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Clostridioides difficile Infection
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Clostridioides difficile Infection

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 (15 May 2021) | Viewed by 29347

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Dr. Guido Granata

E-Mail Website
Guest Editor
Clinical and Research Department, National Institute for Infectious Diseases “L. Spallanzani” IRCCS, Rome, Italy
Interests: Clostridioides difficile infection; antimicrobial resistance; antimicrobial treatment; immune response; host-pathogen interaction; human gut microbiota; infection control
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The Gram-positive, anaerobic bacterium Clostridioides difficile (CD) represents the commonest cause of nosocomial diarrhea worldwide and is responsible for increased morbidity, mortality, and prolonged hospital stay. The focus of this Special Issue includes any aspects concerning Clostridioides difficile infection (CDI). Indeed, there is the need for studies to clarify some important aspects of this complex disease.

First, the intestinal burden of CD has a significant impact on its hospital spread. The persistent shedding of CD even after the completion of anti-CDI antimicrobial therapy significantly contributes to CD transmission. Understanding the routes of in-hospital and community CD transmission is crucial to develop specific interventions to reduce the spread of CDI.

A further issue is the definition and validation of antimicrobial stewardship programs on CD prevention, considering that antimicrobial stewardship programs may reduce CDI incidence.

No less important is the high recurrence rate observed with the currently available CDI therapy. The alarming rate of CDI recurrence urges the proposal and the evaluation of innovative therapeutic approaches.

Finally, many advances in our knowledge of CDI pathogenesis and the role of intestinal microbiota have been recently made. Studies on the innate and adaptive immune response towards CD and on the interplay between CD and other microbiota components may further clarify the complex interaction between CD and the host.

Dr. Guido Granata
Guest Editor

Manuscript Submission Information

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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.

Keywords

  • Clostridioides difficile
  • Clostridioides difficile infection recurrence
  • Antimicrobial use
  • Host and Microbiota Interaction

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Published Papers (12 papers)

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Editorial

Jump to: Research, Review

4 pages, 192 KiB  
Editorial
Introduction to the Special Issue on Clostridioides difficile
by Guido Granata and Davide Roberto Donno
Antibiotics 2021, 10(10), 1233; https://doi.org/10.3390/antibiotics10101233 - 11 Oct 2021
Viewed by 1169
Abstract
The Gram-positive, anaerobic bacterium Clostridioides difficile (CD) represents the most common cause of nosocomial diarrhea worldwide and is responsible for increased morbidity and mortality, and prolonged hospital stays [...] Full article
(This article belongs to the Special Issue Clostridioides difficile Infection)

Research

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12 pages, 866 KiB  
Article
High Serum Levels of Toxin A Correlate with Disease Severity in Patients with Clostridioides difficile Infection
by Guido Granata, Davide Mariotti, Paolo Ascenzi, Nicola Petrosillo and Alessandra di Masi
Antibiotics 2021, 10(9), 1093; https://doi.org/10.3390/antibiotics10091093 - 10 Sep 2021
Cited by 4 | Viewed by 1678
Abstract
Cloistridioides difficile (CD) represents a major public healthcare-associated infection causing significant morbidity and mortality. The pathogenic effects of CD are mainly caused by the release of two exotoxins into the intestine: toxin A (TcdA) and toxin B (TcdB). CD infection (CDI) can also [...] Read more.
Cloistridioides difficile (CD) represents a major public healthcare-associated infection causing significant morbidity and mortality. The pathogenic effects of CD are mainly caused by the release of two exotoxins into the intestine: toxin A (TcdA) and toxin B (TcdB). CD infection (CDI) can also cause toxemia, explaining the systemic complications of life-threatening cases. Currently, there is a lack of sensitive assays to detect exotoxins circulating in the blood. Here, we report a new semi-quantitative diagnostic method to measure CD toxins serum levels. The dot-blot assay was modified to separately detect TcdA and TcdB in human serum with a limit of detection at the pg/mL levels. TcdA and TcdB concentrations in the plasma of 35 CDI patients were measured at the time of CDI diagnosis and at the fourth and tenth day after CDI diagnosis and initiation of anti-CDI treatment. TcdA and TcdB levels were compared to those determined in nine healthy blood donors. Toxemia was detected in the plasma of 33 out of the 35 CDI cases. We also assessed the relationship between TcdA serum levels and CDI severity, reporting that at the time of CDI diagnosis the proportion of severe CDI cases with a TcdA serum level > 60 pg/µL was higher than in mild CDI cases (29.4% versus 66.6%, p = 0.04). In conclusion, data reported here demonstrate for the first time that toxemia is much more frequent than expected in CDI patients, and specifically that high serum levels of TcdA correlate with disease severity in patients with CDI. Full article
(This article belongs to the Special Issue Clostridioides difficile Infection)
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10 pages, 1203 KiB  
Article
Diagnostic Methods of Clostridioides difficile Infection and Clostridioides difficile Ribotypes in Studied Sample
by Elena Novakova, Zuzana Stofkova, Vladimira Sadlonova and Lukas Hleba
Antibiotics 2021, 10(9), 1035; https://doi.org/10.3390/antibiotics10091035 - 25 Aug 2021
Cited by 3 | Viewed by 2094
Abstract
Background: Clostridioides (Clostridium) difficile is the most common nosocomial pathogen and antibiotic-related diarrhea in health-care facilities. Over the last few years, there was an increase in the incidence rate of C. difficile infection cases in Slovakia. In this study, the phenotypic [...] Read more.
Background: Clostridioides (Clostridium) difficile is the most common nosocomial pathogen and antibiotic-related diarrhea in health-care facilities. Over the last few years, there was an increase in the incidence rate of C. difficile infection cases in Slovakia. In this study, the phenotypic (toxigenicity, antimicrobial susceptibility) and genotypic (PCR ribotypes, genes for binary toxins) patterns of C. difficile isolates from patients with CDI were analyzed, from July to August 2016, taken from hospitals in the Horne Povazie region of northern Slovakia. The aim of the study was also to identify hypervirulent strains (e.g., the presence of RT027 or RT176). Methods: The retrospective analysis of biological samples suspected of CDI were analyzed by GDH, anaerobic culture, enzyme immunoassay on toxins A/B, multiplex “real-time” PCR and PCR capillary-based electrophoresis ribotyping, and by MALDI TOF MS. Results: C. difficile isolates (n = 44) were identified by PCR ribotyping, which revealed five different ribotypes (RT001, 011, 017, 081, 176). The presence of hypervirulent RT027 was not identified. The C. difficile isolates (RT001, 011, 081, 176) were susceptible to metronidazole and vancomycin. One isolate RT017 had reduced susceptibility to vancomycin. A statistically significant difference between the most prevalent PCR ribotypes, RT001 and RT176, regarding variables such as albumin, CRP, creatinine, the length of hospitalization (p = 0.175), and glomerular filtration (p = 0.05) was not found. Conclusion: The results of PCR capillary-based electrophoresis ribotyping in the studied samples showed a high prevalence of RT176 and 001. Full article
(This article belongs to the Special Issue Clostridioides difficile Infection)
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12 pages, 2092 KiB  
Article
Teicoplanin Suppresses Vegetative Clostridioides difficile and Spore Outgrowth
by Suvash Chandra Ojha, Matthew Phanchana, Phurt Harnvoravongchai, Surang Chankhamhaengdecha, Sombat Singhakaew, Puey Ounjai and Tavan Janvilisri
Antibiotics 2021, 10(8), 984; https://doi.org/10.3390/antibiotics10080984 - 15 Aug 2021
Cited by 5 | Viewed by 2287
Abstract
In recent decades, the incidence of Clostridioides difficile infection (CDI) has remained high in both community and health-care settings. With the increasing rate of treatment failures and its ability to form spores, an alternative treatment for CDI has become a global priority. We [...] Read more.
In recent decades, the incidence of Clostridioides difficile infection (CDI) has remained high in both community and health-care settings. With the increasing rate of treatment failures and its ability to form spores, an alternative treatment for CDI has become a global priority. We used the microdilution assay to determine minimal inhibitory concentrations (MICs) of vancomycin and teicoplanin against 30 distinct C. difficile strains isolated from various host origins. We also examined the effect of drugs on spore germination and outgrowth by following the development of OD600. Finally, we confirmed the spore germination and cell stages by microscopy. We showed that teicoplanin exhibited lower MICs compared to vancomycin in all tested isolates. MICs of teicoplanin ranged from 0.03–0.25 µg/mL, while vancomycin ranged from 0.5–4 µg/mL. Exposure of C. difficile spores to broth supplemented with various concentrations of antimicrobial agents did not affect the initiation of germination, but the outgrowth to vegetative cells was inhibited by all test compounds. This finding was concordant with aberrant vegetative cells after antibiotic treatment observed by light microscopy. This work highlights the efficiency of teicoplanin for treatment of C. difficile through prevention of vegetative cell outgrowth. Full article
(This article belongs to the Special Issue Clostridioides difficile Infection)
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21 pages, 5338 KiB  
Article
Protective Effect of Baicalin against Clostridioides difficile Infection in Mice
by Abraham Joseph Pellissery, Poonam Gopika Vinayamohan, Deepa Ashwarya Kuttappan, Neha Mishra, Breno de Oliveira Fragomeni, Kendra Maas, Shankumar Mooyottu and Kumar Venkitanarayanan
Antibiotics 2021, 10(8), 926; https://doi.org/10.3390/antibiotics10080926 - 30 Jul 2021
Cited by 7 | Viewed by 2161
Abstract
This study investigated the prophylactic and therapeutic efficacies of baicalin (BC), a plant-derived flavone glycoside, in reducing the severity of Clostridioides difficile infection (CDI) in a mouse model. In the prophylactic trial, C57BL/6 mice were provided with BC (0, 11, and 22 mg/L [...] Read more.
This study investigated the prophylactic and therapeutic efficacies of baicalin (BC), a plant-derived flavone glycoside, in reducing the severity of Clostridioides difficile infection (CDI) in a mouse model. In the prophylactic trial, C57BL/6 mice were provided with BC (0, 11, and 22 mg/L in drinking water) from 12 days before C. difficile challenge through the end of the experiment, whereas BC administration started day 1 post challenge in the therapeutic trial. Both challenge and control groups were infected with 106 CFU/mL of hypervirulent C. difficile BAA 1803 spores or sterile PBS, and the clinical and diarrheal scores were recorded for 10 days post challenge. On day 2 post challenge, fecal and tissue samples were collected from mice prophylactically administered with BC for microbiome and histopathologic analysis. Both prophylactic and therapeutic supplementation of BC significantly reduced the severity of colonic lesions and improved CDI clinical progression and outcome compared with control (p < 0.05). Microbiome analysis revealed a significant increase in Gammaproteobacteria and reduction in the abundance of protective microbiota (Firmicutes) in antibiotic-treated and C. difficile-infected mice compared with controls (p < 0.05). However, baicalin supplementation favorably altered the microbiome composition, as revealed by an increased abundance in beneficial bacteria, especially Lachnospiraceae and Akkermansia. Our results warrant follow-up investigations on the use of BC as an adjunct to antibiotic therapy to control gut dysbiosis and reduce C. difficile infection in humans. Full article
(This article belongs to the Special Issue Clostridioides difficile Infection)
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17 pages, 2745 KiB  
Article
Cationic Peptidomimetic Amphiphiles Having a N-Aryl- or N-Naphthyl-1,2,3-Triazole Core Structure Targeting Clostridioides (Clostridium) difficile: Synthesis, Antibacterial Evaluation, and an In Vivo C. difficile Infection Model
by Muni Kumar Mahadari, Sreenu Jennepalli, Andrew J. Tague, Papanin Putsathit, Melanie L. Hutton, Katherine A. Hammer, Daniel R. Knight, Thomas V. Riley, Dena Lyras, Paul A. Keller and Stephen G. Pyne
Antibiotics 2021, 10(8), 913; https://doi.org/10.3390/antibiotics10080913 - 26 Jul 2021
Cited by 5 | Viewed by 2582
Abstract
Clostridioides (also known as Clostridium) difficile is a Gram-positive anaerobic, spore producing bacterial pathogen that causes severe gastrointestinal infection in humans. The current chemotherapeutic options are inadequate, expensive, and limited, and thus inexpensive drug treatments for C. difficile infection (CDI) with improved [...] Read more.
Clostridioides (also known as Clostridium) difficile is a Gram-positive anaerobic, spore producing bacterial pathogen that causes severe gastrointestinal infection in humans. The current chemotherapeutic options are inadequate, expensive, and limited, and thus inexpensive drug treatments for C. difficile infection (CDI) with improved efficacy and specificity are urgently needed. To improve the solubility of our cationic amphiphilic 1,1′-binaphthylpeptidomimetics developed earlier that showed promise in an in vivo murine CDI model we have synthesized related compounds with an N-arytriazole or N-naphthyltriazole moiety instead of the 1,1′-biphenyl or 1,1′-binaphthyl moiety. This modification was made to increase the polarity and thus water solubility of the overall peptidomimetics, while maintaining the aromatic character. The dicationic N-naphthyltriazole derivative 40 was identified as a C. difficile-selective antibacterial with MIC values of 8 µg/mL against C. difficile strains ATCC 700057 and 132 (both ribotype 027). This compound displayed increased water solubility and reduced hemolytic activity (32 µg/mL) in an in vitro hemolysis assay and reduced cytotoxicity (CC50 32 µg/mL against HEK293 cells) relative to lead compound 2. Compound 40 exhibited mild efficacy (with 80% survival observed after 24 h compared to the DMSO control of 40%) in an in vivo murine model of C. difficile infection by reducing the severity and slowing the onset of disease. Full article
(This article belongs to the Special Issue Clostridioides difficile Infection)
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13 pages, 987 KiB  
Article
Nonalcoholic Fatty Liver Disease—A Novel Risk Factor for Recurrent Clostridioides difficile Infection
by Lara Šamadan, Mia Jeličić, Adriana Vince and Neven Papić
Antibiotics 2021, 10(7), 780; https://doi.org/10.3390/antibiotics10070780 - 27 Jun 2021
Cited by 9 | Viewed by 2307
Abstract
Recurrent Clostridioides difficile infections (rCDI) have a substantial impact on healthcare systems, with limited and often expensive therapeutic options. Nonalcoholic fatty liver disease (NAFLD) affects about 25% of the adult population and is associated with metabolic syndrome, changes in gut microbiome and bile [...] Read more.
Recurrent Clostridioides difficile infections (rCDI) have a substantial impact on healthcare systems, with limited and often expensive therapeutic options. Nonalcoholic fatty liver disease (NAFLD) affects about 25% of the adult population and is associated with metabolic syndrome, changes in gut microbiome and bile acids biosynthesis, all possibly related with rCDI. The aim of this study was to determine whether NAFLD is a risk factor associated with rCDI. A retrospective cohort study included patients ≥ 60 years hospitalized with CDI. The cohort was divided into two groups: those who were and were not readmitted with CDI within 3 months of discharge. Of the 329 patients included, 107 patients (32.5%) experienced rCDI. Patients with rCDI were older, had higher Charlson Age–Comorbidity Index (CACI) and were more frequently hospitalized within 3 months. Except for chronic kidney disease and NAFLD, which were more frequent in the rCDI group, there were no differences in other comorbidities, antibiotic classes used and duration of antimicrobial therapy. Multivariable Cox regression analysis showed that age >75 years, NAFLD, CACI >6, chronic kidney disease, statins and immobility were associated with rCDI. In conclusion, our study identified NAFLD as a possible new host-related risk factor associated with rCDI. Full article
(This article belongs to the Special Issue Clostridioides difficile Infection)
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13 pages, 1369 KiB  
Article
Clostridioides difficile Infection among Cirrhotic Patients with Variceal Bleeding
by Mirela Nicoleta Voicu, Florica Popescu, Dan Nicolae Florescu, Ion Rogoveanu, Adina Turcu-Stiolica, Dan Ionut Gheonea, Vlad Florin Iovanescu, Sevastita Iordache, Sergiu Marian Cazacu and Bogdan Silviu Ungureanu
Antibiotics 2021, 10(6), 731; https://doi.org/10.3390/antibiotics10060731 - 17 Jun 2021
Cited by 5 | Viewed by 1909
Abstract
Clostridioides difficile infection (CDI) stands as the leading cause of nosocomial infection with high morbidity and mortality rates, causing a major burden on the healthcare system. Driven by antibiotics, it usually affects older patients with chronic disease or immunosuppressed or oncologic management. Variceal [...] Read more.
Clostridioides difficile infection (CDI) stands as the leading cause of nosocomial infection with high morbidity and mortality rates, causing a major burden on the healthcare system. Driven by antibiotics, it usually affects older patients with chronic disease or immunosuppressed or oncologic management. Variceal bleeding secondary to cirrhosis requires antibiotics to prevent bacterial translocation, and thus patients become susceptible to CDI. We aimed to investigate the risk factors for CDI in cirrhotic patients with variceal bleeding following ceftriaxone and the mortality risk in this patient’s population. We retrospectively screened 367 cirrhotic patients with variceal bleeding, from which 25 patients were confirmed with CDI, from 1 January 2017 to 31 December 2019. We found MELD to be the only multivariate predictor for mortality (odds ratio, OR = 1.281, 95% confidence interval, CI: 0.098–1.643, p = 0.042). A model of four predictors (age, days of admission, Charlson index, Child–Pugh score) was generated (area under the receiver operating characteristics curve, AUC = 0.840, 95% CI: 0.758–0.921, p < 0.0001) to assess the risk of CDI exposure. Determining the probability of getting CDI for cirrhotic patients with variceal bleeding could be a tool for doctors in taking decisions, which could be integrated in sustainable public health programs. Full article
(This article belongs to the Special Issue Clostridioides difficile Infection)
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13 pages, 5260 KiB  
Article
Alteration of Intestinal Microbiome of Clostridioides difficile-Infected Hamsters during the Treatment with Specific Cow Antibodies
by Hans-Jürgen Heidebrecht, Ilias Lagkouvardos, Sandra Reitmeier, Claudia Hengst, Ulrich Kulozik and Michael W. Pfaffl
Antibiotics 2021, 10(6), 724; https://doi.org/10.3390/antibiotics10060724 - 16 Jun 2021
Cited by 2 | Viewed by 2348
Abstract
Clostridioides difficile infection (CDI) often develops after pretreatment with antibiotics, which can lead to damage of the intestinal microbiome. The approach of this study was to use specific polyclonal antibodies isolated from the milk of immunized cows to treat CDI, in contrast to [...] Read more.
Clostridioides difficile infection (CDI) often develops after pretreatment with antibiotics, which can lead to damage of the intestinal microbiome. The approach of this study was to use specific polyclonal antibodies isolated from the milk of immunized cows to treat CDI, in contrast to the standard application of nonspecific antibiotics. To gain a deeper understanding of the role of the microbiome in the treatment of CDI with bovine antibodies, stool and intestinal fluid samples of hamsters were collected in large quantities from various treatments (>400 samples). The results show that the regeneration of the microbiome instantly begins with the start of the antibody treatment, in contrast to the Vancomycin-treated group where the diversity decreased significantly during the treatment duration. All antibody-treated hamsters that survived the initial phase also survived the entire study period. The results also show that the regeneration of the microbiome was not an antibody-induced regeneration, but a natural regeneration that occurred because no microbiota-inactivating substances were administered. In conclusion, the treatment with bovine antibodies is a functional therapy for both the acute treatment and the prevention of recurrence in hamsters and could meet the urgent need for CDI treatment alternatives in humans. Full article
(This article belongs to the Special Issue Clostridioides difficile Infection)
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15 pages, 1384 KiB  
Article
Temporal Variations in Patterns of Clostridioides difficile Strain Diversity and Antibiotic Resistance in Thailand
by Supapit Wongkuna, Tavan Janvilisri, Matthew Phanchana, Phurt Harnvoravongchai, Amornrat Aroonnual, Sathid Aimjongjun, Natamon Malaisri and Surang Chankhamhaengdecha
Antibiotics 2021, 10(6), 714; https://doi.org/10.3390/antibiotics10060714 - 13 Jun 2021
Cited by 5 | Viewed by 2580
Abstract
Clostridioides difficile has been recognized as a life-threatening pathogen that causes enteric diseases, including antibiotic-associated diarrhea and pseudomembranous colitis. The severity of C. difficile infection (CDI) correlates with toxin production and antibiotic resistance of C. difficile. In Thailand, the data addressing ribotypes, toxigenic, [...] Read more.
Clostridioides difficile has been recognized as a life-threatening pathogen that causes enteric diseases, including antibiotic-associated diarrhea and pseudomembranous colitis. The severity of C. difficile infection (CDI) correlates with toxin production and antibiotic resistance of C. difficile. In Thailand, the data addressing ribotypes, toxigenic, and antimicrobial susceptibility profiles of this pathogen are scarce and some of these data sets are limited. In this study, two groups of C. difficile isolates in Thailand, including 50 isolates collected from 2006 to 2009 (THA group) and 26 isolates collected from 2010 to 2012 (THB group), were compared for toxin genes and ribotyping profiles. The production of toxins A and B were determined on the basis of toxin gene profiles. In addition, minimum inhibitory concentration of eight antibiotics were examined for all 76 C. difficile isolates. The isolates of the THA group were categorized into 27 A−B+CDT− (54%) and 23 A-B-CDT- (46%), while the THB isolates were classified into five toxigenic profiles, including six A+B+CDT+ (23%), two A+B+CDT− (8%), five A−B+CDT+ (19%), seven A−B+CDT− (27%), and six A−B−CDT− (23%). By visually comparing them to the references, only five ribotypes were identified among THA isolates, while 15 ribotypes were identified within THB isolates. Ribotype 017 was the most common in both groups. Interestingly, 18 unknown ribotyping patterns were identified. Among eight tcdA-positive isolates, three isolates showed significantly greater levels of toxin A than the reference strain. The levels of toxin B in 3 of 47 tcdB-positive isolates were significantly higher than that of the reference strain. Based on the antimicrobial susceptibility test, metronidazole showed potent efficiency against most isolates in both groups. However, high MIC values of cefoxitin (MICs 256 μg/mL) and chloramphenicol (MICs ≥ 64 μg/mL) were observed with most of the isolates. The other five antibiotics exhibited diverse MIC values among two groups of isolates. This work provides evidence of temporal changes in both C. difficile strains and patterns of antimicrobial resistance in Thailand. Full article
(This article belongs to the Special Issue Clostridioides difficile Infection)
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11 pages, 306 KiB  
Article
Mortality Following Clostridioides difficile Infection in Europe: A Retrospective Multicenter Case-Control Study
by Jacek Czepiel, Marcela Krutova, Assaf Mizrahi, Nagham Khanafer, David A. Enoch, Márta Patyi, Aleksander Deptuła, Antonella Agodi, Xavier Nuvials, Hanna Pituch, Małgorzata Wójcik-Bugajska, Iwona Filipczak-Bryniarska, Bartosz Brzozowski, Marcin Krzanowski, Katarzyna Konturek, Marcin Fedewicz, Mateusz Michalak, Lorra Monpierre, Philippe Vanhems, Theodore Gouliouris, Artur Jurczyszyn, Sarah Goldman-Mazur, Dorota Wultańska, Ed J. Kuijper, Jan Skupień, Grażyna Biesiada and Aleksander Garlickiadd Show full author list remove Hide full author list
Antibiotics 2021, 10(3), 299; https://doi.org/10.3390/antibiotics10030299 - 13 Mar 2021
Cited by 24 | Viewed by 3621
Abstract
We aimed to describe the clinical presentation, treatment, outcome and report on factors associated with mortality over a 90-day period in Clostridioides difficile infection (CDI). Descriptive, univariate, and multivariate regression analyses were performed on data collected in a retrospective case-control study conducted in [...] Read more.
We aimed to describe the clinical presentation, treatment, outcome and report on factors associated with mortality over a 90-day period in Clostridioides difficile infection (CDI). Descriptive, univariate, and multivariate regression analyses were performed on data collected in a retrospective case-control study conducted in nine hospitals from seven European countries. A total of 624 patients were included, of which 415 were deceased (cases) and 209 were still alive 90 days after a CDI diagnosis (controls). The most common antibiotics used previously in both groups were β-lactams; previous exposure to fluoroquinolones was significantly (p = 0.0004) greater in deceased patients. Multivariate logistic regression showed that the factors independently related with death during CDI were older age, inadequate CDI therapy, cachexia, malignancy, Charlson Index, long-term care, elevated white blood cell count (WBC), C-reactive protein (CRP), bacteraemia, complications, and cognitive impairment. In addition, older age, higher levels of WBC, neutrophil, CRP or creatinine, the presence of malignancy, cognitive impairment, and complications were strongly correlated with shortening the time from CDI diagnosis to death. CDI prevention should be primarily focused on hospitalised elderly people receiving antibiotics. WBC, neutrophil count, CRP, creatinine, albumin and lactate levels should be tested in every hospitalised patient treated for CDI to assess the risk of a fatal outcome. Full article
(This article belongs to the Special Issue Clostridioides difficile Infection)

Review

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17 pages, 1152 KiB  
Review
Opportunities for Nanomedicine in Clostridioides difficile Infection
by Pei-Wen Wang, Wei-Ting Lee, Ya-Na Wu and Dar-Bin Shieh
Antibiotics 2021, 10(8), 948; https://doi.org/10.3390/antibiotics10080948 - 5 Aug 2021
Cited by 4 | Viewed by 2931
Abstract
Clostridioides difficile, a spore-forming bacterium, is a nosocomial infectious pathogen which can be found in animals as well. Although various antibiotics and disinfectants were developed, C. difficile infection (CDI) remains a serious health problem. C. difficile spores have complex structures and dormant [...] Read more.
Clostridioides difficile, a spore-forming bacterium, is a nosocomial infectious pathogen which can be found in animals as well. Although various antibiotics and disinfectants were developed, C. difficile infection (CDI) remains a serious health problem. C. difficile spores have complex structures and dormant characteristics that contribute to their resistance to harsh environments, successful transmission and recurrence. C. difficile spores can germinate quickly after being exposed to bile acid and co-germinant in a suitable environment. The vegetative cells produce endospores, and the mature spores are released from the hosts for dissemination of the pathogen. Therefore, concurrent elimination of C. difficile vegetative cells and inhibition of spore germination is essential for effective control of CDI. This review focused on the molecular pathogenesis of CDI and new trends in targeting both spores and vegetative cells of this pathogen, as well as the potential contribution of nanotechnologies for the effective management of CDI. Full article
(This article belongs to the Special Issue Clostridioides difficile Infection)
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