Hyperoxemia as a risk factor for ventilator-associated pneumonia.

BACKGROUND: Consequences of hyperoxemia, such as acute lung injury, atelectasis, and reduced bacterial clearance, might promote ventilator-associated pneumonia (VAP). The aim of our study was to determine the relationship between hyperoxemia and VAP. METHODS: This retrospective observational study was performed in a 30-bed mixed ICU. All patients receiving invasive mechanical ventilation for more than 48 hours were eligible. VAP was defined using clinical, radiologic, and quantitative microbiological criteria. Hyperoxemia was defined as PaO2 > 120 mmHg. All data, except those related to hyperoxemia, were prospectively collected. Risk factors for VAP were determined using univariate and multivariate analysis. RESULTS: VAP was diagnosed in 141 of the 503 enrolled patients (28 %). The incidence rate of VAP was 14.7 per 1000 ventilator days. Hyperoxemia at intensive care unit admission (67 % vs 53 %, OR = 1.8, 95 % CI (1.2, 29), p <0.05) and number of days spent with hyperoxemia were significantly more frequent in patients with VAP, compared with those with no VAP. Multivariate analysis identified number of days spent with hyperoxemia (OR = 1.1, 95 % CI (1.04, 1.2) per day, p = 0.004), simplified acute physiology score (SAPS) II (OR = 1.01, 95 % CI (1.002, 1.024) per point, p < 0 .05), red blood cell transfusion (OR = 1.8, 95 % CI (1.2, 2.7), p = 0.01), and proton pomp inhibitor use (OR = 1.9, 95 % CI (1.03, 1.2), p < 0.05) as independent risk factors for VAP. Other multiple regression models also identified hyperoxemia at ICU admission (OR = 1.89, 95 % CI (1.23, 2.89), p = 0.004), and percentage of days with hyperoxemia (OR = 2.2, 95 % CI (1.08, 4.48), p = 0.029) as independent risk factors for VAP. CONCLUSION: Hyperoxemia is independently associated with VAP. Further studies are required to confirm our results.

Normalization of eosinophil count is predictive of oxygen weaning over the course of COVID-19 infection among hospitalized adults during the first wave of 2020 pandemic.

Background: Understanding COVID-19 outcomes remains a challenge. While numerous biomarkers have been proposed for severity at admission, limited exploration exists for markers during the infection course, especially for the requirement of oxygen therapy. This study investigates the potential of eosinophil count normalization as a predictor for oxygen weaning during the initial wave of the pandemic. Methods: A retrospective study was conducted between March and April 2020 (first wave) among adults admitted directly to a medicine ward. Biological abnormalities, including lymphocyte count, eosinophil count, and C-reactive protein (CRP), were gathered daily during the first week of admission according to oxygen level. In case of worsening, oxygen level was censored at 15 L/min. The primary aim was to assess whether eosinophil count normalization predicts a subsequent decrease in oxygen requirements. Results: Overall, 132 patients were admitted, with a mean age of 59.0 ± 16.3 years. Of the patients, 72% required oxygen, and 20.5% were admitted to the intensive care unit after a median delay of 48 hours. The median CRP at admission was 79 (26-130) mg/L, whereas the eosinophil count was 10 (0-60)/mm3. Eosinophil count normalization (≥100/mm3) by day 2 correlated significantly with decreased oxygen needs (<2 L) with hazard ratio (HR) = 3.7 [1.1-12.9] (p = 0.04). Likewise, CRP < 80 mg/L was associated with reduced oxygen requirements (p < 0.001). Predictors, including underlying chronic respiratory disease, exhibited a trend toward a negative association (p = 0.06). Conclusion: The study highlights the relationship between eosinophil count and CRP, with implications for predicting oxygen weaning during COVID-19. Further research is warranted to explore the relevance of these biomarkers in other respiratory infections.

Efficacy of Expired Antibiotics: A Real Debate in the Context of Repeated Drug Shortages.

This narrative review aims to discuss the main interest in and cautions associated with the use of expired antibiotics in the context of repeated shortages, notably in Europe. Articles concerning the topic of expiry dates related to antibiotic use were reviewed using keywords in the PubMed®/MEDLINE and Google Scholar databases to identify the most extensive evidence-based documentation. The present review evaluates the potential interest and efficacy of using expired drugs and their possible related adverse events. Overall, in the context of drug shortages, expiry dates could be safely extended for at least one year for most solid antibiotics (tablets or powder) used in daily clinical practice, as long as they are stored under the right conditions, in accordance with the summary of product characteristics.

Real-life impact on antimicrobial prescription of Syndromic Molecular Testing in adults hospitalized in infectious disease departments. Respiratory Syndromic Molecular Testing panel: Is it worth it?

BACKGROUND: While sensitive molecular diagnostic tests enable accurate and rapid diagnosis of many respiratory viruses, their impact on antibiotic management remains uncertain. Our study aimed to evaluate the impact of respiratory syndromic molecular testing panel in real-life clinical practice. METHOD: Retrospective descriptive study involving consecutive hospitalized patients in an infectious disease department who had been prescribed a respiratory syndromic molecular testing panel on nasopharyngeal swab samples (FilmArray Respiratory Panel 2 plus) during hospitalization from October 1st, 2021, to February 28th, 2023. RESULTS: All in all, 94 out of 210 screened patients were included in the study. Syndromic molecular testing results influenced antibiotic treatment in seven cases: discontinuation in four cases (three virus identifications), changes in two (Mycoplasma pneumoniae positive cases), and initiation in two (negative viral PCRs and one positive bacterial culture). CONCLUSION: In our study, respiratory syndromic molecular testing had low impact on antibiotic modification.

Nocardia Infection in Patients With Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies: A Prospective Multicenter French Study.

Background: Nocardiosis, a bacterial opportunistic infection caused by Nocardia spp, has recently been reported in patients with anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies, but insufficient data are available about disease presentation, outcomes, and occurrence of autoimmune pulmonary alveolar proteinosis (aPAP) in this population. Methods: We performed a prospective, multicenter, nationwide study in France and included patients with a Nocardia infection who had anti-GM-CSF autoantibodies. We describe their clinical, microbiological, and radiological characteristics, and their outcome at 1 year of follow-up. Results: Twenty patients (18 [90%] male) were included, with a median age of 69 (interquartile range, 44-75) years. The organs most frequently involved were the brain (14/20 [70%]) and the lung (12/20 [60%]). Half of the infections were disseminated (10/20 [50%]). Nocardia identification was predominantly made in abscess fluid (17/20 [85%]), among which 10 (59%) were brain abscesses. The 1-year all-cause mortality was 5% (1/20), and only 1 case of aPAP (1/20 [5%]) occurred during the follow-up period. Conclusions: Nocardiosis with anti-GM-CSF autoantibodies is associated with a low mortality rate despite a high incidence of brain involvement. Although the occurrence of aPAP was infrequent during the 1-year follow-up period, long-term clinical data are needed to fully understand the potential relationship between nocardiosis, anti-GM-CSF autoantibodies, and aPAP.

Lipid Emulsion to Treat Acute Poisonings: Mechanisms of Action, Indications, and Controversies.

Biodetoxification using intravenous lipid emulsion (ILE) in acute poisoning is of growing interest. As well as for local anesthetics, ILE is currently used to reverse toxicity caused by a broad-spectrum of lipophilic drugs. Both pharmacokinetic and pharmacodynamic mechanisms have been postulated to explain its possible benefits, mainly combining a scavenging effect called "lipid sink" and cardiotonic activity. Additional mechanisms based on ILE-attributed vasoactive and cytoprotective properties are still under investigation. Here, we present a narrative review on lipid resuscitation, focusing on the recent literature with advances in understanding ILE-attributed mechanisms of action and evaluating the evidence supporting ILE administration that enabled the international recommendations. Many practical aspects are still controversial, including the optimal dose, the optimal administration timing, and the optimal duration of infusion for clinical efficacy, as well as the threshold dose for adverse effects. Present evidence supports the use of ILE as first-line therapy to reverse local anesthetic-related systemic toxicity and as adjunct therapy in lipophilic non-local anesthetic drug overdoses refractory to well-established antidotes and supportive care. However, the level of evidence is low to very low, as for most other commonly used antidotes. Our review presents the internationally accepted recommendations according to the clinical poisoning scenario and provides the precautions of use to optimize the expected efficacy of ILE and limit the inconveniences of its futile administration. Based on their absorptive properties, the next generation of scavenging agents is additionally presented. Although emerging research shows great potential, several challenges need to be overcome before parenteral detoxifying agents could be considered as an established treatment for severe poisonings.

Back to the future of viruses: a case of triple coinfection caused by respiratory syncytial virus, human coronavirus OC43, and rhinovirus.

We present the case of an 81-year-old man, who was immunocompetent, who was admitted to the hospital with symptoms of fever and dyspnea suspected to be caused by COVID-19. Further examination revealed a triple coinfection, as determined by multiplex polymerase chain reaction testing, caused by the respiratory syncytial virus, human coronavirus OC43, and rhinovirus. Upon auscultation, diffuse wheezing without crackles was detected. After ruling out the possibility of acute heart failure with pulmonary edema, the patient was treated with nebulization of terbutaline for a period of 72 hours. This case serves to demonstrate the potential dangers of lifting barrier measures, such as mandatory face masks in high-risk areas, during the fall-winter season. In addition, it highlights the challenges that may arise in the post-COVID-19 era because reliance on flu vaccinations alone may not be sufficient.

Antibiotic Consumption and Bacterial Resistance Rates in Hospitalized COVID-19 Patients: A Retrospective Study During the 3 First Surges.

In our hospital, during COVID-19 pandemic, overall consumption of antibiotics increased during the three first surges, mainly due to ICU prescription However, antibiotic consumption decreased in the Infectious Diseases Department. Rates of ESBL Enterobacterales remained stable.

Digital health for remote home monitoring of patients with COVID-19 requiring oxygen: a cohort study and literature review.

Background: The clinical course and outcome of COVID-19 vary widely, from asymptomatic and mild to critical. Elderly patients and patients with comorbidities are at increased risk of respiratory failure and oxygen requirements. Due to the massive surge, the pandemic has created challenges for overwhelmed hospitals. Thus, the original home management of COVID-19 patients requiring oxygen and remote monitoring by a web app and a nurse at home were implemented in our center. We aimed to evaluate the outcome of patients with COVID-19 requiring oxygen who benefited from home remote monitoring management. Methods: We performed a retrospective cohort study on all COVID-19 patients requiring oxygen (< 5 L/min) who consulted from October 2020 to April 2021 at our emergency department and were managed with home remote monitoring by a web app and an in-home nurse. We also carried out a literature review of studies on COVID-19 patients requiring oxygen with remote monitoring. Results: We included 300 patients [184 (61.3%) male patients, median age 51 years]. The main comorbidities were cardiovascular disease (n = 117; 39.0%), diabetes mellitus (n = 72; 24.0%), and chronic respiratory disease (n = 32; 10.7%). Among the 28 (9.3%) patients readmitted to the hospital, 6 (1.9%) were hospitalized in the intensive care unit, and 3 (0.9%) died. In the multivariable analysis, risk factors for unplanned hospitalization were chronic respiratory failure (odds ratio (OR) =4.476, 95%CI 1.565-12.80), immunosuppression (OR = 3.736, 95%CI 1.208-11.552), and short delay between symptoms onset and start of telemonitoring (OR = 0.744, 95%CI 0.653-0.847). In the literature review, we identified seven other experiences of remote monitoring management. Mortality rate and unplanned hospitalization were low (maximum 1.9 and 12%, respectively). Conclusion: Our study confirms the safety of home remote monitoring of patients with COVID-19 who require oxygen, as well as our literature review. However, patients with chronic respiratory failure and immunosuppression should be closely monitored.

Effects of Standard-Dose Prophylactic, High-Dose Prophylactic, and Therapeutic Anticoagulation in Patients With Hypoxemic COVID-19 Pneumonia: The ANTICOVID Randomized Clinical Trial.

Importance: Given the high risk of thrombosis and anticoagulation-related bleeding in patients with hypoxemic COVID-19 pneumonia, identifying the lowest effective dose of anticoagulation therapy for these patients is imperative. Objectives: To determine whether therapeutic anticoagulation (TA) or high-dose prophylactic anticoagulation (HD-PA) decreases mortality and/or disease duration compared with standard-dose prophylactic anticoagulation (SD-PA), and whether TA outperforms HD-PA; and to compare the net clinical outcomes among the 3 strategies. Design, Settings, and Participants: The ANTICOVID randomized clinical open-label trial included patients with hypoxemic COVID-19 pneumonia requiring supplemental oxygen and having no initial thrombosis on chest computer tomography with pulmonary angiogram at 23 health centers in France from April 14 to December 13, 2021. Of 339 patients randomized, 334 were included in the primary analysis-114 patients in the SD-PA group, 110 in the HD-PA, and 110 in the TA. At randomization, 90% of the patients were in the intensive care unit. Data analyses were performed from April 13, 2022, to January 3, 2023. Interventions: Patients were randomly assigned (1:1:1) to receive either SD-PA, HD-PA, or TA with low-molecular-weight or unfractionated heparin for 14 days. Main Outcomes and Measures: A hierarchical criterion of all-cause mortality followed by time to clinical improvement at day 28. Main secondary outcome was net clinical outcome at day 28 (composite of thrombosis, major bleeding, and all-cause death). Results: Among the study population of 334 individuals (mean [SD] age, 58.3 [13.0] years; 226 [67.7%] men and 108 [32.3%] women), use of HD-PA and SD-PA had similar probabilities of favorable outcome (47.3% [95% CI, 39.9% to 54.8%] vs 52.7% [95% CI, 45.2% to 60.1%]; P = .48), as did TA compared with SD-PA (50.9% [95% CI, 43.4% to 58.3%] vs 49.1% [95% CI, 41.7% to 56.6%]; P = .82) and TA compared with HD-PA (53.5% [95% CI 45.8% to 60.9%] vs 46.5% [95% CI, 39.1% to 54.2%]; P = .37). Net clinical outcome was met in 29.8% of patients receiving SD-PA (20.2% thrombosis, 2.6% bleeding, 14.0% death), 16.4% receiving HD-PA (5.5% thrombosis, 3.6% bleeding, 11.8% death), and 20.0% receiving TA (5.5% thrombosis, 3.6% bleeding, 12.7% death). Moreover, HD-PA and TA use significantly reduced thrombosis compared with SD-PA (absolute difference, -14.7 [95% CI -6.2 to -23.2] and -14.7 [95% CI -6.2 to -23.2], respectively). Use of HD-PA significantly reduced net clinical outcome compared with SD-PA (absolute difference, -13.5; 95% CI -2.6 to -24.3). Conclusions and Relevance: This randomized clinical trial found that compared with SD-PA, neither HD-PA nor TA use improved the primary hierarchical outcome of all-cause mortality or time to clinical improvement in patients with hypoxemic COVID-19 pneumonia; however, HD-PA resulted in significantly better net clinical outcome by decreasing the risk of de novo thrombosis. Trial Registration: ClinicalTrials.gov Identifier: NCT04808882.

Superinfection is associated with short-term outcome and mortality in viral respiratory tract infections during the fall-winter seasons 2016-2018 in the Greater Paris area: the SUPERFLUOUS study: outcomes of viral infections.

BACKGROUND: Following a study of predictors of superinfection in viral respiratory tract infections (VRTIs), this study analyzes the predictors of the outcome. METHODS: Multicenter retrospective study conducted among adults who tested positive for VRTIs with reverse-transcription polymerase chain reaction. We compared characteristics between influenza virus, Paramyxoviridae, and Pneumoviridae and identified predictors of favorable short-term outcome, admission to the intensive care unit (ICU), and mortality. RESULTS: A total of 590 patients had VRTI, including 347 (59%) influenza infections. Mean (SD) patient age was 71.0 (18.3) years, with a sex ratio of 0.91. In multivariate analyses, predictors of favorable short-term outcome were age ≤75 years (adjusted odds ratio [aOR] 5.38 [95% confidence interval, 1.59-18.2]), absence of respiratory disease (4.94 [1.01-24.37]), and absence of superinfection (aOR 3.91 [1.37-11.13]). The predictors of ICU admission were age ≤75 years (aOR 3.28 [1.71-6.25]), chronic respiratory disease (aOR 2.49 [1.20-5.19]), and procalcitonin level >0.25 ng/mL (aOR 4.25 [1.55-11.67]). Predictors of mortality were use of inhaled corticosteroids (2.49 [1.10-5.63]), influenza infection (2.73 [1.27-5.85]), Charlson score ≥5 (5.35 [1.90-15.05]), superinfection (2.54 [1.05-6.18]), and eosinophil count <50/µL (4.39 [1.19-16.2]). Certainty of superinfection was significantly associated with mortality (2.23 [1.15-4.3]). CONCLUSION: Our study revealed that superinfection was significantly related to the outcome, and that virus species affects mortality. These findings emphasize the need for improving the tools used in daily practice to confirm certainty of superinfection and for broader implementation of vaccination of individuals at risk of VRTIs.

Does the ICU Requirement Score allow the poisoned patient to be safely managed without admission to the intensive care unit? - a validation cohort study.

BACKGROUND: The Intensive care unit (ICU) Requirement Score (IRS) has been defined as identifying poisoned patients on hospital admission who do not require ICU referral, in an effort to reduce health expenses. However, this score has been poorly validated. We aimed to evaluate the IRS in a large cohort of poisoned patients. METHODS: We performed a single-center retrospective cohort study. IRS was calculated using clinical parameters obtained on admission including age, systolic blood pressure, heart rate, Glasgow coma score, intoxication type, co-morbidities (i.e., arrhythmia, cirrhosis, and respiratory insufficiency), and the combination of the intoxication with another reason for ICU admission. We evaluated the ability of IRS < 6 determined on admission to predict the lack of need for ICU treatment, defined as the need for mechanical ventilation, vasopressors, and/or renal replacement therapy in the first 24 h post-admission and/or death during the hospital stay. This score was compared to the usual prognostic scores, i.e., SAPS II and III, SOFA score, and PSS. RESULTS: During the 10-year study period, 2,514 poisoned patients were admitted, 1,011 excluded as requiring ICU treatment on admission, and 1,503 included. Among these patients, 232 met the endpoint whereas only 23/510 patients with IRS < 6 (4.5%) presented the endpoint and one patient died. The area under the curve of the IRS ROC curve was 0.736 (95% confidence interval (CI), 0.702-0.770). The negative predictive value of IRS < 6 was 95% (95% CI, 93-97), sensitivity 89% (95% CI, 85-93), specificity 38% (95% CI, 36-41), and positive predictive value 21% (95% CI, 18-24). IRS performance was similar to those of the other tested scores, which are however not readily available on admission. CONCLUSION: Our data demonstrate the excellent negative predictive value of the IRS, allowing the exclusion of ICU requirements for poisoned patients with IRS < 6. IRS usefulness should be confirmed based on a prospective multicenter cohort study before extensive routine use.

Continuous positive airway pressure for respiratory support during COVID-19 pandemic: a frugal approach from bench to bedside.

BACKGROUND: We describe a frugal approach (focusing on needs, performance, and costs) to manage a massive influx of COVID-19 patients with acute hypoxemic respiratory failure (AHRF) using the Boussignac valve protected by a filter ("Filter Frugal CPAP", FF-CPAP) in and out the ICU. METHODS: (1) A bench study measured the impact of two filters with different mechanical properties on CPAP performances, and pressures were also measured in patients. (2) Non-ICU healthcare staff working in COVID-19 intermediate care units were trained with a video tutorial posted on a massive open online course. (3) A clinical study assessed the feasibility and safety of using FF-CPAP to maintain oxygenation and manage patients out of the ICU during a massive outbreak. RESULTS: Bench assessments showed that adding a filter did not affect the effective pressure delivered to the patient. The resistive load induced by the filter variably increased the simulated patient's work of breathing (6-34%) needed to sustain the tidal volume, depending on the filter's resistance, respiratory mechanics and basal inspiratory effort. In patients, FF-CPAP achieved pressures similar to those obtained on the bench. The massive training tool provided precious information on the use of Boussignac FF-CPAP on COVID-19 patients. Then 85 COVID-19 patients with ICU admission criteria over a 1-month period were studied upon FF-CPAP initiation for AHRF. FF-CPAP significantly decreased respiratory rate and increased SpO2. Thirty-six (43%) patients presented with respiratory indications for intubation prior to FF-CPAP initiation, and 13 (36%) of them improved without intubation. Overall, 31 patients (36%) improved with FF-CPAP alone and 17 patients (20%) did not require ICU admission. Patients with a respiratory rate > 32 breaths/min upon FF-CPAP initiation had a higher cumulative probability of intubation (p < 0.001 by log-rank test). CONCLUSION: Adding a filter to the Boussignac valve does not affect the delivered pressure but may variably increase the resistive load depending on the filter used. Clinical assessment suggests that FF-CPAP is a frugal solution to provide a ventilatory support and improve oxygenation to numerous patients suffering from AHRF in the context of a massive outbreak.

Management of pharmaceutical and recreational drug poisoning.

BACKGROUND: Poisoning is one of the leading causes of admission to the emergency department and intensive care unit. A large number of epidemiological changes have occurred over the last years such as the exponential growth of new synthetic psychoactive substances. Major progress has also been made in analytical screening and assays, enabling the clinicians to rapidly obtain a definite diagnosis. METHODS: A committee composed of 30 experts from five scientific societies, the Société de Réanimation de Langue Française (SRLF), the Société Française de Médecine d'Urgence (SFMU), the Société de Toxicologie Clinique (STC), the Société Française de Toxicologie Analytique (SFTA) and the Groupe Francophone de Réanimation et d'Urgences Pédiatriques (GFRUP) evaluated eight fields: (1) severity assessment and initial triage; (2) diagnostic approach and role of toxicological analyses; (3) supportive care; (4) decontamination; (5) elimination enhancement; (6) place of antidotes; (7) specificities related to recreational drug poisoning; and (8) characteristics of cardiotoxicant poisoning. Population, Intervention, Comparison, and Outcome (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Analysis of the literature and formulation of recommendations were then conducted according to the GRADE® methodology. RESULTS: The SRLF-SFMU guideline panel provided 41 statements concerning the management of pharmaceutical and recreational drug poisoning. Ethanol and chemical poisoning were excluded from the scope of these recommendations. After two rounds of discussion and various amendments, a strong consensus was reached for all recommendations. Six of these recommendations had a high level of evidence (GRADE 1±) and six had a low level of evidence (GRADE 2±). Twenty-nine recommendations were in the form of expert opinion recommendations due to the low evidences in the literature. CONCLUSIONS: The experts reached a substantial consensus for several strong recommendations for optimal management of pharmaceutical and recreational drug poisoning, mainly regarding the conditions and effectiveness of naloxone and N-acetylcystein as antidotes to treat opioid and acetaminophen poisoning, respectively.

De-escalation of antifungal treatment in critically ill patients with suspected invasive Candida infection: incidence, associated factors, and safety.

BACKGROUND: Antifungal treatment is common in critically ill patients, but only a small proportion of patients receiving antifungals have a proven fungal infection. However, antifungal treatment has side effects such as toxicity, emergence of resistance, and high cost. Moreover, empirical antifungal treatment is still a matter for debate in these patients. Our study aimed to determine the incidence, associated factors, and safety of de-escalation of antifungals in critically ill patients. METHODS: This retrospective study was conducted in a 30-bed mixed ICU, from January 2012 through January 2013. Patients hospitalized for > 5 days and treated with antifungals for first suspected or proven invasive Candida infection were included. Exclusion criteria were prophylactic antifungals, suspected invasive aspergillosis, and neutropenia. De-escalation was defined as switch from initial systemic antifungals (except fluconazole) to triazoles, or stopping initial drugs within the 5 days following their initiation. RESULTS: One hundred and ninety patients were included. Antifungal treatment was empirical, preemptive, and targeted in 55, 27, and 24% of study patients, respectively. Caspofungin (53%), fluconazole (43%), voriconazole (4%), and liposomal amphotericin B (0.5%) were the more frequently used antifungals. De-escalation was performed in 38 (20%) patients. Invasive mechanical ventilation was independently associated with lower rates of de-escalation (OR 0.25 [95% CI 0.08-0.85], p = 0.013). Total duration of antifungal treatment was significantly shorter in patients with de-escalation, compared with those with no de-escalation (med [IQR] 6 (5, 18) vs. 13 days (7, 25), p = 0.023). No significant difference was found in duration of mechanical ventilation (22 [5-31] vs. 20 days [10-35], p = 0.43), length of ICU stay (25 [14-40) vs. 25 days [11-40], p = 0.99), ICU mortality (45 vs. 59%, p = 0.13), or 1-year mortality (55 vs. 64%, p = 0.33) between patients with de-escalation and those with no de-escalation, respectively. CONCLUSIONS: De-escalation was performed in 20% of patients receiving systemic antifungals for suspected or proven invasive Candida infection. Mechanical ventilation was independently associated with lower rates of de-escalation. De-escalation of antifungal treatment seems to be safe in critically ill patients.

Relationship between hyperoxemia and ventilator associated pneumonia.

Previous studies suggest a relationship between hyperoxemia and ventilator-associated pneumonia (VAP). Hyperoxemia is responsible for denitrogenation phenomena, and inhibition of surfactant production, promoting atelectasis in mechanically ventilated patients. Further, hyperoxemia impairs the efficacy of alveolar macrophages to migrate, phagocyte and kill bacteria. Oxygen can also cause pulmonary-specific toxic effect called hyperoxic acute lung injury leading to longer duration of mechanical ventilation. All these hyperoxic effects are well-known risk factors for VAP. A recent retrospective large single center study identified hyperoxemia as an independent risk factor for VAP. However, two recent randomized controlled trials evaluated the impact of conservative oxygen strategy versus a liberal strategy, but did not confirm the role of hyperoxemia in lower respiratory tract infection occurrence. In this review, we discuss animal and human studies suggesting a relationship between these two common conditions in mechanically ventilated patients and potential interventions that should be evaluated. Further large prospective studies in carefully selected groups of patients are required to confirm the potential role of hyperoxemia in VAP pathogenesis and to evaluate the impact of a conservative oxygen strategy vs. a conventional strategy on the incidence of VAP.