BACKGROUND: Immunosuppression at intensive care unit (ICU) admission has been associated with a higher incidence of ICU-acquired infections, some of them related to opportunistic pathogens. However, the association of immunosuppression with the incidence, microbiology and outcomes of ICU-acquired bacterial bloodstream infections (BSI) has not been thoroughly investigated.
METHODS: Retrospective single-centered cohort study in France. All adult patients hospitalized in the ICU of Lille University-affiliated hospital for > 48 h between January 1st and December 31st, 2020, were included, regardless of their immune status. Immunosuppression was defined as active cancer or hematologic malignancy, neutropenia, hematopoietic stem cell and solid organ transplants, use of steroids or immunosuppressive drugs, human immunodeficiency virus infection and genetic immune deficiency. The primary objective was to compare the 28-day cumulative incidence of ICU-acquired bacterial BSI between immunocompromised and non-immunocompromised patients. Secondary objectives were to assess the microbiology and outcomes of ICU-acquired bacterial BSI in the two groups.
RESULTS: A total of 1313 patients (66.9% males, median age 62 years) were included. Among them, 271 (20.6%) were immunocompromised at ICU admission. Severity scores at admission, the use of invasive devices and antibiotic exposure during ICU stay were comparable between groups. Both prior to and after adjustment for pre-specified baseline confounders, the 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between immunocompromised and non-immunocompromised patients. The distribution of bacteria was comparable between groups, with a majority of Gram-negative bacilli (~ 64.1%). The proportion of multidrug-resistant bacteria was also similar between groups. Occurrence of ICU-acquired bacterial BSI was associated with a longer ICU length-of-stay and a longer duration of invasive mechanical ventilation, with no significant association with mortality. Immune status did not modify the association between occurrence of ICU-acquired bacterial BSI and these outcomes.
CONCLUSIONS: The 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between patients with and without immunosuppression at ICU admission.

BACKGROUND: Antivirals and monoclonal antibodies lower the risk of progression in immunocompromised patients. However, combination therapy with both types of agents has not been studied.
METHODS: This was a single-centre, prospective, cohort study. All immunocompromised patients who received treatment for mild-to-moderate COVID-19 from 1 January 2022 to 30 October 2022 were enrolled. The primary endpoint was COVID-19 progression at 90 days, defined as hospital admission or death due to COVID-19 and/or seronegative persistent COVID-19.
RESULTS: A total of 304 patients were included: 43 patients (14.1%) received sotrovimab plus a direct-acting antiviral, and 261 (85.9%) received monotherapy. Primary outcome occurred more frequently after monotherapy (4.6% vs. 0%, P=0.154). Among patients with anti-spike immunoglobulin G (anti-S IgG) titre <750 BAU/mL, COVID-19 progression was more common after monotherapy (23.9% vs. 0%, P=0.001), including more frequent COVID-related admission (15.2% vs. 0%, P=0.014) and seronegative persistent COVID-19 (10.9% vs. 0%, P=0.044). Combination therapy was associated with lower risk of progression (odds ratio [OR] 0.08, 95% confidence interval [95% CI] 0.01-0.64). Anti-S IgG titre <750 BAU/mL and previous anti-CD20 were associated with higher risk of progression (OR 13.70, 95% CI 2.77-67.68; and OR 3.05, 95% CI 1.20-10.94, respectively).
CONCLUSIONS: In immunocompromised patients, combination therapy with sotrovimab plus an antiviral may be more effective than monotherapy for SARS-CoV2.

Remdesivir (REM) and monoclonal antibodies (mAbs) could alleviate severe COVID-19 in at-risk outpatients. However, data on their use in hospitalized patients, particularly in elderly or immunocompromised hosts, are lacking.
All consecutive patients hospitalized with COVID-19 at our unit from 1 July 2021 to 15 March 2022 were retrospectively enrolled. The primary outcome was the progression to severe COVID-19 (P/F < 200). Descriptive statistics, a Cox univariate-multivariate model, and an inverse probability treatment-weighted (IPTW) analysis were performed.
Overall, 331 subjects were included; their median (q1-q3) age was 71 (51-80) years, and they were males in 52% of the cases. Of them, 78 (23%) developed severe COVID-19. All-cause in-hospital mortality was 14%; it was higher in those with disease progression (36% vs. 7%, p < 0.001). REM and mAbs resulted in a 7% (95%CI = 3-11%) and 14% (95%CI = 3-25%) reduction in the risk of severe COVID-19, respectively, after adjusting the analysis with the IPTW. In addition, by evaluating only immunocompromised hosts, the combination of REM and mAbs was associated with a significantly lower incidence of severe COVID-19 (aHR = 0.06, 95%CI = 0.02-0.77) when compared with monotherapy.
REM and mAbs may reduce the risk of COVID-19 progression in hospitalized patients. Importantly, in immunocompromised hosts, the combination of mAbs and REM may be beneficial.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized nonsmall cell lung cancer (NSCLC) treatment and significantly increased overall survival of patients. However, the incidence of concurrent infections and their management is still debated.
METHODS: From August 2015 to October 2019, all consecutive patients with NSCLC who received nivolumab or pembrolizumab as first- or second-line therapy were retrospectively evaluated. At the time of analysis all patients had died. Clinical characteristics of patients, type of infections, and predictors of mortality were analyzed.
RESULTS: A total of 118 patients were identified: 74 in the nivolumab group and 44 in the pembrolizumab group. At least 1 infection was recorded in 22% of the nivolumab-group versus 27% of the pembrolizumab-group (P = .178). In both groups, the main infection was pneumonia, followed by skin and soft tissue infections, urinary tract infections, and gastroenteritis. Crude mortality for first infection was 10.7%, followed by 25% and 40% for the second and third recurrence, respectively (p for trend = .146). No opportunistic infections were recorded. It is notable that, by Cox-regression model, the independent predictor of mortality was a higher Eastern Cooperative Oncology Group performance status at baseline (P < .001), whereas the multidisciplinary diagnosis and treatment of concurrent infections was associated with a reduced probability of mortality (adjusted hazard ratio = 0.50; 95% confidence interval = 0.30-0.83; P < .001).
CONCLUSIONS: In patients with NSCLC treated with ICIs, multidisciplinary management of concurrent infections may reduce the risk of mortality. Further studies to investigate risk factors for infections, as well as appropriate management strategies and preventive measures in this setting, are warranted.

UNASSIGNED: Bronchoalveolar lavage (BAL) is a useful tool in the diagnostic work-up of patients with interstitial lung diseases (ILDs). In this prospective study, we investigated the clinical usefulness of BAL in patients with ILD radiographically.
UNASSIGNED: The enrolled patients were classified into outpatient department (OPD), and inpatients groups who was admitted to general ward (GW) or intensive care unit (ICU) groups based on the time when BAL done. The clinical usefulness of BAL was defined as a new diagnosis established and/or treatment significantly changed. The clinical usefulness of BAL among the three groups of patients and the patients divided by underlying diseases was compared using the χ2 test with or without Fisher\'s exact test.
UNASSIGNED: Among our 184 patients, there were 37 in OPD group, 86 in GW group and 61 in ICU group. The final diagnoses were infectious in 23, non-infectious in 102, mixed etiologies in 19, and non-diagnostic in 40 patients. The diagnostic yields (revised diagnosis after BAL) of BAL among ICU patients, GW patients and OPD patients were 60.6%, 69.7% and 21.6%, respectively (P<0.001), and was 57.1% in total patients. The diagnostic yields of BAL among patients with cancer, organ transplantation and collagen vascular disease were statistically different (P=0.009).
UNASSIGNED: BAL is of use in establishing a diagnosis of ILD and is mandatary especially in the admitted patients with ILD because diagnostic yield was relatively higher in admitted patients than in OPD patients. In addition, BAL should be done more early in the admitted patients with malignancy, stem cell and/or organ transplantation and collagen vascular disease especially when they showed poor response to initial medications.

BACKGROUND: Community-acquired pneumonia (CAP) in autoimmune diseases (AID)-induced immunocompromised host (ICH) had a high incidence and poor prognosis. However, only a few studies had determined the clinical characteristics of these patients. Our study was to explore the characteristics and predictors of mortality in CAP patients accompanied with AID-induced ICH.
METHODS: From 2013 to 2018, a total of 94 CAP patients accompanied with AID-induced ICH, admitted to Emergency Department of Zhongshan Hospital, Fudan University, were enrolled in this study. Clinical data and the risk regression estimates of repeated predictors were evaluated by generalized estimating equations (GEEs) analysis. An open-cohort approach was used to classify patient\'s outcomes into the survival or non-survival group.
RESULTS: The hospital mortality of patients with CAP occurring in AID-induced ICH was 60.64%. No significant differences were found with respect to clinical symptoms and lung images between survival and non-survival groups, while renal insufficiency and dysfunction of coagulation had higher proportions in non-survival patients (P<0.05). Both noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) were performed more frequently in non-survival group (P< 0.05). By the multivariate GEEs analysis, the repeated measured longitudinal indices of neutrophil-to-lymphocyte ratio (NLR) (odds ratio [OR]=1.055, 95% confidence interval [95%CI] 1.025-1.086), lactate dehydrogenase (LDH) (OR=1.004, 95%CI 1.002-1.006) and serum creatinine (sCr) (OR=1.018, 95%CI 1.008-1.028), were associated with a higher risk of mortality.
CONCLUSIONS: The CAP patients in AID-induced ICH had a high mortality. A significant relationship was demonstrated between the factors of NLR, LDH, sCr and mortality risk in these patients.

Antibiotic stewardship programs (ASP) have already demonstrated clinical benefits. However, their effectiveness or safety in immunocompromised hosts needs to be proved.
An ecologic quasi-experimental study was performed from January 2009 to June 2017 in the Oncology department of a tertiary-care hospital. A stable program of Infectious Diseases consultation (IDC) already existed at this unit, and an educational ASP was added in 2011. Its main intervention consisted of face-to-face educational interviews. Antibiotic consumption was assessed through quarterly Defined Daily Doses (DDD) per 100 occupied bed-days. Mortality was evaluated in patients with bloodstream infections through the quarterly incidence density per 1000 admissions, and the annual mortality rates at 7 and 30-days. Time-trends were analysed through segmented-regression analysis, and the impact of the ASP was assessed through before-after interrupted time-series analysis.
Mortality significantly decreased throughout the study period (-13.3% annual reduction for 7-day mortality rate, p < 0.01; -8.1% annual reduction for 30-day mortality, p = 0.03), parallel to a reduction in antibiotic consumption (quarterly reduction -0.4%, p = 0.01), especially for broader-spectrum antibiotics. The before-after study settled a significant inflexion point on the ASP implementation for the reduction of antibiotic consumption (change in level 0.95 DDD, p = 0.71; change in slope -1.98 DDD per quarter, p < 0.01). The decreasing trend for mortality before the ASP also continued after its implementation.
The combination of an ASP with IDC improved antibiotic use among patients with cancer, and was accompanied by a reduction of mortality of bacteraemic infections. Implementation of the ASP was necessary to effectively change antibiotic use.

To compare the effectiveness and tolerability of micafungin versus posaconazole during chemotherapy-induced neutropenia in acute leukemia (AL) and myelodysplastic syndrome (MDS).
Patients with AL or MDS undergoing chemotherapy were randomized to open-label micafungin 100 mg intravenously daily or posaconazole suspension 400 mg orally twice daily until neutrophil recovery, up to 28 days. Patients were followed for 12 weeks. The primary endpoint was prophylaxis failure (premature discontinuation due to infection, intolerance, adverse event, or death). Time to failure and survival were calculated by Kaplan-Meier analysis.
From March 2011 to May 2016, 113 patients who received at least 2 doses of prophylaxis were analyzed (58 patients randomized to micafungin and 55 to posaconazole). Prophylaxis failure occurred in 34.5% and 52.7% of patients on micafungin and posaconazole, respectively (P = 0.0118). The median number of days on prophylaxis was 16 [interquartile range (IQR) 12-20] for micafungin and 13 [IQR 6-16] for posaconazole (P = 0.01). Micafungin failures were largely due to antifungal treatment; posaconazole failures were mostly due to gastrointestinal intolerance or adverse effects. IFI incidence and survival were similar between study arms.
Our data support micafungin as alternative antifungal prophylaxis in patients with AL and MDS.