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PHRM 852 Exam 2 > Infectious Disease > Flashcards

Infectious Disease Flashcards

1
Q

Emerging Infectious DIseases

A

outbreaks of previously unknown diseases or known diseases whose incidence in humans have increased or threatens to increase in the future

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2
Q

Re-emerging Infectious Diseases

A

diseases that have reappeared after a significant decline in incidence

ex) measles, mumps

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3
Q

What percentages of death worldwide each year are associated with ID?

A

25%

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4
Q

Since the 1970’s how many ID have been discovered and primarily what kind?

A

40 infectious diseases that are mostly viruses

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5
Q

Factors that contribute to emergence/re-emergence of ID

A

Human demographics and behavior (HIV)
Human suscpetibility to infection (transplants)
Technology and Industry
Economic development and land use
International travel
Microbial adaptation (resistance and mutations)
Climate/Weather
Changing ecosystems
Breakdown of public health measures
Poverty
Wildlife trade
War and Famine
Lack of political will
Intent to harm
Pathogens in animals spread to humans
Anti-vaccination

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6
Q

COVID-19

A

What is it? viral respiratory infection caused by coronavirus (SARS-CoV-2)
- single strand enveloped RNA virus

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7
Q

When do symptoms appear for COVID-19

A

within 2-14 days after exposure –> can be contagious in this time

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8
Q

Common Symptoms of COVID-19

A

fever, cough, SOB, fatigue, muscle aches, headache, loss of taste/smell,, sore throat, congestion, N/V/D

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9
Q

Risk Groups for COVID-19

A

older age (greater than 65 yo)

comorbidities
- OBESITY
- cancer
- CKD
- COPD
- immunocompromised
- CVD
- sickle cell
- T2DM

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10
Q

Demographics of COVID-19 Hospitalizations

A
  • adults 20-44 accounted for 20% of hospitalizations
  • blacks, native americans, hispanics were hospitalized at greater rates
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11
Q

Transmission of COVID-19

A
  • spread by respiratory droplets
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12
Q

Incubation period for COVID-19

A

mean incubation was 5-6 days (range from 2-12 days)

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13
Q

Viral Shedding

A

ability to culture live virus

  • mild to moderate infection: remains infectious no longer than 10 days after symptoms onset
  • severe: remains infectious no longer than 20 days after symptoms onset

VIRAL RNA MAY BE DETECTED FOR LONGER PERIODS OF TIME DUE TO DEAD VIRUS –> PROBLEM WITH PCR TESTING

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14
Q

Stages of COVID-19 Disease Progression

A

Stage 1: Early Infection
- viral replication occurs
- Symptoms: mild, fever, cough
- Signs: lymphopenia
- Treat: antiviral

Stage 2: Pulmonary Phase
- Symptoms: SOB with/without hypoxia
- Signs: abnormal chest xray, transaminitis, low procalcitonin

Stage 3: Hyperinflammation Phase
- Symptoms: ARDS, SIRS/Shock, Cardiac Failure
- Signs: elevated inflammatory markers
- Treat: antiinflammtory

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15
Q

Evidence for Trials in COVID-19 Era

A

trials were desperate with:
- small sample size
- poor study design
- lack of control group
- rush to publication
- not peer reviewed and pre prints available
- personal experiences

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16
Q

Treatment of COVID-19 Guidelines

A

Critically Ill Patients (mechanical ventilation, organ dysfunction, sepsis) –> Dexamethasone 6 mg IV/PO for 10 days

Severe but not critically ill (SpO2 < 94% on room air) –> suggests Dexamethasone 6 mg IV/PO

Mild to Moderate (SpO2 > 94% not requiring supplemental oxygen) –> no glucocorticoids

Hospitalized adults with progressive severe or critical COVID-19 who have elevated inflammatory markers –> tocilizumab + Dexamethasone
- if tocilizumab is not available, suggests sarilumab

NO INHALED GLUCOCORTICOIDS

Clinical Trial: RECOVERY Trial

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17
Q

Equivalent Dosing to Dexamethasone 6 mg?

A

Methylprednisolone 32 mg
Prednisone 40 mg

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18
Q

Tocilizumab

A

FDA approved monoclonal antibody against the IL-6 receptor
- binds to both membrane bound and soluble IL-6R

benefits in patients with CRP > 7.5 mg/dL

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19
Q

Remdesivir (Veklury)

A

MOA: interferes with viral RNA dependent RNA polymerase –> inhibits viral replication

Initially developed for Ebola virus: failed

PK:
- IV only
- highly protein bound (no BBB access)
- CYP3A4 substrate
- t1/2: 0.84 - 1.04 hours

Side Effects:
- AST/ALT increase
- phlebitis
- constipation
- dyspepsia
- headache
- nausea
- extremity pain

20
Q

What solubilizes Remedesivir in IV?

A

Sulfobutylether-beta cyclodextrin (SBECD)

Remdesivir 150 mg solution –> 9 grams
Remdesivir 150 mg powder –> 4.5 grams
Voriconazole 400 mg –> 6.4 grams

21
Q

Remdesivir Place in Treatment for COVID-19

A

(Ambulatory or hospitalized) Mild to moderate at high risk for progression to severe disease –> suggests initiation within 7 days of symptoms onset
- Dosing: 200 mg on Day 1, 100 mg on Days 2 and 3

Patients on supplemental oxygen but no mechanical ventilation –> suggests treatment with 5 days compared to 10 days

Hospitalized patients with severe COVID-19 –> suggests use

NO USE WITH MECHANICAL VENTILATION

Clinical Trial: ACTT-1

22
Q

Paxlovid Place in Treatment for COVID-19

A

Paxlovid: nirmatrelvir + Ritonavir

MOA: inhibits hepatic metabolism

Ambulatory patients with mild to moderate COVID-19 at high risk of progression to severe disease –> suggests initiation within 5 days of symptoms onset
- must screen for drug drug interactions due to Ritonavir (CYP3A4 and P-gP inhibitor)

Dosing:
- GFR > 60 mL/min: 300/100 mg every 12 hours for 5 days
- GFR < 60 mL/min: 150/100 mg every 12 hours for 5 days
- GFR < 30 mL/min: DO NOT USE

23
Q

Monkeypox

A
  • disease caused by monkeypox virus in Africa
  • part of the same family as smallpox but is rarely fatal
  • outbreak in Marion county in 2022-2023
24
Q

Signs/Symptoms of Monkeypox

A

RASH
fever
chills
enlarged lymph nodes
pruritus
headache
malaise
myalgia

25
Demographics and Clinical Characteristics of MPox
Age: median of 38 years Sex: Male Sexual Orientation: Homosexual Race: majority white HIV: 41% positive STI: 29% Range of sex partners in last 3 months: 5 TRANSMITTED SEXUAL CLOSE CONTACT
26
Treatment of MPox
Tecovirimat MOA: inhibits orthopox virus VP37 wrapping protein
27
Sexual Transmitted Diseases
Chlamydia - females are more likely to be screened - males are more likely to be symptomatic - highest prevalence in 20-24 year old females - #1 reportable ID Gonorrhea - highest prevalence in 20-24 males and females - #2 reportable ID Syphilis
28
Treatment of Chlamydia
Recommended: Doxycycline 100 mg PO BID x 7 days - CANNOT GIVE DURING PREGNANCY Alternatives: - Azithromycin 1 g PO x 1 day - Levofloxacin 500 mg PO x 7 days
29
Treatment of Gonorrhea of cervix, urethra, rectum
Recommended: Ceftriaxone 500 mg IM if patient weighs < 150 kg If patient weighs > 150 kg: Ceftriaxone 1 g IM
30
Treatment of Primary/Secondary Syphilis
Benzathine Penicillin G 2.4 million units IM x 1 day - used especially for pregnancy or Doxycycline 100 mg PO BID x 14 days
31
Treatment of Latent Syphilis
Early Latent: Benzathine Penicillin G 2.4 million units IM x 1 day or Doxycycline 100 mg PO BID x 14 days Late Latent: Benzathine Penicillin G 7.2 million units administered as 3 doses of 2.4 million units at 1 week intervals or Doxycline 100 mg BID x 28 days
32
Treatment of Tertiary Syphilis
Benzathine Penicillin G 7.2 million units administered as 3 doses of 2.4 million units at 1 week intervals
33
Treatment of Neurosyphilis, Ocular Syphilis, Otosyphilis
Aqueous crystalline penicillin G 18-24 million units per day administered as 3-4 million units IV every 4 hours or continuous infusion for 10-14 days
34
Intrinsic vs Acquired Resistance
Intrinsic: - organisms always resistant to an antibiotic - How? absence of target site or bacterial cell impermeability - Examples: B Lactams vs mycoplasma / Vancomycin vs gram negative / Cephalosporin vs enterococci / Aminoglycosides vs anaerobes Acquired: - organisms initially susceptible to drug become resistant - How? change in bacterial DNA (mutation) or acquisition of new DNA - Examples: Fluoroquinolones vs P. aeruginosa
35
Types of Genetic Exchange during Resistance
Conjugation: direct contact or mating via sex pili (MOST COMMON) Transduction: genes are transferred between bacteria by bacteriophage (virus) Transformation: transfer or uptake of free floating DNA from environment and then integrated into host DNA
36
Gram Positive vs Gram Negative Cell Wall
Gram Negative: - thin peptidoglycan cell wall that is surrounded by an outer membrane containing lipopolysacchride Gram Positive: - lack an outer membrane but are surrounded by layers of thick peptidoglycan
37
Mechanisms of Bacterial Resistance
Enzymatic Inactivation - B lactamases - aminoglycoside modifying enzymes Alteration of Target Site - PBP - Cell wall precursors - ribosomes - DNA gyrase/topoisomerase Altered permeability of bacterial cell - efflux pumps - porin changes
38
Mechanism of Resistance in Gram Negative Bacteria
- overexpression of efflux pumps on transmembrane - antibiotic modifying enzymes - target mutations of DNA gyrase and topoisomerase - ribosomal mutations - mutations in lipopolysaccharide structure - bypass targets
39
Antibiotic Resistant Threats in US
Urgent: - carbapenem resistant acinetobacter - carbapenem resistant enterobacterales Serious: - ESBL producing enterobacterales - MDR pseudomonas aeurginosa - drug resistant TB
40
Most Important Carbapenemases
Klebsiella Pneumoniae Carbapenemase (KPC) - Class A - most frequent cause of CRE in US - common variants: KPC-2 and KPC-3 - plasmid mediated New Delhi Metallo-B-Lactamase (NDM) - Class B - transmissible across gram negative bacilli Oxacillinase (OXA) - Class D - cause of CRAB - common cause of CRE in Europe
41
Colistin Resistance
- MCR-1 gene encodes for resistance to colistin which is located on a plasmid and transferrable to other bacteria - possibility of all gram negative bacteria becoming resistant to every available antibiotic
42
Ceftazidime-Avibactam (Avycaz)
Ceftazidime: 3rd generation cephalosporin with activity against P. aeruginosa Avibactam: class of non Beta lactam Beta lactamase inhibitors (DBO) - reversible inhibitor of Class A, C, and some D B lactamases Indications: - intra abdominal infections with metronidazole - UTI - Hospital/Ventilator Associated Pneumonia Dose: 2.5 g every 8 hours (2 hr infusion) - give 2.5 g x 1 as loading dose - adjust for renal dysfunction (GFR < 50 mL/min)
43
Meropenem-Vaborbactam (Vabomere)
Meropenem: broad spectrum carbapenem Vaborbactam: boronic acid-based B lactamase inhibitor - inhibitor of Class A and C B lactamases Indications: - UTI Dose: 4 g IV every 8 hours (3 hr infusion) - adjust for renal dysfunction (GFR < 50 mL/min)
44
Imipenem-Cilastatin-Relebactam (Recarbrio)
Imipenem: carbapenem Relebactam: B lactamase inhibitor - inhibitor of Class A, C, and some D B lactamases Indications: - intra abdominal infections - UTI Dosing: 1.25 g IV over 30 minutes every 6 hours if CrCl > 90 mL/min
45
Cefiderocol (Fetroja)
Trojan horse siderophone cephalosporin MOA: catechol group on cephalosporin chelates iron allowing for uptake into cell via normal iron uptake channel --> dissociates to release active drug Indications: - UTI - Hospital/Ventilation acquired pneumonia Dosing: 2 g IV every 8 hours (3 hr infusion)
46
Sulbactam-Durlobactam (Xacduro)
Sulbactam: 1st generation B lactamase inhibitor against Acinetobacter species Durlobactam: diazabicycloctane B lactamase inhibitor - inhibitor of Class A, C, and D B lactamases especially in CRAB Indications: - hospital/ventilator acquired pneumonia Dosing: 2 g every 6 hours (3 hr infusion)

PHRM 852 Exam 2 (11 decks)

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