CIS: Pharmacotherapy of Respiratory Infections Flashcards by Bryce Harmon

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

most common cause

h flu
mycoplasma are also cap

staph is icu admitted

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CAP –Common Infecting Organisms

outpatient

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

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CAP –Common Infecting Organisms

hospitalized

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

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CAP –Common Infecting Organisms

ICU

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

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

curb score of 1

azithromycin

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CAP –Empiric Antimicrobial Guidelines
Outpatient Recommendations
◦Previously healthy

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

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outpatient recommendations

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

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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azithromycin moa

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Binds DNA gyrase preventing relaxation of DNA supercoils

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Disrupts cell membrane structure

daptomycin

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Prevents initiation of protein synthesis

aminoglycosides or linezolid

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Prevents the attachment of aminoacyl tRNAto acceptor site

tetracyclines

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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

levofloxacin

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S. pneumoniae with high-level penicillin resistance

What is the mechanism for penicillin resistance?

Alteration of the penicillin-binding protein

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Beta-lactamase production

gram negative or staph aureas resitant to natural penicillins

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Efflux pumps

peudomonas and they efflux fq, ag and macrolides

tetracyclines

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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

Cruise within previous two weeks

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Drug-resistant S. pneumoniae (DRSP)

risk

◦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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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

b or e

not e bc she was on cipro earlier

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ceftriaxone has no what coverage

atypical

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doxy covers

atypicals

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CAP –Empiric Antimicrobial Guidelines

Inpatient, Non-Intensive Care Unit Recommendations

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

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Ceftriaxone plus azithromycin

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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

cxr

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Signs of clinical improvement:

* 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

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

ceftriaxone

``` 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

ceftriaxone is not reanlly cleaed it is biliary cleard

levo adrs

cns with toxicity renal excretion

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?

Ventilator-associated pneumonia`

pseudomonas

Bacteroidesfragilis

anaerobe

HCAP, HAP & VAP | Early onset

(

HCAP, HAP & VAP | late onset

(5+ days)

HCAP, HAP & VAP | Aerobic gram-negative

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

HCAP, HAP & VAP | GPCs

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

HCAP, HAP & VAP | Oropharyngeal commensals

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

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

Piperacillin/tazobactam plus gentamicin

Empiric Therapy –Late Onset | Potential pathogens (MDR):

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

Empiric Therapy –Late Onset | Treatment:

◦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)

Carbapenems coverage

broad gram pos neg anaerobe and aerobic use for drug resistant bacteria

macrolides inhibit

inhibitor will ramp up warfarin bc it inhibits cyp enzymes macrolides inhibit cyp enzymes (clarithromycin and erythromycin) tetras interact with antacids

Blocks attachment of aminoacyl-tRNAto the A site

tetracyclines

Causes misreading of mRNA information

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.

acute pulmonary exacerbation of cf admit for iv abs

What is the likely mechanism of resistance of Staphylococcus aureus?

Reduced affinity of penicillin-binding proteins

What is the likely mechanism of resistance of Pseudomonas aeruginosa?

Efflux pumps

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

Tobramycin + piperacillin/tazobactam + vancomycin

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)

azithromycin orally 3xweek in cf

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.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

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

Ampicillin/sulbactam

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

cefotaxime

gram neg

ceftriaxone

gram neg gonorrhea lyme meningitis gram neg

ceftazidime

pseudomonas

nafciillin

staph

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

clindamycin

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

Histoplasma capsulatum loation chickens and on prednisone so immunosuppressed

What is the mechanism of action of the azole antifungals

Inhibition of ergosterol synthesis

azoles

14ademethylase inhibitors

polyenes

ergosterol binding amphotericin b

ampho b adrs

renal dysfunction and infusion related problems

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

flashing lights photophobia and color problems

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 ```

acute bronchitis use codeine

fg macrolides gentamicin efflux for

gram negs

second line agents for isoniazid

Ethionamide mycolic acid synthesiis inhibitors

second line agents for rifampin

Rifabutin | Rifapentine

second line agents for streptomycin

protein sythesis inhibirot for 2nd one Amikacin Capreomycin Kanamycin

capreomycin

ag nephrotoxicity

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

◦Fluoroquinolones ◦Aminosalicylicacid ◦Cycloserine ◦Linezolid

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:

mycolic acid synthesis.

rifampin induces

cyp450 3a4

Isoniazid (INH) MOA

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

Isoniazid (INH) Resistance

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

Isoniazid (INH) Related second line agents

ethionamide

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

actively dividing so rsistance and bacterial load

Drug resistant mutants –1 bacillus in 106

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

Combination therapy, drug resistance –1 bacillus in 1012

◦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)

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

resistance

Why isn’t streptomycin included in this regimen?

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

Streptomycin MOA

Binds S12 ribosomal protein of 30S subunit

Streptomycin Resistance

Mutations in rpsLor rrsgene which alter binding site

Streptomycin Therapeutic use

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

Streptomycin ADRs

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

Streptomycin Related second line agents

capreomycin, kanamycin, amikacin

``` 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?

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

Ethambutol (EMB) MOa

Inhibits mycobacterial arabinosyltransferases (encoded by embCABoperon)

Ethambutol (EMB) Resitance

◦Overexpression of embgene products | ◦Mutation in embBgene

Ethambutol (EMB) ADRS

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

``` 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 ```

D hepatotoxicity for first line treatments is major concern

``` 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 ```

pyrazinime most hepatoxic

Pyrazinamide (PZA) MOA

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

Pyrazinamide (PZA) Reisistance

Impaired biotransformation, mutation in pncA

Pyrazinamide (PZA) ADRs

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

Drug-induced Hepatitis overview

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

Drug-induced Hepatitis risk is age dependant

50 2.3%

INH Biotransformation

OCT 16 slide 81 pharmacotherapy of respiratory infections

``` 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 ```

pyroxidine or b6 thye have increased secretion of b6 alchoolics malourished or diabetes

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

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

P450 Induction by Rifamycins

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

Rifampin (RIF) MOA

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

Rifampin (RIF) Resistance

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

Rifampin (RIF) related second line agents

rifapentine, rifabutin

Rifampin (RIF) | ADRs:

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

CIS: Pharmacotherapy of Respiratory Infections Flashcards

(103 cards)