis inhibitors? Which act on 30S and which on 50S?
30S inhibitors:
Aminoglycosides & Tetracyclines
50S inhibitors:
Macrolides, Linezolid & Clindamycin
Of the protein synthesis inhibitors, which inhibit formation of initiation complex by blocking association of 30S with 50S? Which one also causes code misreading and is the only bactericidal agent?
Aminoglycosides (30S) & Linezolid (50S)
–>aminoglycosides also cause misreading due to steric hinderance
Name 2 Aminoglycosides. Mechanism? Spectrum? Adverse effects?
Gentamicin & Tobramycin
Mech: Oxygen-mediated active uptake- blocks initiation and induces code misreading
Spectrum: aerobic or facultative aerobic Gram- rods (due to O2 uptake)
(Amp + Gent for enterococci)
SE: nephrotoxicity but ONLY w/prolonged use [best to use as initial dose in gram- sepsis due to rapid lethality then switch to safer drug]
What is the mechanism, spectrum and adverse effects of Linezolid?
(protein synthesis inhibitor)
Mech: inhibits peptidyl transferase and the formation of initiation complex
Spectrum: VRSA, MRSA
SE: allergies, agranulocytosis with prolonged use (>2wks)
Which synthesis inhibitor blocks attachment of tRNA to acceptor site? Spectrum? Adverse effects?
Doxycycline (tetracycline)
Spectrum: intracellular pathogens (mycoplasma, chlamydia, legionella, rickettsia); resistant gram+
SE: phototoxicity; contraindicated in pregnancy/children; chelator (Ca2+, Mg2+, etc) so don’t take with food
Which protein synthesis inhibitors act to inhibit translocation of peptidyl-tRNA from acceptor to donor site?
Macrolides and Clindamycin
Name the DOC for Legionella. What is its spectrum and adverse effects?
Azithromycin (protein synthesis inhibitor of translocation)
Spectrum: wide; intracellular pathogens, gram+ cocci, H. influenzae
SE: GI distress (increase peristalsis), potential for v. tach (TdP)
Which antibacterial agent is the most closely associated with C. difficile colitis (pseudomembranous colitis)? What is its spectrum?
Clindamycin (protein synthesis inhibitor of translocation)
–> all anaerobes except for C. difficile; used for resistant pneumococci and MRSA (Especially osteomyelitis)
What is Bactrim? Mechanism? Spectrum? Adverse effects?
Anti-metabolite- Inhibits Folic Acid synthesis:
Sulfamethoxazole- inhibits Dihydropterate synthase
Trimethoprim- inhibits DHFR
–>Uncomplicated UTIs; Pneumocystis pneumonia & Toxoplasmosis infections in AIDS
-SE: Hyperkalemia in patients with severe renal insufficiency (TMP analog to triamterene)
What are the 4 agents used in combination for active TB? Which one of these is given for 9 months if +PPD but no active disease?
Isoniazid - given as chemoprophylaxis
Rifampin
Ethambutol
Pyrazinamide
What is the mechanism of Isoniazid? What are its side effects and what should be co-administered to prevent these?
Isoniazid is a congener of vitamin B6
–>prodrug, inhibits mycolic acid synthesis unique to mycobacterium cell walls
(Therapeutic index: M.tb utilizes B6 to a greater extent than human cells)
-SE: peripheral neuropathy, sideroblastic anemia, status epilepticus if OD
–>NEED TO CO-ADMINISTER PYRIDOXINE
What is a common adverse effect of the anti-tubercular anti-metabolites? What is specific for rifampin? for pyrazinamide? for ethambutol?
- All associated with centrolobular hepatitis except ethambutol
- Rifampin: serious flu-like hypersensitivity if used in intermittent dosing regimens
- Pyrazinamide: increase uric acid -> gout
- Ethambutol: optic neuritis (loss red-green discrimination), gout
