The objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe. A multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU). During the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02–1.06, p < 0.001), severe hepatic failure (OR 3.25, 95% 1.31–8.08, p 0.011), SOFA score at the onset of IC (OR 1.11 per point, 95% CI 1.04–1.17, p 0.001), and septic shock (OR 2.12, 95% CI 1.24–3.63, p 0.006) were associated with increased 30-day mortality in a secondary, exploratory analysis. The cumulative incidence of IC in 23 European ICUs was 7.07 episodes per 1000 ICU admissions. Future in-depth analyses will allow explaining part of the observed between-center variability, with the ultimate aim of helping to improve local infection control and antifungal stewardship projects and interventions.

Coronavirus disease 19 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a severe fungal infection complicating critically ill COVID-19 patients. Numerous retrospective and prospective studies have been performed to get a better grasp on this lethal co-infection. We performed a qualitative review and summarized data from 48 studies in which 7047 patients had been included, of whom 820 had CAPA. The pooled incidence of proven, probable or putative CAPA was 15.1% among 2953 ICU-admitted COVID-19 patients included in 18 prospective studies. Incidences showed great variability due to multiple factors such as discrepancies in the rate and depth of the fungal work-up. The pathophysiology and risk factors for CAPA are ill-defined, but therapy with corticosteroids and anti-interleukin-6 therapy potentially confer the biggest risk. Sampling for mycological work-up using bronchoscopy is the cornerstone for diagnosis, as imaging is often aspecific. CAPA is associated with an increased mortality, but we do not have conclusive data whether therapy contributes to an increased survival in these patients. We conclude our review with a comparison between influenza-associated pulmonary aspergillosis (IAPA) and CAPA.

Invasive Pulmonary Aspergillosis (IPA) has been recognized as a possible secondary infection complicating Coronavirus disease 2019 (COVID-19) and increasing mortality. The aim of this review was to report and summarize the available data in the literature concerning the incidence, pathophysiology, diagnosis, and treatment of COVID-19-Associated Pulmonary Aspergillosis (CAPA). Currently, the incidence of CAPA is unclear due to different definitions and diagnostic criteria used among the studies. It was estimated that approximately 8.6% (206/2383) of mechanically ventilated patients were diagnosed with either proven, probable, or putative CAPA. Classical host factors of invasive aspergillosis are rarely recognized in patients with CAPA, who are mainly immuno-competent presenting with comorbidities, while the role of steroids warrants further investigation. Direct epithelial injury and diffuse pulmonary micro thrombi in combination with immune dysregulation, hyper inflammatory response, and immunosuppressive treatment may be implicated. Discrimination between two forms of CAPA (e.g., tracheobronchial and parenchymal) is required, whereas radiological signs of aspergillosis are not typically evident in patients with severe COVID-19 pneumonia. In previous studies, the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria, a clinical algorithm to diagnose Invasive Pulmonary Aspergillosis in intensive care unit patients (AspICU algorithm), and influenza-associated pulmonary aspergillosis (IAPA) criteria were used for the diagnosis of proven/probable and putative CAPA, as well as the differentiation from colonization, which can be challenging. Aspergillus fumigatus is the most commonly isolated pathogen in respiratory cultures. Bronchoalveolar lavage (BAL) and serum galactomannan (GM), β-d-glucan (with limited specificity), polymerase chain reaction (PCR), and Aspergillus-specific lateral-flow device test can be included in the diagnostic work-up; however, these approaches are characterized by low sensitivity. Early treatment of CAPA is necessary, and 71.4% (135/189) of patients received antifungal therapy, mainly with voriconazole, isavuconazole, and liposomal amphotericin B . Given the high mortality rate among patients with Aspergillus infection, the administration of prophylactic treatment is debated. In conclusion, different diagnostic strategies are necessary to differentiate colonization from bronchial or parenchymal infection in intubated COVID-19 patients with Aspergillus spp. in their respiratory specimens vs. those not infected with severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Following confirmation, voriconazole or isavuconazole should be used for the treatment of CAPA.

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.

A mucormycosis surge was reported during the COVID-19 pandemic in India. A literature search until 14 July 2022, with the aim of updating COVID-19-associated mucormycosis (CAM), identified 663 studies and 88 met inclusion criteria (8727 patients). India reported 8388 patients, Egypt 208 and Europe 40. Rhino-orbito-cerebral mucormycosis (ROCM) was identified among 8082 (98.3%) patients, followed by 98 (1.2%) with pulmonary. In India, 82.6% of patients had diabetes mellitus, with 82% receiving corticosteroids. In Europe, 75% presented pulmonary CAM, 32.5% had diabetes and 40% were immunocompromised. CAM was identified at a median of 17.4 days (IQR 7.5 days) post COVID-19 diagnosis, and PCR was performed in five studies. Rhino-orbital invasion is clinically obvious, while cerebral involvement presents with cavernous sinus thrombosis, meningitis and cerebrovascular disease. Symptoms of pulmonary CAM usually overlap with severe COVID-19 pneumonia. High-dose liposomal Amphotericin B (and early surgical debridement in ROCM) are the mainstay of therapy. The median mortality rate was estimated to be 21.4% (IQR 31.9%), increased by the presence of pulmonary (80% (IQR 50%) or cerebral involvement (50% (IQR 63.9%). In summary, different CAM clinical phenotypes need to be distinguished, influenced by geographical presentation. Opportunities exist for diagnosis and therapy optimization, based on earlier high-dose antifungal therapy, early source control, strict glycemic control and restriction of steroids to COVID-19 patients with oxygen requirements.