Ventilator-associated Lower Respiratory Infections Research Articles

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.

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.

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.

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.

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.

Ventilator-Associated Pneumonia in Immunosuppressed Patients.

Immunocompromised patients-including patients with cancer, hematological malignancies, solid organ transplants and individuals receiving immunosuppressive therapies for autoimmune diseases-account for an increasing proportion of critically-ill patients. While their prognosis has improved markedly in the last decades, they remain at increased risk of healthcare- and intensive care unit (ICU)-acquired infections. The most frequent of these are ventilator-associated lower respiratory tract infections (VA-LTRI), which include ventilator-associated pneumonia (VAP) and tracheobronchitis (VAT). Recent studies have shed light on some of the specific features of VAP and VAT in immunocompromised patients, which is the subject of this narrative review. Contrary to previous belief, the incidence of VAP and VAT might actually be lower in immunocompromised than non-immunocompromised patients. Further, the relationship between immunosuppression and the incidence of VAP and VAT related to multidrug-resistant (MDR) bacteria has also been challenged recently. Etiological diagnosis is essential to select the most appropriate treatment, and the role of invasive sampling, specifically bronchoscopy with bronchoalveolar lavage, as well as new molecular syndromic diagnostic tools will be discussed. While bacteria-especially gram negative bacteria-are the most commonly isolated pathogens in VAP and VAT, several opportunistic pathogens are a special concern among immunocompromised patients, and must be included in the diagnostic workup. Finally, the impact of immunosuppression on VAP and VAT outcomes will be examined in view of recent papers using improved statistical methodologies and treatment options-more specifically empirical antibiotic regimens-will be discussed in light of recent findings on the epidemiology of MDR bacteria in this population.

The rapid detection of respiratory pathogens in critically ill children

PurposeRespiratory infections are the most common reason for admission to paediatric intensive care units (PICU). Most patients with lower respiratory tract infection (LRTI) receive broad-spectrum antimicrobials, despite low rates of bacterial culture confirmation. Here, we evaluated a molecular diagnostic test for LRTI to inform the better use of antimicrobials.MethodsThe Rapid Assay for Sick Children with Acute Lung infection Study was a single-centre, prospective, observational cohort study of mechanically ventilated children (> 37/40 weeks corrected gestation to 18 years) with suspected community acquired or ventilator-associated LRTI. We evaluated the use of a 52-pathogen custom TaqMan Array Card (TAC) to identify pathogens in non-bronchoscopic bronchoalveolar lavage (mini-BAL) samples. TAC results were compared to routine microbiology testing. Primary study outcomes were sensitivity and specificity of TAC, and time to result.ResultsWe enrolled 100 patients, all of whom were tested with TAC and 91 of whom had matching culture samples. TAC had a sensitivity of 89.5% (95% confidence interval (CI95) 66.9–98.7) and specificity of 97.9% (CI95 97.2–98.5) compared to routine bacterial and fungal culture. TAC took a median 25.8 h (IQR 9.1–29.8 h) from sample collection to result. Culture was significantly slower: median 110.4 h (IQR 85.2–141.6 h) for a positive result and median 69.4 h (IQR 52.8–78.6) for a negative result.ConclusionsTAC is a reliable and rapid adjunct diagnostic approach for LRTI in critically ill children, with the potential to aid early rationalisation of antimicrobial therapy.

Predictors and Outcomes of Healthcare-Associated Infections among Patients with COVID-19 Admitted to Intensive Care Units in Punjab, Pakistan; Findings and Implications.

Healthcare-associated infections (HAIs) have a considerable impact on morbidity, mortality and costs. The COVID-19 pandemic resulted in an appreciable number of hospitalized patients being admitted to intensive care units (ICUs) globally with a greater risk of HAIs. Consequently, there is a need to evaluate predictors and outcomes of HAIs among COVID-19 patients admitted to ICUs. A retrospective study of patients with COVID-19 admitted to ICUs of three tertiary care hospitals in the Punjab province over a five-month period in 2021 was undertaken to ascertain predictors and outcomes of HAIs. Of the 4534 hospitalized COVID-19 patients, 678 were admitted to ICUs, of which 636 patients fulfilled the inclusion criteria. Overall, 67 HAIs were identified among the admitted patients. Ventilator-associated lower respiratory tract infections and catheter-related urinary tract infections were the most frequent HAIs. A significantly higher number of patients who developed HAIs were on anticoagulants (p = 0.003), antithrombotic agents (p &lt; 0.001), antivirals (p &lt; 0.001) and IL-6 inhibiting agents (p &lt; 0.001). Secondary infections were significantly higher in patients who were on invasive mechanical ventilation (p &lt; 0.001), had central venous access (p = 0.023), and urinary catheters (p &lt; 0.001). The mortality rate was significantly higher in those with secondary infections (25.8% vs. 1.2%, p &lt; 0.001). Our study concluded that COVID-19 patients admitted to ICUs have a high prevalence of HAIs associated with greater mortality. Key factors need to be addressed to reduce HAIs.

The Biofire® Filmarray® Pneumonia Plus panel for management of lower respiratory tract infection in mechanically-ventilated patients in the COVID-19 era: a diagnostic and cost-benefit evaluation

We assessed the diagnostic performance of the Biofire® Filmarray® Pneumonia Plus panel (FA-PP) compared to standard culture in Intensive Care Unit patients with suspected ventilator-associated lower respiratory tract infection in the COVID-19 era. We determined whether its implementation in routine diagnostic algorithms would be cost-beneficial from a hospital perspective. Of 163 specimens, 96 (59%) returned negative results with FA-PP and conventional culture, and 29 specimens (17.8%) were positive with both diagnostic methods and yielded concordant qualitative bacterial identification/isolation. Thirty-nine specimens (23.9%) gave discordant results (positive via FA-PP and negative via culture). Real-life adjustments of empirical antimicrobial therapy (EAT) after FA-PP results resulted in additional costs beyond EAT alone of 1868.7 €. Adequate EAT adjustments upon FA-PP results would have resulted in a saving of 6675.8 €. In conclusion, the data presented supports the potential utility of FA-PP for early EAT adjustment in patients with ventilator-associated lower respiratory tract infection.

Early Corticosteroid Therapy May Increase Ventilator-Associated Lower Respiratory Tract Infection in Critically Ill Patients with COVID-19: A Multicenter Retrospective Cohort Study.

Background: The coronavirus disease 2019 (COVID-19) pandemic has put significant pressure on hospitals and in particular on intensive care units (ICU). Some patients develop acute hypoxemic respiratory failure with profound hypoxia, which likely requires invasive mechanical ventilation during prolonged periods. Corticosteroids have become a cornerstone therapy for patients with severe COVID-19, though only little data are available regarding their potential harms and benefits, especially concerning the risk of a ventilator-associated lower respiratory tract infection (VA-LRTI). Methods: This retrospective multicenter study included patients admitted in four ICUs from Belgium and France for severe COVID-19, who required invasive mechanical ventilation (MV). We compared clinical and demographic variables between patients that received corticosteroids or not, using univariate, multivariate, and Fine and Gray analyses to identify factors influencing VA-LRTI occurrence. Results: From March 2020 to January 2021, 341 patients required MV for acute respiratory failure related to COVID-19, 322 of whom were included in the analysis, with 60.6% of them receiving corticosteroids. The proportion of VA-LRTI was significantly higher in the early corticosteroid group (63.1% vs. 48.8%, p = 0.011). Multivariable Fine and Gray modeling considering death and extubation as competing events revealed that the factors independently associated with VA-LRTI occurrence were male gender (adjusted sHR:1.7, p = 0.0022) and corticosteroids (adjusted sHR: 1.44, p = 0.022). Conclusions: in our multicenter retrospective cohort of COVID-19 patients undergoing MV, early corticosteroid therapy was independently associated with VA-LRTI.

No increase of device associated infections in German intensive care units during the start of the COVID-19 pandemic in 2020

BackgroundThe COVID-19 pandemic may have had a substantial impact on the incidence of device-associated healthcare-associated infections (HAI), in particular in intensive care units (ICU). A significant increase of HAI was reported by US hospitals when comparing incidence rates from 2019 and 2020. The objective of this study was to investigate the development of the most relevant device-associated HAI in German ICUs during the year 2020 as compared to 2019.MethodsWe utilized the data of the ICU component of the German National Reference Center for Surveillance of Nosocomial Infections (KISS = Krankenhaus-Infektions-Surveillance-System) for the period 2019–2020. We focused on central line-associated bloodstream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), ventilator-associated lower respiratory infections (VALRTI) and bloodstream infections associated with the use of Extracorporeal-Life-Support-Systems (ECLSABSI). Device use was defined as the number device days per 100 patient days; device-associated infection rates as the number of device-associated infections per 1000 device days. To compare the pooled means between the years and quarters we calculated rate ratios of device-associated infection rates with 95% confidence intervals by Poisson regression models.ResultsThe number of participating ICUs in the surveillance system decreased from 982 in 2019 to 921 in 2020 (6.2%). Device utilization rates increased significantly for central lines and ventilator use. VALRTI rates and CAUTI rates decreased in 2020 compared with 2019, however, no increase was shown for CLABSI or ECLSABSI. This result was also confirmed when the corresponding quarters per year were analyzed.ConclusionsThe lack of an increase in device-associated healthcare associated infections (HAI) in German ICUs may be due to the lower overall incidence of COVID-19 cases in Germany in 2020 compared with US, to a very high availability of ICU beds per 100,000 inhabitants compared with many other countries, and a change in the ICU patient mix due to numerous elective procedures that were postponed during the first two waves. The primary reason seems to be that only 7% of all ICU patients in Germany in 2020 were COVID-19 patients.

Ventilator-Associated Lower Respiratory Tract Bacterial Infections in COVID-19 Compared With Non-COVID-19 Patients.

OBJECTIVES:Ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with prolonged length of stay and increased mortality. We aimed to investigate the occurrence of bacterial VA-LRTI among mechanically ventilated COVID-19 patients and compare these findings to non-COVID-19 cohorts throughout the first and second wave of the pandemic.DESIGN:Retrospective cohort study.SETTING:Karolinska University Hospital, Stockholm, Sweden.PATIENTS:All patients greater than or equal to 18 years treated with mechanical ventilation between January 1, 2011, and December 31, 2020.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:The cohort consisted of 20,223 ICU episodes (479 COVID-19), with a VA-LRTI incidence proportion of 30% (129/426) in COVID-19 and 18% (1,081/5,907) in non-COVID-19 among patients ventilated greater than or equal to 48 hours. The median length of ventilator treatment for COVID-19 patients was 10 days (interquartile range, 5–18 d), which was significantly longer than for all other investigated specific diagnoses. The VA-LRTI incidence rate per 1,000 ventilator days at risk was 31 (95% CI, 26–37) for COVID-19 and 34 (95% CI, 32–36) for non-COVID-19. With COVID-19 as reference, adjusted subdistribution hazard ratios for VA-LRTI was 0.29–0.50 (95% CI, < 1) for influenza, bacterial pneumonia, acute respiratory distress syndrome, and severe sepsis, but 1.38 (95% CI, 1.15–1.65) for specific noninfectious diagnoses. Compared with COVID-19 in the first wave of the pandemic, COVID-19 in the second wave had adjusted subdistribution hazard ratio of 1.85 (95% CI, 1.14–2.99). In early VA-LRTI Staphylococcus aureus was more common and Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli less common in COVID-19 patients, while Serratia species was more often identified in late VA-LRTI.CONCLUSIONS:COVID-19 is associated with exceptionally long durations of mechanical ventilation treatment and high VA-LRTI occurrence proportions. The incidence rate of VA-LRTI was compared with the pooled non-COVID-19 cohort, however, not increased in COVID-19. Significant differences in the incidence of VA-LRTI occurred between the first and second wave of the COVID-19 pandemic.

Correction to: Relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study

Correction to: Relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study

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.

Respiratory Microbiome Disruption and Risk for Ventilator-Associated Lower Respiratory Tract Infection.

Ventilator-associated lower respiratory tract infection (VA-LRTI) is common among critically ill patients and has been associated with increased morbidity and mortality. In acute critical illness, respiratory microbiome disruption indices (MDIs) have been shown to predict risk for VA-LRTI, but their utility beyond the first days of critical illness is unknown. We sought to characterize how MDIs previously shown to predict VA-LRTI at initiation of mechanical ventilation change with prolonged mechanical ventilation, and if they remain associated with VA-LRTI risk. We developed a cohort of 83 subjects admitted to a long-term acute care hospital due to their prolonged dependence on mechanical ventilation; performed dense, longitudinal sampling of the lower respiratory tract, collecting 1066 specimens; and characterized the lower respiratory microbiome by 16S rRNA sequencing as well as total bacterial abundance by 16S rRNA quantitative polymerase chain reaction. Cross-sectional MDIs, including low Shannon diversity and high total bacterial abundance, were associated with risk for VA-LRTI, but associations had wide posterior credible intervals. Persistent lower respiratory microbiome disruption showed a more robust association with VA-LRTI risk, with each day of (base e) Shannon diversity <2.0 associated with a VA-LRTI odds ratio of 1.36 (95% credible interval, 1.10-1.72). The observed association was consistent across multiple clinical definitions of VA-LRTI. Cross-sectional MDIs have limited ability to discriminate VA-LRTI risk during prolonged mechanical ventilation, but persistent lower respiratory tract microbiome disruption, best characterized by consecutive days with low Shannon diversity, may identify a population at high risk for infection and may help target infection-prevention interventions.

Usefulness of Sepsis-3 in diagnosing and predicting mortality of ventilator-associated lower respiratory tract infections.

Early distinguishing ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP) remains difficult in the daily practice. However, this question appears clinically relevant, as treatments of VAT and VAP currently differ. In this study, we assessed the accuracy of sepsis criteria according to the Sepsis-3 definition in the early distinction between VAT and VAP. Retrospective single-center cohort, including all consecutive patients with a diagnosis of VAT (n = 70) or VAP (n = 136), during a 2-year period. Accuracy of sepsis criteria according to Sepsis-3, total SOFA and respiratory SOFA, calculated at time of microbiological sampling were assessed in differentiating VAT from VAP, and in predicting mortality on ICU discharge. Sensitivity and specificity of sepsis criteria were found respectively at 0.4 and 0.91 to distinguish VAT from VAP, and at 0.38 and 0.75 for the prediction of mortality in VA-LRTI. A total SOFA ≥ 6 and a respiratory SOFA ≥ 3 were identified as the best cut-offs for these criteria in differentiating VAT from VAP, with sensitivity and specificity respectively found at 0.63 and 0.69 for total SOFA, and at 0.49 and 0.7 for respiratory SOFA. Additionally, for prediction of mortality, a total SOFA ≥ 7 and a respiratory SOFA = 4 were identified as the best-cut-offs, respectively yielding sensitivity and specificity at 0.56 and 0.61 for total SOFA, and at 0.22 and 0.95 for respiratory SOFA. Sepsis criteria according to the Sepsis-3 definition show a high specificity but a low sensitivity for the diagnosis of VAP. Our results do not support the use of these criteria for the early diagnosis of VAP in patients with VA-LRTI.

Relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study.

PurposeAlthough patients with SARS-CoV-2 infection have several risk factors for ventilator-associated lower respiratory tract infections (VA-LRTI), the reported incidence of hospital-acquired infections is low. We aimed to determine the relationship between SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, and the incidence of VA-LRTI.MethodsMulticenter retrospective European cohort performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation > 48 h were eligible if they had: SARS-CoV-2 pneumonia, influenza pneumonia, or no viral infection at ICU admission. VA-LRTI, including ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP), were diagnosed using clinical, radiological and quantitative microbiological criteria. All VA-LRTI were prospectively identified, and chest-X rays were analyzed by at least two physicians. Cumulative incidence of first episodes of VA-LRTI was estimated using the Kalbfleisch and Prentice method, and compared using Fine-and Gray models.Results1576 patients were included (568 in SARS-CoV-2, 482 in influenza, and 526 in no viral infection groups). VA-LRTI incidence was significantly higher in SARS-CoV-2 patients (287, 50.5%), as compared to influenza patients (146, 30.3%, adjusted sub hazard ratio (sHR) 1.60 (95% confidence interval (CI) 1.26 to 2.04)) or patients with no viral infection (133, 25.3%, adjusted sHR 1.7 (95% CI 1.2 to 2.39)). Gram-negative bacilli were responsible for a large proportion (82% to 89.7%) of VA-LRTI, mainly Pseudomonas aeruginosa, Enterobacter spp., and Klebsiella spp.ConclusionsThe incidence of VA-LRTI is significantly higher in patients with SARS-CoV-2 infection, as compared to patients with influenza pneumonia, or no viral infection after statistical adjustment, but residual confounding may still play a role in the effect estimates.Electronic supplementary materialThe online version of this article (10.1007/s00134-020-06323-9) contains supplementary material, which is available to authorized users.

Impact of Each Component of a Ventilator Bundle on Preventing Ventilator-Associated Pneumonia and Lower Respiratory Infection

Background: Ventilator-associated lower respiratory infections (LRIs) and pneumonia (VAP) are important healthcare-associated infections and are among the leading causes of death worldwide. Prevention of these infections are often based on care bundles. We investigated the incidence of VAP+LRI and the preventive efficacy of each component of our ventilator bundle. Methods: Our ventilator bundle includes 6 components that are daily checked by an infection control practitioner. These 6 evidence-based practices were implemented in 3 ICUs from a general tertiary-care private hospital in Belo Horizonte City (Brazil): (1) daily oral care with chlorhexidine; (2) elevate the head of the bed to between 30 and 45; (3) avoid scheduled ventilator circuit change; (4) monitor cuff pressure; (5) use subglottic secretion drainage; and (6) daily sedation interruption and daily assessment of readiness to extubate. VAP and ventilator-LRI definitions were obtained from the CDC NHSN. The impact of adherence rate to items in the ventilator bundle (%) on the incidence rate of VAP+LRI was assessed using linear regression and scatterplot analyses. Results: Between January 2018 and April 2019, 1,888 ventilator days were observed in the 3 ICUs, with 42 VAP and LRI events, an overall incidence rate of 22.2 cases per 1,000 ventilator days. After September 2018, the infection control service started a campaign to increase the ventilator bundle compliance (Fig. 1). Adherence rates to all 6 bundle components increased between January–August 2018 and September 2018–April 2019 from 25% to 55% for daily oral care, from 34% to 79% for elevating the head of the bed, 28% to 86% for avoiding scheduled ventilator circuit change, from 32% to 83% for cuff pressure monitoring, from 32% to 83% for subglottic secretion drainage, and from 33% to 85% for daily sedation interruption. PAV and LRI incidence decreased from 41 to 16 in ICU A, from 22 to 14 in ICU B and from 24 to 18 in ICU C. The impact of each bundle component was identified by linear regression, calculating the percentage of PAV+LRI incidence rate that is explained by bundle item adherence (r2) and correlation coefficient (r): daily sedation interruption (r2 = 48%; r = 0.69; P = .004) (Fig. 2), cuff pressure monitorization (r2 = 0.3721; r = 0.61; P = .016), subglottic secretion drainage (r2 = 36%; r = 0.60; P = .017), avoidance of scheduled ventilator circuit change (r2 = 34%; r = 0.58; P = .023), daily oral care (r2 = 25%; r = 0.50; P = .050), and elevate the head of the bed (r2 = 25%; r = 0.48; P = .067). Conclusions: The impact of each bundle component on preventing PAV+LRI was identified by the study. An educational intervention performed by the infection control service increased the adherence to the ventilator bundle, and the PAV and LRI incidence decreased.Funding: NoneDisclosures: None