Acinetobacter baumannii is a Gram-negative ESKAPE microorganism that poses a threat to public health by causing severe and invasive (mostly nosocomial) infections linked with high mortality rates. During the last years, this pathogen displayed multidrug resistance (MDR), mainly due to extensive antibiotic abuse and poor stewardship. MDR isolates are associated with medical history of long hospitalization stays, presence of catheters, and mechanical ventilation, while immunocompromised and severely ill hosts predispose to invasive infections. Next-generation sequencing techniques have revolutionized diagnosis of severe A. baumannii infections, contributing to timely diagnosis and personalized therapeutic regimens according to the identification of the respective resistance genes. The aim of this review is to describe in detail all current knowledge on the genetic background of A. baumannii resistance mechanisms in humans as regards beta-lactams (penicillins, cephalosporins, carbapenems, monobactams, and beta-lactamase inhibitors), aminoglycosides, tetracyclines, fluoroquinolones, macrolides, lincosamides, streptogramin antibiotics, polymyxins, and others (amphenicols, oxazolidinones, rifamycins, fosfomycin, diaminopyrimidines, sulfonamides, glycopeptide, and lipopeptide antibiotics). Mechanisms of antimicrobial resistance refer mainly to regulation of antibiotic transportation through bacterial membranes, alteration of the antibiotic target site, and enzymatic modifications resulting in antibiotic neutralization. Virulence factors that may affect antibiotic susceptibility profiles and confer drug resistance are also being discussed. Reports from cases of A. baumannii coinfection with SARS-CoV-2 during the COVID-19 pandemic in terms of resistance profiles and MDR genes have been investigated.

Introduction: Invasive fungal diseases (IFDs) are a leading cause of morbidity and mortality among immunocompromised patients with bone marrow failure syndromes, hematological malignancies, hematopoietic stem cell transplantation (HSCT), those admitted in intensive care units (ICUs) and those with prolonged febrile neutropenia. IFDs occur in a setting of multiple morbidities and are associated with case fatality rates between 30 and 70%. Along with the development of classes and compounds, the last two decades have seen substantial improvements in the prevention and management of these infections and an overall increased use of antifungal agents. Areas covered: All antifungal agents, including amphotericin B formulations, echinocandins and the triazoles, may cause hepatic toxicity that ranges from mild and asymptomatic abnormalities in liver function tests to substantial liver injury and fulminant hepatic failure. Expert opinion: The present article reviews incidence and severity of hepatotoxicity associated with different classes and agents to provide a better understanding of this specific end organ toxicity and safer use of antifungal agents A thorough understanding of the distribution, metabolism, elimination and drug-drug interactions of antifungal agents used for management of IFDs in combination with safety data from clinical trials, pharmacokinetic and pharmacodynamic studies may guide the use of antifungal treatment in patients at high risk for the development of hepatic dysfunction and in those with underlying liver damage due to cytotoxic therapy.

The metabolic syndrome is a cluster of potent risk factors for cardiovascular diseases. To provide information on the late complications of chemotherapy for acute lymphoblastic leukemia (ALL), the authors prospectively studied the frequency of overweight, obesity, and metabolic syndrome in survivors of ALL in the initial years after the completion of therapy. Children and adolescents were classified as having the metabolic syndrome if they met three or more of the following criteria: hypertriglyceridemia, low levels of high-density lipoprotein (HDL), high fasting glucose, obesity, and hypertension. Obesity was defined on the basis of Body Mass Index (BMI) (kg/m2) standard deviation scores or z-scores. Cutoff points for triglycerides and HDL were taken from equivalent pediatric percentiles with the cutoff points proposed by the Adult Treatment Panel III (ATPIII). Hyperglycemia was defined using the ATPIII cutoff points. Elevated systolic or diastolic blood pressure was defined as a value greater than the 95th percentile for age, gender, and height. Fifty-two subjects (29 male and 23 female) with a median age of 15.2 years (range 6.1-22.6 years) were evaluated. Median interval since completion of therapy was 37 months (range 13-121 months). All of them had been treated according to the ALL-BFM 90 chemotherapy protocol and none had received cranial radiotherapy. Of the 52 subjects, 25 (48%) were overweight (BMI z-score >1.5) and 3 (5.76%) were obese (BMI z-score >2); among them, 1 was severely obese (BMI z-score >2.5). Three criteria for the metabolic syndrome (high triglyceride levels, glucose intolerance, and obesity) were fulfilled by three subjects (5.76%). Twenty-nine subjects (55.7%) had at least one risk factor for metabolic syndrome. Hyperglycemia and hypertension were infrequent. Prompt recognition of the risk factors for metabolic syndrome and intervention seem mandatory to ensure early prevention of cardiovascular disease in survivors of ALL.

In this retrospective observational study covering 1998 to 2008, 32 patients (mean age: 7.50 years) were identified that had 35 episodes of candidaemia (0.47 cases/1000 hospital discharges). Cancer/allogeneic haematopoietic stem cell transplantation (43%) and congenital malformations/syndromes (21%) were the predominant underlying conditions. Central venous catheterization (90%), a history of antibacterial therapy (69%) and previous bacteraemia (54%) were frequent comorbidities. Candida albicans (46%) was most common, followed by Candida parapsilosis (17%) and Candida glabrata (14%). Resistance was infrequent and limited to non-albicans Candida spp. The 30-day and 100-day mortality rates were 11.4%.

Invasive fungal infections continue to be important causes of morbidity and mortality in severely ill and immunocompromised patient populations. The past three decades saw a considerable expansion ...