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Resp II Exam II > Drugs for the treatment of Resp infections (Kinder - lecture) > Flashcards

Drugs for the treatment of Resp infections (Kinder - lecture) Flashcards

1
Q

what patients are excluded from the general guidelines of management of community acquired pneumonia ?

A

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

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2
Q

what is the CURB-65 score based on? what criteria?

A

it is a tool to assess pneumonia severity

Confusion

Uremia (BUN > 19 mg/dL)

Respiratory rate (≥ 30 breaths/min)

Low blood pressure

SBP < 90 mmHg, DBP ≤ 60 mmHg

Age (≥ 65 Years)

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3
Q

CURB-65 score of 0-1

A

treat as outpatient

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4
Q

score of 2 (CURB-65)

A

admit to hospital

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5
Q

Score of >3 (CURB-65)

A

admit to ICU

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6
Q

what are the minor criteria that are included with CURB - 65 score to determine need for ICU admission (x3)

A

WBC < 4000 cells/mm3
PLT < 100,000 cells/mm3
Core temperature < 36 ˚C

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7
Q

2 absolute indications for ICU admission

A

mechanical ventilation

septic shock

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8
Q

Clinical findings of Community aquired pneumonia?

what if a CXR is negative?

A

cough
fever
sputum production
pleuritic chest pain

demonstratable infiltrate on CXR is required ***

If negative but CAP suspected, initiate antibiotics and repeat CXR in 24-48 hours

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9
Q

what are the atypical bacteria in CAP

3

A

Mycoplasma pneumoniae

Chlamydophila pneumoniae

Legionella spp

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10
Q

what are the most common outpatient bugs in CAP

5

A 
Streptococcus pneumoniae (diplococci)
Mycoplasma pneumoniae
Haemophilus influenzae
Chlamydophila pneumoniae
Respiratory viruses
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11
Q

most common bugs in inpatient CAP (non-ICU) ‘

7

A 
S. pneumoniae 
M. pneumoniae
C. pneumoniae
H. influenzae
Legionella spp
Aspiration
Respiratory viruses
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12
Q

what are the most common bugs in inpatient ICU

5

A 
S. pneumoniae
Staphylococcus aureus
Legionella spp
Gram-negative bacilli
H. influenzae
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13
Q

infecting organisms and disease state of underlying bronchopulmonary disease?

3

A

H. influenzae
Moraxella catarrhalis
+ S. aureus during an influenza outbreak

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14
Q

patient on chronic oral steroids or severe underlying bronchopulmonary disease, alcoholism, frequent antibiotic use? what bugs are frequent in them

2

A

Enterobacteriaceae

Pseudomonas aeruginosa

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15
Q

Classic aspiration pleuropulmonary syndrome in alcohol/drug overdose or in seizures with gingival disease or esophageal motility disorders

1

A

anaerobes (aspiration of the common mouth bugs that leads to pneumonia)

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16
Q

what are common viruses in CAP *4

A

Influenza
RSV
Adenovirus
Parainfluenza virus

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17
Q

Drug resistant s. pneumoniae (DRSP) is more common in what groups…

5

A

Age < 2 years or > 65 years

B-lactam use within previous 3 months*** (amoxicillin?)

Alcoholism

Immunosuppressive illness or therapy

Exposure to child at day care

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18
Q

for a previously healthy patient what would you use for CAP

A

Macrolide PO (***azithromycin)

Doxycycline PO

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19
Q

what patients are at risk for drug resistant strep pneumoniae

what would you use to treat patients

one drug

OR

two drugs

A 
Comorbidities
age 65
use of antimicrobials (beta lactams) within 3 months
alcoholism
immunosuppressive illness or therapy
exposure to child at day care

Respiratory fluoroquinolone PO (levofloxacin***, moxifloxacin)

B-lactam PO [high dose amoxicillin* or amoxicillin-clavulanate* preferred (alternates: ceftriaxone, cefuroxime)]
PLUS** a macrolide PO (azithromycin)

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20
Q

inpatient, non ICU
what do you use to cover CAP

one drug

OR

one drug PLUS one drug

A

Respiratory FQ IV or PO (levofloxacin***, moxifloxacin)

B-lactam IV (ceftriaxone, cefotaxime, or ampicillin preferred)
PLUS macrolide IV (azithromycin*)

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21
Q

inpatient ICU patient . what would you use for coverage for CAP

A

B-lactam IV (ceftriaxone***, cefotaxime, or ampicillin/sulbactam preferred)

PLUS macrolide (azithromycin) IV OR a respiratory FQ (levofloxacin***, moxifloxacin)

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22
Q

what are the risk factors for pseudomonas?

A

Structural lung disease (bronchiectasis)

Repeated COPD exacerbations
Frequent corticosteroid and/or antibiotic use

Prior antibiotic therapy

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23
Q

how do you treat patients with pseudomonas?

2 drugs

OR

1 drug plus 2 drugs

A

Anti-pseudomonal B-lactam IV (piperacillin-tazobactam, cefepime, meropenem)

PLUS FQ–> either ciprofloxacin or levofloxacin

Or

 B-lactam PLUS:
An aminoglycoside (gentamicin) AND azithromycin (covers atypicals)

An aminoglycoside (gentamicin) AND anti-pseudomonal fluoroquinolone (ciprofloxacin)

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24
Q

CA methicillin resistant staphylococcus aureus (CA-MRSA) risks….

4

A

End-stage renal disease (dialysis)
Injection drug abuse
Prior influenza
Prior antibiotic use (especially FQ)

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25
treatment for CA-MRSA
Add vancomycin (Glycopeptide- inhibits cells wall synthesis) IV or linezolid (binds P site of 50S ribosome)
26
what criteria allow you do transition from IV to oral therapy? what are the signs (7) that a person is improving clinically
Hemodynamically stable ``` Improving clinically: 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 ``` Tolerating oral medications Normal functioning GI tract
27
what is the duration of therapy for antibiotics for CAP
Minimum of 5 days treatment | Most patients receive 7-10 days
28
what are the criteria for ending of therapy.... what is the exception?
Must be afebrile for 48-72 hours No more than 1 CAP-associated sign of clinical instability Exception: Pseudomonas – 8 day course led to more relapse compared to 15 day course
29
what is the definition of Hospital acquired pneumonia?
occurs 48 hours or more after admission 2nd most common nosocomial infection in the U.S. Increases hospital LOS ~7-9 days Incidence: 5-10 cases per 1000 admissions
30
what is ventilator associated pneumonia
arises 48-72 hours after endotracheal intubation Occurs in 9-27% of all intubated patients Incidence increases with longer ventilation duration
31
Health care associated pneumonia ?
associated with history of hospitalization or exposure to healthcare settings exposure to health care setting chemo hemodialysis
32
what is early onset of HAP, VAP, HCAP? late onset?
early onset is <4 days 5+ or more days after admission
33
what are the common pathogens in HAP, VAP, HCAP?
``` Aerobic gram-negative P. aeruginosa E. coli K. pneumoniae Acinetobacter spp ``` GPCs (gram positive) MRSA (more common in diabetes, head trauma, those hospitalized in ICUs) ``` Oropharyngeal Viridans group streptococci Coagulase-negative staphylococci Neisseria spp Corynebacterium spp ```
34
Pseduomonas aeruginosa mechanisms for being drug resistant?
multiple efflux pumps **** Decreased expression of outer membrane porin channel Increasing resistance to: piperacillin (b-lactamase inhibitor), ceftazidime (third generation cephalosporin), cefepime (fourth generation cephalosporin), imipenem, meropenem (carbapenem), aminoglycosides, fluoroquinolones
35
MRSA (staph aureus).... resistance mechanisms? DRSP resistance mechanisms?
> 50% of ICU infections caused by S. aureus methicillin resistant PBPs with reduced affinity for B-lactams Concern for linezolid resistance but still rare DRSP: altered PBP All MDR strains in US currently susceptible to vancomycin and linezolid
36
early onset associated pathogens in HAP and no known risk factors for MDR pathogens
S. pneumoniae H. influenzae MSSA Sensitive gram-negative: E. coli, K. pneumoniae, Enterobacter spp, Proteus spp, Serratia marcescens
37
treatment of early onset HAP 4 stand alone drug classes
Ceftriaxone (third generation cephalosporin) OR FQ (levofloxacin, moxifloxacin, ciprofloxacin) = inhibits DNA gyrase OR ampicillin/sulbactam OR ertapenem (Carbapenem)
38
what are the potential pathogens in late onset HAP
P. aeruginosa K. pneumoniae (ESBL+) Acinetobacter MRSA
39
treatment of late onset HAP or known risk factors for MDR pathogens 3 drug classes (Or's) Plus one drug class or another drug class Plus one drug class or another drug class
``` 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) ``` PLUS Linezolid OR vancomycin
40
why use combination therapy ?
Combination therapy recommended to ensure at least one agent is active against the often MDR pathogen Has been recommended to prevent resistance Evidence not well documented Or to add synergy for treatment of P. aeruginosa Only proven valuable in neutropenia or bacteremia Use monotherapy when possible
41
duration of therapy of VAP what do prolonged courses lead to?
Good clinical response after 6 days Prolonged courses leads to MDR pathogen colonization so keep the duration SHORT Shorten duration to as short as 7 days (traditional 14-21 days) Unless P. aeruginosa (8 days led to relapse  requires longer treatment course)
42
drugs of choice for streptococcus pneumoniae non resistant? resistant?
Non-resistant Penicillin G, amoxicillin Resistant Chosen on basis of susceptibility: cefotaxime, ceftriaxone, levofloxacin, moxifloxacin, alternatives--> vancomycin, linezolid
43
drugs for haemophilus influenzae non-Beta lactamase producing bug (1 drug) b-lactamase producing bug (2 drug classes)
Non-B-lactamase producing Amoxicillin B-lactamase producing 2nd or 3rd generation cephalosporin, amoxicillin/cluvulanate
44
drugs for mycoplasma pneumoniae 2 drug classes
Macrolide (azithromycin, clarithromycin) | tetracycline (doxycycline)
45
chlamydophila pneumoniae drugs of choice (2 drugs)
first choice--> tetracycline (doxycycline) 2nd choice--> Macrolide (azithromycin, clarithromycin),
46
drugs for chlamydophilia psittaci
Doxycycline
47
legionella spp drugs of choice 2 drugs 1 alternative
Fluoroquinolone, azithromycin, alternative --> doxycycline
48
drugs of choice for enterobacteriaceae | Klebsiella, E. coli, Enterobacter, Proteus
3rd or 4th generation cephalosporin, carbapenem (if ESBeta Lactamase producer)
49
drugs of choice for pseudomonas aeruginosa 1 drug class PLUS 1 of 2 other drug classes
Antipseudomonal B-lactam (piperacillin-tazobactam) (ampicillin- sulbactam) (amoxicillin-clavulante) PLUS FQ (ciprofloxacin, levofloxacin) , or an aminoglycoside (gentamicin)
50
drugs of choice for Anaerobe (aspiration): Bacteroides, Fusobacterium, Peptostreptococcus
B-lactam/B-lactamase inhibitor, clindamycin (causes diarrhea- 50S inhibitor of translocation)
51
drugs of choice for staph aureus
``` Methicillin-sensitive Antistaphylococcal penicillin (nafcillin, oxacillin, dicloxacillin) ``` Methicillin-resistant Vancomycin or linezolid
52
drugs for Pneumocystis jiroveci (P. carinii pneumonia)
Trimethoprim/sulfamethoxazole (sulfonamides)
53
drugs for bordetella pertussis
Azithromycin, clarithromycin
54
drugs for influenza virus
Oseltamivir, zanamivir
55
drugs for coccidioides spp
No treatment necessary if normal host | Itraconazole, fluconazole
56
drugs for Histoplasmosis and Blastomycosis
Itraconazole
57
MOA of B-lactams
B-lactams are structural analogs of D-Ala-D-Ala; they covalently bind penicillin-binding proteins (PBPs), inhibiting the last transpeptidation step in cell wall synthesis
58
adverse effects of penicillins
``` Allergic reactions (0.7-10%) Anaphylaxis (0.004-0.04%) Interstitial nephritis (rare) Nausea, vomiting, mild to severe diarrhea Pseudomembranous colitis ```
59
resistance mechanisms of B-lactams
Structural difference in PBPs- DRSP Decreased PBP affinity for B-lactams Inability for drug to reach site of action (i.e. gram-negative organisms) Active efflux pumps- pseudomonas Drug destruction and inactivation by B-lactamases- MRSA
60
adverse effects of cephalosporins
1% risk of cross-reactivity to penicillins*** Diarrhea Intolerance to alcohol (disulfram-like reaction due to MTT group of cefotetan)
61
adverse effects of carbapenems
Nausea/vomiting (1-20%) Seizures (1.5%) Hypersensitivity
62
MOA of vancomycin (glycopeptide)
inhibits cell wall synthesis binding with high affinity to D-Ala-D-Ala terminal of cell wall precursor units.
63
adverse effects of vancomycin
Macular skin rash, chills, fever, rash Red-man syndrome*** (histamine release): extreme flushing, tachycardia, hypotension Ototoxicity, nephrotoxicity (33% with initial tr > 20 mcg/mL)
64
resistance mechansims of vancomycin
alteration of D-Ala-D-Ala target to D-alanyl-D-lactate or D-alanyl-D-serine which binds glycopeptides poorly. Intermediate resistance may also occur
65
fluoroquinolones MOA
concentration-dependent, targets bacterial DNA gyrase & topoisomerase IV. Prevents relaxation of positive supercoils
66
resistance mechanisms of bugs to fluorquinolones
mutation in genes encoding DNA gyrase or topoisomerase IV. Active transport out of cell.
67
adverse effects of fluoroquinolones
GI 3-17% (mild nausea, vomiting, abdominal discomfort) CNS 0.9-11% (mild headache, dizziness, delirium, rare hallucinations) Rash, photosensitivity, Achilles tendon rupture*** (CI in children)
68
what are the 30S inhibitors and what are the adverse side effects
Aminoglycosides ADRs: ototoxicity, nephrotoxicity, neuromuscular block Tetracyclines ADRs: GI, superinfections with C. difficile, photosensitivity, teeth discoloration**** (don't use in peds)
69
what are the 50S inhibitors
Macrolides (azithromycin) ADRs: GI, hepatotoxicity, arrhythmia Clindamycin (gram + or anearobes) ADRs: diarrhea, C. difficile, skin rash Streptogramins ADRs: infusion pain and phlebitis Linezolid ADRs: myelosuppression, headache, rash
70
how is influenza transmitted incubation period?
``` Respiratory droplets (cough, sneeze, talk) Contaminated surfaces ``` Incubation: 1-4 days (average 2 days) Viral shedding: day after symptoms to 5-10 days after illness onset
71
what are the symptoms of influenza
``` Symptoms (abrupt onset): Fever Myalgia Headache Malaise Non-productive cough Sore throat Rhinitis ``` Symptoms resolve after 3-7 days (uncomplicated) Cough/malaise can last > 2 weeks
72
Nueurominidase inhibitors MOA
Oseltamivir (PO) analogs of sialic acid, interferes with release of progeny influenza virus from infected host cell
73
what are the neurominidase inhibitors
Oseltamivir (PO), zanamivir (INH)
74
what re the adverse effects of oseltamivir (tamiflu)
nausea, vomiting, abdominal pain (5-10%), headache, fever, diarrhea, neuropsychiatric effects glomerular filtration and tubular secretion are how it is eliminated so you must adjust for renal problems! Approved for children ≥ 1 year
75
what are the resistance mechansims of bugs against neurominidase inhibitors
point mutation in viral hemagglutinin (HA) or neuraminidase (NA) surface proteins 97.4% seasonal H1N1 resistant to oseltamivir 2008-2009 All influenza A & B viruses susceptible to both drugs
76
what is the therapeutic use of neurominidase inhibitors
influenza prophylaxis (household and institutional), influenza treatment
77
what are the resistance mechanisms against M2 channel blockers
point mutations, marked resistance limiting use of these agents
78
what is the therapeutic use of acyclovir and valacyclovir
genital herpes (treatment, prophylaxis, suppression), varicella, HSV encephalitis, neonatal HSV treatment
79
therapeutic use of Ganciclovir (PO, IV), valganciclovir (PO)
CMV retinitis treatment, CMV prophylaxis
80
azole antifungal MOA
inhibits fungal cytochrome P450, reducing production of ergosterol Selective toxicity due to greater affinity for fungal rather than human cytochrome P450 enzymes
81
what is ergosterol
is found in cell membrane of fungi (compared to cholesterol used in bacteria and human cells)
82
what re the therapeutic uses of azole antifungals
wide spectrum of activity against Candida spp, blastomycosis, coccidiodomycosis, histoplasmosis, and even Aspergillus (itraconazole, voriconazole)
83
adverse effects of azole antifungals
minor GI upset, abnormalities in liver enzymes drug interactions - inhibition of hepatic P450's warfarin--> since it inhibits hepatic P450 then it can become toxic more quickly
84
what are 3 azole antifungals
fluconazole itraconazole voriconazole
85
what is the therapeutic use of amphotericin B
broadest spectrum of activity, useful in life-threatening infections but very toxic
86
major adverse effects of Voriconazole
visual changes, photosensitivity
87
what drug has increased drug absorption by food and low gastric pH
itraconazole
88
which azole antifungal has good CSF penetration
fluconazole

Resp II Exam II (11 decks)

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