Diagnostic Guidance for C. difficile Infections.

Diagnosis of Clostridioides difficile infection (CDI) can be challenging. First of all, there has been debate on which of the two reference assays, cell cytotoxicity neutralization assay (CCNA) or toxigenic culture (TC), should be considered the gold standard for CDI detection. Although the CCNA suffers most from suboptimal storage conditions and subsequent toxin degradation, TC is reported to falsely increase CDI detection rates as it cannot differentiate CDI patients from patients asymptomatically colonised by toxigenic C. difficile. Several rapid assays are available for CDI detection and fall into three broad categories: (1) enzyme immunoassays for glutamate dehydrogenase, (2) enzyme immunoassays or single-molecule array assays for toxins A/B and (3) nucleic acid amplification tests detecting toxin genes. All three categories have their own limitations, being suboptimal specificity and/or sensitivity or the inability to discern colonised patients from CDI patients. In light of these limitations, multi-step algorithmic testing has been advocated by international guidelines (IDSA/SHEA and ESCMID) in order to optimize diagnostic accuracy. As a result, a survey performed in 2018-2019 in Europe revealed that most of all hospital sites reported using more than one test to diagnose CDI. CDI incidence rates are also influenced by sample selection criteria, as several studies have shown that if not all unformed stool samples are tested for CDI, many cases may be missed due to an absence of clinical suspicion. Since methods for diagnosing CDI remain imperfect, there has been a growing interest in alternative testing strategies like faecal microbiota biomarkers, immune modulating interleukins, cytokines and imaging methods. At the moment, these alternative methods might play an adjunctive role, but they are not suitable to replace conventional CDI testing strategies.

European Practice for CDI Treatment.

Clostridioides difficile infection (CDI) remains a significant cause of morbidity and mortality worldwide. Historically, two antibiotics (metronidazole and vancomycin) and a recent third (fidaxomicin) have been used for CDI treatment; convincing data are now available showing that metronidazole is the least efficacious agent. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) management guidance for CDI were updated in 2021. This guidance document outlines the treatment options for a variety of CDI clinical scenarios and for non-antimicrobial management (e.g., faecal microbiota transplantation, FMT). One of the main changes is that metronidazole is no longer recommended as first-line CDI treatment. Rather, fidaxomicin is preferred on the basis of reduced recurrence rates with vancomycin as an acceptable alternative. Recommended options for recurrent CDI now include bezlotoxumab as well as FMT.A 2017 survey of 20 European countries highlighted variation internationally in CDI management strategies. A variety of restrictions were in place in 65% countries prior to use of new anti-CDI treatments, including committee/infection specialist approval or economic review/restrictions. This survey was repeated in November 2022 to assess the current landscape of CDI management practices in Europe. Of 64 respondents from 17 countries, national CDI guidelines existed in 14 countries, and 11 have already/plan to incorporate the ESCMID 2021 CDI guidance, though implementation has not been surveyed in 6. Vancomycin is the most commonly used first-line agent for the treatment of CDI (n = 42, 66%), followed by fidaxomicin (n = 30, 47%). Six (9%) respondents use metronidazole as first-line agent for CDI treatment, whereas 22 (34%) only in selected low-risk patient groups. Fidaxomicin is more likely to be used in high-risk patient groups. Availability of anti-CDI therapy influenced prescribing in six respondents (9%). Approval pre-prescription was required before vancomycin (n = 3, 5%), fidaxomicin (n = 10, 6%), bezlotoxumab (n = 11, 17%) and FMT (n = 10, 6%). Implementation of CDI guidelines is rarely audited.Novel anti-CDI agents are being evaluated; it is not yet clear what will be the roles of these agents. The treatment of recurrent CDI is particularly troublesome, and several different live biotherapeutics are being developed, in addition to FMT.

A core-genome multilocus sequence typing scheme for the detection of genetically related Streptococcus pyogenes clusters.

The recently observed increase in invasive Streptococcus pyogenes infections causes concern in Europe. However, conventional molecular typing methods lack discriminatory power to aid investigations of outbreaks caused by S. pyogenes. Therefore, there is an urgent need for high-resolution molecular typing methods to assess genetic relatedness between S. pyogenes isolates. In the current study, we aimed to develop a novel high-resolution core-genome multilocus sequence typing (cgMLST) scheme for S. pyogenes and compared its discriminatory power to conventional molecular typing methods. The cgMLST scheme was designed with the commercial Ridom SeqSphere+ software package. To define a cluster threshold, the scheme was evaluated using publicly available data from nine defined S. pyogenes outbreaks in the United Kingdom. The cgMLST scheme was then applied to 23 isolates from a suspected S. pyogenes outbreak and 117 S. pyogenes surveillance isolates both from the Netherlands. MLST and emm-typing results were used for comparison to cgMLST results. The allelic differences between isolates from defined outbreaks ranged between 6 and 31 for isolates with the same emm-type, resulting in a proposed cluster threshold of <5 allelic differences out of 1,095 target loci. Seven out of twenty-three (30%) isolates from the suspected outbreak had an allelic difference of <2, thereby identifying a potential cluster that could not be linked to other isolates. The proposed cgMLST scheme shows a higher discriminatory ability when compared to conventional typing methods. The rapid and simple analysis workflow allows for extended detection of clusters of potential outbreak isolates and surveillance and may facilitate the sharing of sequencing results between (inter)national laboratories.

Prolonged antibiotic prophylaxis after pancreatoduodenectomy: systematic review and meta-analysis.

BACKGROUND: Previous studies have reported conflicting results of prolonged antibiotic prophylaxis on infectious complications after pancreatoduodenectomy. This study evaluated the effect of prolonged antibiotics on surgical-site infections (SSIs) after pancreatoduodenectomy. METHODS: A systematic review and meta-analysis was undertaken of SSIs in patients with perioperative (within 24 h) versus prolonged antibiotic (over 24 h) prophylaxis after pancreatoduodenectomy. SSIs were classified as organ/space infections or superficial SSI within 30 days after surgery. ORs were calculated using a Mantel-Haenszel fixed-effect model. RESULTS: Ten studies were included in the qualitative analysis, of which 8 reporting on 1170 patients were included in the quantitative analysis. The duration of prolonged antibiotic prophylaxis varied between 2 and 10 days after surgery. Four studies reporting on 782 patients showed comparable organ/space infection rates in patients receiving perioperative and prolonged antibiotics (OR 1.35, 95 per cent c.i. 0.94 to 1.93). However, among patients with preoperative biliary drainage (5 studies reporting on 577 patients), organ/space infection rates were lower with prolonged compared with perioperative antibiotics (OR 2.09, 1.43 to 3.07). Three studies (633 patients) demonstrated comparable superficial SSI rates between patients receiving perioperative versus prolonged prophylaxis (OR 1.54, 0.97 to 2.44), as well as in patients with preoperative biliary drainage in 4 studies reporting on 431 patients (OR 1.60, 0.89 to 2.88). CONCLUSION: Prolonged antibiotic prophylaxis is associated with fewer organ/space infection in patients who undergo preoperative biliary drainage. However, the optimal duration of antibiotic prophylaxis after pancreatoduodenectomy remains to be determined and warrants confirmation in an RCT.

Almost 40 in 100 patients develop an infection after pancreatic surgery. This study collected research that studied the effect of prolonged antibiotics after pancreatic surgery on the number of infections after surgery. Research articles were selected if patients who received antibiotics only during surgery were compared with those who had prolonged antibiotics after surgery. Prolonged antibiotics means antibiotics for longer than 24 h after surgery. Comparing patients who had antibiotics during surgery and those who received prolonged antibiotics after surgery, this study focused on the number of abdominal infections and wound infections. Ten studies were selected, and these studies included 1170 patients in total. The duration of prolonged antibiotics ranged from 2 to 5 days after pancreatic surgery. Four studies (with 782 patients) showed comparable abdominal infections in patients who had antibiotics only during surgery and those who had prolonged antibiotics after surgery (OR 1.35, 95 per cent c.i. 0.94 to 1.93). However, for patients with a stent in the bile duct (5 studies on 577 patients), fewer abdominal infections were seen in patients who had prolonged antibiotics after surgery compared with patients who received antibiotics only during surgery (OR 2.09, 1.43 to 3.07). Three studies (633 patients) showed the same rate of wound infections in patients who had antibiotics only during surgery compared with those who received prolonged antibiotics after operation (OR 1.54, 0.97 to 2.44). The number of wound infections was also the same in patients with a stent in the bile duct (OR 1.60, 0.89 to 2.88). Prolonged antibiotics after pancreatic surgery seem to lower abdominal infections in patients who have a stent placed in the bile duct. However, the best duration of antibiotics is unclear; a decent study is needed.

Prolonged antibiotics after pancreatoduodenectomy reduce abdominal infections in patients with positive bile cultures: a dual-center cohort study.

BACKGROUND: Abdominal infections account for substantial morbidity after pancreatoduodenectomy. Contaminated bile is the presumed main risk factor, and prolonged antibiotic prophylaxis might prevent these complications. This study compared organ/space infection (OSIs) rates in patients receiving perioperative versus prolonged antibiotic prophylaxis after pancreatoduodenectomy. METHODS: Patients undergoing pancreatoduodenectomy in two Dutch centers between 2016 and 2019 were included. Perioperative prophylaxis was compared prolonged prophylaxis (cefuroxime and metronidazole for five days). The primary outcome was an isolated OSI: an abdominal infection without concurrent anastomotic leakage. Odds ratios (OR) were adjusted for surgical approach and pancreatic duct diameter. RESULTS: OSIs occurred in 137 out of 362 patients (37.8%): 93 patients with perioperative and 44 patients with prolonged prophylaxis (42.5% versus 30.8%, P = 0.025). Isolated OSIs occurred in 38 patients (10.5%): 28 patients with perioperative and 10 patients with prolonged prophylaxis (12.8% versus 7.0%, P = 0.079). Bile cultures were obtained in 198 patients (54.7%). Patients with positive bile cultures showed higher isolated OSI rates with perioperative compared to prolonged prophylaxis (18.2% versus 6.6%, OR 5.7, 95% CI: 1.3-23.9). CONCLUSION: Prolonged antibiotics after pancreatoduodenectomy are associated with fewer isolated OSIs in patients with contaminated bile and warrant confirmation in a randomised controlled trial (Clinicaltrials.gov NCT0578431).

Faecal microbiota replacement to eradicate antimicrobial resistant bacteria in the intestinal tract - a systematic review.

PURPOSE OF REVIEW: Antimicrobial resistance is a rising threat to global health and is associated with increased mortality. Intestinal colonisation with multidrug-resistant organisms (MDRO) can precede invasive infection and facilitates spread within communities and hospitals. Novel decolonisation strategies, such as faecal microbiota transplantation (FMT), are being explored. The purpose of this review is to provide an update on how the field of FMT for MDRO decolonisation has developed during the past year and to assess the efficacy of FMT for intestinal MDRO decolonisation. RECENT FINDINGS: Since 2020, seven highly heterogenous, small, nonrandomised cohort studies and five case reports have been published. In line with previous literature, decolonisation rates ranged from 20 to 90% between studies and were slightly higher for carbapenem-resistant Enterobacteriaceae than vancomycin-resistant Enterococcus. Despite moderate decolonisation rates in two studies, a reduction in MDRO bloodstream and urinary tract infections was observed. SUMMARY AND IMPLICATIONS: Although a number of smaller cohort studies show some effect of FMT for MDRO decolonisation, questions remain regarding the true efficacy of FMT (taking spontaneous decolonisation into account), the optimal route of administration, the role of antibiotics pre and post-FMT and the efficacy in different patient populations. The observed decrease in MDRO infections post-FMT warrants further research.

Clinical implications of bile cultures obtained during pancreatoduodenectomy: a cohort study and meta-analysis.

BACKGROUND: The association between intraoperative bile cultures and infectious complications after pancreatoduodenectomy remains unclear. This cohort study and meta-analysis aimed to determine the predictive role of intraoperative bile cultures in abdominal infectious complications after pancreatoduodenectomy. METHODS: The cohort study included 114 patients undergoing pancreatoduodenectomy. Regression analyses were used to estimate the odds to develop an organ space infection (OSI) or isolated OSI (OSIs without a simultaneous complication potentially contaminating the intraabdominal space) after a positive bile culture. A systematic review and meta-analysis was performed on abdominal infectious complications (Mantel-Haenszel fixed-effect model). RESULTS: The positive bile culture rate was 61%, predominantly in patients after preoperative biliary drainage (98% vs 26%, p < 0.001). OSIs occurred in 35 patients (31%) and isolated OSIs in nine patients (8%) and were not associated with positive bile cultures (OSIs: odds ratio = 0.6, 95% CI = 0.25-1.23, isolated OSIs: odds ratio = 0.77, 95% CI = 0.20-3.04). In the meta-analysis, 15 studies reporting on 2047 patients showed no association between positive bile cultures and abdominal infectious complications (pooled odds ratio = 1.3, 95% CI = 0.98-1.65). CONCLUSION: Given the rare occurrence of isolated OSIs and similar odds for patients with positive and negative bile cultures to develop abdominal infectious complications, routine performance of bile cultures should be reconsidered.

Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic.

The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.

Implementing a Clostridium difficile testing algorithm and its effect on isolation duration and treatment initiation: a pre- and post-implementation study.

A proportion of patients suspected of Clostridium difficile infection are unnecessarily placed in contact isolation. By introducing a random-access glutamate dehydrogenase (GDH) test for C. difficile, we aimed to reduce isolation time. In addition, we investigated whether the result of the toxin A&B enzyme immunoassay (EIA) was associated with the decision to initiate antibiotic treatment against C. difficile. This retrospective pre- and post-implementation study was from June 3, 2016, to June 4, 2018. Pre-implementation, only a NAAT was performed. In the post-implementation period, a GDH test was performed; if positive, a toxin A&B EIA followed the same day and subsequently a NAAT. Contact isolation for CDI was discontinued when the GDH test was negative. Median time in isolation was 50.8 h pre-implementation (n = 189) versus 28.0 h post-implementation (n = 119), p < 0.001. The GDH test had a negative predictive value of 98.8% (95% CI 97.9-99.4). In 7/31 (22.6%) patients with a positive NAAT and GDH test and a negative toxin A&B EIA, no antibiotics against C. difficile were initiated versus 4/28 (14.3%) patients who were NAAT, GDH and toxin A&B EIA positive. Introducing a random-access screening test resulted in a significant decrease in patient isolation time. The GDH test had a high negative predictive value making it suitable to determine whether contact isolation can be discontinued. Furthermore, the result of a toxin A&B EIA had limited added value on the percentage of patients in whom antibiotic treatment against C. difficile was initiated.

Hepatosplenic Candidiasis Without Prior Documented Candidemia: An Underrecognized Diagnosis?

INTRODUCTION: Patients with a history of chemotherapy or stem cell transplantation (SCT) and prolonged neutropenia are at risk for hepatic and/or splenic seeding of Candida. In our experience, hepatosplenic candidiasis (HSC) without documented candidemia often remains unrecognized. CASE PRESENTATIONS: We describe three cases of HSC without documented candidemia and the challenges in establishing the diagnosis and adequately treating this condition. The first patient had a history of SCT for treatment of breast cancer and was scheduled for hemihepatectomy for suspected liver metastasis. A second opinion at our institute resulted in the diagnosis of hepatic candidiasis without prior documented candidemia, for which she was treated successfully with fluconazole. The second case demonstrates the limitations of (blood and tissue) cultures and the value of molecular methods to confirm the diagnosis. Case 3 illustrates treatment challenges, with ongoing dissemination and insufficient source control despite months of antifungal therapy, eventually resulting in a splenectomy. LITERATURE REVIEW: A structured literature search was performed for articles describing any patient with HSC and documented blood culture results. Thirty articles were available for extraction of data on candidemia and HSC. Seventy percent (131/187) of patients with HSC did not have documented candidemia. The majority of HSC events were described in hematologic patients, although some cases were described in patients with solid tumors treated with SCT (n = 1) or chemotherapy and a history of leukopenia (n = 2). Current guidelines and practices for diagnosis and treatment are described. CONCLUSION: Clinicians should be aware that HSC most often occurs without documented candidemia. In case of persistent or unexplained fever or lesions in the liver and/or spleen, a history of neutropenia should place disseminated candidiasis in the differential diagnosis. HSC is not limited to hematological patients and may occur in patients with solid tumors treated with bone marrow-suppressing chemotherapy or SCT. In the latter group, HSC as alternative diagnosis for hepatic metastasis should be considered when lesions are not typical for metastasis. This might prevent unnecessary surgery or inappropriate treatment. IMPLICATIONS FOR PRACTICE: Timely diagnosis of hepatosplenic candidiasis (HSC) is challenging, but can prevent further complications and dissemination, and may even prevent unnecessary invasive procedures. Clinicians should realize that HSC often occurs without documented candidemia and that sensitivity of blood cultures for candidemia is limited. HSC is not strictly limited to hematologic patients and might also occur in patients with solid tumors treated with intensive chemotherapy or stem cell transplantation. Increased awareness for HSC in patients with any history of neutropenia is of importance to increase detection and prevent serious sequelae.

Clostridioides difficile in calves, cattle and humans from Dutch dairy farms: Predominance of PCR ribotype 695 (clade 5, sequence type 11) in cattle.

Background: Clostridioides difficile is a leading cause of infectious diarrhea in both humans and livestock. In particular, C. difficile strains belonging to sequence type (ST) 11 are common enteropathogens. The aim of this study was to determine the presence and genetic relatedness of C. difficile types in dairy cattle and calves. Method: Dutch dairy farms were visited between February and December 2021. Feces was collected from adult dairy cattle and calves of two age categories (<4 weeks and 4 weeks-4 months). Fecal samples were also requested from dairy farmers, family members and employees. Fecal samples were cultured in an enrichment medium for 10-15 days and subcultured on solid media for capillary PCR ribotyping and whole genome sequencing. Results: C. difficile was detected on 31 out of 157 (19.8%) dairy farms. The highest prevalence was found in calves <4 weeks (17.5%). None of the 99 human samples collected were positive. Thirty-seven cultured isolates belonged to 11 different PCR ribotypes (RT) of which RT695 (56.8%) and RT078/126 (16.2%) were most abundant. In the database of the Netherlands National Expertise Centre for C. difficile infections (CDI, >10.000 patient isolates), RT695 was found in only two patients with hospital-onset CDI, diagnosed in 2020 and 2021. Sequence analysis of 21C. difficile RT695 from cattle revealed that all isolates belonged to clade 5, ST11 and contained genes encoding toxin A, toxin B and binary toxin. RT695 strains carried antimicrobial resistance genes typically found in clade 5C. difficile. Groups of genetically related RT695 isolates were found between dairy farms, whereas identical strains were only present in individual farms. Conclusions: C. difficile was found in ∼20% of dairy farms with a predominance of the relatively unknown RT695. Isolates of RT695 belonged to the same clade and sequence type as RT078/126, which is recognized as an important zoonotic type.

Dosing and treatment duration of suppressive antimicrobial therapy in orthopedic implant infections: a cohort study.

Introduction: Limited data inform about the optimal dosing and duration of suppressive antimicrobial therapy (SAT) for orthopedic implant infection (OII). We aimed to compare the effectiveness of low-dosage with standard-dosage SAT and evaluate the safety of stopping SAT. Methods: All patients with OII treated with SAT from 2011 to 2022 were retrospectively included. Data were extracted from electronic patient files. Low-dosage SAT was defined as antimicrobial therapy dosed lower than the standard dosage recommended for OII. The association of dosing strategy and other factors with failure-free survival were assessed by Kaplan-Meier and Cox proportional hazard models. Results: One-hundred-and-eight patients were included. The median follow-up time after SAT initiation was 21 months (interquartile range (IQR) 10-42 months). SAT was successful in 74 patients (69 %). Low-dosage SAT ( n = 82 ) was not associated with failure in univariate (hazard ratio (HR) 1.23, 95 % confidence interval (CI) 0.53-2.83) and multivariate analyses (HR 1.24, 95 % CI 0.54-2.90). In 25 patients (23 %), SAT was stopped after a median treatment duration of 26 months. In this group, one patient (4 %) developed a relapse. Conclusions: In this study, low-dosage SAT was as effective as standard dosage SAT. Moreover, stopping SAT after 2 to 3 years may be justified in patients with a good clinical course. These findings warrant further research on optimal dosing and duration of SAT and on the durability of in vivo biofilms.

[Clostridioides difficile infections]. / Clostridioides difficile-infecties in de eerste lijn.

Here, we describe the epidemiology, diagnostics, and treatment of Clostridioides difficile infection (CDI) in the primary health care setting. CDI is traditionally considered as a healthcare associated infection. However, infections with onset in the community represent a large proportion of CDI. Traditional CDI risk factors apply to the population encountered in general practice: age ≥50 years, malignancy or other underlying disease, hospital admission and/or antibiotic treatment in the past 3 months. Notably, about a third has had no recent antibiotic exposure nor has been admitted to a hospital. Based on diagnostic tests requested by the general practitioner, only half of CDI cases will be diagnosed. In this setting, it is advisable to request a diagnostic C. difficile test for patients with persisting or severe diarrhea and negative tests for traditional enteropathogens (Salmonella, Shigella, Yersinia, Campylobacter), also in the absence of traditional risk factors for CDI.

Influence of surface characteristics of implant materials on MRSA biofilm formation and effects of antimicrobial treatment.

Introduction: One of the main causes of treatment failure in bacterial prosthetic joint infections (PJI) is biofilm formation. The topography of the biofilm may be associated with susceptibility to antimicrobial treatment. The aims of this study were to assess differences in topography of biofilms on different implant materials and the correlation thereof with susceptibility to antimicrobial treatment. Methods: Methicillin-resistant Staphylococcus aureus (MRSA) 7-day mature biofilms were generated on disks made from titanium alloys (Ti-6Al-7Nb and Ti-6Al-4V), synthetic polymer and orthopedic bone cement, commonly used in implant surgery. The surface topography of these implant materials and the biofilms cultured on them was assessed using atomic force microscopy. This provided detailed images, as well as average roughness (Ra) and peak-to-valley roughness (Rt) values in nanometers, of the biofilm and the material surfaces. Bacterial counts within biofilms were assessed microbiologically. Antimicrobial treatment of biofilms was performed by 24-h exposure to the combination of rifampicin and ciprofloxacin in concentrations of 1-, 5- and 10-times the minimal bactericidal concentration (MBC). Finally, treatment-induced differences in bacterial loads and their correlation with biofilm surface parameters were assessed. Results: The biofilm surfaces on titanium alloys Ti-6Al-7Nb (Ra = 186 nm) and Ti-6Al-4V (Ra = 270 nm) were less rough than those of biofilms on silicone (Ra = 636 nm). The highest roughness was observed for biofilms on orthopedic bone cement with an Ra of 1,551 nm. Interestingly, the roughness parameters of the titanium alloys themselves were lower than the value for silicone, whereas the surface of the bone cement was the roughest. Treatment with 1- and 5-times the MBC of antibiotics resulted in inter-material differences in colony forming units (CFU) counts, ultimately showing comparable reductions of 2.4-3.0 log CFU/mL at the highest tested concentration. No significant differences in bacterial loads within MRSA biofilms were observed between the various implant materials, upon exposure to increasing concentrations of antibiotics. Discussion: The surface parameters of MRSA biofilms were determined by those of the implant materials on which they were formed. The antibiotic susceptibility of MRSA biofilms on the various tested implant materials did not differ, indicating that the efficacy of antibiotics was not affected by the roughness of the biofilm.

Fecal microbiota transplantation for Parkinson's disease using levodopa - carbidopa intestinal gel percutaneous endoscopic gastro-jejeunal tube.

We report a patient with a 5-year diagnosis of akinetic-rigid Parkinson's disease under treatment with Levodopa-Carbidopa Intestinal Gel therapy through a PEG-J tube due to motor complications, in which, in the context of a clinical study, we successfully and safely administered fecal microbiota transplant through a PEG-J.

How can patients with Clostridioides difficile infection on concomitant antibiotic treatment be best managed?

Antibiotics are modifiable risk factors for Clostridioides difficile infection (CDI), driving pathogenesis via gut microbiome disruption. The management of patients with CDI prescribed concomitant non-CDI antibiotics is problematic and influences CDI outcome and recurrence risk. Though an assessment of the ongoing requirement for concomitant antibiotics is essential, discontinuation is often not possible. Antibiotics for other reasons might also need to be commenced during CDI therapy. Attempts to minimise the number and duration of antibiotics with a change to a low-risk class are recommended. Fidaxomicin might be preferable to vancomycin due to it having less effect on the gut microbiome; however, vancomycin is also acceptable. Metronidazole should be avoided and proton pump inhibitors discontinued. Access to fidaxomicin might be limited; hence, it should be prioritised for patients at high risk of recurrence. There is insufficient evidence to support extending anti-CDI therapy duration and concerns regarding microbiome effect remain. The addition of bezlotoxumab might be considered if multiple additional risk factors for recurrent CDI exist, though the amount of evidence is low. Investigational approaches to reduce the effect of concomitant antibiotics on the gut microbiome could further optimise CDI treatment in the presence of concomitant antibiotic use in the future.

Transmission of Antibiotic-Susceptible Escherichia coli Causing Urinary Tract Infections in a Fecal Microbiota Transplantation Recipient: Consequences for Donor Screening?

Fecal microbiota transplantation (FMT) has been reported to decrease the incidence of recurrent urinary tract infections (UTIs), presumably by restoring microbiome diversity and/or uropathogen competition. We report a 16-year-old female with recurrent UTIs caused by multidrug-resistant Klebsiella pneumoniae, for which frequent intravenous broad-spectrum antibiotic treatment was necessary. The patient was treated with FMT from a well-screened healthy donor without multidrug-resistant bacteria in the feces. After FMT, she developed several UTIs with an antibiotic-susceptible Escherichia coli that could be treated orally. The uropathogenic E. coli could be cultured from donor feces, and whole genome sequencing confirmed donor-to-recipient transmission. Our observation should stimulate discussion on long-term follow-up of all infections after FMT and donor fecal screening for antibiotic-susceptible Enterobacterales.

How to prepare stool banks for an appropriate response to the ongoing COVID-19 pandemic: Experiences in the Netherlands and a retrospective comparative cohort study for faecal microbiota transplantation.

BACKGROUND: Faecal microbiota transplantation (FMT) is an efficacious treatment for patients with recurrent Clostridioides difficile infections (rCDI). Stool banks facilitate FMT by providing screened faecal suspensions from highly selected healthy donors. Due to the ongoing coronavirus disease 2019 (COVID-19) pandemic and the potential risk of SARS coronavirus-2 (SARS-CoV-2) transmission via FMT, many stool banks were forced to temporarily halt and adjust donor activities. GOAL: The evaluation of a strategy to effectively continue stool banking activities during the ongoing COVID-19 pandemic. STUDY: To restart our stool banking activities after an initial halt, we implemented periodic SARS-CoV-2 screening in donor faeces and serum, and frequent donor assessment for COVID-19 related symptoms. FMT donor and recipient data obtained before (2016-2019) and during the COVID-19 pandemic (March 2020-August 2021) were compared to assess stool banking efficacy. RESULTS: Two out of ten donors developed COVID-19. No differences during versus before the COVID-19 pandemic were observed in the number of approved faeces donations (14 vs 22/month, p = 0.06), FMT requests for rCDI (3.9 vs 4.3/month, p = 0.6); rCDI patients eligible for FMT (80.6% vs 73.3%, p = 0.2); rCDI cure rate (90.3% vs 89.2%, p = 0.9); CDI-free survival (p = 0.7); the number of non-rCDI patients treated with FMT (0.5/month vs 0.4/month), and the number of possibly FMT related adverse events (9.5% vs 7.8%, p = 0.7). Two FMTs for rCDI were delayed due to COVID-19. CONCLUSIONS: There is a continued need for FMT treatment of rCDI during the COVID-19 pandemic. Appropriate donor screening and SARS-CoV-2 infection prevention measures can be implemented in existing protocols without increasing the burden for donors, and allow safe, effective and efficient FMT during the ongoing COVID-19 pandemic. Stool banks should evaluate their SARS-CoV-2 donor screening protocols for long-term sustainability and efficacy, and share their experiences to help the utilisation, standardisation and improvement of stool banks worldwide.

Prognostic factors for severe and recurrent Clostridioides difficile infection: a systematic review.

OBJECTIVES: Clostridioides difficile infection (CDI), its subsequent recurrences (rCDIs), and severe CDI (sCDI) provide a significant burden for both patients and the healthcare system. Identifying patients diagnosed with initial CDI who are at increased risk of developing sCDI/rCDI could lead to more cost-effective therapeutic choices. In this systematic review we aimed to identify clinical prognostic factors associated with an increased risk of developing sCDI or rCDI. METHODS: PubMed, Embase, Emcare, Web of Science and COCHRANE Library databases were searched from database inception through March, 2021. The study eligibility criteria were cohort and case-control studies. Participants were patients ≥18 years old diagnosed with CDI, in which clinical or laboratory factors were analysed to predict sCDI/rCDI. Risk of bias was assessed by using the Quality in Prognostic Research (QUIPS) tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool modified for prognostic studies. Study selection was performed by two independent reviewers. Overview tables of prognostic factors were constructed to assess the number of studies and the respective effect direction and statistical significance of an association. RESULTS: 136 studies were included for final analysis. Greater age and the presence of multiple comorbidities were prognostic factors for sCDI. Identified risk factors for rCDI were greater age, healthcare-associated CDI, prior hospitalization, proton pump inhibitors (PPIs) started during or after CDI diagnosis, and previous rCDI. CONCLUSIONS: Prognostic factors for sCDI and rCDI could aid clinicians to make treatment decisions based on risk stratification. We suggest that future studies use standardized definitions for sCDI/rCDI and systematically collect and report the risk factors assessed in this review, to allow for meaningful meta-analysis of risk factors using data of high-quality trials.

How to: prophylactic interventions for prevention of Clostridioides difficile infection.

BACKGROUND: Clostridioides difficile infection (CDI) remains the leading cause of healthcare-associated diarrhoea, despite existing guidelines for infection control measures and antimicrobial stewardship. The high associated health and economic burden of CDI calls for novel strategies to prevent the development and spread of CDI in susceptible patients. OBJECTIVES: We aim to review CDI prophylactic treatment strategies and their implementation in clinical practice. SOURCES: We searched PubMed, Embase, Emcare, Web of Science, and the COCHRANE Library databases to identify prophylactic interventions aimed at prevention of CDI. The search was restricted to articles published in English since 2012. CONTENT: A toxin-based vaccine candidate is currently being investigated in a phase III clinical trial. However, a recent attempt to develop a toxin-based vaccine has failed. Conventional probiotics have not yet proved to be an effective strategy for prevention of CDI. New promising microbiota-based interventions that bind and inactivate concomitantly administered antibiotics, such as ribaxamase and DAV-132, have been developed. Prophylaxis of CDI with C. difficile antibiotics should not be performed routinely and should be considered only for secondary prophylaxis in very selected patients who are at the highest imminent risk for recurrent CDI (R-CDI) after a thorough evaluation. Faecal microbiota transplantation (FMT) has proved to be a very effective treatment for patients with multiple recurrences. Bezlotoxumab provides protection against R-CDI, mainly in patients with primary episodes and a high risk of relapse. IMPLICATIONS: There are no proven effective, evidenced-based prophylaxis options for primary CDI. As for secondary prevention, FMT is considered the option of choice in patients with multiple recurrences. Bezlotoxumab can be added to standard treatment for patients at high risk for R-CDI. The most promising strategies are those aimed at reducing changes in intestinal microbiota and development of a new effective non-toxin-based vaccine.