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.

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Prolonged Carriage of Carbapenemase-Producing Enterobacteriaceae: Clinical Risk Factors and the Influence of Carbapenemase and Organism Types

Journal of Clinical Medicine ◽

10.3390/jcm10020310 ◽

2021 ◽

Vol 10 (2) ◽

pp. 310

Author(s):

Yong Kyun Kim ◽

In Bok Chang ◽

Han Sung Kim ◽

Wonkeun Song ◽

Seung Soon Lee

Keyword(s):

Risk Factors ◽

Odds Ratio ◽

Clinical Specimen ◽

Clinical Factors ◽

Factors Associated ◽

Logistic Analysis ◽

Clostridioides Difficile ◽

Kaplan Meier ◽

Clostridioides Difficile Infection

Prolonged carriage of carbapenemase-producing Enterobacteriaceae (CPE) constitutes a substantial epidemiologic threat. This study aimed to evaluate whether the types of carbapenemase and organism can affect the duration of carriage and to evaluate the clinical factors associated with prolonged carriage. We retrospectively reviewed data for patients admitted between May 2013 and August 2018 who were identified as CPE carriers. A total of 702 patients were identified; the major types of carbapenemase and organism were Oxacillinase (OXA)-48-like (n = 480, 68.4%) and Klebsiella pneumoniae (K. pneumoniae) (n = 584, 83.2%). The analyses of time to spontaneous decolonization using the Kaplan–Meier method showed that OXA-48-like and K. pneumoniae were significantly associated with prolonged carriage (log rank, p = 0.001 and p < 0.001). In multivariable logistic analysis to assess the risk factors for CPE prolonged carriage in the 188 patients with available follow-up culture data for 3 months, K. pneumoniae (adjusted odds ratio [aOR] 6.58; 95% confidence interval [CI], 1.05–41.27; p = 0.044), CPE positive clinical specimen (aOR 11.14; 95% CI, 4.73–26.25; p < 0.001), and concurrent Clostridioides difficile infection (CDI) (aOR 3.98, 95% CI 1.29–12.26; p = 0.016) were predictive of prolonged carriage. Our results suggest that CP-K. pneumoniae may have higher probability of prolonged carriage, while the effect of OXA-48-like CPE is inconclusive. Furthermore, patients with CP-K. pneumoniae who had positive clinical specimen or concurrent CDI can cause a vicious circle in prolonged carriage.

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

Infection ◽

10.1007/s15010-020-01567-5 ◽

2021 ◽

Author(s):

Rosa Escudero-Sánchez ◽

Angela Valencia-Alijo ◽

Sandra Cuéllar Tovar ◽

Esperanza Merino-de Lucas ◽

Sergio García Fernández ◽

...

Keyword(s):

Cohort Study ◽

Life Experience ◽

Real Life ◽

Clostridioides Difficile ◽

Multicentre Cohort Study ◽

Clostridioides Difficile Infection ◽

Multicentre Cohort

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Clinical complications in patients with primary and recurrent Clostridioides difficile infection: A real-world data analysis

SAGE Open Medicine ◽

10.1177/2050312120986733 ◽

2021 ◽

Vol 9 ◽

pp. 205031212098673

Author(s):

Paul Feuerstadt ◽

Mena Boules ◽

Laura Stong ◽

David N Dahdal ◽

Naomi C Sacks ◽

...

Keyword(s):

Loop Ileostomy ◽

Charlson Comorbidity Index Score ◽

Real World Data ◽

Infection Group ◽

Bowel Surgery ◽

Clinical Complications ◽

Clostridioides Difficile ◽

Clostridioides Difficile Infection ◽

Infection Episode

Objective: Clostridioides difficile infection and recurrent C. difficile infection result in substantial economic burden and healthcare resource use. Sepsis and bowel surgery are known to be serious complications of C. difficile infection. This study evaluated clinical complications in patients with C. difficile infection and recurrent C. difficile infection during a 12-month period following the primary C. difficile infection. Methods: A retrospective analysis of commercial claims data from the IQVIA PharMetrics Plus™ database was conducted for patients aged 18–64 years with an index C. difficile infection episode requiring inpatient stay or an outpatient visit for C. difficile infection followed by a C. difficile infection treatment. Each C. difficile infection episode ended after a 14-day C. difficile infection-claim-free period was observed. Recurrent C. difficile infection was defined as a further C. difficile infection episode within an 8-week window following the claim-free period. Clinical complications were documented over 12 months of follow-up and stratified by the number of recurrent C. difficile infection episodes (0 rCDI, 1 rCDI, 2 rCDI, and 3+ rCDI). Results: In total, 46,571 patients with index C. difficile infection episode were included. During the 6-month pre-index, the mean (standard deviation) baseline Charlson comorbidity index score, by increasing the recurrent C. difficile infection group, was 1.2 (1.9), 1.5 (2.2), 1.8 (2.3), and 2.3 (2.5). During the 12-month follow-up, sepsis occurred in 16.5%, 27.3%, 33.1%, and 43.3% of patients, and subtotal colectomy or diverting loop ileostomy was performed in 4.6%, 7.3%, 8.9%, and 10.5% of patients, respectively, by increasing the recurrent C. difficile infection group. Conclusions: Reduction in recurrent C. difficile infection is an important step to reduce the burden of serious clinical complications, and new treatments are needed to reduce C. difficile infection recurrence.

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797. Management of Patients with Multiple Clostridioides difficile Infection Recurrences using a Tapered-Pulsed Fidaxomicin Strategy

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.987 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S441-S442

Author(s):

Xing Tan ◽

Andrew M Skinner ◽

Benjamin Sirbu ◽

Larry H Danziger ◽

Dale N Gerding ◽

...

Keyword(s):

First Episode ◽

Initial Symptom ◽

Once Daily ◽

The Past ◽

Clostridioides Difficile ◽

Time To Recurrence ◽

Clostridioides Difficile Infection ◽

The Mean ◽

Systemic Antibiotics

Abstract Background There is a paucity of data assessing outcomes of alternate fidaxomicin strategies in patients with recurrent Clostridioides difficile infection (rCDI). The objective of our study is to evaluate a tapered-pulsed (T-P) fidaxomicin regimen that was administered immediately following a course of CDI treatment with initial symptom resolution in patients with multiple rCDI. Methods We reviewed the characteristics and outcomes of 46 consecutive patients who received T-P fidaxomicin between January 1, 2014-June 30, 2019 in a specialty CDI clinic. The first episode in which fidaxomicin T-P was administered was analyzed. Failure was defined as the persistence of diarrhea and/or the need for additional CDI treatment at any time on T-P fidaxomicin. Sustained clinical cure (SCC) was defined as resolution of diarrhea without recurrence. Recurrence was defined as the return of diarrhea requiring retreatment with CDI therapy after completion of T-P fidaxomicin. Both SCC and recurrence were evaluated at 30 and 90 days after completion of T-P fidaxomicin. Results The mean±SD age of the 46 patients was 63.2±19.9 years, 71.7% were female, and the mean±SD CDI episodes within the past year was 3±1.4 . Most patients (73.9%) had previously failed a vancomycin tapered and/or pulsed regimen. Prior to administering T-P fidaxomicin, a treatment regimen was given to ensure resolution of symptoms. The CDI treatment most commonly used (58.7%) was vancomycin. The T-P fidaxomicin regimen used consisted of 200 mg given once daily for 7 days followed by 200 mg every other day for a median (min-max) duration of 33 (6-120) days. Two patients (4%) failed to respond to T-P fidaxomicin; 34 (74%) and 28 (61%) achieved SCC at 30 and 90 days, respectively. Among the 44 patients that successfully completed the T-P fidaxomicin regimen, recurrence developed in 10 (22.7%) and 16 (36.4%) of patients at 30 and 90 days, respectively, with a median (min-max) time to recurrence of 20 (3-87) days (Figure 1). Four patients with recurrence had received subsequent systemic antibiotics. Figure 1. Course of CDI therapy and follow-up Conclusion A tapered-pulsed fidaxomicin strategy may be effective in patients with multiply rCDI who are refractory to other treatments, including a vancomycin tapered and pulsed regimen. Disclosures Larry H. Danziger, PharmD, Merck (Speaker’s Bureau)

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A modification of the Ponseti method for clubfoot management: a prospective comparative study

Journal of Children s Orthopaedics ◽

10.1302/1863-2548.15.210038 ◽

2021 ◽

pp. 1-10

Author(s):

Reda Ali Sheta ◽

Mohamed El-Sayed ◽

Hisham Abdel-Ghani ◽

Sameh Saber ◽

Amani Salah Eldin Mohammed ◽

...

Keyword(s):

Treatment Method ◽

Ponseti Method ◽

Level Of Evidence ◽

Home Based ◽

Multicentre Cohort Study ◽

Group A ◽

Prospective Comparative Study ◽

Group B ◽

Multicentre Cohort

Purpose We aimed to compare our parent-based exercise programem’s efficacy with the foot abduction brace (FAB) Ponseti manipulation as a retention programme. Methods We conducted this prospective multicentre cohort study between August 2009 and November 2019. The included children were allocated into one of two groups according to the retention protocol. The Pirani and Laaveg-Ponseti scores were used to assess the feet clinically and functionally. Radiological assessment was performed using standing anteroposterior and lateral radiographs of the feet. We assessed the parents’ satisfaction and adherence to the retention method. SPSS version 25 was used for the statistical analysis. Results A total of 1265 feet in 973 children were included. Group A included 637 feet managed with FAB, while group B included 628 feet managed with our retention programme. All patients were followed up to the age of four years. At the final follow-up, Pirani scores in group A participants were excellent, good and poor in 515, 90, and 32 feet, respectivel, while in group B the scores were excellent, good and poor in 471, 110 and 44 feet, respectively. The mean total score of Laaveg-Ponseti was 87.81 (sd 19.82) in group A and 90.55 (sd 20.71) in group B (p = 0.02). Group B participants showed higher satisfaction with the treatment method (p = 0.011) and more adherence to the treatment (p = 0.013). Conclusion The deformity’s recurrence related to the brace’s non-compliance in the Ponseti method might be reduced by substituting the brace with our home-based daily stretching exercises. Level of Evidence II

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2374. Healthcare Resource Use, Costs, and Recurrences in Patients with Clostridioides difficile Infection: A Real-world Data Analysis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2052 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S819-S819

Author(s):

Winnie Nelson ◽

Laura Stong ◽

Naomi Sacks ◽

Alexandria Portelli ◽

Bridget Healey ◽

...

Keyword(s):

Resource Utilization ◽

Resource Use ◽

Healthcare Resource ◽

Healthcare Resource Utilization ◽

Healthcare Resource Use ◽

Diagnosis Code ◽

Clostridioides Difficile ◽

Clostridioides Difficile Infection ◽

Ed Visits

Abstract Background Clostridioides difficile infection (CDI), especially recurrent CDI (rCDI), is associated with high morbidity and resource use and imposes a significant burden on the US healthcare system. The objective of this study was to evaluate the burden of rCDI on healthcare resource utilization. Methods A retrospective study analyzed commercial claims data from patients aged 18–64 years old in the IQVIA PharMetrics Plus™ database. CDI episodes required an inpatient stay with CDI diagnosis code (ICD-9-CM 008.45; ICD-10-CM A04.7, A04.71, A04.72), or an outpatient medical claim with CDI diagnosis code plus a CDI treatment, and index episodes occurred from January 1, 2010 to June 30, 2017. Only patients who were observable 6 months before and 12 months after the index CDI episode were included. Each CDI episode was followed by a 14-day claim-free period after the end of treatment. rCDI was defined as another CDI episode within an 8-week window immediately after the claim-free period. Number of CDI and rCDI episodes, healthcare resource use, and costs were calculated over 12-month follow-up and stratified by number of rCDI episodes. Costs were adjusted to 2018 dollars. Results 46,571 patients with an index CDI episode were included, with 3,129 (6.7%) who had 1 rCDI, 472 (1.0%) who had 2 rCDI, and 134 (0.3%) who had 3+ rCDI episodes. Mean age was 47.4 years, and 62.4% were female. In the 12-month follow-up, the mean (SD) numbers of inpatient visits were 1.4 (2.1) for those with no rCDI, 2.7 (3.4) for those with 1 rCDI, 3.7 (3.9) for those with 2 rCDI, and 5.8 (6.0) for those with 3+ rCDI episodes. Emergency department (ED) visits had a similar trend, with mean (SD) number of visits of 1.5 (3.5), 2.5 (6.0), 3.7 (7.0), and 4.6 (13), respectively for the four study groups. All-cause costs after the index CDI were $71,980 for those with no rCDI, $131,953 for those with 1 rCDI, $180,574 for those with 2 rCDI, and $207,733 for those with 3+ rCDI. Conclusion CDI and rCDI are associated with substantial healthcare resource utilization and direct medical costs. During the 12 months after an index CDI episode, the number of inpatient admissions and ED visits increased substantially for patients with an rCDI episode. Direct medical costs for patients with rCDI also increased with number of recurrences. Disclosures All authors: No reported disclosures.

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Evaluation of outcome relevance of quality indicators in the emergency department (ENQuIRE): study protocol for a prospective multicentre cohort study

BMJ Open ◽

10.1136/bmjopen-2020-038776 ◽

2020 ◽

Vol 10 (9) ◽

pp. e038776

Author(s):

Susanne Drynda ◽

Wencke Schindler ◽

Anna Slagman ◽

Johannes Pollmanns ◽

Dirk Horenkamp-Sonntag ◽

...

Keyword(s):

Emergency Department ◽

Cohort Study ◽

Quality Indicators ◽

Patient Outcomes ◽

Claims Data ◽

Quality Measures ◽

Patient Questionnaire ◽

Multicentre Cohort Study ◽

Multicentre Cohort

IntroductionQuality of emergency department (ED) care affects patient outcomes substantially. Quality indicators (QIs) for ED care are a major challenge due to the heterogeneity of patient populations, health care structures and processes in Germany. Although a number of quality measures are already in use, there is a paucity of data on the importance of these QIs on medium-term and long-term outcomes. The evaluation of outcome relevance of quality indicators in the emergency department study (ENQuIRE) aims to identify and investigate the relevance of QIs in the ED on patient outcomes in a 12-month follow-up.Methods and analysisThe study is a prospective non-interventional multicentre cohort study conducted in 15 EDs throughout Germany. Included are all patients in 2019, who were ≥18 years of age, insured at the Techniker Krankenkasse (statutory health insurance (SHI)) and gave their written informed consent to the study.The primary objective of the study is to assess the effect of selected quality measures on patient outcome. The data collected for this purpose comprise medical records from the ED treatment, discharge (claims) data from hospitalised patients, a patient questionnaire to be answered 6–8 weeks after emergency admission, and outcome measures in a 12-month follow-up obtained as claims data from the SHI.Descriptive and analytical statistics will be applied to provide summaries about the characteristics of QIs and associations between quality measures and patient outcomes.Ethics and disseminationApproval of the leading ethics committee at the Medical Faculty of the University of Magdeburg (reference number 163/18 from 19 November 2018) has been obtained and adapted by responsible local ethics committees.The findings of this work will be disseminated by publication of peer-reviewed manuscripts and presentations as conference contributions (abstracts, poster or oral presentations).Moreover, results will be discussed with clinical experts and medical associations before being proposed for implementation into the quality management of EDs.Trial registration numberGerman Clinical Trials Registry (DRKS00015203); Pre-results.

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Impact of natural menopause on multiple sclerosis: a multicentre study

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2019-320587 ◽

2019 ◽

Vol 90 (11) ◽

pp. 1201-1206 ◽

Cited By ~ 8

Author(s):

Damiano Baroncini ◽

Pietro Osvaldo Annovazzi ◽

Nicola De Rossi ◽

Giulia Mallucci ◽

Valentina Torri Clerici ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cigarette Smoking ◽

Relapse Rate ◽

Disability Progression ◽

Natural Menopause ◽

Multicentre Cohort Study ◽

Disability Status ◽

Speed Up ◽

Multicentre Cohort

ObjectiveTo study the effect of natural menopause on multiple sclerosis clinical course.MethodsThis was an observational, retrospective, multicentre, cohort study. Menopause onset was defined by the final menstrual period (FMP) beyond which no menses occurred for 12 months. We included multiple sclerosis (MS) patients with FMP occurred after 2005 and a recorded follow-up of at least 2 years pre-FMP and post-FMP. We excluded patients with primary progressive course, iatrogenic menopause and with other confounders that could mask menopause onset. We compared relapse-rate and expanded disability status scale (EDSS) scores pre-FMP and post-FMP, searching for possible interactions with age, disease duration, cigarette smoking and nulliparity status.Results148 patients were included (mean observation: 3.5 years pre-FMP and post-FMP). Most patients (92%) received disease-modifying therapies, mainly first-lines. After menopause the annualised relapse rate (ARR) significantly decreased (from 0.21±0.31 to 0.13± 0.24; p=0.005), while disability worsened (increase of mean 0.4 vs 0.2 points after menopause; p<0.001). Older age and long-lasting disease were associated with ARR reduction (p=0.013), but not with disability worsening. Cigarette smokers showed a trend to a higher disability accumulation after menopause (p=0.059).ConclusionNatural menopause seems to be a turning point to a more progressive phase of MS. Relapse rate is also reduced after menopause, but this effect could be driven most by ageing and shifting to progressive phase in patients with long-lasting disease. Cigarette smoking could speed up disability progression after menopause.

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