It is estimated that antimicrobial resistance (AMR) is responsible for nearly 5 million human deaths worldwide each year and will reach 10 million by 2050. Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a standardized therapy is still lacking. Among the antibiotics under consideration, Sulbactam/durlobactam seems to be the best candidate to replace current back-bone agents. Cefiderocol could play a pivotal role within combination therapy regimens. Due to toxicity and the pharmacokinetics/pharmacodynamics (PK/PD) limitations, colistin (or polymyxin B) should be used as an alternative agent (when no other options are available). Tigecycline (or minocycline) and fosfomycin could represent suitable partners for both NBLs. Randomized clinical trials (RCTs) are needed to better evaluate the role of NBLs in CRAB infection treatment and to compare the efficacy of tigecycline and fosfomycin as partner antibiotics. Synergism should be tested between NBLs and “old” drugs (rifampicin and trimethoprim/sulfamethoxazole). Huge efforts should be made to accelerate pre-clinical and clinical studies on safer polymyxin candidates with improved lung activity, as well as on the iv rifabutin formulation. In this narrative review, we focused the antibiotic treatment of CRAB infections in view of newly developed β-lactam agents (NBLs).

The COVID-19 pandemic may have had an effect on antimicrobial resistance. We compared the prevalence of ESKAPE multidrug-resistant (MDR) bacterial infections in COVID-19 affected/unaffected patients admitted to intensive care units (ICU) or infectious disease units at the “Mater Domini” University Hospital of Catanzaro between 1 March 2020 and 31 July 2021. Moreover, an analysis of MDR rates in ICU comparing the pre-pandemic period with the pandemic period was performed, and the possible consequence on in-hospital mortality was explored. One hundred and eighty-four ESKAPE isolates were analyzed from 362 SARS-CoV-2 positive and 199 negative patients. In total, 116 out of 171 Gram-negative isolates were classified as MDR, and a higher frequency was observed in COVID-19 compared with non-COVID-19 patients (74.2% vs. 60.3%; p = 0.052). A higher rate of MDR ESKAPE bacteria was observed in COVID-19 patients admitted to the ICU compared with COVID-19 unaffected patients admitted to the same ward in 2019 (88% vs. 80.4%; p = 0.186). Acinetobacter baumannii was the main pathogen in COVID-19 patients (58.7%), where it was the most frequent cause of bloodstream infection with the highest mortality rate (68.7%). Increase in MDR appeared to be associated with COVID-19 but only in the ICU setting. Acinetobacter baumannii was associated with the risk of death, indicating the importance of implementing infection control measures urgently.

Asthma is a highly heterogeneous respiratory disease that, in its severe forms, is characterized by persistent symptoms, frequent exacerbations, and a significant impact on patients’ quality of life. Despite high-dose inhaled corticosteroids and long-acting bronchodilators, a subset of patients remains uncontrolled, necessitating advanced therapeutic strategies. The advent of biologic therapies has revolutionized the management of severe asthma, offering targeted interventions based on the underlying inflammatory endotypes, primarily T2-high and T2-low. However, selecting the most appropriate biologic remains challenging due to overlapping phenotypic features and the limited availability of validated biomarkers. This narrative review explores the clinical utility of key biomarkers, including blood eosinophils, fractional exhaled nitric oxide (FeNO), periostin, and total and specific IgE, in guiding biologic therapy. All the information provided is based on an extensive literature search conducted on PubMed. We also examine the clinical characteristics and comorbidities that influence therapeutic choices. Furthermore, we present a practical decision-making platform, including a clinical table matching phenotypes with biologic agents, such as omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab. By integrating biomarker analysis with clinical assessment, based on current guidelines and our extensive real-life experience, we aim to offer a logical framework to help clinicians select the most suitable biologic treatment for patients with uncontrolled severe asthma. Future research should focus on identifying novel biomarkers, refining patient stratification, and evaluating long-term outcomes to further advance precision medicine in the management of severe asthma.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a standardized therapy is still lacking. In this narrative review we focused the antibiotic treatment of CRAB infections in view of newly β-lactam agents (NBLs) like sulbactam/durlobactam and cefiderocol, discussing the main hot points such as the superiority of combination treatment over monotherapy and the best antibiotic partner to use in combination. Sulbactam/durlobactam seems to be the best candi-date to replace current back-bone agents. Cefiderocol, could play a crucial role in combina-tion-regimen. Due to toxicity and the PK/PD limitations, colistin (or polymyxin B) should be used as an alternative agent (when no other options are available). Tigecycline (or minocycline) and fosfomycin could represent suitable partners for both NBLs. Randomized clinical trials (RCTs) are needed to better evaluate the role of NBLs in CRAB infection treatment and to compare the ef-ficacy of tigecycline and fosfomycin as partner antibiotics. Synergism should be tested between NBLs and “old” drugs (rifampicin and trimethoprim/sulfamethoxazole). Huge efforts should be made to accelerate pre-clinical and clinical studies on safer polymyxin candidates with lung im-proved activity, as well as on the i.v. rifabutin formulation.

Background: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) represents a progressively adopted life-sustaining intervention worldwide, particularly in the management of acute respiratory distress syndrome. Nevertheless, data concerning the prognostic significance of fungal isolation in this setting remain unclear. This study aims (i) to assess the incidence of fungal infection and colonization in a homogeneous cohort of V-V ECMO patients, and (ii) to evaluate the association between fungal infection or colonization and 1-year mortality, with a focus on the impact of specific fungal species. Methods: All consecutive adults admitted to the Intensive Care Units of five Italian university-affiliated hospitals and requiring V-V ECMO were screened. Exclusion criteria were age < 18 years, pregnancy, veno-arterial or mixed ECMO-configuration, incomplete records and survival < 24 h after V-V ECMO placement. A standard protocol of microbiological surveillance was applied and the distinction between different fungal species were made through in vivo and vitro tests. Cox-proportional hazards models, Kaplan–Meier curves and linear logistic regressions were applied for investigating mortality. Results: Two-hundred and seventy-nine V-V ECMO patients (72% male) were enrolled. The overall fungal isolation was 41% (n. 114): 23% infections and 18% colonizations. The overall 1-year mortality, among fungal isolations, was 40%, with no different risk in case of fungal infection (26 out of 63, 41%) (aHR 0.85, 95% CI [0.53–1.37], p-value 0.505) and colonization (20 out of 51, 39%) (aHR 0.86, 95%CI [0.51–1.43], p-value 0.556), as compared to patients never detecting fungi (68 out of 165, 41%, reference). According to the isolated mycotic species, as compared to Candida sp. group (reference), the risk of death was greater when different fungal species (e.g., Aspergillus sp. and Candida sp.) were concomitantly isolated in the same patient (OR 1.17, 95%CI [1.12–11.07], p-value 0.031. Conclusions: In the overall population, 23% V-V ECMO patients recorded ‘late’ fungal infections and 18% fungal colonizations, with a similar risk of death as compared to patients never experiencing fungi during the V-V ECMO course. The detection of concomitant different fungal species was an independent risk factor for 1-year mortality.

Adrenomedullin (ADM) is a vasodilatory peptide that plays a crucial role in maintaining cardiovascular health through its various biological functions. ADM was discovered in the acidic extract of human pheochromocytoma tissue and has been recognized for its significant effects on the vascular system. The main functions of ADM include vasodilation, controlling blood pressure and maintaining vascular integrity, although its role on cardiovascular health is broader. Research has shown that elevated levels of adrenomedullin have been observed in a large number of severe diseases, with high risk of death. In this work, we examined the role of ADM as a predictive molecule of the risk of mortality and adverse clinical outcome through a narrative review of the scientific literature. The results were divided based on the pathologies and anatomical districts examined. This review demonstrates how ADM shows, in many diseases and different systems, a close correlation with the risk of mortality. These results prove the value of ADM as a prognostic marker in various clinical contexts and diseases, with utility in the stratification of the risk of clinical worsening and/or death and in the evaluation of therapeutic efficacy. The results open new perspectives with respect to the concrete possibility that ADM enters clinical practice as an effective diagnostic and prognostic marker of death as well as a molecular target for therapies aimed at patient survival.