Antibiotics Flashcards
Penicillin MOA
Time dependent killing
Bind to PBP during cross-linking of cell wall
Resistance: beta lactamases, modification of PBP, efflux, impaired penetration
Penicillin Spectrum
- B-lactamase negative GPC (S.pneumoniae, S.pyrogens, VGS) - oral anaerobes (GPs) (actinomyces, peptococcus, petptostretococcus) - N. meningitis (GN) - syphilis * GRAM POSITIVES**
Penicillin Gaps
- atypical organisms
- B-lactamase (+) GPCs - Staph
- aerobic GNB
- anaerobic GN
Amoxicillin/Ampicillin MOA
PCN + more penetration into outer membrane and higher affinity for PBP so increase in GN
Amoxicillin/Ampicillin Spectrum
PCN + gram positives including enterococcus
some gram negatives
Amoxicillin/Ampicillin Gaps
susceptible to B-lactamases
Piperacillin Spectrum
more GN activity
- harder to treat GN pseudomonas & enterococcus
Gaps in Coverage:
- susceptible to B-lactamases
Piperacillin + Tazobactam Spectrum
Useful for where there is resistance! LARGE spect.
- oral anaerobes
- GP in general (inc. MSSA)
- GN in general
Cephalosporins 1st gen
cefazolin
cephalexin
Cephalosporins 1st gen spectrum
Coverage: PCN PLUS - easy to kill GN: E.coli, proteus spp., klebsiella spp Retain: - aerobic GPC - oral anaerobes
Cephalosporins 2nd gen
cefoxitin
cefaclor
cefuroxime
Cephalosporins 2nd gen spectrum
Coverage: PCN + 1GC PLUS
- gut anaerobes: B. fragillis sp (but resistance high so not often used)
cefuroxime: H.influenza and Moraxella catarrhalis (respiratory organisms)
Cephalosporins 3rd gen
Ceftriaxone
Cefotaxime
Ceftazidime
Cephalosporins 3rd gen spectrum
Ceftriaxone: 1st GC PLUS broader GNB
Gaps in Coverage: LOSE: Staph activity & anaerobic coverage
Ceftazidime: PCN PLUS broader GNB than 2nd GC (b/c of sidechain which inc. penetration of GN membrane) and Pseudomonas
Gaps in Coverage: LOSE GP coverage** NO strep or staph coverage
Cephalosporins 4th gen
Cefepime
Cephalosporins 4th gen spectrum
Coverage: 3GC plus more GNs, AmpC
Retain:
- GP similar to ceftriaxone (3GC)
- PsA similar to ceftazidime (3Gc)
Gaps in Coverage:
- ESBL
Carbapenems: Meropenem and Imipenem
Coverage: added to Pip/tazo OR 3GC
- oral & gut anaerobes
- GP in general (inc. MSSA)
- GN in general
- ESBL
- ampC
- Pseudomonas (M&I)
Carbapenems: Ertapenem
- less activity than mero/imipen against GN
- LOSE: pseudomonas, enterococci, acinetobacter
Vancomycin
Coverage: - GPs only (b/c too large & polar to cross GN CM) - C. difficile (po) - MSSA, MRSA - PCN resistant strep meningitis - enterococcus “drug of last choice” Use when: - B-lactam allergy, B-lactam resistance (MRSA, CoNS)
Vancomycin AE
- red man syndrome: pruritis, red rash of face, neck, upper torso w/ hypoT -> tx by slowing infusion rate (histamine release causes this)
- hypotension, flushing, erythematous rash, chills (infusion related)
- ototxicity (w/ other ototoxic drugs)
- nephrotoxicity (risk ↑w/ high doses or other nephrotoxic drugs)
- neutropenia
Daptomycin
Coverage:
- GPs (inc. MRSA, MRSE, VRE)
Gaps in Coverage:
- no GNs
- no anaerobes
Daptomycin AE
myalgias, myopathies
Ciprofloxacin (early fluroquinolone)
Spectrum:
- aerobic GN activity
- poor GP activity (no staph/strep)
Respiratory Fluroquinolones (moxifloxacin, levofloxacin)
Spectrum:
- better” GP coverate + added gut anaerobe coverage (moxi is broader)
Fluroquinolones AEs
AE: occur in ANY part of body
- N/V/D
- photosensitivity (cipro is WORST)
- CNS: HA, dizziness, drowsiness
- hepatic (transient risk in LFTs, jaundice)
- renal (nephritis)
- skin (rash, photosens)
- MSK (arthopath, tendinitis, tendon rupture)
- CVS (hypoT, tachy, QT prolongation)
- endocrine (hypo or hyper glycemia)
Metronidazole spectrum
- gut anaerobes ONLY (C. diff & parasites)
Sulfonamide-trimethoprim spectrum
Spectrum:
- GP (inc MRSA)
- GN (H. influ, enterobacter SPICA)
What does it lack?
- GAS
- PsA
- anaerobes
- enterococcia
Fidaxomicin Spectrum
Spectrum:
- C. diff
- less effect on the fecal microbial (vs vanco)
Fidaxomicin MOA
RNA polymerase inhibitor – binds to DNA template – RNA polymerase (RNAP) complex prior to RNAP-DNA complex formation
Sulfonamide-Trimethoprim MOA
Block enzyme in bacteria required for synthesis of tetrahydrofolic acid (a cofactor needed for bacteria to make the nucleotide bases T, U, G, A)
Metronidazole MOA
- activated by microbial proteins flavodxin & feredoxin
- when activated puts nicks in the microbial DNA strands
Fluroquinolones MOA
Inhibit bact. DNA synthesis by interacting w/ DNA gyrase & topoisomerase IV
Aminoglycosides
Gentamicin
Tobramycin
Amikacin
Aminoglycosides MOA
- IRreversably bind 30S ribosomal subunit
- may have some activity on cell membrane causing leakage
- uptake enhanced w/ exposure of cell-wall active agents (ie PCN)
Aminoglycosides Spectrum
What do they add:
- GNB: Pseudomonas
- MRSA
- GN aerobic bacilli
What do they lose:
NOT good for GPs or anerobes -> only GP if given synergistically with beta lactams
Aminoglycosides AE
AE:
- nephrotoxicity (reversible) – in elderly + on other nephrotoxic drugs
- ototoxicity (irreversible)
Linezolid (oxazolidinones) MOA
- bind to 50S ribosomal subunit near interface w/ 30S s/u preventing formation of 70S initiation complex
- different from other “protein synthesis” inhibitors which inhibit peptidyl transferase or translation-termination rxn
Linezolid (oxazolidinones) Spectrum
- only GP organisms including resistant ones
- MRSA, VRE
Where does it fit?
- alt to vanco for MRSA
- VRE
Linezolid AE
- reversible inhibitor of monamine oxidase
- thrombocytopenia
- leukopenia
- bone marrow suppression w/ prolonged use or other RFs
- N.V.D
- rash
Macrolides
Erythromycin
Clarithromycin
Azithromycin
Macrolides MOA
- reversibly binds to 50S ribosomal subunit
- prevents translocation of peptidyl-RNA (incoming tRNA c/n be added & pro synthesis stops)
Macrolides AE
- N/V/D (worst for Erythro)
- QT-prolongation* (drug interations)
- seizures
- jaundice
- hepatitis
- rash (uncommon)
- hearing loss (transient)*
Macrolides Spectrum
- PCN spectrum PLUS
- gram negatives
- S. pneumo *30% R in CAN
- atypical pneumo organisms (ie legionella)
- C & A -> H. influenza
Where do they fit? Used if need atypical organism coverage or for STIs/travel
Macrolides DI
DI: (macrolides are P45O inhibitor) theophylline, cyclosporine
- ERY > CLARI w/ CYP P450 but NONE w/ AZITHRO*
Clindamycin MOA
MOA: similar to macrolides
- binds to 50S subunit
- prevents translocation of pepridyl tRNA from the acceptor site to donor site
Clindamycin Spectrum
Coverage: (adds to PCN)
- anaerobes
- aerobic GPs
- most GPs (EXCEPT enterococcus)
- PCPs, MRSA
- some parasites
Gaps in Coverage:
- no gram negatives (b/c c/n cross the outer CM)
- enterococcus
Clindamycin AE
- diarrhea* -> C. difficile
- transient ↑ of liver enz
- neuromuscular blockade
- N/V
Tetracyclines
- passively diffuse through pores in CW (GNs) & through inner mem of GPs w/ nrg dependent pump
- Reversably binds 30S subunit
- binds at site that blocks binding of some AA-charged tRNA to the acceptor site or mRNA comples
- chelates cations essential to protein synthesis (Ca, Mg*)
Tetracyclines spectrum
Coverage: PCN spec PLUS
- GP & GN (similar to macrolides)
- atypical organisms (Mycoplasma, chlamydia, rickettsiae)
Tetracyclines AE
- GI
- photosensitivity (doxy)
- brownish discolouration of teeth
- hepatotoxicity
- hypersensitivity rxns
- drug induced lupus (mino, doxy)
- CNS_ dizziness, ataxia, vertigo
- fanconi-like syndrome (renal tubular dysfxn) -> w/ outdated product
Tigecycline (a tetracycline) spectrum
Coverage:
- GPs (inc. MRSA & VRE) - activity vs resistant organisms, b/c bacteriostatic and no bacteremia action so use is limited
- atypicals
- anaerobes
- most GNs
- ESBL – E.coli/K.pneumo
Gaps in Coverage:
- morganella
- Pseudomonas
- proteus
- providencia
