Immune checkpoint inhibitors (ICIs) have dramatically improved patient outcomes in a variety of tumor types, but with variable efficacy. Recent research has suggested that antibiotic-induced disruption of the microbiota may impact ICI efficacy. We performed a systematic review and metaanalysis of studies that assessed the impact of antibiotic use on the survival of patients diagnosed with NSCLC and treated with ICI. We systematically searched Medline, the Cochrane Library, and major oncology conferences proceedings. Eligible studies mentioned hazard ratio or Kaplan-Meier curves for progression-free survival (PFS) or overall survival (OS) based on antibiotic exposure before or during ICI treatment. We identified 23 eligible studies. The impact of antibiotics was then evaluated in 2208 patients for PFS and 5560 for OS. For both PFS and OS metaanalyses, the between-study heterogeneity was high (Higgins and Thompson I 2 of 69% and 80%, respectively). The pooled hazard ratio was 1.47 (95% confidence interval [CI]: 1.13-1.90) for PFS and 1.69 (95% CI: 1.25-2.29) for OS revealing a significantly reduced survival in patients with NSCLC exposed to antibiotics. The median OS was reduced on average by 6.7 months (95% CI: 5.1-8.4) in the patients exposed to antibiotics. The effect seems to depend on the time window of exposure with stronger effects reported when the patients took antibiotics [À60 days; þ60 days] around ICI initiation. In patients with NSCLC, the findings of the meta-analysis indicate that antibiotic use before or during treatment with ICI leads to a median OS decreased by more than 6 months. Specifically, exposure shortly before or after ICI initiation seems to be particularly detrimental, whereas antibiotic use later during disease course does not seem to alter survival. Because PFS and OS were difficult to compare between studies owing to heterogeneity and the multiple confounding factors identified, further studies are needed to strengthen the understanding of this phenomenon.

Background: Although the incidence, severity and mortality of Clostridioides (Clostridium) difficile infection (CDI) have been increasing, patients' quality of life changes resulting from CDI have not been studied thoroughly. This study aimed at exploring the consequences of CDI on quality of life through patients' perspective. Methods: An observational, cross-sectional study involving 350 participants with a self-reported CDI diagnosis was conducted through an online self-administered survey. Participants were grouped into those who had active disease ("Current CDI") and those who had a history of CDI ("Past CDI"). Results: One hundred fifteen participants (33%) reported Current CDI and 235 (67%) reported Past CDI. A large majority of participants admitted that their daily activities were impacted by the infection (93.9% and 64.7% of Current and Past CDI respondents respectively, p < 0.05). Physical and psychological consequences of CDI were experienced by 63.5% and 66.1% of participants with active CDI. Despite the infection being cleared, these consequences were still frequently experienced in Past CDI cohort with similar rates (reported by 73.2% of respondents for both, physical consequences p = 0.08; psychological consequences p = 0.21). After the infection, 56.6% of respondents noted that post-CDI symptoms remained; 40.9% believed they would never get rid of them. Conclusions: While the societal burden of CDI is well described in the literature, our study is one of the first aimed at understanding the major burden of CDI on quality of life. Our results highlight the long-lasting nature of CDI and further reinforce the need for enhanced therapeutics in the prevention and treatment of this devastating infection.

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Objective:The primary study aim was to describe all direct healthcare costs associated with Clostridioides difficile infection (CDI), both in and out of the hospital, in patients with hematologic malignancies in the United States.Design:A retrospective analysis was conducted utilizing data from US databases of Truven Health Analytics.Patients:We analyzed health insurance claims between January 2014 and December 2017 of patients diagnosed with hematological cancer: acute myeloid leukemia (AML), acute lymphoblastic leukemia, Hodgkin’s lymphoma, and non-Hodgkin’s lymphoma (NHL).Methods:Patients with CDI after cancer diagnosis (CDI+, cases) were matched with patients without CDI reported (CDI−, controls). Matched cases and controls were compared to identify the CDI-associated costs in the 90 days following the onset of CDI.Results:We matched 622 CDI+ patients with 11,111 CDI− patients. NHL (41.7%) and AML (30.9%) were the predominant underlying diseases in the CDI+ groups. During study period, the average time in-hospital of CDI+ patients was 23.1 days longer than for CDI− patients (P < 2×10−16). Overall, CDI onset increased costs of care by an average of US$57,159 per patient (P = 6×10−12), mainly driven by hospital costs.Conclusions:This study confirms the significant economic burden associated with CDI in the United States, especially in patients with hematological malignancies. These findings highlight the need for prevention of CDI in this specific patient population.