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CIS: Pharmacotherapy of Respiratory Infections Flashcards

1
Q 
A 56 y/o male presents to his primary-care provider’s office because of fever, chills, productive cough and confusion for the past 4 days.
Chest X-ray: dense, right lower lobe infiltrate
Most likely infecting pathogen?
A.Haemophilus influenzae
B.Klebsiella pneumoniae
C.Mycoplasma pneumoniae
D.Staphylococcus aureus
E.Streptococcus pneumoniae
A

e

most common cause

h flu
mycoplasma are also cap

staph is icu admitted

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2
Q

CAP –Common Infecting Organisms

outpatient

A

Streptococcus pneumoniae Mycoplasma pneumoniae* Haemophilus influenzae Chlamydophila pneumoniae* Respiratory viruses

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3
Q

CAP –Common Infecting Organisms

hospitalized

A

S. pneumoniae M. pneumoniae* C. pneumoniae* H. influenzae Legionella spp.* Aspiration Respiratory viruses

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4
Q

CAP –Common Infecting Organisms

ICU

A

S. pneumoniae Staphylococcus aureus Legionella spp. * Gram-negative bacilli H. influenzae

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5
Q

A 56 y/o male presents to his primary-care provider’s office because of fever, chills, productive cough and confusion for the past 4 days.
Chest X-ray: dense, right lower lobe infiltrate
Vital signs: Temp 100 ˚F, BP 140/90 mmHg, HR 100 bpm, RR 28 rpm

Which of the following drugs is most appropriate in the treatment of this patient?

A

curb score of 1

azithromycin

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6
Q

CAP –Empiric Antimicrobial Guidelines
Outpatient Recommendations
◦Previously healthy

A

Macrolide PO (azithromycin, clarithromycin) (se for strep pneumo and atypical coverge)
-OR-
Doxycycline PO

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7
Q

outpatient recommendations

DRSP risk (comorbidities, age > 65 years, use of antimicrobials within 3 months)

A

Respiratory fluoroquinolone PO (levofloxacin, moxifloxacin)
-OR-
B-lactam PO [high dose amoxicillin or amoxicillin-clavulanate preferred (alternates: ceftriaxone, cefuroxime)] PLUS a macrolide PO

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8
Q

azithromycin moa

A

Respiratory fluoroquinolone PO (levofloxacin, moxifloxacin)
-OR-
B-lactam PO [high dose amoxicillin or amoxicillin-clavulanate preferred (alternates: ceftriaxone, cefuroxime)] PLUS a macrolide PO

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9
Q

Binds DNA gyrase preventing relaxation of DNA supercoils

A

fg

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10
Q

Disrupts cell membrane structure

A

daptomycin

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11
Q

Prevents initiation of protein synthesis

A

aminoglycosides or linezolid

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12
Q

Prevents the attachment of aminoacyl tRNAto acceptor site

A

tetracyclines

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13
Q

A 56 y/o male presents to his primary-care provider’s office because of fever, chills, productive cough and confusion for the past 4 days.
Chest X-ray: dense, right lower lobe infiltrate
Vital signs: Temp 100 ˚F, BP 140/90 mmHg, HR 100 bpm, RR 28 rpm
Sputum culture: S. pneumoniae with high-level penicillin resistance
Now which antibiotic would be most appropriate?
A.Azithromycin
B.Cefazolin
C.Doxycycline
D.Levofloxacin
E.Trimethoprim/sulfamethoxazole

A

levofloxacin

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14
Q

S. pneumoniae with high-level penicillin resistance

What is the mechanism for penicillin resistance?

A

Alteration of the penicillin-binding protein

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15
Q

Beta-lactamase production

A

gram negative or staph aureas resitant to natural penicillins

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16
Q

Efflux pumps

A

peudomonas and they efflux fq, ag and macrolides

tetracyclines

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17
Q 
Which of the following is NOT a risk factor for penicillin-resistant S. pneumoniae?
A.Age > 65 years
B.Alcoholism
C.Antibiotics within the past 3 months
D.Cruise within previous two weeks
E.Multiple medical comorbidities
A

Cruise within previous two weeks

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18
Q

Drug-resistant S. pneumoniae (DRSP)

risk

A 
◦Age  65 years
◦B-lactam use within previous 3 months
◦Alcoholism
◦Immunosuppressive illness or therapy
◦Exposure to child at day care
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19
Q

Demographics: 68 y/o female, 2 day history productive cough/fever.
Ciprofloxacin three weeks ago for a urinary tract infection.
Temp: 101 ˚F, BP 125/75 mmHg, HR 90 bpm, RR 32 rpm,
O2saturation (RA) 88%
WBC 15,000 cells/mm3, band neutrophils 9%
Chest X-ray: left lower lobe infiltrate

2 inpatient

68 y/o female, admit to hospital with community-acquired pneumonia
Ciprofloxacin three weeks ago for a urinary tract infection.
Which of the following regimens is most appropriate?
A.Ceftriaxone
B.Ceftriaxone plus azithromycin
C.Doxycycline
D.Levofloxacin
E.Levofloxacin plus azithromycin

A

b or e

not e bc she was on cipro earlier

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20
Q

ceftriaxone has no what coverage

A

atypical

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21
Q

doxy covers

A

atypicals

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22
Q

CAP –Empiric Antimicrobial Guidelines

Inpatient, Non-Intensive Care Unit Recommendations

A

Respiratory FQ IV or PO (levofloxacin, moxifloxacin)
-OR-
B-lactam IV (ceftriaxone, cefotaxime, or ampicillin preferred) PLUSmacrolide IV (azithromycin

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23
Q

68 y/o female, admit to hospital with community-acquired pneumonia
Ciprofloxacin three weeks ago for a urinary tract infection.
Which of the following regimens is most appropriate?
A.Ceftriaxone
B.Ceftriaxone plus azithromycin
C.Doxycycline
D.Levofloxacin
E.Levofloxacin plus azithromycin

A

Ceftriaxone plus azithromycin

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24
Q

68 y/o female, admit to hospital with community-acquired pneumonia
Ciprofloxacin three weeks ago for a urinary tract infection.
Which of the following parameters is not routinely monitored during antibiotic therapy to determine response?
A.Adverse effects
B.Chest X-ray
C.Fever
D.Respiratory rate
E.WBC count

A

cxr

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25
Q

Signs of clinical improvement:

A
  • Temperature ≤ 37.8 ˚C
  • HR ≤ 100 bpm
  • RR ≤ 24 breaths/min
  • SBP ≥ 90 mmHg
  • Arterial 02 saturation ≥ 90%
  • Ability to maintain oral intake
  • Normal mental status
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26
Q

68 y/o female, admit to hospital with community-acquired pneumonia
Ciprofloxacin three weeks ago for a urinary tract infection.
Which of the following antimicrobial regimens does not cover atypical pathogens?
A.Azithromycin
B.Ceftriaxone
C.Doxycycline
D.Levofloxacin plus ceftriaxone
E.Moxifloxacin

A

ceftriaxone

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27
Q 
68 y/o female, admit to hospital with community-acquired pneumonia
Height 5’6”, Weight 135 lbs
SCr2 mg/dL
Which of the following does NOT need to be dose adjusted if prescribed to our patient?
A.Amoxicillin
B.Ampicillin/sulbactam
C.Ceftriaxone
D.Levofloxacin
E.Ertapenem[

looking for renal clearance

A

ceftriaxone is not reanlly cleaed it is biliary cleard

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28
Q

levo adrs

A

cns with toxicity renal excretion

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29
Q

A 76 y/o male was admitted to the hospital 13 days ago for coronary artery bypass grafting (CABG).
Post-CABG, patient was recovering slowly and was unable to be extubated.
He developed a fever and became agitated with increasing oxygen demands
76 y/o male, CABG13 days ago, unable to be extubated
Temp 102.8 ˚F, WBC 23,500 cells/mm3, band neutrophils 20%
SCr1.2 mg/dL
Two blood cultures: pending
Sputum culture: 4+ WBC and gram-negative bacilli
Diagnosis?

A

Ventilator-associated pneumonia`

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30
Q

76 y/o male, CABG13 days ago, unable to be extubated
Temp 102.8 ˚F, WBC 23,500 cells/mm3, band neutrophils 20%
SCr1.2 mg/dL
Two blood cultures: pending
Sputum culture: 4+ WBC and gram-negative bacilli
What is the most likely infecting pathogen?

A

pseudomonas

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31
Q

Bacteroidesfragilis

A

anaerobe

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32
Q

HCAP, HAP & VAP

Early onset

A

(

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33
Q

HCAP, HAP & VAP

late onset

A

(5+ days)

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34
Q

HCAP, HAP & VAP

Aerobic gram-negative

A

P. aeruginosa
E. coli
K. pneumoniae
Acinetobacter spp.

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35
Q

HCAP, HAP & VAP

GPCs

A

MRSA (more common in diabetes, head trauma, those hospitalized in ICUs)

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36
Q

HCAP, HAP & VAP

Oropharyngeal commensals

A

Viridansgroup streptococci
Coagulase-negative staphylococci
Neisseriaspp.
Corynebacteriumspp.

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37
Q

76 y/o male, CABG13 days ago, unable to be extubated
Temp 102.8 ˚F, WBC 23,500 cells/mm3, band neutrophils 20%
SCr1.2 mg/dL
Two blood cultures: pending
Sputum culture: 4+ WBC and gram-negative bacilli
Which of the following empiric treatment regimens is most appropriate for this patient?
A.Ceftazidime plus gentamicin plus vancomycin
B.Ceftriaxone
C.Levofloxacin plus metronidazole
D.Piperacillin/tazobactam plus gentamicin
E.Vancomycin

A

Piperacillin/tazobactam plus gentamicin

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38
Q

Empiric Therapy –Late Onset

Potential pathogens (MDR):

A

◦P. aeruginosa
◦K. pneumoniae (ESBL+)
◦Acinetobacter
◦MRSA

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39
Q

Empiric Therapy –Late Onset

Treatment:

A

◦Antipseudomonal cephalosporin (cefepime, ceftazidime) OR antipseudomonal carbapenem (imipenem, meropenem) OR B-lactam/B-lactamase inhibitor (piperacillin-tazobactam)
PLUS
◦Antipseudomonal FQ (ciprofloxacin, levofloxacin) OR aminoglycoside (gentamicin, tobramycin)
PLUS
◦Linezolid OR vancomycin (optional)

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40
Q

Carbapenems coverage

A

broad gram pos neg anaerobe and aerobic

use for drug resistant bacteria

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41
Q

macrolides inhibit

A

inhibitor will ramp up warfarin bc it inhibits cyp enzymes

macrolides inhibit cyp enzymes (clarithromycin and erythromycin)

tetras interact with antacids

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42
Q

Blocks attachment of aminoacyl-tRNAto the A site

A

tetracyclines

43
Q

Causes misreading of mRNA information

A

ag

44
Q

A 25 y/o female presents to the hospital for a CF “tune-up” as she has had increasing yellow-green sputum production, shortness of breath, and post-tussiveemesis.
She complains of a decreased appetite and a 2.8 kg weight loss since her previous clinic visit.

A

acute pulmonary exacerbation of cf

admit for iv abs

45
Q

What is the likely mechanism of resistance of Staphylococcus aureus?

A

Reduced affinity of penicillin-binding proteins

46
Q

What is the likely mechanism of resistance of Pseudomonas aeruginosa?

A

Efflux pumps

47
Q

A 25 y/o female, with cystic fibrosis, admitted to the hospital with an acute pulmonary exacerbation
When this patient experiences another CF exacerbation, which is the most appropriate intravenous antibiotic regimen for empiric management (based on most recent sputum culture)?
A.Meropenem plus ceftazidime
B.Tobramycin
C.Tobramycin + piperacillin/tazobactam
D.Tobramycin + piperacillin/tazobactam + vancomycin
E.Vancomycin

A

Tobramycin + piperacillin/tazobactam + vancomycin

48
Q

A 25 y/o female, with cystic fibrosis, admitted to the hospital with an acute pulmonary exacerbation
Our patient continues to culture Pseudomonas aeruginosaon subsequent sputum cultures. What maintenance therapy may be initiated that acts as an anti-inflammatory and may decrease the virulence of Pseudomonas aeruginosa?
A.Azithromycin
B.Hypertonic saline
C.Inhaled fluticasone
D.Prednisone
E.Tobramycin inhaled (TOBI)

A

azithromycin

orally 3xweek in cf

49
Q

An 8 y/o female presents with recent onset of fever, cough, and chills. Community-acquired pneumonia is suspected. She is to be treated as an outpatient.
Which of the following should NOT be used to treat this patient?
A.Amoxicillin –OK
B.Azithromycin –OK
C.Cefotaxime –IV only 3rdgeneration cephalosporin
D.Doxycycline –NO –teeth discoloration/impaired bone development
E.Levofloxacin –NO –not approved for

A

A.Amoxicillin –OK
B.Azithromycin –OK
C.Cefotaxime –IV only 3rdgeneration cephalosporin
D.Doxycycline –NO –teeth discoloration/impaired bone development
E.Levofloxacin –NO –not approved for

50
Q

An 85 y/o female, admitted to the general medical floor with aspiration pneumonia
You would like to use a B-lactam + azithromycin to follow the CAP guidelines. Which B-lactam has anaerobic activity?
A.Ampicillin/sulbactam
B.Cefotaxime
C.Ceftriaxone
D.Ceftazidime
E.Nafcillin

A

Ampicillin/sulbactam

51
Q

Ampicillin/sulbactam

A

extended bc garm pso and neg

beta lactamse inhibtors also cover anaerobic activity

add to azithromycin or clindamyin (protein inhibitor manage for cdiff)use to treat aspiration pneumonia

carbapenems also cover anaerobes

daptomycin is inactivated in the lung by the surfactant

ag are oxygen dependant

52
Q

cefotaxime

A

gram neg

53
Q

ceftriaxone

A

gram neg

gonorrhea lyme meningitis

gram neg

54
Q

ceftazidime

A

pseudomonas

55
Q

nafciillin

A

staph

56
Q

An 85 y/o female, admitted to the general medical floor with aspiration pneumonia
Which protein synthesis inhibitor has anaerobic activity and is used to treat aspiration pneumonia?
A.Ceftriaxone
B.Clindamycin
C.Daptomycin
D.Gentamicin
E.Metronidazole

A

clindamycin

57
Q

A 47 y/o male with severe RA has been maintained on daily prednisone for the past 6 years. He recently moved to Denver from the St. Louis area where he raised chickens.
For the past 4 weeks, he has experienced daily fevers, drenching night sweats, anorexia, and a 16 lbweight loss.
He is admitted to the hospital.
Chest X-ray: bilateral interstitial infiltrates
Diagnosis

A

Histoplasma capsulatum

loation chickens and on prednisone so immunosuppressed

58
Q

What is the mechanism of action of the azole antifungals

A

Inhibition of ergosterol synthesis

59
Q

azoles

A

14ademethylase inhibitors

60
Q

polyenes

A

ergosterol binding amphotericin b

61
Q

ampho b adrs

A

renal dysfunction and infusion related problems

62
Q

What specific adverse drug reaction is associated with use of voriconazole as opposed to other azole antifungals?

A

flashing lights photophobia and color problems

63
Q

A 35-yo woman presents with a persistent cough following an acute respiratory viral infection that began 7 days ago.
Although the nasal stuffiness and sore throat resolved 3-4 days ago, the cough has persisted and her sputum has become thick and mucoid; a burning, substernal pain is associated with each coughing episode.
Course rales and rhonchi are heard on physical exam of her chest. She is afebrile.
HR 75 bpm, BP 132/92 mmHg, RR 22 rpm.
She is a non-smoker.

What is the diagnosis?
Which of the following is an appropriate treatment for this woman?
A.Azithromycin
B.Clindamycin
C.Levofloxacin
D.Doxycycline
E.Codeine
A

acute bronchitis use codeine

64
Q

fg macrolides gentamicin efflux for

A

gram negs

65
Q

second line agents for

isoniazid

A

Ethionamide

mycolic acid synthesiis inhibitors

66
Q

second line agents for

rifampin

A

Rifabutin

Rifapentine

67
Q

second line agents for

streptomycin

A

protein sythesis inhibirot for 2nd one

Amikacin
Capreomycin
Kanamycin

68
Q

capreomycin

A

ag

nephrotoxicity

69
Q

Additional second-line (and third-line) agents for TB

A

◦Fluoroquinolones
◦Aminosalicylicacid
◦Cycloserine
◦Linezolid

70
Q

A 36 y/o female presents with a 2-month history of cough, which has recently become productive, and an unexplained 15 pound weight loss. Additional symptoms include fatigue and night sweats.
Physical examination is unremarkable.
Chest X-ray: pulmonary infiltrates.
PMH: well-controlled type-1 diabetes mellitus and poor nutritional status secondary to frequent dieting.
She works as a volunteer in a nursing home several days a week where it was recently discovered that two patients who she had been caring for had undiagnosed active tuberculosis.

Tests ordered
•Tuberculin purified protein derivative (PPD) skin test
•Palpable induration of 14 mm, read at 48 hours
•Sputum collections for susceptibility testing of cultures
•Results back in 2-4 weeks
•Sputum acid-fast bacillus (AFB) smear
•Positive for AFB

36 y/o female with active tuberculosis
Well-controlled type-1 diabetes mellitus
Poor nutritional status secondary to frequent dieting
The most active drug for the treatment of TB caused by susceptible strains is prescribed. What is the mechanism of action?
Inhibition of:

A

mycolic acid synthesis.

71
Q

rifampin induces

A

cyp450 3a4

72
Q

Isoniazid (INH)

MOA

A

inhibits synthesis of mycolic acids
◦Prodrug, activated by KatG
◦Active form binds AcpMand KasAinhibits mycolic acid synthesis

73
Q

Isoniazid (INH)

Resistance

A

◦Mutation or deletion of katGgene
◦Overexpression of inhAand ahpC
◦Mutation in kasA

74
Q

Isoniazid (INH)

Related second line agents

A

ethionamide

75
Q

Why is it important to use a combination drug regimen? in tb

A

actively dividing so rsistance and bacterial load

76
Q

Drug resistant mutants –1 bacillus in 106

A

◦Asymptomatic patients –bacillary load of 103
◦Cavitarypulmonary TB –bacillary load > 108
Resistance readily selected out if single drug used

77
Q

Combination therapy, drug resistance –1 bacillus in 1012

A

◦Rates of resistance additive functions of individual rates

◦Example: only 1 in 1013organisms would be naturally resistant to both isoniazid (1 in 106) and rifampin (1 in 107)

78
Q

2+ active agents should always be used for active TB to prevent

A

resistance

79
Q

Why isn’t streptomycin included in this regimen?

A

a lot of resistance in other countried given iv it is a ag

ethambutol or streptomycin can be used as the fourth line

reserved for when you need a injected and last resort

80
Q

Streptomycin

MOA

A

Binds S12 ribosomal protein of 30S subunit

81
Q

Streptomycin

Resistance

A

Mutations in rpsLor rrsgene which alter binding site

82
Q

Streptomycin

Therapeutic use

A

When injectable drug needed/desired –patients with severe, life-threatening forms of TB

83
Q

Streptomycin

ADRs

A

◦Ototoxicity (vertigo and hearing loss)
◦Nephrotoxicity
◦Relatively contraindicated in pregnancy (newborn deafness)

84
Q

Streptomycin

Related second line agents

A

capreomycin, kanamycin, amikacin

85
Q 
Results from the drug-susceptibility testing show that there are tubercle bacilli resistant to one agent in the current regimen. Isolates with mutations in the gene encoding arabinosyltransferase (embgene) have been identified. Which agent is ineffective?
A.Ethambutol
B.Isoniazid
C.Pyrazinamide
D.Rifampin
E.Streptomycin

What change(s) should be made to the current regimen?

A

ethambutol

when proven susceptibility to the other 3 stop this one and you may not need to add streptomycin

86
Q

Ethambutol (EMB)

MOa

A

Inhibits mycobacterial arabinosyltransferases (encoded by embCABoperon)

87
Q

Ethambutol (EMB)

Resitance

A

◦Overexpression of embgene products

◦Mutation in embBgene

88
Q

Ethambutol (EMB)

ADRS

A

◦Retrobulbarneuritis (loss of visual acuity, red-green color blindness)
◦Rash
◦Drug fever
◦Relatively contraindicated in children too young to assess visual acuity

89
Q 
36 y/o female with active tuberculosis
Well-controlled type-1 diabetes mellitus
Poor nutritional status secondary to frequent dieting
The patient returns for follow-up one month after starting the 4 drug regimen. Which of the following lab values is most likely elevated?
A.Creatinephosphokinase
B.Hematocrit
C.Potassium
D.Serum aminotransferase activity
E.Triglycerides
A

D

hepatotoxicity for first line treatments is major concern

90
Q 
36 y/o female with active tuberculosis
Well-controlled type-1 diabetes mellitus
Poor nutritional status secondary to frequent dieting
Which agent is most likely to cause hepatotoxicity in this patient?
A.Ethambutol
B.Isoniazid
C.Pyrazinamide
D.Rifampin
E.Streptomycin
A

pyrazinime

most hepatoxic

91
Q

Pyrazinamide (PZA)

MOA

A

disrupts mycobacterial cell membrane synthesis and transport functions
◦Macrophage uptake, conversion to pyrazinoicacid (POA-)
◦Efflux pump to extracellular milieu
◦POA-protonated to POAH, reenters bacillus

92
Q

Pyrazinamide (PZA)

Reisistance

A

Impaired biotransformation, mutation in pncA

93
Q

Pyrazinamide (PZA)

ADRs

A

◦Hepatotoxicity (1-5%)
◦GI upset
◦Hyperuricemia

94
Q

Drug-induced Hepatitis overview

A

The most common major side effect of isoniazid; can also occur with rifampin; pyrazinamide is probably the most hepatotoxic anti-TB agent
Liver aminotransferases may increase up to 3-4 times normal
◦Patients are typically asymptomatic; continue therapy
Clinical hepatitis (with loss of appetite, nausea, vomiting, jaundice, and right upper quadrant pain) occurs in 1% of isoniazid recipients
◦May be fatal if not promptly discontinued
Hepatitis risk increases in patients who are alcoholics and possibly during pregnancy and the postpartum period

95
Q

Drug-induced Hepatitis risk is age dependant

A

50 2.3%

96
Q

INH Biotransformation

A

OCT 16 slide 81 pharmacotherapy of respiratory infections

97
Q 
36 y/o female with active tuberculosis
Well-controlled type-1 diabetes mellitus
Poor nutritional status secondary to frequent dieting
During the follow-up exam, the patient reports frequent tingling and burning in her hands and feet as well as general muscle aches and weakness. What vitamin supplement should be prescribed to alleviate these symptoms?
A.Vitamin A
B.Vitamin B1
C.Vitamin B6
D.Vitamin C
E.Vitamin D
A

pyroxidine or b6

thye have increased secretion of b6 alchoolics malourished or diabetes

98
Q

What are some important considerations before choosing an anti-TB regimen? in an aids pat

A

rifamycins

choose rifabutin least at inducing p450

rifapentine only given once a week and you have to give it more than that for active tb with hiv

99
Q

P450 Induction by Rifamycins

A

Rifampin is a strong P450 inducer (1A2, 2C9, 2C19, 2D6, 3A4)
◦Use with caution in patients with HIV who are taking protease inhibitors (PIs) and non-nucleoside reverse-transcriptase inhibitors (NNRTIs)
◦Half-lives, and thus efficacy, of agents metabolized by CYP450s (e.g., PIs, NNRTIs) are reduced
◦Other agents metabolized by P450s: isoniazid, digoxin, propranolol, warfarin, oral contraceptives, etc.
Rifampin is the most potent P450 inducer
Rifabutinis the least potent

100
Q

Rifampin (RIF)

MOA

A

inhibits RNA synthesis

◦Binds B-subunit of DNA-dependent RNA polymerase (rpoB)

101
Q

Rifampin (RIF)

Resistance

A

◦Reduced binding affinity to RNA polymerase point mutations within rpoBgene

102
Q

Rifampin (RIF) related second line agents

A

rifapentine, rifabutin

103
Q

Rifampin (RIF)

ADRs:

A 
◦Nausea/vomiting (1.5%)
◦Rash (0.8%)
◦Fever (0.5%)
◦Harmless red/orange color to secretions
◦Hepatotoxicity
◦Flu-like syndrome (20%) in those treated

Resp (11 decks)

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