Fidaxomicin monotherapy versus standard therapy combined with bezlotoxumab for treating patients with Clostridioides difficile infection at high risk of recurrence: a matched cohort study.

BACKGROUND: Both fidaxomicin and bezlotoxumab (used in combination with an antibiotic against Clostridioides difficile) achieve reductions in recurrence rates of C. difficile infection (CDI). However, the two strategies have never been compared. METHODS: Data from two retrospective cohorts of 'real-life' use of fidaxomicin and bezlotoxumab in combination with a standard anti-C. difficile antibiotic were used to compare the rates of recurrence of both strategies. Since the two cohorts were not identical, we used a propensity score analysis. RESULTS: Three hundred and two patients were included: 244 in the fidaxomicin cohort and 78 in the bezlotoxumab cohort. A history of renal failure or immunosuppression was more frequent in patients receiving bezlotoxumab (39.7% and 66.7% versus 26.6% and 38.9%; P = 0.03 and P < 0.001, respectively), but the severity and number of previous CDI episodes were similar in both cohorts. We observed that 19.3% of the patients in the fidaxomicin cohort experienced recurrence, compared with 14.1% in the bezlotoxumab cohort (OR 1.45; 95% CI 0.71-2.96; P = 0.29) but the difference remained non-significant after propensity score matching using previously defined variables (OR 1.24; 95% CI 0.50-3.07; P = 0.64). Moreover, the multivariate analysis did not show differences depending on the drug used. CONCLUSIONS: We observed that fidaxomicin and bezlotoxumab are prescribed in similar clinical scenarios, although those treated with bezlotoxumab have greater comorbidity. The proportion of recurrences was numerically lower in those treated with bezlotoxumab, although the propensity analysis did not find significant differences between the two drugs.

Real-life experience with fidaxomicin in Clostridioides difficile infection: a multicentre cohort study on 244 episodes.

The high cost of fidaxomicin has restricted its use despite the benefit of a lower Clostridioides difficile infection (CDI) recurrence rate at 4 weeks of follow-up. This short follow-up represents the main limitation of pivotal clinical trials of fidaxomicin, and some recent studies question its benefits over vancomycin. Moreover, the main risk factors of recurrence after treatment with fidaxomicin remain unknown. We designed a multicentre retrospective cohort study among four Spanish hospitals to assess the efficacy of fidaxomicin in real life and to investigate risk factors of fidaxomicin failure at weeks 8 and 12. Two-hundred forty-four patients were included. Fidaxomicin was used in 96 patients (39.3%) for a first episode of CDI, in 95 patients (38.9%) for a second episode, and in 53 patients (21.7%) for a third or subsequent episode. Patients treated with fidaxomicin in a first episode were younger (59.9 years vs 73.5 years), but they had more severe episodes (52.1% vs. 32.4%). The recurrence rates for patients treated in the first episode were 6.5% and 9.7% at weeks 8 and 12, respectively. Recurrence rates increased for patients treated at second or ulterior episodes (16.3% and 26.4% at week 8, respectively). Age greater than or equal to 85 years and having had a previous episode of CDI were identified as recurrence risk factors at weeks 8 and 12. We conclude that the outcomes with fidaxomicin in real life are at least as good as those observed in clinical trials despite a more demanding evaluation. Be it 85 years of age or older, and the use after a first episode appears to be independent factors of CDI recurrence after treatment with fidaxomicin.

Effective definition of low humoral response to Clostridioides difficile infection.

BACKGROUND: Determination of the humoral response to Clostridioides difficile (CD) toxins could be of great value in the management of patients with CD infection (CDI). METHODS: A prospective study was conducted on the clinical characteristics and humoral response in patients with CDI. Determination of ELISA IgG CD anti-toxin B (tgcBiomics, Germany) was performed. The following dilutions were planned for each patient, 1:100, 1: 200, 1: 400, 1: 800: 1: 1600. A significant concentration of antibody was considered to be present in each dilution if an optical density 0.2 units higher than the negative control of the technique was evident. RESULTS: Eighty-five patients were included during the study period, November 2018-February 2020. The median age was 73 years (interquartile range: 62.5-85 years), with female predominance (45 patients, 52.9%). Thirty-nine patients (45.9%) had a severe infection. Seven patients (8.2%) had suffered an episode of CDI in the previous three months. Seventeen patients (20%) had one or more recurrent episodes during the three-month follow-up: No patient died during admission or required surgery for severe-complicated infection. The incidence of recurrence in patients with no antibody detected at 1:400 dilution was 25.4% (16 patients) while it was 4.3% (one patient) in patients with antibody present at that dilution (p = 0.03). Liver cirrhosis was associated with higher humoral response against CD. CONCLUSIONS: Antibodies IgG CD anti-toxin B detection at a dilution of 1:400, using a B ELISA technique, effectively identified patients at increased risk of recurrence. This information could help assist in the management of patients.

A Retrospective Controlled Cohort Study of the Impact of Glucocorticoid Treatment in SARS-CoV-2 Infection Mortality.

Evidence to support the use of steroids in coronavirus disease 2019 (COVID-19) pneumonia is lacking. We aim to determine the impact of steroid use for COVID-19 pneumonia on hospital mortality. We performed a single-center retrospective cohort study in a university hospital in Madrid, Spain, during March of 2020. To determine the role of steroids in in-hospital mortality, patients admitted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and treated with steroids were compared to patients not treated with steroids, and we adjusted with a propensity score for patients on steroid treatment. Survival times were compared using the log rank test. Different steroid regimens were compared and adjusted with a second propensity score. During the study period, 463 out of 848 hospitalized patients with COVID-19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) patients were treated with steroids and 67 patients were not. Global mortality was 15.1%. The median time to steroid treatment from symptom onset was 10 days (interquartile range [IQR], 8 to 13 days). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67]; hazard ratio [HR], 0.51 [95% confidence interval, 0.27 to 0.96]; P = 0.044). Steroid treatment reduced mortality by 41.8% relative to the mortality with no steroid treatment (relative risk reduction, 0.42 [95% confidence interval, 0.048 to 0.65]). Initial treatment with 1 mg/kg of body weight/day of methylprednisolone versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86]; odds ratio [OR], 0.880 [95% confidence interval, 0.449 to 1.726]; P = 0.710). Our results show that the survival of patients with SARS-CoV-2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. Rates of in-hospital mortality were not different between initial regimens of 1 mg/kg/day of methylprednisolone and glucocorticoid pulses.

Impact of lung ultrasound during the SARS-CoV-2 pandemic: Distinction between viral and bacterial pneumonia.

INTRODUCTION: Lung Ultrasound is an accessible, low-cost technique that has demonstrated its usefulness in the prognostic stratification of COVID-19 patients. In addition, according to previous studies, it can guide us towards the potential aetiology, especially in epidemic situations such as the current one. PATIENTS AND METHODS: 40 patients were prospectively recruited, 30 with confirmed SARS-CoV-2 pneumonia and 10 with community-acquired pneumonia (CAP). The patients included underwent both a chest X-ray and ultrasound. RESULTS: There were no differences in the 2 groups in terms of clinical and laboratory characteristics. The main ultrasound findings in the SARS-CoV-2 group were the presence of confluent B lines and subpleural consolidations and hepatinization in the CAP group. Pleural effusion was more frequent in the CAP group. There were no normal lung ultrasound exams. Analysis of the area under the curve (AUC) curves showed an area under the curve for Lung Ultrasound of 89.2% (95% CI: 75%.0-100%, p < .001) in the identification of SARS-CoV-2 pneumonia. The cut-off value for the lung score of 10 had a sensitivity of 93.3% and a specificity of 80.0% (p < .001). DISCUSSION: The combination of the findings of the Lung Ultrasound, with a Lung Score greater than 10, added to the rest of the additional tests, can be an excellent tool to predict the aetiology of the pneumonia.

[Impact of Lung Ultrasound dUring the SARS-CoV-2 Pandemic: Distinction Between Viral and Bacterial Pneumonia]. / Impacto de la ecografía pulmonar Durante la pandemia por SARS-CoV-2: distinción entre la neumonía viral y la bacteriana.

Introduction: Lung ultrasound is an accessible, low-cost technique that has demonstrated its usefulness in the prognostic stratification of COVID-19 patients. In addition, according to previous studies, it can guide us towards the potential aetiology, especially in epidemic situations such as the current one. Patients and methods: 40 patients were prospectively recruited, 30 with confirmed SARS-CoV-2 pneumonia and 10 with community-acquired pneumonia. The patients included underwent both a chest X-ray and ultrasound. Results: There were no differences in the 2 groups in terms of clinical and laboratory characteristics. The main ultrasound findings in the SARS-CoV-2 group were the presence of confluent B lines and subpleural consolidations and hepatinization in the community-acquired pneumonia group. Pleural effusion was more frequent in the community-acquired pneumonia group. There were no normal lung ultrasound exams. Analysis of the area under the curve curves showed an area under the curve for lung ultrasound of 89.2% (95% CI: 75.0-100%, p < .001) in the identification of SARS-CoV-2 pneumonia. The cut-off value for the lung score of 10 had a sensitivity of 93.3% and a specificity of 80.0% (p < .001). Discussion: The combination of the findings of the lung ultrasound, with a lung score greater than 10, added to the rest of the additional tests, can be an excellent tool to predict the aetiology of the pneumonia.

Risk Factors for Clostridioides Difficile Diarrhea In Solid Organ Transplantation Recipients.

BACKGROUND: There is limited knowledge about risk factors for Clostridioides difficile infection (CDI) and recurrent CDI in solid organ transplant (SOT) recipients. METHODS: A case-control study of CDI in SOT recipients compared with controls (SOT recipients who did not present CDI). RESULTS: Sixty-seven patients from 1089 SOT recipients (6.2%) suffered at least one episode of CDI. The mean age was 55 ± 12 years and 20 cases (69%) were men. The accumulated incidence was 8% in liver transplantation, 6.2% in lung transplantation, 5.4% in heart transplantation, and 4.7% in kidney transplantation. Twenty-nine cases (43.3%) were diagnosed during the first 3 months after SOT. Forty-one cases (61.2%) were hospital acquired. Thirty-one patients with CDI presented with mild-moderate infection (46.3%), 30 patients with severe infection (44.8%), and 6 patients with severe-complicated disease (9%). Independent variables found to be related with CDI were hospitalization in the previous 3 months (odds ratio: 2.99; [95% confidence interval 1.21-7.37]) and the use of quinolones in the previous month (odds ratio: 3.71 [95% confidence interval 1.16-11.8]). Eleven patients (16.4%) had at least one recurrence of CDI. Previous treatment with amoxicillin-clavulanate, severe-complicated index episode, and high serum creatinine were associated with recurrent CDI in the univariant analysis CONCLUSIONS: Liver transplant recipients presented the highest incidence of CDI among SOT recipients. Risk factors for CDI were hospitalization in the previous 3 months and the use of quinolones in the previous month.

Real-World Experience with Bezlotoxumab for Prevention of Recurrence of Clostridioides difficile Infection.

Bezlotoxumab is marketed for the prevention of recurrent Clostridioides difficile infection (rCDI). Its high cost could be determining its prescription to a different population than that represented in clinical trials. The objective of the study was to verify the effectiveness and safety of bezlotoxumab in preventing rCDI and to investigate factors related to bezlotoxumab failure in the real world. A retrospective, multicentre cohort study of patients treated with bezlotoxumab in Spain was conducted. We compared the characteristics of cohort patients with those of patients treated with bezlotoxumab in the pivotal MODIFY trials. We assessed recurrence rates 12 weeks after completion of treatment against C. difficile, and we analysed the factors associated with bezlotoxumab failure. Ninety-one patients were included in the study. The cohort presented with more risk factors for rCDI than the patients included in the MODIFY trials. Thirteen (14.2%) developed rCDI at 12 weeks of follow-up, and rCDI rates were numerically higher in patients with two or more previous episodes (25%) than in those who had fewer than two previous episodes of C. difficile infection (CDI) (10.4%); p = 0.09. There were no adverse effects attributable to bezlotoxumab. Despite being used in a more compromised population than that represented in clinical trials, we confirm the effectiveness of bezlotoxumab for the prevention of rCDI.