Ventilator-associated Infections Research Articles

Ventilator-associated respiratory infections in children on home invasive mechanical ventilation.

Ventilator-associated respiratory tract infections (VARTI) are among the most common indications for hospitalization among children with chronic respiratory failure requiring at-home ventilation. This review aims to provide an overview of the key clinical features, diagnostic approaches, and management strategies for home VARTIs while highlighting the challenges in diagnosis and management.

A prospective study on clinical profile, severity, microbiology, and outcome of patients with ventilator associated infective complications admitted in intensive care unit of a tertiary care hospital

: Mechanical ventilation epitomizes intensive care medicine. Ventilator‑associated complications are mainly Ventilator associated respiratory infections (VARI); These are a major cause of concern in the intensive care units (ICUs) worldwide, especially in developing countries. VARI includes patients with ventilator‑associated tracheobronchitis (VAT) and ventilator‑associated pneumonia (VAP).The clinical profile, severity, microbiology, and outcomes of such infections is not well described in Eastern India. The primary objective of the study was to study the risk factors, severity scoring, microbiological profile and 28 days outcome of patients admitted in intensive care unit of our hospital.Secondary objective of our study was to find out any correlation between risk factors, severity scoring, microbiological profile, and outcome of patients with VAT and VAP admitted in intensive care unit of our hospital.: This was a prospective observational study done in the ICU of a tertiary care centre in eastern India. A total 50 patients of clinically, microbiologically and/or radiologically diagnosed case of VAP and VAT were included in the study. A structured data collection proforma was prepared and data collection was done. Raw data was tabulated and analysed: 66% of our patients were male, Smoking was the commonest addiction(24%), VARI developed early with 17% on Day 3, 72% developed VARI within 5 days of ventilation. 16% had history of recent admission, Diabetes and hypertension were the commonest comorbidities. 58% of the patients developed VAP, the median SOFA score in VAP was 6 also similar in VAT. Patients with neurological diseases had the maximum number of VAT and VAP. Klebsiella pneumoniae was the commonest organism causing VAT (42%) while Acinetobacter Baumanii was commonest to cause VAP (44%). 51% of VAP patients were on volume control mode, while it was 52% of VAT patients. Most isolates are MDR pathogens with intermediate sensitivity to Polymyxin being most common (66%) 1 isolate was pan resistant. Mortality was 58% for VAP and 19% in VAT. Both Klebsiella and Acinetobacter accounts for 41% death in VAP group, in VAT group Klebsiella was commonest however no statistical significance with other organism.: Gram negative bacteria were the predominant cause of VAT and VAP, Acinetobacter and Klebsiella are the commonest organisms. Most Isolates are MDR with intermediate sensitivity to Polymyxins. Median SOFA scores were the same in both. Mortality was high in VAP group. Volume control mode was predominant mode of ventilation, Neurological causes was predominant cause that leads to ventilation and subsequent VARI.

Outcomes associated with ventilator-associated events (VAE), respiratory infections (VARI), pneumonia (VAP) and tracheobronchitis (VAT) in ventilated pediatric ICU patients: A multicentre prospective cohort study

ObjectivesAn objective categorization of respiratory infections based on outcomes is an unmet clinical need. Ventilator-associated pneumonia and tracheobronchitis remain used in clinical practice, whereas ventilator-associated events (VAE) are limited to surveillance purposes. Research methodology/designThis was a secondary analysis from a multicentre observational prospective cohort study. VAE were defined as a sustained increase in minimum Oxygen inspired fraction (FiO2) and/or Positive end-expiratory pressures (PEEP) of ≥ 0.2/2 cm H2O respectively, or an increase of 0.15 FiO2 + 1 cm H20 positive end-expiratory pressures for ≥ 1 calendar-day. Setting15 Paediatric Intensive Care Units. Main outcome measuresMechanical ventilation duration, intensive care and hospital length of stay; (LOS) and mortality. ResultsA cohort of 391 ventilated children with an age (median, [Interquartile Ranges]) of 1 year[0.2–5.3] and 7 days[5–10] of mechanical ventilation were included. Intensive care and hospital stays were 11 [7–19] and 21 [14–39] days, respectively. Mortality was 5.9 %. Fifty-eight ventilator-associated respiratory infections were documented among 57 patients: Seventeen (29.3 %) qualified as ventilator-associated pneumonia (VAP) and 41 (70.7 %) as ventilator-associated tracheobronchitis (VAT). Eight pneumonias and 16 tracheobronchitis (47 % vs 39 %,P = 0.571) required positive end-expiratory pressure or oxygen increases consistent with ventilator-associated criteria. Pneumonias did not significantly impact on outcomes when compared to tracheobronchitis. In contrast, infections (pneumonia or tracheobronchitis) following VAEs criteria were associated with > 6, 8 and 15 extra-days of ventilation (16 vs 9.5, P = 0.001), intensive care stay (23.5 vs 15; P = 0.004) and hospital stay (39 vs 24; P = 0.015), respectively. ConclusionWhen assessing ventilated children with respiratory infections, VAE apparently is associated with higher ventilator-dependency and LOS compared with pneumonia or tracheobronchitis. Implications for practiceIncorporating the modification of ventilatory settings for further categorization of the respiratory infections may facilitate therapeutic management among ventilated patients.

Continuous Versus Intermittent Control Cuff Pressure for Preventing Ventilator-Associated Pneumonia: An Updated Meta-Analysis.

This study aimed to evaluate the effect of continuous control cuff pressure (CCCP) versus intermittent control cuff pressure (ICCP) for the prevention of ventilator-associated pneumonia (VAP) in critically ill patients. Relevant literature was searched in several databases, including PubMed, Embase, Web of Science, ProQuest, the Cochrane Library, Wanfang Database and China National Knowledge Infrastructure between inception and September 2022. Randomized controlled trials were considered eligible if they compared CCCP with ICCP for the prevention of VAP in critically ill patients. This meta-analysis was performed using the RevMan 5.3 and Trial Sequential Analysis 0.9 software packages. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to assess the level of evidence. We identified 14 randomized control trials with a total of 2080 patients. Meta-analysis revealed that CCCP was associated with a significantly lower incidence of VAP compared with ICCP (relative risk [RR] = 0.52; 95% confidence interval [CI]: 0.37-0.74; P < 0.001), although considerable heterogeneity was observed (I2 = 71%). Conducting trial sequential analysis confirmed the finding, and the GRADE level was moderate. Subgroup analysis demonstrated that CCCP combined with subglottic secretion drainage (SSD) had a more significant effect on reducing VAP (RR = 0.39; 95% CI = 0.29-0.52; P < 0.001). The effect of CCCP on ventilator-associated respiratory infection (VARI) incidence was uncertain (RR = 0.81; 95% CI = 0.53-1.24; P = 0.34; I2 = 61%). Additionally, CCCP significantly reduced the duration of mechanical ventilation (MV) (mean difference [MD] = -2.42 days; 95% CI = -4.71-0.12; P = 0.04; I2 = 87%). Descriptive analysis showed that CCCP improved the qualified rate of cuff pressure. However, no significant differences were found in the length of intensive care unit (ICU) stay (MD = 2.42 days; 95% CI = -1.84-6.68; P = 0.27) and ICU mortality (RR = 0.86; 95% CI = 0.74-1.00; P = 0.05). Our findings suggest that the combination of CCCP and SSD can reduce the incidence of VAP and the duration of MV and maintain the stability of cuff pressure. A combination of CCCP and SSD applications is suggested for preventing VAP.

Ventilator-Associated Lower Respiratory Tract Infections and Their Association With COVID-19: A Retrospective Cohort Study in a Portuguese Intensive Treatment Unit.

Introduction Ventilator-associated pneumonia (VAP) is the most common infectious complication related to admission to an Intensive Treatment Unit (ITU). Ventilator-associated lower respiratory tract infection (VA-LRTI) is a broader diagnosis than VAP. By disregarding radiological criteria, it will include both VAP and ventilator-associated tracheobronchitis. This study,conducted in the setting of a Portuguese ITU, aims to study the incidence, microbiology and clinical outcome of VA-LRTI and its association with COVID-19. Methods A retrospective cohort study included patients admitted to a Portuguese ITU who underwent invasive mechanical ventilation (IMV) for over 48 hours between 01/01/2021 and 31/12/2021. The Hospitals in Europe Link for Infection Control through Surveillance (HELICS) criteria were applied, disregarding the radiological criteria, for the diagnosis of VA-LRTI. Results The group of patients with COVID-19 had 46.38 episodes of VA-LRTI/1000 days of ventilation, while patients without COVID-19 had 16.35 episodes/1000 days of ventilation (RR 2.78, p < 0.001). Of the 85 microorganisms isolated, 82% were gram-negative microorganisms, with species of the genus Klebsiella being the most prevalent (22.4%). There was a lower prevalence of beta-lactam-resistant organisms in patients with COVID-19 (RR 0.35, p = 0.031). The development of VA-LRTI is associated with longer times ofIMV (difference in medians 10 days, p < 0.001), but with no significant differences in mortality (RR 1.21, p = 0.14). Discussion Patients with COVID-19 seem more predisposed to developing VA-LRTI, possibly due to intrinsic characteristics of the disease. Although no increase in mortality has been demonstrated, VA-LRTI can entail important costs related to morbidity, antibiotic pressure and economic costs that must be considered.

ICU-acquired infections in immunocompromised patients.

Immunocompromised patients account for an increasing proportion of the typical intensive care unit (ICU) case-mix. Because of the increased availability of new drugs for cancer and auto-immune diseases, and improvement in the care of the most severely immunocompromised ICU patients (including those with hematologic malignancies), critically ill immunocompromised patients form a highly heterogeneous patient population. Furthermore, a large number of ICU patients with no apparent immunosuppression also harbor underlying conditions altering their immune response, or develop ICU-acquired immune deficiencies as a result of sepsis, trauma or major surgery. While infections are associated with significant morbidity and mortality in immunocompromised critically ill patients, little specific data are available on the incidence, microbiology, management and outcomes of ICU-acquired infections in this population. As a result, immunocompromised patients are usually excluded from trials and guidelines on the management of ICU-acquired infections. The most common ICU-acquired infections in immunocompromised patients are ventilator-associated lower respiratory tract infections (which include ventilator-associated pneumonia and tracheobronchitis) and bloodstream infections. Recently, several large observational studies have shed light on some of the epidemiological specificities of these infections-as well as on the dynamics of colonization and infection with multidrug-resistant bacteria-in these patients, and these will be discussed in this review. Immunocompromised patients are also at higher risk than non-immunocompromised hosts of fungal and viral infections, and the diagnostic and therapeutic management of these infections will be covered. Finally, we will suggest some important areas of future investigation.

Etiology of nosocomial infections in intensive care patients in German hospitals: An analysis of trends between 2008 and 2022

PurposeData from the intensive care component of the German hospital infection surveillance system (KISS) was used to investigate the epidemiology of pathogens responsible for the most frequent device-associated infections and their development over time. MethodThe 10 most common pathogens were identified for ventilator-associated lower respiratory tract infections (VALRTI), catheter associated urinary tract infections (CAUTI), and central venous catheter associated bloodstream infections (CVC-BSI). The development over time was analyzed based on three five-year time periods: 2008–2012, 2013–2017, 2018–2022. ResultsData from 1425 ICUs were included together with 121,762 device-associated infections with 138,299 isolated pathogens. A remarkable and significant increase in the frequency of Klebsiella spp. was found for VALRTI, that was almost twice as high during 2018–2022 compared to 2008–2012. For CAUTI, there was a significant increase of all Enterobacterales with the most prominent increase in Klebsiella spp. With regard to CVC-BSI, the situation for coagulase-negative staphylococci and E. coli was relatively stable; while there was a significant increase in Enterococcus spp. and Klebsiella spp. and a decrease in S. aureus. ConclusionKnowledge about the current frequency of pathogens responsible for nosocomial infections in intensive care units is important for guiding empirical antimicrobial therapy. Data from national nosocomial infection surveillance systems can provide relevant information about the development of pathogens.

Knowledge and practices of healthcare workers in prevention and control of hospital-acquired infections in the Maternity Department at Bindura Provincial Hospital, Zimbabwe

Infections acquired in hospitals are the most frequent negative consequences of the healthcare delivery system, which affects both developed and developing nations. Among hospitalized patients and healthcare professionals, they are among the top causes of mortality and morbidity. Therefore, healthcare professionals are crucial in preventing and controlling hospital-acquired illnesses and safeguarding patients. The purpose of this study was to determine the knowledge and practices of healthcare workers (HCWs) in the prevention and control of hospital-acquired infections (HAIs) in the Maternity Department at Bindura Provincial Hospital. A cross-sectional study design was used to collect data from 46 participants using a self-administered questionnaire. Of which, 54.3% had 2 to 5 years of experience. With regard to the knowledge of HAIs, 59% of HCWs did not know what HAIs were, 57% did not know that cleaners and mothers should be engaged in infection prevention and control (IPC) activities, whereas 85% did not know that ventilator-associated infections and COVID-19 (57%) are HAIs. Segregation of waste was shown to be poorly practiced with 56% of HCWs, 65% were unaware of the hospital’s IPC policy, and 7% had never utilize the manuals of standard operating procedures when performing their jobs. This study recommended that every HCW should receive instruction on IPC methods from the facilities’ IPC coordinators, who should also regularly supervise the staff to monitor compliance with IPC. Mothers should receive more education on the prevention of infections when first admitted to the ward.

Healthcare‑associated infections in intensive care unit patients with and without COVID-19: a single center prospective surveillance study

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic led to a global increase in healthcare-associated infections (HAI) among intensive care unit (ICU) patients. Whether this increase is directly attributable to COVID-19 or whether the pandemic indirectly (via staff shortages or breaches in infection prevention measures) led to this increase, remains unclear. The objectives of this study were to assess HAI incidence and to identify independent risk factors for HAI in COVID-19 and non-COVID-19 ICU patients.MethodsWe established a monocentric prospective HAI surveillance in the medical ICU of our tertiary care center from September 1st 2021 until August 31st 2022, during circulation of the SARS-CoV-2 delta and omicron variants. We consecutively included patients ≥ 18 years of age with an ICU length of stay of > 2 calendar days. HAI were defined according to the European Centre for Disease Prevention and Control definitions. HAI rate was calculated per 1,000 patient-days or device-days; risk ratios (RR) and corresponding 95% confidence intervals (CI) for COVID-19 versus non-COVID-19 patients were calculated. We used multivariable Cox regression to identify independent risk factors for HAI. As a proxy for institutional COVID-19 burden, weekly COVID-19 density (i.e. percentage of COVID-19 patients among all ICU patients) was included in the model as time-dependent co-variable.ResultsWe included 254 patients, 64 (25.1%) COVID-19 and 190 (74.9%) non-COVID-19 patients; 83 HAI in 72 patients were recorded, thereof 45 ventilator-associated lower respiratory tract infections (VA-LRTI) (54.2%) and 18 blood stream infections (BSI) (21.6%). HAI incidence rate was 49.1/1,000 patient-days in COVID-19 and 22.5/1,000 patient-days in non-COVID-19 patients (RR 2.2, 95%-CI 1.4–3.4). This result was mainly due to different VA-LRTI rates (40.3 vs. 11.7/1,000 ventilator days, p < 0.001), whereas BSI rates were not statistically different (9.4 vs. 5.6/1,000 patient days, p = 0.27). Multivariable analysis identified COVID-19 as main risk factor for HAI development, whereas age, mechanical ventilation and COVID-19 density were not significant.ConclusionsThese data from the fourth and fifth wave of the pandemic show a higher HAI incidence in COVID-19 than in non-COVID-19 ICU patients, mainly due to an increase in pulmonary infections. A diagnosis of COVID-19 was independently associated with HAI development, whereas institutional COVID-19 burden was not.

A Survey of PICU Clinician Practices and Perceptions regarding Respiratory Cultures in the Evaluation of Ventilator-Associated Infections in the BrighT STAR Collaborative.

To characterize respiratory culture practices for mechanically ventilated patients, and to identify drivers of culture use and potential barriers to changing practices across PICUs. Cross-sectional survey conducted May 2021-January 2022. Sixteen academic pediatric hospitals across the United States participating in the BrighT STAR Collaborative. Pediatric critical care medicine physicians, advanced practice providers, respiratory therapists, and nurses. None. We summarized the proportion of positive responses for each question within a hospital and calculated the median proportion and IQR across hospitals. We correlated responses with culture rates and compared responses by role. Sixteen invited institutions participated (100%). Five hundred sixty-eight of 1,301 (44%) e-mailed individuals completed the survey (median hospital response rate 60%). Saline lavage was common, but no PICUs had a standardized approach. There was the highest variability in perceived likelihood (median, IQR) to obtain cultures for isolated fever (49%, 38-61%), isolated laboratory changes (49%, 38-57%), fever and laboratory changes without respiratory symptoms (68%, 54-79%), isolated change in secretion characteristics (67%, 54-78%), and isolated increased secretions (55%, 40-65%). Respiratory cultures were likely to be obtained as a "pan culture" (75%, 70-86%). There was a significant correlation between higher culture rates and likelihood to obtain cultures for isolated fever, persistent fever, isolated hypotension, fever, and laboratory changes without respiratory symptoms, and "pan cultures." Respondents across hospitals would find clinical decision support (CDS) helpful (79%) and thought that CDS would help align ICU and/or consulting teams (82%). Anticipated barriers to change included reluctance to change (70%), opinion of consultants (64%), and concern for missing a diagnosis of ventilator-associated infections (62%). Respiratory culture collection and ordering practices were inconsistent, revealing opportunities for diagnostic stewardship. CDS would be generally well received; however, anticipated conceptual and psychologic barriers to change must be considered.

Transcriptomics reveals shared immunosuppressive landscapes in ventilator-associated lower respiratory tract infections (VA-LRTI) patients

ABSTRACT Background Ventilator-associated pneumonia (VAP) represents a transitory status of immunoparalysis, and we hypothesized that ventilator-associated tracheobronchitis (VAT) could share also some degree of immune response to a respiratory infection. Research design and methods A prospective observational study in five medical ICUs to evaluate immunological alterations of patients with VA-LRTI. Immunological gene expression profiles in the blood using whole transcriptome microarrays in the first 24 hours following diagnosis. The area under the receiver operating characteristic curve (AUROC) was used to assess the accuracy of mRNA levels to differentiate VA-LRTI and lack of infection. A principal component analysis (PCA) was employed for analyzing the impact of each genetic expression footprint variable in explaining the variance of the cohort. Results There was overlapping between the three classes of patients encompassing gene expression levels of 8 genes (i.e. HLA, IL2RA, CD40LG, ICOS, CCR7, CD1C, CD3E). HLA-DRA was equally low among VAT and VAP patients characterizing immune depression, and significantly lower than the control group. Conclusions Our findings suggest that VAP and VAT are not so different regarding gene expression levels suggesting a degree of immunosuppression. Our results indicate a state of immunoparalysis in respiratory infections in critically ill patients.

Influence of a Structured Microbiological Endotracheal Monitoring Program on the Outcome of Critically Ill COVID-19 Patients: An Observational Study.

In past influenza pandemics and the current COVID-19 pandemic, bacterial endotracheal superinfections are a well-known risk factor for higher morbidity and mortality. The goal of this study was to investigate the influence of a structured, objective, microbiological monitoring program on the prognosis of COVID-19 patients with mechanical ventilation. A structured microbiological monitoring program (at intubation, then every 3 days) included collection of endotracheal material. Data analysis focused on the spectrum of bacterial pathogens, mortality, as well as intensive care unit (ICU), hospital, and mechanical ventilation duration. A total of 29% of the patients showed bacterial coinfection at the time of intubation, and within 48 h, 56% developed ventilator-associated pneumonia (VAP). Even though patients with VAP had significantly longer ICU, hospital, and mechanical ventilation durations, there was no significant difference in mortality between patients with VAP pneumonia and patients without bacterial infection. VAP is a common complication in COVID-19 patients. In contrast to already published studies, in our study implementing a structured microbiological monitoring program, COVID-19 patients with bacterial coinfection or VAP did not show higher mortality. Thus, a standardized, objective, microbiological screening can help detect coinfection and ventilator-associated infections, refining anti-infective therapy and positively influencing patient outcomes.

Virtual Reality Simulation for Advanced Infection Control Education in Neonatal Intensive Care Units: Focusing on the Prevention of Central Line-Associated Bloodstream Infections and Ventilator-Associated Infections.

This study examined the effects of a virtual reality simulation for advanced infection control education in neonatal intensive care units (VR_AICENICU) on nurses' infection control knowledge and performance confidence. We examined nurses' presence, empathy, and program satisfaction using a non-equivalent control group pre-post design. Nurses were divided into an experimental group (n = 20) experiencing VR simulation and routine NICU practice and a control group (n = 20) with routine NICU practice. The VR_AICENICU program comprised three scenarios: high-risk medication with lipid solution, dressing and management for peripheral inserted central line, and aspiration prevention and skincare management during ventilator use for premature infants. Data were collected between February and July 2022. The experimental group showed significantly greater improvements in infection control knowledge and performance confidence compared to the pre-test. The average scores of presence, empathy, and program satisfaction of the experimental group were 4.39 ± 0.36, 4.33 ± 0.75, and 4.90 ± 0.31, respectively. The VR_AICENICU program has implications for the education needs of nurses working in NICUs and enhances their knowledge and performance of infection control. Future studies should apply the VR_AICENICU program to different severity grades of NICU patients and develop additional VR programs.

Study of incidence, microbiological profile of nosocomial infections in pediatric intensive care unit of tertiary care center

Background: Prevalence of nosocomial infections in pediatric intensive care unit (PICU) ranges between from 6-26%. Increased use of broad-spectrum antibiotics, urinary and central venous catheterization and endotracheal intubation put patients at an increased risk of affecting with nosocomial infections in pediatric patients. Methods: A hospital based prospective study was carried out on 725 patients aged between 1 month and 12 years admitted in PICU of Al-Ameen medical college hospital, Bijapur, Karnataka, India and institute of child health and hospital for children, Madras medical college, Chennai, Tamil Nadu, India from 15-09-2020 to 15-08-2022. All patients who were admitted with fever or developed fever in first 48 hours of life were excluded from the study. The data obtained in the course of study was analyzed by appropriate statistical methods. Results: Out of 725 pediatric admissions, the incidence of nosocomial infection in the present was found to be 108 (14.8%). Concerning the type of infection, the commonest reported types were central-line associated bloodstream infection (CABI) 59 (54.6%) and ventilator-associated infection (VAI) 52 (48.1%), followed by bloodstream infection 45 (41.6%), catheter associated urinary tract infection (CA-UTI) 38 (35.1%) and urinary tract infection (UTI) 30 (27.7%) respectively. Conclusions: The incidence of nosocomial infection was 14.8%. The central line associated blood stream infection was the predominant cause of nosocomial infection. This information can help decision makers establish preventive strategies and implement effective and reliable plans.

Cefto Real-Life Study: Real-World Data on the Use of Ceftobiprole in a Multicenter Spanish Cohort.

Ceftobiprole is a fifth-generation cephalosporin that has been approved in Europe solely for the treatment of community-acquired and nosocomial pneumonia. The objective was to analyze the use of ceftobiprole medocaril (Cefto-M) in Spanish clinical practice in patients with infections in hospital or outpatient parenteral antimicrobial therapy (OPAT). This retrospective, observational, multicenter study included patients treated from 1 September 2021 to 31 December 2022. A total of 249 individuals were enrolled, aged 66.6 ± 15.4 years, of whom 59.4% were male with a Charlson index of four (IQR 2-6), 13.7% had COVID-19, and 4.8% were in an intensive care unit (ICU). The most frequent type of infection was respiratory (55.8%), followed by skin and soft tissue infection (21.7%). Cefto-M was administered to 67.9% of the patients as an empirical treatment, in which was administered as monotherapy for 7 days (5-10) in 53.8% of cases. The infection-related mortality was 11.2%. The highest mortality rates were identified for ventilator-associated pneumonia (40%) and infections due to methicillin-resistant Staphylococus aureus (20.8%) and Pseudomonas aeruginosa (16.1%). The mortality-related factors were age (OR: 1.1, 95%CI (1.04-1.16)), ICU admission (OR: 42.02, 95%CI (4.49-393.4)), and sepsis/septic shock (OR: 2.94, 95%CI (1.01-8.54)). In real life, Cefto-M is a safe antibiotic, comprising only half of prescriptions for respiratory infections, that is mainly administered as rescue therapy in pluripathological patients with severe infectious diseases.

A national survey of PICU clinician practices and perceptions about respiratory cultures for invasively ventilated patients

Background: Respiratory cultures are commonly obtained from patients with suspicion for ventilator-associated infections (VAIs). In the absence of specimen ordering and collection guidelines, management practices may differ. We characterized current respiratory culture collection practices and perceptions and identified potential barriers to changing practices among a national collaborative of pediatric intensive care units (PICUs). Methods: We conducted an electronic survey of PICU physicians, advanced practice providers (APPs), respiratory therapists (RTs), and nurses at 16 US academic pediatric hospitals across the United States. Positive Likert-scale responses (eg, “agree” and “strongly agree”) were grouped. To account for varying hospital representation, we analyzed the results as the median proportion of participants with that response across the hospitals. Results: After excluding incomplete responses, 568 (44%) of 1,301 invited participants responded (range, 16–107 per site); the median hospital response rate was 60% (range, 17%–83%). Roles included physicians (35%), APPs (10%), RTs (24%), and nurses (31%). Moreover, 44% of the participating units cared for cardiac surgery patients. Across hospitals, specimens are often collected by RTs, followed by nurses, typically via inline endotracheal aspirate for either endotracheal tubes or tracheostomies. Saline lavage is a common practice, but only 4% reported a standardized approach. Examining the likeliness to obtain cultures for different clinical symptoms, the widest variation in responses were for fever and inflammatory markers without respiratory symptoms (median proportion, 68%; IQR, 54%–79%), isolated change in secretion characteristics (67%; IQR, 54%–78%), isolated increased secretions (55%; IQR, 40%–65%), isolated inflammatory markers (49%; IQR, 38%–57%) or isolated fever (49%; IQR, 38%–61%). Overall, 75% (IQR, 70%–86%) of reported respiratory cultures were likely to be obtained as a “pan culture.” Most respondents (median proportion, 69%) felt confident about the indications to obtain cultures, but 60% felt that clinicians had a low threshold, and 84% reported clinical practice variation. Barriers to change included reluctance to change (70%), opinion of consultants (64%), and fear of missing a diagnosis of VAI (62%). Respondents agreed that they would find clinical decision support (CDS) tools helpful (79%). In addition, 83% expected that they would follow CDS, and 82% thought that CDS would help align ICU and/or consulting teams. Conclusions: Among 16 participating hospitals, we detected a lack of standardized respiratory-culture specimen collection and ordering practices. Most respondents agreed that CDS tools would be helpful. Diagnostic stewardship of respiratory cultures using CDS must account for potential reluctance to change and needs to address stakeholder perspectives, including fear of missing infections.Disclosure: None

Lysine Trimethylation in Planktonic and Pellicle Modes of Growth in Acinetobacter baumannii.

Over the past 30 years, Acinetobacter baumannii has been described as an important nosocomial pathogen due to frequent ventilator-associated infections. Many biological processes of A. baumannii remain elusive, such as the formation of an air-liquid biofilm (pellicle). Several studies demonstrated the importance of post-translational modifications (PTMs) in A. baumannii physiology. Here, we investigated K-trimethylation in A. baumannii ATCC 17978 in planktonic and pellicle modes using proteomic analysis. To identify the most high-confidence K-trimethylated peptides, we compared different sample preparation methods (i.e., strong cation exchange, antibody-capture) and processing software (i.e., different database search engines). We identified, for the first time, 84 K-trimethylated proteins, many of which are involved in DNA and protein synthesis (HupB, RplK), transporters (Ata, AdeB), or lipid metabolism processes (FadB, FadD). In comparison with previous studies, several identical lysine residues were observed acetylated or trimethylated, indicating the presence of proteoforms and potential PTM cross-talks. This is the first large-scale proteomic study of trimethylation in A. baumannii and will be an important resource for the scientific community (availability in Pride repository under accession PXD035239).

COVID-19 associated infections in the ICU setting: A retrospective analysis in a tertiary-care hospital

IntroductionOur work describes the frequency of superinfections in COVID-19 ICU patients and identifies risk factors for its appearance. Second, we evaluated ICU length of stay, in-hospital mortality and analyzed a subgroup of multidrug-resistant microorganisms (MDROs) infections. MethodsRetrospective study conducted between March and June 2020. Superinfections were defined as appeared ≥48h. Bacterial and fungal infections were included, and sources were ventilator-associated lower respiratory tract infection (VA-LRTI), primary bloodstream infection (BSI), secondary BSI, and urinary tract infection (UTI). We performed a univariate analysis and a multivariate analysis of the risk factors. ResultsTwo-hundred thirteen patients were included. We documented 174 episodes in 95 (44.6%) patients: 78 VA-LRTI, 66 primary BSI, 9 secondary BSI and 21 UTI. MDROs caused 29.3% of the episodes. The median time from admission to the first episode was 18 days and was longer in MDROs than in non-MDROs (28 vs. 16 days, p<0.01). In multivariate analysis use of corticosteroids (OR 4.9, 95% CI 1.4–16.9, p 0.01), tocilizumab (OR 2.4, 95% CI 1.1–5.9, p 0.03) and broad-spectrum antibiotics within first 7 days of admission (OR 2.5, 95% CI 1.2–5.1, p<0.01) were associated with superinfections. Patients with superinfections presented respect to controls prolonged ICU stay (35 vs. 12 days, p<0.01) but not higher in-hospital mortality (45.3% vs. 39.7%, p 0.13). ConclusionsSuperinfections in ICU patients are frequent in late course of admission. Corticosteroids, tocilizumab, and previous broad-spectrum antibiotics are identified as risk factors for its development.

Aerosolized Antibiotics to Manage Ventilator-Associated Infections: A Comprehensive Review.

Ventilator-associated lower respiratory tract infectious complications in critically ill patients cover a wide spectrum of one disease process (respiratory infection), initiating from tracheal tube and/or tracheobronchial colonization, to ventilator associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP). VAP occurence has been associated with increased intensive care unit (ICU) morbidity (ventilator days, as well as length of ICU and hospital stay) and ICU mortality. Therefore, treatments that aim at VAP/VAT incidence reduction are a high priority. The aim of the present review is to discuss the current literature concerning two major aspects: (a) can aerosolized antibiotics (AA) administered in a pre-emptive way prevent the occurrence of ventilator-associated infections? and (b) can VAT treatment with aerosolized avert the potential evolution to VAP? There were identified eight studies that provided data on the use of aerosolized antibiotics for the prevention of VAT/VAP. Most of them report favorable data on reducing the colonisation rate and the progression to VAP/VAT. Another four studies dealt with the treatment of VAT/VAP. The results support the decrease in the incidence to VAP transition and/or the improvement in signs and symptoms of VAP. Moreover, there are concise reports on higher cure rates and microbiological eradication in patients treated with aerosolized antibiotics. Yet, differences in the delivery modality adopted and resistance emergence issues preclude the generalisability of the results. Aerosolized antibiotic therapy can be used to manage ventilator-associated infections, especially those with difficult to treat resistance. The limited clinical data raise the need for large randomized controlled trials to confirm the benefits of AA and to evaluate the impact on antibiotic selection pressure.

Risk factors for developing ventilator-associated lower respiratory tract infection in patients with severe COVID-19: a multinational, multicentre study, prospective, observational study

Around one-third of patients diagnosed with COVID-19 develop a severe illness that requires admission to the Intensive Care Unit (ICU). In clinical practice, clinicians have learned that patients admitted to the ICU due to severe COVID-19 frequently develop ventilator-associated lower respiratory tract infections (VA-LRTI). This study aims to describe the clinical characteristics, the factors associated with VA-LRTI, and its impact on clinical outcomes in patients with severe COVID-19. This was a multicentre, observational cohort study conducted in ten countries in Latin America and Europe. We included patients with confirmed rtPCR for SARS-CoV-2 requiring ICU admission and endotracheal intubation. Only patients with a microbiological and clinical diagnosis of VA-LRTI were included. Multivariate Logistic regression analyses and Random Forest were conducted to determine the risk factors for VA-LRTI and its clinical impact in patients with severe COVID-19. In our study cohort of 3287 patients, VA-LRTI was diagnosed in 28.8% [948/3287]. The cumulative incidence of ventilator-associated pneumonia (VAP) was 18.6% [610/3287], followed by ventilator-associated tracheobronchitis (VAT) 10.3% [338/3287]. A total of 1252 bacteria species were isolated. The most frequently isolated pathogens were Pseudomonas aeruginosa (21.2% [266/1252]), followed by Klebsiella pneumoniae (19.1% [239/1252]) and Staphylococcus aureus (15.5% [194/1,252]). The factors independently associated with the development of VA-LRTI were prolonged stay under invasive mechanical ventilation, AKI during ICU stay, and the number of comorbidities. Regarding the clinical impact of VA-LRTI, patients with VAP had an increased risk of hospital mortality (OR [95% CI] of 1.81 [1.40–2.34]), while VAT was not associated with increased hospital mortality (OR [95% CI] of 1.34 [0.98–1.83]). VA-LRTI, often with difficult-to-treat bacteria, is frequent in patients admitted to the ICU due to severe COVID-19 and is associated with worse clinical outcomes, including higher mortality. Identifying risk factors for VA-LRTI might allow the early patient diagnosis to improve clinical outcomes.Trial registration: This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.