1. HAP and VAP Guidelines Update
Sarah-Catherine Formiller, PharmD
PGY1 Pharmacy Resident
Baptist Health Medical Center- North Little Rock
September 27th 2016
HAP and VAP Guidelines Update
My name is Sarah-Catherine Formiller and I am currently one of the PGY1 pharmacy residents at Baptist Health Medical Center in North Little Rock. I will be presenting the most recent update to the clinical practice guidelines of Hospital acquired pneumonia and ventilator associated pneumonia. published by the Infectious disease society of America and the American Thoracic Society on July 14th of this year.

2. These guidelines were published by the Infectious disease society of America and the American Thoracic Society on July 14th of this year.

3. Objectives
Interpret new clinical recommendations provided in the 2016 HAP/VAP guidelines.
Design an empiric medication regimen for a patient with HAP/VAP.
Assess the need for antibiotic de-escalation and discontinuation.
By the end of this presentation, I would like for you to have interpreted the clinical recommendations provided by these guidelines, to be able to design an empiric medication regimen for a patient with HAP or VAP, and to be able to appropriately assess the need for antibiotic de-escalation and discontinuation.

4. Outline Major differences introduced in the 2016 guidelines
Empiric treatment of VAP and HAP
Antimicrobial de-escalation and discontinuation
Practice patient case
In this brief presentation I will do my best to cover the major differences introduced in these guidelines, discuss an overview of empiric regimens, antibiotic de-escalation and discontinuation, and we will conclude with a practice case.

5. Additional recommendations not covered
Diagnosis recommendations
Invasive vs. noninvasive
Quantitative vs. qualitative
Using clinical criteria to diagnose HAP/VAP
PCT, sTERM-1, CRP, CPIS
Inhaled Antibiotic Therapy
Pathogen specific therapy
Due to the brevity of this presentation I have listed some areas of change that are presented in these guidelines that I will not have time to cover.

6. Major Differences
There are a few major differences in these guidelines that I want to bring forward.

7. Major Differences in New Guidelines
Removal of the concept of healthcare-associated pneumonia (HCAP)
Recommendation that each hospital generate antibiograms to base antimicrobial choice upon
Shorter duration of therapy independent of microbial etiology
Firstly the concept of healthcare associated pneumonia or HCAP has been removed.
HCAP was included in the 2005 guidelines due to the proposed risk for MDR organisms due to their contact with the healthcare system.
There is increasing evidence from a growing number of studies that many patients defined as having HCAP are not at high risk for MDR pathogens [15–19].
Furthermore, although interaction with the healthcare system is potentially a risk for MDR pathogens, underlying patient characteristics are also important independent determinants of risk for MDR pathogens [15–17].
Even if HCAP would be considered as a separate clinical entity, it was thought that this could be included in the upcoming community-acquired pneumonia (CAP) guidelines because patients with HCAP, like those with CAP, frequently present from the community and are initially cared for in emergency departments.
Finally, in light of the more recent data regarding the HCAP population, the panel anticipated that recommendations regarding coverage for MDR pathogens among community-dwelling patients who develop pneumonia would likely be based on validated risk factors for MDR pathogens, not solely on whether or not the patient had previous contacts with the healthcare system.
For these reasons, the panel unanimously decided that HCAP should not be included in the HAP/VAP guidelines.
HAP: pneumonia not incubating at the time of admission and occurring 48 hours or more after admission
VAP: pneumonia occurring more than 48 hours after endotracheal intubation
Secondly, the recommendation that each hospital generate antibiograms to guide and base antimicrobial choice upon has be introduced.
Thirdly, they have shortened the duration of antibiotic therapy for most patients with HAP or VAP independent of microbial etiology, as well as antibiotic de-escalation.

8. Antibiograms Empiric treatment regimens based on antibiograms
Minimize patient harm and exposure
Reduce the development of antibiotic resistance
Decrease the unnecessary use of dual gram-negative and empiric MRSA treatment
Specific to VAP populations (ICU)
Specific to HAP populations
In an effort to minimize patient harm and exposure to unnecessary antibiotics and reduce the development of antibiotic resistance, the new guidelines recommend that the antibiogram data be utilized to decrease the unnecessary use of dual gram-negative and empiric MRSA coverage. Empiric treatment regimens should now be based off of the local distribution of pathogens associated with VAP or HAP and their antimicrobial susceptibilities.

9. Empiric Treatment
So lets talk briefly about empiric treatment.

10. Prior IV antibiotic use within 90 day
Risk Factors for MDR Pathogens
VAP
HAP
MRSA or
P. aeruginosa
Prior IV antibiotic use within 90 day
Septic shock at time of VAP
ARDS prior to the occurrence of VAP
5 or more days of hospitalization prior to the occurrence of VAP
Acute renal replacement therapy prior to the occurrence of VAP
I listed the risk factors for multi drug resistant pathogens in here for your reference as we discuss in the next two slides the empiric treatment guidelines. For VAP and HAP and the development of MRSA or resistant pseudomonas, the use of IV antibiotics in the previous 90 days the the most apparent risk factor seen consistently in prior research. Additionally, for VAP a patient is at risk of MDR organism if they had septic shock at the time of VAP, they had ARDS preceding VAP, if they were hospitalized 5 or more days prior to the occurrence of VAP, or if they had acute renal replacement therapy prior to VAP onset.
VAP:
Sepsis may alter the response of cellular elements that comprise the innate immune system
Nonetheless, the reviewed evidence suggests that overall, patients who develop VAP after >5 days of hospitalization are at higher risk of infection with MDR organisms than patients who develop VAP earlier in their hospitalization.
HAP:
Risk factors for MDR HAP have only rarely been studied (Table 2). Fifteen potential risk factors were included in our meta-analysis.
Only one risk factor was significantly associated with MDR HAP: prior intravenous antibiotic use (OR, 5.17; 95% CI, 2.11–12.67) [39, 40].
While other risk factors may be relevant, evidence is lacking. With regard to the early vs late pneumonia concept, no data are available for HAP.
MRSA:
Prior use of IV ABX – most predictive RF for MRSA
no specific antibiotic has been identified as an independent risk factor
More often seen in late onset pneumonia
Psudomonas aeruginosa
Prior use of antibiotics
prior receipt of carbapenems, broad-spectrum cephalosporins, and fluoroquinolones have been identified as independent risk factors.
mechanical ventilation
history of chronic obstructive pulmonary disease

11. Empiric Therapy for VAP
S. aureus, P. aeruginosa and other gram-negative bacilli
MRSA coverage if
Risk factors for antimicrobial resistance
Units where >10%-20% of S. aureus isolates are methicillin resistant
Units where the prevalence of MRSA is not known
MSSA coverage only, if
Without risk factors for antimicrobial resistance
ICUs where <10%-20% of S. aureus isolates are methicillin resistant
For ventilator associated pneumonia we need to cover for staph aureus, pseudomonas aeruginosa and other gram negative bacilli. We then need to add MRSA coverage only if the patient has RF for antimicrobial resistance that we previously discussed for VAP patients, if the pt is in a unit with either an unknown amount or more than 10-20% MRSA isolates. MSSA coverage is indicated in patients without these factors.
If empiric MRSA coverage is indicated the guidelines suggest the use of Vancomycin or linezolid.
If MSSA empiric coverage is indicated the guidelines suggest using Zosyn, cefepime. Levofloxacin, imipenem, or meropenem.
If MSSA is proven the use of oxacillin, nafcillin, or cefazolin is recommended. - but not for empiric treatment

12. Empiric Antipseudomonal Coverage VAP
Double Coverage
Risk factors for resistance
Units where >10% of gram-negative isolates are resistant to an agent being considered for monotherapy
Susceptibility rates for ICU not available
Monotherapy
No risk factors for resistance
ICU’s where ≤ 10% of gram-negative isolates are resistant to the agent being considered for monotherapy
Avoid aminoglycosides or colistin when possible
The guidelines recommend double coverage for pseudomonas if there are risk factors present for resistance which we discussed previously, if the patient is in a unit where more than 10% of gram negative isolates are resistant to the agent being considered for monotherapy or if the susceptibility rates for the ICU where the patient is located are not known.
They suggest monotherapy when risk factors for resistant are not present and where the isolates are less than or equal to 10% resistant to the agent being considered for monotherapy
However, they suggest against the use of monotherapy with aminoglycosides or colistin when alternative agents with adequate gram negative activity are available.
The 10%–20% threshold for deciding
whether or not to target MRSA and the 10% threshold for
deciding whether or not to prescribe one antipseudomonal
agent or 2 were chosen by the panel with a goal of trying
to assure that ≥95% of patient receive empiric therapy
active against their likely pathogens; when implementing
these recommendations, individual ICUs may elect to
modify these thresholds. If patient has structural lung disease
increasing the risk of gram-negative infection (ie,
bronchiectasis or cystic fibrosis), 2 antipseudomonal
agents are recommended.

13. Empiric Therapy for HAP
S. aureus, P. aeruginosa and other gram-negative bacilli
MRSA coverage if
IV antibiotics in last 90 days
Unit where >20% of S. aureus isolates are methicillin resistant
Prevalence of MRSA is not known
High risk for mortality
MSSA coverage if
Empiric treatment and have no risk factors for MRSA
Not at high risk of mortality
For hospital acquired pneumonia we need to cover for staph aureus, pseudomonas aeruginosa and other gram negative bacilli. We then need to add MRSA coverage only if the patient has received IV antibiotics in the past 90days because that is the risk factor for MDR organisms in HAP patients and the risk factor for the development of MRSA. Also, if the pt is in a unit with either an unknown prevalence of or more than 20% MRSA isolates, empiric therapy needs to include MRSA coverage. Also if the patient has a high risk of mortality, MRSA coverage needs to be provided empirically. The risk factors for mortality identified by the committee include the need for ventilary support due to HAP and septic shock. MSSA coverage is indicated in patients without these factors.
If empiric MRSA coverage is indicated the guidelines suggest the use of Vancomycin or linezolid.
If MSSA empiric coverage is indicated the guidelines suggest using Zosyn, cefepime. Levofloxacin, imipenem, or meropenem.
If MSSA is proven the use of oxacillin, nafcillin, or cefazolin is recommended. - but not for empiric treatment

14. Empiric Antipseudomonal Coverage HAP
Double Coverage
Risk factors for Pseudomonas or other gram-negative infection
IV antibiotics in the last 90 days
Structural lung disease
High risk of mortality
Monotherapy
All other patients with HAP who are being treated empirically
Do not use aminoglycoside as sole antipseudomonal agent
The guidelines recommend double coverage for pseudomonas if there are risk factors present for resistance which only include IV antibiotics in the previous 90 days. Also, double coverage is indicated in those patients who have structural lung disease like COPD or those at a higher risk for mortality. Risk factors for mortality again include the need for ventilator support due to HAP or septic shock.
They suggest monotherapy when risk factors for resistant are not present and the patient is not at a high risk of mortality.
However, they suggest against the use of monotherapy with aminoglycosides when other therapies are available

15. Definitive Treatment

16. Monotherapy vs. Combination therapy for P. aeruginosa
Not in septic shock or at high risk of death
Susceptibility results are known
Combination therapy
Septic shock
High risk of death when the results of antibiotic susceptibility testing are known
Recommend against aminoglycoside monotherapy
If pseudomonas is isolated, the guidelines provide recommendations of when to use monotherapy versus combination therapy. If the patient is not septic and not at a high risk of death with a known pseudomonas infection monotherapy is indicated.
Dual coverage is indicated in patients who are septic and are at a high risk of death.
Pathogen Specific
MRSA - Vancomycin or Linezolid (Choice guided by blood cell counts, concurrent prescriptions for SSRIs, renal function, and cost
Pseudomonas - Based upon the results of antimicrobial susceptibility testing, Recommend against aminoglycoside monotherapy
ESBL GNB - Based on susceptibility testing/pt specific factors (comorbidities/increased risks of SE)
Acinetobacter - Carbapenem or amp/sulbactem if susceptible, S to polymyxins (IV colistin/polymyxin B) PLUs inhaled colistin, S only to colistin - dont use rifampin as adjunctive, Dont use tigecycline
HAP/VAP due to Carbapenem Resistant organism - Polymyxins:IV Colistin or polymyxin B PLUS inhaled colistin

17. Duration of Therapy 7 day course of antimicrobial therapy
Discontinue based on PCT levels + clinical criteria vs. clinical criteria alone
De-escalation of therapy recommended rather than fixed therapy
For patients with VAP or HAP, the committee recommends a 7 day course of antimicrobial therapy rather than a longer duration. There are situations when a shorter or longer duration of therapy is indicated. This depends on the rate of improvement of clinical, radiologic, and laboratory parameters. They are in favor of utilizing procalcitonin levels plus clinical features to assess the need for antibiotic discontinuation. They also recommend de-escalation of therapy once susceptibilities are known.

18. Practice Patient Case

19. Practice Patient Case
MD is a 69 yo WM admitted to the hospital for a 1 week history of cough and dyspnea. Review of his symptoms reveals fever, chills, productive cough, and dyspnea. PMH includes T2DM, HTN, COPD, and glaucoma. Patient was admitted 1 month ago with sepsis due to a UTI and received IV antibiotics. The physician ask you for recommendations on empiric therapy for this patient. Patient was admitted to a unit where the susceptibility rates are unknown.

20. What do you suggest for empiric coverage?
Vancomycin + Zosyn + Cefepime
Vancomycin+ Cefepime + Gentamicin
Linezolid + Ceftazidime
Azithromycin + Ceftriaxone
Not A because two beta-lactams to double cover for pseudomonas. There is no variety in mechanism of action.
Correct (MRSA coverage, double cover for pseudomonas due to IV abx in last 90 days)
Not C because there is not double coverage for pseudomonas (IV abx in last 90 d, copd)
Not D, this may be acceptable as CAP treatment but not for HAP need MRSA treatment

21. Definitive therapy
Patient is clinically improving and cultures have resulted.
Pseudomonas aeruginosa
Pansensitive
Physician narrows therapy based on the susceptibility results which you determine to be appropriate.
A couple days later the pt is clinically improved and cultures have resulted pseudomonas aeruginosa that is pansensitive. Additionally, the physician appropriately narrows therapy.

22. How many days of ABX does this pt need?
The patient is clinically improving, this set of guidelines recommend that the standard duration of 7 days be used in most patients no matter what the microbial etiology of the infection resulted.

23. Summary HCAP is no longer a classification of pneumonia
Empiric therapy of VAP and HAP should be driven by local antibiograms
Empiric therapy should be individualized based on RF for MDR organisms
Antibiotic de-escalation is recommended
Duration of therapy is 7 days if clinically improving
In conclusion, HCAP is no longer a classification of pneumonia, empiric therapy of HAP and VAP should be driven by local antibiograms, and individualized by based on the patient’s risk factors for muti drug resistant organisms. Antibiotic de-escalation is encouranged and duration of antibiotic therapy has been shortened to 7 days independent of microbial etiology.

24. Reference
Kalil, A. C., Metersky, M. L., Klompas, M., et al (2016). Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. Clinical Infectious Diseases, 63(5).
I referenced the current guidelines for HAP and VAP published this year to formulate this presentation.

25. HAP and VAP Guidelines Update
Sarah-Catherine Formiller, PharmD
PGY1 Pharmacy Resident
Baptist Health Medical Center- North Little Rock
September 27th 2016
HAP and VAP Guidelines Update
What Questions do you have