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

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.

2020 ◽  
Vol 19 (10) ◽  
pp. 1688-1705
Author(s):  
Khyatiben V. Pathak ◽  
Marissa I. McGilvrey ◽  
Charles K. Hu ◽  
Krystine Garcia-Mansfield ◽  
Karen Lewandoski ◽  
...  

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.


2020 ◽  
Author(s):  
Khyatiben V. Pathak ◽  
Marissa I. McGilvrey ◽  
Charles K. Hu ◽  
Krystine Garcia- Mansfield ◽  
Karen Lewandoski ◽  
...  

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


2008 ◽  
Vol 52 (12) ◽  
pp. 4388-4399 ◽  
Author(s):  
Chris M. Pillar ◽  
Mohana K. Torres ◽  
Nina P. Brown ◽  
Dineshchandra Shah ◽  
Daniel F. Sahm

ABSTRACT Doripenem, a 1β-methylcarbapenem, is a broad-spectrum antibiotic approved for the treatment of complicated urinary tract and complicated intra-abdominal infections. An indication for hospital-acquired pneumonia including ventilator-associated pneumonia is pending. The current study examined the activity of doripenem against recent clinical isolates for the purposes of its ongoing clinical development and future longitudinal analysis. Doripenem and comparators were tested against 12,581 U.S. clinical isolates collected between 2005 and 2006 including isolates of Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus pneumoniae, Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. MICs (μg/ml) were established by broth microdilution. By MIC90, doripenem was comparable to imipenem and meropenem in activity against S. aureus (methicillin susceptible, 0.06; resistant, 8) and S. pneumoniae (penicillin susceptible, ≤0.015; resistant, 1). Against ceftazidime-susceptible Enterobacteriaceae, the MIC90 of doripenem (0.12) was comparable to that of meropenem (0.12) and superior to that of imipenem (2), though susceptibility of isolates exceeded 99% for all evaluated carbapenems. The activity of doripenem was not notably altered against ceftazidime-nonsusceptible or extended-spectrum β-lactamase screen-positive Enterobacteriaceae. Doripenem was the most potent carbapenem tested against P. aeruginosa (MIC90/% susceptibility [%S]: ceftazidime susceptible = 2/92%S, nonsusceptible = 16/61%S; imipenem susceptible = 1/98.5%S, nonsusceptible = 8/56%S). Against imipenem-susceptible Acinetobacter spp., doripenem (MIC90 = 2, 89.1%S) was twice as active by MIC90 as were imipenem and meropenem. Overall, doripenem potency was comparable to those of meropenem and imipenem against gram-positive cocci and doripenem was equal or superior in activity to meropenem and imipenem against Enterobacteriaceae, including β-lactam-nonsusceptible isolates. Doripenem was the most active carbapenem tested against P. aeruginosa regardless of β-lactam resistance.


Author(s):  
David D. M. Rosario ◽  
Anitha Sequeira

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.


Author(s):  
A. P. R. Wilson ◽  
Preet Panesar

The pharmacokinetics of antimicrobials are altered in critically-ill patients, particularly in the presence of renal or hepatic failure. Maintaining a choice or diversity of antibiotics is important due to the emergence of resistance. Antibiotic use should also be kept to the minimum and local protocols need to be established. For community-acquired infection, co-amoxiclav or a parenteral cephalosporin can be used, while for hospital-acquired infection, piperacillin/tazobactam, ciprofloxacin, or ceftazidime are recommended. For suspected vascular catheter infection or methicillin-resistant Staphylococcus aureus (MRSA) infection, teicoplanin or vancomycin should be used, with meropenem or imipenem reserved for second line treatment. Prophylactic antibiotics should not be continued once a surgical patient has returned from the theatre. Patients with febrile neutropenia receive piptazobactam, meropenem, ceftazidime or ciprofloxacin and a glycopeptide. Antifungals, usually caspofungin or liposomal amphotericin, are used if fungal infection is suspected, especially after failed antibacterial treatment. Cephalosporin use has declined as they have been linked with emergence of MRSA and Clostridium difficile. However, this reflects overuse and they still have a place as part of a diverse choice of antibiotics. Vancomycin and teicoplanin use has increased greatly in order to treat MRSA and line infections, but resistance remains unusual. Carbapenem use has increased rapidly with the emergence of extended spectrum beta-lactamase producing Gram-negative bacteria.


2020 ◽  
Vol 117 (37) ◽  
pp. 22967-22973
Author(s):  
Amanda C. Zangirolami ◽  
Lucas D. Dias ◽  
Kate C. Blanco ◽  
Carolina S. Vinagreiro ◽  
Natalia M. Inada ◽  
...  

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.


2020 ◽  
Vol 8 (6) ◽  
pp. 821 ◽  
Author(s):  
Antonella Cotoia ◽  
Savino Spadaro ◽  
Guido Gambetti ◽  
Despoina Koulenti ◽  
Gilda Cinnella

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.


Author(s):  
Rituja Kaushal ◽  
Sanjeev Gupta ◽  
Aashish Saraogi ◽  
Sandhya Singh

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


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