Healthcare-associated Diarrhea Research Articles

Evaluating the antibacterial, antibiofilm, and anti-toxigenic effects of postbiotics from lactic acid bacteria on Clostridium difficile.

The most common cause of healthcare-associated diarrhea is Clostridium difficile infection (CDI), which causes severe and recurring symptoms. The increase of antibiotic-resistant C. difficile requires alternate treatments. Postbiotics, metabolites produced by probiotics, fight CDI owing to their antibacterial capabilities. This study aims to evaluate the antibacterial, antibiofilm, and anti-toxigenic potential of postbiotics in combating CDI. GC-MS evaluated postbiotics from Bifidobacterium bifidum and Lactobacillus plantarum. Disk diffusion and broth microdilution determined C. difficile antibacterial inhibition zones and MICs. Microtiter plates assessed antibiofilm activity. MTT assay evaluated postbiotics anti-viability on HEK293. ELISA testing postbiotic detoxification of toxins A and B. Postbiotics were examined for tcdA and tcdB genes expression using real-time PCR. The most identified B. bifidum and L. plantarum postbiotic compounds were glycolic acid (7.2%) and butyric acid (13.57%). B. bifidum and L. plantarum displayed 13 and 10 mm inhibition zones and 2.5 and 5 mg/ml MICs against C. difficile. B. bifidum reduced biofilm at 1.25 mg/ml by 49% and L. plantarum by 31%. MTT assay showed both postbiotics had little influence on cell viability, which was over 80%. The detoxification power of postbiotics revealed that B. bifidum decreased toxin A and B production more effectively than L. plantarum, and also their related tcdA and tcdB genes expression reduction were statistically significant (p < 0.05). Postbiotics' ability to inhibit bacterial growth, biofilm disruption, and toxin reduction makes them a promising adjunctive for CDI treatment and a good solution to pathogens' antibiotic resistance.

Mortality Attributable to Clostridioides difficile Infection: The Rising Burden of Disease in European Countries.

Background and Objectives: Clostridioides difficile infection is a major public health issue, being among the main causes of mortality due to healthcare-associated diarrhea. This study aimed to assess the trends in mortality attributable to Clostridioides difficile infections in European countries over a period of 30 years. Materials and Methods: A descriptive epidemiological study was conducted, with the application of an ecological study design, to evaluate the trends in mortality due to Clostridioides difficile infection in the Central, Eastern, and Western European sub-regions from 1990 to 2019. The Global Burden of Disease study database was used. Trends were evaluated with the joinpoint regression analysis. Results: In both sexes, about 76% of all deaths attributable to Clostridioides difficile infections were recorded in the Western European sub-region in 2019. The age-standardized rates of the burden of Clostridioides difficile infection in 2019 were the highest in the Central European sub-region, followed by the Western European sub-region, while the lowest rates were observed in the Eastern European sub-region. A significantly increasing trend in mortality attributable to Clostridioides difficile infection from 1990 to 2019 was recorded both in males (by +2.1% per year) and females (by +2.8% per year). The burden of Clostridioides difficile infection showed increasing trends in most of the European countries, significantly correlating with the country's development, according to the Human Development Index. Conclusions: The rising burden of Clostridioides difficile infection in European countries in the last few decades suggests a need for improving public health measures, with a focus both on the hospital setting and community.

Acute diarrhea in the hospitalized immunocompromised patient: what is new on diagnostic and treatment?

This article aims to provide an intuitive framework for diagnosing and managing healthcare-associated diarrhea (HCAD) in the immunocompromised (IC) host. Our understanding of diarrhea in hospitalized IC patients has significantly evolved. However, the challenge lies in distinguishing between these patients' numerous causes of diarrhea. The incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels has led to a paradigm shift in our approach to diarrhea. However, using these panels judiciously is of utmost importance, as their misuse can lead to over-testing, overtreatment, and increased hospital costs. We propose a stepwise diagnostic algorithm that ensures diagnostic stewardship, optimal patient care, and resource utilization. Diarrhea is a common complication in hospitalized IC patients and is associated with significant morbidity and rare mortality. The advent of new diagnostics, such as GI multiplex PCR panels, holds promise in facilitating the detection of recognized pathogens and may allow for improved outcomes using pathogen-targeted therapy.

Healthcare-associated Diarrhea due to Clostridioides difficile in Patients Attending a Tertiary Care Teaching Hospital of North India.

Healthcare-associated diarrhea (HCAD) is diarrhea that develops at least after 3 days of hospitalization, with the most common infectious cause being Clostridioides difficile. Over the last decade, there has been a remarkable growth in the frequency and severity of C. difficile infection (CDI), making it one of the most prevalent healthcare-associated infections. This study aimed to analyze the prevalence and risk factors associated with CDI. A total of 107 patients with clinical suspicion of having HCAD were included in this study. Enzyme-linked fluorescent assay (ELFA) technique-based glutamate dehydrogenase (GDH) and toxin A/B assay were used as per the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) for diagnosing CDI. The details about associated comorbidities were retrieved from the hospital information system records. The presence of risk factors was noted. Risk factors associated with CDI were looked for. Out of the 107 stool samples received in the microbiology laboratory from patients with suspected HCAD eight (7.6%) samples were positive for CDI. The most frequent comorbidity observed in these patients was renal illness (acute or chronic kidney disease). In this study, a total of 7/8 cases were on multiple antibiotics most common being carbapenem. The 6-year prevalence of CDI observed in this study was found to be 7.6% risk factors, associated with CDI were kidney disease, diabetes mellitus, malignancy, and exposure to broad-spectrum antibiotics. Raj N, Agarwal J, Singh V, et al. Healthcare-associated Diarrhea due to Clostridioides difficile in Patients Attending a Tertiary Care Teaching Hospital of North India. Euroasian J Hepato-Gastroenterol 2024;14(1):60-64.

Genomic and phenotypic studies among Clostridioides difficile isolates show a high prevalence of clade 2 and great diversity in clinical isolates from Mexican adults and children with healthcare-associated diarrhea.

Clostridioides difficile is a toxin-producing bacterial pathogen recognized as the most common cause of diarrhea acquired primarily in healthcare settings. This bacterial species is diverse; its global population has been divided into five different clades using multilocus sequence typing, and strains may express different toxin subtypes that may be related to the clades and, importantly, to the severity and progression of disease. Genotyping of children strains differed from adults suggesting toxins might present a reduced toxicity. We studied extensively cytotoxicity, expression of toxins, whole genome phylogeny, and toxin typing in clinical C. difficile isolates. Most isolates presented a tcdA+/ tcdB+/cdt+ pattern, with high diversity in cytotoxicity and clade 2/ST1 was the most prevalent. However, they all had the same TcdA2/TcdB2 toxin subtype. Advances in genomics and bioinformatics tools offer the opportunity to understand the virulence of C. difficile better and find markers for better clinical use.

The Impact of Gastroesophageal Disease on Clostridium difficile Infection Hospitalization: A Nationwide Analysis From the United States.

Background Enterocolitis due to Clostridium difficile infection (CDI) is one of the most common infectious causes of healthcare-associated diarrhea and a significant cause of morbidity and mortality among hospitalized patients. Gastroesophageal reflux disease (GERD) is notable for its high prevalence, variety of clinical presentations, and underrecognized morbidity. It is widely treated with acid suppression, both with over-the-counter and prescription medications. There are no studies evaluating the impact of GERD on CDI hospitalization. In this study, we aimed to analyze the influence of concomitant GERD on patients hospitalized for CDI enterocolitis. Methodology This was a retrospective, observational study where we extracted data from 2016 to 2020 from the National Inpatient Sample database. We included all patients hospitalized with a primary discharge diagnosis of CDI with or without a secondary diagnosis of GERD. We compared the demographics, comorbidities, and in-hospital outcomes between these two groups. Results This study identified 239,603 hospitalizations with a discharge diagnosis of CDI. Of these, 67,000 (28%) had a concurrent diagnosis of GERD. Patients with GERD had a higher prevalence of hypertension (41% vs. 35.5%, p < 0.01), hyperlipidemia (50% vs. 36.5%, p < 0.01), obesity (13.7% vs. 10.5%, p < 0.01), coronary artery disease (24.4% vs. 19.6%, p < 0.01), and chronic kidney disease (20.7% vs. 19.2%, p < 0.01). Notably, inpatient mortality was lower in CDI hospitalizations with GERD (0.66% vs. 1.46%, p < 0.01). The total hospital charge was reduced in the CDI with GERD group in comparison to the CDI without GERD group (39,599 vs. 43,589, p < 0.01). The length of hospital stay was similar between the two groups (5.3 vs. 5.4 days, p = 0.07). Regarding complications, CDI hospitalizations with GERD demonstrated lower rates of hypovolemic shock (0.5% vs. 0.73%, p = 0.06), septic shock (0.6% vs. 1.05%, p < 0.01), acute kidney injury (1.48% vs. 2.04%, p < 0.01), intestinal perforation (0.008% vs. 0.16%, p = 0.03), and lactic acidosis (0.008% vs. 0.16%, p = 0.03). Conversely, CDI patients with GERD had a higher rate of ileus (2.66% vs. 2.16%, p < 0.01). Conclusions Patients with CDI and concurrent GERD exhibited favorable in-hospital outcomes in terms of complication rates, mortality, and total hospital charges. Further research is required to comprehensively explore and validate these findings.

A retrospective budget impact analysis of fidaxomicin treatment for Clostridioides difficile infections (CDI) in Germany

ABSTRACT Background Clostridioides difficile is the most common cause of healthcare-associated diarrhea. Research suggests that treating C. difficile infections (CDI) with fidaxomicin (FDX) is more effective than vancomycin (VAN), with potential cost savings. The objective was to calculate the budget impact of FDX treatment compared to VAN from a German payer perspective. Research design and methods The analysis used real-world data of patients discharged from University Hospital Cologne between Jan-01–2018 and Dec-31–2019. We identified recurrent and non-recurrent CDI cases and calculated direct treatment costs based on G-DRG flat rates. To calculate average costs per treatment and the budget impact, recurrence probabilities for VAN and FDX were taken from published evidence (28-day and 90-day scenarios). Results Totally, 475 cases were analyzed, thereof 421 non-recurrent, causing mean costs of €32,901 per case (95% CI: 27.752–38.050). Thirty-two patients experienced a recurrence within 28 days, yielding mean costs of €10,952 (95% CI: 5.627–16.277) for their additional hospital stay. The resulting budget impact was €1,303 (95% CI: 670–1.937) in favor of FDX, ranging from €148.34 to €2,190.30 in scenario analyses. Conclusion The analysis indicates FDX treatment can lead to cost savings compared to VAN. Future research should focus on specific patient groups, such as refractory CDI patients.

Comparison of rectal swabs and fecal samples for the detection of Clostridioides difficile infections with a new in-house PCR assay.

Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea, resulting in high morbidity, mortality, and economic burden. In clinical laboratories, CDI testing is currently performed on stool samples collected from patients with diarrhea. However, the diagnosis of CDI can be delayed by the time required to collect stool samples. Barriers to sample collection could be overcome by using a rectal swab instead of a stool sample. Our study showed that CDI can be identified rapidly and reliably by a new PCR assay developed in our laboratory on both stool and rectal swab specimens. The use of PCR tests on rectal swabs could reduce the time for the detection of CDI and improve the management of this infection. It should also provide a useful alternative for infection-control practitioners to better control the spread of C. difficile.

In vitro Activity of Dalbavancin and Fourteen Other Antimicrobial Agents against Toxigenic Clostridioides difficile Clinical Isolates in a Greek Tertiary-Care Hospital

Objective: Clostridioides difficile is a major cause of healthcare-associated diarrhea worldwide. For years, metronidazole and vancomycin were considered the standard treatment for C. difficile infection. However, they are increasingly being associated with treatment failure and recurrence. In this study, we investigated the in vitro activity of dalbavancin and fourteen other antimicrobials against 155 toxigenic C. difficile isolates originating from patients with C. difficile-associated diarrhea. Materials and Methods: Antimicrobial susceptibility was evaluated by the MIC Test Strip, and the results were interpreted using both the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. Results: C. difficile isolates were fully susceptible to metronidazole, vancomycin, amoxicillin/clavulanate, piperacillin/tazobactam, and tigecycline. All isolates were dalbavancin susceptible by the CLSI breakpoint (≤0.25 μg/mL) compared with 97.4% susceptibility by the EUCAST breakpoint (≤0.125 μg/mL). Dalbavancin demonstrated significantly lower MIC50 and MIC90 values compared to vancomycin (0.047 vs. 0.38 and 0.125 vs. 0.5, respectively, p 0.001). Resistance rates to penicillin, ampicillin, cefoxitin, imipenem, meropenem, clindamycin, moxifloxacin, chloramphenicol, and tetracycline were 20%, 14.2%, 100%, 75.5%, 0.6%, 51%, 36.1%, 3.2%, and 14.8%, respectively. Multidrug-resistant phenotypes were detected among 41.3% of the isolates. Conclusion: Dalbavancin exhibited potent activity against the isolates tested. As C. difficile is an important healthcare-associated pathogen, continued surveillance is required to monitor for development of resistance.

Identification of Clostridioides difficile mutants with increased daptomycin resistance.

C. difficile is the leading cause of healthcare-associated diarrhea and is a threat to public health due to the risk of recurrent infections. Understanding biosynthesis of the atypical cell envelope of C. difficile may provide insight into novel drug targets to selectively inhibit C. difficile. Here, we identified mutations that increased daptomycin resistance and allowed us to better understand phospholipid synthesis, cell envelope biogenesis, and stress response in C. difficile.

Genomic surveillance of Clostridioides difficile transmission and virulence in a healthcare setting.

Clostridioides difficile infection remains a leading cause of hospital-associated diarrhea, despite increased antibiotic stewardship and transmission prevention strategies. This suggests a changing genomic landscape of C. difficile. Our study provides insight into the nature of prevalent C. difficile strains in a hospital setting and transmission patterns among carriers. Longitudinal sampling of surfaces and patient stool revealed that both toxigenic and nontoxigenic strains of C. difficile clade 1 dominate these two wards. Moreover, quantification of transmission in carriers of these clade 1 isolates underscores the need to revisit infection prevention measures in this patient group. We identified unique genetic signatures associated with virulence in this clade. Our data highlight the complexities of preventing transmission of this pathogen in a hospital setting and the need to investigate the mechanisms of in vivo persistence and virulence of prevalent lineages in the host gut microbiome.

Clostridioides difficile Infection: Diagnosis and Treatment Challenges.

Clostridioides difficile is the most important cause of healthcare-associated diarrhea in the United States. The high incidence and recurrence rates of C. difficile infection (CDI), associated with high morbidity and mortality, pose a public health challenge. Although antibiotics targeting C. difficile bacteria are the first treatment choice, antibiotics also disrupt the indigenous gut flora and, therefore, create an environment that is favorable for recurrent CDI. The challenge of treating CDI is further exacerbated by the rise of antibiotic-resistant strains of C. difficile, placing it among the top five most urgent antibiotic resistance threats in the USA. The evolution of antibiotic resistance in C. difficile involves the acquisition of new resistance mechanisms, which can be shared among various bacterial species and different C. difficile strains within clinical and community settings. This review provides a summary of commonly used diagnostic tests and antibiotic treatment strategies for CDI. In addition, it discusses antibiotic treatment and its resistance mechanisms. This review aims to enhance our current understanding and pinpoint knowledge gaps in antimicrobial resistance mechanisms in C. difficile, with an emphasis on CDI therapies.

Using whole genome sequencing to characterize Clostridioides difficile isolates at a tertiary center in Melbourne, Australia.

Clostridioides difficile infection (CDI) is the commonest cause of healthcare-associated diarrhea and undergoes standardized surveillance and mandatory reporting in most Australian states and territories. Historically attributed to nosocomial spread, local and international whole genome sequencing (WGS) data suggest varied sources of acquisition. This study describes C. difficile genotypes isolated at a tertiary center in Melbourne, Australia, their likely source of acquisition, and common risk factors. Retrospective observational study. The Royal Melbourne Hospital (RMH), a 570-bed tertiary center in Victoria, Australia. Short-read whole genome sequencing was performed on 75 out of 137 C. difficile isolates obtained from 1/5/2021 to 28/2/2022 and compared to previous data from 8/11/2015 to 1/11/2016. Existing data from infection control surveillance and electronic medical records were used for epidemiological and risk factor analysis. Eighty-five (62.1%) of the 137 cases were defined as healthcare-associated from epidemiological data. On genome sequencing, 33 different multi-locus sequence type (MLST) subtypes were identified, with changes in population structure compared to the 2015-16 period. Risk factors for CDI were present in 130 (94.9%) cases, including 108 (78.8%) on antibiotics, 86 (62.8%) on acid suppression therapy, and 25 (18.2) on chemotherapy. In both study periods, most C. difficile isolates were not closely related, suggesting varied sources of acquisition and that spread of C. difficile within the hospital was unlikely. Current infection control precautions may therefore warrant review. Underlying risk factors for CDI were common and may contribute to the proportion of healthcare-associated infections in the absence of proven hospital transmission.

Clostridiumdifficile infection in pediatric patients (Review).

Clostridium difficile (C. difficile) infection (CDI) is the most common cause of healthcare-associated diarrhea and among adults, the worldwide incidence rate of the infection is increasing. There is a small amount of data in the literature for pediatric patients, but most indicate an increasing trend. C. difficile is a constituent of the normal microbiota; however, under specific conditions that cause a disruption of the normal bacterial flora, colonization of C. difficile and the released toxins that cause inflammation and mucosal damage occurs. Risk factors for CDI at any age include hospitalization, exposure to antibiotics, administration of proton pump inhibitors, invasive mechanical ventilation, immunosuppression and presence of associated comorbidities. Clinical manifestations range from asymptomatic colonization to fulminant disease characterized by toxic megacolon, intestinal perforation and, rarely, death. The aim of the present review was to outline the features of CDI in pediatric patients.

Clostridioides difficile infection in neurosurgical patients in a national centre over 10 years: less common but associated with longer hospital stays.

Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated (HA) diarrhoea, contributing to patient morbidity and prolonged length-of-stay (LOS). We retrospectively assessed CDI over a decade in a national neurosurgical centre, with a multi-disciplinary approach to CDI surveillance and antimicrobial stewardship, by comparing CDI patients with other patient groups. Data on CDI in neurosurgical inpatients between January 2012 and December 2021 were collated. Disease-specific variables were compared to other inpatients with CDI. Rates per 10,000 bed days used were calculated. Patient-specific differences were compared with neurosurgical patients without CDI. CDI rates by patient group were explored using odds ratio (OR) and χ2 analyses. Negative binomial regression was used to investigate CDI rates over time. Of 50 neurosurgical patients with CDI, all were HA; the average age was 53 years (standard deviation (SD) 16.3 years), 49 were first-episode CDI, and three had severe CDI. The majority (76.7%) had received recent antimicrobials. Compared with non-neurosurgical CDI patients, neurosurgical CDI rates differed significantly (1.9 versus 3.6 per 10,000 bed days used, p < 0.05), neurosurgical patients were younger (p ≤ 0.01), C. difficile testing was more likely to be requested by neurosurgeons (OR 2.4; p ≤ 0.01), and the proportion of severe CDI was higher (6% versus 2%, OR 3.0, p = 0.07, confidence interval (CI) 0.54 to 11.3). Within the neurosurgical cohort, CDI patients had an average LOS four times that of other patients (CI 15.2 to 35.1; p < 0.01) and were older (53.5 versus 47.8 years, CI 0.1 to 11 years; p < 0.05). Only one CDI outbreak was linked to neurosurgical patients. CDI in neurosurgery patients differed from the wider hospital, with greater awareness of CDI testing. Longer LOS impacted bed utilisation with limited capacity. Robust surveillance supports proactive antimicrobial stewardship programmes in this vulnerable population.

Impact of the COVID-19 pandemic on Clostridioides difficile infection in a tertiary healthcare institution in Belgium

ABSTRACT Objectives Clostridioides difficile infection (CDI) causes the greatest number of healthcare-associated infectious diarrhoea. CDIs are transmitted by direct and indirect patient-to-patient contact and risk increases with the use of antibiotics. Since early 2020, the COVID-19 pandemic has affected healthcare systems in many ways including substantial changes in hygiene behaviour. The aim of this study was to assess whether CDI incidence differed during the COVID-19 pandemic compared to a year before. Methods All tests for suspected CDI cases were recorded for a hospital in Brussels, Belgium. The percentage of CDI-positive results and incidences (total and healthcare-associated (HA)-CDI)) for years 2019, 2020, 2021, and 2022 were calculated. Antibiotic consumption was analysed for years 2019 and 2020. Results Since the COVID-19 pandemic struck, a significant reduction of up to 39% was observed in the number of Clostridioides difficile stool tests in our hospital. A significant decrease in the percentage of positive tests and a 50% decrease in the incidence of CDI (total and HA-CDI) was found for 2020 compared with 2019 and confirmed for years 2021 and 2022. The decrease in CDI incidence was mostly marked in haematology, nephrology, and gastroenterology units. No significant change in the use of antibiotics was found. Conclusion The global decrease in CDI incidence observed in our hospital was not associated with a change in the use of antibiotics. The control measures implemented to prevent COVID-19 transmission may explain a reduction in CDI incidence. An underdiagnosis of CDI cannot be excluded.

Role of probiotics in preventing Clostridioides difficile infection in older adults: an integrative review.

Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea. This infection can particularly affect older adults, the most susceptible to CDI. Currently, the standard therapeutic measure is antibiotic therapy, which in turn increases the risk of recurrence of the infection by its collateral damage to the patient's microbiota. Probiotics are live microorganisms capable of maintaining balance in the intestinal microbiota. This study aims to perform an integrative review of the protective benefit of probiotics in CDI and diarrhea associated with C. difficile. The PubMed, Scopus, and Web of Science databases, the 10-year time cutoff, and the Prism Flow diagram were used for data collection. We observed no consensus among the studies; however, three of the seven evaluated studies demonstrated that the use of probiotics in older adults could contribute to reducing the incidence of hospital-onset CDI. We also found that the studies evaluated a wide variety of microorganisms, particularly Saccharomyces boulardii, associated with beneficial effects. More research is needed to understand the successful use of probiotics in the prevention of CDI in hospitalized older adults receiving antibiotics.

Recurrent Clostridioides difficile Infection: Current Clinical Management and Microbiome-Based Therapies.

Clostridioides difficileis one of the most important causes of healthcare-associated diarrhea. The high incidence and recurrence rates ofC. difficile infection, as well as its associated morbidity and mortality, are great concerns. The most common complication of C. difficile infection is recurrence, with rates of 20-30% after a primary infection and 60% after three or more episodes. Medical management of recurrent C. difficile infection involves a choice of therapy that is different from the antibiotic used in the primary episode. Patients with recurrent C. difficile infection also benefit from fecal microbiota transplantation or standardized microbiome restoration therapies (approved or experimental) to restore eubiosis. In contrast to antibiotics, microbiome restoration therapies restore a normal gut flora and eliminateC. difficilecolonization and infection. Fecal microbiota transplantation in recurrent C. difficile infection has demonstrated higher success rates than vancomycin, fidaxomicin, or placebo. Fecal microbiota transplantation has traditionally been considered safe, with the most common adverse reactions being abdominal discomfort,and diarrhea, and rare serious adverse events. Significant heterogeneity and a lack of standardization regarding the process of preparation, and administration of fecal microbiota transplantation remain a major pitfall. Standardized microbiome-based therapies provide a promising alternative. In the ECOSPOR III trial of SER-109, an oral formulation of bacterial spores, a significant reduction in the recurrence rate (12%) was observed compared with placebo (40%). In the phase III PUNCH CD3 trial, RBX2660 also demonstrated high efficacy rates of 70.6% versus 57.5%. Both these agents are now US Food and Drug Administration approved for recurrent C. difficile infection. Other standardized microbiome-based therapies currently in the pipeline are VE303, RBX7455, and MET-2. Antibiotic neutralization strategies, vaccines, passive monoclonal antibodies, and drug repurposing are other therapeutic strategies being explored to treat C. difficile infection.

The influence of exposure to various concentrations of five antimicrobial agents on intracellular cytotoxin B production in &lt;i&gt;Clostridioides difficile&lt;/i&gt;

Background: Clostridioides difficile is an important cause of healthcare-associated diarrhea. Several anti- microbial agents are known to promote C. difficile infection (CDI). The impact of various concentrations of ampicillin (AMP), cefotaxime (CTX), clindamycin (CC), metronidazole (MTZ) and vancomycin (VAN) on intra-cellular cytotoxin B production was investigated in this study.&#x0D; Methodology: Six clinical strains of C. difficile were grown at minimum inhibitory concentration (MIC) and sub-MIC concentrations of these antibiotics. Inoculum standardization was performed by Miles and Misra method. Intracellular toxin B production was detected using Vero cell cytotoxicity assay in sonicated cultures on days 1, 2, 3, 4, 5 and 7 days of incubation.&#x0D; Results: There was a heterogeneous relationship between antibiotic exposure and the intra-cellular toxin production by the toxigenic strains. Clinical strains of C. difficile when exposed to MIC and sub-inhibitory concentrations of certain antibiotics produced high cytotoxin levels. All toxigenic isolates produced increased levels of cell-bound cytotoxin after exposure to antibiotics but there was no consistent pattern and the response to different doses varied considerably. Metronidazole was the most potent inducer of cell-bound cytotoxin followed by cefotaxime and clindamycin. Vancomycin induced the least amount of cytotoxin activity.&#x0D; Conclusion: The effects of sub-inhibitory concentration of antibiotic that predispose to C. difficile infection may partially suppress the normal gut flora, allowing colonization and growth of C. difficile, and may affect the level of toxin produced.

A decade of Clostridioides difficile infection: a constant challenge to maintain the status quo

Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated (HA) diarrhoea. We retrospectively investigated data from a comprehensive, multidisciplinary C. difficile surveillance programme focusing on hospitalised patients in a tertiary Irish hospital over ten years.