Next-Generation Sequencing Supports Targeted Antibiotic Treatment for Culture Negative Orthopedic Infections.

The isolation of an infective pathogen can be challenging in some patients with active, clinically apparent infectious diseases. Despite efforts in the microbiology lab to improve the sensitivity of culture in orthopedic implant-associated infections, the clinically relevant information often falls short of expectations. The management of peri-prosthetic joint infections (PJI) provides an excellent example of the use and benefits of newer diagnostic technologies to supplement the often-inadequate yield of traditional culture methods as a substantial percentage of orthopedic infections are culture-negative. Next-generation sequencing (NGS) has the potential to improve upon this yield. Bringing molecular diagnostics into practice can provide critical information about the nature of the infective organisms and allow targeted therapy in these otherwise challenging situations. This review article describes the current state of knowledge related to the use and potential of NGS to diagnose infections, particularly in the setting of PJIs.

Demographic Representation Among Speakers and Program Committee Members at the IDWeek Conference, 2013-2021.

BACKGROUND: In 2016, the IDWeek program committee was charged with ensuring gender equity in speaker sessions. Whether this charge also resulted in more opportunities for historically underrepresented speakers is unknown. METHODS: We conducted a retrospective analysis of trends in the demographic composition of IDWeek speakers and program committee members between 2013 and 2021. We used descriptive statistics to summarize data, χ2 tests to compare speaker demographics between 2013-2016 (before 2016) and 2017-2021 (after 2016), and Cochran-Armitage tests for trend. Each speaker slot was considered an independent event. RESULTS: A total of 5482 speaker slots were filled by 3389 individuals from 2013 to 2021. There was a linear increase in female speakers from 38.6% in 2013 to 58.4% in 2021 (P < .001). The proportion of white speakers decreased overall from 84.9% in 2013 to 63.5% in 2021. Compared with white speakers, more slots were filled by Asian speakers after 2016 versus before 2016 (20.1% vs 14.8%, respectively; P < .001). Program committee members from 2013-2021 were >80% non-Hispanic white; <5% of committee members identified as black, American Indian, Alaska Native, Native Hawaiian, Pacific Islander, or Hispanic. More program committee slots were filled by women after 2016 than before 2016 (52.7% vs 33.9%; P = .004). CONCLUSIONS: Intentional consideration of gender equity by the program committee was associated with equitable gender representation of invited speakers at IDWeek after 2016. Gradually, the proportions of IDWeek speakers from historically excluded racial/ethnic approached their respective proportions in the IDSA membership. White speakers remained overrepresented relative to membership proportions until 2021, and gaps in program committee racial/ethnic demographic representation highlights opportunities for continued inclusion, diversity, access, and equity at IDWeek.

Bringing Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) to the Surface: Is There a Role for Fomites?

Understanding the contribution of routes of transmission, particularly the role of fomites in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) transmission is important in developing and implementing successful public health infection prevention and control measures. This article will look at case reports, laboratory findings, animal studies, environmental factors, the need for disinfection, and differences in settings as they relate to SARS-CoV-2 transmission.

Lesbian, Gay, Bisexual, Transgender, and Queer (LGBTQ+) Communities and the Coronavirus Disease 2019 Pandemic: A Call to Break the Cycle of Structural Barriers.

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately impacted lesbian, gay, bisexual, transgender, and queer (LGBTQ+) communities. Many disparities mirror those of the human immunodeficiency virus (HIV)/AIDS epidemic. These health inequities have repeated throughout history due to the structural oppression of LGBTQ+ people. We aim to demonstrate that the familiar patterns of LGBTQ+ health disparities reflect a perpetuating, deeply rooted cycle of injustice imposed on LGBTQ+ people. Here, we contextualize COVID-19 inequities through the history of the HIV/AIDS crisis, describe manifestations of LGBTQ+ structural oppression exacerbated by the pandemic, and provide recommendations for medical professionals and institutions seeking to reduce health inequities.

Profiles of multidrug-resistant organisms among patients with bacteremia in intensive care units: an international ID-IRI survey.

Evaluating trends in antibiotic resistance is a requisite. The study aimed to analyze the profile of multidrug-resistant organisms (MDROs) among hospitalized patients with bacteremia in intensive care units (ICUs) in a large geographical area. This is a 1-month cross-sectional survey for blood-borne pathogens in 57 ICUs from 24 countries with different income levels: lower-middle-income (LMI), upper-middle-income (UMI), and high-income (HI) countries. Multidrug-resistant (MDR), extensively drug-resistant (XDR), or pan-drug-resistant isolates were searched. Logistic regression analysis determined resistance predictors among MDROs. Community-acquired infections were comparable to hospital-acquired infections particularly in LMI (94/202; 46.5% vs 108/202; 53.5%). Although MDR (65.1%; 502/771) and XDR (4.9%; 38/771) were common, no pan-drug-resistant isolate was recovered. In total, 32.1% of MDR were Klebsiella pneumoniae, and 55.3% of XDR were Acinetobacter baumannii. The highest MDR and XDR rates were in UMI and LMI, respectively, with no XDR revealed from HI. Predictors of MDR acquisition were male gender (OR, 12.11; 95% CI, 3.025-15.585) and the hospital-acquired origin of bacteremia (OR, 2.643; 95%CI, 1.462-3.894), and XDR acquisition was due to bacteremia in UMI (OR, 3.344; 95%CI, 1.189-5.626) and admission to medical-surgical ICUs (OR, 1.481; 95% CI, 1.076-2.037). We confirm the urgent need to expand stewardship activities to community settings especially in LMI, with more paid attention to the drugs with a higher potential for resistance. Empowering microbiology laboratories and reports to direct prescribing decisions should be prioritized. Supporting stewardship in ICUs, the mixed medical-surgical ones in particular, is warranted.

Cost-effectiveness of Universal Hepatitis C Screening in Pregnant Women: A Systematic Review.

BACKGROUND: Hepatitis C virus (HCV) epidemiology has shifted from the baby-boomer generation to young women of childbearing age. The health benefits and cost-effectiveness (CE) of screening pregnant women remain controversial. AIM: To systematically review published studies evaluating the CE of screening pregnant women for HCV in the era of direct-acting antivirals (DAAs). MATERIALS AND METHODS: We conducted a systematic literature search of CE studies evaluating the costs and benefits of screening pregnant women for HCV. Pertinent information including antiviral agent, drug costs, incremental cost-effective ratio (ICER), and infant care was collected. The authors' definition of the threshold price at which screening was deemed CE was also recorded. The quality of studies was assessed using the Consolidated Health Economic Evaluation Reports Standards (CHEERS) checklist. RESULTS: We identified 5 studies that evaluated the ICER of screening pregnant women for HCV. Of these, 2 utilized all oral DAAs, with universal screening CE. The ICER of these 2 studies was $3000 and $41,000 per quality of life-years gained. The remaining studies were interferon-based regimens. Most studies did not include screening of infants. CONCLUSIONS: Universally screening pregnant women for HCV was CE in studies that utilized oral DAAs. Most pharmacoeconomic studies failed to incorporate the impact of vertical transmission on infants.

Location Matters: Geographic Disparities and Impact of Coronavirus Disease 2019.

The coronavirus disease 2019 (COVID-19) pandemic in the United States has revealed major disparities in the access to testing and messaging about the pandemic based on the geographic location of individuals, particularly in communities of color, rural areas, and areas of low income. This geographic disparity, in addition to deeply rooted structural inequities, have posed additional challenges to adequately diagnose and provide care for individuals of all ages living in these settings. We describe the impact that COVID-19 has had on geographically disparate populations in the United States and share our recommendations on what might be done to ameliorate the current situation.

Racial Disparity of Coronavirus Disease 2019 in African American Communities.

The coronavirus disease 2019 (COVID-19) pandemic has unveiled unsettling disparities in the outcome of the disease among African Americans. These disparities are not new but are rooted in structural inequities that must be addressed to adequately care for communities of color. We describe the historical context of these structural inequities, their impact on the progression of COVID-19 in the African American (black) community, and suggest a multifaceted approach to addressing these healthcare disparities. (Of note, terminology from survey data cited for this article varied from blacks, African Americans, or both; for consistency, we use African Americans throughout.).

Estimating paediatric hepatitis C prevalence in the United States.

Over 70 million individuals are infected with hepatitis C virus (HCV) worldwide. Yet most prevalence data are in the adult population, with little focus on paediatrics, partially due to the scarcity of public data. The objective of this paper is to examine HCV prevalence in children by estimating prevalence rates among women, given the assumption that most cases are vertically transmitted. Between 2001 and 2017, maternal HCV infection affected ~ 0.24% of all births, with prevalence increasing by at least 261%. On average, approximately 0.01% of the total number of live births were infected with HCV, with a 245% increase in the number of children born with the infection. HCV epidemiology has evolved, with women of childbearing age representing a greater proportion of infected individuals in the United States, and infants born to infected mothers being at risk. We therefore recommend a greater public health focus of HCV on the paediatric population.

Meeting the WHO hepatitis C virus elimination goal: Review of treatment in paediatrics.

Over 3 million paediatric patients globally and ~50 000 in the United States are estimated to be infected with HCV. Eradicating HCV in children helps prevent liver fibrosis, cirrhosis and hepatocellular carcinoma; reduces extra-hepatic manifestations of HCV; improves quality of life; and increases survival. The 2019 American Association for the Study of Liver Diseases-Infectious Diseases Society of America (AASLD-IDSA) guidelines now recommend direct-acting antiviral (DAA) treatment with an approved regimen for all children and adolescents with HCV infection aged ≥3 years. We conducted a descriptive review of the new DAA treatments for HCV infection in the paediatric population. Ledipasvir/sofosbuvir (LDV/SOF) and sofosbuvir with ribavirin (SOF/RBV) are now approved for those ≥3 years old under specific clinical scenarios; sofosbuvir/velpatasvir (SOF/VEL) is the only pangenotypic agent approved for those ≥6 years or ≥17 kg, and glecaprevir/pibrentasvir (GLE/PIB) is approved for adolescents ≥12 years old or ≥45 kg. These DAA regimens are well-tolerated and have comparable sustained virologic response rates at 12 weeks post-treatment compared to those reported in adults (close to 100%). The introduction of DAAs has significantly changed the landscape of HCV treatment in adults and children with HCV infection and has increased confidence that the 2030 World Health Organization elimination goal may be attainable. Further studies are warranted to determine the optimal treatment for children with HCV infection, including timing, regimen and duration. Additionally, with the recent paediatric approvals, long-term safety data are needed.

WITHDRAWN: The next frontier: universal hepatitis C virus screening in pregnant women.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Hepatic Injury in Patients With COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has infected over 2 million people worldwide over the course of just several months. Various studies have highlighted that patients infected with COVID-19 may develop various degrees of liver injury. Here, we discuss the impact of underlying liver disease and manifestations of hepatic injury with COVID-19. We also review mechanisms of hepatic injury. METHODS: We searched the database PubMed for all studies focused on hepatic injury in COVID-19. RESULTS: We identified 13 studies that assessed the impact of underlying liver disease in patients infected with COVID-19 (N=3046). Underlying liver disease was one of the most common known comorbid categories in patients infected with COVID-19. Overall, 25% of the patients identified from the 13 studies had hepatic injury. Twenty-one percent and 24% had elevated alanine transaminase and aspartate transaminase values, respectively. Nine percent of the patients had elevated total bilirubin values. Ten of the 13 studies assessed COVID-19 acuity with severity of hepatic injury. In 9 of the 10 studies, clinical outcomes were worse with hepatic injury. CONCLUSIONS: Liver injury is highly prevalent in patients that present with COVID-19. Since the liver is one of the most affected organs outside of the respiratory system in COVID-19, more intensive surveillance is warranted for severe cases, particularly among those with pre-existing advanced liver disease.

Preferred Noninvasive Testing for Nonalcoholic Steatohepatitis.

BACKGROUND: There has been an increased interest in the use of noninvasive tests (NITs) to identify advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NALFD). The aim of our study was to define the change in tests' characteristics (sensitivity and specificity) of different combinations of NITs to detect advanced fibrosis in NAFLD. METHODS: We stratified NITs into first and second tiers and compared two different strategies of combining NITs to screen for advanced fibrosis in patients with NAFLD. One strategy was using NITs in parallel, and the other was using NITs sequentially. Within both of these strategies, there were two ways of interpreting the overall results. The first way was called "the AND rule," where a positive result required both individual test results to be positive. The second way was called "the OR rule," where a positive result required only one individual test to be positive. Accuracy of NITs was obtained from the literature search. Combined accuracy and likelihood ratio (LR) were calculated. RESULTS: Combination testing with parallel and sequential order testing under the AND Rule resulted in overall higher specificity and LR+ then using the NITs alone. Specificity ranged from 0.91 to 0.99, and LR+ from 9.3 to 68.6. The subsequent use of MRE was associated with LR+ between 36 and 69. Sensitivity was higher with parallel and sequential order testing under the OR Rule. LR+ ranged from 1.4 to 7.5, and sensitivity from 0.82 to 0.98. CONCLUSION: Screening for advanced fibrosis should be performed sequentially, with positive results confirmed by additional testing. Specificity and LR+ were highest when MRE was employed as the confirmatory test.

Going for the Gold: A Description of the Centers of Excellence Designation by the Infectious Diseases Society of America.

Antimicrobial stewardship programs (ASPs) are recommended by the Centers for Disease Control and Prevention and World Health Organization and mandated by the Joint Commission to curb antimicrobial resistance. However, <50% of institutions have optimal ASPs in place. Building on its experience of antimicrobial stewardship (AMS) advocacy, the Infectious Diseases Society of America (IDSA) developed the AMS Centers of Excellence (CoE) program, which will serve as a conduit to share best practices and highlight the standards for other hospitals to achieve in order to advance the field of AMS. A designation of CoE signifies that these institutions deliver high-quality care consistently, serve as the "gold" standard for executing novel AMS principles, and demonstrate commitment to their ASP. Here, we describe the process and purpose of designating institutions as AMS CoEs, provide awareness to clinicians on opportunities available through IDSA with this CoE designation, and discuss the evolution of the program.

Clinical Data on Daptomycin plus Ceftaroline versus Standard of Care Monotherapy in the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia.

Vancomycin (VAN) and daptomycin (DAP) are approved as a monotherapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A regimen of daptomycin plus ceftaroline (DAP+CPT) has shown promise in published case series of MRSA salvage therapy, but no comparative data exist to compare up-front DAP+CPT head-to-head therapy versus standard monotherapy as an initial treatment. In a pilot study, we evaluated 40 adult patients who were randomized to receive 6 to 8 mg/kg of body weight per day of DAP and 600 mg intravenous (i.v.) CPT every 8 h (q8h) (n = 17) or standard monotherapy (n = 23) with vancomycin (VAN; dosed to achieve serum trough concentrations of 15 to 20 mg/liter; n = 21) or 6 to 8 mg/kg/day DAP (n = 2). Serum drawn on the first day of bacteremia was sent to a reference laboratory post hoc for measurement of interleukin-10 (IL-10) concentrations and correlation to in-hospital mortality. Sources of bacteremia, median Pitt bacteremia scores, Charlson comorbidity indices, and median IL-10 serum concentrations were similar in both groups. Although the study was initially designed to examine bacteremia duration, we observed an unanticipated in-hospital mortality difference of 0% (0/17) for combination therapy and 26% (6/23) for monotherapy (P = 0.029), causing us to halt the study. Among patients with an IL-10 concentration of >5 pg/ml, 0% (0/14) died in the DAP+CPT group versus 26% (5/19) in the monotherapy group (P = 0.057). Here, we share the full results of this preliminary (but aborted) assessment of early DAP+CPT therapy versus standard monotherapy in MRSA bacteremia, hoping to encourage a more definitive clinical trial of its potential benefits against this leading cause of infection-associated mortality. (The clinical study discussed in this paper has been registered at ClinicalTrials.gov under identifier NCT02660346.).

Antibiotics and adverse events: the role of antimicrobial stewardship programs in 'doing no harm'.

PURPOSE OF REVIEW: Antimicrobial resistance (AMR) is a global threat worldwide, with deaths associated with AMR infections projected to exceed 10 million per year by the year 2050. The overuse and misuse of antibiotics is the primary driver of this resistance, with up to 50% of antibiotics prescribed in the hospital setting being either unnecessary or inappropriate. Antimicrobial stewardship (AMS) programs (ASPs) can mitigate some of this resistance, with the benefits well recognized; however, if we are to truly advance the state of AMS, the principles and practices should align with patient safety. RECENT FINDINGS: In a recent evaluation, among 1488 adult patients receiving systemic antibiotic therapy, 298 (20%) experienced at least one antibiotic-associated adverse drug event (ADE). Fifty-six (20%) nonclinically indicated antibiotic regimens were associated with an ADE. It is also well recognized that besides ADEs, the inappropriate use of antibiotics is associated the development of multidrug-resistant infections and Clostridium difficile infection. SUMMARY: Currently, there is a significant gap in ASPs correlating initiatives with patient safety goals, including reductions in antibiotic-associated ADEs and multidrug-resistant infections. Therefore, in this article, we provide the rationale for why ASPs are best suited to lead a collaborative effort to prevent antibiotic-associated ADEs and multidrug-resistant infections.

A Roadmap to Implementing Antimicrobial Stewardship Principles in Long-term Care Facilities (LTCFs): Collaboration Between an Acute-Care Hospital and LTCFs.

Effective 28 November 2017, the Centers for Medicare & Medicaid Services (CMS) mandated long-term care facilities (LTCFs) to have antimicrobial stewardship programs (ASPs) in place. Although guidance exists for establishing ASPs in LTCFs, limited data exist on the "how." As comprehensive ASPs already exist in many acute-care hospitals (ACHs) and with the known "sharing of patients" between both settings, extending ACH ASP expertise to LTCFs will not only aid LTCFs in complying with the CMS mandate but will likely also facilitate in decreasing multidrug-resistant organisms and Clostridium difficile infection rates in patients at both organizations. Here, we provide a roadmap on how to implement ASPs in LTCFs, using examples from our own ACH's collaboration with local LTCFs to develop and sustain LTCF ASPs. We discuss critical elements to achieving successful LTCF ASPs, including the potential barriers and how to overcome them.

Eight Habits of Highly Effective Antimicrobial Stewardship Programs to Meet the Joint Commission Standards for Hospitals.

In an effort to decrease antimicrobial resistance and inappropriate antibiotic use, The Joint Commission (TJC) recently issued new antimicrobial stewardship standards, consisting of 8 elements of performance, applicable to hospitals effective January 1, 2017. These standards coincide with those recommended by the Infectious Diseases Society of America (IDSA) and the Society of Healthcare Epidemiology (SHEA) guidelines. Little guidance exists on the "how" from these guidance documents. We review the 8 standards and provide real-world experience from established antimicrobial stewardship programs (ASPs) on how institutions can comply with these guidelines to reduce inappropriate antibiotic usage, decrease antimicrobial resistance, and optimize patient outcomes. TJC antimicrobial stewardship standards demonstrate actions being taken at the national level to make quality and patient safety a priority.