Severe mold fungal infections in critically ill patients with COVID-19.

The SARS-CoV-2 pandemic put an unprecedented strain on modern societies and healthcare systems. A significantly higher incidence of invasive fungal co-infections was noted compared with the pre-COVID-19 era, adding new diagnostic and therapeutic challenges in the critical care setting. In the current narrative review, we focus on invasive mold infections caused by Aspergillus and Mucor species in critically ill COVID-19 patients. We discuss up-to-date information on the incidence, pathogenesis, diagnosis and treatment of these mold-COVID-19 co-infections, as well as recommendations on preventive and prophylactic interventions. Traditional risk factors were often not recognized in COVID-19-associated aspergillosis and mucormycosis, highlighting the role of other determinant risk factors. The associated patient outcomes were worse compared with COVID-19 patients without mold co-infection.

Invasive Fungal Diseases in Adult Patients in Intensive Care Unit (FUNDICU): 2024 consensus definitions from ESGCIP, EFISG, ESICM, ECMM, MSGERC, ISAC, and ISHAM.

PURPOSE: The aim of this document was to develop standardized research definitions of invasive fungal diseases (IFD) in non-neutropenic, adult patients without classical host factors for IFD, admitted to intensive care units (ICUs). METHODS: After a systematic assessment of the diagnostic performance for IFD in the target population of already existing definitions and laboratory tests, consensus definitions were developed by a panel of experts using the RAND/UCLA appropriateness method. RESULTS: Standardized research definitions were developed for proven invasive candidiasis, probable deep-seated candidiasis, proven invasive aspergillosis, probable invasive pulmonary aspergillosis, and probable tracheobronchial aspergillosis. The limited evidence on the performance of existing definitions and laboratory tests for the diagnosis of IFD other than candidiasis and aspergillosis precluded the development of dedicated definitions, at least pending further data. The standardized definitions provided in the present document are aimed to speed-up the design, and increase the feasibility, of future comparative research studies.

Epidemiology and risk factors for mortality in critically ill patients with pancreatic infection.

Background: The AbSeS-classification defines specific phenotypes of patients with intra-abdominal infection based on the (1) setting of infection onset (community-acquired, early onset, or late-onset hospital-acquired), (2) presence or absence of either localized or diffuse peritonitis, and (3) severity of disease expression (infection, sepsis, or septic shock). This classification system demonstrated reliable risk stratification in intensive care unit (ICU) patients with intra-abdominal infection. This study aimed to describe the epidemiology of ICU patients with pancreatic infection and assess the relationship between the components of the AbSeS-classification and mortality. Methods: This was a secondary analysis of an international observational study ("AbSeS") investigating ICU patients with intra-abdominal infection. Only patients with pancreatic infection were included in this analysis (n=165). Mortality was defined as ICU mortality within 28 days of observation for patients discharged earlier from the ICU. Relationships with mortality were assessed using logistic regression analysis and reported as odds ratio (OR) and 95% confidence interval (CI). Results: The overall mortality was 35.2% (n=58). The independent risk factors for mortality included older age (OR=1.03, 95% CI: 1.0 to 1.1 P=0.023), localized peritonitis (OR=4.4, 95% CI: 1.4 to 13.9 P=0.011), and persistent signs of inflammation at day 7 (OR=9.5, 95% CI: 3.8 to 23.9, P<0.001) or after the implementation of additional source control interventions within the first week (OR=4.0, 95% CI: 1.3 to 12.2, P=0.013). Gram-negative bacteria were most frequently isolated (n=58, 49.2%) without clinically relevant differences in microbial etiology between survivors and non-survivors. Conclusions: In pancreatic infection, a challenging source/damage control and ongoing pancreatic inflammation appear to be the strongest contributors to an unfavorable short-term outcome. In this limited series, essentials of the AbSeS-classification, such as the setting of infection onset, diffuse peritonitis, and severity of disease expression, were not associated with an increased mortality risk.ClinicalTrials.gov number: NCT03270345.

Risk factors for surgical site infection following cardiac surgery in a region endemic for multidrug resistant organisms.

OBJECTIVES: To identify risk factors for surgical site infections following cardiosurgery in an area endemic for multidrug resistant organisms. DESIGN: Single-center, historical cohort study including patients who underwent cardiosurgery during a 6-year period (2014-2020). SETTING: Joint Commission International accredited, multiorgan transplant center in Palermo, Italy. MAIN OUTCOME MEASURES: Surgical site infection was the main outcome. RESULTS: On a total of 3609 cardiosurgery patients, 184 developed surgical site infection (5.1 %). Intestinal colonization with multidrug resistant organisms was more frequent in patients with surgical site infections (69.6 % vs. 33.3 %; p < 0.001). About half of surgical site infections were caused by Gram-negative bacteria (n = 97; 52.7 %). Fifty surgical site infections were caused by multidrug resistant organisms (27.1 %), with extended-spectrum Beta-lactamase-producing Enterobacterales (n = 16; 8.7 %) and carbapenem-resistant Enterobacterales (n = 26; 14.1 %) being the predominant resistance problem. However, in only 24 of surgical site infections caused by multidrug resistant organisms (48 %), mostly carbapenem-resistant Enterobacterales (n = 22), a pathogen match between the rectal surveillance culture and surgical site infections clinical culture was demonstrated. Nevertheless, multivariate logistic regression analysis identified a rectal swab culture positive for multidrug resistant organisms as an independent risk factor for SSI (odds ratio 3.95, 95 % confidence interval 2.79-5.60). Other independent risk factors were female sex, chronic dialysis, diabetes mellitus, previous cardiosurgery, previous myocardial infarction, being overweight/obese, and longer intubation time. CONCLUSION: In an area endemic for carbapenem-resistant Enterobacterales, intestinal colonization with multidrug resistant organisms was recognized as independent risk factor for surgical site infections. IMPLICATIONS FOR CLINICAL PRACTICE: No causal relationship between colonization with resistant pathogens and subsequent infection could be demonstrated. However, from a broader epidemiological perspective, having a positive multidrug resistant organisms colonization status appeared a risk factor for surgical site infections. Therefore, strict infection control measures to prevent cross-transmission remain pivotal (e.g., nasal decolonization, hand hygiene, and skin antisepsis).

Prevention of ventilator-associated pneumonia through care bundles: A systematic review and meta-analysis.

Background: Ventilator-associated pneumonia (VAP) represents a common hospital-acquired infection among mechanically ventilated patients. We summarized evidence concerning ventilator care bundles to prevent VAP. Methods: A systematic review and meta-analysis were performed. Randomized controlled trials and controlled observational studies of adults undergoing mechanical ventilation (MV) for at least 48 h were considered for inclusion. Outcomes of interest were the number of VAP episodes, duration of MV, hospital and intensive care unit (ICU) length of stay, and mortality. A systematic search was conducted in the MEDLINE, the Cochrane Library, and the Web of Science between 1985 and 2022. Results are reported as odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CI). The PROSPERO registration number is CRD42022341780. Results: Thirty-six studies including 116,873 MV participants met the inclusion criteria. A total of 84,031 participants underwent care bundles for VAP prevention. The most reported component of the ventilator bundle was head-of-bed elevation (n=83,146), followed by oral care (n=80,787). A reduction in the number of VAP episodes was observed among those receiving ventilator care bundles, compared with the non-care bundle group (OR=0.42, 95% CI: 0.33, 0.54). Additionally, the implementation of care bundles decreased the duration of MV (MD=-0.59, 95% CI: -1.03, -0.15) and hospital length of stay (MD=-1.24, 95% CI: -2.30, -0.18) in studies where educational activities were part of the bundle. Data regarding mortality were inconclusive. Conclusions: The implementation of ventilator care bundles reduced the number of VAP episodes and the duration of MV in adult ICUs. Their application in combination with educational activities seemed to improve clinical outcomes.

Severe Candida infections in critically ill patients with COVID-19.

The frequency of co-infections with bacterial or fungal pathogens has constantly increased among critically ill patients with coronavirus disease 2019 (COVID-19) during the pandemic. Candidemia was the most frequently reported invasive fungal co-infection. The onset of candidemia in COVID-19 patients was often delayed compared to non-COVID-19 patients. Additionally, Candida invasive infections in COVID-19 patients were more often linked to invasive procedures (e.g., invasive mechanical ventilation or renal replacement therapy) during the intensive care stay and the severity of illness rather than more "classic" risk factors present in patients without COVID-19 (e.g., underlying diseases and prior hospitalization). Moreover, apart from the increased incidence of candidemia during the pandemic, a worrying rise in fluconazole-resistant strains was reported, including a rise in the multidrug-resistant Candida auris. Regarding outcomes, the development of invasive Candida co-infection had a negative impact, increasing morbidity and mortality compared to non-co-infected COVID-19 patients. In this narrative review, we present and critically discuss information on the diagnosis and management of invasive fungal infections caused by Candida spp. in critically ill COVID-19 patients.

Clinical Sepsis Phenotypes in Critically Ill Patients.

Sepsis, defined as the life-threatening dysregulated host response to an infection leading to organ dysfunction, is considered as one of the leading causes of mortality worldwide, especially in intensive care units (ICU). Moreover, sepsis remains an enigmatic clinical syndrome, with complex pathophysiology incompletely understood and a great heterogeneity both in terms of clinical expression, patient response to currently available therapeutic interventions and outcomes. This heterogeneity proves to be a major obstacle in our quest to deliver improved treatment in septic critical care patients; thus, identification of clinical phenotypes is absolutely necessary. Although this might be seen as an extremely difficult task, nowadays, artificial intelligence and machine learning techniques can be recruited to quantify similarities between individuals within sepsis population and differentiate them into distinct phenotypes regarding not only temperature, hemodynamics or type of organ dysfunction, but also fluid status/responsiveness, trajectories in ICU and outcome. Hopefully, we will eventually manage to determine both the subgroup of septic patients that will benefit from a therapeutic intervention and the correct timing of applying the intervention during the disease process.

Invasive pulmonary aspergillosis in the ICU: tale of a broadening risk profile.

PURPOSE OF REVIEW: In the absence of histopathological proof, the diagnosis of invasive pulmonary aspergillosis (IPA) is usually based on mycology (not on tissue), medical imaging, and the patient's risk profile for acquiring invasive fungal disease. Here, we review the changes in risk profile for IPA that took place over the past decades. RECENT FINDINGS: In the early 2000s IPA was considered exclusively a disease of immunocompromised patients. Particularly in the context of critical illness, the risk profile has been broadened steadily. Acute viral infection by influenza or SARS-Cov-2 are now well recognized risk factors for IPA. SUMMARY: The classic risk profile ('host factors') reflecting an immunocompromised status was first enlarged by a spectrum of chronic conditions such as AIDS, cirrhosis, and chronic obstructive pulmonary disease. In the presence of critical illness, especially characterized by sepsis and/or severe respiratory distress, any chronic condition could add to the risk profile. Recently, acute viral infections have been associated with IPA leading to the concepts of influenza-associated IPA and COVID-19-associated IPA. These viral infections may affect patients without underlying disease. Hence, the risk for IPA is now a reality for ICU patients, even in the absence of any chronic conditions.

Novel Antimicrobial Agents for Gram-Negative Pathogens.

Gram-negative bacterial resistance to antimicrobials has had an exponential increase at a global level during the last decades and represent an everyday challenge, especially for the hospital practice of our era. Concerted efforts from the researchers and the industry have recently provided several novel promising antimicrobials, resilient to various bacterial resistance mechanisms. There are new antimicrobials that became commercially available during the last five years, namely, cefiderocol, imipenem-cilastatin-relebactam, eravacycline, omadacycline, and plazomicin. Furthermore, other agents are in advanced development, having reached phase 3 clinical trials, namely, aztreonam-avibactam, cefepime-enmetazobactam, cefepime-taniborbactam, cefepime-zidebactam, sulopenem, tebipenem, and benapenem. In this present review, we critically discuss the characteristics of the above-mentioned antimicrobials, their pharmacokinetic/pharmacodynamic properties and the current clinical data.

The effect of late-onset sepsis on mortality across different gestational ages in a neonatal intensive care unit: A historical study.

OBJECTIVES: Late-onset sepsis is a frequent complication in neonatal intensive care units. This study aims to understand the effect of late-onset sepsis on mortality in hospitalised neonatal patients across different gestational ages. DESIGN: This is a single-centre, historical cohort study including neonates admitted to hospital during a 10-year period (2002 - 2011). Neonates were stratified by gestational age: extremely preterm (<28 weeks), very preterm (28 to 32 weeks), late preterm (33 to 36 weeks), full term (>37 weeks). SETTING: Tertiary NICU in Ghent, Belgium. MAIN OUTCOME MEASURES: Logistic regression analysis was used to assess adjusted relationships between late-onset sepsis and mortality, reported as odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 4928 neonates were included, of which 2071 were term (42.0%), 1425 were late preterm (28.9%), 1165 very preterm (23.6%) and 264 were extremely preterm neonates (5.4%). 40 neonates developed late-onset sepsis (8.2 episodes/1000 patient days). Overall, in-hospital mortality was 5.4%. Late-onset sepsis was an independent risk factor for mortality in the total cohort (OR = 2.41; 95% CI = 1.46-3.96). However, when gestational age groups were considered separately, late-onset sepsis was associated with mortality in very preterm neonates (OR = 2.45; 95% CI = 1.03-5.84) and in the late preterm neonates (OR = 3.92; 95% CI = 1.41-10.87), but not in other neonates. Comorbidities burdening neonatal hospital survival include acute lung disease, brain damage, periventricular leukomalacia, surgery, and broncho-pulmonary dysplasia. CONCLUSION: Late-onset sepsis is an independent risk factor for mortality in very preterm and late preterm neonates. Understanding how late-onset sepsis among other factors impact mortality enables a patient and family-centred approach to nursing care including the anticipation of realistic milestones. IMPLICATIONS FOR CLINICAL PRACTICE: Late-onset sepsis is especially detrimental to preterm neonates and this could be taken into consideration by nurses when communicating with families in the perinatal period.