Antimicrobials Flashcards
MOA:Binds bacteria’s PBPs (transpeptidase) preventing crosslinking of AAs in cell wall synthesis (resistance develops by production of b-lactamase by bacteria that alters the structure of b-lactams so they cannot bind PBPs)
Spectrum:”* Narrowest spectrum
* Treponema pallidum (syphilis)
* Streptococcus spp (GAS)
* Oral anaerobes”
PK:“Oral drugs do not achieve same conc as IV
* Short half-life, time-dependent manner
* Most are renally eliminated (Except Nafcillin/oxacillin)”
Side Effects/AEs: “ * HS: Penicillins > cephalosporins > carbapenems
* Crossreactivity (from side chains) w cephalosporins decreases with increasing generation/structure changes
* GI: upset stomach PO
* Seizures: Greatest w carbapenems (imipenem)
Bone marrow suppression (long term use)”
Extra Notes: No resistance documented with GAS with penicillin (VERY RARE)
Resistance:“B-lactamases (MDR-AB/PA, MRSA)
- Penicillinases
- Extended-spect B-Lactamases (ESBLs - penicillins, cephalosporins, monobactam)
- Carbapenemases (penicillins, cephalosporins, monobactam AND carbapenems)
*Alteration of PBPs (MRSA, MDR-AB)”
Antibiotics - Cell Wall & Membrane Active Antibiotics
PENICILLINS
MOA:Binds bacteria’s PBPs (transpeptidase) preventing crosslinking of AAs in cell wall synthesis (resistance develops by production of b-lactamase by bacteria that alters the structure of b-lactams so they cannot bind PBPs)
Spectrum: “* Above + Limited GN (E coli, Proteus, H pylori)
* DOC Enterococcus
* Listeria monocytogenes”
PK:“*Oral drugs do not achieve same conc as IV
* Short half-life, time-dependent manner
* Most are renally eliminated (Except Nafcillin/oxacillin)”
Side Effects/AEs:” * HS: Penicillins > cephalosporins > carbapenems
* Crossreactivity (from side chains) w cephalosporins decreases with increasing generation/structure changes
* GI: upset stomach PO
* Seizures: Greatest w carbapenems (imipenem)
Bone marrow suppression (long term use)”
Extra Notes:
Resistance: “B-lactamases (MDR-AB/PA, MRSA)
- Penicillinases
- Extended-spect B-Lactamases (ESBLs - penicillins, cephalosporins, monobactam)
- Carbapenemases (penicillins, cephalosporins, monobactam AND carbapenems)
*Alteration of PBPs (MRSA, MDR-AB)”
Antibiotics - Cell Wall & Membrane Active Antibiotics
PENICILLINS
MOA:Binds bacteria’s PBPs (transpeptidase) preventing crosslinking of AAs in cell wall synthesis (resistance develops by production of b-lactamase by bacteria that alters the structure of b-lactams so they cannot bind PBPs)
Spectrum: “* Above + broader GN
Pseudomonas (when combined w tazobactam)”
PK: “Oral drugs do not achieve same conc as IV
* Short half-life, time-dependent manner
* Most are renally eliminated (Except Nafcillin/oxacillin)”
Side Effects/AEs:” * HS: Penicillins > cephalosporins > carbapenems
* Crossreactivity (from side chains) w cephalosporins decreases with increasing generation/structure changes
* GI: upset stomach PO
* Seizures: Greatest w carbapenems (imipenem)
Bone marrow suppression (long term use)”
Extra Notes:
Resistance: “B-lactamases (MDR-AB/PA, MRSA)
- Penicillinases
- Extended-spect B-Lactamases (ESBLs - penicillins, cephalosporins, monobactam)
- Carbapenemases (penicillins, cephalosporins, monobactam AND carbapenems)
*Alteration of PBPs (MRSA, MDR-AB)”
Antibiotics - Cell Wall & Membrane Active Antibiotics
PENICILLINS
MOA:Binds bacteria’s PBPs (transpeptidase) preventing crosslinking of AAs in cell wall synthesis (resistance develops by production of b-lactamase by bacteria that alters the structure of b-lactams so they cannot bind PBPs)
Spectrum: “*Staphylococcus + Strep
* NO Enterococcus or GN
MSSA “
PK: “Oral drugs do not achieve same conc as IV
* Short half-life, time-dependent manner
* Most are renally eliminated (Except Nafcillin/oxacillin)”
Side Effects/AEs:” * HS: Penicillins > cephalosporins > carbapenems
* Crossreactivity (from side chains) w cephalosporins decreases with increasing generation/structure changes
* GI: upset stomach PO
* Seizures: Greatest w carbapenems (imipenem)
Bone marrow suppression (long term use)”
Extra Notes: * Bulky side chain prevents it from being inactivated by beta-lactamases
Resistance: “B-lactamases (MDR-AB/PA, MRSA)
- Penicillinases
- Extended-spect B-Lactamases (ESBLs - penicillins, cephalosporins, monobactam)
- Carbapenemases (penicillins, cephalosporins, monobactam AND carbapenems)
*Alteration of PBPs (MRSA, MDR-AB)”
Antibiotics - Cell Wall & Membrane Active Antibiotics
PENICILLINS
MOA:Binds bacteria’s PBPs (transpeptidase) preventing crosslinking of AAs in cell wall synthesis (resistance develops by production of b-lactamase by bacteria that alters the structure of b-lactams so they cannot bind PBPs)
Spectrum: Targets those that produce b-lactamases including S aureus, B fragilis
PK:“*Oral drugs do not achieve same conc as IV
* Short half-life, time-dependent manner
* Most are renally eliminated (Except Nafcillin/oxacillin)”
Side Effects/AEs:” * HS: Penicillins > cephalosporins > carbapenems
* Crossreactivity (from side chains) w cephalosporins decreases with increasing generation/structure changes
* GI: upset stomach PO
* Seizures: Greatest w carbapenems (imipenem)
Bone marrow suppression (long term use)”
Extra Notes:
Resistance: “B-lactamases (MDR-AB/PA, MRSA)
- Penicillinases
- Extended-spect B-Lactamases (ESBLs - penicillins, cephalosporins, monobactam)
- Carbapenemases (penicillins, cephalosporins, monobactam AND carbapenems)
*Alteration of PBPs (MRSA, MDR-AB)”
Antibiotics - Cell Wall & Membrane Active Antibiotics
PENICILLINS
MOA:Binds bacteria’s PBPs (transpeptidase) preventing crosslinking of AAs in cell wall synthesis (resistance develops by production of b-lactamase by bacteria that alters the structure of b-lactams so they cannot bind PBPs)
Spectrum: “* Streptococcus spp
MSSA
Little GN “
PK: * Renally excreted (Excetp ceftriaxone, which is primarily biliary)
Side Effects/AEs:” * HS: Penicillins > cephalosporins > carbapenems
* Crossreactivity (from side chains) w cephalosporins decreases with increasing generation/structure changes
* GI: upset stomach PO
* Seizures: Greatest w carbapenems (imipenem)
*Bone marrow suppression (long term use)”
Extra Notes: “ Various generations that increase in GN coverage and decrease in GP coverage over time
* NO Enterococcal or anaerobic activity
* 4/5th generations have strong GP & GN”
Resistance: “B-lactamases (MDR-AB/PA, MRSA)
- Penicillinases
- Extended-spect B-Lactamases (ESBLs - penicillins, cephalosporins, monobactam)
- Carbapenemases (penicillins, cephalosporins, monobactam AND carbapenems)
*Alteration of PBPs (MRSA, MDR-AB)”
Antibiotics - Cell Wall & Membrane Active Antibiotics
CEPHALOSPORINS
MOA:Binds bacteria’s PBPs (transpeptidase) preventing crosslinking of AAs in cell wall synthesis (resistance develops by production of b-lactamase by bacteria that alters the structure of b-lactams so they cannot bind PBPs)
Spectrum: * Anaerobic coverage
PK:* Renally excreted (Excetp ceftriaxone, which is primarily biliary)
Side Effects/AEs:” * HS: Penicillins > cephalosporins > carbapenems
* Crossreactivity (from side chains) w cephalosporins decreases with increasing generation/structure changes
* GI: upset stomach PO
* Seizures: Greatest w carbapenems (imipenem)
Bone marrow suppression (long term use)”
Extra Notes:
“ Various generations that increase in GN coverage and decrease in GP coverage over time
* NO Enterococcal or anaerobic activity
* 4/5th generations have strong GP & GN”
Resistance: “*B-lactamases (MDR-AB/PA, MRSA)
- Penicillinases
- Extended-spect B-Lactamases (ESBLs - penicillins, cephalosporins, monobactam)
- Carbapenemases (penicillins, cephalosporins, monobactam AND carbapenems)
*Alteration of PBPs (MRSA, MDR-AB)”
Antibiotics - Cell Wall & Membrane Active Antibiotics
CEPHALOSPORINS
MOA:Binds bacteria’s PBPs (transpeptidase) preventing crosslinking of AAs in cell wall synthesis (resistance develops by production of b-lactamase by bacteria that alters the structure of b-lactams so they cannot bind PBPs)
Spectrum: “No anaerobic
* GP (Streptococcus, MSSA)
LFGN (E coli, K pneumoniae)
Ceftriaxone - Good GP, No Pseudomonas
Ceftazidine - Unreliable GP, Pseudomonas”
PK: biliary excretion
Side Effects/AEs:” * HS: Penicillins > cephalosporins > carbapenems
* Crossreactivity (from side chains) w cephalosporins decreases with increasing generation/structure changes
* GI: upset stomach PO
* Seizures: Greatest w carbapenems (imipenem)
*Bone marrow suppression (long term use)”
Extra Notes: “ Various generations that increase in GN coverage and decrease in GP coverage over time
* NO Enterococcal or anaerobic activity
* 4/5th generations have strong GP & GN”
Resistance: “B-lactamases (MDR-AB/PA, MRSA)
- Penicillinases
- Extended-spect B-Lactamases (ESBLs - penicillins, cephalosporins, monobactam)
- Carbapenemases (penicillins, cephalosporins, monobactam AND carbapenems)
*Alteration of PBPs (MRSA, MDR-AB)”
Antibiotics - Cell Wall & Membrane Active Antibiotics
CEPHALOSPORINS
MOA:Binds bacteria’s PBPs (transpeptidase) preventing crosslinking of AAs in cell wall synthesis (resistance develops by production of b-lactamase by bacteria that alters the structure of b-lactams so they cannot bind PBPs)
Spectrum: “Pseudomonas (Ceftazidine)
* GP (Ceftriaxone)”
PK: “Pseudomonas (Ceftazidine)
* GP (Ceftriaxone)”
Side Effects/AEs:” * HS: Penicillins > cephalosporins > carbapenems
* Crossreactivity (from side chains) w cephalosporins decreases with increasing generation/structure changes
* GI: upset stomach PO
* Seizures: Greatest w carbapenems (imipenem)
Bone marrow suppression (long term use)”
Extra Notes:” Various generations that increase in GN coverage and decrease in GP coverage over time
* NO Enterococcal or anaerobic activity
* 4/5th generations have strong GP & GN”
Resistance: “*B-lactamases (MDR-AB/PA, MRSA)
- Penicillinases
- Extended-spect B-Lactamases (ESBLs - penicillins, cephalosporins, monobactam)
- Carbapenemases (penicillins, cephalosporins, monobactam AND carbapenems)
*Alteration of PBPs (MRSA, MDR-AB)”
Antibiotics - Cell Wall & Membrane Active Antibiotics
CEPHALOSPORINS
MOA:Binds bacteria’s PBPs (transpeptidase) preventing crosslinking of AAs in cell wall synthesis (resistance develops by production of b-lactamase by bacteria that alters the structure of b-lactams so they cannot bind PBPs)
Spectrum: MRSA (only b-lactam)
PK: * Renally excreted (Excetp ceftriaxone, which is primarily biliary)
Side Effects/AEs:” * HS: Penicillins > cephalosporins > carbapenems
* Crossreactivity (from side chains) w cephalosporins decreases with increasing generation/structure changes
* GI: upset stomach PO
* Seizures: Greatest w carbapenems (imipenem)
Bone marrow suppression (long term use)”
Extra Notes: “ Various generations that increase in GN coverage and decrease in GP coverage over time
* NO Enterococcal or anaerobic activity
* 4/5th generations have strong GP & GN”
Resistance: “B-lactamases (MDR-AB/PA, MRSA)
- Penicillinases
- Extended-spect B-Lactamases (ESBLs - penicillins, cephalosporins, monobactam)
- Carbapenemases (penicillins, cephalosporins, monobactam AND carbapenems)
*Alteration of PBPs (MRSA, MDR-AB)”
Antibiotics - Cell Wall & Membrane Active Antibiotics
CEPHALOSPORINS
MOA:Binds bacteria’s PBPs (transpeptidase) preventing crosslinking of AAs in cell wall synthesis (resistance develops by production of b-lactamase by bacteria that alters the structure of b-lactams so they cannot bind PBPs)
Spectrum: “*GN only
*Pseudomonas
*Mainly used in pts with severe IgE mediated HS to other b-lactams (different structure)”
PK:
Side Effects/AEs:” * HS: Penicillins > cephalosporins > carbapenems
* Crossreactivity (from side chains) w cephalosporins decreases with increasing generation/structure changes
* GI: upset stomach PO
* Seizures: Greatest w carbapenems (imipenem)
Bone marrow suppression (long term use)”
Extra Notes:
Resistance: “B-lactamases (MDR-AB/PA, MRSA)
- Penicillinases
- Extended-spect B-Lactamases (ESBLs - penicillins, cephalosporins, monobactam)
- Carbapenemases (penicillins, cephalosporins, monobactam AND carbapenems)
*Alteration of PBPs (MRSA, MDR-AB)”
Antibiotics - Cell Wall & Membrane Active Antibiotics
MONOBACTAMS
MOA:Binds bacteria’s PBPs (transpeptidase) preventing crosslinking of AAs in cell wall synthesis (resistance develops by production of b-lactamase by bacteria that alters the structure of b-lactams so they cannot bind PBPs)
Spectrum: “*VERY broad GP, GN, anaerobes (no MRSA)
*Pseudomonas (except ertapenem)”
PK:
Side Effects/AEs:” * HS: Penicillins > cephalosporins > carbapenems
* Crossreactivity (from side chains) w cephalosporins decreases with increasing generation/structure changes
* GI: upset stomach PO
* Seizures: Greatest w carbapenems (imipenem)
Bone marrow suppression (long term use)”
Extra Notes:
Resistance: “ Carbapenemases (CRE, MDR-AB/PA)
*Alteration of PBPs (MRSA, MDR-AB)
*Reduced porins (MDR-AB/PA)”
Antibiotics - Cell Wall & Membrane Active Antibiotics
Carbapenems
MOA: Binds D-Ala-D-Ala chain terminus of peptidoglycan toweaken cell wall, inhibiting cell wall synthesis
Spectrum: “* GP (Staphylococcus, Enterococcus, Streptococcus)
MRSA
* Oral for C. diff only”
PK:
Side Effects/AEs: “ Nephrotoxic (increased risk w concomitant meds)
* Red Man’s Syndrome: NOT an allergy, but is histamine mediated (slow infusion to prevent rxn)”
Extra Notes: “*D-Ala-D-Lac insertion into peptidoglycan (VRE, VRSA)
*Thicker/altered peptidoglycan (VISA, h-VISA)
Resistance:
Antibiotics - Cell Wall & Membrane Active Antibiotics
MOA: Binds bacterial membrane causing depolarization of cell -> leakage of contents -> cell death
Spectrum: “*GP agent
*MRSA + VRE
* NOT used to tx pneumonia (lung surfactant inactivates it)”
PK:
Side Effects/AEs: * Cr kinase elevation –> myalgia/myopathy & rarely rhabdomyolysis (muscle destruction)
Extra Notes:
Resistance:
Antibiotics - Cell Wall & Membrane Active Antibiotics
MOA: Protein synthesis inhibitor; binds 30S subunit preventing tRNA binding –> inhibits addition of AA to growing chain
Spectrum: “* S aureus + MRSA
*GN (no Pseudomonas)
Atypicals (chlamydia), Rickettsiae, Borrelia”
PK:
Side Effects/AEs: “ Photosensitivity
* Esophageal ulcerations
* GI intolerance
* Slows bone growth in fetus up to 8 yo (contraindicated in pregnant women)
* Tooth discoloration of those < 8 yo”
Extra Notes:
Resistance:
*Expression of protein that interferes with drug binding 30S ribosome target (MDR-AB)
*Expression of efflux pumps (MDR-AB/PA)”
Antibiotics - Inhibitors of Bacterial Protein Synthesis
MOA: Tetracycline mechanism (structurally similar, but more sturdy). Protein synthesis inhibitor; binds 30S subunit preventing tRNA binding –> inhibits addition of AA to growing chain
Spectrum: “VERY broad
GP (MRSA + VRE)
* GN (no Pseudomonas)
* Anaerobes”
PK:
Side Effects/AEs: “Severe vomiting
*Pancreatitis/hepatitis”
Extra Notes:
Resistance:
Antibiotics - Inhibitors of Bacterial Protein Synthesis
MOA: Protein synthesis inhibitor; Reversibly binds 50S subunit inhibiting transpeptidation/translocation, preventing cell growth
Spectrum: “Atypicals (chlamydia, mycoplasma, legionella with azithro)
Non-TB mycobacteria (clarithro)”
PK:
Side Effects/AEs: “ GI upset, liver impairment
* QTc prolongation
* Erythromycin only used to aid with gut motility due to its strong GI effect”
Extra Notes: “Commonly used for STDs
*Was used often for Streptococcus pneumoniae (now resistant & NOT commonly used)”
Resistance:
Antibiotics - Inhibitors of Bacterial Protein Synthesis
MOA: Binds 50S subunit
Spectrum: “GP + MRSA
Anaerobic GPs”
PK:
Side Effects/AEs: “ Main cause of C. diff diarrhea (targets all GP anaerobes besides C diff –> C diff overgrowth)
* Anti-toxin effect for GAS infections
* upper infections”
Extra Notes: “Main tx for PCP pneumonia
*LOTS of resistance to this & only used if susceptibility results indicate that it is susceptible”
Resistance:
Antibiotics - Inhibitors of Bacterial Protein Synthesis
MOA: Protein synthesis inhibitor; binds 50S subunit to prevent initiation of protein synthesis
Spectrum: “*GP agent
MRSA + VRE”
PK:
Side Effects/AEs: “ Myelosuppression –> Thrombocytopenia (low plt) after 2 wk with long term usage; requires monitoring plt every week (not good for those with cancer chemotherapies)
* Serotonin syndrome: if combined with other serotonergic agents (SSRIs, MAOIs, some pain meds) –> increased levels of serotonin to be released (ONLY antibiotic that does this)”
Extra Notes:
Resistance:
Antibiotics - Inhibitors of Bacterial Protein Synthesis
MOA: Irreversibly binds 30S ribosomal subunit preventing protein synthesis initiation –> premature termination of protein synthesis
Spectrum: “GN
Pseudomonas (Amikacin > Tobra > Genta)”
PK:
Side Effects/AEs: “High toxicity
Nephrotoxicity: acute tubular necrosis; reversible
*Ototoxicity: auditory & vestibular; IRREVERSIBLE
*Post-abx effect: must monitor serum conc with trough levels”
Extra Notes: “Amikacin is IV only
Resistance: Aminoglycoside modifying enzymes (AMEs) (MDR-AB/PA)
* Modification of rRNA”
Antibiotics - Inhibitors of Bacterial Protein Synthesis
MOA: Inhibits bacterial folic acid synthesis (sulfamethoxazole - dihydropteroate synthase, trimeth - DHT reductase)
Spectrum: “S aureus + MRSA
GN (no Pseudomonas)
* Fungus - Pneumocystis carinii (pneumonia)”
PK: “ HS skin rxns (bactrim & b-lactams most commonly cause these)
* Nephrotoxicity (crystalluria)”
Side Effects/AEs:
Extra Notes:
Resistance: Mutation of target DHR (MDR-AB)
Antibiotics - Other
MOA: Binds DNA gyrase (topoisomerase II) and topoisomerase IV (DNA repair) –> inhibition of DNA synthesis in bacteria
Spectrum: “BROAD spectrum, but lots of bacteria have developed resistance to them
Pseudomonas”
PK: *Oral bioavailability is similar to that of IV
Side Effects/AEs: “ GI: Nausea, C difficile
* MS: Tendonitis, tendon rupture (elderly), muscle weakness
* Peripheral neuropathy (long term use)
* Cardiac: QTc prolongation**”
Extra Notes:
Resistance:
* Mutations to DNA gyrase or topoisomerase (MDR-AB/PA)
Antibiotics - Other
MOA: Disrupts energy metabolism of bacteria by stopping DNA replication/transcription
Spectrum: Anaerobes ONLY (No E coli, Pseudomonas, MRSA) - belly-down infections (mostly GI)
PK:
Side Effects/AEs: “Metallic taste
*Peripheral neuropathy with long term use
*disulfiram-like rxn with alcohol”
Extra Notes:
Resistance:
Antibiotics - Other
MOA: Binds ergosterol –> alters cell membrane permeability –> leakage of cell components
Spectrum: Yeasts:
Candida species (e.g., Candida albicans, Candida glabrata)
Cryptococcus neoformans
Molds:
Aspergillus species
Mucorales (e.g., Rhizopus, Mucor)
Dimorphic Fungi:
Blastomyces dermatitidis
Histoplasma capsulatum
Coccidioides immitis
Other Fungi:
Sporothrix schenckii (causative agent of sporotrichosis)
Penicillium marneffei (causative agent of penicilliosis)
PK: Binds ergosterol –> alters cell membrane permeability –> leakage of cell components
Side Effects/AEs: “*Nephrotoxic (damage of distal tubules)
- Amp B deoxycholate: MOST
- Amp B liposomal: LEAST
* Hypo-K/Mg/Ca (give fluids & electrolytes daily)
* Infusion related rxns (may require premed or slowed infusion rate)”
Extra Notes:
Resistance:
Antifungals
MOA: Pyrimidine analog; penetrates fungal cells and converted to fluorouracil that competes with uracil –> intereferes with fungal RNA/protein synthesis
Spectrum: “Cryptococcal meningitis + Candida (resistance develops rapidly)
*4x daily (short half-life)
* TDM monitoring (70-80 mcg/mL)”
PK: Dose adjustment w renal dysfunction
Side Effects/AEs: “ GI
*Leukopenia/thrombocytopenia
* Hepatotoxic
*Aplastic anemia
* Photosensitivity
*increased risk of bone marrow suppression with other immunosuppressive agents”
Extra Notes:
Resistance:
Antifungals
MOA: Inhibits fungal CYP450 (lanosterol 14-alpha-demethlase) -> decreased ergosterol synthesis -> inhibition of cell membrane formation
Spectrum: Candida albicans (NOT crucii), Coccidioides, Cryptococcus
PK: PO = excellent bioavailability
Side Effects/AEs: “ LFT elevations (long term use > 1 wk)
* QTc prolongation
* GI upset
* DDIs (CYP3A4 inhibitor -> higher levels of substrates such as immunosuppressants, warfarin, statins, etc.)”
Extra Notes:
Resistance:
Antifungals - Azoles
PO + IV
MOA: Inhibits fungal CYP450 (lanosterol 14-alpha-demethlase) -> decreased ergosterol synthesis -> inhibition of cell membrane formation
Spectrum: Candida albicans (NOT crucii), Coccidioides, Cryptococcus, Aspergillus, Histoplasmosis, Blastomycosis
PK: “*Poor CNS penetration
*Capsules taken w acidic beverage
Susp taken at any time”
Side Effects/AEs: “ LFT elevations (long term use > 1 wk)
* QTc prolongation
* GI upset
* DDIs (CYP3A4 inhibitor -> higher levels of substrates such as immunosuppressants, warfarin, statins, etc.)”
Extra Notes:
Resistance:
Antifungals - Azoles
PO + IV
MOA: Inhibits fungal CYP450 (lanosterol 14-alpha-demethlase) -> decreased ergosterol synthesis -> inhibition of cell membrane formation
Spectrum: Candida, Aspergillus, Fusarium, Cryptococcus, Blastomyces, Coccidioides, Histoplasma, Sporothrix
PK: “*Poor CNS penetration
*CNS toxicity (hallucinations)
*Requires TDM (2-5 mcg/mL)
IV w renal dysfunction –> cyclodextrin (what its made with) accumulation”
Side Effects/AEs:
visual disturbances
“ LFT elevations (long term use > 1 wk)
* QTc prolongation
* GI upset
* DDIs (CYP3A4 inhibitor -> higher levels of substrates such as immunosuppressants, warfarin, statins, etc.)”
Extra Notes:
Resistance:
Antifungals - Azoles
PO + IV
MOA: Inhibits fungal CYP450 (lanosterol 14-alpha-demethlase) -> decreased ergosterol synthesis -> inhibition of cell membrane formation
Spectrum: Candida, Aspergillus, Fusarium, Cryptococcus, Blastomyces, Coccidioides, Histoplasma, Mucormycosis
PK: “* Susp taken w acidic beverage
Tablets at any time
* Requries TDM (> 0.7-1 mcg/mL)”
Side Effects/AEs: “ LFT elevations (long term use > 1 wk)
* QTc prolongation
* GI upset
* DDIs (CYP3A4 inhibitor -> higher levels of substrates such as immunosuppressants, warfarin, statins, etc.)”
Extra Notes:
Resistance:
Antifungals - Azoles
PO + IV
MOA: Inhibits fungal CYP450 (lanosterol 14-alpha-demethlase) -> decreased ergosterol synthesis -> inhibition of cell membrane formation
Spectrum: Candida (NOT IDEAL), Aspergillus, Fusarium, Cryptococcus, Blastomyces, Coccidioides, Histoplasma, Mucormycosis, Sporothrix
PK: * No TDM required
Side Effects/AEs: “* LFT elevations (long term use > 1 wk)
* NO QTc prolongation (all other azoles do) may be QTc shortening even
* GI upset
* DDIs (CYP3A4 inhibitor -> higher levels of substrates such as immunosuppressants, warfarin, statins, etc.)”
Extra Notes:
Resistance:
Antifungals - Azoles
PO + IV
MOA: Inhibits synthesis of b-(1,3)-D-glucan –> reduced formation of polysaccharide in cell walls –> osmotic instability & cell lysis
Spectrum: “* Candida & salvage therapy for Aspergillus
* All IV only (No PO forms)
* Works well against biofilms
Fungicidal against Candida”
PK: “ NO CNS penetration
*High protein binding (daily dosing)”
LD + daily dosing, no LD for micafungin
Side Effects/AEs: “* LFT elevation
* Mild infusion site rxn”
DDI w immunosuppressants
Extra Notes:
Resistance:
Antifungals - ECHINOCANDINS
MOA: Inhibits NA preventing release of virions from plasma membranes
Spectrum:
PK: PO (cap or susp) BID for 5 days, daily for 10 days if ppx, renal dose adjustments
Side Effects/AEs: “*GI disturbance
Insomnia
* Vertigo
* Neuropsychiatric events”
Extra Notes: “ Resistance possible, but NOT tested
* Tx started within 48 hr of symptoms for benefit”
Resistance:
Antivirals - Influenza
MOA: Inhibits NA preventing release of virions from plasma membranes
Spectrum:
PK: Inhaled BID for 5 days, daily for 10 days if ppx
Side Effects/AEs: “*GI disturbance
Insomnia
* Vertigo
* Neuropsychiatric events”
* Bronchospasm (inhaled)
Extra Notes: “ Resistance possible, but NOT tested
* Tx started within 48 hr of symptoms for benefit”
Resistance:
Antifungals
MOA: Inhibits NA preventing release of virions from plasma membranes
Spectrum: IV, very expensive, only for use in critically ill, once daily
PK: renal dose adjustments
Side Effects/AEs: “*Hyperglycemia
*LFT/CPK elevations
SJS”
Extra Notes: “ Resistance possible, but NOT tested
* Tx started within 48 hr of symptoms for benefit”
Resistance:
Antivirals - Influenza
MOA: Prodrug hydrolyzed to baloxavir –> inhibits replication by interfering w “cap snatching” in which virus hijacks host mRNA transcription system) & inhibits endonuclease activity of selective pol acidic protein required for viral gene transcription
Spectrum:
PK: Tablets or susp once daily
Side Effects/AEs:
Extra Notes:
Resistance:
Antivirals - Influenza
MOA:
Spectrum: Influ A only
PK:
Side Effects/AEs:
Extra Notes:
Resistance:
Antivirals - Influenza
MOA: Converted to acyclovir-triP by viral TK then host enzymes –> inhibits viral DNA synthesis by competing with deoxyguanoside triP for incorporation into viral DNA –> termination of viral replication
Spectrum: (VZV/HSV)
PK: IV + PO (poor bioavailability) 3-5x daily, renal dose adjustments (weight based)
Side Effects/AEs: “*GI upset
* Neurotoxic
*LFT elevations (longer term > 1 wk)
* Avoid in pts with AKI (crystalluria)”
Extra Notes:
Resistance: Resistance due to viral mutants deficient in TK or reduced affinity of TK for acyclovir-triP
Antivirals - Herpesviridae (HSV, VZV)
MOA: Prodrug –> acyclovir
Spectrum:(VZV/HSV)
PK: PO (better bioavailability) 2-3x daily –> preferred over acyclovir! renal dose adjustments (weight based)
Side Effects/AEs: “*GI upset
* Neurotoxic
*LFT elevations (longer term > 1 wk)
* Avoid in pts with AKI (crystalluria)”
Extra Notes: * Resistance due to viral mutants deficient in TK or reduced affinity of TK for acyclovir-triP
Resistance:
Antivirals - Herpesviridae (HSV, VZV)
MOA: Viral TK then host enzymes phosphorylate drug –> triphosphate form that competes with deoxyguanosine triphosphate –> inhibition of DNA pol –> termination of viral replication
Spectrum: (HSV only)
PK: Topical (poor PO bioavailability), q2h for 4 days
Side Effects/AEs: “*Headache
* GI upset”
Extra Notes:
Resistance:
Antivirals - Herpesviridae (HSV, VZV)
MOA: Prodrug –> penciclovir
Spectrum: (VZV/HSV)
PK: PO only (better bioavailability), 2-3x daily
Side Effects/AEs: “*Headache
* GI upset”
Extra Notes:
Resistance:
Antivirals - Herpesviridae (HSV, VZV)
MOA: Activated through triphosphorylation by host UL97 + kinases –> incorporated into host DNA (guanine analog)
Spectrum: (CMV & some HSV activity if worried about both)
PK: IV only (PO poor bioavailability)
* Induction period of 2-3 wk to lower VL, then lower MD (less toxicity)
Side Effects/AEs:
“*Cytopenias (granulocytopenia)
*GI upset (more with oral)
* rash
* increased LFT
*neurotoxicity
* Bone marrow suppression –> cytopenia (granulocytopenia)”
Extra Notes:
Resistance:
* Resistance due to mutation in UL97 (encodes DNA Pol)
Antivirals - Herpesviridae (CMV)
MOA: Prodrug –> ganciclovir
Spectrum: (CMV)
PK: PO only (great bioavailability)
* Induction period of 2-3 wk to lower VL, then lower MD (less toxicity)
Side Effects/AEs:
“*Cytopenias (granulocytopenia)
*GI upset (more with oral)
* rash
* increased LFT
*neurotoxicity
* Bone marrow suppression –> cytopenia (granulocytopenia)”
Extra Notes:
Resistance:
* Resistance due to mutation in UL97 (encodes DNA Pol)
Antivirals - Herpesviridae (CMV)
MOA: Inhibits pyrophosphate binding on DNA pol –> inhibits DNA chain elongation (greater affinity for viral DNA Pol > host cell); does NOT require TK/intracellular activation
Spectrum: CMV
PK: “*Confusing dose adjustments
Induction period of 2-3 wk to lower VL, then lower MD”
Side Effects/AEs: “Nephrotoxic
*Myelosuppression (anemia)
* Hypocalcemia, -kalemia, -phsophatemia, - magnesemia (hydration/electrolytes) “
Extra Notes:
Resistance:
* Resistance due to UL54 mutations
Antivirals - Herpesviridae (CMV)
MOA: Nucleotide analong that is converted to cidofovir diP by host enzymes –> incorporated into viral DNA –> inhibition of DNA Pol
Spectrum: (CMV)
PK: “* Short half-life –> prolonged when administered with probenecid (reduces renal excretion)
* Induction period of 2-3 wk to lower VL, then lower MD”
Side Effects/AEs: “*Nephrotoxic
*Myelosuppression
* Ocular hypotony, uveitis, iritis”
Extra Notes:
Resistance:
Antivirals - Herpesviridae (CMV)
MOA: Inhibits CMV terminase complex –> No functional CMV DNA
Spectrum: (CMV ppx)
PK: “Used in HSCT
* IV/PO daily 100 days”
Side Effects/AEs: “GI upset
*Headache
*Peripheral edema
*DDIs”
Extra Notes:
* Active against UL97 mutations
Resistance:
Antivirals - Herpesviridae (CMV)
MOA: Inhibits mycolic acid/cell wall synthesis (active against actively replicating organisms in all tissues)
Spectrum: “Oral
TB & LTBI (alone or w RIF)”
PK: Hepatic (few DDIs)
Side Effects/AEs: “ Heptatitis (age, alcohol)
* Peripheral neuropathy (Vit B6 helps)
* Rash
* Lupus-like
*CNS effects (alt mental status, seizures)”
Extra Notes: KatG, inh
Resistance:
TB drugs
MOA: Inhibits protein synthesis (bactericidal for actively replicating, active at all sites)
Spectrum: “Oral & IV
TB & LTBI (alone or w INH)”
PK: * Hepatic
Side Effects/AEs: “* Orange staining (urine, tears, etc.)
* Rash, itchy
* Flu-like syndrome
* Hepatitis (less common than in INH & PZA)
* Thrombocytopenia
* CYP450 inducer –> dec conc of drugs”
Extra Notes:
Resistance:
TB drugs
MOA: Not understood (shortens tx course)
Spectrum: Oral
PK: * Hepatic/renal
Side Effects/AEs: “* Hepatitis (increased risk w INH/RIF)
* Uric acid/gout
* GI symptoms
*Photosensitivity”
Extra Notes: pnc, BCG resistant
Resistance:
TB drugs
MOA: Inhibits cell wall synthesis (bacteriostatic)
Spectrum: Oral (poor CNS penetration)
PK: * Renal
Side Effects/AEs: “* Retrobulbar/optic neuritis (dose dep)
* Rare rash
* rare peripheral neuropathy”
Extra Notes: embB gene cluster
Resistance:
TB drugs
Unique bug and drug combosbug a
