Antibiotic Treatment Pipeline for Clostridioides difficile Infection (CDI): A Wide Array of Narrow-Spectrum Agents

2020 ◽  
Vol 22 (8) ◽  
Author(s):  
T. J. Carlson ◽  
A. J. Gonzales-Luna
Keyword(s):  
Antibiotic Treatment ◽  
Narrow Spectrum ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection

scholarly journals Ridinilazole, a narrow spectrum antibiotic for treatment of Clostridioides difficile infection, enhances preservation of microbiota-dependent bile acids

2020 ◽  
Vol 319 (2) ◽  
pp. G227-G237 ◽  
Author(s):  
Xi Qian ◽  
Karin Yanagi ◽  
Anne V. Kane ◽  
Nicholas Alden ◽  
Ming Lei ◽  
...  
Keyword(s):  
Bile Acid ◽  
Antibiotic Treatment ◽  
Broad Spectrum ◽  
Acid Metabolism ◽  
Bile Acid Metabolism ◽  
Treatment Cessation ◽  
Broad Spectrum Antibiotic ◽  
Narrow Spectrum ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection

This is the first study to demonstrate in humans the relationships between Clostridioides difficile antibiotic treatment choice and bile acid metabolism both during therapy and after treatment cessation. The results show a microbiota- and metabolome-preserving property of a novel narrow-spectrum agent that correlates with the agent’s favorable sustained clinical response rates compared with broad-spectrum antibiotic treatment.

scholarly journals Assessment of Testing and Treatment of Asymptomatic Bacteriuria Initiated in the Emergency Department

2020 ◽  
Vol 7 (12) ◽  
Author(s):  
Lindsay A Petty ◽  
Valerie M Vaughn ◽  
Scott A Flanders ◽  
Twisha Patel ◽  
Anurag N Malani ◽  
...  
Keyword(s):  
Emergency Department ◽  
Antibiotic Treatment ◽  
Asymptomatic Bacteriuria ◽  
Antibiotic Use ◽  
Altered Mental Status ◽  
Estimating Equation ◽  
Hospitalized Patients ◽  
Clostridioides Difficile ◽  
Cord Injury ◽  
Clostridioides Difficile Infection

Abstract Background Reducing antibiotic use in patients with asymptomatic bacteriuria (ASB) has been inpatient focused. However, testing and treatment is often started in the emergency department (ED). Thus, for hospitalized patients with ASB, we sought to identify patterns of testing and treatment initiated by emergency medicine (EM) clinicians and the association of treatment with outcomes. Methods We conducted a 43-hospital, cohort study of adults admitted through the ED with ASB (February 2018–February 2020). Using generalized estimating equation models, we assessed for (1) factors associated with antibiotic treatment by EM clinicians and, after inverse probability of treatment weighting, (2) the effect of treatment on outcomes. Results Of 2461 patients with ASB, 74.4% (N = 1830) received antibiotics. The EM clinicians ordered urine cultures in 80.0% (N = 1970) of patients and initiated treatment in 68.5% (1253 of 1830). Predictors of EM clinician treatment of ASB versus no treatment included dementia, spinal cord injury, incontinence, urinary catheter, altered mental status, leukocytosis, and abnormal urinalysis. Once initiated by EM clinicians, 79% (993 of 1253) of patients remained on antibiotics for at least 3 days. Antibiotic treatment was associated with a longer length of hospitalization (mean 5.1 vs 4.2 days; relative risk = 1.16; 95% confidence interval, 1.08–1.23) and Clostridioides difficile infection (CDI) (0.9% [N = 11] vs 0% [N = 0]; P = .02). Conclusions Among hospitalized patients ultimately diagnosed with ASB, EM clinicians commonly initiated testing and treatment; most antibiotics were continued by inpatient clinicians. Antibiotic treatment was not associated with improved outcomes, whereas it was associated with prolonged hospitalization and CDI. For best impact, stewardship interventions must expand to the ED.

scholarly journals Microbiota-based markers predictive of development of Clostridioides difficile infection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Matilda Berkell ◽  
◽  
Mohamed Mysara ◽  
Basil Britto Xavier ◽  
Cornelis H. van Werkhoven ◽  
...  
Keyword(s):  
Antibiotic Treatment ◽  
Intestinal Microbiota ◽  
Healthcare Costs ◽  
Beta Lactams ◽  
Clostridioides Difficile ◽  
Before And After ◽  
Clostridioides Difficile Infection ◽  
Patients At Risk ◽  
Risk Patients ◽  
Considerable Morbidity

AbstractAntibiotic-induced modulation of the intestinal microbiota can lead to Clostridioides difficile infection (CDI), which is associated with considerable morbidity, mortality, and healthcare-costs globally. Therefore, identification of markers predictive of CDI could substantially contribute to guiding therapy and decreasing the infection burden. Here, we analyze the intestinal microbiota of hospitalized patients at increased CDI risk in a prospective, 90-day cohort-study before and after antibiotic treatment and at diarrhea onset. We show that patients developing CDI already exhibit significantly lower diversity before antibiotic treatment and a distinct microbiota enriched in Enterococcus and depleted of Ruminococcus, Blautia, Prevotella and Bifidobacterium compared to non-CDI patients. We find that antibiotic treatment-induced dysbiosis is class-specific with beta-lactams further increasing enterococcal abundance. Our findings, validated in an independent prospective patient cohort developing CDI, can be exploited to enrich for high-risk patients in prospective clinical trials, and to develop predictive microbiota-based diagnostics for management of patients at risk for CDI.

scholarly journals 218. Evaluation of Clinical Outcomes with Shorter Vs. Longer Duration of Treatment for Common Inpatient Bacterial Infections Associated with Bacteremia

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S128-S128
Author(s):  
Leila Hojat ◽  
Mary T Bessesen ◽  
Margaret Reid ◽  
Bryan C Knepper ◽  
Matthew A Miller ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Antibiotic Treatment ◽  
Primary Outcome ◽  
Safety Net ◽  
Duration Of Treatment ◽  
Duration Of Therapy ◽  
Clostridioides Difficile ◽  
Short Course ◽  
Tertiary Center ◽  
Clostridioides Difficile Infection

Abstract Background Pneumonia (PNA), urinary tract infection (UTI), and acute bacterial skin and skin structure infection (ABSSSI) are the most common infections treated in the inpatient setting and often are associated with bacteremia. Though short courses of treatment are advocated for these infections in general, no established guidelines exist for cases involving bacteremia. We evaluated the clinical outcomes of patients receiving short (5–9 days) vs. long (10–15 days) duration of antibiotic treatment. Methods A retrospective study was conducted at 3 area hospitals comprising a university-based tertiary center, a public safety net hospital, and a Veterans’ Affairs hospital. We included hospitalized adult patients with transient bacteremia associated with uncomplicated cases of PNA, UTI, or ABSSSI. The primary outcome consisted of a composite of rehospitalization or resumption of antibiotic treatment attributed to the original infection or death due to any cause within 30 days of the antibiotic start date. Secondary outcomes included the individual composite components, Clostridioides difficile infection, and antibiotic-related adverse effects leading to change in antibiotic therapy. A propensity score weighted logistic regression model was used to mitigate factors which could bias a patient toward receiving a shorter or longer treatment duration. Results Of 411 patients included in the study, 123 (29.9%) received a short duration of therapy and 288 (70.1%) received a long duration of therapy. The median duration of treatment was 8 days in the short group and 13 days in the long group. In the propensity-weighted analysis, the probability of meeting the composite primary outcome was not statistically different between the short and long groups (Table 1). However, receiving a short course was associated with a higher probability of restarting antibiotics and Clostridioides difficile infection. Conclusion Shorter vs. longer courses of antibiotic treatment for bacteremia associated with PNA, UTI, and ABSSSI were not significantly different in a composite of readmission, restart of antibiotics, and mortality; however, further study is needed to evaluate the safety and effectiveness of short-course therapy. Disclosures All authors: No reported disclosures.

scholarly journals 219. Characteristics Associated with Inappropriate Antibiotic Prescribing in Patients with Asymptomatic Bacteriuria (ASB)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S111-S111
Author(s):  
Morgan L Bixby ◽  
Brian R Raux ◽  
Aakansha Bhalla ◽  
Christopher McCoy ◽  
Elizabeth B Hirsch
Keyword(s):  
Antibiotic Treatment ◽  
Inappropriate Prescribing ◽  
White Blood Cells ◽  
Asymptomatic Bacteriuria ◽  
Panel Member ◽  
Culture Collection ◽  
Antibiotic Prescribing ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Klebsiella Spp

Abstract Background Antibiotic treatment of asymptomatic bacteriuria (ASB) is considered inappropriate, does not improve patient outcomes, and may lead to adverse events such as antibiotic resistance and Clostridioides difficile infection. Previous stewardship interventions have focused on reducing unnecessary urine culture collection in individuals without urinary symptoms; however, further interventions to reduce inappropriate prescribing in ASB are warranted. This study sought to identify characteristics associated with treatment of ASB in order to implement future stewardship interventions. Methods This two-center, retrospective cohort study included unique emergency department or inpatient adults with consecutive non-duplicate monomicrobial urine isolates of Enterobacterales or Pseudomonas aeruginosa collected between 8/2013 and 1/2014 from two academic hospitals in Boston, Massachusetts. Patients with ASB (without chart-documented urinary-specific symptoms) were identified through chart review and stratified into two groups: those treated with empiric urinary tract infection (UTI) antibiotics and those untreated. Logistic regression analyses were performed to identify variables independently associated with antibiotic treatment of ASB. Results During the study, 255 patients were determined to have ASB and a majority (80.8%) were treated with empiric UTI antibiotics. Most patients were female (71.4%) and elderly (mean age 70 years). The most common organisms isolated were Escherichia coli (59.2%), Klebsiella spp. (23.1%), and P. aeruginosa (9.8%). The presence of isolated fever (OR, 7.83 [95% confidence interval, 1.51, 144.20]); p = 0.05), urinalysis positive for pyuria (>10 white blood cells) (OR, 2.52 [95% CI, 1.15, 5.54]; p = 0.02), and Klebsiella spp. urine isolate (OR, 2.99 [95% CI, 1.19, 8.60]; p = 0.02) were independently associated with treatment. Conclusion A large proportion of ASB patients were treated with antibiotics despite clinical practice guidelines recommending against this practice. Isolated fever, pyuria, and Klebsiella spp. culture were all significantly associated with the treatment of ASB; targeted review of these patients by stewardship programs may help to reduce inappropriate ASB treatment within these institutions. Disclosures Elizabeth B. Hirsch, PharmD, Merck (Grant/Research Support) Nabriva Therapeutics (Advisor or Review Panel member)

scholarly journals 1211. Response to Fecal Microbiota Transplant (FMT) in Refractory Clostridioides difficile Infection (CDI) is Modest Compared to Recurrent CDI in Hospitalized Patients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S627-S627
Author(s):  
Jae Hyun Shin ◽  
R Ann Hays ◽  
Cirle Warren
Keyword(s):  
Health System ◽  
Complete Resolution ◽  
Fecal Microbiota ◽  
Inpatient Setting ◽  
University Of Virginia ◽  
Cure Rate ◽  
Fecal Microbiota Transplant ◽  
Safety And Efficacy ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection

Abstract Background There are limited options for Clostridioides difficile infection (CDI) refractory to conventional antibiotic therapy (metronidazole, vancomycin, or fidaxomicin). Fecal microbiota transplant (FMT) is considered a safe and effective treatment for recurrent CDI but has not been widely utilized for refractory CDI due to concerns about safety. Even when included in studies, refractory CDI has not been analyzed separately from recurrent CDI. We reviewed cases of FMT performed in the inpatient setting for CDI to evaluate its safety and efficacy for refractory CDI. Methods Patients who received FMT inpatient at University of Virginia Health System for recurrent or refractory CDI after Infectious Diseases and Gastroenterology consultation signed informed consent acknowledging that FMT was considered investigational use in CDI not responding to standard of care as per 2014 FDA guidance. Charts were reviewed as part of quality improvement efforts to evaluate safety and efficacy of FMT in inpatient setting. Results Starting in July 2014, 13 patients received FMT for CDI as inpatients. Six received FMT for recurrent CDI, with four having complete resolution, one had recurrent CDI, and one had persistent C. difficile-negative diarrhea, for cure rate of 83%, comparable to published studies. Seven patients received FMT for refractory CDI, with three resulting in complete resolution. One responded to FMT but refused further care, one died from multiorgan failure after initial response to FMT that was possibly related to CDI, strongyloides, and/or CMV. Two patients had ongoing diarrhea suggestive of post-infectious irritable bowel syndrome, one was C. difficile-negative and one was not tested. The cure rate was 57%, lower than that of the recurrent CDI, but without any clear evidence of microbiologic failure. Outcome of patients undergoing FMT for CDI in the inpatient setting at University of Virginia Health System Conclusion Cure rate for FMT for refractory CDI was lower than recurrent CDI, but review of the cases of treatment failures did not reveal any microbiologic evidence of failure. FMT should be considered an alternative option when treating refractory CDI. Disclosures All Authors: No reported disclosures

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

2020 ◽  
Vol 10 (1) ◽  
pp. 2
Author(s):  
Rosa Escudero-Sánchez ◽  
María Ruíz-Ruizgómez ◽  
Jorge Fernández-Fradejas ◽  
Sergio García Fernández ◽  
María Olmedo Samperio ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Recurrence Rates ◽  
Factors Associated ◽  
Clostridioides Difficile ◽  
Multicentre Cohort Study ◽  
Clostridioides Difficile Infection ◽  
Prevention Of Recurrence ◽  
Multicentre Cohort

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.

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

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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