Bronchitis+Influenza+Pneumonia+Tuberculosis Pharmacology

Acute Bronchitis NP Tx

1st line tx

sx tx

• antipyretics

• fluid intake

• guaifenesin

mist tx

• vaporizer

cough

• antitussive agents

• mucolytic agents

Acute Bronchitis Mx Tx

2nd line tx
tx within 48h for efficiency

influenza→PO oseltamivir BID x 5 days

parainfluenza→NP

RSV→NP

coronavirus→NP

adenovirus→NP

rhinovirus→NP

m. pneumoniae
azithromycin x 5 days
doxycycline BID x 5 days

c. pneumoniae
azithroycin x 5 days
doxycycline BID x 5 days

no abx→explain to pt why not+how unnecessary use can cause superbacteria

Acute Bronchitis Supportive Tx

acetaminophen q4-6h

ibuprofen q6-8h

PO/IV corticosteroids (controversial)

inhaled beta 2 agonists

Influenza Mx Tx

TX
adults
PO oseltamivir BID x 5 days
inhaled zanarnivir BID x 5 days
IV peramivir (not recommended)
PO baloxavir daily

peds
PO oseltamivir BID x 5 days
inhaled zanarnivir BID x 5 days (7+ y/o)
IV peramivir
PO baloxavir daily (12+ y/o+ 40+kg)

chemoprophx
adults
PO oseltamivir daily x 10 days
inhaled zarnarnivir daily x 10 days
PO baloxavir daily

peds
PO oseltamivir daily x 10 days
inhaled zarnarnivir daily x 10 days
PO baloxavir daily (12+ y/o+ 40+kg)

Community Acquired Pneumonia (CAP) Inpatient Mx Tx

no pseudomonas+MRSA RFs (non-severe CAP)
mono tx:
PO levofloxacin daily
PO moxifloxacin daily
IV levofloxacin daily
IV moxifloxacin daily

combo tx:
IV unasyn q6h
IV cefotaxime q8h
IV ceftriaxone daily
+
PO azithromycin daily
IV azythromycin daily
PO doxycycline q12h
IV doxycyline q12h

MRSA RF
add on anti-MRSA agent
+IV vancomycin q12h
+PO linezolid q12h
+IV linezolid q12h

pseudomonas RF
replace beta lactam→antipseudomonal agent
IV zosyn q6h
IV cefepime q8h
IV ceftazadime q8h
IV aztreonam q8h
IV metropenem q8h
IV levofloxacin daily

Community Acquired Pneumonia (CAP) Outpatient Mx Tx

healthy+no comorbidities
PO amoxicillin TID
PO doxycycline BID
macrolide (northeast→resistance)
PO azithromycin x 5 days
PO clarithromycin BID
PO clarithromycin ER daily

comorbidities
mono tx:
PO moxifloxacin daily
PO levofloxacin daily
PO gemifloxacin daily

combo tx:
PO augmentin TID
PO augmentin BID
PO cephalosporin Q12h
+
macrolide
tetracycline

no pseudomonas+MRSA RFs (severe CAP)
IV ceftriaxone daily+IV/PO azithromycin q24h
IV ceftriaxone daily+IV/PO doxycycline q12h

critically ill
IV ceftriaxone daily+IV/PO levofloxacin q24h

beta lactam allergy/anaphylaxis
PO levofloxacin q24h
IV levofloxacin q24h

Community Acquired Pneumonia (CAP) Mx Tx Duration

most pts→5 days
-have to demonstrate clinical stability
-need tx improvement in 48-72 hrs

pneumonia/MRSA/pseudomonas→7 days

Acute Bronchitis

PP: inflammation of large airways
infxn→inflammation of epithelium of bronchi

RF: 5% adults
9th m/c dx

E:
virus
influenza
RSV
parainfluenza
rhinovirus
coronavirus
adenovirus

bx
m. pneumoniae
s. pnuemoniae
h. influenzae
m. catarrhalis

environment
air pollution
cigarette smoke

CM: non-specific mild upper respiratory sx→acute cough
no PNA
lasts over 5+ days (2-3 weeks)
slow tx
lower respiratory tract infxn

DX: clinical
r/o ddx
extended respiratory viral panel
antigen-based PCR test

Influenza CM+C

CM: sudden onset
cough
sore throat
dyspnea
high-grade fevers (102-104°F)
severe body ache
severe pain

C: primary viral dx
secondary bx PNA

Pneumonia (General)

E: community-acquired pneumonia (CAP)→outside hospital setting
hospital-acquired pneumonia (HAP)→48+hrs post-admission+didn’t incubate during admission
ventilator associated pneumonia (VAP)→48+hrs post endotracheal intubation

CM: abrupt onset
fever
chills
dyspnea
angina
productive cough→rust colored sputum/hemoptysis
pleuritic chest pain

PE: tachypnea
tachycardia
dullness to percussion
increased tactile fremitus
whisper pectriloquy
egophony
chest wall retractions
grunting respirations
diminished breath sounds over affected area
inspiratory crackles during expansion

DX: CXR/chest CT
dense lobar/segmental infiltrate

Community Acquired Pneumonia (CAP) (General)

CM: cough
dyspnea
pleuritic angina
fever

PE: tachycardia
tachypnea
increased tactile fremitus
egophony
dullness to percussion
chest wall retractions
grunting respirations
diminished breath sounds over affected area
lung expansion→inspiratory crackles

DX: inflammatory markers
ESR
CRP
procalcitonin→elevated (0.25+)

Community Acquired Pneumonia (CAP) Inpatient vs Outpatient Dx

inpatient
CXR
sputum culture
blood culture
severe CAP→s pneumoniae+legionella urinary antigen tests
procalcitonin

outpatient
no sputum gram stain
no sputum culture

Community Acquired Pneumonia (CAP) Major vs Minor Criteria

minor CAP
RR: 30+ BPM
PaO2/FiO2: u250
multi lobar infltrates
confusion
disorientation
BUN: 20+mg/dL
WBC: u4000 cells/uL
platelets: u100k/uL
hypothermia
hypotension+fluid resuscitation

major CAP
septic shock+vasopressors
RF+mechanical ventilation

1+ major criteria/3+minor criteria=severe CAP

Community Acquired Pneumonia (CAP) Empiric Tx Considerations+ Strong MRSA+Pseudomonas RFs

m/c bx pathogens

• s pneumonia

• h influenza

• m pneumoina

• s aureus

• legionella species

• c pneumonia

• m catarrhalis

MRSA strong RFs
known MRSA colonization
past MRSA infxn
sputum gram stain→gram+ cocci

pseudomonas strong RFs
known pseudomonas colonization
past pseudomonas infxn
sputum gram stain→gram- cocci
hospitalization+IV abx x past 3 months

Hospital-Acquired Pneumonia (HAP)+Ventilator Associated Pneumonia (VAP) Pathogens

HAP (x48 hrs post-hospital admission)+VAP (x48 hrs post-intubation+mechanical ventilation)

• s aureus (MRSA/MSSA)

• p aeruginosa

• acinetobacter species

• k pneumoniae

• enterobacter species

• proteus species

Hospital-Acquired Pneumonia (HAP)+Ventilator Associated Pneumonia (VAP) Dx

non-invasive (recommended)
expectorated sputum
nasopharyngeal culture
endotracheal aspiration→semi-quantitative cultures

invasive
10^4 colony forming units (CFU)→bronchoalveolar lavage (BAL)
10³ colony forming units (CFU)→protected specimen brush (PSB)

Hospital-Acquired Pneumonia (HAP)+Ventilator Associated Pneumonia (VAP) Empiric Tx Considerations

institutional RF→antibiograms
-local distribution of pathogens
-cause HAP/VAP+antimicrobial susceptibility patterns

multidrug-resistant (MDR) pathogen RFs

past microbiology data

MRSA vs MSSA coverage

double pseudomonas coverage

Hospital-Acquired Pneumonia (HAP)+Ventilator Associated Pneumonia (VAP) MRSA Coverage RFs

HAP

• high RF for mortality

• tx in area where MRSA prevalence unknown

• unit where 20+% s aureus isolates are MRSA→tx danger

VAP

• unit where 10+-20% of s aureus isolates are MRSA→tx danger

• tx in area where MRSA prevalence unknown

• colonization+isolation of MRSA

• colonization+past isolation of MRSA

Hospital-Acquired Pneumonia (HAP)+Ventilator Associated Pneumonia (VAP) Double Coverage Indications

HAP

• IV abx x u90 days

• high mortality RF

• structural lung dx

VAP

• IV abx use x u90 days

• septic shock

• ARDS

• past acute renal replacement tx

• past 5+ hospital admission days

Hospital-Acquired Pneumonia (HAP)+Ventilator Associated Pneumonia (VAP) Mx Tx

1st line
augmentin/unasyn/zosyn+vancomycin x 7 days
augmentin/unasyn/zosyn+linezolid x 7 days

gram+ abx+MRSA activity
IV vancomycin q8-12h
IV linezolid q12h

gram- abx+antipseudomonal activity: beta lactam based agents
IV zosyn q6h
IV cefepime q8h
IV ceftazidime q8h
IV imipenem q6h
IV meropenem q8h
allergy→IV aztreonam q8h

gram- abx+antipseudomonal activity: non-beta lactam based agents
IV ciprofloxacin q8h
IV levofloxacin q24h
IV amikacin q24h
IV gentamicin q24h
IV tobramycin q24h
IV colistin q12h
IV polymyxin b BID

Hospital-Acquired Pneumonia (HAP)+Ventilator Associated Pneumonia (VAP) Tx De-Escalation

de-escalate based on clinical improvement+dx results
non-critically ill pts→PO tx ASAP

culture-negative step down tx
admission→obtain MRSA nasal PCR swab
-no MRSA isolated+nasal screen engative→discontinue vancomycin
no culture+pt improving→complete abx course+empiric regimen

Tuberculosis (TB) (General)

PP: respiratory droplet transmission→saliva contains MTB bacilli→move into lungs→settle into alveoli

RF:m/c infectious dx
USA→immigrant+minorities
m/c HIV pt infxn mortality

E: m tuberculosis (MTB)

Tuberculosis (TB) Disease vs Infection

latent TB infection (LTBI)

• immune system contains TB→encased in hard shell (tubercle)→does not develop dx

• ~10% pts

• TB doesn’t grow in body

• can’t spread to other pts

• can progress to dx without long “latent” period

active TB disease

• TB not contained by immune response→causes dx

• TB grows in body

• shows active sx in pts

• can spread to other pts

• untxd→death

Active Tuberculosis (TB) Disease Mx Tx

1st line
IV rifamycins
PO rifamycins
IV isoniazid
PO isoniazid
PO pyrazinamide
PO ethambutol

initial phase: daily x 8 weeks
rifamycins
isoniazid
pyrazinamide
ethambutol

continuation phase: daily x 18 weeks
rifamycins
isoniazid

Latent Tuberculosis (TB) Mx Tx

1st line
PO isoniazid+rifapentine weekly x 3 months
PO rifampin daily x 4 months
PO isoniazid+rifampin daily x 3 months

alternatives
PO isoniazid daily x 6 months
PO isoniazid daily BIW x 6 months
PO isoniazid daily x 9 months
PO isoniazid BIW x 9 months

Rifamycins

MX: rifampin (RIF)
rifabutin
rifapentine

MOA: inhibits RNA polymerase+blocks DNA transcription

I: m tuberculosis
m kansasii
gram +
gram -

AE: rash
hepatitis
flu-like syndrome
discolored secretions→orange/red (red blood/sweat/tears/etc.)

DX: liver fxn

CI: CYP450 inhibitors

Isoniazid (INH)

MOA: inhibits essential enzymes for bx cell wall synthesis→inhibits synthesis of mycolic acid

I: m tuberculosis
m kansasii

AE: hepatotoxicity
peripheral neuropathy (tx→pyroxidine)

uncommon
rash
mx fever
lupus-like syndrome

CI: never use alone→neurosensitivity rxns
food→decreases absorption
antacids
phenytoin
azoles
antifungals
increased age
alcohol
rifampin (RIF)

Pyrazinamide

MOA: unknown
susceptible strains of mycobacterium→converted into pyrazinoic acid→lowers environmental pH

I: m tuberculosis

AE: hepatotoxicity
myalgia
hyperuricemia→asx
gout (uncommon)

CI: hepatotoxicity
severe renal impairment→dose adjustment

Ethambutol (EMB)

MOA: inhibits arabinosyl transferase→inhibits cell wall synthesis