Effect of peripartum Clostridioides difficile infection on pregnancy and neonatal outcomes: an observational study.

Background: The incidence of Clostridioides difficile infection (CDI) in peripartum women is rising, but limited data on its effect on maternal and neonatal outcomes are available. Objective: To study the effect of peripartum CDI on pregnancy and neonatal outcomes. Design: Retrospective cohort study. Methods: Patients with peripartum CDI 12 weeks before pregnancy through 6 weeks postpartum (January 1996-February 2018) were matched with controls (peripartum women without CDI) 1:1 by age, year of delivery, and prior pregnancies. McNemar's test and conditional logistic regression were used to analyze the effect of CDI on pregnancy and neonatal outcomes (complications, mode of delivery). p < 0.05 was considered statistically significant. Results: Overall, 101 cases and 100 controls (1997-2018) were included; median age 27 (range, 20-41) years. Timing of CDI was as follows: pre-pregnancy: 15.8% (n = 16), during pregnancy: 51.5% (n = 52), and postpartum: 32.7% (n = 33). The commonest risk factor was outpatient/emergency room visits. Pregnancy and neonatal outcomes were analyzed for 67 matched pairs with CDI before or during pregnancy. Cases had higher odds of cesarean delivery (p = 0.02) and lower odds of Group B Streptococcus (GBS) infection/colonization (p = 0.03). Odds of cesarean delivery remained high after controlling for labor arrest disorders [odds ratio (OR): 17.23 (95% confidence interval (CI), 2.19-543.19; p = 0.004)]; odds of GBS remained low after controlling for antibiotic use (OR: 0.25, 95% CI, 0.04-0.99; p = 0.049). Neonatal outcomes were similar in cases and controls. CDI treatment did not affect treatment-related or delivery outcomes. Conclusion: Peripartum CDI was associated with higher odds of cesarean delivery and lower odds of GBS infections. Larger studies exploring the effect of CDI on pregnancy and neonatal outcomes are needed.

Declining rates of opioid/acetaminophen combination product overdose: 2011-2020.

BACKGROUND: During the opioid epidemic, misuse of acetaminophen-opioid products resulted in supratherapeutic acetaminophen ingestions and cases of hepatotoxicity. In 2014, the US Food and Drug Administration (FDA) limited the amount of acetaminophen in combination products to 325 mg, and the US Drug Enforcement Administration (DEA) changed hydrocodone/acetaminophen from schedule III to schedule II. This study assessed whether these federal mandates were associated with changes in acetaminophen-opioid supratherapeutic ingestions. METHODS: We identified emergency department encounters at our institution of patients with a detectable acetaminophen concentration and manually reviewed these charts. RESULTS: We found a decline in acetaminophen-opioid supratherapeutic ingestions after 2014. A downtrend in hydrocodone/acetaminophen ingestions accompanied a relative increase in codeine/acetaminophen ingestions from 2015 onwards. CONCLUSION: This experience at one large safety net hospital suggests a beneficial impact of the FDA ruling in reducing likely unintentional acetaminophen supratherapeutic ingestions, carrying a risk of hepatotoxicity, in the setting of intentional opioid ingestions.

What Should I Eat? Dietary Recommendations for Patients with Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic disorder thought to be caused by enteric inflammation in a genetically susceptible host. Although the pathogenesis of IBD is largely unknown, it is widely accepted that dietary components play an important role. Human and animal-based studies have explored the role of various dietary components such as meat, artificial sweeteners and food additives in causing enteric inflammation. Several diets have also been studied in patients with IBD, specifically their role in the induction or maintenance of remission. The most well-studied of these include exclusive enteral nutrition and specific carbohydrate diet. A diet low in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols), typically prescribed for patients with irritable bowel syndrome, has also been studied in a specific subgroup of patients with IBD. In this review, we describe the current evidence on how various dietary components can induce enteric and colonic inflammation, and the clinical-epidemiological evidence exploring their role in predisposing to or protecting against the development of IBD. We also discuss several special diets and how they affect clinical outcomes in IBD patients. Based on the available evidence, we provide guidance for patients and clinicians managing IBD regarding the best practice in dietary modifications.

Postinfection Irritable Bowel Syndrome Following Clostridioides difficile Infection: A Systematic-review and Meta-analysis.

BACKGROUND: Postinfection irritable bowel syndrome (PI-IBS) affects ~14% patients after acute bacterial enterocolitis. AIM: The aim of this study was to conduct a systematic review and meta-analysis to find the prevalence of PI-IBS following Clostridioides difficile infection (CDI). METHODS: We systematically searched Medline, Embase, and Web of Science from inception through January 20, 2020 for cohort studies assessing PI-IBS following CDI. Primary outcome was pooled prevalence calculated using inverse variance heterogeneity model [MetaXL (v. 5.3)]. A priori subgroup analyses were done [by irritable bowel syndrome (IBS) diagnostic criteria-Rome vs. others, time of IBS diagnosis-<6 or >6 mo, exclusion or inclusion of pre-existing IBS and CDI treatment-antibiotic with fecal microbiota transplantation vs. antibiotic only]. Heterogeneity was considered substantial if I2>50%. RESULTS: From 2007 to 2019, 15 studies were included (10 prospective, 5 retrospective; 9 full-text, 6 abstracts). Data from 1218 patients were included in the quantitative analysis. Risk of bias was low in 7, medium in 4 and high in 4 studies. Pooled prevalence of PI-IBS was 21.1% (95% confidence interval, 8.2%-35.7%), I2=96%. Common PI-IBS subtypes were diarrhea-predominant in 46.3% (50) patients, and mixed in 33.3% (36) patients. Subgroup analyses by IBS diagnostic criteria, time of IBS diagnosis or CDI treatment did not significantly change the primary outcome (all P>0.05), nor decrease heterogeneity. Funnel plot analysis revealed publication bias. CONCLUSIONS: Over 20% of patients develop PI-IBS after CDI. Factors such as diagnostic criteria for IBS and CDI treatment did not affect prevalence, though small numbers limit the confidence in these conclusions. Larger, well conducted studies are needed to study PI-IBS in CDI.

Kinetics of polymerase chain reaction positivity in patients with Clostridioides difficile infection.

BACKGROUND: Polymerase chain reaction (PCR) is a sensitive test for diagnosing Clostridioides difficile infection (CDI) and could remain positive following resolution of CDI. The kinetics of PCR positivity following antibiotics for CDI is unknown. We studied this and whether it predicted CDI recurrence. METHODS: Adults with CDI from October 2009 to May 2017 were included. Serial stool samples within 60 days of treatment were collected. Recurrent CDI was defined as diarrhea after interim symptom resolution with positive stool PCR within 56 or 90 days of treatment completion. Contingency table analysis was used to assess the risk of recurrence. RESULTS: Fifty patients were included [median age: 51 (range = 20-86) years, 66% women]. Treatment given was metronidazole, 50% (25); vancomycin, 44% (22); both, 4% (2); and fidaxomicin, 2% (1). Median duration of treatment for all 50 patients was 14 (range = 8-60) days. The median duration of treatment in patients who got prolonged therapy (>14 days) (n = 10) was 47 (range = 18-60) days. Median time to negative PCR was 9 (95% CI, 7-14) days from treatment initiation, which did not differ by antibiotics given (p = 0.5). A positive PCR during or after treatment was associated with a higher risk of recurrence at 56 days (p = 0.02) and at 90 days (p = 0.009). CONCLUSION: The median time to negative PCR in CDI was 9 days from treatment initiation. The PCR positivity during or after treatment may be useful for recurrence prediction; larger studies are needed to validate these results.

Clinical features and outcomes of COVID-19 in older adults: a systematic review and meta-analysis.

BACKGROUND: Few studies have focused on exploring the clinical characteristics and outcomes of COVID-19 in older patients. We conducted this systematic review and meta-analysis to have a better understanding of the clinical characteristics of older COVID-19 patients. METHODS: A systematic search of PubMed and Scopus was performed from December 2019 to May 3rd, 2020. Observational studies including older adults (age ≥ 60 years) with COVID-19 infection and reporting clinical characteristics or outcome were included. Primary outcome was assessing weighted pooled prevalence (WPP) of severity and outcomes. Secondary outcomes were clinical features including comorbidities and need of respiratory support. RESULT: Forty-six studies with 13,624 older patients were included. Severe infection was seen in 51% (95% CI- 36-65%, I2-95%) patients while 22% (95% CI- 16-28%, I2-88%) were critically ill. Overall, 11% (95% CI- 5-21%, I2-98%) patients died. The common comorbidities were hypertension (48, 95% CI- 36-60% I2-92%), diabetes mellitus (22, 95% CI- 13-32%, I2-86%) and cardiovascular disease (19, 95% CI - 11-28%, I2-85%). Common symptoms were fever (83, 95% CI- 66-97%, I2-91%), cough (60, 95% CI- 50-70%, I2-71%) and dyspnoea (42, 95% CI- 19-67%, I2-94%). Overall, 84% (95% CI- 60-100%, I2-81%) required oxygen support and 21% (95% CI- 0-49%, I2-91%) required mechanical ventilation. Majority of studies had medium to high risk of bias and overall quality of evidence was low for all outcomes. CONCLUSION: Approximately half of older patients with COVID-19 have severe infection, one in five are critically ill and one in ten die. More high-quality evidence is needed to study outcomes in this vulnerable patient population and factors affecting these outcomes.

Long-term Safety of Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.

BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridioides difficile infection (CDI), with emerging data on intermediate and long-term safety. METHODS: A prospective survey-based study was conducted (September 2012-June 2018) in patients undergoing FMT for recurrent CDI. Data on demographics and comorbidities were abstracted from medical records. Patients were contacted at 1 week, 1 month, 6 months, 1 year (short-term), and ≥2 years post-FMT (long-term). Symptoms and new medical diagnoses were recorded at each time point. Data were weighted to account for survey nonresponse bias. Multivariate logistic regression models for adverse events were built using age (per 10-year increment), sex, time of survey, and comorbidities. P < .05 was considered statistically significant. RESULTS: Overall, 609 patients underwent FMT; median age was 56 years (range, 18-94), 64.8% were women, 22.8% had inflammatory bowel disease (IBD). At short-term follow-up (n = 609), >60% of patients had diarrhea and 19%-33% had constipation. At 1 year, 9.5% reported additional CDI episodes. On multivariable analysis, patients with IBD, dialysis-dependent kidney disease, and multiple FMTs had higher risk of diarrhea; risk of constipation was higher in women and lower in IBD (all P < .05). For long-term follow-up (n = 447), median time of follow-up was 3.7 years (range, 2.0-6.8). Overall, 73 new diagnoses were reported: 13% gastrointestinal, 10% weight gain, 11.8% new infections (all deemed unrelated to FMT). Median time to infections was 29 months (range, 0-73) post-FMT. CONCLUSION: FMT appears safe with low risk of transmission of infections. Several new diagnoses were reported, which should be explored in future studies.

Durability of Response to Fecal Microbiota Transplantation After Exposure to Risk Factors for Recurrence in Patients With Clostridioides difficile Infection.

BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective for preventing recurrent Clostridioides difficile infection (CDI). Durability (no recurrence despite additional risk factor exposure) of FMT protection is largely unknown. We studied the durability of FMT in patients with recurrent CDI. METHODS: We conducted a retrospective study of adults undergoing FMT for recurrent CDI. Data collected included demographics, CDI risk factors (comorbidities, healthcare exposure, non-CDI antibiotic use, acid suppressant medications), and future CDI episodes. Durable response to FMT was defined as lack of CDI episodes within 1 year post-FMT despite risk factor exposure. RESULTS: Overall, 460 patients were included (median age, 57 years [18-94]; 65.2% female). Comorbidities included chronic liver disease, 12.8% (n = 59); cancer, 11.7% (n = 54); chronic kidney disease, 3.9% (n = 18); and inflammatory bowel disease, 21.9% (n = 101). Overall, 31.3% (n = 144) received antibiotics, 21.7% (n = 100) received acid suppressants, and 76.8% (n = 350) had healthcare exposure after FMT. Of 374 patients with risk factor exposure, 78.1% (95% confidence interval [CI], 72.7%-84.0%) had durable response to FMT at 1 year. On multivariable analysis, antibiotic use was independently associated with decreased durability of FMT (hazard ratio, 0.27; 95% CI, .15-.49; P < .001). CONCLUSIONS: The majority of patients had a durable response to FMT despite exposure to CDI risk factors. Antibiotic exposure after FMT independently predicted loss of durability of FMT. Larger studies are needed to define predictors of durable response in patients with and without exposure to antibiotics.

Fecal Microbiota Transplantation Is Safe and Effective in Patients With Clostridioides difficile Infection and Cirrhosis.

BACKGROUND & AIMS: Clostridioides difficile infection (CDI) harms a large proportion of patients with cirrhosis. Fecal microbiota transplantation (FMT) is recommended for recurrent CDI, but its effects in patients with cirrhosis have not been established. We performed a multicenter observational study to evaluate the efficacy and safety of FMT for CDI in patients with cirrhosis. METHODS: We performed a retrospective study of 63 adults with cirrhosis (median model for end-stage liver disease score, 14.5; 24 patients with decompensated cirrhosis) who underwent FMT for CDI from January 2012 through November 2018 at 8 academic centers in the United States, Canada, and Italy. We collected data on patient demographics and characteristics of cirrhosis, CDI, and FMT from medical records and compared differences among patients with different severities of cirrhosis, and FMT successes vs failures at the 8-week follow-up evaluation. We also obtained data on adverse events (AEs) and severe AEs within 12 weeks of FMT. RESULTS: Patients underwent FMT for recurrent CDI (55 of 63; 87.3%), severe CDI (6 of 63; 9.5%), or fulminant CDI (2 of 63; 3.2%) primarily via colonoscopy (59 of 63; 93.7%) as outpatients (47 of 63; 76.8%). FMT success was achieved for 54 patients (85.7%). Among FMT failures, a higher proportion used non-CDI antibiotics at the time of FMT (44.4% vs 5.6%; P < .001), had Child-Pugh scores of B or C (100% vs 37.7%; P < .001), used probiotics (77.8% vs 24.1%; P = .003), had pseudomembranes (22.2% vs 0; P = .018), and underwent FMT as inpatients (45.5% vs 19%; P = .039), compared with FMT successes. In multivariable analysis, use of non-CDI antibiotics at the time of FMT (odds ratio, 17.43; 95% CI, 2.00-152.03; P = .01) and use of probiotics (odds ratio, 11.9; 95% CI, 1.81-78.3; P = .01) were associated with a greater risk of FMT failure. FMT-related AEs occurred in 33.3% of patients (21 of 63)-most were self-limited abdominal cramps or diarrhea. There were only 5 severe AEs that possibly were related to FMT; none involved infection or death. CONCLUSIONS: In a retrospective study, we found FMT to be safe and effective for the treatment of CDI in patients with cirrhosis.

Predictors and Management of Failed Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.

BACKGROUND AND GOALS: Clostridioides difficile infection (CDI) recurs in 10% to 15% after fecal microbiota transplantation (FMT). We identify predictors, and describe management and outcome of patients with recurrent CDI after FMT in a predominantly outpatient cohort. METHODS: A nested case-control study of patients undergoing FMT for recurrent CDI from August 2012 to January 2017 was performed. FMT failure was defined as recurrent diarrhea with positive C. difficile stool test during follow-up (≥2 mo). Controls (patients without FMT failures) were matched to cases 1:1 for sex and timing of FMT±1 month. RESULTS: Overall, 522 patients underwent FMT; 70 [13.4%; median age 53.8 years (range, 18 to 89 y), 54.3% females] recurred within a median 5.6 months (range, 0.2 to 34.9 mo). Number of prior CDI episodes, prior CDI treatment, and prior CDI-related hospitalizations were similar in cases and controls. Systemic antibiotics after FMT (54.3% vs. 21.4%, P<0.0001), inflammatory bowel disease (IBD) (34.3% vs. 15.7%, P=0.01), pseudomembranes at FMT (4.3% vs. 0%, P=0.03), and poor bowel preparation (68.5% vs. 31.4%, P=0.01) were associated with FMT failure. On multivariate analysis, IBD [odds ratio (OR) 4.34; 95% confidence interval (CI), 1.24-15.15], systemic antibiotics (OR 7.39; 95% CI, 3.02-18.07), and poor bowel preparation (OR 3.84; 95% CI, 1.59-9.28) predicted FMT failure with an area under the curve of 0.78. Among FMT failures, 37 (52.8%) were managed with antibiotics, 32 (45.7%) with repeat FMT after antibiotics and 1 with colectomy. CONCLUSIONS: Use of systemic antibiotics, IBD, and poor bowel preparation predict FMT failure. Patients with FMT failure can be managed with antibiotics and/or repeat FMT.

Incidence of Clostridioides difficile infection in peripartum women: a retrospective cohort study.

BACKGROUND: The incidence of Clostridioides difficile infection (CDI) is increasing in the general population. Data on the epidemiology of CDI in peripartum women - a highly vulnerable patient population - is scarce. The objective of this study was to report the incidence of CDI in peripartum women. METHODS: A single-center retrospective cohort study was conducted in peripartum women from 1997 to 2017. Peripartum CDI was defined as definite CDI (watery diarrhea for >24 h with positive stool assay) during pregnancy, or within 6 weeks postpartum. Incidence was reported per 100,000 pregnancies and time trends in incidence were analyzed using Poisson regression. Analyses were done separately for time trends before and after 2007, when CDI testing strategy changed to polymerase chain reaction. RESULTS: From 1997 to 2017, 80 patients with peripartum CDI (47 during pregnancy, 33 postpartum) out of 125,683 pregnancies (0.064%) were identified. Incidence of CDI increased 3.4 fold (95% confidence interval 1.5-7.4, p = 0.005) over the 21 year period. Time trends were evident after (p = 0.054), but not before 2007 (p = 0.97). CONCLUSION: Incidence of CDI in peripartum women increased over the 21 year study period. The rise in incidence is concerning, and calls for heightened surveillance for CDI in this highly vulnerable population.

Prevalence and Mortality of COVID-19 Patients With Gastrointestinal Symptoms: A Systematic Review and Meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis evaluating the prevalence of gastrointestinal (GI) symptoms and mortality in patients with coronavirus disease 2019 (COVID-19) diagnosed. METHODS: A systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was performed from December 1, 2019 to May 7, 2020. Observational studies including adults with COVID-19 infection and reporting GI symptoms were included. The primary outcome was assessing the weighted pooled prevalence (WPP) of GI symptoms in patients with COVID-19 infection. Secondary outcomes were WPP of overall mortality, and mortality in patients with COVID-19 infection with GI symptoms. RESULTS: A total of 78 studies with 12,797 patients were included. Among GI symptoms (at onset of illness in 6, at admission in 17, data given separately for both in 3, and data unavailable in 52 studies), the WPP of diarrhea was 12.4% (95% CI, 8.2% to 17.1%), I2=94%; nausea and/or vomiting, 9.0% (95% CI, 5.5% to 12.9%), I2=93%; loss of appetite, 22.3% (95% CI, 11.2% to 34.6%, I2=94%; and abdominal pain, 6.2% (95% CI, 2.6% to 10.3%), I2=92%. Mortality among patients with GI symptoms (0.4%; 95% CI, 0% to 1.1%; I2=74%) was similar to overall mortality (2.1%; 95% CI, 0.2% to 4.7%; I2=94%), P=.15. Most studies had high risk of bias and overall quality of evidence was low to very low for all outcomes. CONCLUSION: Gastrointestinal symptoms are seen in up to 1 in 5 patients with COVID-19 infection. More high-quality evidence is needed to confirm these findings and explore factors causing mortality in these patients.

Therapies to modulate gut microbiota: Past, present and future.

The human gut microbiota comprises of a complex and diverse array of microorganisms, and over the years the interaction between human diseases and the gut microbiota has become a subject of growing interest. Disturbed microbial milieu in the gastrointestinal tract is central to the pathogenesis of several diseases including antibiotic-associated diarrhea and Clostridioides difficile infection (CDI). Manipulation of this microbial milieu to restore balance by microbial replacement therapies has proven to be a safe and effective treatment for recurrent CDI. There is considerable heterogeneity in various aspects of stool processing and administration for fecal microbiota transplantation (FMT) across different centers globally, and standardized microbioal replacement therapies offer an attractive alternative. The adverse effects associated with FMT are usually mild. However, there is paucity of data on long term safety of FMT and there is a need for further studies in this regard. With our increasing understanding of the host-microbiome interaction, there is immense potential for microbial replacement therapies to emerge as a treatment option for several diseases. The role of microbioal replacement therapies in diseases other than CDI is being extensively studied in ongoing clinical trials and it may be a potential treatment option for inflammatory bowel disease, irritable bowel syndrome, obesity, multidrug resistant infections, and neuropsychiatric illnesses. Fecal microbiota transplantation for non-CDI disease states should currently be limited only to research settings.