Antimicrobial Review Flashcards
Penicillin
MOA
Inhibits cell wall synthesis
Penicillin
Mechanisms of Resistance
- B-lactamase production
- Altered PBP
- Decreased drug permability
Penicillin
Gram Pos Coverage
List specific bacteria
Streptococcus spp
Listeria spp
Clostridium spp
Penicillin
Gram Neg Coverage
List specific bacteria
Neisseria spp
Pasteurella
Penicillin
Overall Coverage
Gram Positives
Gram Negatives (more limited)
Spirochete (Treponema pallidum)
Penicillin
Side Effects
- IgE-mediated anaphylaxis
- Integumentary (Maculopapular rash)
- GI upset- Nausea, vomiting, diarrhea
Antistaphylococcal Penicillins
List the Meds
Nafcillin
Oxacillin
Dicloxacillin
Antistaphylococcal Penicillins
Gram Positive Bacterial Coverage
list specific species
Gram Positives
* streptococcus spp
* Clostridium spp
* Methicillin-susceptible Staphylococcus Aureus
Antistaphylococcal Penicillins
Side Effects
Hematologic/Oncologic: agranulocytosis
GI: cholestasis, n/v/d
Aminopenicillins
Overall Coverage
Gram Positives
Gram Negatives
Improved gram neg coverage compared to penicillins
Aminopenicillins
Amoxicillin
Aminopenicillins
Gram Positive Coverage
Streptococcus spp
Enterococcus spp
Aminopenicillins
Gram Neg Coverage
E. Coli
Proteus mirabilis
H. Influenzae
Salmonella spp
Shigella spp
Neisseria meningitidis
Aminopenicillins
Side Effects
GI: n/d
Renal: nephrotoxicity
What can aminopenicillins be combined with?
beta-lactamase inhibitors
Which is better absorbed, amoxicillin or ampicillin?
Oral amoxicillin
Piperacillin/Tazobactam
Side Effects
Hypersensitivity (anaphylaxis)
Integumentary: Stevens-Johnson Syndrome, Toxic epidermal necrosis
Renal: nephrotoxicity
GI: n/v/d
Piperacillin/Tazobactam
Overall Bacterial Coverage
BROAD SPECTRUM (positives, negatives, anaerobes)
How are piperacillin/tazobactams administered?
Infusion (over 4 hrs)
Cephalosporins
MOA
binds to penicillin binding proteins to prevent cell wall synthesis
Cephalosporins
Time or concentration dependent?
Bactericidial or bacteriostatic?
Time dependent
Bactericidal
Penicillins
Time or concentration dependent?
Bactericidial or bacteriostatic?
Time dependent
Bactericidal
Cephalosporins
Class
Beta-Lactams
Cephalosporin
Coverage
1st Gen: great w/ gram positives, poor gram neg coverage
3rd Gen: equalish gram neg/pos coverage
5th Gen: great gram neg coverage, poor gram pos coverage
Cephalosporins
1st Gen Meds & Admin Route
List med names & PO/IV/IM
Cefazolin (IV)
Cephalexin (PO)
Cefadroxil (PO)
Cephalosporins
1st Gen Coverage
MSSA
Beta-hemolytic Streptococcus
PEcK
Define
PEcK
Proteus
E. coli
Klebsiella
Cephalosporins
2nd Gen Meds & Admin Route
List med names & PO/IV/IM
Cefaclor (PO)
Cefprozil (PO)
Cefuroxime (IV/IM/PO)
Cefoxitin (IV/IM)
Cefotetan (IV/IM)
Cephalosporins
2nd Gen Coverage
MSSA
Beta-hemolytic Streptococcus
HEN PEcKS
Oral Anaerobes
Define
HEN PEcKS
H. Influenzae
Enterobacter aerogenes
Neisseria
Proteus
E. coli
Klebsiella
Serratia marcescens
Cephalosporins
3rd Gen Meds & Admin Route
List med names & PO/IV/IM
Cefotaxime (IV/IM)
Ceftazidime (IV/IM/Neb/Intravitreal)
Ceftriaxone (IV/IM)
Cefixime (PO)
Cefpodoxime (PO)
Cefdinir (PO)
Cephalosporins
3rd Gen Coverage
MSSA & Streptococcus
Neisseria meningitidis & gonnorhea
Oral anaerobes
Pseudomonas
Moraxella
H. Influenzae
Cephalosporins
Pearls
- Cross BBB, so can be utilized for meningitis
- Ceftazidime has pseudomona coverage
Cephalosporins
3rd Gen Contraindications
- Infants < 28 days when also using calcium containing products
- Neonates w/ hyperbilirubinemia
Cephalosporins
4th Gen Meds & Admin Route
Cefepime (IV/IM)
Cephalosporins
4th Gen Coverage
MSSA & Streptococcus
Neisseria meningitidis & gonnorhea
Oral anaerobes
Pseudomonas
Cephalosporins
Which generations can be used to treat meningitis because they cross the BBB?
- 3rd Gens
- 4th Gen
Cephalosporins
4th Gen Contraindications
- use with caution in patients w/ seizures (neurotoxicity)
Cephalosporins
5th Gen Meds & Admin Routes
Ceftaroline (IV)
Ceftolozone/Tazobactam (IV)
Cephalosporins
Ceftaroline Coverage
MSSA, MRSA, & Streptococcus
Neisseria meningitidis & gonnorhea
Pseudomonas
Moraxella
H. Influenzae
Cephalosporins
Ceftolozone/Tazobactam Coverage
pseudomonas
No MRSA coverage
Cephalosporins
Side Effects
n/v, loss of appetite, abd pain, nephrotoxicity, hemolytic anemia, super infection (C. diff)
Do cephalosporins have cross reactivity with pencillin allergy?
Yes- greatest in Gen 1 and decreases throughout rest of gens.
3rd Gen and beyond show minimal cross reactivity, but we still avoid in allergy
Do cephalosporins cover Enterococcus spp?
NO
Which cephalosporin does not require renal dose adjustment?
Ceftriaxone
Carbapenem Meds
Doripenem
ertapenem
Imipenem
Meropenem
Carbapenems
MOA
inhibit cell wall synthesis by binding to PBPs, thus, causing bacterial cell wall defect
Carbapenems
Time or concentration dependent?
Bactericidial or bacteriostatic?
Concentration Dependent
Bactericidal
Carbapenem
Bacterial Coverage
Gram neg cocci and bacilli
MSSA and Streptococcus
Anaerobes
Carbapenems
Side Effects
n/v, abd pain, seizures, nephrotoxicity, injection site rxn
Carbapenems
Does ertapenem cover pseudomonas?
NO
Monobactam Med
Aztreonam
Monobactam
MOA
inhibits synthesis of bacterial cell wall by blocking peptidoglycan crosslinking
Monobactams
Time or concentration dependent?
Bactericidial or bacteriostatic?
Time Dependent
Bactericidal
Monobactam
Coverage
Citrobacter spp
Enterobacter spp
E. coli
Haemophilus spp
Klebsiella spp
Proteus spp
Serratia spp
Monobactams
Side Effects
n/v/d, pain at injection site, increase in serum transaminases, neutropenia
Macrolide Meds
Azithromycin
Clarithromycin
Erythromycin
Fidaxomicin
Macrolides
MOA
EXCLUDES FIDAXOMICIN
inhibits RNA-dependent protein synthesis by binds to the 50S ribosomal subunit
Macrolides
MOA
Fidaxomicin
Inhibits RNA polymerase by binding to the DNA template RNA polymerase complex
Macrolides
Time or concentration dependent?
Bactericidial or bacteriostatic?
Time Dependent
Bacteriostatic
At high concentrations can be bactericidal
Macrolides
Side Effects
GI: n/v/d, abd pain
Hepatic: cholestatic jaundice
Cardiac: QT prolongation
Macrolides
What is the only bacteria Fidaxomicin is used for?
PPP
C. diff
Macrolides
Which macrolide has the largest risk of GI disturbance?
PPP
Erythromycin
Macrolides
Overall Bacterial Coverage
Excludes fidaxomicin
Gram Positives
Atypical Bacteria
Spirochete
Limited Gram Negatives
Macrolides
Gram Positive Coverage
Excludes Fidaxomicin
Group A Streptococci
Corynebacterium diphtheriae
Cutibacterium acnes
Macrolides
Atypical Bacterial Coverage
Excludes Fidaxomicin
Mycoplasma pneumoniae
Chlamydia trachomatis
Chlamydophila pneumoniae
Legionella spp
Macrolides
Spirochete Coverage
Excludes Fidaxomicin
Treponema pallidum
Borrelia burgdorferi
Macrolides
Gram Negative Coverage
Excludes Fidaxomicin
Campy
Lincosamide
MOA
inhibits protein synthesis by binding to the 50S ribosomal subunit
Lincosamide Med
Clindamycin
Lincosamide
Time or concentration dependent?
Bactericidial or bacteriostatic?
Time Dependent
Bacteriostatic
at high concentrations it can be bactericidal
Lincosamides
Side Effects
GI: n/v/d, C. diff infection
Integum: Stevens-Johnson Syndrome
Cardiac: QT prolongation
Lincosamides
Overall Coverage
Gram Positives
Anaerobes
Can Clindamycin be used for community acquired MRSA?
Yes
Tetracycline Meds
Doxycycline
Minocycline
Tetracycline
Tetracyclines
MOA
Binds to the 30S ribosomal unit, inhibiting protein synthesis
Tetracyclines
Time or concentration dependent?
Bactericidial or bacteriostatic?
Combination of concentration and time dependent
Bacteriostatic
Tetracyclines
Risk of what injury if patient doesn’t take with water & remain upright?
PPP
Esophageal injury
Tetracyclines
Contraindications
PPP
Avoid in children < 8 and pregnant women due to concern of dental discoloration & bone development delay
Tetracyclines
Overall Coverage
Broad Spectrum AF
Tetracyclines
Gram Positive Coverage
MRSA
Streptococcus (watch for increasing resistance)
Bacillus anthracis
Tetracyclines
Gram Negative Coverage
Rickettsiae
H. Influenzae
Helicobacter pylori
Vibrio cholerae
Tetracyclines
Anaerobe/Spirochete/Atypical Bacteria Coverage
Anaerobe: bacteriodes fragilis
Spirochetes: treponema pallidum, berelia burgodrferi
Atypicals: mycoplasma pneumoniae, chlamydia trachomatis, chlamydophila pneumoniae, Legionella spp
Tetracyclines
Side Effects
- Teeth & Bone Effects
- Integum: photosensitivity
- GI: n/d/v, C. diff infection
Aminoglycosides
MOA
interferes with bacterial protein synthesis by irreversibly binding to the 30S ribosomal subunit
Aminoglycoside Meds
Gentamicin
Tobramycin
Amikacin
Aminoglycosides
Time or concentration dependent?
Bactericidial or bacteriostatic?
Concentration Dependent
Bactericidal
Aminoglycosides
Gram Negative Coverage
PEcK
Pseudomonas
Enterobacter
Shigella
Aminoglycosides
Side Effects
Renal Toxicity
Vestibular/Auditory Toxicity
Neuromuscular Blockades
Are aminoglycosides uses as a mono treatment?
PPP
NO- paired with broad spectrum beta-lactams
Sulfonamide Meds
Sulfamethoxazole
Trimethoprim
Sulfonamides
Time or concentration dependent?
Bactericidial or bacteriostatic?
Time Dependent
Bacteriostatic
Sulfonamides
Sulfamethoxazole MOA
Inhibits bacterial folic acid synthesis via competing with para-aminobenzoic acid inhibiting formation of dihydrofolic acid formation
Sulfonamides
Bacteria Coverage
Broad Spectrum
Gram Positives (including MRSA)
Gram Negatives
Protozoa (cyclo)
Fungi
Sulfonamides
Trimethoprim MOA
competitively inhibits folic acid production by inhibiting dihydrofolic acid reduction to tetrahydrofolate, leading to inhibition of the enzymes in folic acid production
Sulfonamides
Side Effects
GI: n/v/d
Heme: thrombocytopenia, hemolytic anemia, severe hyperkalemia
Integum: photosensitivity
Sulfonamides
Contraindications
PPP
- hypersensitivity to sulfa
- hx of drug induced thrombocytopenia
- infants < 2 mo
- pregnancy
Fluoroquinolones
MOA
Inhibiting the activity of DNA gyrase and topoisomerase which are enzymes essential for bacterial DNA replication
Fluoroquinolones Meds
Ciprofloxacin
Levofloxcain
Moxifloxacin
Ofloxacin
Gemifloxacin
Delafloxacin
Fluoroquinolones
Time or concentration dependent?
Bactericidial or bacteriostatic?
Concentration Dependent
Bactericidal
Fluoroquinolones
Gram Pos Coverage
Staphylococcus spp
Streptococcus spp (minus cipro)
Enterococcus faecalis
Listeria monocytogenes
Fluoroquinolones
Gram Neg Coverage
PEcK
H. influenzae
pseudomonas (only cipro)
Fluoroquinolones
Which meds have coverage against addition atypical bacteria?
2
levo
moxi
Fluoroquinolones
Side Effects
GI: n/v
Cardio: QT prolongation
Neuro: CNS adverse effects (insomnia, hallucinations, seizures)
Integum: photosensitivity
Musculo: TENDON RUPTURE
Nitroimidazole Meds
Metronidazole
Nitroimidazoles
MOA
diffuses into the organism and inhibits protein synthesis by interacting with DNA which leads to the loss of DNA helical structure and strand breakage
Nitroimidazoles
Time or concentration dependent?
Bactericidial or bacteriostatic?
Concentration Dependent
Bactericidal
Nitroimidazoles
Bacterial Coverage
Anaerobic bacteria
Protozoan parasites
Nitroimidazoles
Side Effects
GI: n/v/d
Neuro: seizures, peripheral neuropathy
Nitroimidazoles
Describe restrictions on alcohol use
PPP
Avoid alcohol during therapy and 3 days after completion of series.
Disulfiram-like reaction occurs which will induce severe nausea and vomiting if alcohol is used with this med.
Glycopeptide/Lipoglycopeptide Meds
Vancomycin
Dalbavancin
Telavancin
Oitavancin
Glycopeptides/Lipoglycopeptides
MOA
inhibits transpeptidation by binding to the D-alanyl-D-alanine residues of the bacterial cell wall.
Glycopeptide
Time or concentration dependent?
Bactericidial or bacteriostatic?
Vancomycin
Time Dependent
Bactericidal
Lipoglycopeptides
Time or concentration dependent?
Bactericidial or bacteriostatic?
Dalbavancin, telavancin, oritavancin
Concentration Dependent
Bactericidal
Glycopeptide
Bacterial Coverage
Vancomycin
- most gram positive cocci & bacilli (good for resistant strains)
- Enterococcus
- C. diff (PO ONLY)
Lipoglycopeptides
Bacterial Coverage
Dalba/Tela/Orita
Streptococcus
Enterococcus spp- including VRE
Staphylococcus aureus- Orita active against VRSA
Glycopeptides/Lipoglycopeptides
Side Effects
GI: n/v, taste disturbance
GU: nephrotoxicity (vanco, tela), foamy urine
Vancomycin infusion related rxn
PPP
Red Man Syndrome
- flushing, redness, hypotension, chest pain
- Directly related to infusion rate, should not be administered faster than 1 gram/hr
Polypeptides Meds
Colistin
Bacitracin
Polymyxin B
Bacitracin
MOA
Polypeptide antibiotic that inhibits cell wall synthesis
Colstin & Polymyxin B
MOA
Binds to the anionic outer membrane and thereby neutralizes the bacteria’s toxicity and causes cell death
Colstin & Polymyxin B
Time or concentration dependent?
Bactericidial or bacteriostatic?
Concentration Dependent
Bactericidal
Polypeptide
Bacterial Coverage
for Colistin & Polymyxin B
E. coli
Enterobacter spp
Klebsiella spp
Citrobacter spp
Salmonella spp
Shigella spp
Polypeptides
Bacterial Coverage
Bacitracin
most superficial skin infections caused by Staph aureus
Polypeptides
Side Effects
Nephrotoxicity, paresthesia, vertigo, slurred speech, muscle weakness
What type of infections is Bacitracin used for?
PPP
topical infections
Streptogramins
Quinupristin
Dalfopristin
Streptogramin
Quinupristin MOA
inhibits the early phase of protein synthesis
Streptogramin
Quinupristin MOA
inhibits the late phase of protein synthesis
Streptogramin
Bacterial Coverage
- Streptococcus
- Staphylococcus
- C. perf
- Peptostreptococcus spp
- Enterococcus faecium including VRE
- some gram negative anaerobic bacilli
- Atypical respiratory pathogens
Streptogramin
Side Effects
muscle/joint pain, n/v/d, rash, headache
How should streptogramins be administered?
PPP
via central line due to phlebitis when given peipherally
When do we adjust the dose of streptogramins?
PPP
in hepatic insufficiency
Oxazolidanones Meds
Linezolid
Tidezolid
Oxazolidanones
MOA
binds 50S subunit and blocks bacteria’s ability to assemble transfer RNA-ribosomal complex which ultimately inhibits protein synthesis
Oxazolidanones
Time or concentration dependent?
Bactericidial or bacteriostatic?
Time Dependent
Bacteriostatic: Enterococcus and Staphylococcus
Bactericidal: Streptococcus
Oxazolidanones
Bacterial Coverage
Streptococcus
Enterococcus includes VRE
Staphylococcus includes MRSA
Mycobacteria spp
Anaerobes
Oxazolidanones
Side Effects
Reversible myelosuppression, irreversible peripheral neuropathy, reversible optic neuropathy, serotonin syndrome
What drug use is contraindicated with oxazolidanones?
PPP
Hint: think of the side effects
MAOIs
Do not use oxazolidanones within 2 wks of MAOI use
Nitrofurantoin
MOA
inhibits bacterial enzymes responsible for cell wall synthesis
Nitrofurantoin
Time or concentration dependent?
Bactericidial or bacteriostatic?
Concentration dependent
Bactericidal
Nitrofurantoin
Bacterial Coverage
E. coli
Citrobacter spp
S. saprophyticus
E. faecalis
Nitrofurantoin
Side Effects
GI disturbance, headache, dizziness, confusion, pancreatitis
Which E. coli does nitrofurantoin specifically cover due to resistance?
PPP
ESBL E. coli
Rifampin
MOA
binds to and inhibits DNA dependent RNA polymerase
Rifampin
Time or concentration dependent?
Bactericidial or bacteriostatic?
Concentration Dependent
Bactericidal
Rifampin
Bacterial Coverage
Staphylococcus spp
Streptococcus spp
Legionella spp
B. fragilis
Y. pestis
C. burnetti
Neisseria meningitides
Rifampin
Side Effects
hepatotoxicity, thrombocytopenia, AKI, flu-like syndrome
What is Rifampin a strong inducer of?
PPP
CYP enzymes, many drug-drug interactions
Acyclic Analogues of 2’ deoxyguanosine
Acyclovir
Valacyclovir
Penciclovir
Famciclovir
Nucleoside Analogues of Guanosine
Ganciclovir
Valganciclovir
Neuraminidase Inhibitors
Oseltamivir
Zanamivir
Acyclic Phosphonate Nucleotide Analog
Cidofovir
Brincidofovir
Acyclovir & Valacyclovir
MOA
competitively inhibits viral DNA polymerase, incorporates into and terminates the growing viral DNA chain, and inactivates the viral DNA polymerase
Acyclovir & Valacyclovir
Coverage
Herpes virus
Acyclovir & Valacyclovir
Side Effects
n/v, abd pain, dizziness
nephrotoxicity (more w/ acyclovir)
Acyclovir & Valacyclovir
____ is a prodrug of ____
PPP
- Valacyclovir
- Acyclovir
What do you give the pt to prevent nephrotoxicity with IV formulations?
PPP
hydrate with 1mL/kg/hr
Penciclovir & Famciclovir
MOA
selectively inhibits viral DNA polymerase by competing with deoxyguanosine triphosphate
Penciclovir & Famciclovir
Coverage
Herpes virus & hepatits B virus
Penciclovir & Famciclovir
Side Effects
Mild erythema, headache, fatigue, GI disturbances
Penciclovir & Famciclovir
____ is a prodrug of ___
- Famciclovir
- Penciclovir
Penciclovir is formulated as:
Famciclovir is available as:
- cream only
- tablet
Ganciclovir & Valganciclovir
MOA
competitively inhibits incorporation of deoxyguanosine triphosphate into elongating DNA resulting in short subgenomic CMV DNA fragments that are not considered infectious
Ganciclovir & Valganciclovir
Coverage
primary & secondary coverages
herpes virus
some coverage for vaccina virus, HPV, and influenza A
Ganciclovir & Valganciclovir
____ is a prodrug of ____
PPP
- valganciclovir
- ganciclovir
What is ganciclovir’s main use?
PPP
treatment or prevention of CMV infection in immunocompromised pts
Oseltamivir & Zanamivir
MOA
reversible inhibitor of influenza neuraminidase which inhibits the release and spread of the infectious form of the virus
Oseltamivir & Zanamivir
Coverage
Influenza A
some Influenza B activity
Oseltamivir & Zanamivir
Side Effects
n/v/d, headache, rash
Bronchospasm (zanamivir)
When must oseltamivir & zanamivir therapy begin following sx onset?
48 hrs
How is zanamivir formulated?
powder for inhalation
CMV
cytomegalovirus
Cidofovir & Brincidofovir
MOA for CMV
competitive inhibitor and an alternate substrate for CMV DNA poly. Incorporates into the CMV DNA strand and blocks further viral DNA synthesis leading to non-productive infection.
Cidofovir & Brincidofovir
MOA for HPV
infected cells are trapper in the S phase which stops DNA synthesis.
Also causes induction of DNA fragment and caspase-3-protease activity leading to apoptosis
Cidofovir & Brincidofovir
Coverage
Herpes virus, adenoviruses, papillomavirus
Cidofovir & Brincidofovir
Side Effects
nephrotoxicity, neutropenia, alopecia, application site rxn
____ is a prodrug of ____
Cidofovir & Brincidofovir
- brincidofovir
- cidofovir
Foscarnet
MOA
binds reversibly near the pyrophosphate-binding site of DNA polymerase and then blocks the cleavage of the pyrophosphate moeity from deoxynucleotide triphophate which halts DNA chain elongation
Foscarnet
Coverage
Herpes virus
Hep B
HIV
Foscarnet
Side Effects
GI Disturbances, injection site rxn, vision changes
What is foscarnet almost exclusively used for?
PPP
CMV- esp if ganciclovir cannot be used
Acyclovir resistant HSV and VZV
Docosanol
MOA
inhibits the fusion between human cell plasma membrane and HSV envelope preventing viral entry into the cell and subsequent viral replication
Docosanol
Coverage
herpes labialis
Docosanol
Side Effects
application site rxn (redness, burning, dryness, swelling)
When is the best time to use Docosanol? At what point is efficacy reduced?
PPP
- Best time is at the first sign of a cold sore
- Efficacy is reduced if blisters have already formed.
Polyene Meds
Amphotericin B
Nystatin
-azole derivatives
Clotrimazole
Ketoconazole
Fluconazole
Itraconazole
Voriconazole
Posaconazole
Echinocandins
Anidulafungin
Caspofungin
Micafungin
Nystatin
MOA
binds to ergosterol
Nystatin
Time or concentration dependent?
Fungicidal or Fungiostatic?
Concentration Dependent
Fungicidal
Nystatin
Fungal Coverage
Aspergillus fumigatus
Candida albicans
Coccidoides immitis
Cryptococcus neoformans
Histoplasma capsulatum
Nystatin
Side Effects
Mouth irritation, n/v/d
How is Nystatin most commonly used?
PPP
Mouth rinse for thrush
Amphotericin B
MOA
binds to ergosterol in the fungal cell membrane, which leads to the formation of pores, ion leakage, and ultimately fungal cell death
Amphotericin B
Time or concentration dependent?
Fungicidal or Fungiostatic?
Concentration Dependent
Fungicidal
Amphotericin B
Overall Fungal Coverage
Broad Spectrum
Amphotericin B
What does it not cover fungally?
Candida lusitaniee, Aspergillus terreus, Scedosporium spp, Trichosporon spp
Amphotericin B
Side Effets
- infusion rxn (chills, fever, anorexia, headache, hypotension, n/v)
- Nephrotoxicity
- Electrolyte abnormalities
What must Amphotericin B standard formulation be given with? Why?
PPP
- 5% dextrose in water
- Precipitation
Why is the lipid formulation of Amphotericin B preferred?
PPP
Less nephrotoxicity, fewer infusion related rxns
-azole derivatives
MOA
inhibits the C14-alpha demethylation of lanosterol in fungi, which intereferes with the synthesis of ergosterol in the fungal cell membrane
-azole derivitaves
Time or concentration dependent?
Fungicidal or Fungistatic?
Time Dependent
Fungistatic
-azole derivatives
Clotrimazole Coverage
Candida spp
Malassezia furfur
Dermatophytes
-azole derivatives
Ketoconazole Coverage
Candida spp
Malassezia furfur
Dermatophytes
some dimorphic fungi
-azole derivatives
Fluconazole Coverage
Candida spp (not glabrata or krusei)
Malassezia furfur
Dermatophytes
Cryptococcus neoformans
Blastomyces dermatitidis
Coccidioides immitis
Histoplasma capsulatum
Prototheca spp
Demitiaceous molds
-azole derivatives
Itraconazole Coverage
Fluconazole coverage +
Aspergillus spp
Sporothrix schenckii
-azole derivatives
Voriconazole Coverage
Candida spp (resistant strands)
Aspergillus spp (Ampho B resistant A. terreus)
Fusarium spp
Scedosporium apiospermum
Trichosporon spp
molds
-azole derivatives
Posaconazole
Fluconzole Coverage plus
Zygomycetes
-azole derivatives
Shared Side Effects
GI discomfort
-azole derivatives
Clotrimazole Side Effects
skin irritation, elevated LFTs
-azole derivatives
Ketonconazole Side Effects
acne, cracked/dry skin
BB: hepatotoxicity
-azole derivatives
Fluconazole Side Effects
rash
-azole derivatives
Itraconazole Side Effects
Hypertension, hypokalemia
BB: heart failure
-azole derivatives
Voriconazole Side Effects
hepatotoxicity, visual disturbances, QT interval prolongation
-azole derivatives
Posaconazole Side Effects
QT interval prolongation, hepatitis
Which -azole derivative has the fewest drug-drug interactions via CYP enzymes?
PPP
Fluconazole
In what environment should itraconazole/ketoconazole capsules be taken for optimal absorption?
PPP
I: Acidic- empty stomach
K: acidic- with an acidic beverage
What increases the bioavailability of posaconazole?
PPP
high fat meal- increases by 400%
Echinocandins
MOA
inhibits beta-1,3,-D-glucan synthase which is an ezyme neccesary for the synthesis of an essential component of the fungal cell wall
Echinocandins
Time or concentration dependent?
Fungicidal or Fungistatic?
Concentration Dependent
Fungicidal (Candida)
Fungistatic (Aspergillus)
Echinocandins
Fungal Coverage
Candida spp
Aspergillus spp
Echinocandins
Side Effects
All: infusion site rxn
C/M: GI disturbances, electrolyte disturbances
Why do echocandins have fewer drug-drug interactions than -azole derivatives?
PPP
Echocandins are not hepatically metabolized
Flucytosine
MOA
penetrates the fungal cell wall which is converted to 5-fluorouracil which competes with uracil, this interfering with fungal RNA
Flucytosine
Time or concentration dependent?
Fungicidal or Fungistatic?
Concentration Dependent
Fungistatic
Flucytosine
Fungal Coverage
Candida spp
Crypto spp
Flucytosine
Side Effects
Bone marrow suppression, hepatotoxicity, enterocolitis, GI disturbances
Why can Flucytosine not be used as a mono treatment?
Rapid development of resistance if used as mono treatment
3 types of parasites
- single cell organisms
- multicellular helminths
- ectoparasites
Which areas are most impacted by parasitic infetions?
Tropical areas with poor sanitation
Antimalarial Meds
Pyrimethamine
Chloroquine/Hydroxycholorquine
Artemether
Artesunate
Malarone
Mefloquine
Primaquine
Tafenoquine
Pyrimethamine
MOA
inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines
Pyrimethamine
Parasitic Coverage
Plasmodia
Toxoplasma
Pyrimethamine
Side Effects
n/v, insomnia, anorexia
(Hydroxy)Cholorquine
MOA
inhibits the formation of hemozoin (Hz) from the heme released by the digestion of hemoglobin (Hb). The free heme lyses membranes leading to parasitic death.
(Hydroxy)Chloroquine
Parasitic Coverage
asexual erythrocytic stages of:
* Plasmodium falciparum (not active against mature gametocytes)
* Plasmoidum vivax
* Plasmodium malariae
* Plasmodium ovale
(Hydroxy)Chloroquine
Side Effects
n/v, tremors, convulsions, coma
Artesunate and Artemether
MOA
reacts with heme, generating free radicals which inhibit protein and nucleic acid synthesis of the Plasmodium parasites during all erythrocytic stages
Artesunate and Artemether
Parasitic Coverage
All human malarial parasites including multi-drug resistant Plasmodium falciparum strains
Artesunate and Artemether
Side Effects
QT prolongation, bradycardia, n/v/d
What 2 drugs constitute Malarone?
atovaquone + proguanil
Malarone
MOA of atovaquone
causes collapse of the parasitic mitochondrial membrane potential
Malarone
MOA of proguanil
inhibits dihydrofolate reductase after CYP catalyzed cyclization
Malarone
Parasitic Coverage of Atovaquone
asexual stages of many parasites
Malarone
Parasitic Coverage of Proguanil
only used for the prevention of falciparum malaria
Malarone
Side Effects
n/v, anorexia, insomnia, weakness
Mefloquine
MOA
inhibit merozoite invasion and interact with proteins involved with lipid trafficking and nutrient uptake
Mefloquine
Coverage
sexual forms of Plasmodium spp
some activity against sexual forms of P. vivax, malariae and ovale
Mefloquine
Side Effects
dizziness, anxiety, insomnia, vivid dreams, visual disturbances, depression, psychosis
Primaquine & Tafenoquine
MOA
not well understood
possibly generates reactive O2 species or interferes with ETC
Primaquine & Tafenoquine
Parasitic Coverage
all stages of the plasmodium development in humans & Pneumocystis jiroveci
Primaquine & Tafenoquine
What is radicle cure?
anti-relapse therapy
Primaquine & Tafenoquine
Against what parasites do Primaquine & Tafenoquine induce radical cure?
PPP
P. vivax
P ovale
Primaquine & Tafenoquine
Side Effects
n/v/, tarry stools, dizziness, anorexia, hemolytic anemia
Antihelmentics
Albenazole
Mebendazole
Ivermectin
Praziquantel
Pyrantel pamoate
Albendazole & Mebendazole
MOA
Selectively bind to nematode beta-tubulin, inhibiting polymerization, thus preventing the formation of microtubules and so stopping cell division
Albendazole & Mebendazole
Coverage
helminths and protozoa
Albendazole & Mebendazole
Side Effects
prolonged courses can cause liver function abnormalities, bone marrow toxicity
Ivermectin
MOA
influx of chloride ions through the cell membrane of invertebrates by activation of specifc ivermectin-sensitive ion channels. The hyperpolarization leads to muscle paralysis
Ivermectin
Coverage
most nematode parasites, ectoparasites infeestations, helminth parasites
Ivermectin
Side Effects
fever, myalgia, malaise, lightheadedness
Praziquantel
MOA
causes a rapid calcium influx leading to severe spasms and paralysis of the worm
Praziquantel
Coverage
trematodes except Fasciola spp
Praziquantel
Side Effects
headache, dizziness, abd pain, nausea, ithcing
Parasiticides
Permethrin
Spinosad
Permethrin
MOA
acts on the nerve cell membrane to disrupt the sodium channel current by which the polarization of the membrane is regulared leading to paralysis of the scabies/lice
Permethrin
Coverage
lice, ticks, fleas, mites, other arthropods
Permetrin
Side Effects
irritation, burning, itching
Spinosad
MOA
alters the function of nicotinic and GABA-gated ion channels leading to rapid excitation of the parasites nervous system. Leads to involuntary muscle contractions, tremors, paralysis, and death.
Spinosad
Coverage
lice, scabies
Spinosad
Side Effects
application site rxns (redness, swelling, itching, burning)