Antibiotic Therapy for Clostridioides difficile Infections

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 23795

Special Issue Editors

College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA
Interests: antimicrobial stewardship; penicillin allergy management; Clostridioides difficile infection; expanding the pharmacy services and scholarship
Special Issues, Collections and Topics in MDPI journals
College of Pharmacy, University of Georgia, Savannah, GA 31405, USA
Interests: critical care; infectious diseases; drug dosing in obesity; antimicrobial stewardship

Special Issue Information

Dear Colleagues,

The increase in Clostridioides difficile infection (CDI) cases during the past 2 decades has played a major role in the advancement of antimicrobial stewardship programs. CDI rates are often the focus of many antimicrobial- and syndrome-specific interventions deployed by ASPs. However, despite ASP and infection control efforts, CDI remains a problematic, opportunistic infection. Recent guideline updates from leading national and international expert panels have occurred with the advent of new therapeutics and evolving data. This Special Issue will seek manuscripts on ASP interventions that may impact CDI, therapeutic approaches to CDI, and additional healthcare-related research on CDI management including education, access, and more.

Prof. Dr. Brandon Bookstaver
Prof. Dr. Christopher M. Bland
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (10 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

13 pages, 2042 KiB  
Article
Clostridioides difficile Infection in an Italian Tertiary Care University Hospital: A Retrospective Analysis
Antibiotics 2023, 12(5), 837; https://doi.org/10.3390/antibiotics12050837 - 30 Apr 2023
Viewed by 1390
Abstract
Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality, mostly in frail patients. Notification is not mandatory in Italy, and data on incidence, risk of death, and recurrence are lacking. The purpose of this study was to determine CDI incidence [...] Read more.
Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality, mostly in frail patients. Notification is not mandatory in Italy, and data on incidence, risk of death, and recurrence are lacking. The purpose of this study was to determine CDI incidence and risk factors for mortality and recurrence. The “ICD-9 00845” code in hospital-standardized discharged forms (H-SDF) and microbiology datasets were used to retrieve CDI cases at Policlinico Hospital, Palermo between 2013 and 2022. Incidence, ward distribution, recurrence rate, mortality, and coding rate were considered. The risk of death and recurrence was predicted through multivariable analysis. There were 275 CDIs, 75% hospital-acquired, the median time between admission and diagnosis was 13 days, and the median stay was 21 days. Incidence increased from 0.3 to 5.6% (an 18.7-fold increase) throughout the decade. Only 48.1% of cases were coded in H-SDF. The rate of severe/severe-complicated cases increased 1.9 times. Fidaxomicin was used in 17.1% and 24.7% of cases overall and since 2019. Overall and attributable mortalities were 11.3% and 4.7%, respectively. Median time between diagnosis and death was 11 days, and recurrence rate was 4%. Bezlotoxumab was administered in 64% of recurrences. Multivariable analysis revealed that only hemodialysis was associated with mortality. No statistically significant association in predicting recurrence risk emerged. We advocate for CDI notification to become mandatory and recommend coding CDI diagnosis in H-SDF to aid in infection rate monitoring. Maximum attention should be paid to preventing people on hemodialysis from getting CDI. Full article
(This article belongs to the Special Issue Antibiotic Therapy for Clostridioides difficile Infections)
Show Figures

Figure 1

9 pages, 498 KiB  
Article
Impact of Nucleic Acid Amplification Test on Clinical Outcomes in Patients with Clostridioides difficile Infection
Antibiotics 2023, 12(3), 428; https://doi.org/10.3390/antibiotics12030428 - 21 Feb 2023
Viewed by 1048
Abstract
A nucleic acid amplification test (NAAT) is recommended to determine whether or not patients have a Clostridioides difficile infection (CDI) when the glutamate dehydrogenase activity assay is positive and the rapid membrane enzyme immunoassays for toxins is negative. In our hospital, a NAAT [...] Read more.
A nucleic acid amplification test (NAAT) is recommended to determine whether or not patients have a Clostridioides difficile infection (CDI) when the glutamate dehydrogenase activity assay is positive and the rapid membrane enzyme immunoassays for toxins is negative. In our hospital, a NAAT was introduced to diagnose CDI precisely in April 2020. This study aimed to investigate the impact of a NAAT on the clinical outcomes in patients with CDI at our hospital. Seventy-one patients diagnosed with CDI between April 2017 and March 2022 were included in our study. Patients with CDI were divided into two groups: before (pre-NAAT) and after (post-NAAT) the introduction of NAAT. The clinical outcome was compared between the two groups. Of the 71 patients with CDI, 41 were sorted into the pre-NAAT group and 30 into the post-NAAT group. The clinical cure rate was significantly higher in the post-NAAT group compared to the pre-NAAT group (76.7% vs. 48.8%, p = 0.018). In the multivariable analysis, the clinical cure was significantly associated with the introduction of NAAT (p = 0.022). Our findings suggest that the introduction of NAAT can improve the clinical outcomes in CDI patients. Full article
(This article belongs to the Special Issue Antibiotic Therapy for Clostridioides difficile Infections)
Show Figures

Figure 1

11 pages, 655 KiB  
Article
Melatonin as an Antimicrobial Adjuvant and Anti-Inflammatory for the Management of Recurrent Clostridioides difficile Infection
Antibiotics 2022, 11(11), 1472; https://doi.org/10.3390/antibiotics11111472 - 25 Oct 2022
Cited by 1 | Viewed by 1398
Abstract
Background: Clostridioides difficile (C. difficile) infection (CDI) is strongly associated with inflammation and has the potential to cause recurrent infections. Pre-clinical data suggest that melatonin has beneficial effects in the gastrointestinal tract due to its anti-inflammatory and antibacterial properties. This analysis [...] Read more.
Background: Clostridioides difficile (C. difficile) infection (CDI) is strongly associated with inflammation and has the potential to cause recurrent infections. Pre-clinical data suggest that melatonin has beneficial effects in the gastrointestinal tract due to its anti-inflammatory and antibacterial properties. This analysis examines the association between melatonin and the risk of recurrent CDI. Methods: A retrospective cohort study was conducted among patients with an inpatient diagnosis of CDI along with a positive C. difficile polymerase chain reaction (PCR) or enzyme immunoassay (EIA) test result. Patients were followed until the first study end point (death) or the first instance of recurrent infection. Propensity-score weighting was utilized accounting for confounding factors and weighted Cox models were estimated. Results: A total of 24,782 patients met the inclusion criteria, consisting of 3457 patients exposed to melatonin and 21,325 patients with no melatonin exposure. The results demonstrate that those exposed to melatonin were associated with a 21.6% lower risk of recurrent CDI compared to patients without melatonin exposure (HR = 0.784; 95% CI = 0.674–0.912). Conclusion: Our results demonstrate a decreased rate of recurrent CDI in patients exposed to melatonin. Further research on melatonin as an antimicrobial adjuvant and anti-inflammatory is warranted for the management of recurrent CDI. Full article
(This article belongs to the Special Issue Antibiotic Therapy for Clostridioides difficile Infections)
Show Figures

Figure 1

24 pages, 2594 KiB  
Article
Long-Term Lactulose Administration Improves Dysbiosis Induced by Antibiotic and C. difficile in the PathoGutTM SHIME Model
Antibiotics 2022, 11(11), 1464; https://doi.org/10.3390/antibiotics11111464 - 24 Oct 2022
Cited by 2 | Viewed by 1506
Abstract
Clostridioides difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea and an important nosocomial infection with different severity degrees. Disruption of the gut microbiota by broad-spectrum antibiotics creates a proper environment for C. difficile colonization, proliferation, and clinical disease onset. Restoration of [...] Read more.
Clostridioides difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea and an important nosocomial infection with different severity degrees. Disruption of the gut microbiota by broad-spectrum antibiotics creates a proper environment for C. difficile colonization, proliferation, and clinical disease onset. Restoration of the gut microbial ecosystem through prebiotic interventions can constitute an effective complementary treatment of CDI. Using an adapted simulator of the human gut microbial ecosystem, the PathoGutTM SHIME, the effect of different long-term and repeated dose lactulose treatments was tested on C. difficile germination and growth in antibiotic-induced dysbiotic gut microbiota environments. The results showed that lactulose reduced the growth of viable C. difficile cells following clindamycin treatment, shifted the antibiotic-induced dysbiotic microbial community, and stimulated the production of health-promoting metabolites (especially butyrate). Recovery of the gut microenvironment by long-term lactulose administration following CDI was also linked to lactate production, decrease in pH and modulation of bile salt metabolism. At a structural level, lactulose showed a significant bifidogenic potential and restored key commensal members of the gut ecosystem such as Lactobacillaceae, Veillonellaceae and Lachnospiraceae. These results support further human intervention studies aiming to validate the in vitro beneficial effects of lactulose on gut microbiome recovery during antibiotic exposure and CDI. Full article
(This article belongs to the Special Issue Antibiotic Therapy for Clostridioides difficile Infections)
Show Figures

Figure 1

13 pages, 267 KiB  
Article
Clostridioides difficile Infection Treatment and Outcome Disparities in a National Sample of United States Hospitals
Antibiotics 2022, 11(9), 1203; https://doi.org/10.3390/antibiotics11091203 - 06 Sep 2022
Cited by 3 | Viewed by 1325
Abstract
Clostridioides difficile infection (CDI) disproportionately affects certain populations, but few studies have investigated health outcome disparities among patients with CDI. This study aimed to characterize CDI treatment and health outcomes among patients by age group, sex, race, and ethnicity. This was a nationally [...] Read more.
Clostridioides difficile infection (CDI) disproportionately affects certain populations, but few studies have investigated health outcome disparities among patients with CDI. This study aimed to characterize CDI treatment and health outcomes among patients by age group, sex, race, and ethnicity. This was a nationally representative, retrospective cohort study of patients with laboratory-confirmed CDI within the Premier Healthcare Database from January 2018 to March 2021. CDI therapies received and health outcomes were compared between patients by age group, sex, race, and Hispanic ethnicity using bivariable and multivariable statistical analyses. A total of 45,331 CDI encounters were included for analysis: 38,764 index encounters and 6567 recurrent encounters. CDI treatment patterns, especially oral vancomycin use, varied predominantly by age group. Older adult (65+ years), male, Black, and Hispanic patients incurred the highest treatment-related costs and were at greatest risk for severe CDI. Male sex was an independent predictor of in-hospital mortality (aOR 1.17, 95% CI 1.05–1.31). Male sex (aOR 1.25, 95% CI 1.18–1.32) and Black race (aOR 1.29, 95% CI 1.19–1.41) were independent predictors of hospital length of stay >7 days in index encounters. In this nationally representative study, CDI treatment and outcome disparities were noted by age group, sex, and race. Full article
(This article belongs to the Special Issue Antibiotic Therapy for Clostridioides difficile Infections)

Review

Jump to: Research, Other

11 pages, 387 KiB  
Review
Is Three Company or a Crowd? Comparing and Contrasting U.S. and European Clostridioidesdifficile Clinical Practice Guidelines
Antibiotics 2022, 11(9), 1247; https://doi.org/10.3390/antibiotics11091247 - 14 Sep 2022
Cited by 1 | Viewed by 2074
Abstract
In 2021, the American College of Gastroenterology (ACG), the Infectious Diseases Society of America in conjunction with the Society for Healthcare Epidemiology of America (IDSA/SHEA), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published updated clinical practice guidelines (CPGs) for [...] Read more.
In 2021, the American College of Gastroenterology (ACG), the Infectious Diseases Society of America in conjunction with the Society for Healthcare Epidemiology of America (IDSA/SHEA), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published updated clinical practice guidelines (CPGs) for the management of Clostridioides difficile infections. The differences, sometimes subtle, between these guideline recommendations have caused some debate among clinicians. This paper delves into select key recommendations from each respective CPG and analyzes the differences and evidence associated with each. One primary difference between the CPGs is the preference given to fidaxomicin over vancomycin for initial treatment in non-severe and severe disease endorsed by IDSA/SHEA and ESCMID guidelines, while the ACG-sponsored CPGs do not offer a preference. The emphasis on cost effective data was also a noticeable difference between the CPGs and thus interpretation of the available evidence. When using guidelines to help support local practice or institutional treatment pathways, clinicians should carefully balance CPG recommendations with local patient populations and feasibility of implementation, especially when multiple guidelines for the same disease state exist. Full article
(This article belongs to the Special Issue Antibiotic Therapy for Clostridioides difficile Infections)
11 pages, 1289 KiB  
Review
SER-109: An Oral Investigational Microbiome Therapeutic for Patients with Recurrent Clostridioides difficile Infection (rCDI)
Antibiotics 2022, 11(9), 1234; https://doi.org/10.3390/antibiotics11091234 - 10 Sep 2022
Cited by 14 | Viewed by 8225
Abstract
Clostridioides difficile infection (CDI) is classified as an urgent health threat by the Centers for Disease Control and Prevention (CDC), and affects nearly 500,000 Americans annually. Approximately 20–25% of patients with a primary infection experience a recurrence, and the risk of recurrence [...] Read more.
Clostridioides difficile infection (CDI) is classified as an urgent health threat by the Centers for Disease Control and Prevention (CDC), and affects nearly 500,000 Americans annually. Approximately 20–25% of patients with a primary infection experience a recurrence, and the risk of recurrence increases with subsequent episodes to greater than 40%. The leading risk factor for CDI is broad-spectrum antibiotics, which leads to a loss of microbial diversity and impaired colonization resistance. Current FDA-approved CDI treatment strategies target toxin or toxin-producing bacteria, but do not address microbiome disruption, which is key to the pathogenesis of recurrent CDI. Fecal microbiota transplantation (FMT) reduces the risk of recurrent CDI through the restoration of microbial diversity. However, FDA safety alerts describing hospitalizations and deaths related to pathogen transmission have raised safety concerns with the use of unregulated and unstandardized donor-derived products. SER-109 is an investigational oral microbiome therapeutic composed of purified spore-forming Firmicutes. SER-109 was superior to a placebo in reducing CDI recurrence at Week 8 (12% vs. 40%, respectively; p < 0.001) in adults with a history of recurrent CDI with a favorable observed safety profile. Here, we discuss the role of the microbiome in CDI pathogenesis and the clinical development of SER-109, including its rigorous manufacturing process, which mitigates the risk of pathogen transmission. Additionally, we discuss compositional and functional changes in the gastrointestinal microbiome in patients with recurrent CDI following treatment with SER-109 that are critical to a sustained clinical response. Full article
(This article belongs to the Special Issue Antibiotic Therapy for Clostridioides difficile Infections)
Show Figures

Figure 1

15 pages, 306 KiB  
Review
The Role of Bezlotoxumab for the Prevention of Recurrent Clostridioides difficile Infections: A Review of the Current Literature and Paradigm Shift after 2021
Antibiotics 2022, 11(9), 1211; https://doi.org/10.3390/antibiotics11091211 - 07 Sep 2022
Cited by 6 | Viewed by 2163
Abstract
Clostridioides difficile infections (CDIs), and particularly recurrent infections, cause a significant burden on the health-care system. Bezlotoxumab is a new agent for the prevention of recurrent CDIs that has shown strong efficacy and high tolerability in clinical trials. The purpose of this review [...] Read more.
Clostridioides difficile infections (CDIs), and particularly recurrent infections, cause a significant burden on the health-care system. Bezlotoxumab is a new agent for the prevention of recurrent CDIs that has shown strong efficacy and high tolerability in clinical trials. The purpose of this review is to evaluate the published literature for bezlotoxumab, with a focus on literature published since the release of the 2021 focused update to the CDI treatment guidelines. A Medline/PubMed search for “bezlotoxumab” was conducted, resulting in 152 articles. Seventeen studies are included in this review, after excluding non-English-language papers, phase I and II trials, and review articles. Studies published since the 2021 focused update support the recommendations in those guidelines. Furthermore, real-world studies have shown similar results to larger clinical trials. Those with more risk factors for recurrent CDI appear to benefit most from bezlotoxumab. Currently, there are no data to support the use of bezlotoxumab outside current guideline recommendations, but future trials may build on the data seen in real-world studies to further elucidate the place in therapy for bezlotoxumab. Full article
(This article belongs to the Special Issue Antibiotic Therapy for Clostridioides difficile Infections)

Other

Jump to: Research, Review

8 pages, 1866 KiB  
Brief Report
Effect of Reduced Fluoroquinolone Use on Cephalosporin Use, Susceptibilities and Clostridioides difficile Infections
Antibiotics 2022, 11(10), 1312; https://doi.org/10.3390/antibiotics11101312 - 27 Sep 2022
Cited by 1 | Viewed by 1198
Abstract
Background: Overuse of fluoroquinolones has led to concerning rates of resistance, particularly among Gram-negative organisms. They are also highly implicated as a risk factor for Clostridioides difficile infection, and reports of other serious adverse events led to recommendations to restrict their use. Our [...] Read more.
Background: Overuse of fluoroquinolones has led to concerning rates of resistance, particularly among Gram-negative organisms. They are also highly implicated as a risk factor for Clostridioides difficile infection, and reports of other serious adverse events led to recommendations to restrict their use. Our health system began targeting the reduction in unnecessary fluoroquinolone prescribing in 2018, aiming to promote their safe and effective use. Broad-spectrum cephalosporins are often used as an alternative to fluoroquinolones. We sought to evaluate whether decreased fluoroquinolone use was associated with increased third- and fourth-generation cephalosporin use and whether these changes in utilization impacted other outcomes, including C. difficile infection (CDI) rates and susceptibilities among Gram-negative organisms. Methods: This retrospective descriptive analysis included adult patients who received a fluoroquinolone or broad-spectrum cephalosporin in a three-year time period across a large healthcare system. The primary objective was to evaluate the change in days of therapy (DOT) of fluoroquinolones and third- and fourth-generation cephalosporins. Secondary objectives included rates of resistance among common Gram-negative organisms, CDI, and analyses stratified by antibiotic indication. Results: Cephalosporin use increased by an average of 1.70 DOT/1000 PD per month (p < 0.001). Additionally, fluoroquinolone use decreased by an average of 1.18 DOT/1000 PD per month (p < 0.001). C. difficile infections decreased by 0.37 infections/10,000 patient-days per month (p < 0.001). Resistance to fluoroquinolones remained stable from 2018 to 2020, and a declining trend was observed in 2021. Conclusion: This study demonstrated that reduced fluoroquinolone use in a large healthcare system was associated with increased usage of broad-spectrum cephalosporins, decreased CDI and improvements in resistance patterns. Full article
(This article belongs to the Special Issue Antibiotic Therapy for Clostridioides difficile Infections)
Show Figures

Figure 1

8 pages, 814 KiB  
Brief Report
The Risk of Clostridioides difficile Recurrence after Initial Treatment with Vancomycin or Fidaxomicin Utilizing Cerner Health Facts
Antibiotics 2022, 11(3), 295; https://doi.org/10.3390/antibiotics11030295 - 23 Feb 2022
Cited by 2 | Viewed by 1915
Abstract
(1) Background: Fidaxomicin has been shown to significantly reduce Clostridioides difficile infection (CDI) recurrences rates in randomized, controlled trials. However, national data from the Veterans Affairs has called the real-world applicability of these findings into question. Therefore, we conducted a retrospective cohort study [...] Read more.
(1) Background: Fidaxomicin has been shown to significantly reduce Clostridioides difficile infection (CDI) recurrences rates in randomized, controlled trials. However, national data from the Veterans Affairs has called the real-world applicability of these findings into question. Therefore, we conducted a retrospective cohort study of patients receiving fidaxomicin or vancomycin as initial therapy for an index case of CDI in the hospital to evaluate the relative rates CDI recurrence within 90 days of an index case. (2) Methods: We retrieved patients 18 years and older who were admitted between July 2011 through June 2018 and diagnosed and treated for CDI with vancomycin or fidaxomicin. The first occurrence of CDI with treatment was designated as the index case. Patients with CDI within 1 year prior to index case were excluded. From the remaining index cases (vancomycin = 14,785; fidaxomicin = 889) the primary outcome (a recurrence of CDI within 90 days of the index case) was determined. The CDI recurrence rates for fidaxomicin and vancomyicn were evaluated using a Cox Proportional Hazards model on a propensity score matched cohort. (3) Results: A statistically significantly lower risk of CDI recurrence was observed with fidaxomicin use in the matched cohort (889 patients per treatment) using a Cox Proportional Hazards model (HR 0.67, 95% CI 0.50–0.90). (4) Conclusions: Fidaxomicin was independently associated with a decreased CDI recurrence, as defined by readmission for CDI within 90 days. Full article
(This article belongs to the Special Issue Antibiotic Therapy for Clostridioides difficile Infections)
Show Figures

Figure 1

Back to TopTop