Length of hospital and intensive care unit stay in patients with invasive candidiasis and/or candidemia treated with rezafungin: a pooled analysis of two randomised controlled trials.

Background: Invasive candidiasis/candidemia (IC/C) is associated with a substantial health economic burden driven primarily by prolonged hospital stay. The once-weekly IV echinocandin, rezafungin acetate, has demonstrated non-inferiority to caspofungin in the treatment of IC/C. This paper reports a post hoc pooled exploratory analysis of length of stay (LoS) for hospital and intensive care unit (ICU) stays in two previously published clinical trials (ReSTORE [NCT03667690] and STRIVE [NCT02734862], that compared rezafungin with daily IV caspofungin (stable patients in the caspofungin group who met relevant criteria could step down to fluconazole after 3 days or more).

Performance of Risk Models for Antimicrobial Resistance in Adult Patients With Sepsis.

Importance: The results of prediction models that stratify patients with sepsis and risk of resistant gram-negative bacilli (GNB) infections inform treatment guidelines. However, these models do not extrapolate well across hospitals.

Objective: To assess whether patient case mix and local prevalence rates of resistance contributed to the variable performance of a general risk stratification GNB sepsis model for community-onset and hospital-onset sepsis across hospitals.

Rezafungin versus caspofungin for patients with candidaemia or invasive candidiasis in the intensive care unit: pooled analyses of the ReSTORE and STRIVE randomised trials.

Background: Rezafungin is an echinocandin approved in the US and EU to treat candidaemia and/or invasive candidiasis. This post-hoc, pooled analysis of the Phase 2 STRIVE and Phase 3 ReSTORE trials assessed rezafungin versus caspofungin in patients with candidaemia and/or invasive candidiasis (IC) in the intensive care unit (ICU) at randomisation.

Methods: STRIVE and ReSTORE were randomised double-blind trials in adults with systemic signs and mycological confirmation of candidaemia and/or IC in blood or a normally sterile site ≤ 96 h before randomisation.

Preventing New Gram-negative Resistance Through Beta-lactam De-escalation in Hospitalized Patients With Sepsis: A Retrospective Cohort Study.

Background: Whether antibiotic de-escalation reduces the risk of subsequent antibiotic resistance is uncertain. We sought to determine if beta-lactam (BL) antibiotic de-escalation is associated with decreased incidence of new Gram-negative resistance in hospitalized patients with sepsis.

Methods: In a retrospective cohort study, patients with sepsis who were treated with at least 3 consecutive days of BL antibiotics, the first 2 days of which were with a broad-spectrum BL agent defined as a spectrum score (SS) of ≥7 were enrolled.

Impact of Gram-Negative Bacilli Resistance Rates on Risk of Death in Septic Shock and Pneumonia.

Background: Sepsis is a major cause of morbidity and mortality worldwide. When selecting empiric antibiotics for sepsis, clinicians are encouraged to use local resistance rates, but their impact on individual outcomes is unknown. Improved methods to predict outcomes are needed to optimize treatment selection and improve antibiotic stewardship.

Quantitative SARS-CoV-2 RT-PCR and Bronchoalveolar Cytokine Concentrations Redefine the COVID-19 Phenotypes in Critically Ill Patients.

Rationale: Recent studies suggest that both hypo- and hyperinflammatory acute respiratory distress syndrome (ARDS) phenotypes characterize severe COVID-19-related pneumonia. The role of lung Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2) viral load in contributing to these phenotypes remains unknown.

Objectives: To redefine COVID-19 ARDS phenotypes when considering quantitative SARS-CoV-2 RT-PCR in the bronchoalveolar lavage of intubated patients.

Use of Inhaled Epoprostenol in Patients With COVID-19 Receiving Humidified, High-Flow Nasal Oxygen Is Associated With Progressive Respiratory Failure.

Background: The clinical benefit of using inhaled epoprostenol (iEpo) through a humidified high-flow nasal cannula (HHFNC) remains unknown for patients with COVID-19.

Research Question: Can iEpo prevent respiratory deterioration for patients with positive SARS-CoV-2 findings receiving HHFNC?

Study Design And Methods: This multicenter retrospective cohort analysis included patients aged 18 years or older with COVID-19 pneumonia who required HHFNC treatment. Patients who received iEpo were propensity score matched to patients who did not receive iEpo.

Comparison of Empiric Antibiotic Treatment Regimens for Hospitalized, Non-severe Community-acquired Pneumonia: A Retrospective, Multicenter Cohort Study.

Purpose: Consensus guidelines for hospitalized, non-severe community-acquired pneumonia (CAP) recommend empiric macrolide + β-lactam or respiratory fluoroquinolone monotherapy in patients with no risk factors for resistant organisms. In patients with allergies or contraindications, doxycycline + β-lactam is a recommended alternative. The purpose of this study was to compare differences in outcomes among guideline-recommended regimens in this population.

Understanding the nebulisation of antibiotics: the key role of lung microdialysis studies.

Background: Nebulisation of antibiotics is a promising treatment for ventilator-associated pneumonia (VAP) caused by multidrug-resistant organisms. Ensuring effective antibiotic concentrations at the site of infection in the interstitial space fluid is crucial for clinical outcomes. Current assessment methods, such as epithelial lining fluid and tissue homogenates, have limitations in providing longitudinal pharmacokinetic data.

Patient and Hospital Characteristics Associated With the Interhospital Transfer of Adult Patients With Sepsis.

Importance: The interhospital transfer (IHT) of patients with sepsis to higher-capability hospitals may improve outcomes. Little is known about patient and hospital factors associated with sepsis IHT.

Objectives: We evaluated patterns of hospitalization and IHT and determined patient and hospital factors associated with the IHT of adult patients with sepsis.

Is Zero Ventilator-Associated Pneumonia Achievable? Updated Practical Approaches to Ventilator-Associated Pneumonia Prevention.

Ventilator-associated pneumonia (VAP) remains a significant clinical entity with reported incidence rates of 7% to 15%. Given the considerable adverse consequences associated with this infection, VAP prevention became a core measure required in most US hospitals. Many institutions took pride in implementing effective VAP prevention bundles that combined at least head of bed elevation, hand hygiene, chlorhexidine oral care, and subglottic drainage.

Efficacy and safety of ceftazidime/avibactam in patients with infections caused by β-lactamase-producing Gram-negative pathogens: a pooled analysis from the Phase 3 clinical trial programme.

Objectives: This post hoc pooled analysis evaluated clinical and microbiological outcomes and safety in patients with infections caused by β-lactamase-producing Gram-negative pathogens across five Phase 3, randomized, controlled, multicentre trials of ceftazidime/avibactam in adults with complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI)/pyelonephritis and nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP).

Methods: In each trial, RECLAIM/RECLAIM 3 (cIAI), REPRISE (cIAI/cUTI), RECAPTURE (cUTI) and REPROVE (NP, including VAP) patients were randomized 1:1 to IV ceftazidime/avibactam (plus metronidazole for patients with cIAI) or comparators (carbapenems in >97% patients) for 5-21 days. Clinical and microbiological responses at the test-of-cure visit were assessed for patients with ESBLs, and/or plasmidic and/or overexpression of chromosomal AmpC, and/or serine carbapenemases without MBLs identified in baseline Gram-negative isolates by phenotypic screening and molecular characterization in the pooled microbiological modified ITT (mMITT) population.

Addition of aminoglycosides reduces recurrence of infections with multidrug-resistant Gram-negative bacilli in patients with sepsis and septic shock.

Objectives: Aminoglycosides and β-lactams have been recommended for treatment of sepsis/septic shock despite a lack of mortality benefit. Previous studies have examined resistance emergence for the same bacterial isolate using old dosing regimens and during a narrow follow-up window. We hypothesised that combination regimens employing aminoglycosides will decrease the cumulative incidence of infections due to multidrug-resistant (MDR) Gram-negative bacilli (GNB) compared with β-lactams alone.

Participant- and Disease-Related Factors as Independent Predictors of Treatment Outcomes in the RESTORE-IMI 2 Clinical Trial: A Multivariable Regression Analysis.

Background: In the RESTORE-IMI 2 trial, imipenem/cilastatin/relebactam (IMI/REL) was noninferior to piperacillin/tazobactam in treating hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia. This post hoc analysis was conducted to determine independent predictors of efficacy outcomes in the RESTORE-IMI 2 trial, to assist in treatment decision making.

Methods: A stepwise multivariable regression analysis was conducted to identify variables that were independently associated with day 28 all-cause mortality (ACM), favorable clinical response at early follow-up (EFU), and favorable microbiologic response at end of treatment (EOT).

The Relationship Between Hospital Capability and Mortality in Sepsis: Development of a Sepsis-Related Hospital Capability Index.

Objectives: Regionalized sepsis care could improve sepsis outcomes by facilitating the interhospital transfer of patients to higher-capability hospitals. There are no measures of sepsis capability to guide the identification of such hospitals, although hospital case volume of sepsis has been used as a proxy. We evaluated the performance of a novel hospital sepsis-related capability (SRC) index as compared with sepsis case volume.

Prospective role of cefiderocol in the management of carbapenem-resistant Acinetobacter baumannii infections: Review of the evidence.

Carbapenem-resistant Acinetobacter baumannii (CRAB) has been classified by the World Health Organization as being in the critical category of pathogens requiring urgent new antibiotic treatment options. Cefiderocol, the first approved siderophore cephalosporin, was designed for the treatment of carbapenem-resistant Gram-negative pathogens, particularly the non-fermenting species A. baumannii and Pseudomonas aeruginosa.

Effect of Early Administration of Vasopressin on New-Onset Arrhythmia Development in Patients With Septic Shock: A Retrospective, Observational Cohort Study.

Adjunctive vasopressin use in septic shock reduces catecholamine requirements and is associated with a lower incidence of new-onset arrhythmias (NOAs). The association of vasopressin timing on NOA development is ill-described. To determine whether early administration of vasopressin was associated with a lower incidence of NOA in septic shock patients.

ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia.

Purpose: Severe community-acquired pneumonia (sCAP) is associated with high morbidity and mortality, and whilst European and non-European guidelines are available for community-acquired pneumonia, there are no specific guidelines for sCAP.

Methods: The European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and Latin American Thoracic Association (ALAT) launched a task force to develop the first international guidelines for sCAP. The panel comprised a total of 18 European and four non-European experts, as well as two methodologists.

Determinants of Mortality for Ventilated Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia.

Unlabelled: Hospital-acquired pneumonia (HAP) is the most common hospital-acquired infection, accounting for 22% of all nosocomial infections. The available studies to date have not attempted to assess whether confounding factors may account for the observed difference in mortality for the two forms of nosocomial pneumonia associated with mechanical ventilation, namely ventilated HAP (vHAP) and ventilator-associated pneumonia (VAP).

Objectives: To determine if vHAP is an independent predictor of mortality among patients with nosocomial pneumonia.