Term
| Aminoglycosides: General Mechanism of Action |
|
Definition
Binds 30S ribosomal subunit
BacteriCIDAL (except against enterococcus)
Concentration dependant |
|
|
Term
| Aminoglycosides: Spectrum of Activity |
|
Definition
G(+): Activity against Staph and Strep (but only used for synergy)
Synergy with B-Lactam expands spectrum to enterococcus
G(-): Active against many
Pseudomonas coverage
Anaerobes: None! (MOA requires O2) |
|
|
Term
| Aminoglycosides: Clinical Uses |
|
Definition
Gram (+): Only in series infections for synergy (B-lactam disrupts cell walls to allow more AMG to enter)
Gram (-): Should be avoided as definitive monotherapy
(Except for UTIs) |
|
|
Term
| Aminoglycosides: Pharmacokinetics |
|
Definition
Poor oral absorption
Hydrophilic (poor tissue concentration)
Highly concentrated in Urine (UTIs)
Requires Renal Dosing |
|
|
Term
| Aminoglycosides: Adverse Effects |
|
Definition
Nephotoxicity: Most common and most serious
Ototoxicity
(Both related to trough concentrations)
NM Blockade: Exacerbates Myasthenia Gravis (MG) |
|
|
Term
| Gentamicin: Drug Class and Clinical Use |
|
Definition
Aminoglycoside (AMG)
Synergy with B-Lactams: Serious Staph and Enterococcus infections
IV Formulation
Eye Ointment |
|
|
Term
| Tobramycin: Drug Class and Clinical Use |
|
Definition
Aminoglycoside (AMG)
Combined with Amikacin (AMG): Emperic coverage of Nosocomial Infections (possible definitive therapy)
IV Formulation
Eye Ointment |
|
|
Term
| Amikacin: Drug Class and Clinical Use |
|
Definition
Aminoglycoside (AMG)
Combined with Tobramycin (AMG): Emperic coverage of Nosocomial Infections (possible definitive therapy)
Some Mycobacterial infections
IV Formulation |
|
|
Term
| Streptomycin: Drug Class and Clinical Use |
|
Definition
Aminoglycoside (AMG)
Synergy with B-Lactams: Enterococcal infections with resistance to Gentamicin
Mycobacterial Infections
IV Formulation |
|
|
Term
| Neomycin: Drug Class and Clinical Use |
|
Definition
Aminoglycoside (AMG)
Decontamination of GI Tract prior to surgery
Topical Cream (Neosporin)
PO/Topical |
|
|
Term
| Azoles: General Mechanism of Action |
|
Definition
Inhibit production of Ergosterol (key component in fungal cell membrane)
Inhibition via blocking a fungal CYP450 Enzyme (specific for fungus, but can also inhibit human cyp450) |
|
|
Term
| Azoles: General spectrum of Activity |
|
Definition
-Candida Species (excellent for Albicans, variable for glabrata)
-Cryptococcus neoformans
-Endemic Fungi
-Some dermatophytes (not mainstay of therapy)
-Aspergillus
-Mucormycoses |
|
|
Term
| Azoles: Pharmokinetics (Absorption, metabolism, and Excretion) |
|
Definition
Absorption: Highly bioavailable (IV=PO)
Therapeutic drug monitoring for dose adjustment
Metabolism: CYP450 system (DDI's)
Excretion: Only Fluconazole requires renal dosing |
|
|
Term
|
Definition
Hepatotoxicity: Main issue, need to monitor LFTs
Others based on individual drug (Voriconazole especially) |
|
|
Term
| Azoles: Drug-Drug Interactions |
|
Definition
Always check concomitant drugs!
Notable DDIs: HIV medications,
Calcineurin inhibitors (cyclosporine, tacrolimus)
Anticonvulsants
Rifampin |
|
|
Term
| Fluconazole: Spectrum of Activity and Clinical Use |
|
Definition
Azole
No activity for: Glabrata, Endemic Fungi, Aspergillus, and Mucormycoses
Empiric Antifungal treatment: Candida Infections
Only Azole which needs to be Renally dosed |
|
|
Term
| Itraconazole: Spectrum of Activity and Clinical Use |
|
Definition
Azole
No activity for Mucormycoses
DOC for Non-Life Threatening cases of endemic mycoses
Can also be used for Aspergillus
DDI's with Voriconazole |
|
|
Term
| Voriconazole: Spectrum of Activity and Clinical Use |
|
Definition
Azole
No activity for Mucormycoses
DOC for Aspergillus
SE: Nephrotoxicity (IV Only)
Visual Disturbances: concentration related
DDI's with Itraconazole |
|
|
Term
| Posaconazole: Spectrum of Activity and Clinical Use |
|
Definition
Azole
Use for Mucormycoses.
Some prophylaxix regimens, also used for Aspergillus
Requires High Fatty Meals for absorption |
|
|
Term
| Amphotericin B: Mechanism of Action and Spectrum of Activity |
|
Definition
Drug Class: Polyene
Binds to Ergosterol and forms pores that allow molecules to leak in/out of cells
--> Results in Cell Death
Activity against: -Candida spp (includes Glabrata, but NO Lusitaniae)
-Cryptococcus Neoformans
-Endemic Fungi
-Aspergillus
-Mucormycoses |
|
|
Term
| Amphotericin B: Clinical Use and Adverse Effects |
|
Definition
DOC for Cryptopcoccus Neoformans
DOC for Life threatening endemic Mycoses
DOC for Mucormycoses
Aspergillus (second line)
Oddball fungi
SE: Nephrotoxicity: puts holes in renal cell walls (>20%, dose-dependent, usually reversible, Electrolyte abnormalities, and renal tubular acidosis)
Infusion Reactions Hepatotoxicity
Now use Lipid formulations, less toxic (no deoxycholate) |
|
|
Term
| Echinocandins: Drug names and Mechanism of Action |
|
Definition
Capsofungin
Micafungin
Anidulafungin
Inhibits production of 1-3-B-D-Glucan, key component of SOME fungal cell walls
Inhibits the 1-3-B-D glucan synthase enzyme |
|
|
Term
| Echinocandins: Spectrum of Activity and Clinical Use |
|
Definition
DOC for Candida glabrata (NOT C. parapsilosis) (definitive and empiric)
Aspergillus: Combination or Prophylaxis. Monotherapy only when patients can't tolerate Voriconzole or Amphotericin
IV Only, NOT Renally eliminated (Can't use for UTIs)
Very well tolerated, Hepatotoxicity rare. |
|
|
Term
| Flucytosine: Mechanism of Action and Clinical Use |
|
Definition
Converted by fungal cells to 5-FU, and then to other products to Inhibit DNR/RNA synthesis
SoA: Candida, Aspergillus, Cryptopcocus
NEVER use as monotherapy!
Synergy with Amphotericin B in severe infections: Candida endocarditis or Cryptococcus neoformans CNS infections
SE: Bone marrow suppression (Dose dependent, therapeutic drug monitoring to avoid)
Hepatotoxicity |
|
|
Term
| Terbinafine: Mechanism of Action and Clinical Uses |
|
Definition
Antifungals for Dermatophytes
Blocks ergosterol production by inhibiting Squalene Epoxidase production
SE: Hepatotoxicity |
|
|
Term
| Griseofulvin: Mechanism of Action and Clinical Uses |
|
Definition
Antifungals for Dermatophytes
Prevents infections of new skin structures. Eventually the infected ones die and get replaced
SE: Allergic Reactions
Hepatotoxicity |
|
|
Term
| Acyclovir: Mechanism of Action and Pharmacokinetics |
|
Definition
Inactive entity that becomes modified by Viral Thymidine Kinase
Host Enzymes convert it to triphosphate that mimics nucleotides
Acts as Chain Terminator and also competitively inhibits DNA Polymerase
Not well absorbed orally: Requires higher dosing
Requires IV Dosing for severe infections |
|
|
Term
| Acyclovir: Spectrum of Activity and Clinical Use |
|
Definition
Herpes Simplex Virus (HSV): both 1 and 2
Varicella Zoster Virus (VZV): Requires higher doses to be active
No Activity against Cytomegalovirus (CMV) or Influenza
SE: -Headaches
-Crystallization in urine: IV formulation (high doses); avoid by hydration
-Neurotoxicity: IV formulation (high doses); rare |
|
|
Term
| Valcyclovir: Mechanism of Action and Pharmacokinetics |
|
Definition
Oral Pro-Drug of Acyclovir (Chain Terminator and competitively inhibits DNA Polymerase)
Well Absorbed, then converted to Acyclovir
IV Acyclovir still used for severe infections |
|
|
Term
| Valcyclovir: Spectrum of Activity and Clinical Use |
|
Definition
Same as Acyclovir:
Herpes Simplex Virus (HSV): both 1 and 2
Varicella Zoster Virus (VZV): Requires higher doses to be active
No Activity against Cytomegalovirus (CMV) or Influenza
SE: -Headaches
-Crystallization in urine:(high doses); avoid by hydration
-Neurotoxicity: high doses; rare |
|
|
Term
| Ganciclovir: Mechanism of Action |
|
Definition
Varies based on virus that it is targeting:
HSV/VZV: Similar to Acyclovir (TK activation)
Cytomegalovirus (CMV): Inactive drug activated by Kinase Phosphotransferase in CMV (then follows same path as Acyclovir)
Note: Does NOT act as true chain terminator: causes formation of small, ineffective DNA fragments |
|
|
Term
| Ganciclovir: Spectrum of Activity and Clinical Uses |
|
Definition
DOC for Cytomegalovirus (CMV) (First Line)
HSV: Both 1 and 2, but less than Acyclovir
VZV: Less than Acyclovir
NO activity against Influenza
SE: -Bone Marrow Suppression: occurs often, CMV often in immunosuppressed patients
-CNS Effects: Range from headache to Coma (5-15%) |
|
|
Term
| Valganciclovir: Mechanism of Action and Clinical Use |
|
Definition
Oral Pro-Drug of Ganciclovir
Well Absorped, then converted to ganciclovir
Same MOA, SOA, and SE as Acyclovir |
|
|
Term
| Cidofovir: Mechanism of Action and Clinical Use |
|
Definition
Cytosine Nucleotide, but does NOT require Viral Activation
Activity against HSV, VZV, CMV and Oddball Viruses
Use for CMV if resistant to other agents (Ganciclovir/Foscarnet)
SE: -Nephrotoxicity (20-30%)
-Neutropenia (~25%) |
|
|
Term
| Foscarnet: Mechanism of Action and Clinical Use |
|
Definition
Inorganic Pyrophosphate compound that Inhibits DNA Polymerase, RNA Polymerase and HIV Reverse Transcriptase
Activity against HSV, VZV, CMV, Oddball Viruses, and HIV (in vitro only!)
SE: -Nephrotoxicity (33%)
-Seizures and Headaches
-Chelator of Divalent cations in blood: Hypokalemia, Hypocalcemia, hypomagnesmia |
|
|
Term
| Adamantanes: Drug names and Mechanism of Action |
|
Definition
-Amantadine
-Rimantadine
MOA: Prevents viral uncoding of Influenza A (blocks penetration into the host) |
|
|
Term
| Adamantanes: Clinical Uses and Side Effects |
|
Definition
Use against Influenza A: recently showing increasing resistance though
Parkinson's Disease: DA reuptake
SE: CNS Effects (due to DA reuptake): Nervousness, Lightheadedness, and inability to concentrate |
|
|
Term
| Neuraminidase Inhibitors: Drug names and Mechanism of Action |
|
Definition
-Zanamivir
-Oseltamivir
Inhibits Viral Neuraminidase, which is necessary for viral replication and release from Host |
|
|
Term
| Neuraminidase Inhibitors: Clinical Uses and Side Effects |
|
Definition
Influenza A and B
Effective against H1N1
SE: Zanamivir: is an inhalation drug that can exacerbate COPD |
|
|
Term
| Penicillin (B-Lactam): General Mechanism of Action |
|
Definition
Blocks cross-linking of Peptidoglycan by PBPs
Inhibits the final step of cell wall synthesis
BacterioCIDAL
Time Dependent
Concentration Independent |
|
|
Term
| Penicillin: Spectrum of Activity |
|
Definition
Gram (+): -Streptococci (pyogenese, viridans)
-Enterococci (faecalis)
Anaerobes: -Clostridium spp. (NOT C.diff)
Other mouth anaerobes
Other: Treponema pallidum (Syphilis) |
|
|
Term
|
Definition
-Syphilis
-Dental Coverage
-Necrotizing Faciitis
-DOC for Strep. pyogenese (Only if Strep ALONE) |
|
|
Term
| Penicillin: Pharmacokinetics and Mehcanism of Resistance |
|
Definition
Renal dosing Required (Exceptions: Nafcillin, Oxacillin, Methicillin, Dicloxacillin)
Probenecid: used to increase 1/2 life
MoR: -Beta-lactamases
-PBP Alterations (resistance to all B-lactams) |
|
|
Term
| Penicillin: Adverse Effects |
|
Definition
-Allergic Reactions
-Acute Interstitial Nephritis (AIN)
-Bone Marrow Suppression
-Seizures (High Doses)
-GI effects
-Contact Dermititis |
|
|
Term
| Benzathine Penicillin: Clinical Use and Pharmacokinetics |
|
Definition
Use for Extremely susceptible bugs
-Treponema pallidum (Syphilis)
Long acting depot preparation
Must be given Intramuscularly (IM injection) |
|
|
Term
| Nafcillin: Drug Class and Clinical Uses |
|
Definition
Penicillinase-Resistant (Anti-Staph Penicillins)
Gram(+): Staphylococcus (S. aureus) (DOC for MSSA)
Some Strep
NO Enterococcus activity
Gram(-): none
Not an Oral option (IV and IM only) |
|
|
Term
| Nafcillin: Pharmacokinetics and Mechanism of Resistance |
|
Definition
Designed to overcome Penicillinases
-NO Renal Dosing!
SE: Acute Interstitial Nephritis (AIN) most common
MoR: PBP2A alterations --> results in MRSA |
|
|
Term
| Oxacillin: Drug Class and Clinical Uses |
|
Definition
Penicillinase-Resistant (Anti-Staph Penicillins)
Gram(+): Staphylococcus (S. aureus) (DOC for MSSA)
Some Strep
NO Enterococcus activity
Gram(-): none
Not an Oral option (IV and IM only) |
|
|
Term
| Oxacillin: Pharmacokinetics and Mechanism of Resistance |
|
Definition
Designed to overcome Penicillinases
-NO Renal Dosing!
SE: Acute Interstitial Nephritis (AIN) most common
MoR: PBP2A alterations --> results in MRSA |
|
|
Term
| Methicillin: Clinical Uses and General Info |
|
Definition
Not used Clinically: Lab reports MSSA or MRSA
Activity and SE same as Nafcillin/Oxacillin |
|
|
Term
| Dicloxacillin: Clinical Uses and General Info |
|
Definition
Oral option for MSSA
Activity and SE same as Nafcillin/Oxacillin |
|
|
Term
| Ampicillin: Drug Class and Spectrum of Activity |
|
Definition
Aminopenicillins
HELPS Bugs:
-H. influenzae
-E. faecalis (static)
-L. monocytogenes
-P. mirabalis
-Salmonella and Shigella spp. |
|
|
Term
| Ampicillin: Clinical Uses and Mechanism of Resistance |
|
Definition
-Enterococcal infections (use with Gentamicin for synergy in serious infections)
-Meningitis when concern for Listeria
IV Formulation
SE: Most common occurrence of GI effects and Contact Dermititis
MoR: Beta-Lactamases and PBP Alterations |
|
|
Term
| Amoxicillin: Clinical Uses |
|
Definition
Aminopenicillin Drug Class
HELPS bugs (same as Ampicillin)
Better absorption, so PO formulation
MoR: Beta-Lactamases and PBP Alterations |
|
|
Term
|
Definition
Penicillin drug class
No longer available by itself (use with Tazobactam)
HELPS Bugs PLUS Pseudomonas aeruginosa
Use for Enterococcus and Pseudomonas |
|
|
Term
|
Definition
| Same as Penicillin, Not clinically used |
|
|
Term
| Amoxicillin/Clauvulanic Acid: Clinical Use |
|
Definition
Penicillin + B-Lactamase inhibitor
MOA: Same as Penicillin PLUS inhibition of B-Lactamase (Suicide Inhibitor)
Combination allows for better Gram(-) and anaerobe coverage
Empiric regimens for broad coverage of Community based pathogens (Diabetic Ulcers, intra-adbominal infections) and Pasturella (animal bites
PO formulation |
|
|
Term
| Ampicillin/Sublactam: Clinical Uses |
|
Definition
MOA: Same as Penicillin PLUS inhibition of B-Lactamase (Suicide Inhibitor)
Combination allows for better Gram(-) and anaerobe coverage
Clinically same as Amox/CA, PLUS DOC for A.baumannii (due to sublactam)
-HACEK organisms endocarditis
IV formulation |
|
|
Term
| Ticaracillin/Clauvulanic Acid: Clinical Uses |
|
Definition
MOA: Same as Penicillin PLUS inhibition of B-Lactamase (Suicide Inhibitor)
Combination allows for better Gram(-) and anaerobe coverage
-Activity against S.maltophilia due to Clauvulanic Acid |
|
|
Term
| Pipercillin/Tazobactam: Clinical Uses |
|
Definition
MOA: Same as Penicillin PLUS inhibition of B-Lactamase (Suicide Inhibitor)
Combination allows for better Gram(-) and anaerobe coverage
-Pseudomonas Coverage!!
Empiric broad spectrum for nosocomial infections (because of Pseudomonas action!) |
|
|
Term
| Cephalosporins: General Mechanism of Action and Spectrum of Activity |
|
Definition
MOA: Same as B-Lactams, Bacteriocidal, Time Dependent (Concentration Independent)
Gram(+) Good coverage
No Enterococcus Activity!! (Except "fifth gen") |
|
|
Term
| Cephalosporins: Pharmacokinetics and Adverse Effects |
|
Definition
Most Renally Eliminated
Renal Dosing required
SE: Similar to Penicillin (allergic, AIN, GI, etc)
MoR: Beta-Lactamases, PBP Alterations |
|
|
Term
| Cephalosporins (First Generation): Drug names and Clinical Uses |
|
Definition
Cephalexin, Cefaxolin, and Cefadroxil
Gram(+): Good Staph coverage
Good Strep Coverage (S.pneumo varies)
Gram(-): Some activity vs. PEK Bugs (Proteus, E.coli, and K.pneumoniae
No Anaerobic or P.Aeruginosa coverage
Use for MSSA, skin coverage (as long as MRSA not concern) |
|
|
Term
| Cephalosporins (Second Generation (2A)): Drug names and Clinical Uses |
|
Definition
Cefaclor, Cefuroxime
Gram(+): Improved against S.pneumo
Gram(-): A little better
No Anaerobic or P.Aeruginosa coverage
Respiratory Tract Infections: S.pneumo, H.influenza, and M.cattarhalis |
|
|
Term
| Cephalosporins (Second Generation (2B)): Drug names and Clinical Uses |
|
Definition
Cefotetan, Cefoxitin
Adds Anaerobic coverage from 2A drugs: EXCELLENT
No P.Aeruginosa coverage
Cefoxitin: use for B.fragilis intra-abdominal infections.
-Also for surgical Prophylaxis
Cefotetan: SE of Hypothrombinemia and Disulfiram-like-Rxns when taking Alcohol |
|
|
Term
| Cephalosporins (Classic Third Generation (not Ceftriaxone)): Drug names and Clinical Uses |
|
Definition
Cefotaxime, Cefixime, Cefpodoxime
Gram(+): Excellent against S.pneumo, variable vs. MSSA
Gram(-): Excellent against most nosocomial bacilli
No Anaerobic or P.Aeruginosa coverage
Caution with SPICE: Using 3rd gen. can confer Resistance! Cefepime (4th) or Carbapenems better. |
|
|
Term
| Cephalosporins (Classic Third Generation (Ceftriaxone only)):Clinical Uses |
|
Definition
IV form, no Renal Dosing!
S.pneumo: DOC for Community Acquired (CAP)
DOC for CA meningitis
DOC for Spontaneous Bacterial Perinitis (SBP)
-Intra-abdominal infections: pair with Metronidazole for anaerobes)
-UTI's
SE: Biliary sludging in Neonates |
|
|
Term
| Cephalosporins (Unique Third Generation): Clinical Uses |
|
Definition
Ceftazadime
Gram(+): Decreased action against Staph (MSSA) and Strep
Gram(-): Good
Anaerobic: None
P.Aeruginosa: YES! Can cover Nosocomial Meningitis
Limited use due to propensity to induce resistance |
|
|
Term
| Cephalosporins (Fourth Generation): Clinical Uses |
|
Definition
Cefepime
Gram(+): Excellent against Staph (MSSA) and Strep
Gram(-): Excellent against most nosocomial agents, SPICE organisms, and ESBL (questionable)
Anaerobic: None
P.Aeruginosa: YES! |
|
|
Term
| Cephalosporins ("Fifth Generation"): Clinical Uses |
|
Definition
Ceftaroline
Gram(+): Can be used for MRSA, better S.Pneumo coverage, activity against E.faecalis
Gram(-): Intermediate between 2nd/3rd generation
Anaerobic: ??
P.Aeruginosa: ??
Newer Drug: Clinically against CAP and Skin infections |
|
|
Term
| Carbapenems: General Mechanism of Action and Spectrum of Activity |
|
Definition
B-Lactam, Blocks crosslinking, BacterioCIDAL
Gram(+): Good, not great.
-No MRSA, or Enterococcus resistant to Ampicillin
Gram(-): Excellent
-No S.maltophilia
Anaerobes: Excellent
-No C.difficile |
|
|
Term
| Carbepenams: General Pharmacokinetics and Adverse Effects |
|
Definition
Renally Eliminated
Renal Dosing
SE: Seizures!! More likely at higher dose
Cross-reactivity with Penicillins less likely than with Cepholasporins |
|
|
Term
| Carbepenams (Group 1): Clinical Uses |
|
Definition
Ertapenem
More narrow spectrum than Group 2
Notable Holes: APE (Acinetobacter, Pseudomonas, and Enterococcus)
DOC for ESBL producing organisms: typically resistant to all Penicillins, Cephalosporins, and Aztreonam |
|
|
Term
| Carbepenams (Group 2): Clinical Uses |
|
Definition
Imipenem, Meropenem, Doripenem
Gram(-): Excellent. Covers ESBL and A.baumannii
-Pseudomonas (even those resistant to Pip/Tazo)
Clinical use for Multi-Drug Resistant Organisms |
|
|
Term
| Monobactam: Clinical Uses |
|
Definition
Aztreonam (Monocyclic B-Lactam)
Gram(-) Activity ONLY
-Pseudomonas Coverage
-No ESBL
No Cross-reactivity with Penicillin: Empiric G(-) coverage with penicillin allergies
Renally Eliminated --> Renal Dosing |
|
|
Term
| Fluoroquinolones: General Mechanism of Action and Clinical Use |
|
Definition
MOA: Inhibition of bacterial DNA replication by inhibiting Bacterial DNA Gyrase and Topoisomerase
-BacterioCIDAL and Concentration Dependent
Gram(+): Levo > Moxi > Cipro
Gram(-): Cirpo > Levo > Moxi
Anaerobes: Only Moxi
Respiratory FQs: Good against CAP (Levo, Moxi, Gemi)
Gram(-) FQs: Cover most and Pseudomonas (Cipro, Levo)
Anaerobic FQs: Moxifloxacin |
|
|
Term
| Fluoroquinolones: General Pharmacokinetics and Adverse Effects |
|
Definition
-CNS Toxicity: Headaches, seizures, insomnia
-Damage to growing Cartilage: esp. in kids
-Tendon Rupture: Rare
-Dysglycemia
-Cardiac Arrhythmias and possible torsades
DDIs: Multivitamins (reduced absorption) and QT elongation drugs
Excellent Bioavailability, Highly Lipophilic
Renal Elimination (renal dosing)
MoR: TSM (decrease binding site), Efflux pumps |
|
|
Term
| Moxifloxacin: Clinical Uses |
|
Definition
Fluoroquinolones
Gram(+): Excellent Strep coverage (including S.pneumo)
Anaerobic: Not reliable against B.fragilis
NOT Renally eliminated (No Renal Dosing)
Highest Risk for Cardiac Arrhythmias |
|
|
Term
| Gemifloxacin: Clinical Uses |
|
Definition
Respiratory FQ (CAP Bugs):
-S.pneumo
-H.influenzae
-M.cat
-Other atypical
100% bioavailability |
|
|
Term
| Ciprofloxacin: Clinical Uses |
|
Definition
Fluoroquinolones Drug Class
Gram(-): Coverage against most, including Pseudomonas
80% bioavailability |
|
|
Term
| Levofloxacin: Clinical Uses |
|
Definition
Gram(+): Some Staph and Enterococcus activity
Excellent Strep coverage (incl. S.pneumo)
Gram(-): covers most, including Pseudomonas (not as good as Ciprofloxacin)
Respiratory FQ (CAP Bugs)
100% bioavailability
Simple Mutation --> Resistance!!
Do NOT rely on to treat Staph or Enterococcus! |
|
|
Term
| Norfloxacin: Clinical Uses |
|
Definition
Fluoroquinolone Drug Class
UTI's and Gut Decontamination
Not Readily absorbed |
|
|
Term
| Vancomycin: Mechanism of Action and Pharmacokinetics |
|
Definition
Glycopeptide Drug Class (1st Gen)
MOA: Binds D-ala-D-ala terminal portion of Peptidoglycan precursors
Bacteriocidal (slowly)
IV: Systemic infections
PO: Not absorbed (C.diff colitis)
Renal Elimination (requires Dose adjustment)
Monitor Trough Levels for efficacy |
|
|
Term
| Vancomycin: Clinical Use and Adverse Effects |
|
Definition
Gram(+) ONLY: Broader spectrum but weaker killing than B-Lactams
Empiric MRSA coverage (Standard of Care)
For patients with B-Lactam allergy
SE: -Nephrotoxicity (higher doses)
-Ototoxicity (rare), Rash
-Redman's Syndrome (Rapid infusion -> histamine response) |
|
|
Term
| Telavancin: Mechanism of Action and Clinical Uses |
|
Definition
Glycopeptide Drug Class (2nd gen)
MOA: Same as Vancomycin + direct binding to bacterial membrane (bactericidal)
Increased Gram(+) activity: MRSA
SE: Worse Nephrotoxicity, Interference with Coagulation tests
-Teratogenicity! |
|
|
Term
| Daptomycin: Mechanism of Action and Spectrum of Activity |
|
Definition
Cyclic-lipopeptide Drug Class
MOA: Embeds in membrane to create K+ efflux channel -> Depolarize membrane & cell death
Highly BacteriCIDAL
Gram(+) ONLY
-Staphylococcus
-Streptococcus
-Enterococcus |
|
|
Term
| Daptomycin: Clinical Uses and Adverse Effects |
|
Definition
MRSA and VRE: Bloodstream endocarditis and soft tissue infections
Do NOT use for Pneumonia!! (irreversibly binds to pulmonary Sulfactant)
SE: -CPK elevation, Rhabdomyolosis
DDIs: Caution with Statins!
Cross-Resistance: Cell-wall thickening in some MRSA strains (high vancomycin MIC) |
|
|
Term
| Linezolid: Mechanism of Action and Pharmacokinetics |
|
Definition
Oxazolidinone Drug Class
Binds 50S Ribosomal Subunit (inhibit protein synthesis)
BacterioSTATIC
Great Absorption
NOT Renally Eliminated (No dose adjust) |
|
|
Term
| Linezolid: Clinical Use and Adverse Effects |
|
Definition
Gram(+) Only: -DOC for VRE!
-Some use in MRSA (pneumonia positive or elevated Vancomycin MIC)
SE: -Thrombocytopenia (Long course > 14 days)
-Peripheral/optic Neuropathy (rare)
DDI: **Weak MAOI** (Seratonin Syndrome with SSRI, Tyramine!! |
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Term
| Quinupristin/Dalfopristin: Clinical Uses and Adverse Effects |
|
Definition
Streptogramin Drug Class
MAO: Binds 50S Ribosomal Subunit
First drug for VRE (not used anymore)
No Activity against E.faecalis
High SE Rates: -Infusion Reactions
-Arthralgias
-Myalgias
-Hepatotoxicity |
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Term
| General Macrolides: Mechanism of Action and Spectrum of Activity |
|
Definition
MAO: Binds 50S Ribosomal subunit
Respiratory Bugs: Streptococcus, H.influenza, M.catarrhalis, Mycoplasma pneumonia, Chlamydia pneumonia, Legionella pneumophilia.
-C.trachomatis (chlamydia)
-Mycobacterium Avium Complex (MAC)
-H.pylori |
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Term
| General Macrolides: Clinical Use and Adverse Effects |
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Definition
Use for Respiratory Tract Infections, H.pylori, and Mycobacterial regimens,
IV=PO Dose
DDIs: Inhibitors and substrates of CYP3A4
No Renal Dosing
Nausea/Vomiting/Diarrhea biggest concert
Heptatotoxicity (rare)
MoR: TSM (change 50S binding) and efflux pumps |
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Term
| Azithromycin: Clinical Uses |
|
Definition
Macrolide Drug Class
First line for CAP
-Traceobronchitis, COPD, Mycobacterial regimens, C.trachomatis infections (Chlamydia)
IV or PO forms, Very long 1/2 Life (72 hours)
Less DDI's, less Side Effects
WORKHORSE for the Class!! |
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Term
| Clarithromycin: Clinical Uses |
|
Definition
Macrolide Drug Class
-Mycobacterial regimens
-H.pylori infections (standard of care)
PO formulation, more prominent DDIs |
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Term
| Erythromycin: Clinical Uses |
|
Definition
Macrolide Drug Class
Severe Constipation in Hospital: takes advantage of N/V/D SEs (binds Motilin-R in GI Tract)
IV or PO Forms
More prominent DDIs |
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Term
| Telithromycin: Mechanism of Action and Clinical Uses |
|
Definition
Ketolide Drug Class
Binds 50S subunit (Bacteristatic)
-Similar to Azithromycin PLUS increased activity vs. S.pneumo
Originally: a niche drug for CAP
High Rates of Hepatotoxicity (limits use) |
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Term
| Tetracyclines: Drug names, MAO, and Pharmacokinetics |
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Definition
Tetracycline, Doxyclicine, Minocycline, and Demeclocycline
Binds 30S Ribosomal Subunit (Bacteriostatic)
Not highly renally eliminated (but sufficient for UTIs)
Highly Lipophillic (penetrate tissues well)
Doxi/Mino: IV or PO formulations
TSM and Efflux pumps -> Resistance |
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Term
| Tetracyclines: General Spectrum of Activity |
|
Definition
Gram(+): -S.pneumo
-S.aureus (includes MRSA)
-Enterococcus
Gram(-): -H.influenzae
-M.Catarrhalis
-Enterobacteraciae (variable, includes MDRO)
Anaerobes: variable
-Atypical pneumonia bugs
-Organisms associated with animal bites (Lyme Disease) |
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Term
| Tetracyclines: Clinical Uses and Adverse Effects |
|
Definition
Dosicycline and Minocycline most clinically used:
-Respiratory tract infections (CAP)
-UTI's, Skin and soft Tissue (esp. CA-MRSA)
Demeclocycline: Used in SIADH
SE: -N/V/D (lessened with food)
-Binding to growing Teeth and Bones (avoid in kids)
-Photosensitization
DDIs: Chelate with divalent and trivalent cations
Avoid with Multivitamins!! |
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Term
| Tigecycline: Mechanism of Action and Spectrum of Activity |
|
Definition
Glycycyclines Drug Class (Tetracycline derivative)
Binds to 30S Ribosomal Subunit (Static)
Gram(+): Broad (MRSA, VRE)
Gram(-): Same as Tetracycline
-PLUS ESBL, Acinetobacter
Anaerobes: Some Coverage
No Pseudomonas or Proteus coverage |
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Term
| Tigecycline: Clinical Use and Adverse Effects |
|
Definition
Last line for many nasty Gram(-) bugs
-Carbapenem Resistant Acinetobacter
-Klebsiella
Polymicrobial wounds: incl. MRSA and VRE
PK: Same as Tetracycline
SE: N/V (20%) and Pancreatitis
Different structure than Tetracycline (allows it to overcome Resistance) |
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Term
| Clindamycin (Lincomycin): Mechanism of Action and Spectrum of Activity |
|
Definition
Lincosamides Drug Class
Binds 50S ribosomal subunit (static)
Gram(+): -S.aureus (inc. MRSA)
-Streptococcus (usually)
Gram(-): NONE
Anaerobes: good (better for oral than lower GI)
Toxin Suppression for necrotizing G(+)!! |
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Term
| Clindamycin (Lincomycin): Clinical Uses and Adverse Effects |
|
Definition
Skin Infections, Aspiration pneumonia, alternative for general anaerobe coverage
PO and IV Forms
SE: Diarrhea, Nausea
-C.Diff Diarrhea (FQ and other broad spectrums also cause this)
MLS Resistance |
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|
Term
| Macrolide-Lincosamide-Steptogramin (MLS) Resistance Information |
|
Definition
Staph. aureus can possess 'erm" gene, encodes resistance to all three classes!
All have same MOA (50S subunit)
May lead to inducible Clindamycin Resistance
-Only issue when isolate Erythromycin Resistanta nd Clindamycin susceptible
-A Special D Test utilized to detect it |
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|
Term
| Trimethoprim/Sulfamethoxazole (Bactrim): Mechanism of Action |
|
Definition
Sulfonamide + TMP
SMX: Structural analog of PABA, blocks production of DHF Acid
TMP: Inhibitor of DHF Acid Reductase (next step in production of Purines)
EACH are Bacteriostatic
BOTH are Bactericidal!! SYNERGY |
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Term
| Trimethoprim/Sulfamethoxazole (Bactrim): Spectrum of Activity |
|
Definition
Gram(+): -Staph (incl. MRSA)
-Some Strep (no group B Strep)
-NO Enterococcus
Gram(-): Variable against enteric G(-) (Klebsiella, Proteus, E.Coli)
-SPICE organisms
-NO Pseudomonas
Anaerobes: Minimal
Miscellaneous: Listeria, Nocardia, S.maltophilia |
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|
Term
| Trimethoprim/Sulfamethoxazole (Bactrim): Clinical Uses |
|
Definition
-Outpatient UTI's
-Skin Infections (when MRSA is concern)
DOC for nasty infections:
-PCP (pneumocystis) pneumonia
-S.maltophilia
-Nocardia
Treatment for MDR Gram (-)? (debated) |
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Term
| Trimethoprim/Sulfamethoxazole (Bactrim): Adverse Effects |
|
Definition
Hypersensitivity Reactions: Most common agent to cause these!
-Simple Rash --> SJS/TEN
High Concentration can crystallize in Urine
TMP SEs: Bone Marrow suppression, Hyperkalemia
DDIs: Increased INR when given with Warfarin |
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Term
| Nitro-Imidizole: Drugs, Mechanism of Action and Spectrum of Availability |
|
Definition
Metronidazole*, Tinidazole
MAO: Not clearly defined (DNA helical structure loss and strand breaking)
Anaerobes ONLY!! Better for lower GI anaerobes than mouth anaerobes
Some Parasitic activity: T.vaginalis |
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Term
| Nitro-Imidizole: Clinical Uses and Adverse Effects |
|
Definition
Metronidazole: Anaerobic coverage for Nosocomial patients
-DOC for C.diff (also T.vaginalis)
100% bioavailability, minimal renal elimination
SE: N/V, Metallic Taste, Peripheral Neuropaties (rare)
-Disulfuram-like reaction with Alcohol
DDIs: increased INR when given with warfarin |
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Term
| Rifampin: Mechanism of Action and Spectrum of Activity |
|
Definition
MAO: Binds B-Subunit of DNA-dependent RNA-Polymerase (blocks RNA Synthesis)
-Bactericidal
Gram(+): Staph (MRSA) and Strep
Gram(-): Used with cell wall agent for synergy
Miscellaneous: Mycobacterial infections |
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Term
| Rimfampin: Clinical Uses and Adverse Effects |
|
Definition
**NOT MONOTHERAPY**
Synergy: -Severe Staph
-MDR Gram(-) Bacilli
TB: Standard of Care
100% Bioavailibitily (food may affect abs.)
No Renal dosing
SE: HIGHLY Hepatotoxic, Discolored Fluids |
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|
Term
| Polymixins: Mechanism of Action and Spectrum of Activity |
|
Definition
Drugs: Polymixin B, Colistin
-Cationic detergent that damages the cytoplasmic membrane -> leading to leakage of intracellular substances
Gram(+): NONE
Gram(-): Pseudomonas, A.baumanni, K.pneumoniae, and E.coli
-NO Serratia or Proteus
Anaerobic: NONE |
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Term
| Polymixins: Clinical Uses and Adverse Effects |
|
Definition
MDR Gram(-) organisms in the hospital when there are no other options!
PK: Poorly understood
SE: -Nephrotoxicity (40%, dose dependent and reversible)
-Neurotoxicity: parasthesias
DDIs: Additive toxicities |
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|
Term
| Chloramphenicol: Mechanism of Action and Adverse Effects |
|
Definition
Inhibits 50S Ribosomal Subunit
Not used Clinically due to Toxicity!
SE: -BM Suppression: dose dependent
-Aplastic Anemia: not dose dependent
-Gray-Baby Syndrome (accumulation of toxic metabolite) |
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Term
| Nitrofurantoin: Mechanism of Action and Clinical Uses |
|
Definition
MAO: Inhibition of variety of bacterial enzyme systems interfering with metabolism (CIDAL)
Only used to treat lower UTI's
Completely filtered by Kidney (cannot use if GFR < 600 mL/min)
SE: Rare inflammatory lung process |
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Term
| Dapsone: Mechanism of Action and Clinical Uses |
|
Definition
MAO: Antagonist of PABA (bacteriostatic)
Prevention and Treatment of PCP Pneumonia when TMP/SMX cannot be used (allergy)
SE: Hemolysis: infrequent, more common in patients with G6P deficiency |
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Term
| Drugs which work against Pseudomonas |
|
Definition
-Piperacillin, Piperacillin/Tazobactam
-Cefepime, Ceftazadime
-Aztreonam
-Imipenem, Meropenem, Doripenem
-Gentamicin, Tobramycin, Amikacin
-Ciprofloxacin, Levofloxacin
-Polymixins |
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Term
| What is the common Pseudomonal Treatment |
|
Definition
IV Beta-Lactam therapy for 4-6 weeks
-4 weeks join; 6 weeks bone
Some add in anti-pseudomonal Aminoglycoside or Fluoroquinolone for 2 weeks |
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