Clostridioides difficile is a leading cause of healthcare-associated infections globally with proton pump inhibitor (PPI) use as important modifiable risk factor. This study aimed to systematically synthesise global evidence on the dose-response relationship of PPI usage and the Clostridioides difficile infection (CDI) risk and to identify potential safe thresholds of PPI usage regarding CDI.

PubMed, Embase, Web of Science, and Cochrane Library were searched for longitudinal studies regarding PPIs and CDI. Aggregated data were included in two separate two-stage random-effects dose-response meta-analyses regarding Defined Daily Dose (DDD) and PPI therapy duration. Pooled adjusted relative risks (RRs) with 95% confidence intervals compared to non-users of PPIs were estimated.

Overall, 15 observational cohort and case-control studies were included with 7 studies (n=483,821) in the meta-analysis per DDD and 7 studies (n=516,441) per PPI therapy duration. The risk of bias was modest. Pooled dose-response estimates suggest linear trends with a RR of 1.05 (95% CI 0.89,1.23) per 10 mg DDD and of 1.02 (95% CI 1.00,1.05) per day of PPI therapy. Substantial residual heterogeneity was detected in both analyses (I2=91.4% per DDD and I2=99.4% per therapy duration), but inferring potential sources was limited.

Our results indicate a possible increase in the risk of CDI with increasing dose and duration of PPI therapy. Underlying mechanisms and dosage thresholds for a clinically relevant risk increase remain unclear.

The primary concern with prolonged hospitalization following birth is the risk of acquiring hospital-acquired infections (HAIs) caused by opportunistic bacteria, which can alter the early establishment of gut microbiota.

To assess the association between postpartum hospital length of stay (LOS) and the composition of gut microbiota at 3 and 12 months of age according to birth mode.

In total, 1313 Canadian infants from the CHILD Cohort Study were involved in this study. Prolonged LOS was defined as ≥2 days following vaginal delivery (VD) and ≥3 days following caesarean section (CS). The gut microbiota of infants was characterized by Illumina 16S rRNA sequencing of faecal samples at 3-4 months and 12 months of age.

Following prolonged LOS, VD infants with no exposure to intrapartum antibiotics had a higher abundance of bacteria known to cause HAIs in their gut, including Enterococcus spp. at 3 and 12 months, Citrobacter spp. at 3 months, and Clostridioides difficile at 12 months. Abundance of Enterococcus spp. or Citrobacter spp. at 3 months significantly mediated the association between LOS and low abundance of Bacteroidaceae, or higher Enterococcaeae/Bacteriodaceae or Enterobacterales/Bacteroidaceae abundance ratios at 12 months of age in VD infants without intrapartum antibiotic exposure. HAI-causing Enterobacterales were also more abundant in later infancy in infants with prolonged LOS following CS. In the absence of exclusive breastfeeding at 3 months or any breastfeeding at 12 months, Porphyromonadaceae (of Bacteroidota) were depleted in CS infants with prolonged LOS.

Prolonged hospital stay after birth is associated with infant gut dysbiosis.

Clostridium difficile infection (CDI) has been increasing due to the effect of recurrent hospitalizations. The use of antibiotics has been shown to alter the gut microbiome and lead to CDIs. The treatment is limited to three major antibiotics; however, the incidence of recurrent CDIs has been increasing and drug resistance is a major concern. This aspect is a growing concern in modern medicine especially in the elderly population, critical care patients, and immunocompromised individuals who are at high risk of developing CDIs. Clostridium difficile can lead to various complications including septic shock and fulminant colitis that could prove to be lethal in these patients. Newer modalities of treatment have been developed including bezlotoxumab, a monoclonal antibody and fecal microbiota transplant. There have been studies showing asymptomatic carriers and drug resistance posing a major threat to the healthcare system. Newer treatment options are being studied to treat and prevent CDIs. This review will provide an insight into the current treatment modalities, prevention and newer modalities of treatment and challenges faced in the treatment of CDIs.

Clostridioides difficile infection (CDI) is a well-known cause of hospital-acquired infectious diarrhea in developed countries, though it has not been a top priority in the healthcare policies of developing countries. In the last decade, several studies have reported a wide range of CDI rates between 1.3% and 96% in developing nations, raising the concern that this could represent a healthcare threat for these nations. This review defines developing countries as those with a human development index (HDI) below 0.8. We aim to report the available literature on CDI epidemiology, diagnostics, management, and prevention in developing countries. We identify limitations for CDI diagnosis and management, such as limited access to CDI tests and unavailable oral vancomycin formulation, and identify opportunities to enhance CDI care, such as increased molecular test capabilities and creative solutions for CDI. We also discuss infection prevention strategies, including antimicrobial stewardship programs and opportunities emerging from the COVID-19 pandemic, which could impact CDI care.

SUMMARYClostridioides difficile infection (CDI) is one of the major issues in nosocomial infections. This bacterium is constantly evolving and poses complex challenges for clinicians, often encountered in real-life scenarios. In the face of CDI, we are increasingly equipped with new therapeutic strategies, such as monoclonal antibodies and live biotherapeutic products, which need to be thoroughly understood to fully harness their benefits. Moreover, interesting options are currently under study for the future, including bacteriophages, vaccines, and antibiotic inhibitors. Surveillance and prevention strategies continue to play a pivotal role in limiting the spread of the infection. In this review, we aim to provide the reader with a comprehensive overview of epidemiological aspects, predisposing factors, clinical manifestations, diagnostic tools, and current and future prophylactic and therapeutic options for C. difficile infection.

Clostridioides Difficile Infection (CDI) is a serious antibiotic related complication that has been reported among children undergoing treatment of appendicitis. CDI likelihood amongst different empiric antibiotic regimens for appendicitis remains unclear but likely has important implications for antibiotic stewardship.

A retrospective cohort study of the Pediatric Health Information System was used to examine patients ages 1 through 18 who received operative management of acute appendicitis. Common empiric antibiotic regimens 1) Ceftriaxone & Metronidazole (CM) 2) Piperacillin & Tazobactam (PT) and 3) Cefoxitin were compared. Study outcomes were CDI within 28 days post-appendectomy and 30-day post-appendectomy percutaneous drainage procedures. Subset analyses were repeated to only include hospitals that standardized empiric antibiotic choice.

Of 105,911 patients, 220 (0.21 %) developed CDI. CDI was more common in patients that received CM (CM 0.29 % vs PT 0.15 % vs Cefoxitin 0.18 %; P < 0.01). On adjusted analysis, PT was associated with a lower likelihood of CDI (OR, 0.48; 95%CI, 0.31-0.74) compared to CM which was consistent in hospitals with standardized antibiotic choice. Exposure to more unique antibiotic regimens (OR, 1.70; 95 % CI, 1.50-1.93) and higher total antibiotic days (OR, 1.17; 95 % CI 1.13-1.21) were associated with an increased likelihood of CDI. There was no significant difference in the likelihood of post-appendectomy percutaneous drainage between antibiotic regimens.

CDI is rare following appendectomy for pediatric appendicitis. While PT was associated with statistically lower rates of CDI compared to CM, antibiotic stewardship efforts to avoid mixed regimens and decrease overall antibiotic exposure warrant exploration.

Level III.

Clostridioides difficile is the most common causative agent of antibiotic-associated diarrhea. This spore forming, obligate anaerobic, gram-positive bacillus is becoming responsible for an increasing number of infections worldwide, both in community and in hospital settings, whose severity can vary widely from an asymptomatic infection to a lethal disease. While discontinuation of antimicrobial agents and antibiotic treatment of the infection remain the cornerstone of therapy, more recent fecal microbiota transplantation has also been valid as a therapy. The use of probiotics, especially Saccharomyces boulardii CNCM I-745 have become valid forms of prevention therapy. Although there are studies in adults with microbiota-targeted new generation therapies and Clostridium difficile vaccines, there are no data in the paediatric age group yet.

This study aimed to determine the predictors of hospital-onset Clostridioides difficile infection (CDI) in pediatric patients with antibiotic-associated diarrhea (AAD) and to develop a predictive scoring system to identify at-risk patients.

This retrospective case-control study included patients aged ≥2-18 years with AAD who underwent C. difficile polymerase chain reaction testing >3 days after hospital admission. Patients with hospital-onset CDI were selected as cases and matched with the control patients without CDI. Univariate and multivariate logistic regressions were used to determine predictors of CDI and to construct a prediction score for the outcomes of interest.

Sixty-five patients with hospital-onset CDI and 130 controls were enrolled. Independent predictors for CDI identified and combined into the prediction score included abdominal pain (adjusted odds ratio [95% confidence interval]: 7.940 [3.254-19.374]), hospitalization for ≥14 days before the onset of diarrhea (3.441 [1.034-11.454]), antibiotic use for ≥10 days before the onset of diarrhea (6.775 [1.882-24.388]), receipt of meropenem (4.001 [1.098-14.577]) and clindamycin (14.842 [4.496-49.000]). The area under the receiver operating characteristic curve for this score was 0.883.

The presented scoring system can be easily applied by clinicians at the bedside to decide which patients with AAD are likely to have CDI.

Clostridioides difficile (C. difficile) is the major pathogen causing antibiotic-associated diarrhea. There are a variety of symptoms associated with C. difficile infection (CDI) in adults, including self-limiting diarrhea, pseudomembranous colitis, toxic megacolon, septic shock, and even death from the infection. However, the infant's intestine appears to be completely resistant to the effects of C. difficile toxins A and B with rare development of clinical symptoms.

In this study, we reported a 1-month-old girl with CDI who was born with neonatal hypoglycemia and necrotizing enterocolitis. Her symptom of diarrhea occurred after extensive use of broad-spectrum antibiotics during hospitalization and was accompanied by elevated white blood cell, platelet, and C-reactive protein levels, and repeated routine stool examinations were abnormal. She was recovered by norvancomycin (an analogue of vancomycin) and probiotic treatment. The results of 16 S rRNA gene sequencing also demonstrated the recovery of intestinal microbiota with the enrichment of Firmicutes and Lactobacillus.

Based on the literature review and this case report, clinicians should also pay attention to diarrhea caused by C. difficile in infants and young children. More strong evidence is needed to explain the true prevalence of CDI in this population and to better understand the C. difficile-associated diarrhea in infants.

Clostridioides difficile infections (CDIs) have decreased in the past years, but since 2021, some hospitals have reported an increase in CDI rates. CDI remains a global concern and has been identified as an urgent threat to healthcare. Although multiple treatment options are available, prevention strategies are more limited. As CDI is an opportunistic infection that arises after the normally protective microbiome has been disrupted, preventive measures aimed at restoring the microbiome have been tested. Our aim is to update the present knowledge on these various preventive strategies published in the past five years (2018-2023) to guide clinicians and healthcare systems on how to best prevent CDI. A literature search was conducted using databases (PubMed, Google Scholar, and clinicaltrials.gov) for phase 2-3 clinical trials for the primary or secondary prevention of CDI and microbiome and probiotics. As the main factor for Clostridium difficile infections is the disruption of the normally protective intestinal microbiome, strategies aimed at restoring the microbiome seem most rational. Some strains of probiotics, the use of fecal microbial therapy, and live biotherapeutic products offer promise to fill this niche; although, more large randomized controlled trials are needed that document the shifts in the microbiome population.