A systematic review of tools for predicting complications in patients with acute infectious diarrhea.

OBJECTIVE: To identify tools that predict the risk of complications in patients presenting to outpatient clinics or emergency departments (ED) with acute infectious diarrhea. METHODS: Medline, Embase, Cochrane Library, Web of Science and CINAHL were searched from inception to July 2021. Articles reporting on the derivation or validation of a score to stratify the risk of intravenous rehydration or hospitalization among patients with acute infectious diarrhea in the ED or outpatient clinic were retained for analysis. RESULTS: Five articles reporting on two different tools were identified. Developed to assess the risk of hospitalization of children, the EsVida scale has not been externally validated. Developed originally to assess the level of dehydration in children, the Clinical Dehydration Scale (CDS) was evaluated as a risk stratification tool. For predicting intravenous rehydration, a CDS score ≥ 1 showed a sensitivity between 0.73 and 0.88 and specificity between 0.38 and 0.69, whereas a CDS score ≥ 5 showed a sensitivity between 0.06 and 0.32 and specificity between 0.94 and 0.99. For predicting hospitalization, a CDS score ≥ 1 showed a sensitivity between 0.74 and 1.00 and specificity between 0.34 and 0.38, whereas a CDS score ≥ 5 showed a sensitivity between 0.26 and 0.62 and specificity between 0.66 and 0.96. High heterogeneity among studies and unclear risk of bias precluded meta-analysis. CONCLUSION: As a risk-stratification tool, the CDS has been validated only for children. Further research is needed to develop and validate a tool suitable for adults in the ED.

Update on Shigella and Nontyphoidal Salmonella Antimicrobial Drug Resistance: Implications on Empirical Treatment of Acute Infectious Diarrhea in Cambodia.

Information on causative diarrheal pathogens and their associated antimicrobial susceptibility remains limited for Cambodia. This study describes antimicrobial resistance patterns for Shigella and nontyphoidal Salmonella isolates collected in Cambodia over a 5-year period. Multidrug resistance was shown in 98% of Shigella isolates, with 70%, 11%, and 29% of isolates being resistant to fluoroquinolones, azithromycin, and cephalosporin, respectively. As many as 11% of Shigella isolates were resistant to nearly all oral and parenteral drugs typically used for shigellosis, demonstrating extreme drug resistance phenotypes. Although a vast majority of nontyphoidal Salmonella isolates remained susceptible to cephalosporins (99%) and macrolides (98%), decreased susceptibility to ciprofloxacin was found in 67% of isolates, which is notably higher than previous reports. In conclusion, increasing antimicrobial resistance of Shigella and nontyphoidal Salmonella is a major concern for selecting empirical treatment of acute infectious diarrhea in Cambodia. Treatment practices should be updated and follow local antimicrobial resistance data for the identified pathogens.

Trends in healthcare visits and antimicrobial prescriptions for acute infectious diarrhea in individuals aged 65 years or younger in Japan from 2013 to 2018 based on administrative claims database: a retrospective observational study.

BACKGROUND: The inappropriate use of antimicrobials for acute infectious diarrhea is widespread and leads to the problem of antimicrobial resistance. To improve the use of antimicrobials, it is first necessary to understand the actual situation of diarrheal disease and to identify potential targets for intervention. This study aimed to investigate the recent epidemiological characteristics of and antimicrobial prescriptions for acute infectious diarrhea in Japan. METHODS: This was a retrospective observational study of outpatients aged 0-65 years, separated into children (age 0-17 years) and adults (age 18-65 years), diagnosed with acute infectious diarrhea, using the administrative claims database of the Japan Medical Data Center from 2013 to 2018. We evaluated the number of eligible visits/number of database registrants (defined as the visit rate). The analysis of the antimicrobial prescription rate was restricted to otherwise healthy individuals diagnosed with acute infectious diarrhea alone by excluding patients with multiple disease diagnoses and with medical backgrounds of chronic bowel diseases or immunocompromised conditions. We further classified them by diagnosis of bacterial or nonbacterial acute infectious diarrhea. RESULTS: The total number of eligible visits for acute infectious diarrhea was 2,600,065. The visit rate, calculated based on the number of eligible visits by database registrants, was higher in children (boys, 0.264; girls, 0.229) than in adults (men, 0.070; women, 0.079), with peaks in early summer and winter. The peaks for visits in adults lagged those of children. In total, 482,484 visits were analyzed to determine the antimicrobial prescription rate; 456,655 (94.6%) were diagnosed with nonbacterial acute infectious diarrhea. Compared with children (boys, 0.305; girls, 0.304), the antimicrobial prescription rate was higher in adults, and there were differences between sexes in adults (men, 0.465; women, 0.408). Fosfomycin and fluoroquinolone were most frequently used for nonbacterial acute infectious diarrhea in children (44.1%) and adults (50.3%), respectively. CONCLUSIONS: These results revealed overprescription of antimicrobials for acute infectious diarrhea in this administrative claims database in Japan and contribute to the development of antimicrobial stewardship strategies and the identification of targets for efficiently reducing inappropriate antimicrobial use.

Presentations of Children with Suspected Sepsis Caused by Acute Infectious Diarrhea in the Pediatric Emergency Department.

BACKGROUND: Acute infectious diarrhea is a common cause of hospitalization in children. Hence, early identification of acute bacterial gastroenteritis with suspected sepsis in pediatric emergency departments (EDs) is important. This study aimed to describe the clinical spectrum and initial characteristics of children who were presented to a pediatric ED with acute infectious diarrhea and suspected sepsis. METHODS: Between April 2020 to March 2021, children with clinical diagnoses of acute bacterial colitis and suspected sepsis who were admitted to the pediatric ED were prospectively enrolled. The following data were obtained and compared between different age groups of children: including demographics, presentation, laboratory tests, culture results, treatment modalities, complications, and short-term outcomes. RESULTS: A total of 105 patients (70 males and 35 females; mean age: 3.75 ± 3.52 years) were enrolled in this study. Of them, 89 (84.8%) patients were <6 years of age, and 80 (76.2%) patients required hospitalization for a duration of 4.7 ± 2.08 days. C-reactive protein (CRP) and procalcitonin (PCT) levels were significantly higher in the admission (both p < 0.001) and anti-biotic treatment groups (both p < 0.001). Salmonella enteritidis was the most common organism cultured from the stool and blood samples (39 of 91 (38.5%) and 2 of 105 (1.9%), respectively). CONCLUSIONS: The primary causative organism of acute infectious diarrhea identified in this study was S. enteritidis. Age and elevated serum CRP or PCT levels could be important factors in the decisions of emergency physicians regarding hospitalization and antibiotic therapies for pediatric acute infectious diarrhea.

Dormant Crohn's Disease Reactivated by Clostridioides difficile Infection.

Crohn's disease (CD) is a type of inflammatory bowel disease (IBD) characterized by chronic transmural inflammation of any portion of the gastrointestinal tract. The etiology of CD remains unknown although genetic, immunological, and acquired factors have been recognized as contributing to its development. Alterations of intestinal microbiota, including Clostridioides difficile (C. difficile), are theorized to alter humoral immunity and contribute toward CD flare pathogenesis. As such, cases of IBD remission can be undone by alterations in the gut microbiota and subsequently confound the diagnosis of inflammatory or infectious etiologies of diarrhea. We present a case of a 73-year-old female with dormant CD for 25 years who experienced an atypical course of diarrhea found to have a CD flare in the setting of acute C. difficile colitis.

Shigella as a Cause of Diarrhea Hospitalization in Children Under Five: Evaluation by Conventional and Molecular Methods.

BACKGROUND AND OBJECTIVES: Shigella is an important cause of diarrhea in children under five, often missed by conventional laboratory methods. Blood in stools has always been a syndromic indicator for Shigella diarrhea, but most cases present with watery diarrhea without blood. This study aimed to determine the frequency of Shigella detected by molecular and conventional methods in children under five. Additionally, we aimed to study the clinical profile and outcome of children with Shigella diarrhea managed as per current diarrhea treatment guidelines. METHODS: In this hospital-based prospective observational study, stool samples from 150 children (age range: one month to five years) with acute diarrhea (duration < seven days) were subjected to routine microscopic examination, stool culture, and DNA extraction. The extracted DNA from stored stool samples was subjected to polymerase chain reaction (PCR) amplification using a specific primer for the invasion plasmid antigen H gene sequence (ipaH) gene at 424 bp. Results were interpreted in the context of the percentage of isolation of Shigella by molecular (PCR) and conventional methods (stool microscopy and culture) and the follow-up outcome in terms of recurrence of diarrhea or dysentery and growth faltering over three months after discharge. RESULTS: Shigella infection was diagnosed in stool samples by PCR from 13 (8.7%) children, whereas it was isolated by conventional stool culture in only one (0.7%) child. The sensitivity of culture was only 7.7% against PCR for the diagnosis of Shigella infection, whereas blood in stools had a sensitivity of 15.4%. The majority of Shigella PCR-positive cases (11 out of 13) presented with non-bloody diarrhea. None of the evaluated clinical predictors had a significant association with the Shigella infection. No statistically significant difference was found between PCR-positive and PCR-negative children at the end of follow-up (P>0.05). CONCLUSION: The majority of children with Shigella infection present with watery diarrhea rather than bloody diarrhea, and a history of blood in stools is a poor marker for the diagnosis of shigellosis. The diagnostic performance of stool culture is also very low compared to stool PCR for the diagnosis of Shigella diarrhea.

Efficacy of stool multiplex polymerase chain reaction assay in adult patients with acute infectious diarrhea.

BACKGROUND: Recently, stool multiplex polymerase chain reaction (PCR) tests have been developed for identifying diarrhea-causing bacterial pathogens. Furthermore, fecal calprotectin is a well-known effective marker for intestinal mucosal inflammation. AIM: To evaluate the efficacy of stool multiplex PCR and fecal calprotectin in acute infectious diarrhea. METHODS: Overall, 400 patients with acute infectious diarrhea were enrolled from Kangdong Sacred Heart Hospital (January 2016 to December 2018). Multiplex PCR detected 7 enteropathogenic bacteria including Salmonella, Campylobacter, Shigella, Escherichia coli O157:H7, Aeromonas, Vibrio, and Clostridium difficile. We reviewed clinical and laboratory findings using stool multiplex PCR. RESULTS: Stool multiplex PCR test detected considerably more bacterial pathogens than stool culture (49.2% vs 5.2%), with Campylobacter as the most common pathogen (54%). Patients with positive stool PCR showed elevated fecal calprotectin expression compared to patients with negative stool PCR (1124.5 ± 816.9 mg/kg vs 609 ± 713.2 mg/kg, P = 0.001). C-reactive protein (OR = 1.01, 95%CI: 1.001-1.027, P = 0.034) and sigmoidoscopy-detected colitis (OR = 4.76, 95%CI: 1.101-20.551, P = 0.037) were independent factors in stool PCR-based detection of bacterial pathogens. Sensitivity and specificity of calprotectin were evaluated to be 70.5% and 60.9%, respectively (adjusted cut-off value = 388 mg/kg). CONCLUSION: Stool multiplex PCR test has increased sensitivity in detecting pathogens than conventional culture, and it is correlated with calprotectin expression. Stool multiplex PCR and calprotectin may be effective in predicting clinical severity of infectious diarrhea.

Time Series Analysis of the Microbiota of Children Suffering From Acute Infectious Diarrhea and Their Recovery After Treatment.

Gut microbiota is closely related to acute infectious diarrhea, one of the leading causes of mortality and morbidity in children worldwide. Understanding the dynamics of the recovery from this disease is of clinical interest. This work aims to correlate the dynamics of gut microbiota with the evolution of children who were suffering from acute infectious diarrhea caused by a rotavirus, and their recovery after the administration of a probiotic, Saccharomyces boulardii CNCM I-745. The experiment involved 10 children with acute infectious diarrhea caused by a rotavirus, and six healthy children, all aged between 3 and 4 years. The children who suffered the rotavirus infection received S. boulardii CNCM I-745 twice daily for the first 5 days of the experiment. Fecal samples were collected from each participant at 0, 3, 5, 10, and 30 days after probiotic administration. Microbial composition was characterized by 16S rRNA gene sequencing. Alpha and beta diversity were calculated, along with dynamical analysis based on Taylor's law to assess the temporal stability of the microbiota. All children infected with the rotavirus stopped having diarrhea at day 3 after the intervention. We observed low alpha diversities in the first 5 days (p-value < 0.05, Wilcoxon test), larger at 10 and 30 days after probiotic treatment. Canonical correspondence analysis (CCA) showed differences in the gut microbiota of healthy children and of those who suffered from acute diarrhea in the first days (p-value < 0.05, ADONIS test), but not in the last days of the experiment. Temporal variability was larger in children infected with the rotavirus than in healthy ones. In particular, Gammaproteobacteria class was found to be abundant in children with acute diarrhea. We identified the microbiota transition from a diseased state to a healthy one with time, whose characterization may lead to relevant clinical data. This work highlights the importance of using time series for the study of dysbiosis related to diarrhea.

The 12 Gastrointestinal Pathogens Spectrum of Acute Infectious Diarrhea in a Sentinel Hospital, Shenzhen, China.

Acute infectious gastroenteritis is one of the most common diseases among all ages, particularly in developing countries. The pathogen spectrum may differ among different regions and seasons. To investigate the etiology of acute diarrhea in Shenzhen, a prospective study was conducted from August 2014 to September 2015. Stools from 412 patients with diarrhea (286 of whom were adults) including the general epidemiological information of the patients were collected. The 19 pathogens were detected by conventional culture method or multiplex PCR assay, which included five viruses (rotavirus, adenovirus, sapovirus, norovirus, and astrovirus), 11 bacterial pathogens (Salmonella, Campylobacter jejuni, Shigella, Listeria monocytogenes, Vibrio parahaemolyticus, Vibrio cholera, Enterohemorrhagic (EHEC), enteropathogenic (EPEC), enteroinvasive (EIEC), enterotoxigenic (ETEC); and enteroaggregative Escherichia coli (EAEC)) and three parasites (Entamoeba histolytica, Giardia lamblia, and Cryptosporidium parvum). A potential pathogen and coinfection was found in 41.5 and 7.0% of cases, respectively. The bacterial infection was the dominant cause of diarrhea (32.3%), and the three most frequently identified organisms were Salmonella (12.1%), ETEC (8.0%), and Campylobacter jejuni (4.9%). Salmonella enteritidis was the leading serotype of Salmonella sp. Norovirus (8.3%) and sapovirus (2.2%) were the most common viral pathogens, followed by adenovirus (1.5%) and rotavirus (1.2%). No EHEC, L. monocytogenes, V. cholera, Shigella, and parasites were found. The single most important causes of diarrhea were Salmonella spp. and Campylobacter jejuni, which points toward the need for testing and surveillance for these pathogens in this region.

Rifaximin for the treatment of acute infectious diarrhea.

Rifaximin is a nonabsorbable rifamycin derivative with an excellent safety profile and a broad spectrum of antimicrobial activity against a variety of enteropathogens causing acute infectious diarrhea. After oral ingestion, its bioavailability is known to be less than 0.4%, and it has a low potential for significant drug interactions. In the treatment of travelers' diarrhea caused by noninvasive diarrheagenic Escherichia coli, it has been demonstrated that rifaximin significantly shortens the duration of diarrhea and has an efficacy similar to that of ciprofloxacin. Moreover, according to two randomized placebo-controlled trials, prophylactic treatment with rifaximin reduced the risk of developing travelers' diarrhea by more than 50% compared with the placebo group. For the treatment of acute diarrhea unrelated to travel, a short course of rifaximin significantly reduced the duration of diarrhea, and its overall efficacy was comparable to that of ciprofloxacin. The discrepancy between the in vitro and in vivoantimicrobial activities of rifaximin, however, and the clinical implication of the rapid appearance of bacterial resistance, must be further elucidated. In conclusion, this gut-selective antibiotic seems to be a promising option for the treatment of acute infectious diarrhea secondary to noninvasive E. coli and also appears to be effective in chemoprophylaxis for travelers' diarrhea.

Efficacy of rifaximin compared with ciprofloxacin for the treatment of acute infectious diarrhea: a randomized controlled multicenter study.

BACKGROUND/AIMS: Ciprofloxacin has been widely prescribed for acute infectious diarrhea. However, the resistance to this drug is increasing. Rifaximin is a novel but poorly absorbed rifamycin derivative. This study evaluated and compared the efficacies of rifaximin and ciprofloxacin for the treatment of acute infectious diarrhea. METHODS: We performed a randomized controlled multicenter study in Korea. Patients with acute diarrhea were enrolled and randomized to receive rifaximin or ciprofloxacin for 3 days. The primary efficacy endpoint was the time to last unformed stool (TLUS). Secondary endpoints were enteric wellness (reduction of at least 50% in the number of unformed stools during 24-hour postenrollment intervals), general wellness (subjective feeling of improvement), and proportion of patients with treatment failure. RESULTS: Intent-to-treat analysis (n=143) showed no significant difference between the rifaximin and ciprofloxacin groups in the mean TLUS (36.1 hours vs 43.6 hours, p=0.163), enteric wellness (49% vs 57%, p=0.428), general wellness (67% vs 78%, p=0.189), or treatment failure rate (9% vs 12%, p=0.841). The adverse events did not differ significantly between the two groups. CONCLUSIONS: These results suggest that rifaximin is as safe and effective as ciprofloxacin in the treatment of acute infectious diarrhea.

Guía de práctica clínica sobre el diagnóstico y tratamiento de la diarrea aguda infecciosa en pediatría Perú - 2011 / Clinical practice guidelines on the diagnosis and treatment of infectious acute diarrhea in children Peru - 2011

Guía de Práctica Clínica sobre el Diagnóstico y Tratamiento de la Diarrea Aguda Infecciosa en Pediatría del Perú es una información resumida sobre la definición criterios de inclusión y exclusión epidemiología y etiología de la diarrea infecciosa; considerando aspectos en el dignóstico y tratamiento (desidratación, tratamiento antibiótico, tratamientos de apoyo), soporte nutricional criterios de transferencias y alta y aspectos de prevención.

The Clinical Practice Guidelines cover the Diagnosis and Treatment of Acute Diarrhea in Pediatric Infectious is a consice information about definition, inclusion and exclusion criteria; epidemiology and etiology of infectious diarrhea. The guidelines cover aspects of diagnosis and treatment (dehydration, antibiotics, supportive therapy), nutritional support and other aspects of transferences and prevention.