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Food and Drug Administration approval of the first microbiome therapies represents a true expansion the treatment paradigm for Clostridioides difficile but raises new questions about the future role of fecal microbiota transplantation. The authors outline the advances in microbiome therapeutic development that have addressed fecal microbiota transplantation's (FMT's) inherent limitations of safety and scalability. The authors also suggest that as microbiome therapeutic development continues for other indications, FMT will likely remain a necessary model of human microbiota dynamics for translational research. [ABSTRACT FROM AUTHOR]

The Antibacterial Resistance Leadership Group (ARLG) has prioritized infections caused by gram-positive bacteria as one of its core areas of emphasis. The ARLG Gram-positive Committee has focused on studies responding to 3 main identified research priorities: (1) investigation of strategies or therapies for infections predominantly caused by gram-positive bacteria, (2) evaluation of the efficacy of novel agents for infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci, and (3) optimization of dosing and duration of antimicrobial agents for gram-positive infections. Herein, we summarize ARLG accomplishments in gram-positive bacterial infection research, including studies aiming to (1) inform optimal vancomycin dosing, (2) determine the role of dalbavancin in MRSA bloodstream infection, (3) characterize enterococcal bloodstream infections, (4) demonstrate the benefits of short-course therapy for pediatric community-acquired pneumonia, (5) develop quality of life measures for use in clinical trials, and (6) advance understanding of the microbiome. Future studies will incorporate innovative methodologies with a focus on interventional clinical trials that have the potential to change clinical practice for difficult-to-treat infections, such as MRSA bloodstream infections. [ABSTRACT FROM AUTHOR]

Background Multidrug-resistant organisms (MDROs) frequently contaminate hospital environments. We performed a multicenter, cluster-randomized, crossover trial of 2 methods for monitoring of terminal cleaning effectiveness. Methods Six intensive care units (ICUs) at 3 medical centers received both interventions sequentially, in randomized order. Ten surfaces were surveyed each in 5 rooms weekly, after terminal cleaning, with adenosine triphosphate (ATP) monitoring or an ultraviolet fluorescent marker (UV/F). Results were delivered to environmental services staff in real time with failing surfaces recleaned. We measured monthly rates of MDRO infection or colonization, including methicillin-resistant Staphylococcus aureus , Clostridioides difficile , vancomycin-resistant Enterococcus, and MDR gram-negative bacilli (MDR-GNB) during a 12-month baseline period and sequential 6-month intervention periods, separated by a 2-month washout. Primary analysis compared only the randomized intervention periods, whereas secondary analysis included the baseline. Results The ATP method was associated with a reduction in incidence rate of MDRO infection or colonization compared with the UV/F period (incidence rate ratio [IRR] 0.876; 95% confidence interval [CI], 0.807–0.951; P  = .002). Including the baseline period, the ATP method was associated with reduced infection with MDROs (IRR 0.924; 95% CI, 0.855–0.998; P  = .04), and MDR-GNB infection or colonization (IRR 0.856; 95% CI, 0.825–0.887; P  < .001). The UV/F intervention was not associated with a statistically significant impact on these outcomes. Room turnaround time increased by a median of 1 minute with the ATP intervention and 4.5 minutes with UV/F compared with baseline. Conclusions Intensive monitoring of ICU terminal room cleaning with an ATP modality is associated with a reduction of MDRO infection and colonization. [ABSTRACT FROM AUTHOR]

Background Ventilator-associated lower respiratory tract infection (VA-LRTI) is common among critically ill patients and has been associated with increased morbidity and mortality. In acute critical illness, respiratory microbiome disruption indices (MDIs) have been shown to predict risk for VA-LRTI, but their utility beyond the first days of critical illness is unknown. We sought to characterize how MDIs previously shown to predict VA-LRTI at initiation of mechanical ventilation change with prolonged mechanical ventilation, and if they remain associated with VA-LRTI risk. Methods We developed a cohort of 83 subjects admitted to a long-term acute care hospital due to their prolonged dependence on mechanical ventilation; performed dense, longitudinal sampling of the lower respiratory tract, collecting 1066 specimens; and characterized the lower respiratory microbiome by 16S rRNA sequencing as well as total bacterial abundance by 16S rRNA quantitative polymerase chain reaction. Results Cross-sectional MDIs, including low Shannon diversity and high total bacterial abundance, were associated with risk for VA-LRTI, but associations had wide posterior credible intervals. Persistent lower respiratory microbiome disruption showed a more robust association with VA-LRTI risk, with each day of (base e) Shannon diversity <2.0 associated with a VA-LRTI odds ratio of 1.36 (95% credible interval, 1.10–1.72). The observed association was consistent across multiple clinical definitions of VA-LRTI. Conclusions Cross-sectional MDIs have limited ability to discriminate VA-LRTI risk during prolonged mechanical ventilation, but persistent lower respiratory tract microbiome disruption, best characterized by consecutive days with low Shannon diversity, may identify a population at high risk for infection and may help target infection-prevention interventions. [ABSTRACT FROM AUTHOR]

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) has been used to estimate quantitative viral load, with the goal of targeting isolation precautions for individuals with coronavirus disease 2019 (COVID-19) and guiding public health interventions. However, variability in specimen quality can alter the Ct values obtained from SARS-CoV-2 clinical assays. We sought to define how variable nasopharyngeal (NP) swab quality impacts clinical SARS-CoV-2 test sensitivity. Methods We performed amplification of a human gene target (β-actin) in parallel with a clinical RT-PCR targeting the SARS-CoV-2 ORF1ab gene for 1282 NP specimens collected from patients with clinical concern for COVID-19. We evaluated the relationship between NP specimen quality, characterized by late Ct values for the human gene target β-actin Ct, and the probability of SARS-CoV-2 detection via logistic regression, as well as the linear relationship between SARS-CoV-2 and β-actin Ct. Results Low-quality NP swabs are less likely to detect SARS-CoV-2 (odds ratio, 0.607 [95% credible interval {CrI},.487–.753]). We observed a positive linear relationship between SARS-CoV-2 and β-actin Ct values (slope, 0.181 [95% CrI,.097–.264]), consistent with a reduction in detection of 0.181 cycles for each additional cycle of the β-actin target. COVID-19 disease severity was not associated with β-actin Ct values. Conclusions Variability in NP specimen quality significantly impacts the performance of clinical SARS-CoV-2 assays, and caution should be taken when interpreting quantitative SARS-CoV-2 Ct results. If unrecognized, low-quality NP specimens, which are characterized by a low level of amplifiable human DNA target, may limit the successful application of SARS-CoV-2 Ct values to direct infection control and public health interventions. [ABSTRACT FROM AUTHOR]

Motivation: The variation in community composition between microbiome samples, termed beta diversity, can be measured by pairwise distance based on either presence--absence or quantitative species abundance data. PERMANOVA, a permutation-based extension of multivariate analysis of variance to a matrix of pairwise distances, partitions within-group and between-group distances to permit assessment of the effect of an exposure or intervention (grouping factor) upon the sampled microbiome. Within-group distance and exposure/intervention effect size must be accurately modeled to estimate statistical power for a microbiome study that will be analyzed with pairwise distances and PERMANOVA. Results: We present a framework for PERMANOVA power estimation tailored to marker-gene microbiome studies that will be analyzed by pairwise distances, which includes: (i) a novel method for distance matrix simulation that permits modeling of within-group pairwise distances according to pre-specified population parameters; (ii) a method to incorporate effects of different sizes within the simulated distance matrix; (iii) a simulation-based method for estimating PERMANOVA power from simulated distance matrices; and (iv) an R statistical software package that implements the above. Matrices of pairwise distances can be efficiently simulated to satisfy the triangle inequality and incorporate group-level effects, which are quantified by the adjusted coefficient of determination, omega-squared (ω²). From simulated distance matrices, available PERMANOVA power or necessary sample size can be estimated for a planned microbiome study. [ABSTRACT FROM AUTHOR]

Background Clostridioides difficile infection (CDI) is the leading cause of antibiotic-associated and health care–associated diarrhea in humans. Recurrent CDI (R-CDI) occurs in ~20%–30% of patients with CDI and results in increased morbidity, mortality, and hospital costs. Genomic analyses have shown overlap of C. difficile isolates from animals and people, suggesting that a zoonotic reservoir may contribute to recurrence. The objective of this study was to determine whether pet ownership is a risk factor for recurrence of CDI. Methods We conducted a case–control study among patients with recurrent CDI (cases; n = 86) and patients with nonrecurrent CDI (controls; n = 146). Multivariable logistic regression modeling was used to determine the association between recurrence of CDI and pet ownership while accounting for patient-level risk factors. Results Pet ownership was not significantly associated with recurrence of CDI (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.38–2.72; P  = 0.965) among all patients (n = 232). However, among the subset of patients with community-associated or community-onset health care facility–acquired CDI (n = 127), increasing contact with pets was increasingly protective against recurrence: for every point increase in a pet contact score (out of 7 possible points), the odds of recurrence decreased by 14% (OR, 0.86; 95% CI, 0.74–1.00; P  = 0.051). Conclusions Close interactions with pets appear protective against the recurrence of community-acquired CDI. A potential mechanism may involve beneficial contributions to the microbiota of pet owners afflicted with CDI, as has been observed for other conditions such as atopy, obesity, and food allergies. However, more research is needed to understand the interactions between pets, owners, and their microbiota. [ABSTRACT FROM AUTHOR]

Background We evaluated the differential impact of levofloxacin administered for the prophylaxis of bloodstream infections compared with broad-spectrum beta-lactam (BSBL) antibiotics used for the treatment of neutropenic fever on the gut microbiome in patients with hematologic malignancy. Methods Stool specimens were collected from patients admitted for chemotherapy or stem cell transplant in the setting of the evaluation of diarrhea from February 2017 until November 2017. Microbiome characteristics were compared among those exposed to levofloxacin prophylaxis vs those who received BSBL antibiotics. Results Sixty patients were included, most with acute myeloid leukemia (42%) or multiple myeloma (37%). The gut microbiome of patients with BSBL exposure had significantly reduced Shannon's alpha diversity compared with those without (median [interquartile range {IQR}], 3.28 [1.73 to 3.71] vs 3.73 [3.14 to 4.31]; P =.01). However, those with levofloxacin exposure had increased alpha diversity compared with those without (median [IQR], 3.83 [3.32 to 4.36] vs 3.32 [2.35 to 4.02]; P =.03). Levofloxacin exposure was also associated with a trend toward lower risk of dominance of non-Bacteroidetes genera compared with those without levofloxacin exposure (3 [14%] vs 15 [38%]; P =.051). Conclusions The impact of antibiotics on the gut microbiome varies by class, and levofloxacin may disrupt the gut microbiome less than BSBLs in this patient population. [ABSTRACT FROM AUTHOR]