Short Course of Antifungal Therapy in Patients With Uncomplicated Candida Bloodstream Infection: Another Case of Less Is More in the Clinical Setting?

Background: The objective of this study was to compare the clinical outcomes of patients receiving a short course (SC) vs a prolonged course (PC) of antifungal therapy for uncomplicated Candida bloodstream infections (BSIs). Methods: All episodes of uncomplicated Candida BSI from September 1, 2018, to August 31, 2020, were reviewed. We compared the primary (all-cause 90-day mortality) and secondary study end points (1-year recurrent Candida BSI and all-cause 1-year mortality) among patients who underwent SC (5-11 days) or PC (12-24 days) therapy using propensity score analysis with the inverse probability of treatment weighting (IPTW) method. Results: A total of 114 patients with uncomplicated Candida BSI were included: 35 (30.7%) were classified into the SC group (median [interquartile range {IQR}], 9 [7-11] days) and 79 (69.3%) into the PC group (median [IQR], 14 [14-16] days). Patients in the SC group compared with the PC group had a higher rate of hospitalization in the surgical ward (40.0% vs 19.0%; P = .02) or septic shock at the time of Candida BSI onset (11.4% vs 1.3%; P = .03). The risk of 90-day mortality was not different between the SC and PC groups (n = 8 [22.9%] vs 17 [21.5%], respectively; IPTW-adjusted subdistribution hazard ratio [sHR], 0.67; 95% CI, 0.31-1.47; P = .20). The risk for recurrent Candida BSI within 1 year of completing therapy (IPTW-adjusted sHR, 1.07; 95% CI, 0.20-5.80; P = .94) or for all-cause 1-year mortality (IPTW-adjusted HR, 0.72; 95% CI, 0.35-1.50; P = .38) did not differ between groups. Conclusions: Receiving a short vs prolonged course of antifungal therapy did not affect mortality or BSI recurrence in patients with uncomplicated candidemia.

T2Bacteria and T2Resistance Assays in Critically Ill Patients with Sepsis or Septic Shock: A Descriptive Experience.

The use of rapid molecular tests may anticipate the identification of causative agents and resistance determinants in the blood of critically ill patients with sepsis. From April to December 2021, all intensive care unit patients with sepsis or septic shock who were tested with the T2Bacteria and T2Resistance assays were included in a retrospective, single center study. The primary descriptive endpoints were results of rapid molecular tests and concomitant blood cultures. Overall, 38 combinations of T2Bacteria and T2Resistance tests were performed. One or more causative agent(s) were identified by the T2Bacteria assay in 26% of episodes (10/38), whereas negative and invalid results were obtained in 66% (25/38) and 8% (3/38) of episodes, respectively. The same pathogen detected by the T2Bacteria test grew from blood cultures in 30% of cases (3/10). One or more determinant(s) of resistance were identified by the T2Resistance assay in 11% of episodes (4/38). Changes in therapy based on T2Bacteria and/or T2Resistance results occurred in 21% of episodes (8/38). In conclusion, T2Bacteria/T2Resistance results can influence early treatment decisions in critically ill patients with sepsis or septic shock in real-life practice. Large, controlled studies remain necessary to confirm a favorable impact on patients' outcomes and antimicrobial stewardship interventions.

Sensitivity of Serum Beta-D-Glucan in Candidemia According to Candida Species Epidemiology in Critically Ill Patients Admitted to the Intensive Care Unit.

Serum beta-D-glucan (BDG) determination plays an important role in the diagnosis of candidemia among critically ill patients admitted to the intensive care unit (ICU). However, BDG levels measured may be lower in the case of infections caused by some non-albicans species, such as C. parapsilosis and C. auris. The aim of this single-center study was to investigate the sensitivity of serum BDG for the diagnosis of candidemia stratified according to causative Candida species in ICU patients. This was a single-center, retrospective study, including all adult patients admitted to ICU during the period 2018-2021. All episodes of candidemia with a determination of BDG available within 3 days before or after positive blood culture were recorded. The preplanned primary objective was to investigate the sensitivity of serum BDG to detect candidemia early and the effect of different Candida species. The secondary objective was to measure serum BDG in patients with candidemia from different Candida species. In total, 146 candidemia episodes in 118 patients were analyzed. Median BDG value for C. albicans candidemia (182 pg/mL) was higher than that observed for C. parapsilosis (78 pg/mL, p = 0.015) and C. auris (48 pg/mL, p = 0.022). The overall sensitivity of BDG for the diagnosis of candidemia was low (47%, 95% CI 39-55%). In conclusion, in critically ill patients admitted to ICU, serum BDG levels for candidemia were different among species, with lower levels confirmed for C. parapsilosis and C. auris. Serum BDG sensitivity for early detection of candidemia was lower than previously reported in other ICU populations.

The Mystery of Mount Vesuvius's Crosses: Belief, Credulity, and Credibility in Post-Reformation Catholicism.

In the summer of 1660, Mount Vesuvius began to erupt. After about a month, the volcano quieted down, but a strange and upsetting phenomenon started to manifest: all over the city of Naples and in the neighboring communities, a series of red and black crosses appeared on people's linens, clothes, and bodies. This essay focuses on this mysterious appearance and on the debate it provoked, using it as a case study to investigate the relationship between credulity, credibility, and belief in post-Reformation Catholicism.

Mind the gap: IgG4-related disease mimicking infectious cerebral mass lesions.

BACKGROUND: Cerebral intraparenchymal masses represent usually a neoplastic, or infectious differential diagnostic workup in neurology or infectious disease units. CASE PRESENTATION: Our patient was an 82-year-old male presenting with seizures, cerebral masses and a history of past treated pulmonary tuberculosis. Initial workup included a differential diagnosis of an infectious mass/multiple abscess. After exclusion of infectious or primary neoplastic origins by negative HIV serology, the absence of immune suppression, endocarditic lesions, negative results of blood cultures and bronchoalveolar lavage, negative cerebrospinal fluid workout on spinal tap led to exclusion of infectious causes. A surgical procedure was performed to access one of the lesions. This yielded a firm, cyst-like mass of histiocytic granulomatous tissue with a conspicuous plasmacellular component and a relevant IgG4 plasmacellular component consistent with IgG4-related disease. Steroid treatment determined conspicuous improvement and led to discharge of the patient. CONCLUSION: Parenchymal IgG4-related disease may be included as a new entity in the differential diagnosis of single or multiple cerebral masses in addition to infectious or neoplastic etiology.

Enterococcal bloodstream infections in critically ill patients with COVID-19: a case series.

BACKGROUND: An unexpected high prevalence of enterococcal bloodstream infection (BSI) has been observed in critically ill patients with COVID-19 in the intensive care unit (ICU). MATERIALS AND METHODS: The primary objective was to describe the characteristics of ICU-acquired enterococcal BSI in critically ill patients with COVID-19. A secondary objective was to exploratorily assess the predictors of 30-day mortality in critically ill COVID-19 patients with ICU-acquired enterococcal BSI. RESULTS: During the study period, 223 patients with COVID-19 were admitted to COVID-19-dedicated ICUs in our centre. Overall, 51 episodes of enterococcal BSI, occurring in 43 patients, were registered. 29 (56.9%) and 22 (43.1%) BSI were caused by Enterococcus faecalis and Enterococcus faecium, respectively. The cumulative incidence of ICU-acquired enterococcal BSI was of 229 episodes per 1000 ICU admissions (95% mid-p confidence interval [CI] 172-298). Most patients received an empirical therapy with at least one agent showing in vitro activity against the blood isolate (38/43, 88%). The crude 30-day mortality was 42% (18/43) and 57% (4/7) in the entire series and in patients with vancomycin-resistant E. faecium BSI, respectively. The sequential organ failure assessment (SOFA) score showed an independent association with increased mortality (odds ratio 1.32 per one-point increase, with 95% confidence interval 1.04-1.66, p = .021). CONCLUSIONS: The cumulative incidence of enterococcal BSI is high in critically ill patients with COVID-19. Our results suggest a crucial role of the severity of the acute clinical conditions, to which both the underlying viral pneumonia and the enterococcal BSI may contribute, in majorly influencing the outcome.KEY MESSAGESThe cumulative incidence of enterococcal BSI is high in critically ill patients with COVID-19.The crude 30-day mortality of enterococcal BSI in critically ill patients with COVID-19 may be higher than 40%.There could be a crucial role of the severity of the acute clinical conditions, to which both the underlying viral pneumonia and the enterococcal BSI may contribute, in majorly influencing the outcome.

Spread of Carbapenem-Resistant Gram-Negatives and Candida auris during the COVID-19 Pandemic in Critically Ill Patients: One Step Back in Antimicrobial Stewardship?

The possible negative impact of severe adult respiratory distress caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19) on antimicrobial stewardship and infection control has been postulated, but few real-life data are available. The aim of this study was to report our experience with colonization/infection of carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Klebsiella pneumoniae (CR-Kp) and Candida auris among critically ill COVID-19 patients admitted to the intensive care unit (ICU). All COVID-19 patients admitted to the ICUs at San Martino Policlinico Hospital-IRCCS in Genoa, Italy, were screened from 28 February to 31 May 2020. One-hundred and eighteen patients admitted to COVID-19 ICUs were included in the study. Among them, 12 (10.2%) became colonized/infected with CRPA, 6 (5.1%) with C. auris and 2 (1.6%) with CR-Kp. All patients with CRPA received prior treatment with meropenem, and in 11 (91.7%) infection was not preceded by colonization. Four patients (66.7%) developed C. auris candidemia. A significant spread of resistant pathogens was observed among critically ill COVID-19 patients. Dedicated strategies are warranted to prevent horizontal spread and maintain effective antimicrobial stewardship programs in the setting of COVID-19 care.

Clinical characteristics, management and in-hospital mortality of patients with coronavirus disease 2019 in Genoa, Italy.

OBJECTIVES: To describe clinical characteristics, management and outcome of individuals with coronavirus disease 2019 (COVID-19); and to evaluate risk factors for all-cause in-hospital mortality. METHODS: This retrospective study from a University tertiary care hospital in northern Italy, included hospitalized adult patients with a diagnosis of COVID-19 between 25 February 2020 and 25 March 2020. RESULTS: Overall, 317 individuals were enrolled. Their median age was 71 years and 67.2% were male (213/317). The most common underlying diseases were hypertension (149/317; 47.0%), cardiovascular disease (63/317; 19.9%) and diabetes (49/317; 15.5%). Common symptoms at the time of COVID-19 diagnosis included fever (285/317; 89.9%), shortness of breath (167/317; 52.7%) and dry cough (156/317; 49.2%). An 'atypical' presentation including at least one among mental confusion, diarrhoea or nausea and vomiting was observed in 53/317 patients (16.7%). Hypokalaemia occurred in 25.8% (78/302) and 18.5% (56/303) had acute kidney injury. During hospitalization, 111/317 patients (35.0%) received non-invasive respiratory support, 65/317 (20.5%) were admitted to the intensive care unit (ICU) and 60/317 (18.5%) required invasive mechanical ventilation. All-cause in-hospital mortality, assessed in 275 patients, was 43.6% (120/275). On multivariable analysis, age (per-year increase OR 1.07; 95% CI 1.04-1.10; p < 0.001), cardiovascular disease (OR 2.58; 95% CI 1.07-6.25; p 0.03), and C-reactive protein levels (per-point increase OR 1.009; 95% CI 1.004-1.014; p 0.001) were independent risk factors for all-cause in-hospital mortality. CONCLUSIONS: COVID-19 mainly affected elderly patients with predisposing conditions and caused severe illness, frequently requiring non-invasive respiratory support or ICU admission. Despite supportive care, COVID-19 remains associated with a substantial risk of all-cause in-hospital mortality.

Tocilizumab and steroid treatment in patients with COVID-19 pneumonia.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome. METHODS: This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. SOC consisted of hydroxychloroquine 400mg bid plus, in those admitted before March 24th, also darunavir/ritonavir. Anti-inflammatory treatment consisted of either tocilizumab (8mg/kg intravenously or 162mg subcutaneously) or methylprednisolone 1 mg/kg for 5 days or both. Failure was defined as intubation or death, and the endpoints were failure-free survival (primary endpoint) and overall survival (secondary) at day 30. Difference between the groups was estimated as Hazard Ratio by a propensity score weighted Cox regression analysis (HROW). RESULTS: Overall, 196 adults were included in the analyses. They were mainly male (67.4%), with comorbidities (78.1%) and severe COVID-19 pneumonia (83.7%). Median age was 67.9 years (range, 30-100) and median PaO2/FiO2 200 mmHg (IQR 133-289). Among them, 130 received early anti-inflammatory treatment with: tocilizumab (n = 29, 22.3%), methylprednisolone (n = 45, 34.6%), or both (n = 56, 43.1%). The adjusted failure-free survival among tocilizumab/methylprednisolone/SOC treated patients vs. SOC was 80.8% (95%CI, 72.8-86.7) vs. 64.1% (95%CI, 51.3-74.0), HROW 0.48, 95%CI, 0.23-0.99; p = 0.049. The overall survival among tocilizumab/methylprednisolone/SOC patients vs. SOC was 85.9% (95%CI, 80.7-92.6) vs. 71.9% (95%CI, 46-73), HROW 0.41, 95%CI: 0.19-0.89, p = 0.025. CONCLUSION: Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients with COVID-19 pneumonia.

Epidemiology and outcome of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-KP) infections in cardiac surgery patients: a brief narrative review.

Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-KP) is a difficult-to-treat pathogen due to its multidrug-resistant phenotype. Cardiac surgery patients are at increased risk of developing KPC-KP infections compared to other populations, with previous KPC-KP colonization being a critical factor in influencing the risk of subsequent infection. Two different pieces of information are essential to comprehensively assess the local characteristics of KPC-KP colonization in cardiac surgery patients: (i) the local prevalence of colonization; (ii) the timing of colonization. Treatment of KPC-KP infections in cardiac surgery patients is a complex task, but more effective treatment options have recently become available. Nonetheless, implementation and full adherence to infection-control measures remain of pivotal importance for reducing the burden of KPC-KP infections in this peculiar population. The aim of this narrative review is to summarize the available literature on the epidemiology and outcome of KPC-KP infections in cardiac surgery patients.