Lower Respiratory Infections: Nosocomial

Question 1

What are the two types of nosocomial pneumonias?

Answer 1

HAP and VAP

Question 2

What is the criteria for pneumonia to be HAP or VAP?

Answer 2

Must occur at least 48 hours after admission (thus it was not already present at admission), or after intubation (for VAP).

Question 3

What’s the big deal about HAP and VAP?

Answer 3

They are the leading cause of mortality among hospitalized patients! Mortality is 15-50% depending on severity.

Question 4

What are the common pathogens for HAP/VAP?

Answer 4

Mostly gram negative rods. (Psuedomonas, acinetobacter, Enteric g-‘s like e coli, klebsiella, enterbatcer, proteus, etc.)

Staph Aureus is also a concern 16% HAP, 25% VAP. methacillin resistant about half the time.

Question 5

How do you diagnose HAP/VAP

Answer 5

Via clinical criteria alone. Procalcitonin and the CPIS score are not sensitive enough.

Question 6

Should you aggressively search for offending pathogen in HAP/VAP?

Answer 6

Yes! Blood and sputum cultures for everyone! Resistant orgs are much more common than in CAP, and we need to have a way to de-escalate. Non-invasive cultures are preferred (sputum) over more invasive (BAL).

Question 7

Who gets double antipseudomonal coverage in HAP?

Answer 7

• People who have have IV abx in prior 90 days
• People with structural lung disease (bronctiectasis or CF).
• Anyone at high mortality risk (on vent, septic shock)

Question 8

Who needs MRSA coverage with HAP?

Answer 8

• IV abx in prior 90 days
• In treatment unit/hosp with MRSA prevalence > 20%
• Anyone at high mortality risk (on vent, septic shock)

Question 9

Empiric Coverage for HAP (low-risk of mortality)

Answer 9

Single agent antipseudomonal +/- MRSA coverage

beta-lactam (cefepime, imipenem, merrem, zosyn)
OR
Levaquin/Cipro
AND
Vanc or Zyvox if MRSA > 20%

*beta-lactam could be aztreonam or even ceftaz, and FQ could be Cipro, if providing Vanc/Zyvox since MSSA coverage is there.

Question 10

Empiric Coverage for HAP with High risk of mortality or high risk of MDR orgs?

Answer 10

Double antipsuedomonal coverage + MRSA coverage

Two of either:
   Beta-lactam (cefepime, imipenem, meropenem, 
   zosyn, aztreonam)
   OR
   FQ (levaquin, cipro)
   OR 
   AG (Amikacin, Gent, Tobra)
PLUS
   Vanc/Zyvox

Question 11

Considerations for Empiric Coverage for VAP?

Answer 11

If one of the following risk of MDR, double pseudomonas and MRSA coverage:

• IV abx in last 90 days
• septic shock
• ARDS preceding VAP
• 5 or more days in hospital prior to VAP
• Acute renal replacement prior to VAP

Regardless, if MRSA > 10-20%, cover, and if risk of resistant G- bacilli > 10% or unknown, double cover pseudomonas. If you can use an agent that is more than 90% active for all g- bacilli per antibiogram, you can use that single agent.

Question 12

How does Empiric Coverage for VAP differ from HAP?

Answer 12

Polymyxins are an option for gram- coverage: Colistin or Polymyxin B. Otherwise it’s the same as HAP.

Question 13

Can you use Aminoglycoside Monotherapy for pathogen directed therapy of HAP/VAP?

Answer 13

No! There risk of treatment failure and emergence of resistance.

Question 14

Should you still use combination therapy for directed therapy against Pseudomonas?

Answer 14

If patient still in septic shock, yes, there is a mortality benefit. But once septic shock resolves, de-escalate to one active agent per C&S (just not AG monotherapy).

Question 15

Which organism can be treated with the Sulbactam component of Unasyn?

Answer 15

Acinetobacter!

Question 16

What about directed therapy against Acinetobacter?

Answer 16

Notoriously drug resistant. These are the preferred agents, if supported by C&S.
First - Carbapenem
Second - Unasyn (because of sulbactam)
Third - Polymyxin + adjunctive inhaled colistin

Question 17

Can you use Daptomycin for MRSA pneumonia?

Answer 17

NO! The surfactant destroys the drug.

Question 18

What about ESBL producing organisms?

Answer 18

Carbapenems are often the treatment of choice

Question 19

What about Carbapenem resistant organisms?

Answer 19

Base it on C&S results:
Polymyxins, inhaled colistin.
Potential role for newer agents:
 - Cefolozane-tazobactam (Zerbaxa)
 - Ceftazidime-avibactam (Avicaz)
 - Meropenem-vaborbactam 
Zosyn may still retain activity, but questionable

Question 20

What about Ceftolozane-tazobactam in HAP/VAP?

Answer 20

• Zerbaxa
• It’s a novel cephalosporin with beta-lactamase inhibitor.
• Active against most ESBL and AmpC producters
• Retains activity against many strains of carbapenem resistant P. aeruginosa.
• Does NOT have activity against carbapenemase producers.
• Does NOT have much G+ activity (no Staph activity)
• FDA approved for HAP/VAP in adults
• Reserve for when other therapies won’t work

Question 21

What about Ceftazidime-Avibactam for HAP/VAP?

Answer 21

• Avicaz
• Novel beta-lactamase + ceftaz
• Retains activity against many MDR GNR, including ESBL, AmpC, and CRE (including KPC and OXA-48)
• FDA approved for HAP/VAP

Question 22

What about Meropenem-vaborbactam for HAP/VAP?

Answer 22

• Vabomere
• Espeically useful for CRE (carbapenem enterbaceriaceae).
• Active against most ESBL, AmpC, and KPC-producting CRE (similar to Avicaz).
• No MRSA activity
• Does not inhibit OXA-48 enzymes.

Question 23

Are PK/PD dose optimizations recommended by the guidelines?

Answer 23

Yes! Vanc/AG’s should be weight-based and utilize TDM. Beta-lactams should be administered via extended infusions.

Question 24

What about inhaled abx for HAP/VAP?

Answer 24

Use for VAP due to MDR GNRs suscebtible only to AG’s or polymyxins.

Question 25

What’s the role of Polymyxins in HAP/VAP?

Answer 25

Use only when unavoidable. Exposures required for success in pneumonia are above the maximum tolerable range. Polymyxin is preferred to colistin (to limit kidney injury). Always use in combination with inhaled. Use also with 1-2 other systemic agents, even if non-susceptible.

Question 26

How long should you treat HAP/VAP?

Answer 26

7 days. You can use clinical improvement and procalcitonin levels to help too.

Question 27

Should you de-escalate based on cultures with HAP/VAP?

Answer 27

Yes!