10.1 AI Q&A

Define hospital-acquired pneumonia (HAP)

>48 hours after hospital admission and not present on admission

Define ventilator-associated pneumonia (VAP)

>48 hours after endotracheal intubation/mechanical ventilation

Community acquired pneumonia

< 48 hours after hospital admission

What are the 3 ways you can develop an acute respiratory infection?

– Impaired host defenses
– Exposure to a highly virulent pathogen
– Large inoculum of microorganism

Key pathogen entry mechanisms

Aspiration, inhalation of aerosols, hematogenous spread

Non-modifiable risk factors for HAP/VAP

Older age, COPD, altered mental status, aspiration, chest surgery

Modifiable risk factors for HAP/VAP

Mechanical ventilation, gastric pH modifiers, prior antibiotics, supine position, NG tube, re-intubation

Typical clinical presentation

Fever, chills, dyspnea, productive cough, chest pain, tachypnea, tachycardia, diminished breath sounds, new infiltrate, leukocytosis, low oxygenation

How do you diagnose pneumonia?

Look for clinical signs/symptoms, radiographic findings (CXR, CT chest), sputum/blood cultures

Preferred respiratory cultures for HAP (non-invasive)

Expectorated sputum

Preferred respiratory cultures for VAP (non-invasive)

Endotracheal aspirate

How do you take an invasive respiratory culture?

Bronchoscopy (i.e. bronchoalveolar lavage -
BAL)

Role of biomarkers in HAP/VAP diagnosis

Not recommended for diagnosis or to start antibiotics; may help with discontinuation

Examples of biomarkers

– Procalcitonin (PCT)
– C-reactive protein (CRP)

Most common gram-negative pathogens in HAP/VAP

Pseudomonas, Klebsiella, Enterobacter, Acinetobacter, E. coli, Serratia

Most common gram-positive pathogens in HAP/VAP

Staphylococcus aureus including MRSA

S.pneumoniae but less common compared to CAP

When candida in culture should be treated

Do not treat; usually colonization

What fungal species pathogen is common in immunocompromised patient?

Aspergillus

General treatment approach

Broad empiric therapy, obtain cultures first, narrow when susceptibilities available

What is empiric therapy?

Use local antibiogram to guide empiric therapy decisions

Empiric therapy ALWAYS should cover which organisms

MRSA and Pseudomonas

What medications cover both pseudomonas and Extended spectrum beta Lactamases?

Carbapenams: Imipenam-Cillistatin, Meropenam

Fluoroquinalones: Ciprofloxacin, Levofloxacin

Aminoglycoside: Gentamicin, Tobramycin Amikacin

What medications cover MSSA and MRSA?

Vancomycin (not well)

Linezolid

What is a typical empiric therapy regimen?

Consists of 2-3 different antibiotics

– MRSA: 1 agent
– Pseudomonas: 1 or 2 agents (from different antibiotic classes)

What is the dose for pip-tazo?

4.5 grams IV q6h

Administered as an extended infusion at many hospitals (3.375 grams IV q8h infused over 4 hours)

What is the dose for Cefepime and Ceftazadine?

2 grams IV every 8 hours

Ceftazidime (Fortaz®) should not be used against infections caused by what pathogen?

Enterrobacter sp

What cephalasporins are used for MDR pneumonia?

– Ceftolozane-tazobactam (Zerbaxa®)
– Ceftazidime-avibactam (Avycaz®)
– Cefiderocol (Fetroja®)

What carbapenams are preferred if pathogen is ESBL +?

Imipenem and meropenem

What carbapenam does not have activity against psuedamonas and can not be used for empiric therapy?

Ertapenem (Invanz®)

What carabapenam is used for resistant infections?

Meropenem/vaborbactam (Vabomere®)

What monobactam is used for people with penicillin allergies?

Aztreonam

Why must Aztreonam be paired with a gram-positive antibiotic?

ONLY covers gram negative bacteria (ie psuedamonas)

What fluoroquinnalones have antipsedomnal activity?

Cipro and levoflaxacin

What fluoroquinnalone does NOT have antipsuedomanal activity?

Moxiflaxacin

What is the effect of fluoroquinnalones increasing VD?

Good penetration to lung tissue and fluid

Imipenam should be used cautiously in what patients?

Those w/seizure disorder

Meropenam sometimes requires an increased dose in which patients?

obese or cystic fibrosis

What should you consider when using Fluoroquinnolones?

– Clostridium difficile infection

– Gram negative resistance

– Prolonged QTc

When double pseudomonas coverage is needed for HAP

IV antibiotics in last 90 days, high mortality risk, structural lung disease

When double pseudomonas coverage is needed for VAP

• Risk factor for antimicrobial resistance*

• > 10% gram-negative isolates are resistant

• Local antimicrobial susceptibility rates not available • Structural lung disease

When empiric MRSA coverage is needed for HAP?

>20% local MRSA, prior IV antibiotics, high mortality risk

When is empiric MRSA coverage needed for VAP?

• > 10-20% of S. aureus isolates are MRSA

• Risk factor for resistance*

Recommended empiric duration of therapy

7 days

Key antipseudomonal beta-lactams

Choose 1 during empiric therapy

Piperacillin-tazobactam, cefepime, ceftazidime, imipenem, meropenem, aztreonam

Non-beta lactam antipseudomonal agents

Choose 1 during empiric therapy

Ciprofloxacin, levofloxacin, aminoglycosides, colistin, polymyxin B

Aminoglycoside monotherapy role

Not recommended

What aminoglycosides have the best antipsedomanal activity?

Amikacin > tobramycin > gentamicin

Aminoglycosides have _____ lung pentration

poor

Aminoglycosides have a _____ therapuetic window

narrow

Aminoglycosides may be given via ____

inhalation

aminoglycoside dosing is based on what?

weight

Hartford Nomogram

Gentamicin or tobramycin 7 mg/kg/dose 

Uses IBW or ABW (obese)

Initial dosing based on creatinine clearance

For the Hartford Monogram, it is adjusted based on random serum concentration drawn ______

6 to 12 hours after first dose

The Hartford Nomogram takes advantage of what PK/PD aminoglycoside benefit?

Post antibiotic effect

Give an example of a Hartform Monogram drawn at 9 hours post start?

If concentration dran is 4mcg/ml, dose every 24 hours

If concentration drawn is 10mcg/ml, dose evry 48 hours

Vancomycin dosing is based on what?

wieght 15 mg/kg (rounded to the nearest 250 mg)

What is the goal serum trough concentration for vancomycin?

15-20 mcg/mL for pneumonia

What should be considered in the case of severely ill patients recieving vacomycin?

loading dose of 25-30mg/kg IV
x 1 dose

Whatis the AUC/MIC for vancomycin

400-600

Why does vancomycin have poor lung penetration?

Big molecule

What should be monitored in vancomycin?

Monitor closely/adjust for renal
impairment

How is Linezolid Lung penetration?

Good

What is a concern for Linezolid?

myelosupression, serotonin syndrom

Risk factors for MDR VAP

Prior IV antibiotic use within 90 d
Septic shock at time of VAP
ARDS preceding VAP
5+ d of hospitalization prior to the
occurrence of VAP
Acute renal replacement therapy
prior to VAP onse

Patient risk for MDR HAP

MRS HAP/VAP

PSA HAP/VAP

Prior IV antibiotic use w/i 90 days

Definitive therapy principle

De-escalate based on susceptibilities

Total treatment duration recommendation

7 days unless slow response

Clinical monitoring parameters

WBC, oxygenation, temperature; avoid changing antibiotics before 48-72 hours

Role of inhaled antibiotics

Consider only when organism susceptible only to aminoglycosides or polymyxins; give inhaled plus IV

Procalcitonin role

Used with clinical criteria to help discontinue antibiotics; reduces exposure and adverse events

Cefepime activity

Antipseudomonal; stable against most beta-lactamases

Ceftazidime caution

Increased ESBL selection; avoid for Enterobacter infections

Aminoglycoside toxicity concerns

Monotherapy associated w/treatment faliure

Nephrotoxicity and ototoxicity

HAP/VAP diagnosis requirement

Clinical signs plus radiographic infiltrate plus cultures

Colistin or Polymyxin B risks

Nephrotoxicity

When should patients remain on 2 drugs for pneumonia?

Persistent shock, high mortality risk, treatment of resistent organisms

What drugs should be used to treat acinetobacter species in definitive therapy?

– Carbapenem (imipenem or meropenem)
– Ampicillin-sulbactam if isolate is
susceptible
– Use IV polymyxin (colistin or polymyxin B)
with inhaled colistin if only susceptible to
polymyxins

What drugs should be used to treat carbapenam resistant pathogens?

– If sensitive only to polymyxins, use IV
polymyxin (colistin or polymyxin B) with
inhaled colistin
– Consider Avycaz®, Zerbaxa®, Vabomere®

What drugs can be used to treat MSSA in definitive therapy?

Nafcillin/oxacillin or cefazolin

What drugs can be used to treat ESBL-producing gram-negative bacilli in definitive therapy?

Carbapenems (imipenem or meropenem)
preferred

When is PCT not necessary?

Thary less than 7 days