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Keywords = C. diff toxin

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11 pages, 214 KB  
Case Report
Challenges and Strategies in Managing Recurrent Clostridioides difficile Infection in Older Adults
by Imaan Hirji, Divya John, Jeena Jith, Hiro Khoshnaw and Myooran Ganeshananthan
Geriatrics 2025, 10(6), 158; https://doi.org/10.3390/geriatrics10060158 - 2 Dec 2025
Viewed by 1184
Abstract
Background: Clostridioides difficile infections (CDIs) are caused by a Gram-positive, spore-forming bacillus and are defined by more than three episodes of watery diarrhoea per day. CDI is a major cause of morbidity and mortality in older adults, particularly over 65 years. Recurrent CDI [...] Read more.
Background: Clostridioides difficile infections (CDIs) are caused by a Gram-positive, spore-forming bacillus and are defined by more than three episodes of watery diarrhoea per day. CDI is a major cause of morbidity and mortality in older adults, particularly over 65 years. Recurrent CDI leads to higher mortality and prolonged, debilitating illness. Case Presentations: This article presents two patients, aged over 80 years old, who developed recurrent CDI causing complicated and prolonged treatment courses. Patient 1 required an extended course of antibiotics for treatment of discitis and a congruent psoas abscess. Patient 2 developed CDI after multiple short courses of antibiotics for urinary tract infections (UTIs) in the context of multiple comorbidities. Both patients experienced three distinct episodes of CDI and were treated in collaboration with microbiology specialists. Following the third episode, both were successfully treated with oral capsule faecal microbiome transplants (FMTs). Their cases highlight the challenge of balancing systemic antibiotic use against CDI risk. Discussions: These cases underscore known risk factors for recurrent CDI, including advanced age and prolonged antibiotic exposure. Recurrence rates in patients over 65 can reach 58%. The British Society of Gastroenterology and Healthcare Infection Society support the use of FMTs in recurrent cases. Environmental decontamination, including terminal cleaning with sporicidal agents, is critical in reducing reinfection in hospital settings. Conclusions: Recurrent CDI in elderly patients reflects a complex interplay between infection control and managing comorbidities. New guidelines suggest that FMTs can significantly reduce morbidity and mortality. These cases emphasise the need for individualised, multidisciplinary care, adherence to guidelines, and further research to improve safe, effective CDI management in older adults. Full article
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11 pages, 1028 KB  
Article
Potential for Misinterpretation in the Laboratory Diagnosis of Clostridioides difficile Infections
by Alexandra Kalacheva, Metodi Popov, Valeri Velev, Rositsa Stoyanova, Yordanka Mitova-Mineva, Tsvetelina Velikova and Maria Pavlova
Diagnostics 2025, 15(9), 1166; https://doi.org/10.3390/diagnostics15091166 - 3 May 2025
Cited by 1 | Viewed by 1404
Abstract
Background/Objective. Toxin-producing strains of Clostridioides difficile (C. diff) are the most commonly identified cause of healthcare-associated infection in the elderly. Risk factors include advanced age, hospitalization, prior or concomitant systemic antibacterial therapy, chemotherapy, and gastrointestinal surgery. Patients with unspecified and [...] Read more.
Background/Objective. Toxin-producing strains of Clostridioides difficile (C. diff) are the most commonly identified cause of healthcare-associated infection in the elderly. Risk factors include advanced age, hospitalization, prior or concomitant systemic antibacterial therapy, chemotherapy, and gastrointestinal surgery. Patients with unspecified and new-onset diarrhea with ≥3 unformed stools in 24 h are the target population for C. diff infection (CDI) testing. To present data on the risks of laboratory misdiagnosis in managing CDI. Materials. In two general hospitals, we examined 116 clinical stool specimens from hospitalized patients with acute diarrhea suspected of nosocomial or antibiotic-associated diarrhea (AAD) due to C. diff. Enzyme immunoassay (EIA) tests for the detection of C. diff toxins A (cdtA) and B (cdtB) in stool, automated CLIA assay for the detection of C. diff GDH antigen and qualitative determination of cdtA and B in human feces and anaerobic stool culture were applied for CDI laboratory diagnosis. MALDI-TOF (Bruker) was used to identify the presumptive anaerobic bacterial colonies. The following methods were used as confirmatory diagnostics: the LAMP method for the detection of Salmonella spp. and simultaneous detection of C. jejuni and C. coli, an E. coli Typing RT-PCR detection kit (ETEC, EHEC, STEC, EPEC, and EIEC), API 20E and aerobic stool culture methods. Results. A total of 40 toxigenic strains of C. diff were isolated from all 116 tested diarrheal stool samples, of which 38/40 produced toxin B and 2/40 strains were positive for both cdtA and cdtB. Of the stool samples positive for cdtA (6/50) and/or cdtB (44/50) by EIA, 33 were negative for C. diff culture but positive for the following diarrheal agents: Salmonella enterica subsp. arizonae (1/33, LAMP, culture, API 20E); C. jejuni (2/33, LAMP, culture, MALDI TOF); ETEC O142 (1/33), STEC O145 and O138 (2/33, E. coli RT-PCR detection kit, culture); C. perfringens (2/33, anaerobic culture, MALDI TOF); hypermycotic enterotoxigenic K. pneumonia (2/33) and enterotoxigenic P. mirabilis (2/33, culture; PCR encoding LT-toxin). Two of the sixty-six cdtB-positive samples (2/66) showed a similar misdiagnosis when analyzed using the CLIA method. However, the PCR analysis showed that they were cdtB-negative. In contrast, the LAMP method identified a positive result for C. jejuni in one sample, and another was STEC positive (stx1+/stx2+) by RT-PCR. We found an additional discrepancy in the CDI test results: EPEC O86 (RT-PCR eae+) was isolated from a fecal sample positive for GHA enzyme (CLIA) and negative for cdtA and cdtB (CLIA and PCR). However, the culture of C. diff was negative. These findings support the hypothesis that certain human bacterial pathogens that produce enterotoxins other than C. diff, as well as intestinal commensal microorganisms, including Klebsiella sp. and Proteus sp., contribute to false-positive EIA card tests for C. diff toxins A and B, which are the most widely used laboratory tests for CDI. Conclusions. CDI presents a significant challenge to clinical practice in terms of laboratory diagnostic management. It is recommended that toxin-only EIA tests should not be used as the sole diagnostic tool for CDI but should be limited to detecting toxins A and B. Accurate diagnosis of CDI requires a combination of laboratory diagnostic methods on which proper infection management depends. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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12 pages, 1252 KB  
Article
Clostridioides difficile Infections in Children: What Is the Optimal Laboratory Diagnostic Method?
by Mohammed Suleiman, Patrick Tang, Omar Imam, Princess Morales, Diyna Altrmanini, Jill C. Roberts and Andrés Pérez-López
Microorganisms 2024, 12(9), 1785; https://doi.org/10.3390/microorganisms12091785 - 28 Aug 2024
Cited by 2 | Viewed by 3661
Abstract
The diagnosis of Clostridioides difficile infection (CDI) in the pediatric population is complicated by the high prevalence of asymptomatic colonization, particularly in infants. Many laboratory diagnostic methods are available, but there continues to be controversy over the optimal laboratory testing approach to diagnose [...] Read more.
The diagnosis of Clostridioides difficile infection (CDI) in the pediatric population is complicated by the high prevalence of asymptomatic colonization, particularly in infants. Many laboratory diagnostic methods are available, but there continues to be controversy over the optimal laboratory testing approach to diagnose CDI in children. We evaluated commonly used C. difficile diagnostic commercial tests in our pediatric hospital population at Sidra Medicine in Doha, Qatar. Between June and December 2023, 374 consecutive stool samples from pediatric patients aged 0–18 years old were tested using: Techlab C. diff Quik Chek Complete, Cepheid GeneXpert C. difficile, QIAstat-Dx Gastrointestinal Panel, and culture using CHROMagar C. difficile. The results of these tests as standalone methods or in four different testing algorithms were compared to a composite reference method on the basis of turnaround time, ease of use, cost, and performance characteristics including specificity, sensitivity, negative predictive value, and positive predictive value. Our study showed variability in test performance of the different available assays in diagnosing CDI. In our population, a testing algorithm starting with Cepheid GeneXpert C. difficile PCR assay or QIAstat-Dx Gastrointestinal panel as a screening test followed by toxin immunoassay for positive samples using the Techlab C. diff Quik Chek Complete kit showed the best performance (100% specificity and 100% positive predictive value) when combined with clinical review of the patient to assess risk factors for CDI, clinical presentation, and alternative causes of diarrhea. Full article
(This article belongs to the Special Issue Advances in Medical Microbiology)
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12 pages, 840 KB  
Article
The Molecular Epidemiology of Clostridioides difficile Infection in Central India: A Prospective Observational Cohort Study
by Rima Biswas, Nick Pinkham, Seth T. Walk, Qian Wang, Shrikant Ambalkar, Ashish R. Satav, Mark H. Wilcox, Rahul Reghunath, Kiran Chawla, Padmaja A. Shenoy, Amit R. Nayak, Aliabbas A. Husain, Dhananjay V. Raje, Rajpal Singh Kashyap and Tanya M. Monaghan
Microbiol. Res. 2023, 14(3), 1279-1290; https://doi.org/10.3390/microbiolres14030086 - 8 Sep 2023
Cited by 1 | Viewed by 3478
Abstract
This prospective observational cohort study aimed to establish and compare baseline rates of Clostridioides difficile infection (CDI) in community and hospitalized patients in Nagpur and rural Melghat Maharashtra, including adults aged ≥18 years with a diagnosis of diarrhoea as defined as 3 or [...] Read more.
This prospective observational cohort study aimed to establish and compare baseline rates of Clostridioides difficile infection (CDI) in community and hospitalized patients in Nagpur and rural Melghat Maharashtra, including adults aged ≥18 years with a diagnosis of diarrhoea as defined as 3 or more loose stools in a 24 h period. All diarrhoeal samples were tested for CDI using the C. diff Quik Chek Complete enzyme immunoassay. C. difficile-positive stool samples were characterised by toxigenic culture, antimicrobial susceptibility testing and PCR ribotyping. C. difficile testing was performed on 1683 patients with acute diarrhoea. A total of 54 patients (3.21%; 95% CI: 2.42–4.17) tested positive for both the GDH antigen and free toxin. The risk factors for CDI included the presence of co-morbidities, antibiotic usage, and immunosuppression. The detected PCR ribotypes included 053-16, 017, 313, 001, 107, and 216. Our findings show that toxigenic C. difficile is an important but neglected aetiologic agent of infective diarrhoea in Central India. These results underscore the need to enhance the awareness and testing of patients with diarrhoea in India regarding the presence of toxigenic C. difficile, particularly in high-risk individuals with multiple co-morbidities, immunosuppression, and recent or ongoing antibiotic exposure or hospitalization. Full article
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10 pages, 1625 KB  
Article
Detection and Analysis of Clostridioides difficile Spores in a Hospital Environment
by Zofia Maria Kiersnowska, Ewelina Lemiech-Mirowska, Michał Michałkiewicz, Aleksandra Sierocka and Michał Marczak
Int. J. Environ. Res. Public Health 2022, 19(23), 15670; https://doi.org/10.3390/ijerph192315670 - 25 Nov 2022
Cited by 7 | Viewed by 3791
Abstract
Clostridioides difficile, due to its long survival time in a hospital environment, is considered to be one of the most frequent factors in healthcare-associated infections. Patient care requires not only rapid and accurate diagnosis, but also knowledge of individual risk factors for [...] Read more.
Clostridioides difficile, due to its long survival time in a hospital environment, is considered to be one of the most frequent factors in healthcare-associated infections. Patient care requires not only rapid and accurate diagnosis, but also knowledge of individual risk factors for infections, e.g., with C. difficile, in various clinical conditions. The goal of this study was to analyse the degree of contamination of a hospital environment with C. difficile spores. Culturing was performed using C diff Banana BrothTM medium, which enables germination of the spores of these bacteria. Samples were collected from inanimate objects within a hospital environment in a specialist hospital in Poland. The results of the study demonstrated the presence of 18 positive samples of Clostridioides spp. (15.4%). Of these, C. difficile spores were detected in six samples, Clostridioides perfringens in eight samples, Clostridioides sporogenes in two samples and Clostridioides innocuum and Clostridioides baratii in one sample each. Among the six samples of C. difficile, a total of four strains which produce the B toxin were cultured. The binary toxin related to ribotype 027 was not detected in our study. Nosocomial infection risk management is a significant problem, mainly concerning the issues of hygiene maintenance, cleaning policy and quality control, and awareness of infection risk. Full article
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11 pages, 441 KB  
Article
Comparative Evaluation of Three Immunoassays for the Simultaneous Detection of Clostridioides difficile Glutamate Dehydrogenase and Toxin A/B
by Namsu Kim, Seung Yeob Lee, Joonhong Park and Jaehyeon Lee
Microorganisms 2022, 10(5), 947; https://doi.org/10.3390/microorganisms10050947 - 30 Apr 2022
Cited by 4 | Viewed by 3910
Abstract
Background: In the medical laboratory, a step-by-step workflow for Clostridioides difficile infection (CDI) detection using glutamate dehydrogenase (GDH) and toxin A/B assays for initial screening, along with a nucleic acid amplification test (NAAT), has been recommended recently. In this study, we evaluated these [...] Read more.
Background: In the medical laboratory, a step-by-step workflow for Clostridioides difficile infection (CDI) detection using glutamate dehydrogenase (GDH) and toxin A/B assays for initial screening, along with a nucleic acid amplification test (NAAT), has been recommended recently. In this study, we evaluated these three immunoassays for the simultaneous detection of GDH and Clostridioides difficile (CD) toxin A/B. Methods: A total of 304 stool samples were tested for the presence of GDH antigen and CD toxin A/B using VIDAS C. difficile GDH and toxin A/B (CDAB), RIDASCREEN C. difficile GDH and toxin A/B (RIDA), and C. DIFF QUIK CHEK COMPLETE according to the manufacturers’ recommendations. As complementary reference methods for GDH and toxin A/B detection in the three immunoassays, CD cultures using ChromID C. difficile agar and the Xpert C. difficile assay, respectively, were tested. Results: All three GDH assays showed overall substantial agreement with the CD culture. All three toxin A/B assays showed overall moderate agreement with the Xpert C. difficile assay. In comparison with consensus results, VIDAS GDH and QCC GDH showed almost perfect agreement, whereas RIDA GDH showed inferior but substantial agreement. All three toxin A/B assays showed almost perfect agreement. Conclusions: Since the QCC GDH and toxin A/B assay is relatively more sensitive and specific than the other two immunoassays for discriminating toxigenic or non-toxigenic CDI, QCC is very helpful for the simultaneous identification of GDH and CD toxin A/B in the initial step of the two-round workflow for diagnosing CDI. Full article
(This article belongs to the Special Issue Clostridioides difficile Infections)
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13 pages, 1722 KB  
Article
Genetic Adjuvants in Replicating Single-Cycle Adenovirus Vectors Amplify Systemic and Mucosal Immune Responses against HIV-1 Envelope
by William E. Matchett, Goda Baddage Rakitha Malewana, Haley Mudrick, Michael J. Medlyn and Michael A. Barry
Vaccines 2020, 8(1), 64; https://doi.org/10.3390/vaccines8010064 - 2 Feb 2020
Cited by 14 | Viewed by 4636
Abstract
Most infections occur at mucosal surfaces. Providing a barrier of protection at these surfaces may be a useful strategy to combat the earliest events in infection when there are relatively few pathogens to address. The majority of vaccines are delivered systemically by the [...] Read more.
Most infections occur at mucosal surfaces. Providing a barrier of protection at these surfaces may be a useful strategy to combat the earliest events in infection when there are relatively few pathogens to address. The majority of vaccines are delivered systemically by the intramuscular (IM) route. While IM vaccination can drive mucosal immune responses, mucosal immunization at intranasal (IN) or oral sites can lead to better immune responses at mucosal sites of viral entry. In macaques, IN immunization with replicating single-cycle adenovirus (SC-Ads) and protein boosts generated favorable mucosal immune responses. However, there was an apparent “distance effect” in generating mucosal immune responses. IN immunization generated antibodies against HIV envelope (env) nearby in the saliva, but weaker responses in samples collected from the distant vaginal samples. To improve on this, we tested here if SC-Ads expressing genetic adjuvants could be used to amplify antibody responses in distant vaginal samples when they are codelivered with SC-Ads expressing clade C HIV env immunogen. SC-Ads env 1157 was coadministered with SC-Ads expressing 4-1BBL, granulocyte macrophage colony-stimulating factor (GMCSF), IL-21, or Clostridoides difficile (C. diff.) toxin fragments by IN or IM routes. These data show that vaginal antibody responses were markedly amplified after a single immunization by the IN or IM routes, with SC-Ad expressing HIV env if this vaccine is complemented with SC-Ads expressing genetic adjuvants. Furthermore, the site and combination of adjuvants appear to “tune” these antibody responses towards an IgA or IgG isotype bias. Boosting these priming SC-Ad responses with another SC-Ad or with SOSIP native-like env proteins markedly amplifies env antibody levels in vaginal washes. Together, this data may be useful in informing the choice of route of delivery adenovirus and peptide vaccines against HIV-1. Full article
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8 pages, 1094 KB  
Article
Effectiveness of a Two-Step Testing Algorithm for Reliable and Cost-Effective Detection of Clostridium difficile Infection in a Tertiary Care Hospital in Saudi Arabia
by Mohammed Qutub, Prasanth Govindan and Anupama Vattappillil
Med. Sci. 2019, 7(1), 6; https://doi.org/10.3390/medsci7010006 - 8 Jan 2019
Cited by 9 | Viewed by 10904
Abstract
The aim of this study was to evaluate the effectiveness of a two-step algorithm for the detection of Clostridium difficile infection. Setting and Design: A two-step testing algorithm was evaluated for testing stool samples from patients suspected of Clostridium difficile infection (CDI). A [...] Read more.
The aim of this study was to evaluate the effectiveness of a two-step algorithm for the detection of Clostridium difficile infection. Setting and Design: A two-step testing algorithm was evaluated for testing stool samples from patients suspected of Clostridium difficile infection (CDI). A total of 103 stool specimens were tested using the C. diff Quik Chek Complete enzyme immunoassay (EIA) test and the Xpert C. difficile PCR test. A two-step algorithm was implemented, and data from 3518 patient samples tested during a two-year period after implementation were analyzed to evaluate the effectiveness. The sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of the Quik Chek Complete EIA test were calculated using the Xpert C. difficile PCR test as a reference method. The sensitivity, specificity, PPV, and NPV of the Quik Chek Complete EIA test for C. difficile toxin were 46.7%, 100%, 100%, and 91%, respectively. The two-step algorithm, which combined the Quik Chek Complete EIA with Xpert C. difficile PCR, improved the sensitivity and also provided rapid detection. When algorithm-based testing was performed daily, there was a 66% reduction in turnaround time compared to batch testing using a lengthy ELISA procedure. Postimplementation data analysis showed that almost 89% of the samples could be reported immediately by initial screening with Quik Chek Complete EIA. Only 11% of the samples gave discrepant results and required PCR confirmation. According to our results, the two-step algorithm is an effective tool for the rapid and reliable detection of toxigenic C. difficile from stool samples. Full article
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5 pages, 140 KB  
Article
Diagnosis of Clostridium difficile Infection: Comparison of Four Methods on Specimens Collected in Cary-Blair Transport Medium and tcdB PCR on Fresh Versus Frozen Samples
by Noah A. Brown, William D. Lebar, Carol L. Young, Rosemary E. Hankerd and Duane W. Newton
Infect. Dis. Rep. 2011, 3(1), e5; https://doi.org/10.4081/idr.2011.2331 - 5 May 2011
Cited by 17 | Viewed by 1
Abstract
Clostridium difficile infection (CDI) caused by toxigenic strains of C. difficile is primarily a nosocomial infection with increasing prevalence. Stool specimens are typically collected in Cary-Blair transport medium to maximize culture-based detection of common stool pathogens. The goal of this study was to [...] Read more.
Clostridium difficile infection (CDI) caused by toxigenic strains of C. difficile is primarily a nosocomial infection with increasing prevalence. Stool specimens are typically collected in Cary-Blair transport medium to maximize culture-based detection of common stool pathogens. The goal of this study was to establish an analytically accurate and efficient algorithm for the detection of CDI in our patient population using samples collected in Cary-Blair transport medium. In addition, we wished to determine whether the sensitivity and specificity of PCR was affected by freezing samples before testing. Using 357 specimens, we compared four methods: enzyme immunoassay for the antigen glutamate dehydrogenase (Wampole™ C. DIFF CHEK-60 Assay, GDH), toxin A and B enzyme immunoassay (Remel ProSpecT™ C. difficile Toxin A/B Microplate Assay, Toxin EIA), cell culture cytotoxicity neutralization assay (Bartels™ Cytotoxicity Assay, CT), and real-time PCR targeting the toxin B gene (BD GeneOhm™ Cdiff Assay, PCR). The analytic sensitivity and specificity of each as determined using a combined gold standard were as follows: GDH, 100% and 93.2%; Toxin EIA, 82.9% and 82.9%; CT, 100% and 100%; PCR (performed on frozen specimens) 74.3% and 96.6%; respectively. However, the sensitivity and specificity of PCR improved to 100% when performed on 50 fresh stool samples collected in Cary-Blair. While CT remains a sensitive method for the detection of CDI, GDH offers an excellent initial screening method to rule out CDI. While the performance of each assay did not appear to be affected by collection in Cary-Blair medium, PCR performed better using fresh specimens. Full article
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