Detection of Mpox Virus Using Microbial Cell-Free DNA: The Potential of Pathogen-Agnostic Sequencing for Rapid Identification of Emerging Pathogens.

BACKGROUND: The 2022 global outbreak of Monkeypox virus (MPXV) highlighted challenges with polymerase chain reaction detection as divergent strains emerged and atypical presentations limited the applicability of swab sampling. Recommended testing in the United States requires a swab of lesions, which arise late in infection and may be unrecognized. We present MPXV detections using plasma microbial cell-free DNA (mcfDNA) sequencing. METHODS: Fifteen plasma samples from 12 case-patients were characterized through mcfDNA sequencing. Assay performance was confirmed through in silico inclusivity and exclusivity assessments. MPXV isolates were genotyped using mcfDNA, and phylodynamic information was imputed using publicly available sequences. RESULTS: MPXV mcfDNA was detected in 12 case-patients. Mpox was not suspected in 5, with 1 having documented resolution of mpox >6 months previously. Six had moderate to severe mpox, supported by high MPXV mcfDNA concentrations; 4 died. In 7 case-patients, mcfDNA sequencing detected coinfections. Genotyping by mcfDNA sequencing identified 22 MPXV mutations at 10 genomic loci in 9 case-patients. Consistent with variation observed in the 2022 outbreak, 21 of 22 variants were G > A/C > T. Phylogenetic analyses imputed isolates to sublineages arising at different time points and from different geographic locations. CONCLUSIONS: We demonstrate the potential of plasma mcfDNA sequencing to detect, quantify, and, for acute infections with high sequencing coverage, subtype MPXV using a single noninvasive test. Sequencing plasma mcfDNA may augment existing mpox testing in vulnerable patient populations or in patients with atypical symptoms or unrecognized mpox. Strain type information may supplement disease surveillance and facilitate tracking emerging pathogens.

Recommendations to Improve Quality of Probiotic Systematic Reviews With Meta-Analyses.

Importance: Systematic reviews and meta-analyses often report conflicting results when assessing evidence for probiotic efficacy, partially because of the lack of understanding of the unique features of probiotic trials. As a consequence, clinical decisions on the use of probiotics have been confusing. Objective: To provide recommendations to improve the quality and consistency of systematic reviews with meta-analyses on probiotics, so evidence-based clinical decisions can be made with more clarity. Evidence Review: For this consensus statement, an updated literature review was conducted (January 1, 2020, to June 30, 2022) to supplement a previously published 2018 literature search to identify areas where probiotic systematic reviews with meta-analyses might be improved. An expert panel of 21 scientists and physicians with experience on writing and reviewing probiotic reviews and meta-analyses was convened and used a modified Delphi method to develop recommendations for future probiotic reviews. Findings: A total of 206 systematic reviews with meta-analysis components on probiotics were screened and representative examples discussed to determine areas for improvement. The expert panel initially identified 36 items that were inconsistently reported or were considered important to consider in probiotic meta-analyses. Of these, a consensus was reached for 9 recommendations to improve the quality of future probiotic meta-analyses. Conclusions and Relevance: In this study, the expert panel reached a consensus on 9 recommendations that should promote improved reporting of probiotic systematic reviews with meta-analyses and, thereby, assist in clinical decisions regarding the use of probiotics.

Enhanced Clostridioides difficile Infection Prevention With a Pharmacy-Controlled Policy That Adds a 3-Strain Lactobacillus Probiotic Concomitantly to Antibiotic Therapy.

When 70% of antibiotic users took a 3-strain Lactobacillus probiotic preparation the hospital-wide rate of healthcare-associated Clostridioides difficile infection improved significantly. The incidence of C. difficile infection for those taking the probiotic along with multiple antibiotics or a single high-risk antibiotic was decreased by at least half.

Choosing an appropriate probiotic product for your patient: An evidence-based practical guide.

INTRODUCTION: Clinicians and patients face a daunting task when choosing the most appropriate probiotic for their specific needs. Available preparations encompass a diverse and continuously expanding product base, with most available products lacking evidence-based trials that support their use. Even when evidence exists, not all probiotic products are equally effective for all disease prevention or treatment indications. At this point in time, drug regulatory agencies offer limited assistance with regard to guidance and oversight in most countries, including the U.S. METHODS: We reviewed the current medical literature and sources on the internet to survey the types of available probiotic products and to determine which probiotics had evidence-based efficacy data. Standard medical databases from inception to June 2018 were searched and discussions with experts in the field were conducted. We graded the strength of the evidence for probiotics having multiple, randomized controlled trials and developed a guide for the practical selection of current probiotic products for specific uses. RESULTS: We found the efficacy of probiotic products is both strain-specific and disease-specific. Important factors involved in choosing the appropriate probiotic include matching the strain(s) with the targeted disease or condition, type of formulation, dose used and the source (manufacturing quality control and shelf-life). While we found many probiotic products lacked confirmatory trials, we found sufficient evidence for 22 different types of probiotics from 249 trials to be included. For example, several types of probiotics had strong evidence for the prevention of antibiotic-associated diarrhea [Saccharomyces boulardii I-745, a three-strain mixture (Lactobacillus acidophilus CL1285, L. casei Lbc80r, L. rhamnosus CLR2) and L. casei DN114001]. Strong evidence was also found for four types of probiotics for the prevention of a variety of other diseases/conditions (enteral-feed associated diarrhea, travellers' diarrhea, necrotizing enterocolits and side-effects associated with H. pylori treatments. The evidence was most robust for the treatment of pediatric acute diarrhea based on 59 trials (7 types of probiotics have strong efficacy), while an eight-strain multi-strain mixture showed strong efficacy for inflammatory bowel disease and two types of probiotics had strong efficacy for irritable bowel disease. Of the 22 types of probiotics reviewed, 15 (68%) had strong-moderate evidence for efficacy for at least one type of disease. CONCLUSION: The choice of an appropriate probiotic is multi-factored, based on the mode and type of disease indication and the specific efficacy of probiotic strain(s), as well as product quality and formulation. TRIAL REGISTRATION: This review was registered with PROSPERO: CRD42018103979.