Antibiotics

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Open AccessEditorial

Introduction to the Special Issue on Clostridioides difficile Infection, Second Edition

by Guido Granata

Antibiotics 2024, 13(7), 607; https://doi.org/10.3390/antibiotics13070607 - 29 Jun 2024

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Abstract

Clostridioides difficile (CD) is a Gram-positive, anaerobic bacterium that is one of the most common causes of infective diarrhoea worldwide [...] Full article

(This article belongs to the Special Issue Clostridioides difficile Infection, 2nd Edition)

Research

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13 pages, 619 KiB

Open AccessArticle

COVID-19 and Clostridioides difficile Coinfection Analysis in the Intensive Care Unit

by Mircea Stoian, Adina Andone, Alina Boeriu, Sergio Rareș Bândilă, Daniela Dobru, Sergiu Ștefan Laszlo, Dragoș Corău, Emil Marian Arbănași, Eliza Russu and Adina Stoian

Antibiotics 2024, 13(4), 367; https://doi.org/10.3390/antibiotics13040367 - 17 Apr 2024

Cited by 3 | Viewed by 1593

Abstract

Since the emergence of SARS-CoV-2 in late 2019, the global mortality attributable to COVID-19 has reached 6,972,152 deaths according to the World Health Organization (WHO). The association between coinfection with Clostridioides difficile (CDI) and SARS-CoV-2 has limited data in the literature. This retrospective [...] Read more.

Since the emergence of SARS-CoV-2 in late 2019, the global mortality attributable to COVID-19 has reached 6,972,152 deaths according to the World Health Organization (WHO). The association between coinfection with Clostridioides difficile (CDI) and SARS-CoV-2 has limited data in the literature. This retrospective study, conducted at Mureș County Clinical Hospital in Romania, involved 3002 ICU patients. Following stringent inclusion and exclusion criteria, 63 patients were enrolled, with a division into two subgroups—SARS-CoV-2 + CDI patients and CDI patients. Throughout their hospitalization, the patients were closely monitored. Analysis revealed no significant correlation between comorbidities and invasive mechanical ventilation (IMV) or non-invasive mechanical ventilation (NIMV). However, statistically significant associations were noted between renal and hepatic comorbidties (p = 0.009), death and CDI-SARS-CoV-2 coinfection (p = 0.09), flourochinolone treatment and CDI-SARS-CoV-2 infection (p = 0.03), and an association between diabetes mellitus and SARS-CoV-2-CDI infection (p = 0.04), as well as the need for invasive mechanical ventilation (p = 0.04). The patients with CDI treatment were significantly younger and received immuno-modulator or corticotherapy treatment, which was a risk factor for opportunistic agents. Antibiotic and PPI (proton pump inhibitor) treatment were significant risk factors for CDI coinfection, as well as for death, with PPI treatment in combination with antibiotic treatment being a more significant risk factor. Full article

(This article belongs to the Special Issue Clostridioides difficile Infection, 2nd Edition)

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21 pages, 2924 KiB

Open AccessArticle

A Real-World Study on the Clinical Characteristics, Outcomes, and Relationship between Antibiotic Exposure and Clostridioides difficile Infection

by Bogdan Ioan Vintila, Anca Maria Arseniu, Claudiu Morgovan, Anca Butuca, Victoria Bîrluțiu, Carmen Maximiliana Dobrea, Luca Liviu Rus, Steliana Ghibu, Alina Simona Bereanu, Rares Arseniu, Ioana Roxana Codru, Mihai Sava and Felicia Gabriela Gligor

Antibiotics 2024, 13(2), 144; https://doi.org/10.3390/antibiotics13020144 - 1 Feb 2024

Cited by 5 | Viewed by 1771

Abstract

Clostridioides difficile is a Gram-positive bacteria that causes nosocomial infections, significantly impacting public health. In the present study, we aimed to describe the clinical characteristics, outcomes, and relationship between antibiotic exposure and Clostridioides difficile infection (CDI) in patients based on reports from two [...] Read more.

Clostridioides difficile is a Gram-positive bacteria that causes nosocomial infections, significantly impacting public health. In the present study, we aimed to describe the clinical characteristics, outcomes, and relationship between antibiotic exposure and Clostridioides difficile infection (CDI) in patients based on reports from two databases. Thus, we conducted a retrospective study of patients diagnosed with CDI from Sibiu County Clinical Emergency Hospital (SCCEH), Romania, followed by a descriptive analysis based on spontaneous reports submitted to the EudraVigilance (EV) database. From 1 January to 31 December 2022, we included 111 hospitalized patients with CDI from SCCEH. Moreover, 249 individual case safety reports (ICSRs) from EVs were analyzed. According to the data collected from SCCEH, CDI was most frequently reported in patients aged 65–85 years (66.7%) and in females (55%). In total, 71.2% of all patients showed positive medical progress. Most cases were reported in the internal medicine (n = 30, 27%), general surgery (n = 26, 23.4%), and infectious disease (n = 22, 19.8%) departments. Patients were most frequently exposed to ceftriaxone (CFT) and meropenem (MER). Also, in the EV database, most CDI-related ADRs were reported for CFT, PIP/TAZ (piperacillin/tazobactam), MER, and CPX (ciprofloxacin). Understanding the association between previous antibiotic exposure and the risk of CDI may help update antibiotic stewardship protocols and reduce the incidence of CDI by lowering exposure to high-risk antibiotics. Full article

(This article belongs to the Special Issue Clostridioides difficile Infection, 2nd Edition)

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9 pages, 434 KiB

Open AccessArticle

Clinical Efficacy of Fidaxomicin and Oral Metronidazole for Treating Clostridioides difficile Infection and the Associated Recurrence Rate: A Retrospective Cohort Study

by Nobuaki Mori, Jun Hirai, Wataru Ohashi, Nobuhiro Asai, Yuichi Shibata and Hiroshige Mikamo

Antibiotics 2023, 12(8), 1323; https://doi.org/10.3390/antibiotics12081323 - 16 Aug 2023

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Abstract

Clostridioides difficile infection (CDI) has significant implications for healthcare economics. Although clinical trials have compared fidaxomicin (FDX) and vancomycin, comparisons of FDX and oral metronidazole (MNZ) are limited. Therefore, we compared the therapeutic effects of FDX and oral MNZ. Patients diagnosed with CDI [...] Read more.

Clostridioides difficile infection (CDI) has significant implications for healthcare economics. Although clinical trials have compared fidaxomicin (FDX) and vancomycin, comparisons of FDX and oral metronidazole (MNZ) are limited. Therefore, we compared the therapeutic effects of FDX and oral MNZ. Patients diagnosed with CDI between January 2015 and March 2023 were enrolled. Those treated with oral MNZ or FDX were selected and retrospectively analyzed. The primary outcome was the global cure rate. Secondary outcomes included factors contributing to the CDI global cure rate; the rate of medication change owing to initial treatment failure; and incidence rates of clinical cure, recurrence, and all-cause mortality within 30 days. Of the 264 enrolled patients, 75 and 30 received initial oral MNZ and FDX treatments, respectively. The corresponding CDI global cure rates were 53.3% and 70% (p = 0.12). In multivariate analysis, FDX was not associated with the global cure rate. In the MNZ group, 18.7% of the patients had to change medications owing to initial treatment failure. The FDX group had a higher clinical cure rate and lower recurrence rate than the MNZ group, although not significant. However, caution is necessary owing to necessary treatment changes due to MNZ failure. Full article

(This article belongs to the Special Issue Clostridioides difficile Infection, 2nd Edition)

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13 pages, 1536 KiB

Open AccessArticle

Real-World Data in Pharmacovigilance Database Provides a New Perspective for Understanding the Risk of Clostridium difficile Infection Associated with Antibacterial Drug Exposure

by Dongxuan Li, Yi Song, Zhanfeng Bai, Xin Xi, Feng Liu, Yang Zhang, Chunmeng Qin, Dan Du, Qian Du and Songqing Liu

Antibiotics 2023, 12(7), 1109; https://doi.org/10.3390/antibiotics12071109 - 27 Jun 2023

Cited by 6 | Viewed by 2060

Abstract

Antibacterial drug exposure (ADE) is a well-known potential risk factor for Clostridium difficile infection (CDI), but it remains controversial which certain antibacterial drugs are associated with the highest risk of CDI occurrence. To summarize CDI risk associated with ADE, we reviewed the CDI [...] Read more.

Antibacterial drug exposure (ADE) is a well-known potential risk factor for Clostridium difficile infection (CDI), but it remains controversial which certain antibacterial drugs are associated with the highest risk of CDI occurrence. To summarize CDI risk associated with ADE, we reviewed the CDI reports related to ADE in the FDA Adverse Event Reporting System database and conducted disproportionality analysis to detect adverse reaction (ADR) signals of CDI for antibacterial drugs. A total of 8063 CDI reports associated with ADE were identified, which involved 73 antibacterial drugs. Metronidazole was the drug with the greatest number of reports, followed by vancomycin, ciprofloxacin, clindamycin and amoxicillin. In disproportionality analysis, metronidazole had the highest positive ADR signal strength, followed by vancomycin, cefpodoxime, ertapenem and clindamycin. Among the 73 antibacterial drugs, 58 showed at least one positive ADR signal, and ceftriaxone was the drug with the highest total number of positive signals. Our study provided a real-world overview of CDI risk for AED from a pharmacovigilance perspective and showed risk characteristics for different antibacterial drugs by integrating its positive–negative signal distribution. Meanwhile, our study showed that the CDI risk of metronidazole and vancomycin may be underestimated, and it deserves further attention and investigation. Full article

(This article belongs to the Special Issue Clostridioides difficile Infection, 2nd Edition)

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7 pages, 520 KiB

Open AccessArticle

Clinical Determinants Predicting Clostridioides difficile Infection among Patients with Chronic Kidney Disease

by Łukasz Lis, Andrzej Konieczny, Michał Sroka, Anna Ciszewska, Kornelia Krakowska, Tomasz Gołębiowski and Zbigniew Hruby

Antibiotics 2022, 11(6), 785; https://doi.org/10.3390/antibiotics11060785 - 8 Jun 2022

Cited by 3 | Viewed by 2107

Abstract

The majority of recently published studies indicate a greater incidence rate and mortality due to Clostridioides difficile infection (CDI) in patients with chronic kidney disease (CKD). The aim of this study was to assess the clinical determinants predicting CDI among hospitalized patients with [...] Read more.

The majority of recently published studies indicate a greater incidence rate and mortality due to Clostridioides difficile infection (CDI) in patients with chronic kidney disease (CKD). The aim of this study was to assess the clinical determinants predicting CDI among hospitalized patients with CKD and refine methods of prevention. We evaluated the medical records of 279 patients treated at a nephrological department with symptoms suggesting CDI, of whom 93 tested positive for CDI. The survey showed that age, poor kidney function, high Padua prediction score (PPS) and patients’ classification of care at admission, treatment with antibiotics, and time of its duration were significantly higher or more frequent among patients who suffered CDI. Whereas BMI, Norton scale (ANSS) and serum albumin concentration were significantly lowered among CDI patients. In a multivariate analysis we proved the stage of CKD and length of antibiotics use increased the risk of CDI, whereas higher serum albumin concentration and ANSS have a protective impact. Full article

(This article belongs to the Special Issue Clostridioides difficile Infection, 2nd Edition)

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16 pages, 3153 KiB

Open AccessArticle

Impact of Subinhibitory Concentrations of Metronidazole on Morphology, Motility, Biofilm Formation and Colonization of Clostridioides difficile

by Tri-Hanh-Dung Doan, Marie-Françoise Bernet-Camard, Sandra Hoÿs, Claire Janoir and Séverine Péchiné

Antibiotics 2022, 11(5), 624; https://doi.org/10.3390/antibiotics11050624 - 5 May 2022

Cited by 7 | Viewed by 2975

Abstract

Clostridioides difficile infection (CDI) is the primary cause of health-care-associated infectious diarrhea. Treatment requires mostly specific antibiotics such as metronidazole (MTZ), vancomycin or fidaxomicin. However, approximately 20% of treated patients experience recurrences. Treatment with MTZ is complicated by reduced susceptibility to this molecule, [...] Read more.

Clostridioides difficile infection (CDI) is the primary cause of health-care-associated infectious diarrhea. Treatment requires mostly specific antibiotics such as metronidazole (MTZ), vancomycin or fidaxomicin. However, approximately 20% of treated patients experience recurrences. Treatment with MTZ is complicated by reduced susceptibility to this molecule, which could result in high failure and recurrence rates. However, the mechanism remains unclear. In this study, we investigated the impact of subinhibitory concentrations of MTZ on morphology, motility, biofilm formation, bacterial adherence to the intestinal Caco-2/TC7 differentiated monolayers, and colonization in monoxenic and conventional mouse models of two C. difficile strains (VPI 10463 and CD17-146), showing different susceptibility profiles to MTZ. Our results revealed that in addition to the inhibition of motility and the downregulation of flagellar genes for both strains, sub-inhibitory concentrations of MTZ induced various in vitro phenotypes for the strain CD17-146 exhibiting a reduced susceptibility to this antibiotic: elongated morphology, enhanced biofilm production and increased adherence to Caco-2/TC7 cells. Weak doses of MTZ induced higher level of colonization in the conventional mouse model and a trend to thicker 3-D structures entrapping bacteria in monoxenic mouse model. Thus, sub-inhibitory concentrations of MTZ can have a wide range of physiological effects on bacteria, which may contribute to their persistence after treatment. Full article

(This article belongs to the Special Issue Clostridioides difficile Infection, 2nd Edition)

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9 pages, 994 KiB

Open AccessArticle

Clostridioides difficile Toxin B PCR Cycle Threshold as a Predictor of Toxin Testing in Stool Specimens from Hospitalized Adults

by Sean Lee, Neha Nanda, Kenichiro Yamaguchi, Yelim Lee and Rosemary C. She

Antibiotics 2022, 11(5), 576; https://doi.org/10.3390/antibiotics11050576 - 26 Apr 2022

Cited by 2 | Viewed by 2126

Abstract

Rapid, accurate detection of Clostridioides difficile toxin may potentially be predicted by toxin B PCR cycle threshold (tcdB C_t). We investigated the validity of this approach in an inpatient adult population. Patients who tested positive by C. difficile PCR (Cepheid [...] Read more.

Rapid, accurate detection of Clostridioides difficile toxin may potentially be predicted by toxin B PCR cycle threshold (tcdB C_t). We investigated the validity of this approach in an inpatient adult population. Patients who tested positive by C. difficile PCR (Cepheid GeneXpert) from December 2016 to October 2020 (n = 368) at a tertiary medical center were included. All stool samples were further tested by rapid glutamate dehydrogenase (GDH)/toxin B EIA and cell cytotoxin neutralization assay (CCNA). Receiver operating characteristic curves were analyzed. The area under the curve for tcdB C_t predicting toxin result by EIA was 0.795 (95% confidence interval (CI) 0.747–0.843) and by CCNA was 0.771 (95% CI 0.720–0.822). The Youden C_t cutoff for CCNA was ≤27.8 cycles (sensitivity 65.0%, specificity 77.2%). For specimens with C_t ≤ 25.0 cycles (n = 115), CCNA toxin was positive in >90%. The negative predictive value of tcdB C_t for CCNA was no greater than 80% regardless of cutoff chosen. In summary, very low C_t values (≤25.0) could have limited value as a rapid indicator of positive toxin status by CCNA in our patient population. A broad distribution of C_t values for toxin-negative and toxin-positive specimens precluded more robust prediction. Additional data are needed before broader application of C_t values from qualitatively designed assays to clinical laboratory reporting. Full article

(This article belongs to the Special Issue Clostridioides difficile Infection, 2nd Edition)

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8 pages, 541 KiB

Open AccessCommunication

The Regulatory Approach for Faecal Microbiota Transplantation as Treatment for Clostridioides difficile Infection in Italy

by Maria Chiara de Stefano, Benedetta Mazzanti, Francesca Vespasiano, Letizia Lombardini and Massimo Cardillo

Antibiotics 2022, 11(4), 480; https://doi.org/10.3390/antibiotics11040480 - 5 Apr 2022

Cited by 7 | Viewed by 2416

Abstract

Faecal microbiota transplantation (FMT) is regarded as an efficacious treatment for recurrent C. difficile infection. Unfortunately, widespread patient access is hindered by regulatory hurdles, which are the primary barriers to incorporating FMT into clinical practice. At the European and International level, there is [...] Read more.

Faecal microbiota transplantation (FMT) is regarded as an efficacious treatment for recurrent C. difficile infection. Unfortunately, widespread patient access is hindered by regulatory hurdles, which are the primary barriers to incorporating FMT into clinical practice. At the European and International level, there is no uniform perspective on FMT classification, and a coordinated effort is desirable to solve this regulatory puzzle. In this communication, we report the regulatory principles and the implementation approach for FMT application in Italy. Our experience suggests that the EU Tissue and Cell Directives are suited to ensure safe and efficient FMT for C. difficile management, especially through extensive high-quality donor selection and full traceability maintenance. Full article

(This article belongs to the Special Issue Clostridioides difficile Infection, 2nd Edition)

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Review

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16 pages, 340 KiB

Open AccessReview

Fidaxomicin for the Treatment of Clostridioides difficile Infection in Adult Patients: An Update on Results from Randomized Controlled Trials

by Daniele Roberto Giacobbe, Antonio Vena, Marco Falcone, Francesco Menichetti and Matteo Bassetti

Antibiotics 2022, 11(10), 1365; https://doi.org/10.3390/antibiotics11101365 - 6 Oct 2022

Cited by 7 | Viewed by 3246

Abstract

In recently updated international guidelines, fidaxomicin is preferentially recommended as first-line treatment over vancomycin both for the first episode of CDI and for rCDI, based on the results of different randomized controlled trials (RCTs). Although noninferiority was the rule in phase-3 RCTs with [...] Read more.

In recently updated international guidelines, fidaxomicin is preferentially recommended as first-line treatment over vancomycin both for the first episode of CDI and for rCDI, based on the results of different randomized controlled trials (RCTs). Although noninferiority was the rule in phase-3 RCTs with regard to the primary endpoint of clinical cure, for shaping these recommendations, particular attention was devoted to the improved global cure and reduced risk of recurrent CDI (rCDI) observed with fidaxomicin compared to vancomycin in RCTs. Overall, while the major driver of choice should remain the global benefit for the patient, consideration of available resources should be necessarily weighed in the balance, since fidaxomicin still remains more costly than vancomycin. Against this background, precisely stratifying risk groups for rCDI will represent a crucial research trajectory of future real-life studies on the treatment of first CDI episodes. In the current narrative review, we discuss the updated evidence from RCTs on the efficacy of fidaxomicin for the treatment of either the first CDI episode or rCDI, which eventually supports its positioning within current treatment algorithms and guidelines. Full article

(This article belongs to the Special Issue Clostridioides difficile Infection, 2nd Edition)

11 pages, 7528 KiB

Open AccessReview

Clostridioides Difficile Enteritis: Case Report and Literature Review

by Artsiom Klimko, Cristian George Tieranu, Ana-Maria Curte, Carmen Monica Preda, Ioana Tieranu, Andrei Ovidiu Olteanu and Elena Mirela Ionescu

Antibiotics 2022, 11(2), 206; https://doi.org/10.3390/antibiotics11020206 - 6 Feb 2022

Cited by 4 | Viewed by 3078

Abstract

Background: Clostridioides Difficile is a well-known pathogen causing diarrhea of various degrees of severity through associated infectious colitis. However, there have been reports of infectious enteritis mainly in patients with ileostomy, causing dehydration through high-output volume; Case presentation: We report the case of [...] Read more.

Background: Clostridioides Difficile is a well-known pathogen causing diarrhea of various degrees of severity through associated infectious colitis. However, there have been reports of infectious enteritis mainly in patients with ileostomy, causing dehydration through high-output volume; Case presentation: We report the case of a 46-year-old male patient, malnourished, who presented with high-output ileostomy following a recent hospitalization where he had suffered an ileo-colic resection with ileal and transverse colon double ostomy, for stricturing Crohn’s disease. Clostridioides Difficile toxin A was identified in the ileal output confirming the diagnosis of acute enteritis. Treatment with oral Vancomycin was initiated with rapid reduction of the ileostomy output volume; Conclusion: We report a case of Clostridioides Difficile enteral infection as a cause for high-output ileostomy, successfully treated with oral Vancomycin. We also review the existing literature data regarding this specific localized infection. Full article

(This article belongs to the Special Issue Clostridioides difficile Infection, 2nd Edition)

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Other

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7 pages, 561 KiB

Open AccessPerspective

Bezlotoxumab in Patients with a Primary Clostridioides difficile Infection: A Literature Review

by Guido Granata, Francesco Schiavone and Giuseppe Pipitone

Antibiotics 2022, 11(11), 1495; https://doi.org/10.3390/antibiotics11111495 - 28 Oct 2022

Cited by 7 | Viewed by 1764

Abstract

Background: Nowadays, one of the main issues in the management of Clostridioides difficile infection (CDI) is the high rate of recurrences (rCDI), causing increased mortality and higher health care costs. Objectives: To assess the available evidence on the use of bezlotoxumab for the [...] Read more.

Background: Nowadays, one of the main issues in the management of Clostridioides difficile infection (CDI) is the high rate of recurrences (rCDI), causing increased mortality and higher health care costs. Objectives: To assess the available evidence on the use of bezlotoxumab for the prevention of rCDI during a first CDI episode. Methods: Published articles on bezlotoxumab during a primary CDI episode were identified through computerized literature searches with the search terms [(bezlotoxumab) AND (CDI) OR (Clostridioides difficile infection)] using PubMed and by reviewing the references of retrieved articles. PubMed was searched until 31 August 2022. Results: Eighty-eight studies were identified as published from December 2014 to June 2022. Five studies were included in this study, one was a phase III clinical trial and four were sub-analyses or extensions of the previous phase III clinical trial. In the phase III clinical trial, the subgroup analysis on the included primary CDI patients showed that 13.5% of patients receiving bezlotoxumab had an rCDI, whilst 20.9% of patients in the placebo group had an rCDI at the twelve weeks follow-up (absolute difference: −7.4). Conclusions: Bezlotoxumab administration during the standard of care antibiotic therapy is effective and safe in reducing the rate of rCDI. Despite its high cost, evidence suggests considering bezlotoxumab in patients with a primary CDI episode. Further studies are needed to assess the benefit in specific subgroups of primary CDI patients and to define the risk factors to guide bezlotoxumab use. Full article

(This article belongs to the Special Issue Clostridioides difficile Infection, 2nd Edition)

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