Efficacy of Fecal Microbiota, Live-jslm (REBYOTA®), Among Patients Exposed to Non-Clostridioides difficile Infection Antibiotics: Post Hoc Subgroup Analysis of a Phase 2 Open-Label Study.

Background: Antibiotic use is a major risk factor for recurrent Clostridioides difficile infection (CDI) due to the associated disruption in gut microbiota. Fecal microbiota, live-jslm (REBYOTA®; RBL, previously RBX2660), is the first microbiota-based live biotherapeutic approved by the US Food and Drug Administration to prevent recurrent CDI in adults following standard-of-care antibiotic treatment. To investigate the impact of non-CDI antibiotics on the durability of RBL, a subgroup analysis was conducted on PUNCH™ Open-Label study participants who received non-CDI antibiotics during the period between RBL administration and up to 2 years after. Methods: Participants in PUNCH™ Open-Label who received non-CDI antibiotics after RBL administration were included in this subgroup analysis. Treatment response was defined as the absence of CDI diarrhea needing retreatment at the last evaluable time point (8 weeks, 6 months, 1 year, or 2 years) after RBL administration. Results: Among participants from PUNCH™ Open-Label, 43 received non-CDI antibiotics after RBL administration but before CDI recurrence as evaluated over a 2-year period. Across all evaluable time points, 86% (37/43) of participants had a treatment response regardless of when non-CDI antibiotic exposure occurred. Treatment response was sustained for a median 470 days (IQR, 212-648) from the first day of non-CDI antibiotic use. Most participants (5/6) with CDI recurrences received a high-risk antibiotic. Conclusions: RBL remained efficacious in participants with a history of recurrent CDI after subsequent non-CDI antibiotic exposure. Clinical Trials Registration: NCT02589847 (https://clinicaltrials.gov/study/NCT02589847).

National Outpatient Sexually Transmitted Infection Testing in Pregnant Patients in the United States.

Introduction: Sexually transmitted infections (STIs) continue to increase in the United States and pregnant patients who acquire STIs are at risk for serious complications. This study estimated the utilization of preventative STI testing among pregnant outpatients on a national scale. Methods: This was a retrospective, cross-sectional study of outpatient visits in the National Ambulatory Medical Care Survey from 2014 to 2016 and 2018 to 2019. All patients reported as pregnant were included to assess STI testing for chlamydia, gonorrhea, hepatitis, and HIV. STI testing was described per 1,000 total visits overall and by subpopulations. Data weights were applied to generate national estimates. Results: Over 177 million visits were included, of which 87.5 per 1,000 included an STI test. Chlamydia testing was the most common, followed by HIV, gonorrhea, and hepatitis (58.0 vs. 42.3 vs. 41.5 vs. 20.3 per 1,000). STI testing rates varied across subpopulations (72.1-236.6 per 1,000 visits). Patients of Hispanic ethnicity, Black race, age ≤25 years old, and those seen by an obstetrics and gynecology (OB/GYN) provider had the highest rates of STI testing. Independent predictors of STI testing included: Black race (adjusted odds ratio [aOR]: 2.24, 95% confidence interval [95% CI]: 2.23-2.24), first trimester (aOR: 5.15, 95% CI: 5.14-5.16), government and private insurance (aOR: 1.90, 95% CI: 1.89-1.91 and aOR: 1.70, 95% CI: 1.69-1.71), and an OB/GYN provider specialty (aOR: 2.93, 95% CI: 2.93-2.94). Conclusions: STI testing in United States outpatient physician offices varied by subpopulations and across individual test types. Certain patient attributes, such as race, provider specialty, and payment source, were predictive of testing.

Developing the Common Marmoset as a Translational Geroscience Model to Study the Microbiome and Healthy Aging.

Emerging data support associations between the depletion of the healthy gut microbiome and aging-related physiological decline and disease. In humans, fecal microbiota transplantation (FMT) has been used successfully to restore gut microbiome structure and function and to treat C. difficile infections, but its application to healthy aging has been scarcely investigated. The marmoset is an excellent model for evaluating microbiome-mediated changes with age and interventional treatments due to their relatively shorter lifespan and many social, behavioral, and physiological functions that mimic human aging. Prior work indicates that FMT is safe in marmosets and may successfully mediate gut microbiome function and host health. This narrative review (1) provides an overview of the rationale for FMT to support healthy aging using the marmoset as a translational geroscience model, (2) summarizes the prior use of FMT in marmosets, (3) outlines a protocol synthesized from prior literature for studying FMT in aging marmosets, and (4) describes limitations, knowledge gaps, and future research needs in this field.

Association of Gabapentinoids With Opioid-Related Overdose in the Inpatient Setting: A Single Center Retrospective Case-Control Study.

Objectives: Recent data suggest concomitant gabapentinoid use increases opioid-related overdose (ORO) risk; however, this association has not been well studied in the hospital setting. The primary objective of this study was to compare ORO risk, indicated by naloxone administration, in patients receiving opioids plus gabapentinoids versus opioids alone. Methods: In this retrospective case-control study of adults admitted to a large community hospital from 1/1/20 to 12/31/21, all cases (defined as patients who received naloxone more than 24 hours after admission) identified were matched 1:1 to randomly selected controls (defined as patients on opioids who did not receive naloxone). The primary outcome was the percentage of cases and controls with concomitant inpatient gabapentinoid use. Logistic regression was performed to determine the independent association between gabapentinoids and ORO (as evidenced by inpatient naloxone administration). Results: Baseline characteristics were similar between the 144 cases and 144 controls. Gabapentinoid exposure was greater for cases than controls (34.0%vs 20.8%, P = .0118). Median hospital length of stay (11vs 4 days, P < .0001) and mortality (19%vs 5%; P = .0018) were also higher for cases. In logistic regression analysis, ORO (adjusted OR 4.91; 95% CI 1.86-12.96) and serotonergic medication exposure (adjusted OR 4.31; 95% CI 1.50-12.38) were significantly associated with gabapentinoid use. Conclusions: Concomitant gabapentinoid use with opioids was associated with increased ORO risk in the inpatient setting. When considering prescribing gabapentinoids in conjunction with opioids in the hospital setting, potential benefits should be weighed against increased overdose risk.

Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance among Carbapenem-Resistant Enterobacterales.

Among carbapenem-resistant Enterobacterales (CRE) are diverse mechanisms, including those that are resistant to meropenem but susceptible to ertapenem, adding further complexity to the clinical landscape. This study investigates the emergence of ertapenem-resistant, meropenem-susceptible (ErMs) Escherichia coli and Klebsiella pneumoniae CRE across five hospitals in San Antonio, Texas, USA, from 2012 to 2018. The majority of the CRE isolates were non-carbapenemase producers (NCP; 54%; 41/76); 56% of all NCP isolates had an ErMs phenotype. Among ErMs strains, E. coli comprised the majority (72%). ErMs strains carrying blaCTX-M had, on average, 9-fold higher copies of blaCTX-M than CP-ErMs strains as well as approximately 4-fold more copies than blaCTX-M-positive but ertapenem- and meropenem-susceptible (EsMs) strains (3.7 vs. 0.9, p < 0.001). Notably, carbapenem hydrolysis was observed to be mediated by strains harboring blaCTX-M with and without a carbapenemase(s). ErMs also carried more mobile genetic elements, particularly IS26 composite transposons, than EsMs (37 vs. 0.2, p < 0.0001). MGE- ISVsa5 was uniquely more abundant in ErMs than either EsMs or ErMr strains, with over 30 more average ISVsa5 counts than both phenotype groups (p < 0.0001). Immunoblot analysis demonstrated the absence of OmpC expression in NCP-ErMs E. coli, with 92% of strains lacking full contig coverage of ompC. Overall, our findings characterize both collaborative and independent efforts between blaCTX-M and OmpC in ErMs strains, indicating the need to reappraise the term "non-carbapenemase (NCP)", particularly for strains highly expressing blaCTX-M. To improve outcomes for CRE-infected patients, future efforts should focus on mechanisms underlying the emerging ErMs subphenotype of CRE strains to develop technologies for its rapid detection and provide targeted therapeutic strategies.

Effects of COVID-19 hospitalization rates on the incidence of hospital-acquired Candida central line-associated bloodstream infection.

BACKGROUND: An increase in central line-associated bloodstream infections (CLABSIs) has been reported during the Coronavirus (COVID-19) pandemic; however, few studies have documented causative pathogens, particularly Candida species associated with candidemia. METHODS: This was a retrospective study based on the National Health Care Safety Network surveillance definitions of CLABSI caused by Candida species during pre-COVID-19 (October 2017 to February 2020) and COVID-19 (March 2020 to December 2021) periods within a local community hospital. Candida CLABSI incidence per 1,000 central line days was compared between periods using the χ2 test and correlated with COVID-19 inpatient hospitalization rates using Pearson correlation. RESULTS: Overall CLABSI (0.68 vs 1.98 per 1,000, P = .004) and Candida CLABSI incidence (0.06 vs 0.77 per 1,000, P = .003) significantly increased from pre-COVID-19 to COVID-19 periods. There was a significant correlation between COVID-19 ICU hospitalizations and CLABSIs (R = 0.18, P = .048), but not acute care hospitalizations and CLABSIs (R = 0.065, P = .250). Conversely, there was a significant association between COVID-19 acute care hospitalizations and Candida CLABSIs (R = 0.50, P < .001), but not COVID-19 ICU hospitalizations and Candida CLABSIs (R = 0.01, P = .631). CONCLUSIONS: During the COVID-19 pandemic, our facility experienced a significant increase in Candida CLABSI and a significant correlation of Candida CLABSIs with acute care COVID-19 hospitalizations.

Changes in oral health during aging in a novel non-human primate model.

Oral health plays a significant role in the quality of life and overall well-being of the aging population. However, age-related changes in oral health are not well understood due to challenges with current animal models. In this study, we analyzed the oral health and microbiota of a short-lived non-human primate (i.e., marmoset), as a step towards establishing a surrogate for studying the changes that occur in oral health during human aging. We investigated the oral health of marmosets using cadaveric tissues in three different cohorts: young (aged ≤6 years), middle-aged, and older (>10 years) and assessed the gingival bacterial community using analyses of the V3-V4 variable region of 16S rRNA gene. The oldest cohort had a significantly higher number of dental caries, increased dental attrition/erosion, and deeper periodontal pocket depth scores. Oral microbiome analyses showed that older marmosets had a significantly greater abundance of Escherichia-Shigella and Propionibacterium, and a lower abundance of Agrobacterium/Rhizobium at the genus level. Alpha diversity of the microbiome between the three groups showed no significant differences; however, principal coordinate analysis and non-metric multidimensional scaling analysis revealed that samples from middle-aged and older marmosets were more closely clustered than the youngest cohort. In addition, linear discriminant analysis effect size (LEFSe) identified a higher abundance of Esherichia-Shigella as a potential pathogenic biomarker in older animals. Our findings confirm that changes in the oral microbiome are associated with a decline in oral health in aging marmosets. The current study suggests that the marmoset model recapitulates some of the changes in oral health associated with human aging and may provide opportunities for developing new preventive strategies or interventions which target these disease conditions.

Infectious Inequity: How the Gut Microbiome and Social Determinants of Health May Contribute to Clostridioides difficile Infection Among Racial and Ethnic Minorities.

Infectious diseases are a leading contributor to death in the United States, and racial differences in clinical outcomes have been increasingly reported. Clostridioides difficile infection (CDI) is a growing public health concern, as it causes nearly half a million infections per year and considerable excess hospital costs. Concurrent with other infectious diseases, recent literature denotes racial disparities in CDI incidence rates, mortality, and associated morbidity. Of note, investigations into CDI and causative factors suggest that inequities in health-related social needs and other social determinants of health (SDoH) may cause disruption to the gut microbiome, thereby contributing to the observed deleterious outcomes in racially and ethnically minoritized individuals. Despite these discoveries, there is limited literature that provides context for the recognized racial disparities in CDI, particularly the influence of structural and systemic barriers. Here, we synthesize the available literature describing racial inequities in CDI outcomes and discuss the interrelationship of SDoH on microbiome dysregulation. Finally, we provide actionable considerations for infectious diseases professionals to aid in narrowing CDI equity gaps.

Comparative Effectiveness Randomized Clinical Trial Using Next-generation Microbial Sequencing to Direct Prophylactic Antibiotic Choice Before Urologic Stone Lithotripsy Using an Interprofessional Model.

Background: Next-generation sequencing (NGS) methods for microbial profiling have increased sensitivity to detect urinary pathogens. Objective: To determine whether NGS microbial profiling can be used to guide antibiotic prophylaxis and reduce infection compared with the standard of care. Design setting and participants: A prospective randomized controlled clinical trial of patients undergoing urologic stone interventions at an academic health center from December 2019 to January 2022 was conducted. Urine was collected at the preoperative visit for standard culture and intervention NGS diagnostics. Evaluable patients were culture negative, met 2-wk follow-up, and did not cancel surgery. Of 240 individuals (control = 121, intervention = 119), 83 control and 74 intervention patients were evaluable. Intervention: Microbial findings (paired quantitative polymerase chain reaction and NGS) were sent to an infectious disease pharmacist to recommend prophylactic antimicrobial regimen. Outcome measurements and statistical analysis: The primary outcome was postoperative urinary infection within the follow-up period (Fisher's exact test). The primary outcome was analyzed by modified intent-to-treat (mITT) and per-protocol analyses. Secondary endpoints considered included positive culture concordance, antibiotic use, and adverse events. Additional post hoc analyses investigated factors contributing to infection (univariate logistic regression). Results and limitations: The intervention significantly reduced postsurgical urinary infection risk by 7.1% (-0.73%, 15%) compared with the standard of care in the mITT analysis (1.4% vs 8.4%, p = 0.045) or by 8.5% (0.88%, 16%) compared with the per-protocol analysis (0% vs 8.5%, p = 0.032). NGS-guided treatment altered the distribution of antibiotics used (p = 0.025), and antibiotics poorly matched with NGS findings were associated with increased infection odds (odds ratio [OR] = 5.9, p = 0.046). Women were at greater odds to develop infection (OR = 10, p = 0.03) and possessed differentiated microbial profiles (p < 0.001). Conclusions: Urinary microbial NGS-guided antibiotic prophylaxis before endoscopic urologic stone lithotripsy improves antibiotic selection to reduce healthcare-associated urinary infections; however, treatment efficacy may be limited by the ability to adhere to the recommended protocol. Patient summary: We investigated whether microbial DNA sequencing could improve the selection of antibiotics before kidney stone surgery in patients not known to have any bacteria in the urine on standard culture. We found that using microbe DNA to guide antibiotic choices decreased postoperative infection rate and may encourage individualized use of available antibiotics.

Durvalumab Treatment Patterns for Patients with Unresectable Stage III Non-Small Cell Lung Cancer in the Veterans Health Administration (VHA): A Nationwide, Real-World Study.

BACKGROUND: Durvalumab is approved for the treatment of adults with unresectable stage III non-small cell lung cancer (NSCLC) post-chemoradiotherapy (CRT). This real-world study describes patient characteristics and durvalumab treatment patterns (number of doses and therapy duration; treatment initiation delays, interruptions, discontinuations, and associated reasons) among VHA-treated patients. METHODS: This was a retrospective cohort study of adults with unresectable stage III NSCLC receiving durvalumab at the VHA between 1 January 2017 and 30 June 2020. Patient characteristics and treatment patterns were presented descriptively. RESULTS: A total of 935 patients were included (median age: 69 years; 95% males; 21% Blacks; 46% current smokers; 16% ECOG performance scores ≥ 2; 50% squamous histology). Durvalumab initiation was delayed in 39% of patients (n = 367). Among the 200 patients with recorded reasons, delays were mainly due to physician preference (20%) and CRT toxicity (11%). Overall, patients received a median (interquartile range) of 16 (7-24) doses of durvalumab over 9.0 (2.9-11.8) months. Treatment interruptions were experienced by 19% of patients (n = 180), with toxicity (7.8%) and social reasons (2.6%) being the most cited reasons. Early discontinuation occurred in 59% of patients (n = 551), largely due to disease progression (24.2%) and toxicity (18.2%). CONCLUSIONS: These real-world analyses corroborate PACIFIC study results in terms of the main reasons for treatment discontinuation in a VHA population with worse prognostic factors, including older age, predominantly male sex, and poorer performance score. One of the main reasons for durvalumab initiation delays, treatment interruptions, or discontinuations was due to toxicities. Patients could benefit from improved strategies to prevent, identify, and manage CRT and durvalumab toxicities timely and effectively.

A Survey of Vaping Use, Perceptions, and Access in Adolescents from South-Central Texas Schools.

Despite efforts to dissuade major manufacturers and retailers from marketing and selling vape products to adolescents, the practice of vaping continues to increase in this population. Few studies have assessed adolescent perceptions of vaping, access to vaping, and use of vaping, and most rely, at least in part, on inferential conclusions drawn from data on smoking traditional combustible cigarettes. A novel electronic survey was created to assess the use of vapes, perceptions of vaping, and access to vaping among a convenience sample of adolescents (ages 12-20 years) in eleven schools in South-Central Texas from May to August 2021. The students' perceived threat of negative health outcomes due to vaping was calculated based on questions soliciting perceptions of severity (perceived danger) and susceptibility (perceived likelihood of illness). Trends were identified using descriptive and bivariate statistical tests. A total of 267 respondents were included; 26% had tried vaping. A majority (63%) did not believe vaping and smoking were synonymous. Most (70%) thought it was easy to obtain supplies and (76%) vape before and after (88%) or even during (64%) school. Respondents who vaped had a 34% lower perceived threat when compared to respondents who did not vape. In this sample of adolescents from South-Central Texas, one in four reported that they had tried vaping. Easy access to vapes and misperceptions regarding the safety of vaping might create a false sense of security with respect to vaping as an alternative to smoking, particularly among those who reported vaping, and is likely contributing to the increased use of vapes.

Health Equity in Patients Receiving Durvalumab for Unresectable Stage III Non-Small Cell Lung Cancer in the US Veterans Health Administration.

BACKGROUND: Real-world evidence is limited regarding the relationship between race and use of durvalumab, an immunotherapy approved for use in adults with unresectable stage III non-small cell lung cancer (NSCLC) post-chemoradiotherapy (CRT). This study aimed to evaluate if durvalumab treatment patterns differed by race in patients with unresectable stage III NSCLC in a Veterans Health Administration (VHA) population. MATERIALS AND METHODS: This was a retrospective analysis of White and Black adults with unresectable stage III NSCLC treated with durvalumab presenting to any VHA facility in the US from January 1, 2017, to June 30, 2020. Data captured included baseline characteristics and durvalumab treatment patterns, including treatment initiation delay (TID), interruption (TI), and discontinuation (TD); defined as CRT completion to durvalumab initiation greater than 42 days, greater than 28 days between durvalumab infusions, and more than 28 days from the last durvalumab dose with no new durvalumab restarts, respectively. The number of doses, duration of therapy, and adverse events were also collected. RESULTS: A total of 924 patients were included in this study (White = 726; Black = 198). Race was not a significant factor in a multivariate logistic regression model for TID (OR, 1.39; 95% CI, 0.81-2.37), TI (OR, 1.58; 95% CI, 0.90-2.76), or TD (OR, 0.84; 95% CI, 0.50-1.38). There were also no significant differences in median (interquartile range [IQR]) number of doses (White: 15 [7-24], Black: 18 [7-25]; P = .25) or median (IQR) duration of therapy (White: 8.7 months [2.9-11.8], Black: 9.8 months [3.6-12.0]; P = .08), although Black patients were less likely to experience an immune-related adverse event (28% vs. 36%, P = .03) and less likely to experience pneumonitis (7% vs. 14%, P < .01). CONCLUSION: Race was not found to be linked with TID, TI, or TD in this real-world study of patients with unresectable stage III NSCLC treated with durvalumab at the VHA.

Economic Impact of Recurrent Clostridioides difficile Infection in the USA: A Systematic Literature Review and Cost Synthesis.

INTRODUCTION: Up to 35% of patients with a first episode of Clostridioides difficile infection (CDI) develop recurrent CDI (rCDI), and of those, up to 65% experience multiple recurrences. A systematic literature review (SLR) was conducted to review and summarize the economic impact of rCDI in the United States of America. METHODS: English-language publications reporting real-world healthcare resource utilization (HRU) and/or direct medical costs associated with rCDI in the USA were searched in MEDLINE, MEDLINE In-Process, Embase, and the Cochrane Library databases over the past 10 years (2012-2022), as well as in selected scientific conferences that publish research on rCDI and its economic burden over the past 3 years (2019-2022). HRU and costs identified through the SLR were synthesized to estimate annual rCDI-attributable direct medical costs to inform the economic impact of rCDI from a US third-party payer's perspective. RESULTS: A total of 661 publications were retrieved, and 31 of them met all selection criteria. Substantial variability was found across these publications in terms of data source, patient population, sample size, definition of rCDI, follow-up period, outcomes reported, analytic approach, and methods to adjudicate rCDI-attributable costs. Only one study reported rCDI-attributable costs over 12 months. Synthesizing across the relevant publications using a component-based cost approach, the per-patient per-year rCDI-attributable direct medical cost was estimated to range from $67,837 to $82,268. CONCLUSIONS: While real-world studies on economic impact of rCDI in the USA suggested a high-cost burden, inconsistency in methodologies and results reporting warranted a component-based cost synthesis approach to estimate the annual medical cost burden of rCDI. Utilizing available literature, we estimated the average annual rCDI-attributable medical costs to allow for consistent economic assessments of rCDI and identify the budget impact on US payers.

Risk of Coronavirus Disease 2019-Associated Pulmonary Aspergillosis Based on Corticosteroid Duration in Intensive Care Patients.

Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a potential complication in critically ill COVID-19 patients. Corticosteroids are standard of care for hospitalized COVID-19 patients but carry an increased risk of secondary infections including CAPA. The objective of this study was to evaluate if duration of corticosteroid therapy ≤10 days versus >10 days affects the risk of developing CAPA. Methods: This was a retrospective cohort study of adult patients with severe COVID-19 pneumonia requiring mechanical ventilation who received at least 3 days of corticosteroid treatment. Incidence of CAPA and secondary outcomes were compared using appropriate bivariable analyses. Steroid duration was evaluated as an independent predictor in a logistic regression model. Results: A total of 278 patients were included (n = 169 for ≤10 days' steroid duration; n = 109 for >10 days). CAPA developed in 20 of 278 (7.2%) patients. Patients treated with >10 days of corticosteroid therapy had significantly higher incidence of CAPA (11.9% vs 4.1%; P = .0156), and steroid duration >10 days was independently associated with CAPA (odds ratio, 3.17 [95% confidence interval, 1.02-9.83]). Secondary outcomes including inpatient mortality (77.1% vs 43.2%; P < .0001), mechanical ventilation-free days at 28 days (0 vs 1.5; P < .0001), and secondary infections (44.9% vs 28.4% P = .0220) were worse in the >10 days cohort. Conclusions: Corticosteroid treatment >10 days in critically ill COVID-19 patients is associated with an increased risk of CAPA. Patients may require corticosteroids for reasons beyond COVID-19 and clinicians should be cognizant of risk of CAPA with prolonged courses.

Comparison of Droperidol and Midazolam Versus Haloperidol and Lorazepam for Acute Agitation Management in the Emergency Department.

BACKGROUND: Acute agitation accounts for up to 2.6% of visits to the emergency department (ED). To date, a standard of care for the management of acute agitation has not been established. Few studies have evaluated antipsychotic and benzodiazepine combinations. OBJECTIVE: The purpose of this study was to evaluate effectiveness and safety of combination therapy for acute agitation with intramuscular (IM) droperidol and midazolam (D+M) compared with IM haloperidol and lorazepam (H+L) in patients in the ED. METHODS: This was a single-center, retrospective medical record review of patients presenting to a large, academic ED with acute agitation from July 2020 through October 2021. The primary outcome was percentage of patients requiring additional agitation medication within 60 minutes of combination administration. Secondary outcomes included average time to repeat dose administration and average number of repeat doses required before ED discharge. RESULTS: A total of 306 patients were included for analysis: 102 in the D+M group and 204 in the H+L group. Repeat dose within 60 minutes occurred in 7 (6.9%) and 28 (13.8%) patients in the D+M and H+L groups, respectively (P = 0.065). A total of 28.4% of D+M patients and 30.9% of H+L patients required any repeat dose during their ED visit. Time to repeat dose was 12 and 24 minutes in the D+M and H+L, respectively (P = 0.22). The adverse event rate was 2.9% in each group. CONCLUSION AND RELEVANCE: IM D+M resulted in a lower rate of repeat doses of acute agitation medication compared with IM H+L, though this was not statistically significant. Both therapies were safe, and the adverse event rate was low.

Controversies in the Prevention and Treatment of Clostridioides difficile Infection in Adults: A Narrative Review.

Clostridioides difficile remains a problematic pathogen resulting in significant morbidity and mortality, especially for high-risk groups that include immunocompromised patients. Both the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America (IDSA/SHEA), as well as the American College of Gastroenterology (ACG) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recently provided guideline updates for C. difficile infection (CDI). In this narrative review, the authors reviewed available literature regarding the prevention or treatment of CDI in adults and focused on disagreements between the IDSA/SHEA and ACG guidelines, as well as articles that have been published since the updates. Several options for primary prophylaxis are available, including probiotics and antibiotics (vancomycin, fidaxomicin). The literature supporting fidaxomicin is currently quite limited. While there are more studies evaluating probiotics and vancomycin, the optimal patient populations and regimens for their use have yet to be defined. While the IDSA/SHEA guidelines discourage metronidazole use for mild CDI episodes, evidence exists that it may remain a reasonable option for these patients. Fidaxomicin has an advantage over vancomycin in reducing recurrences, but its use is limited by cost. Despite this, recent studies suggest fidaxomicin's cost-effectiveness as a first-line therapy, though this is highly dependent on institutional contracts and payment structures. Secondary prophylaxis should focus on non-antimicrobial options to lessen the impact on the microbiome. The oral option of fecal microbiota transplantation (FMT), SER109, and the now FDA-approved RBX2660 represent exciting new options to correct dysbiosis. Bezlotoxumab is another attractive option to prevent recurrences. Further head-to-head studies of newer agents will be needed to guide selection of the optimal therapies for CDI primary and secondary prophylaxis.

Population based cohort to examine association between geospatial antibiotic factors and urinary tract infection outcomes.

INTRODUCTION: Urinary tract infections (UTIs) pose a significant health care burden. Outpatient antibiotic geospatial factors (eg, geographic prescribing and geographic resistance) may be associated with inpatient outcomes. This study examined the relationship between these factors, severe UTI, and hospitalization for severe UTI. METHODS: The first cohort included hospitalized, female, Medicare beneficiaries, aged >50 years. The primary outcome was severe UTI (defined as CSS diagnosis code of 159 with an APR-DRG severity of illness code of 3 or 4). The association between geospatial first-line prescribing (FLP) and severe UTI was assessed. The second cohort examined the association between these geospatial FLP and risk of hospitalization with severe UTI. Multivariable regression was used to produce adjusted odds ratios and adjusted risk ratios. RESULTS: In the first cohort (n = 14,474), low FLP was not associated with severe UTI (P = .87) in univariable analysis. In multivariable analysis, low FLP was associated with severe UTI was (aOR: 1.08 [95% CI 1.00, 1.16]). In the second cohort (n = 2,972,174), the admission rate was 47.0 and 49.8 per 10,000 (low FLP vs high FLP, respectively [P < .001]). The aRR for admission was 1.26 (95% CI 1.14, 1.39) in areas with low FLP. CONCLUSIONS: This study suggests that geospatial antibiotic factors may influence inpatient outcomes in women aged >50 with UTI. Further research is needed to corroborate our findings.

Effectiveness and Safety of High-Dose Thromboprophylaxis in Morbidly Obese Major Trauma Patients.

BACKGROUND: Trauma increases risk for venous thromboembolism (VTE) and obesity is a known independent risk factor for VTE development. Currently, no consensus on an optimal prophylactic dosing strategy for morbidly obese trauma patients exists. The objective of this study is to evaluate the effectiveness and safety of a BMI-stratified dosing strategy for VTE prophylaxis in morbidly obese trauma patients. METHODS: This was a single center, retrospective cohort study of adult major trauma patients with a body mass index (BMI) of ≥40 kg/m2 admitted to the surgical-trauma intensive care unit from April 2014 to July 2020. Patients included were those who received enoxaparin 40 mg subcutaneously (SQ) every 12 hours (Q12H) for BMI of 40 to 49.9 kg/m2 or 60 mg SQ Q12H BMI ≥ 50 kg/m2 (per protocol), or enoxaparin 40 mg SQ Q12H for BMI of 40 to 49.9 kg/m2 (non-protocol). The primary endpoint was confirmed incidence of VTE. Secondary endpoints included occurrence of deep vein thrombosis (DVT) or pulmonary embolism (PE) during hospitalization, bleeding events, intensive care unit (ICU) and hospital length of stay (LOS) and hospital mortality. RESULTS: One hundred forty-five morbidly obese major trauma patients were included, with 123 patients (84.8%) in the per-protocol group. The primary outcome of in-hospital VTE did not occur in any patients in this group. Bleeding events occurred in 3 patients (2.7%) with a BMI of 40 to 49.9 kg/m2 and in 2 patients (16.7%) with a BMI of ≥50 kg/m2 (P = .064). Twenty-two patients in the non-protocol group were reviewed. One VTE event (4.5%) and no bleeding events occurred in this group. Median ICU LOS was 5 days, and hospital LOS was 11 days for the entire study group. CONCLUSIONS: Administration of enoxaparin 40 mg SQ Q12H to morbidly obese major trauma patients with a BMI of 40 to 49.9 kg/m2 and enoxaparin 60 mg SQ Q12H in those with a BMI of ≥50 kg/m2 resulted in low rates of VTE and bleeding events in the current study. However, future larger studies using this BMI-stratified dosing strategy are necessary to confirm these findings.

Electronic cigarette or vaping use among adolescents in the United States: A call for research and legislative action.

Vaping among adolescents is increasingly common and may result in poor health outcomes; however, little research has been conducted evaluating the risks of vaping among adolescents and the knowledge and perceptions that drive use. We must gain a better understanding of vaping outcomes and adolescents' perceptions while identifying potential ways to lessen or eradicate the health burdens associated with vaping. This knowledge could then inform robust educational and public health programs to prevent and mitigate vaping among youths. Health education incorporating a target populations' world view, spheres of influence, readiness, motivation, intention, and determination promotes informed decision making. There are few resources currently being allocated to the problem even though legislators and enforcement agencies are aware. We cannot simply rely on existing laws to serve as a sufficient deterrent to prevent underaged usage. Further efforts are needed in the areas of behavioral science, health education, and public policy to tackle this urgent public health concern.

The Risk and Clinical Implications of Antibiotic-Associated Acute Kidney Injury: A Review of the Clinical Data for Agents with Signals from the Food and Drug Administration's Adverse Event Reporting System (FAERS) Database.

Antibiotic-associated acute kidney injury (AA-AKI) is quite common, especially among hospitalized patients; however, little is known about risk factors or mechanisms of why AA-AKI occurs. In this review, the authors have reviewed all available literature prior to 1 June 2022, with a large number of AKI reports. Information regarding risk factors of AA-AKI, mechanisms behind AA-AKI, and treatment/management principles to decrease AA-AKI risk were collected and reviewed. Patients treated in the inpatient setting are at increased risk of AA-AKI due to common risk factors: hypovolemia, concomitant use of other nephrotoxic medications, and exacerbation of comorbid conditions. Clinicians should attempt to correct risk factors for AA-AKI, choose antibiotic therapies with decreased association of AA-AKI to protect their high-risk patients, and narrow, when clinically possible, the use of antibiotics which have decreased incidence of AKI. To treat AKI, it is still recommended to discontinue all offending nephrotoxic agents and to renally adjust all medications according to package insert recommendations to decrease patient harm.