Antibiotic-associated diarrhea (AAD) is a common side effect of antibiotic therapy, characterized by intestinal inflammation which reduces the quality of life of patients. Xianglian Pill (XLP) has long been used to treat abdominal pain, diarrhea, bacillary dysentery and enteritis. Studies found that XLP has curative effect on AAD; however, the chemical constituents and mechanism of XLP have not been fully elucidated because of the lack of in vitro and in vivo studies. In this study, ultra-high performance liquid chromatography mass spectrometry method (UPLC-Q-Exactive-Orbitrap-HRMS) was used to examine the components of the XLP. Then, the binding between active compounds and the key targets was studied using network pharmacology and molecular docking. A comparative tissue distribution study was established for the simultaneous determination of the 10 active components in healthy and AAD mouse models. Forty-six components were characterized from XLP. According to the network pharmacology degree value, a prediction was made that encompassed 42 components and 14 core targets, which were intricately involved in crucial biological pathways, such as the AGE-RAGE signaling, cellular senescence, and MAPK signaling. Tissue distribution analysis showed that the 10 components were widely distributed in the heart, liver, spleen, lungs, kidneys, small intestine, and large intestine of mice, with varying concentrations in healthy and AAD mice. Molecular docking analysis also indicated that the active compounds in the tissue distribution could bind tightly to key targets of network pharmacological studies. This study provides a reference for further investigations of the relationships between the chemical components and pharmacological activities of XLP.

Our study aimed to assess the risk signals of antibiotic-associated diarrhea (AAD) caused by various antibiotics using real-world data and provide references for safe clinical applications.
We analyzed data extracted from the FDA Adverse Event Reporting System (FAERS) database, covering the period from the first quarter of 2004 to the third quarter of 2022. We computed the reporting odds ratio (ROR) for each antibiotic or antibiotic class to compare the signal difference. Furthermore, we also examined the differences in the onset times and outcomes of AAD caused by various antibiotics.
A total of 5,397 reports met the inclusion requirements. Almost all antibiotics, except tobramycin and minocycline (ROR 0.98; 95%CI: 0.64-1.51 and 0.42; 95%CI: 0.16-1.11, respectively), showed a significant correlation with AAD. The analysis of the correlation between different classes of antibiotics and AAD revealed that lincomycins (ROR 29.19; 95%CI: 27.06-31.50), third-generation cephalosporins (ROR 15.96; 95%CI: 14.58-17.47), and first/second generation cephalosporins (ROR 15.29; 95%CI: 13.74-17.01) ranked the top three. The ROR values for antibiotics from the same class of antibiotics also varied greatly, with the ROR values for third-generation cephalosporins ranging from 9.97 to 58.59. There were also differences in ROR values between β-lactamase inhibitors and their corresponding β-lactamase drugs, such as amoxicillin-clavulanate (ROR = 13.31; 95%CI: 12.09-14.65) and amoxicillin (ROR = 6.50; 95%CI: 5.69-7.44). 91.35% of antibiotics have an onset time of less than four weeks.
There is a significant correlation between almost all antibiotics and AAD, particularly lincomycins and β-lactam antibiotics, as well as a different correlation within the same class. These findings offer valuable evidence for selecting antibiotics appropriately.

A recent study from Taiwan suggested that Clostridium innocuum may be an unrecognized cause of antibiotic-associated diarrhea (AAD) and clinically indistinguishable from Clostridioides difficile infection. Our objective was to compare C. innocuum prevalence and strain between those with AAD and asymptomatic controls.
In this cross-sectional study, we collected stool from 200 individuals with AAD and 100 asymptomatic controls. We evaluated the association between AAD and C. innocuum in stool using anaerobic culture and quantitative polymerase chain reaction (qPCR). To identify strain-specific associations with AAD, we performed whole-genome sequencing of C. innocuum isolates using Illumina MiSeq and constructed comparative genomics analyses.
C. innocuum was isolated from stool of 126/300 (42%) subjects and more frequently from asymptomatic controls than AAD subjects (50/100 [50%] vs 76/200 [38%], respectively; P = .047). C. innocuum isolation frequency was not associated with AAD in either the adult or pediatric subgroups. C. innocuum and C. difficile were frequently co-prevalent in individuals with and without diarrhea. There were no phylogenetic differences or accessory genome associations between C. innocuum isolates from AAD subjects and asymptomatic controls.
C. innocuum was frequently isolated and at a greater frequency in asymptomatic controls than those with AAD. We did not identify strain lineages or accessory genomic elements associated with AAD. These data highlight that differentiating C. innocuum-associated diarrhea from asymptomatic colonization, and differentiating diarrhea caused by C. difficile from C. innocuum, are clinical microbiology challenges that require additional investigation to identify host-specific factors and/or biomarkers that distinguish these conditions.

The use of probiotics in gastrointestinal ailments has shown therapeutic effects. The imbalance of the microbiota caused by antibiotic treatment or others has been shown to be restored to normal with probiotic treatment. In this study, a genomically and phenotypically safe probiotic Alkalihalobacillus clausii 088AE has been evaluated for ameliorating antibiotic-associated diarrhea (AAD) in pediatrics (PE, n = 60, 2-10 years), adolescent and adults (AA, n = 60, 11-65 years) through a randomized controlled clinical trial. A. clausii 088AE was administered for seven days (PE, 4 and AA, 6 billion/day) and primary and secondary endpoints were evaluated on different visits. Compared to the respective placebo arms, A. clausii 088AE improved the diarrheal (time to last unformed stool and diarrheal frequency) conditions in children, adolescents and adults. A. clausii 088AE treatment decreased AAD-severity score on visit 5 in both pediatric (0.12 ± 0.33, 12.39 folds), adult and adolescent (0.54 ± 0.36, 2.34 folds) groups compared to those respective placebo arm (p < 0.05). A. clausii 088AE was well tolerated, did not cause significant changes in vital and clinical safety parameters and subjects reported no adverse effects or serious adverse reactions. A. clausii 088AE is safe and therapeutically effective against AAD, reducing onset of diarrhea and related severity symptoms including abdominal discomfort and pain, bloating and flatulence. A. clausii 088AE may be recommended as a live bio-therapeutic agent for improving clinical pathophysiology of gastrointestinal ailments, in particular antibiotic-associated diarrhea and related symptoms.

Introduction: Antibiotic-associated diarrhea (AAD) is a common adverse reaction to antibiotic treatment affecting up to 21% of children. The aim of the study is to evaluate whether bovine lactoferrin (bLf) might be used for AAD prevention. Materials and Methods: In this prospective, randomized, double-blind, placebo-controlled, single-center study, we enrolled 156 children aged between 1 and 18 years, treated with antibiotic due to acute respiratory or urinary tract infection. We randomly allocated children 1:1 to receive 100 mg of bLf or a placebo twice a day orally for the whole period of antibiotic therapy. The primary outcome was the occurrence of antibiotic-associated diarrhea during and up to 2 weeks after antibiotic therapy. The secondary endpoint was intravenous rehydration or antibiotic withdrawal due to diarrhea. We performed intention-to-treat analysis. Results: We included 150 patients in intention-to-treat analysis. AAD occurred in 16 of 75 (21.3%) patients in bLf group and in 7 of 75 (9.3%) individuals in placebo group [OR = 2.6, (95% CI: 1.01-6.84), p = 0.04]. Relative risk was 2.29 (95% CI: 0.89-5.88). The need for intravenous rehydration occurred in one patient in the placebo group (p = 0.3). We observed no adverse effects in neither of the groups. Discussion: The trial indicated that bLf is not effective in AAD prevention. The risk for AAD was higher in bovine lactoferrin group as compared with placebo. We registered the study protocol on ClinicalTrials.gov (NCT02626104).

Background: Antibiotic-associated gastrointestinal signs occurred in 100% of dogs administered enrofloxacin with metronidazole in a previous study, and signs partially were mitigated by synbiotics. The objective of this randomized, double-blinded, placebo-controlled trial was to compare the fecal microbiome and metabolome of dogs administered enrofloxacin and metronidazole, followed by either a placebo or a bacterial/yeast synbiotic combination. Methods: Twenty-two healthy research dogs were randomized to two treatment groups. There were three study periods: baseline, treatment, and washout. Dogs were administered enrofloxacin (10 mg/kg qd) and metronidazole (12.5 mg/kg BID), followed 1 h later by placebo or a commercially-available synbiotic combination (BID), per os for 21 days with reevaluation 56 days thereafter. Fecal samples were collected on days 5-7 (baseline), 26-28, and 82-84. The fecal microbiome was analyzed by qPCR and sequencing of 16S rRNA genes; time-of-flight mass spectrometry was used to determine metabolomic profiles. Split plot repeated measures mixed model ANOVA was used to compare results between treatment groups. P < 0.05 was considered significant, with Benjamini and Hochberg\'s False Discovery Rate used to adjust for multiple comparisons. Results: Alpha diversity metrics differed significantly over time in both treatment groups, with incomplete recovery by days 82-84. Beta diversity and the dysbiosis index differed significantly over time and between treatment groups, with incomplete recovery at days 82-84 for dogs in the placebo group. Significant group-by-time interactions were noted for 15 genera, including Adlercreutzia, Bifidobacterium, Slackia, Turicibacter, Clostridium (including C. hiranonis) [Ruminococcus], Erysipelotrichaceae_g_, [Eubacterium], and Succinivibrionaceae_g_. Concurrent group and time effects were present for six genera, including Collinsella, Ruminococcaceae_g_, and Prevotella. Metabolite profiles differed significantly by group-by-time, group, and time for 28, 20, and 192 metabolites, respectively. These included short-chain fatty acid, bile acid, tryptophan, sphingolipid, benzoic acid, and cinnaminic acid metabolites, as well as fucose and ethanolamine. Changes in many taxa and metabolites persisted through days 82-84. Conclusion: Antibiotic administration causes sustained dysbiosis and dysmetabolism in dogs. Significant group-by-time interactions were noted for a number of taxa and metabolites, potentially contributing to decreased antibiotic-induced gastrointestinal effects in dogs administered synbiotics.

This study sought to identify the association of antibiotic prescribing and the risk of antibiotic-associated diarrhoea (AAD) in Korle Bu Teaching Hospital (KBTH) in Ghana.
Patients from the Male Urology Ward and Treatment Room of the Surgical Department of KBTH were followed up over three months to determine if they had experienced any unusual diarrhoeal illness after antibiotic therapy. 81 eligible patients (adults) were included in the study but a total of 70 patients (mean age of 56.71 years) were successfully followed up during the study period.
The top conditions presented by patients were urological infection (66.7%), cancer (15.3%) and leg ulcer (18.1%). Ciprofloxacin (50%) and ceftriaxone (28.5%) were the most prescribed antibiotics. Eleven patients (more than 1 in 7) developed diarrhoea that could be associated with their use of antibiotics. The occurrence of AAD was significantly associated with type of antibiotic used by patient. 73% of patients who developed symptoms of AAD had received Clindamycin. Risk of AAD was not significantly associated with age and comorbidities.
The rate of AAD in the Male Urology Ward and the Treatment Room of the Surgical Department of KBTH during the period of this study was 15.7%. Clindamycin was identified as the most implicated antibiotic.

Clostridioides (Clostridium) difficile is the main etiology underlying antibiotic-associated diarrhea (AAD). Still, few Brazilian data are available on this infection. The aims of this multicenter study were to identify the prevalence, clinical characteristics, and outcomes of C. difficile infection (CDI) in patients with antibiotic associated diarrhea at eight hospitals in Curitiba, southern Brazil, during the years 2017-2019. Stool samples were tested using enzyme immunoassay for glutamate dehydrogenase antigen (GDH) and A/B toxins. Positive GDH samples were further evaluated by real-time polymerase chain reaction (PCR) for the presence of genes encoding toxin B (tcdB), binary toxin (cdt), and marker of hypervirulent C. difficile strain (tcdC deletion). The prevalence of CDI in 351 patients with AAD included in the study was 17.7% (n = 62). Among the CDI cases, tcdB was positive in all 62 stool samples, while cdt was positive in 10 samples, and tcdC deletion was positive in only two. Carriage of carbapenem-resistant Gram-negative bacilli, previous hospitalization, and use of broad-spectrum cephalosporin and carbapenem were associated with CDI. Among patients with CDI, 64.5% presented with severe diarrhea, and 8% (5/62) progressed with colitis and required intensive care. The 30-day mortality was 24% (15/62), and the CDI-associated mortality was 4.8% (3/62). Overall, 83.8% (52/62) of the patients achieved primary cure, and 20.8% of the evaluated patients (10/48) presented CDI recurrence. The treatment administered was not significantly associated with the 60-day recurrence or mortality. In conclusion, we reported in this study data of prevalence and recurrence rates of CDI in patients with AAD and evaluated the number of severe cases and infection-related mortality, which were up to now unknown in Southern Brazilian hospitals.

Using an ambidirectional case-control study, we found that the odds of Clostridioides difficile infection (CDI) were 3.38 (P = .01) times higher for patients with multidrug-resistant organism (MDRO) colonization compared to those without. MDRO colonization or infection 1-12 months before CDI testing significantly increased risk of positive CDI diagnosis (odds ratio 4.71, P = .02 and odds ratio = 5.03, P = .05, respectively) independent of antibiotic use, age, and comorbidity status. MDRO colonization and infection are associated with CDI, most significantly if they precede CDI.

OBJECTIVE: Gastrointestinal symptoms are often related to antibiotic treatment. Their incidence, risk and protective conditions in children are not well defined and represent the aims of this study.
METHODS: We prospectively enrolled inpatient children submitted to antibiotic treatment. Indication, type, dose and duration of treatment, probiotic supplementation and gastrointestinal symptoms were recorded at recruitment, after two and four weeks. Antibiotic-associated diarrhea (AAD) was defined as the presence of at least 3 loose/liquid stools within 14 days from antibiotic onset.
RESULTS: AAD occurred in 59/289 (20.4%) of patients, with increased risk in children younger than 3 years (relative risk [RR]=4.25), in lower respiratory (RR=2.11) and urinary infections (RR=3.67), intravenous administration (RR=1.81) and previous AAD episodes (RR=1.87). Abdominal pain occurred in 27/289 (9.3%), particularly in children >6 years (RR=4.15), with previous abdominal pain (RR=7.2) or constipation (RR=4.06). Constipation was recorded in 23/289 (8.0%), with increased risk in children having surgery (RR=2.56) or previous constipation (RR=7.38). Probiotic supplementation significantly reduced AAD (RR=0.30) and abdominal pain (RR=0.36). Lactobacillus rhamnosus GG (LGG) and L. reuteri significantly reduced AAD (RR=0.37 and 0.35) and abdominal pain (RR=0.37 and 0.24).
CONCLUSIONS: AAD occurred in 20.4% of children, with increased risk at younger age, lower respiratory and urinary tract infections, intravenous treatment and previous AAD. LGG and L. reuteri reduced both AAD and associated abdominal pain.