VAP

Are strict diagnostic criteria

advisable? Javier Garau, MD, PhD

18th Infection and Sepsis Symposium, Porto, 27th February 2013

• Limitations of current definitions

• Alternatives

-Streamlined definition of VAP

-VAC (?)

- New molecular methods for

microbiological diagnosis

• Conclusions

Limitations of current definitions of

VAP

• 2 major limitations of the standard VAP definition by the CDC:

(1) many of the diagnostic criteria are very subjective

(2) the definition correlates poorly with histological pneumonia

• Interpretation of these criteria is at the discretion of the physician; reasonable observers are likely to arrive at different conclusions and hence very different VAP rates.

Beyersmann J et al. Infect Cont Hosp Ep 2006

Klompas M. Am J Infect Control 2010

Schurink CA et al. Intens Care Med 20046

Numbers of patients with VAP and selected clinical features among 50 medical-

surgical intensive care patients according to 4 different observers

Komplas M. Am J Infect Control 2010

Interobserver variability in the assessment of ventilator-associated pneumonia is high.

Interobserver agreement between three infection control personnel on the

assessment for VAP in 50 medical-surgical intensive care patients

Agreement defined as the total number of patients where the observers agreed on the presence and absence of the clinical finding.

Klompas M. Am J Infect Control 2010

Forest plot of comparison: Quantitative vs qualitative culture, outcome: Mortality

Burton DC et al. Cochrane Database of Systematic Reviews 2012

Quantitative versus qualitative cultures of respiratory

secretions for clinical outcomes

in patients with VAP

Pulmonary Infiltrates

• The requirement for radiographic evidence

has been identified as the most

problematic because the interpretations of

radiographs and the language used in

reporting radiographic findings vary within

and among institutions.

NNIS missed almost all of the VAPs: the result of the chest x-ray

not meeting the initial criteria of the algorithm. This patient

population had abnormal chest x-rays at admission or did

not have progression of infiltrates.

Comparison of NNIS Definition of VAP to BAL Diagnosis

Ventilator-Associated Pneumonia: Depends on Your Definition

Novosel TJ et al. Am Surgeon 2012

• It might be possible, however, to improve

surveillance objectivity by limiting the

definition to objective and quantifiable

components.

• Focusing on objective criteria should also

improve efficiency

Comparison of Conventional and Streamlined Surveillance Definitions for VAP

Komplas M et al. CID 2012

Characteristics and Adjusted Outcomes for Patients Included in the Multivariate Analysis

Analysis adjusted for hospital, unit type, age, sex, and Charlson index.

Komplas M et al. CID 2012

Faster and more reproducible than the conventional definition and predicts prolongation

of MV and intensive care length of stay as effectively as the conventional definition.

VAC

• The streamlined definition uses similar clinical criteria to the

conventional definition and therefore is likely equally prone to

mislabel VAP

• It might make more sense to focus surveillance and benchmarking

on the syndrome of ventilator-associated complications in general

rather than on pneumonia in particular

• Efforts focused on creating a new outcome measure for

mechanically ventilated patients that captures ventilator associated,

pneumonia-like events in a way that is reliable, objective, clinically

meaningful, and straightforward.

Komplas M et al. CID 2012

VAC

• We retrospectively assessed patients on mechanical

ventilation for ≥48 hours in our study ICU

• VAC was defined as a sustained increase in ventilator

settings after a period of stable or decreasing ventilator

support. Subjective measures such as radiographic

interpretations are not part of this definition

• Using electronic medical record data. We analyzed the

association between VAC and clinical diagnoses, ICU

length of stay, duration of mechanical ventilation,

antibiotic use, and mortality.

Hayashi Y et al. CID 2013

VAC-DEFINITION

• “≥2 days of stable or decreasing daily

minimum PEEP or FiO2 followed by a rise

in daily minimum PEEP by ≥2.5 cm H2O

lasting ≥2 days or a rise in daily minimum

FiO2 by ≥15% lasting ≥2 days”

Komplas M et al. PLoS One 2011

Descriptive Statistics on Outcomes by Ventilator-

Associated Complication Status

Data are mean (standard deviation), median, unless otherwise specified.

Please note that these data are descriptive only and formal comparison of the

groups is not appropriate because of the time-dependent nature of ventilatorassociated

complications status.

Hayashi Y et al. CID 2013

Consumption of Selected Antibiotics During the Stay in ICU by

Ventilator-Associated Complication Status

Hayashi Y et al. CID 2013

• VAC events were due to:

- “Potential VAP”

(VAC with positive culture of respiratory pathogens in respiratory

specimens plus antibiotic prescription with intention to

treat as VAP by intensivist) in 30.7%

- Atelectasis in 16.3%

- Acute pulmonary edema in 11.8%

- ARDS in 6.5%.

• VAC events were associated with significantly increased ICU length of stay, duration of mechanical ventilation, and consumption of broad-spectrum antibiotics but not with longer hospital stays or ICU mortality.

Hayashi Y et al. CID 2013

VAC

• We believe that VAC is a more suitable surveillance

target in patients on mechanical ventilation than VAP

We support calls for improved diagnostic methods (such

as the use of pneumonia specific biomarkers) for VAP

Hayashi Y et al. CID 2013

Validation of a novel high multiplexing real-time

PCR array for the identification of key pathogens

causative of VAP and their associated R genes

• Rapid diagnosis and appropriate empirical antimicrobial therapy is of pivotal importance for the

clinical outcome of VAP.

.

• The Real-time Array PCR for Infectious Diseases (RAP-ID) is a novel technology that combines

multiplex PCR with real-time microarray detection. The VAPChip is a closed cartridge kit adapted

to the RAP-ID instrument that targets 13 key respiratory pathogens causative of VAP and 24

relevant antimicrobial resistance genes to B-lactams.

• Validation VAPChip was carried out on a collection of 292 genotypically characterized bacterial

reference and clinical isolates (including 67 bacterial isolates belonging to the oropharyngeal flora

not targeted by the array)

• The limit of detection of the assay lies between 10 and 100 genome copies/PCR and the dynamic

range is five orders of magnitude permitting at least semi-quantitative reporting of the results.

• Sensitivity, specificity and negative and positive predictive values ranged from 95.8% to 100% for

species identification and detection of resistance genes.

• Conclusions: VAPChip is a novel diagnostic tool able to identify resistant bacterial isolates by

RAP-ID technology. The results of this analytical validation have to be confirmed on clinical

specimens.

Bogaerts P et al. JAC 2013

List of the targets detected by the VAPChip assay

Bogaerts P et al. JAC 2013

Repertoire of Intensive Care Unit

Pneumonia Microbiota • To highlight the different compositions of microbiota in

patients with four different types of ICU-pneumonia.

• 185 episodes of ICU pneumonia and 25 control cases.

• Using 16S rDNA gene amplification followed by clone libraries sequencing.They also used specific quantitative PCR. (qPCR) to target fastidious bacteria and a spectrum of viruses.

• Moreover, they tested samples from our patients by standardized routine culture, amoebal co-culture, blood culture, ELISA targeted antibody detection, immunofluorescent assay antigenemia and antigenuria testing as routinely performed in such cases to compare these routine tests with molecular approaches

Bousbia S et al. PLoS ONE 2012

Summary of the number of bacteria, fungi and viruses identified by molecular assays in BAL fluids

Bousbia S et al. PLoS One 2012

Results

• Overall, patients exhibited 146 different species belonging to 7 different phyla (13 classes, 23 orders, 44 families and 71 genera) of which 73 had not been previously observed in BAL from pneumonia, whereas bacterial clone libraries of controls identified 38 species belonging to 4 different phyla (9 classes, 13 orders, 22 families and 27 genera).

• Moreover, 51 strictly anaerobic bacteria (35%) were found in patients versus 17 anaerobic bacteria (44%) found in controls (p=0.26)

Bousbia S et al. PLoS One 2012

The phylogenetic tree inferred from bacterial 16S rDNA sequences which were

identified in all patients using the Neighbor-Joining and the Kimura 2-parameter methods.

Bacteria previously identified in pneumonia are shown in black.

Bacteria previously identified in pneumonia and which were identified in this study only in pneumonia patients are shown in red.

Bacteria not previously identified in pneumonia patients and which were identified in this study in both

pneumonia and control patients are shown in blue,

Bacteria which have been identified in this study only in control subjects and not in pneumonia patients are shown in green

Bousbia S et al. PLoS One 2012

Differences in bacterial microbiota composition between community- acquired

pneumonia (CAP), ventilator-associated pneumonia (VAP), non-ventilator ICU

pneumonia (NV ICU-P), aspiration pneumonia (AP) and control subjects (CS) cohorts.

Bousbia S et al. PLoS One 2012

• Our results demonstrate that nearly 50%

of the microbial species found had not

been previously reported in lung samples

from pneumonia.

• Therefore, the composition of ICU-

pneumonia microbiota is more complex,

more extensive and more diverse than

originally expected.

Bousbia S et al. PLoS One 2012

Conclusions

• Diagnosis of VAP and its etiology is essential if we are to rationalise its management

• None of the available diagnostic tests, performed alone, can provide an accurate diagnosis of VAP.

• A diagnostic strategy incorporating several criteria seems to be a good compromise.

• Further evaluation by imaging procedures, microbiological cultures, and pneumonia specific biomarkers to refine the probability of diagnosing VAP

- Limiting the definition to objective and quantifiable components.

- Systematic use of microbiological methods

- Non-invasive vs. Invasive techniques

- Systematic use of quantitative techniques

- Explore other image diagnostic modalities

• Incorporate rapid, molecular quantitative diagnostics

• VAC is a good tool for surveillance purposes but is not going to improve our diagnostic ability of VAP