1

A LONG AWAITED UPDATE

THE NEW 2016 IDSA HAP/VAP

GUIDELINES
INTRODUCTION 2

ABOUT ME
Dr. Curtis K. Harder
Clinical Pharmacy Specialist - Adult Intensive Care
Coordinator, Pharmacy Education & Practice Residency
Vancouver Island Health Authority
Clinical Assistant Professor
University of British Columbia
curtis.harder@viha.ca
INTRODUCTION 3

DISCLOSURE

I have no real or potential conflicts to declare.

I have received an honorarium from CSHP for this learning

activity.
INTRODUCTION 4

LEARNING OBJECTIVES
After attending this session, the learner will be able to:

Describe the relative importance of hospital-acquired pneumonia (HAP)

and ventilator-associated pneumonia (VAP) for patients and the health
care system.

Name three major differences in the 2016 IDSA HAP/VAP Guidelines vs

the previously published version.

Interpret and use the new Guidelines for determining optimal

antimicrobial management of patients with HAP or VAP (drug, dose,
route, duration).

Identify challenges for application of the new Guidelines to practice in BC.

 INTRODUCTION 5

WHY IS THIS WORTH TALKING ABOUT?

HAP/VAP together account for 22% of all hospital-associated infections

~10% incidence of VAP in patients requiring ventilation

VAP is bad

All-cause mortality in patients with VAP 20-50%, attributable mortality is 13%

prolongs length of ventilation by 7.6 to 11.5 days

prolongs hospitalization by 11.5 to 13.1 days

$40K excess cost per patient (US data)

$46 million excess cost annually (Canadian data)

HAP less severe, but serious complications still occur in ~50% of patients

Clin Infect Dis 2016; 63: e61-e111

J Crit Care 2008; 23: 5-10
 6

Am J Respir Crit Care Med 2005; 171:388-416

Clin Infect Dis 2016; 63: e61-e111
 7

ORIENTATION TO
WHATS NEW IN 2016
WHATS NEW IN 2016 8

THE BIG STUFF

GRADE methodology (Grading of Recommendations

Assessment, Development and Evaluation)

Removal of healthcare-associated pneumonia (aka

HCAP)

Recommendation that each hospital generate

antibiograms to guide healthcare professionals with
respect to optimal choice of antibiotics
WHATS NEW IN 2016 9

SOME OF THE MORE SUBTLE FEATURES*

Anti-pseudomonal coverage for all

Procalcitonin is now a thing

Dont treat tracheobronchitis

Clarity on when MRSA requires empiric coverage

Clarity on combination vs monotherapy with focus on Pseudomonas

Guidance in the management of carbapenem-resistant pathogens

7-day courses for all

*A selection that happened to catch the eye of the presenter. This document is 51 pages
longi.e., the curious reader may very well find other interesting nuggets.
 WHATS NEW IN 2016 10

INCORPORATION OF EVIDENCE INTO RECOMMENDATIONS

GRADE methodology (Grading of Recommendations Assessment,
Development and Evaluation)

Division of strong vs weak (conditional) recommendations

We recommend = strong recommendation

We suggest = weak (conditional) recommendation

Strong recommendations were sometimes made in the setting of

lower-quality evidence when the panelists believed that most
individuals would desire the recommended course of action, and that
most well-informed clinicians would agree, despite the low-quality
evidence.

Clin Infect Dis 2016; 63: e61-e111

WHATS NEW IN 2016 11

STATS ON THE EVIDENCE

25 questions, 47 recommendations (4 uncategorized)

Strong Recommendations (19) Weak Recommendations (24)

We recommend We suggest

Moderate Quality Evidence

Low Quality Evidence
Very Low Quality Evidence
 WHATS NEW IN 2016 12

DEFINITIONS
Pneumonia = presence of a new lung infiltrate plus clinical
evidence that the infiltrate is of an infectious origin, which
includes the new onset of fever, purulent sputum, leukocytosis,
and decline in oxygenation (same as 2005)

HAP = pneumonia not incubating at time of admission,

occurring 48 hours or more after admission (same as 2005)

VAP = pneumonia occurring >48 hours after intubation (same

as 2005)

New in 2016 - HAP and VAP are mutually exclusive

Clin Infect Dis 2016; 63: e61-e111

ILLUSTRATIVE CASE 13

CASE (SP)
60 year-old male, initially brought by EHS to hospital after being struck by a car
while crossing the road. SP required surgical management for multiple fractures
of his left leg. After one day in hospital he developed a fever and a productive
cough and is requiring supplemental oxygen by nasal prongs to maintain an
adequate SaO2.

Recent hospitalization for diverticulitis (1 mo prior, medical management only)

Pertinent labs/imaging

CXR - patchy consolidation, right lower lobe

CBC - elevated WBC and neutrophils

Sputum Gram stain - +3 GNB, +1 oropharyngeal flora

 WHATS NEW IN 2016 14

HCAP IS NO LONGER A THING

Definition too blunt of an instrument - many patients defined as having
HCAP are not at high risk for MDR pathogens (i.e., they may just have CAP)

individual studies assessing for risk of antibiotic-resistant pathogens are

of poor quality

meta-analysis confounded by publication bias, doesnt show any

difference in mortality when adjusted for age/comorbidities

Underlying patient characteristics are important independent determinants

of risk for MDR pathogens

Look to see these determinants incorporated into upcoming CAP

guidelines (projected publication, Summer 2017)

Clin Infect Dis 2014; 58: 330-9

IDSA Practice Guidelines. Accessed at http://www.idsociety.org/IDSA_Practice_Guidelines/, Nov 12, 2016.
 15

PATHOGENESIS OF HAP/VAP
& PREDICTING MULTIDRUG
RESISTANCE (MDR)
 PATHOGENESIS & RESISTANCE 16

PATHOGENESIS OF HAP AND VAP

Can J Infect Dis Med Microbiol 2008; 19: 19-53

 PATHOGENESIS & RESISTANCE 17

UNDERSTANDING RISK OF RESISTANCE IN VAP

OR 12.3 (95% CI 6.48-23.35)

OR 2.01 (95% CI 1.12-3.61)
OR 3.1 (95% CI 1.88-5.1)

OR 2.5 (95% CI 1.14-5.49)

Clin Infect Dis 2016; 63: e61-e111

 PATHOGENESIS & RESISTANCE 18

RISK OF MDR IN VAP

Early antimicrobial therapy may reduce VAP by susceptible
organisms, but it is clearly tied to risk of MDR VAP later on in
hospitalization

MDR bugs = MRSA, Pseudomonas, other non-glucose fermenting

organisms

Upper airway colonization > tracheobronchial colonization > VAP

Timing of colonization is the key predictor of MDR emergence

Early vs late VAP should be based on timing of hospitalization

rather than intubation

Clin Infect Dis 2016; 63: e61-e111

 PATHOGENESIS & RESISTANCE 19

UNDERSTANDING RISK OF RESISTANCE IN HAP

OR 5.17 (95% CI, 2.11-12.67)

No data available for distinguishing early vs late onset for HAP

Clin Infect Dis 2016; 63: e61-e111

 PATHOGENESIS & RESISTANCE 20

RISK OF SPECIFIC ORGANISMS

MRSA

Few published data, but prior IV antibiotics as the risk factor most
consistently related to onset of HAP/VAP (no statistics presented)

Conflicting data to support the association of colonization with

subsequent infection (no prospective studies)

MDR Pseudomonas

Few published data, but prior IV antibiotics as the risk factor most
consistently related to onset of HAP/VAP (no statistics presented)

Insufficient data to draw conclusions on the risk of resistance conferred by

specific antibiotics

Clin Infect Dis 2016; 63: e61-e111

 21

ANTIMICROBIAL
TREATMENT
 TREATMENT 22

VENTILATOR-ASSOCIATED TRACHEOBRONCHITIS (VAT)

VAT = fever with no other recognizable cause + new or
6
increased sputum production + positive ETA culture (>10 CFU/
mL) yielding a new bacteria + no radiographic evidence of
pneumonia

Evidence comprised of one unblinded RCT (stopped early) and

4 observational studies

antibiotics might shorten duration of mechanical ventilation

In patients with VAT, we suggest not providing antibiotic

therapy (weak recommendation, low-quality evidence)

Clin Infect Dis 2016; 63: e61-e111

 TREATMENT 23

VAP EPIDEMIOLOGY (USA DATA)

S. aureus - 20-30% of isolates

50% methicillin-resistant

P. aeruginosa 10-20% of isolates

28-35% resistant to cefepime, 19-29% resistant to piperacillin/

tazobactam

Enteric GNB 20-40% of isolates

Acinetobacter baumannii 5-10% of isolates

56-61% resistant to carbapenems

Clin Infect Dis 2016; 63: e61-e111

 TREATMENT 24

THE ROLE OF YOUR MICROBIOLOGY DEPARTMENT

We recommend that all hospitals regularly generate and
disseminate a local antibiogram, ideally one that is specific to

their intensive care population(s) if possible

their HAP population, if possible

We recommend that empiric treatment regimens be informed

by the local distribution of pathogens associated with

VAP and their antimicrobial susceptibilities

HAP and their antimicrobial susceptibilities

Clin Infect Dis 2016; 63: e61-e111

 TREATMENT 25

EXAMPLES OF LOCAL ANTIBIOGRAM DATA

Klebsiella Entero- Serratia Pseudo- Acineto-
E coli
pneumo bacter spp marcescens monas bacter spp

VGH/UBC 2013 87% 92% 73% 95% 0% 33%

Ceftriaxone / VGH ICU 2013 72% 88% 65% 100% 0% 24%
Cefotaxime SMH 2015 82% 90% NR NR R NT
VIHA - South 2012 92% 99% 0% 0% NT NT

VGH/UBC 2013 75% 94% 95% 96% 87% 93%

VGH ICU 2013 73% 92% 89% 100% 93% 93%
Ciprofloxacin
SMH 2015 68% 93% 98% 98% 90% 98%
VIHA - South 2012 81% 97% 98% 96% 88% 96%

VGH/UBC 2013 98% 95% 78% 96% 97% 90%

Piperacillin/ VGH ICU 2013 94% 91% 69% 100% 100% 86%
tazobactam SMH 2015 94% 92% - - 84% -
VIHA - South 2012 94% 96% 0% 0% 96% 96%

VGH/UBC 2013 100% 98% 100% 98% 94% 96%

Imipenem / VGH ICU 2013 100% 94% 100% 100% 97% 93%
Meropenem SMH 2015 99% 99% 99% 99% 85% 99%
VIHA - South 2012 100% 100% 100% 99% 96% 100%
TREATMENT 26

EXAMPLES OF LOCAL ANTIBIOGRAM - REFERENCES

Vancouver Coastal Annual Report 2013/14. Accessed at https://www.vch.ca/media/VCH-quality-
annual-report-2013-2014.pdf on November 13, 2016.

Surrey Memorial Hospital Antibiogram 2015. Accessed at http://physicians.fraserhealth.ca/

getattachment/Clinical-Resources/Strips/Clinical-Services/Antimicrobial-Stewardship/
Antimicrobial-Stewardship-Handbook/Fraser-2015-Antibiogram-SMH.pdf.aspx/ on November
13, 2016.

Vancouver Island Health Authority 2012 Antibiograms. Accessed at http://www.viha.ca/quality/

care/clinical/antibiotics/antibiograms.htm on November 13, 2016.
ILLUSTRATIVE CASE 27

CASE (VS)
71 year-old female, post-op Day 5, aortic valve replacement.
In the last 24 hours, has developed a fever and worsening
confusion. There are worries that she has been aspirating.
Course crackles are noted bilaterally on auscultation.

T = 38.9, RR = 25, HR = 95, BP = 120/80

PMHx: Parkinsons, CVA (6 months ago), atrial fibrillation

MPTA: warfarin 4 mg daily, levodopa/carbidopa 100 mg/25

SR tid, metoprolol 50 mg bid
 TREATMENT 28

EMPIRIC COVERAGE FOR HAP

Cover for S. aureus, P. aeruginosa, and other GNB (strong

recommendation, very low-quality evidence)

When covering MRSA, use vancomycin or linezolid

(strong recommendation, low quality evidence)

Dont use aminoglycosides as sole antipseudomonal agent

(strong recommendation, very low-quality evidence)

Clin Infect Dis 2016; 63: e61-e111

 TREATMENT 29

COMPARISON WITH CANADIAN RECOMMENDATIONS

Scenario 2016 IDSA Guidelines

ONE OF THE FOLLOWING:

Uncomplicated late
onset HAP ONE OF THE FOLLOWING: piperacillin/tazobactam 4.5 g IV q6h

B & D definition - hosp > cefepime 2 g IV q8h

4 days, non-ICU, no ceftriaxone 1-2 g IV daily
mechanical ventilation, no levofloxacin 750 mg IV daily
broad-spectrum levofloxacin 750 mg IV/PO
antibiotics, no other risk daily imipenem 500 mg iv q6h or
factors meropenem 1 g IV q8h
+/-
(B & D - early onset HAP, (ceftazidime or ciprofloxacin are
treat as hospitalized CAP) gentamicin 7 mg/kg IV daily options if additional agents to cover
S. aureus are added)

Clin Infect Dis 2016; 63: e61-e111

Bugs & Drugs App Version 2.0.5, Content Date: June 16, 2016
ILLUSTRATIVE CASE 30

CASE (VS) CONTINUED

VSs blood pressure begins to fall. Within 4 hours, it is 90/55
and drifting downward, despite having received 2 L of IV
fluids. Her dyspnea is worsening, her SaO2 is falling, and it
appears that she will require transfer to the ICU and
intubation/mechanical ventilation.
 TREATMENT 31

HAP SCENARIOS REQUIRING EXPANDED EMPIRIC COVERAGE IN 2016 GUIDELINES

Cover MRSA if: (weak recommendation, very low-quality evidence)

prior IV antibiotic use within 90 days

>20% prevalence of MRSA among S. aureus isolates

local resistance patters are unknown

high risk of mortality (need for ventilatory support, septic shock)

Cover Pseudomonas with two antibiotics from different classes if: (weak
recommendation, very low-quality evidence):

prior IV antibiotic use within 90 days

structural lung disease (i.e., bronchiectasis, cystic fibrosis)

high risk of mortality (need for ventilatory support, septic shock)

Clin Infect Dis 2016; 63: e61-e111

 TREATMENT 32

EMPIRIC COVERAGE FOR VAP

As for HAP, cover for S. aureus, P. aeruginosa, and other

GNB in all empiric regimens (strong recommendation, low-
quality evidence)

When covering MRSA, use vancomycin or linezolid

(strong recommendation, moderate-quality evidence)

Avoid aminoglycosides and colistin if you can (both weak

recommendations, low-quality and very low-quality
evidence, respectively)

Clin Infect Dis 2016; 63: e61-e111

 TREATMENT 33

COMPARISON WITH CANADIAN RECOMMENDATIONS

Scenario 2016 IDSA Guidelines

VAP with lower risk

ONE OF THE FOLLOWING:
for multi-drug ONE OF THE FOLLOWING:
resistance
piperacillin/tazobactam 4.5 g IV q6h
ceftriaxone 1-2 g IV daily
B & D - hosp 5 days or
cefepime or ceftazidime 2 g IV q8h
less, no prior broad levofloxacin 750 mg IV/PO daily
spectrum antibiotics in
imipenem 500 mg iv q6h or
last 3 months
meropenem 1 g IV q8h

Clin Infect Dis 2016; 63: e61-e111

Bugs & Drugs App Version 2.0.5, Content Date: June 16, 2016
 TREATMENT 34

VAP SCENARIOS REQUIRING EXPANDED EMPIRIC COVERAGE IN 2016 GUIDELINES

Cover MRSA if: (weak recommendation, very low-quality

evidence)

prior IV antibiotic use within 90 days

>10-20% prevalence of MRSA among S. aureus isolates

local resistance patters are unknown

Clin Infect Dis 2016; 63: e61-e111

TREATMENT 35

VAP SCENARIOS REQUIRING EXPANDED EMPIRIC COVERAGE IN 2016 GUIDELINES

Cover Pseudomonas with two antibiotics from different classes if: (weak
recommendation, low-quality evidence)

>10% of Gram-negative isolates are resistant to monotherapy options

presence of risk factor(s) for antimicrobial resistance:

prior IV antibiotic use within 90 days,

septic shock at time of VAP,

ARDS preceding VAP,

5 or more days of hospitalization prior to the occurrence of VAP,

acute renal replacement therapy before VAP onset

 TREATMENT 36

PATHOGEN-SPECIFIC THERAPY FOR HAP/VAP

MRSA - vancomycin or linezolid (strong recommendation, moderate-
quality evidence)

consider patient-specific factors, e.g., blood cell count, concurrent

use of serotonin reuptake inhibitors, renal function, cost

Pseudomonas - refer to antimicrobial susceptibilities (strong

recommendation, low-quality evidence), dont use aminoglycosides
alone (strong recommendation, very low-quality evidence)

combination therapy for those who remain in septic shock or are

at high risk of death when susceptibilities are known (weak
recommendation, very low-quality evidence)

Clin Infect Dis 2016; 63: e61-e111

 TREATMENT 37

PATHOGEN-SPECIFIC THERAPY FOR HAP/VAP

ESBL - refer to antimicrobial susceptibilities and patient-specific factors
(allergies and comorbidities that may increase risk of adverse effects)
(strong recommendation, very low-quality evidence)

Acinetobacter spp - carbapenem or ampicillin/sulbactam if susceptible

(weak recommendation, low-quality evidence), not tigecycline (strong
recommendation, low-quality evidence)

IV polymyxin (colistin or polymyxin B) if no other susceptibilities (strong

recommendation, low-quality evidence) plus inhaled colistin (weak
recommendation, moderate-quality evidence)

Carbapenem-resistant pathogens - same as above (strong recommendation,

moderate-quality evidence)

Clin Infect Dis 2016; 63: e61-e111

 TREATMENT 38

DOSING FOR HAP/VAP

We suggest that antibiotic dosing be determined using PK/PD data,
rather than the manufacturers prescribing information. (weak
recommendation, very low-quality evidence)

based on internal meta-analysis showing

reduction of mortality (12 vs 24%; RR 0.49, 95% CI 0.34-0.72) and

ICU LOS (-2.48 days, 95% CI -3.09 to -1.87 days)

improvement in clinical cure rate (81 vs 64%; RR 1.40, 95% CI

1.16-1.69)

however, low confidence in estimated effects, most included

studies were observational

Clin Infect Dis 2016; 63: e61-e111

 TREATMENT 39

LENGTH OF THERAPY
8 vs 15 days for VAP?

We recommend a 7-day course of antimicrobial therapy rather than a

longer duration (strong recommendation, moderate-quality evidence)

internal meta-analysis assessing VAP due to non-glucose-fermenting

GNB showed no difference in pneumonia recurrence (OR 1.42, 95% CI
0.66-3.04) or mortality (OR 0.94, 95% CI 0.56-1.59)

MUST consider the clinical scenario, i.e., rate of improvement

Optimal duration for HAP?

7 days (strong recommendation, very low-quality evidence),

recommendation largely follows evidence for VAP

Clin Infect Dis 2016; 63: e61-e111

 40

ROLE OF
BIOMARKERS
 BIOMARKERS 41

SHOULD __________ BE USED TO DECIDE

WHETHER OR NOT TO INITIATE ANTIBIOTIC THERAPY?
Procalcitonin - no (strong recommendation, moderate-
quality evidence)

sTREM-1 - no (strong recommendation, moderate-quality

evidence)

CRP - no (weak recommendation, low-quality evidence)

Modified CPIS - no (weak recommendation, low-quality

evidence)

Clin Infect Dis 2016; 63: e61-e111

 BIOMARKERS 42

SHOULD DISCONTINUATION OF ANTIBIOTIC THERAPY BE

BASED UPON __________?
Procalcitonin - yes, plus clinical criteria, vs clinical criteria
alone (weak recommendation, low-quality evidence)

CPIS - no (weak recommendation, low-quality evidence)

Clin Infect Dis 2016; 63: e61-e111

 BIOMARKERS 43

DATA AROUND USE OF PROCALCITONIN

Meta-analysis of 14 trials (4221 patients) investigating PCT

use in acute respiratory infections, demonstrated a
decrease in antibiotic exposure of 3.47 days (95% CI
3.17-3.78)

Pooled data for 308 patients with VAP from 3 RCTs,

investigating PCT use in VAP, demonstrated a decrease in
antibiotic duration of 3 days (9.1 vs 12.1 days; p>0.00001)

HOWEVER, trials are routinely unblinded, control groups

often receive treatment courses of 9-15 days
Cochrane Database Syst Rev 2012; 9: CD007498
Clin Infect Dis 2016; 63: e61-e111
 44

FINAL THOUGHTS
 CONCLUSION 45

DOES GUIDELINE COMPLIANCE GUARANTEE SUCCESS?

2005 ATS-IDSA HAP guidelines recommend empirical combination therapy for
patients at risk of infection with multidrug resistant organisms
Kett 2011 (n=303)
prospective, observational comparison, guideline compliance vs non-compliance
vast majority of non-compliant treatment was due to failure to use a secondary anti-
Gram-negative drug

Combination tx =
antipseudomonal
cephalosporin, carbapenem,
or b-lactam/b-lactamase
inhibitor
PLUS
aminoglycoside or
antipseudomonal FQ
PLUS
linezolid or vancomycin

Lancet 2011; 11:181-9

 CONCLUSION 46

DOES GUIDELINE COMPLIANCE GUARANTEE SUCCESS?

Retrospective
cohort study

Included
patients with
VAP, April 1,
2007 to May
31, 2010

4 adult ICUs in
Calgary
AMMI = Association of Medical Microbiology and Infectious
Disease (Canadian)
Can J Infect Dis Med Micro 2016; http://dx.doi.org/10.1155/2016/3702625
CONCLUSION 47

TAKE HOME POINTS

The 2016 IDSA HAP/VAP Guidelines address heterogeneous practice
setttings, with significant differences in resistance patterns

Guidelines, not laws and regulations - be smart, know your

microbiologist(s), and refer to your antibiograms

The underlying principle is judicious use of a finite resource - these

guidelines mark a shift toward more intelligently identifying those at
risk of MDR

Antibiotic courses should be 7 days long by default

Procalcitonin may be a helpful new biomarker in places were

antibiotic courses tend to be longer
 48

THANK YOU.