scholarly journals Molecular profiling of innate immune response mechanisms in ventilator-associated pneumonia

2020 ◽  
Author(s):  
Khyatiben V. Pathak ◽  
Marissa I. McGilvrey ◽  
Charles K. Hu ◽  
Krystine Garcia- Mansfield ◽  
Karen Lewandoski ◽  
...  
Keyword(s):  
Treatment Options ◽  
Diagnostic Value ◽  
High Morbidity ◽  
Ventilator Associated Pneumonia ◽  
Membrane Degradation ◽  
Upper Airways ◽  
Hospital Acquired Infection ◽  
Neutrophil Degranulation ◽  
Hospital Acquired

AbstractVentilator-associated pneumonia (VAP) is a common hospital-acquired infection, leading to high morbidity and mortality. Currently, bronchoalveolar lavage (BAL) is utilized in hospitals for VAP diagnosis and guiding treatment options. While BAL collection procedures are invasive, alternatives such as endotracheal aspirates (ETA) may be of diagnostic value, however, their utility has not been thoroughly explored. Longitudinal ETA and BAL were collected from 16 intubated patients up to 15 days, of which 11 developed VAP. We conducted a comprehensive LC-MS/MS based proteome and metabolome characterization of longitudinal ETA and BAL to detect host and pathogen responses to VAP infection. We discovered a diverse ETA proteome of the upper airways reflective of a rich and dynamic host-microbe interface. Prior to VAP diagnosis by microbial cultures from BAL, patient ETA presented characteristic signatures of reactive oxygen species and neutrophil degranulation, indicative of neutrophil mediated pathogen processing as a key host response to the VAP infection. Along with an increase in amino acids, this is suggestive of extracellular membrane degradation resulting from proteolytic activity of neutrophil proteases. Days prior to VAP diagnosis, detection of pathogen peptides with species level specificity in ETA may increase specificity over culture-based diagnosis. Our findings suggest that ETA may provide early mechanistic insights into host-pathogen interactions associated with VAP infection and therefore facilitate its diagnosis and treatment.Graphical abstract

scholarly journals Molecular Profiling of Innate Immune Response Mechanisms in Ventilator-associated Pneumonia

2020 ◽  
Vol 19 (10) ◽  
pp. 1688-1705
Author(s):  
Khyatiben V. Pathak ◽  
Marissa I. McGilvrey ◽  
Charles K. Hu ◽  
Krystine Garcia-Mansfield ◽  
Karen Lewandoski ◽  
...  
Keyword(s):  
Treatment Options ◽  
Simultaneous Detection ◽  
Diagnostic Value ◽  
High Morbidity ◽  
Ventilator Associated Pneumonia ◽  
Membrane Degradation ◽  
Upper Airways ◽  
Hospital Acquired Infection ◽  
Neutrophil Degranulation ◽  
Hospital Acquired

Ventilator-associated pneumonia (VAP) is a common hospital-acquired infection, leading to high morbidity and mortality. Currently, bronchoalveolar lavage (BAL) is used in hospitals for VAP diagnosis and guiding treatment options. Although BAL collection procedures are invasive, alternatives such as endotracheal aspirates (ETA) may be of diagnostic value, however, their use has not been thoroughly explored. Longitudinal ETA and BAL were collected from 16 intubated patients up to 15 days, of which 11 developed VAP. We conducted a comprehensive LC–MS/MS based proteome and metabolome characterization of longitudinal ETA and BAL to detect host and pathogen responses to VAP infection. We discovered a diverse ETA proteome of the upper airways reflective of a rich and dynamic host-microbe interface. Prior to VAP diagnosis by microbial cultures from BAL, patient ETA presented characteristic signatures of reactive oxygen species and neutrophil degranulation, indicative of neutrophil mediated pathogen processing as a key host response to the VAP infection. Along with an increase in amino acids, this is suggestive of extracellular membrane degradation resulting from proteolytic activity of neutrophil proteases. The metaproteome approach successfully allowed simultaneous detection of pathogen peptides in patients' ETA, which may have potential use in diagnosis. Our findings suggest that ETA may facilitate early mechanistic insights into host-pathogen interactions associated with VAP infection and therefore provide its diagnosis and treatment.

scholarly journals Pathogenesis-Targeted Preventive Strategies for Multidrug Resistant Ventilator-Associated Pneumonia: A Narrative Review

2020 ◽  
Vol 8 (6) ◽  
pp. 821 ◽  
Author(s):  
Antonella Cotoia ◽  
Savino Spadaro ◽  
Guido Gambetti ◽  
Despoina Koulenti ◽  
Gilda Cinnella
Keyword(s):  
Treatment Options ◽  
Multidrug Resistant ◽  
Convincing Evidence ◽  
Narrative Review ◽  
Ventilator Associated Pneumonia ◽  
Effective Prevention ◽  
Hospital Acquired Infection ◽  
Effective Combination ◽  
Oral Decontamination ◽  
Hospital Acquired

Ventilator-associated pneumonia (VAP) is the most common hospital-acquired infection in the intensive care unit (ICU), accounting for relevant morbidity and mortality among critically ill patients, especially when caused by multidrug resistant (MDR) organisms. The rising problem of MDR etiologies, which has led to a reduction in treatment options, have increased clinician’s attention to the employment of effective prevention strategies. In this narrative review we summarized the evidence resulting from 27 original articles that were identified through a systematic database search of the last 15 years, focusing on several pathogenesis-targeted strategies which could help preventing MDR-VAP. Oral hygiene with Chlorhexidine (CHX), CHX body washing, selective oral decontamination (SOD) and/or digestive decontamination (SDD), multiple decontamination regimens, probiotics, subglottic secretions drainage (SSD), special cuff material and shape, silver-coated endotracheal tubes (ETTs), universal use of gloves and contact isolation, alcohol-based hand gel, vaporized hydrogen peroxide, and bundles of care have been addressed. The most convincing evidence came from interventions directly addressed against the key factors of MDR-VAP pathogenesis, especially when they are jointly implemented into bundles. Further research, however, is warranted to identify the most effective combination.

scholarly journals Future Directions and Molecular Basis of Ventilator Associated Pneumonia

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Kubra Aykac ◽  
Yasemin Ozsurekci ◽  
Sevgen Tanir Basaranoglu
Keyword(s):  
Pediatric Patients ◽  
Pediatric Intensive Care ◽  
Molecular Pathogenesis ◽  
High Morbidity ◽  
Gram Negative Bacteria ◽  
Ventilator Associated Pneumonia ◽  
Future Directions ◽  
Hospital Acquired Infection ◽  
Hospital Acquired ◽  
Near Future

Mechanical ventilation is a lifesaving treatment and has complications such as ventilator associated pneumonia (VAP) that lead to high morbidity and mortality. Moreover VAP is the second most common hospital-acquired infection in pediatric intensive care units. Although it is still not well understood, understanding molecular pathogenesis is essential for preventing and treating pneumonia. A lot of microbes are detected as a causative agent of VAP. The most common isolated VAP pathogens in pediatric patients areStaphylococcus aureus, Pseudomonas aeruginosa,and other gram negative bacteria. All of the bacteria have different pathogenesis due to their different virulence factors and host reactions. This review article focused on mechanisms of VAP with molecular pathogenesis of the causative bacteria one by one from the literature. We hope that we know more about molecular pathogenesis of VAP and we can investigate and focus on the management of the disease in near future.

scholarly journals Incidence of ventilator associated pneumonia in tracheostomised and non tracheostomised patients

2018 ◽  
Vol 6 (8) ◽  
pp. 2754
Author(s):  
David D. M. Rosario ◽  
Anitha Sequeira
Keyword(s):  
Mechanical Ventilation ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Ventilator Associated Pneumonia ◽  
Care Hospital ◽  
Early Tracheostomy ◽  
Hospital Acquired Infection ◽  
Total Incidence ◽  
Hospital Acquired Pneumonia ◽  
Hospital Acquired

Background: Pneumonia is the most common hospital acquired infection in the intensive care unit. One of the causes for hospital acquired pneumonia is ventilator associated pneumonia. Tracheostomy is known to prevent occurrence of ventilator associated pneumonia as it decreases the respiratory dead space, assists in better clearance of secretions and prevents chances of aspiration. Generally, tracheostomy is done after 2 weeks of endotracheal intubation to prevent tracheal complications. The aim of this study is to identify the incidence of ventilator associated pneumonia in tracheostomised and non tracheostomised patients and to see if early tracheostomy can prevent development of ventilator associated pneumonia.Methods: The study was conducted at a tertiary care hospital during a period of four years. 100 patients who were on mechanical ventilation for more than 7 days where taken up for the study. APACHE 4 scoring system was used. The incidence of Ventilator associated pneumonia in tracheostomised and non tracheostomised patients was studied.Results: In our study the total incidence of VAP was 44 %. In our study out of the 42 patients who had undergone tracheostomy 13 (30.95%) patients had ventilator associated pneumonia. Among the non-tracheostomised patients 31 (53.44%) out of 58 patients developed ventilator associated pneumonia. In our study the incidence of ventilator associated pneumonia was much lesser (12%) in patients who underwent tracheostomy in the period 7 to 10 days after mechanical ventilation, whereas in those who underwent tracheostomy after 11 days incidence of ventilator associated pneumonia was much higher.Conclusions: Our study showed that the incidence of ventilator associated pneumonia was much higher among non tracheostomised patients compared to patients who underwent tracheostomy. Hence patients undergoing earlier tracheostomy had a clear advantage than those undergoing tracheostomy late or non tracheostomised patients in preventing ventilator associated pneumonia.

scholarly journals Avoiding ventilator-associated pneumonia: Curcumin-functionalized endotracheal tube and photodynamic action

2020 ◽  
Vol 117 (37) ◽  
pp. 22967-22973
Author(s):  
Amanda C. Zangirolami ◽  
Lucas D. Dias ◽  
Kate C. Blanco ◽  
Carolina S. Vinagreiro ◽  
Natalia M. Inada ◽  
...  
Keyword(s):  
Endotracheal Tube ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Ventilator Associated Pneumonia ◽  
Hospital Acquired Infection ◽  
Hospital Acquired Infections ◽  
Hospitalization Costs ◽  
Hospital Acquired

Hospital-acquired infections are a global health problem that threatens patients’ treatment in intensive care units, causing thousands of deaths and a considerable increase in hospitalization costs. The endotracheal tube (ETT) is a medical device placed in the patient’s trachea to assist breathing and delivering oxygen into the lungs. However, bacterial biofilms forming at the surface of the ETT and the development of multidrug-resistant bacteria are considered the primary causes of ventilator-associated pneumonia (VAP), a severe hospital-acquired infection for significant mortality. Under these circumstances, there has been a need to administrate antibiotics together. Although necessary, it has led to a rapid increase in bacterial resistance to antibiotics. Therefore, it becomes necessary to develop alternatives to prevent and combat these bacterial infections. One possibility is to turn the ETT itself into a bactericide. Some examples reported in the literature present drawbacks. To overcome those issues, we have designed a photosensitizer-containing ETT to be used in photodynamic inactivation (PDI) to avoid bacteria biofilm formation and prevent VAP occurrence during tracheal intubation. This work describes ETT’s functionalization with curcumin photosensitizer, as well as its evaluation in PDI against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. A significant photoinactivation (up to 95%) against Gram-negative and Gram-positive bacteria was observed when curcumin-functionalized endotracheal (ETT-curc) was used. These remarkable results demonstrate this strategy’s potential to combat hospital-acquired infections and contribute to fighting antimicrobial resistance.

scholarly journals Emergence of DIM-1 and KPC-1 Genes Associated Carbapenem-Resistant Pseudomonas Aeruginosa Isolates in Three Major Hospitals in Hanoi, Vietnam (2010-2015)

2021 ◽  
Author(s):  
Tran Hai Anh ◽  
Tran Huy Hoang ◽  
Vu Thi Ngoc Bich ◽  
Trinh Son Tung ◽  
Tran Dieu Linh ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Phylogenetic Tree Analysis ◽  
Antibiotic Resistant ◽  
Hospital Acquired Infection ◽  
Healthcare Settings ◽  
Carbapenem Resistant ◽  
Hospital Acquired

Abstract Background: Multidrug-resistant bacteria including carbapenem resistant Pseudomonas aeruginosa are recognised as an important cause of hospital-acquired infections worldwide. To determine the molecular characterisation and antibiotic resistant genes associated with carbapenem-resistant P. aeruginosa. Methods: we conducted whole-genome sequencing and phylogenetic analysis of 72 carbapenem-resistant P. aeruginosa isolated from hospital-acquired infection patients from 2010 to 2015 in three major hospitals in Hanoi, Vietnam. Results: We identified three variants of IMP genes, among which IMP-15 gene was the most frequent (n= 34) in comparison to IMP-26 (n= 2) and IMP-51 (n=12). We observed two isolates with imipenem MIC >128mg/L that co-harboured IMP-15 and DIM-1 genes and seven isolates (imipenem MIC> 128mg/L) with KPC-1 gene from the same hospital. MLST data showed that sequence types (ST) of 72 isolates were classified into 18 STs and phylogenetic tree analysis divided these isolates into nine groups. Conclusion: Our results provide evidence that not only IMP-26, but other variants of IMPs like IMP-15 and IMP-51 genes and several STs (ST235, ST244, ST277, ST310, ST773 and ST3151) have been disseminated in health care settings in Vietnam. Also, we report the first finding in Vietnam that two isolates belonging to ST1240 and ST3340 harboured two important carbapenemase genes (IMP-15 and, DIM-1) and seven isolates belonging to ST3151 of P. aeruginosa carried the KPC-1 gene, which could be a potential cause of seriously restricted available treatment options in healthcare settings.

An Update on the Management of Nosocomial Pneumonia

2008 ◽  
Vol 21 (5) ◽  
pp. 380-389 ◽  
Author(s):  
Rahul Gupta ◽  
Kurt A. Wargo
Keyword(s):  
Nosocomial Pneumonia ◽  
Stenotrophomonas Maltophilia ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Early Recognition ◽  
Treatment Options ◽  
Acinetobacter Species ◽  
Hospital Acquired Infection ◽  
Appropriate Treatment ◽  
Dosing Strategies ◽  
Hospital Acquired

Nosocomial pneumonia is the second most common hospital-acquired infection, after urinary tract infection; however, it carries with it a mortality rate estimated to be between 20% and 50%. Furthermore, patients with nosocomial pneumonia are hospitalized for an additional 7 to 9 days with an attributable cost of $40 000 or more per patient compared to patients without nosocomial pneumonia. While treatment options vary, initial empiric treatment of nosocomial pneumonia should include antimicrobials that will have activity against the organisms that will likely be encountered, including, but not limited to, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter species, Klebsiella pneumoniae, Enterobacter subspecies, Serratia marcescens, and Stenotrophomonas maltophilia. During a time of increasing resistance, it is crucial that early recognition along with appropriate treatment and dosing strategies are employed to achieve successful outcomes. The goal of this article is to update clinicians about nosocomial pneumonia and provide information regarding caveats to selecting and dosing antimicrobials, so informed decisions can be made when treating this serious condition.

scholarly journals Lack of bundled care intervention training program will trip up rates of ventilator associated pneumonia: the contemporary trend

2019 ◽  
Vol 6 (6) ◽  
pp. 2623
Author(s):  
Rituja Kaushal ◽  
Sanjeev Gupta ◽  
Aashish Saraogi ◽  
Sandhya Singh
Keyword(s):  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Secondary Data ◽  
Evidence Based ◽  
Ventilator Associated Pneumonia ◽  
Care Hospital ◽  
Hospital Acquired Infection ◽  
Intervention Training ◽  
Care Intervention ◽  
Hospital Acquired

Background: Ventilator associated pneumonia (VAP) is the deadliest hospital acquired infection in many low resource settings of developing countries. For VAP prevention, the concept of bundle of care was defined. Evidence based resources showed it enabled great successes in VAP prevention. It has been observed in clinical practice due to insufficient compliance, there is a need to address related issues in order to define easier-to-apply procedures.Methods: It is a retrospective analytical secondary data based study. It was conducted in a tertiary care hospital of Bhopal city.Results: T value of Mann Whitney/U test was found to be statistically significant and is indicating need of “Bundle Care Intervention” training for the prevention of increase in ventilator associated pneumonia rates in any health care setting.Conclusions: Expanded bevy of options related to infect

scholarly journals Ventilator Associated Pneumonia in Pediatric Trauma Patients

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Dalton Sullivan ◽  
Matthew P. Landman ◽  
Rachel E. Gahagen Gahagen
Keyword(s):  
Risk Factors ◽  
Pediatric Trauma ◽  
Trauma Patients ◽  
Ventilator Associated Pneumonia ◽  
Hospital Acquired Infection ◽  
Trauma Population ◽  
Hospital Acquired ◽  
Cultured Bacteria ◽  
The Impact ◽  
Overall Mortality

Background: Ventilator associated pneumonia (VAP) is a common hospital-acquired infection found in intubated trauma patients. In previous adult studies, VAP has been associated with an increase in length of stay, cost, morbidity, mortality, and longer mechanical ventilation. There remains little examination of the risk factors, prognosis, and microbiology of VAP within the pediatric trauma population. This study aims to analyze factors associated with VAP in pediatric trauma patients. Methods: The Riley Hospital for Children Trauma Registry was utilized to identify intubated pediatric trauma patients from 2016-2020. Patients were excluded if intubated for less than 48 hours.   VAP was defined as positive if patients met either Centers for Disease Control definition and or were clinically diagnosed with and treated for VAP. Univariate and multivariate modeling was performed. Results: A total of 171 patients met inclusion criteria and 43 (25%) were diagnosed with VAP. The median age was 8 years (2-13) and ISS was 26.5 (22-35). The median duration of intubation was 203.8 hours (117.3-331.3). The overall mortality was 55 (32.2%). While variables such as lower age and use of MTP resulted in a higher likelihood of mortality, VAP diagnosis was not associated with increased mortality. BAL analysis displayed that the most common cultured bacteria were H. influenzae, Staph. aureus, and Strep. Pneumoniae with most VAPs being diagnosed on day 2 of admission. When analyzing the impact of age, ISS, intubation hours, ICU days, and GI prophylaxis on VAP, only age was significantly associated with VAP: for each year the odds of VAP rose by 10%. Conclusions: A quarter of the pediatric trauma patients were diagnosed with VAP during the study period.  No modifiable risk factors were found for VAP with only patient age demonstrating significance for the diagnosis.  Further investigation into VAP definition and prevention in pediatric trauma patients should occur given it’s prevalence.

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