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 medicalsurgical intensive care patients according to 4 different observers Interobserver variability in the assessment of ventilator-associated pneumonia is high. Komplas M. Am J Infect Control 2010
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
Quantitative versus qualitative cultures of respiratory secretions for clinical outcomes in patients with VAP Forest plot of comparison: Quantitative vs qualitative culture, outcome: Mortality Burton DC et al. Cochrane Database of Systematic Reviews 2012
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.
Ventilator-Associated Pneumonia: Depends on Your Definition Comparison of NNIS Definition of VAP to BAL Diagnosis 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. 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. 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. Komplas M et al. CID 2012
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 FiO 2 followed by a rise in daily minimum PEEP by 2.5 cm H2O lasting 2 days or a rise in daily minimum FiO 2 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
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 ICUpneumonia 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