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Sepsis and bloodstream infection are associated with significant morbidity and mortality, and early effective antimicrobial therapy has been demonstrated to improve patient outcomes. Traditional culture-based methods, however, have several limitations that hamper a prompt diagnosis in bloodstream infection, including long turnaround times and limited sensitivity. In recent years, advances have been made in the development of several technologies that allow the identification of pathogens and their resistance markers directly from whole blood, possibly representing promising alternatives to conventional culture-based methods. To review the currently commercially available emerging assays for the diagnosis of bloodstream infections directly from whole blood, including their performance and the available data about their impact on patient outcome. Peer-reviewed publications relevant to the topic have been searched through PubMed; manufacturers' websites have also been consulted as a data source. We have reviewed available data about the following technologies: multiplex real-time PCR working directly from whole blood (Magicplex Sepsis Real-Time test, Seegene), PCR combined with T2 Magnetic Resonance (T2Candida and T2Bacteria panel, T2Biosystem), and metagenomics-based assays (including SepsiTest, Molzym; iDTECT Dx Blood, PathoQuest; Karius NGS plasma Test, Karius). Performance characteristics, advantages and pitfalls of each method are described, and available data about their impact on patients' clinical outcomes are discussed. The potential of rapid diagnostic tests applied on whole blood for improving the management of patients with bloodstream infection and sepsis is high, both in terms of reducing turnaround times and improving the sensitivity of pathogen and antimicrobial resistance detection. However, overall, there is still a scarcity of data about the real-life performance of such tests, and well-designed studies are awaited for assessing the impact of these emerging technologies on patient outcomes. [ABSTRACT FROM AUTHOR]

Infections due to carbapenem-resistant Gram-negative bacteria are burdened by high mortality and represent an urgent threat to address. Clinicians are currently at a dawn of a new era in which antibiotic resistance in Gram-negative bacilli is being dealt with by the availability of the first new antibiotics in this field for many years. Although new antibiotics have shown promising results in clinical trials, there is still uncertainty over whether their use will improve clinical outcomes in real world practice. Some observational studies have reported a survival benefit in carbapenem-resistant Enterobacteriaceae bloodstream infections using combination therapy, often including "old" antibiotics such as colistin, aminoglycosides, tigecycline, and carbapenems. These regimens, however, are linked to increased risk of antimicrobial resistance, and their efficacy has yet to be compared to new antimicrobial options. While awaiting more definitive evidence, antibiotic stewards need clear direction on how to optimize the use of old and novel antibiotic options. Furthermore, carbapenem-sparing regimens should be carefully considered as a potential tool to reduce selective antimicrobial pressure. • Carbapenem resistance represents one of the biggest challenges for clinicians managing severe Gram-negative infections. • Novel antimicrobials active on carbapenem-resistant Enterobacteriaceae, ceftazidime-avibactam and meropenem-vaborbactam, have been recently approved for clinical use. • Ceftazidime-avibactam and meropenem-vaborbactam showed improved clinical outcomes in the treatment of infections caused by KPC-producing Enterobacteriaceae compared with old antibiotics. • Optimization in the use of old antibiotics (carbapenems, aminoglycosides, fosfomycin, colistin) and careful use of novel compounds currently represent key elements to optimize antimicrobial stewardship programs. [ABSTRACT FROM AUTHOR]

• Pneumocystis jirovecii pneumonia (PCP) has a high mortality (20%) among non-HIV immunocompromised patients. • The main risk factors are hematologic malignancies followed by autoimmune diseases. • PCP cases occur in patients not receiving anti-pneumocystis prophylaxis. • Strict adherence to prophylaxis guidelines is critical to preventing PCP. Pneumocystis jirovecii pneumonia (PCP) still has substantial morbidity and mortality. For non-HIV patients, the course of infection is severe, and management guidelines are relatively recent. We collected all PCP cases (European Organization for Research and Treatment of Cancer criteria) diagnosed in HIV-negative adult inpatients in 2019-2020 at our center in northern Italy. Of 20 cases, nine had microbiologic evidence of probable (real-time polymerase chain reaction, RT-PCR) and 11 proven (immunofluorescence) PCP on respiratory specimens. Half were female; the median age was 71.5 years; 14 of 20 patients had hematologic malignancies, five had autoimmune/hyperinflammatory disorders, and one had a solid tumor. RT-PCR cycle threshold (Ct) was 24-37 for bronchoalveolar lavage (BAL) and 32-39 for sputum; Ct was 24-33 on BAL proven cases. Of 20 cases, four received additional diagnoses on BAL. At PCP diagnosis, all patients were not on anti-pneumocystis prophylaxis. We retrospectively assessed prophylaxis indications: 9/20 patients had a main indication, 5/9 because of prednisone treatment ≥ 20 mg (or equivalents) for ≥4 weeks. All patients underwent antimicrobial treatment according to guidelines; 18/20 with concomitant corticosteroids. A total of 4/20 patients died within 28 days from diagnosis. Despite appropriate treatment, PCP is still associated to high mortality (20%) among non-HIV patients. Strict adherence to prophylaxis guidelines, awareness of gray areas, and prompt diagnosis can help manage this frequently overlooked infection. [ABSTRACT FROM AUTHOR]

• Primary Neuro-Whipple is a rare entity that might be fatal if not promptly diagnosed. • Primary Neuro-Whipple diagnosis is challenging given its heterogeneous presentation. • Rhombencephalitis is a unique presentation of Neuro-Whipple disease. • Clinicians should be aware about atypical presentation of primary Neuro-Whipple. Primary Whipple disease of the Central Nervous System is a rare entity whose outcome might be fatal if not promptly diagnosed and treated. Few cases are reported in the literature with heterogeneous clinical and radiological presentations which often make the diagnosis extremely challenging. We report a case of primary Whipple disease of the Central Nervous System presenting with rhombencephalitis in a female patient in immunosuppressive treatment for rheumatoid arthritis. We describe the management of our patient and discuss the features of this rare clinical entity. [ABSTRACT FROM AUTHOR]