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107. Drugs for Respiratory Infections

Terms in this set (83)

Protein Synth Inhibitors MOA
1. Which drugs target the 30S subunit?

2. Which drugs target the 50S subunit?
1. Aminoglycosides & Tetracyclines

2. Macrolides, Clindamycin, Linezolid
Protein Synth Inhibitors MOA
3. Aminoglycosides (30S): Interferes with what? Causes what?

4. Tetracyclines (30S): block what?
3. Interferes w/initiation → misreading & aberrant proteins (incorporated into bact. cell membrane)

4. Blocks aminoacyl tRNA acceptor site
Protein Synth Inhibitors MOA
5. Macrolides (50S): Inhibits what?

6. Clindamycin (50S): Inhibits what?

7. Linezolid (50S): Blocks formation of what?
5. Inhibits translocation

6. Inhibits translocation

7. Blocks formation of initiation complex
Protein Synthesis Inhibitors ADRs
3. Aminoglycosides (30S): 2 tox, 1 Neuro?

4. Tetracyclines (30S): 2 GI, 1 skin, 1 mouth?
3. Ototoxicity, nephrotoxicity, Neuromuscular block

4. GI distress, C. difficile, photosensitivity, teeth discoloration
Protein Synthesis Inhibitors ADRs
5. Macrolides (50S): 1 GI, 1 tox, 1 CV?

6. Clindamycin (50S): 2 GI, 1 skin?

7. Linezolid (50S): 1 Heme, 1 HEENT, 1 skin?
5. GI distress, hepatotoxicity, arrhythmia (esp. prolonged QT when taking another QT prolong drug, or other Cardiac Dz)

6. GI diarrhea, pseudomembranous colitis (C. diff), skin rashes

7. Myelosuppression, headache, rash
Community-Acquired Pneumonia (CAP)
=Pneumonia + Influenza=
1. What is the Goal of CAP treatment?

2. What is the mainstay of therapy?

3. What is Therapy guided by?
1. Eradicate organism, resolve clinical disease

2. Antibiotics

3. organism and susceptibility
(Must have knowledge of most likely infecting pathogen & local susceptibility)
CAP - Guidelines: Infectious Diseases Society of America (IDSA)/ American Thoracic Society (ATS) - Management of CAP...
- What 7 patients are excluded from these guidelines? (Hint: think immuno problems)
• Immunocompromised patients
• Solid organ, bone marrow, or stem cell transplant
• Those receiving chemotherapy
• Long-term high dose corticosteroids (> 30 days)
• Congenital or acquired immunodeficiency
• HIV with CD4 count < 350 cells/mm3
• Children ≤ 18 years

(the above will have different & resistant microorganisms)
CAP - Initial Assessment
1. What's the first thing to assess?

2. What are 3 good reasons to avoid unnecessary admissions?
1. Severity: Outpatient, inpatient (non-ICU), intensive care unit

2. • 25x greater cost inpatient vs. outpatient
• Resume normal activities faster as outpatient
• Hospitalization carries risks (thromboembolism & superinfections)
CAP - Severity of Illness Scores
1. What 3 things go into development of a score for someone?

2. 2 tools to figure out the score?
1. Lab data, clinical evaluation, physician interpretation (In conjunction)

2. CURB-65 & Pneumonia severity index (PSI)
CAP - Severity of Illness Scores - CURB-65
What's the acronym (& cutoff values)?
• CC*onfusion
• UU*remia (BUN > 20 mg/dL)
• RR*espiratory rate (≥ 30 breaths/min)
• Low BB*P (SBP < 90, DBP ≤ 60)
• Age (≥ 65*65* Years)
30-Day Mortality Based on Risk Factors
1. At which score does mortality risk really shoot up?

2. What do we do w/someone w/a Score 0-1?

3. What do we do w/someone w/a Score 2?

4. What do we do w/someone w/a Score ≥ 3?
1. I would say 4, but check it out ⤪

2. 0-1: treat as an outpatient

3. 2: admit to hospital

4. ≥ 3: often require ICU care
CAP - General Medical vs. ICU
• 10% of hospitalized CAP patients require ICU
• Use CURB-65 + what 5 minor criteria to determine need for ICU admission?
• Multilobar infiltrates
• WBC < 4000 cells/mm3
• PLT < 100,000 cells/mm3
• Core temperature < 36 ˚C
• Hypotension requiring aggressive fluid resuscitation
CAP - General Medical vs. ICU
What are Two absolute indications for ICU admission?
• Mechanical ventilation
• Septic shock (+ vasopressors)
CAP - Diagnosis
1. 4 Clinical findings:
2. What imaging thing is required?
3. What if #2 is negative but CAP suspected?
4. What other way can you diagnose? Why is this way important?
1. Cough, fever, sputum production, pleuritic chest pain

2. Demonstrable infiltrate on CXR required

3. Initiate antibiotics and repeat CXR in 24-48 hours

4. Culture: ↑ mortality & risk of Tx failure if inappropriate antimicrobials used
Organism ID
1. What is the most valuable, time tested method for immediate ID of bacteria?
2. What is the 1º G+ organism do we think about for pneumonia?
3. What G+ organism do we think about more in the hospital setting, more severe infxn?
4. What G- organisms do we think about for pneumonia? (3)
5. What G- organism do we think about more in the hospital setting or underlying bronchopulm Dz (CF/COPD/bronchiectasis)?
1. Gram stain

2. S. Pneumoniae

3. S. Aureus, MRSA

4. H. Flu, Moroxella, Klebsiella

5. Pseudomonas
CAP - Common Infecting Organisms
5 most common organisms in outpatient CAP?
CAP - Common Infecting Organisms
7 most common organisms in Hospitalized (Non-ICU) CAP?
CAP - Common Infecting Organisms
5 most common organisms in ICU CAP?
CAP - Infecting Organisms/Disease State
1. 3 bugs causing underlying bronchopulmonary disease?

2. 2 bugs underlying Chronic oral steroids or severe underlying bronchopulmonary disease, alcoholism, frequent antibiotic use?

3. 1 bug category underlying Classic aspiration pleuropulmonary syndrome in alcohol/drug overdose or in seizures with gingival disease or esophageal motility disorders?
1. • H. influenzae
• Moraxella catarrhalis
• + S. aureus during an influenza outbreak

2. • Enterobacteriaceae
• Pseudomonas aeruginosa

3. Anaerobes
CAP - Other Infecting Organisms
1. 4 Common viruses?

2. 4 Other viruses?
1. • Influenza
• Respiratory syncytial virus (RSV)
• Adenovirus
• Parainfluenza virus

2. • Human metapneumovirus
• Herpes simplex virus (HSV)
• Varicella-zoster virus (VSV)
• SARS-associated coronavirus
CAP - Other Infecting Organisms
Rarer ones? - I say just flip this one...
And yet more review
you know this crap
CAP - Resistant Organisms
Drug-resistant S. pneumoniae (DRSP):
• Affects what age groups?
• _________ use within previous 3 months
• What 2 other conditions may be present?
• How might a kid pick this up?
• Age < 2 years or > 65 years

• B-lactam use within previous 3 months

• Alcoholism
• Immunosuppressive illness or therapy

• Exposure to child at daycare
Hey look! New information!
=This is important=
CAP - Empiric Antimicrobial Guidelines
Outpatient Recommendations:
1. 2 options if they're Previously Healthy?
1. •Macrolide PO (azithro-/clarithromycin)
-OR-
• Doxycycline PO
=This is important=
CAP - Empiric Antimicrobial Guidelines
Outpatient Recommendations:
2. 2 options if they have DRSP risk? (comorbidities, age > 65 years, use of antimicrobials w/in 3 mo)
2. • Respiratory Fluoroquinolone (FQ) PO (levo-/moxifloxacin)

-OR-

• B-lactam PO [high dose amoxicillin, amoxicillin-clavulanate, ceftriaxone, cefuroxime]
PLUS macrolide PO
=This is important=
CAP - Empiric Antimicrobial Guidelines
Inpatient Recommendations:
3. 2 options if they're Non-Intensive Care Unit?
3. • Respiratory FQ IV or PO (levo/moxifloxacin)

-OR-

• B-lactam IV (ceftriaxone, cefotaxime, ampicillin)
PLUS macrolide IV (azithromycin)
=This is important=
CAP - Empiric Antimicrobial Guidelines
Inpatient Recommendations:
4. 2 options if they're ICU?
• B-lactam IV (ceftriaxone, cefotaxime, or ampicillin/sulbactam)
PLUS azithromycin IV

-OR-

• B-lactam IV (ceftriaxone, cefotaxime, or ampicillin/sulbactam)
PLUS respiratory FQ (levofloxacin, moxifloxacin)
=This is important=
CAP - Empiric Antimicrobial Guidelines
Quick review:
1. Outpatient?
2. Outpatient w/DRSP Risk?
3. Inpatient, Non-ICU?
4. Inpatient, ICU?
1. Macrolide (PO)
or Tetracycline (PO)

2. FQ (PO)
or B lactam + Macrolide (PO)

3. FQ (IV or PO)
or B lactam + Macrolide (IV)

4. B-lactam (IV) + FQ (IV)
or B-lactam (IV) + Macrolide (IV)
CAP - Modifying Empiric Regimen
3 risks for getting Pseudomonas aeruginosa?
• Structural lung Dz (bronchiectasis)

• Repeated COPD exacerbations
(w/corticosteroid and/or antibiotic use)

• Prior antibiotic therapy
CAP - Modifying Empiric Regimen
2 options to treat Pseudomonas aeruginosa?
• Antipseudomonal B-lactam IV (piperacillin-tazobactam, cefepime, imipenem, meropenem)
PLUS ciprofloxacin or levofloxacin
(B-lactam + FQ)

-OR-

• Antipseudomonal B-lactam
PLUS aminoglycoside (gentamicin)
AND azithromycin or antipneumococcal FQ
(B-lactam + Gentamicin + FQ/Macrolide)
CAP - Modifying Empiric Regimen
4 risks of getting the CA-MRSA?
• End-stage renal disease (dialysis)

• Injection drug abuse

• Prior influenza

• Prior antibiotic use (especially FQ)
CAP - Modifying Empiric Regimen
1. 2 options to add on for CA-MRSA Tx?
2. 2 options to add on for Panton-Valentine leukocidin (PVL) necrotizing pneumonia Tx?
• Add vancomycin IV or linezolid

• Add clindamycin or use linezolid
CAP - Intravenous to Oral Therapy
With what 4 situations would you Transition to oral therapy?
• Hemodynamically stable

• Improving clinically

• Tolerating oral medications

• Normal functioning GI tract
CAP - Duration of Therapy
• Minimum of __ days treatment
• Most patients receive __-__ days
• Must be afebrile for __-__ hours
• No more than __ CAP-associated sign of clinical instability
• Exception to the above rules?
• Minimum of 55* days treatment

• Most patients receive 7-100* days

• Must be afebrile for 48-722* hours

• No more than 11* CAP-associated sign of clinical instability

• Exception: Pseudomonas - 8 day course led to more relapse compared to 15 day course (need to treat longer)
1. What does HCAP stand for?
2. What does HAP stand for?
3. What does VAP stand for?
1. Healthcare-Associated Pneumonia (HCAP)

2. Hospital-Acquired Pneumonia (HAP)

3. Ventilator-Associated Pneumonia (VAP)
HCAP, HAP, & VAP
HCAP: what would you see in their history?
history of hospitalization or exposure to healthcare settings
HCAP, HAP, & VAP
• HAPP* occurs how long after admission

• What is the leading cause of death among patients with hospital-acquired infections?

• 3 Serious complications seen in 50%
• 48 hours or more after admission

• HAP

• Pleural effusions, septic shock, renal failure
HCAP, HAP, & VAP
• VAPP* occurs __-__ hours after what?

• Estimated all-cause mortality __-__%

• Prolongs length of ___ ___ 7.6-11.5 days

• Prolongs ____ 11.5-13.1 days

• Excess cost per patient?
• 48-72 hours after endotracheal intubation

• Estimated all-cause mortality 20-50%

• Prolongs mechanical ventilationn* 7.6-11.5 days

• Prolongs hospitalizationn* 11.5-13.1 days

• $40,000
=This is Important=
HAP & VAP - Microbiology (wide variety of pathogens and can be polymicrobial)

3 Common pathogenic groups?
• Aerobic G-

• G+ Coccii* (GPC)

• Oropharyngeal commensals
=This is Important=
HAP & VAP - Microbiology (wide variety of pathogens and can be polymicrobial)
1. Aerobic G-: 5 specific species?

2. GPC: which in particular & more common in what 3 patients?

3. Oropharyngeal commensals: 4 specific species?
1. E. coli, Klebsiella, Enterobacter spp., Pseudomonas, Acinetobacter spp.

2. S. aureus, incl. MRSA (more common in diabetes, head trauma, those hospitalized in ICUs)


3. Strep. Viridans, Coag (-) staph, Neisseria spp., Corynebacterium spp.
HAP & VAP - Diagnosis
2 major ways?
• New or progressive radiographic infiltrate

• Clinical findings suggestive of infection
(Fever, Purulent sputum, Leukocytosis
↓ oxygenation)
HAP & VAP - Antibiogram
1. What is that & what does it show?

2. The 2016 guidelines recommend data should be used to do what?

3. 3 Goals of the Antibiogram & guidlines?
1. Profile of antimicrobial susceptibility: shows % of organisms tested that are susceptible to a range of anitmicrobial drugs

2. To ↓ unnecessary dual G- & empiric MRSA coverage

3. • ↓ patient harm
• ↓ exposure to unnecessary antibiotics
• ↓ development of resistance
VAP - MDR Pathogens
Risk factors (just flip - dont memorize):
• IV antibiotic use w/in last __ days
• ___ ___ at the time of VAP
• _____ preceding VAP
• ≥ ___ days of hospitalization prior to VAP
• Acute ____ replacement therapy prior to VAP
• Tx in ICU in which > 10% of G- isolates are___ to drug being considered for monotherapy
• Tx in ICU in which local antimicrobial susceptibility rates are ___ ____
• Tx in a unit in which > 10-20% of _____ isolates are methicillin-resistant
• Treatment in a unit in which the prevalence of ____ is not known
Risk factors:
• IV ABT use w/in last 900* days

• Septic shockk* at the time of VAP

• ARDSS* preceding VAP

• ≥ 5 *5* days of hospitalization prior VAP

• Acute renall* replacement before VAP

-Use Antibiogram for the following-
• Tx in ICU where > 10% of G- isolates are resistantt* to drug being considered for monotherapy

• Tx in ICU where local antimicrobial susceptibility rates are not known

• Tx in unit where > 10-20% of S. aureuss* isolates are methicillin-resistant

• Tx in unit where prevalence of MRSAA* is not known
For the following few cards here is what she says in her objectives...
do not memorize specific agents for HAP/VAP but be able to describe general treatment strategies
VAP - Empiric Therapy
5 options for Patients without risk factors?
• Piperacillin-tazobactam -OR-
• Cefepime -OR-
• Imipenem -OR-
• Meropenem -OR-
• Levofloxacin

(1 agent - B lactam or Resp. FQ)
VAP - Empiric Therapy
• 2 musts for Patients withh* risk factors?
• Then 3 options that you add too* those other 2?
• Antipseudomonal B-lactamm* -PLUS-
• MRSA coveragee* -PLUS-

• Antipseudomonall* FQ -OR-
• Aminoglycosidee* -OR-
• Polymyxin

(need 2 Antipseudomonals + MRSA coverage)
VAP - Empiric Therapy
• 2 musts for those with only MRSAA* risk factors?
• Antipseudomonal B-lactamm* -PLUS-
• MRSA coverage

(1 G- + MRSA coverage)
HAP - Risk Factors
1. What 2 factors will increase mortality?

2. What factor increases risk of MDR Pseudomonas, other gram-negative bacilli, and MRSA?

3. What 2 factors increases risk of MDR Pseudomonas and other gram-negative bacilli (w/o MRSA?)?

4. What 2 factors increases risk of MRSA?
1. • Ventilatory support for HAP
• Septic shock

2. IV antibiotics w/in past 90 days

3. • Structural lung disease
• Respiratory specimen w/numerous & prominent G- bacilli

4. • Tx in unit where > 20% of S. aureus isolates are methicillin-resistant
• Tx in a unit where prevalence of MRSA is not known
HAP - Empiric Therapy
5 options for patients without risk factors or increased risk of mortality?
• Piperacillin-tazobactamm* -OR-
• Cefepimee* -OR-
• Imipenemm* -OR-
• Meropenemm* -OR-
• Levofloxacin

(1 agent - B lactam or Resp. FQ)
HAP - Empiric Therapy
• 2 musts for Patients withh* risk factors or increased risk of mortality?
• Then 3 options that you add too* those other 2?
• Antipseudomonal B-lactamm* -PLUS-
• MRSA coveragee* -PLUS-

• Antipseudomonal FQQ* -OR-
• Aminoglycosidee* -OR-
• Polymyxin

(need 2 Antipseudomonals + MRSA coverage)
HAP - Empiric Therapy
• If risk factors for MRSA are absent, what should you eliminate from your Tx?

• If risk factors for MRSA present, but not MDR Pseudomonas, what coverage is required?
• Eliminate MRSA coverage

• Only 1 agent w/Pseudomonas coverage required plus MRSA coverage
HAP & VAP - Duration of Therapy
• __-day course of antibiotics recommended

• May adjust based on what?
• 7-day course recommended

• Based on rate of improvement of clinical, radiologic, and laboratory parameters
Pneumonia: DOC if Organism Known
1. DOC for Non-resistant Strep pneumoniae (2)
2. Resistant Strep pneumoniae DOC chosen on what basis?
1. Penicillin G or Amoxicillin

2. Basis of susceptibility:
(Cefotaxime, ceftriaxone, levofloxacin, moxifloxacin, vancomycin, linezolid)
Pneumonia: DOC if Organism Known
3. DOC for Non-B-lactamase producing H. influenzae

4. DOC for B-lactamase producing H. influenzae (2ish)
3. Amoxicillin

4. 2nd or 3rd gen cephalosporin, amoxicillin/clavulanate
Pneumonia: DOC if Organism Known
5. DOC for Mycoplasma pneumoniae (2)

6. DOC for Chlamydophila pneumoniae (2)
5. • Macrolide (azithromycin, clarithromycin)
• Tetracycline (doxycycline)

6. • Macrolide (azithromycin, clarithromycin)
• Tetracycline (doxycycline)
Pneumonia: DOC if Organism Known
7. DOC for Chlamydophila psittaci

8. DOC for Legionella spp. (3)
7. Doxycycline

8. • FQ
• Azithromycin
• Doxycycline
Pneumonia: DOC if Organism Known
9. DOC for Enterobacteriaceae (Klebsiella, E. coli, Proteus) (2ish)

10. DOC for Pseudomonas aeruginosa (4ish)
9. • 3rd or 4th generation cephalosporin
• Carbapenem (if ESBL producer)


10. • Antipseudomonal B-lactam PLUSS*
• Ciprofloxacin -or-
• Levofloxacin -or-
• Aminoglycoside
Pneumonia: DOC if Organism Known
11. DOC for Anaerobe (aspiration): Bacteroides, Fusobacterium, Peptostreptococcus (2)

12. DOC for Influenza virus (2)
11. • B-lactam/B-lactamase inhibitor
• Clindamycin

12. • Oseltamivir
• Zanamivir
Pneumonia: DOC if Organism Known
13. DOC for Methicillin-sensitive Staphylococcus aureus

14. DOC for Methicillin-resistant Staphylococcus aureus (2)
13. • Anti-staphylococcal penicillin (nafcillin, oxacillin, dicloxacillin)

14. Vancomycin or Linezolid
Pneumonia: DOC if Organism Known
15. DOC for Pneumocystis jiroveci (P. carinii pneumonia)

16. DOC for Bordetella pertussis
15. Trimethoprim/sulfamethoxazole

16. Azithromycin, clarithromycin
Pneumonia: DOC if Organism Known
17. DOC for Coccidioides spp.

18. DOC for Histoplasmosis and Blastomycosis (2)
17. No Tx necessary if normal host =BUT= if not then Itraconazole, fluconazole

18. Itraconazole & Amphoterocin B
Influenza
1. How is it transmitted (2)?
2. How long is Incubation?
3. When is the whole Viral shedding thing?
1. • Respiratory droplets (cough, sneeze, talk)
• Contaminated surfaces

2. 1-4 days (average 2 days)

3. 1 day after symptoms to 5-10 days after illness onset
Influenza
1. Some Symptoms (abrupt onset)?

2. Symptoms resolve after how long (if uncomplicated)

3. Cough/malaise can last how long?
1. • Fever
• Myalgia
• Headache
• Malaise
• Non-productive cough
• Sore throat
• Rhinitis

2. 3-7 days

3. > 2 weeks
whoa
Pay attention to:
• Neuraminidase
• Hemagglutinin
• M2 Channel
• Sialic Acid
• Cell membrane
These are the sites of drug action
Replicative Cycle of Influenza
1. What happens after Hemagglutinin binds to the cell surface?
2. In the endosome, the M2 protein of influenza virus allows an influx of what?
3. #2, in turn, promotes dissociation of what?
4. Influenza virus mRNA synthesis requires a _____ cleared from cellular mRNA and used by the viral RNAp complex?
5. Where does the viral progeny go?
1. Endocytosis of the virus.

2. Influx of hydrogen ions into the virion interior.

3. Dissociation of the RNP segments and release into the cytoplasm (uncoating).

4. primer

5. Buds off & exits the cell
Specific Drugs (finally)
Neuraminidase Inhibitors
1. What is the 1 we need to know? How is it administered?
2. MOA?
1. Oseltamivir (PO)
(& zanamivir (INH), peramivir (IV))

2. Analogs of sialic acid, interferes w/release of progeny influenza virus from infected host cell
Neuraminidase Inhibitors
3. ADR for Oseltamivir: GI? HEENT? Neuro?
4. Approved for what age group?
3. • nausea, vomiting, abdominal pain, diarrhea
• headache, fever,
• neuropsychiatric effects

4. children ≥ 1 year
Neuraminidase Inhibitors
Here are the ADRs for the non-red drugs...
Zanamivir:
cough, bronchospasm, ↓pulmonary function (reversible), nasal/throat discomfort, not recommended in underlying airway disease
• Approved for children ≥ 7 years

Peramivir:
diarrhea, increased serum glucose, neutropenia, insomnia
• Approved for adults ≥ 18 years
Neuraminidase Inhibitors
Resistance:
• Common resistance mechanism of Influenza virus?
Point mutation in viral hemagglutinin (HA) or neuraminidase (NA) surface proteins

FYI:
97.4% seasonal H1N1 resistant to oseltamivir
Still susceptible to other drugs
Neuraminidase Inhibitors
Therapeutic Uses (2):
• Influenza prophylaxis (household and institutional)

• Influenza treatment
M2 Channel Blockers
1. Which ones do we have to know?
2. Guess what the MOA is (just flip)?
3. Active against only which virus?
1. NONE! But here are those we don't have to know: Amantadine (PO), rimantadine (PO)

2. block M2 proton ion channels of virus inhibiting uncoating of viral RNA within host cell

3. influenza A
M2 Channel Blockers
4. ADRs: Affects which systems (just flip)?
5. Resistance (just flip)?
4. • GI (nausea, anorexia)
• CNS (nervousness, insomnia, light-headedness, severe behavioral changes, delirium, agitation, seizures)

5. Point mutations, marked resistance limiting use of these agents
Other Antivirals - HSV & VSV
Acyclovir (PO, IV, topical), valacyclovir (PO)
• MOA? Just flip it
3 phosphorylation steps for activation...
1st step virus specific thymidine kinase: Inhibits DNA synthesis - Inhibits DNA synthesis:
• Competition with deoxyGTP for DNA polymerase → binds DNA template irreversible complex
• Chain termination following incorporation into viral DNA
Other Antivirals - HSV & VSV
Acyclovir (PO, IV, topical), valacyclovir (PO)
• Therapeutic Use:

• ADRs (just flip)?
• Tx: genital herpes (treatment, prophylaxis, suppression), varicella, HSV encephalitis, neonatal HSV

• ADR: nausea, diarrhea, headache
Other Antivirals - CMV
Ganciclovir (PO, IV), valganciclovir (PO)
• MOA (just flip)?
• Acyclic guanosine analog, requires activation by triphosphorylation before inhibiting DNA polymerase. Termination of DNA elongation.
Other Antivirals
Ganciclovir (PO, IV), valganciclovir (PO)
• Therapeutic Use?

• ADRs (just flip)?
• Tx: CMV retinitis treatment, CMV prophylaxis

• ADR: myelosuppression, nausea, diarrhea, fever, peripheral neuropathy
Common fungi of clinical interest
Can you name 6?
• Candida albicans
• Histoplasma capsulatum
• Cryptococcus neoformans
• Coccidioides immitis
• Aspergillus spp.
• Blastomyces dermatitidis
Azole Antifungals
1a. What is found in cell membrane of fungi (instead of cholesterol, as is seen in bacteria and human cells)
1b: What 2 do we need to know?
2. MOA of azole antifungals?
3. Why is there Selective toxicity to fungus?
1a. Ergosterol

1b. Fluconazole (PO, IV)
Voriconazole (PO, IV)

2. ↓ fungal cytochrome P450 → ↓ production of ergosterol

3. due to greater affinity for fungal rather than human cytochrome P450 enzymes
Azole Antifungals
4. Wide therapeutic Use against which fungi (5)?

5. 2 ADRs?

6. Are there Drug-drug interactions?
4. • Candida spp.
• Blastomycosis
• Coccidiodomycosis
• Histoplasmosis
• Aspergillus

5. minor GI upset, abnormalities in liver enzymes

6. Yes
Amphotericin B
1. MOA (3 actions)?
2. Therapeutic Use:
• Spectrum?
• Useful for?
3. ADRs: 2 types and their symptoms?
1. • Binds ergosterol → Changes permeability of cell → Forms pores in membrane

2. • Broadest spectrum of activity • Useful in life-threatening infections (but very toxic)

3. • Infusion related (fever, chills, vomiting, headache)
• Cumulative toxicity (renal damage)
Echinocandins
Caspofungin, micafungin, anidulafungin (IV)

1. MOA?

2. Therapeutic Use: which 2 fungi?

3. 2 ADRs?
1. Inhibits synthesis of B(1-3)-glucan → disrupts fungal cell wall → cell death

2. Candida and Aspergillus

3. Minor GI & Flushing
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