OXA-48-Like ß-Lactamases: Global Epidemiology, Treatment Options, and Development Pipeline.

Modern medicine is threatened by the rising tide of antimicrobial resistance, especially among Gram-negative bacteria, where resistance to ß-lactams is most often mediated by ß-lactamases. The penicillin and cephalosporin ascendancies were, in their turn, ended by the proliferation of TEM penicillinases and CTX-M extended-spectrum ß-lactamases. These class A ß-lactamases have long been considered the most important. For carbapenems, however, the threat is increasingly from the insidious rise of a class D carbapenemase, OXA-48, and its close relatives. Over the past 20 years, OXA-48 and "OXA-48-like" enzymes have proliferated to become the most prevalent enterobacterial carbapenemases across much of Europe, Northern Africa, and the Middle East. OXA-48-like enzymes are notoriously difficult to detect because they often cause only low-level in vitro resistance to carbapenems, meaning that the true burden is likely underestimated. Despite this, they are associated with carbapenem treatment failures. A highly conserved incompatibility complex IncL plasmid scaffold often carries blaOXA-48 and may carry other antimicrobial resistance genes, leaving limited treatment options. High conjugation efficiency means that this plasmid is sometimes carried by multiple Enterobacterales in a single patient. Producers evade most ß-lactam-ß-lactamase inhibitor combinations, though promising agents have recently been licensed, notably ceftazidime-avibactam and cefiderocol. The molecular machinery enabling global spread, current treatment options, and the development pipeline of potential new therapies for Enterobacterales that produce OXA-48-like ß-lactamases form the focus of this review.

Choosing Wisely in Pediatric Hospital Medicine: 5 New Recommendations to Improve Value.

OBJECTIVES: The health care system faces ongoing challenges due to low-value care. Building on the first pediatric hospital medicine contribution to the American Board of Internal Medicine Foundation Choosing Wisely Campaign, a working group was convened to identify additional priorities for improving health care value for hospitalized children. METHODS: A study team composed of nominees from national pediatric medical professional societies was convened, including pediatric hospitalists with expertise in clinical care, hospital leadership, and research. The study team surveyed national pediatric hospitalist LISTSERVs for suggestions, condensed similar responses, and performed a literature search of articles published in the previous 10 years. Using a modified Delphi process, the team completed a series of structured ratings of feasibility and validity and facilitated group discussion. The sum of final mean validity and feasibility scores was used to identify the 5 highest priority recommendations. RESULTS: Two hundred seven respondents suggested 397 preliminary recommendations, yielding 74 unique recommendations that underwent evidence review and rating. The 5 highest-scoring recommendations had a focus on the following aspects of hospital care: (1) length of intravenous antibiotic therapy before transition to oral antibiotics, (2) length of stay for febrile infants evaluated for serious bacterial infection, (3) phototherapy for neonatal hyperbilirubinemia, (4) antibiotic therapy for community-acquired pneumonia, and (5) initiation of intravenous antibiotics in infants with maternal risk factors for sepsis. CONCLUSIONS: We propose that pediatric hospitalists can use this list to prioritize quality improvement and scholarly work focused on improving the value and quality of patient care for hospitalized children.

Reducing Outpatient Infant Blood Draws with Transcutaneous Measurement of Bilirubin.

INTRODUCTION: Newborn jaundice is a common outpatient problem. Transcutaneous bilirubin (TcB) measurements correlate well with total serum bilirubin (SB) measurements below 15 mg/dl and are efficient and noninvasive. Some concern exists that TcB measurement may subsequently lead to an increase in the number of SB measurements performed in the outpatient setting. We aimed to implement the use of a TcB device in an outpatient clinic. By doing so, we sought to increase the number of newborns screened solely by TcB as opposed to SB, by 30%, within 12 months. METHODS: We conducted plan-do-study-act cycles with targeted interventions to promote the use of TcB in an outpatient clinic for eligible newborns older than 35 weeks gestational age, aged 1-20 days, and without a history of transfusion, phototherapy, extensive bruising, or risk of hemolysis. We used statistical process control methods to measure proportions of newborns evaluated with TcB (run chart) and patients-between SB measurements (G-chart) over time in the outpatient clinic. RESULTS: We collected preintervention data for 18-months and intervention data for 12 months. For newborns attending the outpatient clinic, the proportion of TcB measurements increased after implementation of the use of TcB measurement. There was an increase in patients-between SB measurements. At project inception, SB was drawn for every 8 eligible patients. By the end of the project, there were 98 eligible newborns between instances of SB testing. CONCLUSION: Implementation of a quality-improvement initiative to measure TcB in the outpatient clinic was feasible and reduced the number of SB tests.

Bacterial and Fungal Coinfection in Individuals With Coronavirus: A Rapid Review To Support COVID-19 Antimicrobial Prescribing.

BACKGROUND: To explore and describe the current literature surrounding bacterial/fungal coinfection in patients with coronavirus infection. METHODS: MEDLINE, EMBASE, and Web of Science were searched using broad-based search criteria relating to coronavirus and bacterial coinfection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-CoV-2, and other coronavirus) and bacterial/fungal coinfection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal coinfections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-CoV-2 even in absence of coinfection was performed. RESULTS: 1007 abstracts were identified. Eighteen full texts reporting bacterial/fungal coinfection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140; 61%). Nine of 18 (50%) studies reported on COVID-19, 5/18 (28%) on SARS-1, 1/18 (6%) on MERS, and 3/18 (17%) on other coronaviruses. For COVID-19, 62/806 (8%) patients were reported as experiencing bacterial/fungal coinfection during hospital admission. Secondary analysis demonstrated wide use of broad-spectrum antibacterials, despite a paucity of evidence for bacterial coinfection. On secondary analysis, 1450/2010 (72%) of patients reported received antimicrobial therapy. No antimicrobial stewardship interventions were described. For non-COVID-19 cases, bacterial/fungal coinfection was reported in 89/815 (11%) of patients. Broad-spectrum antibiotic use was reported. CONCLUSIONS: Despite frequent prescription of broad-spectrum empirical antimicrobials in patients with coronavirus-associated respiratory infections, there is a paucity of data to support the association with respiratory bacterial/fungal coinfection. Generation of prospective evidence to support development of antimicrobial policy and appropriate stewardship interventions specific for the COVID-19 pandemic is urgently required.

Antimicrobial resistance in cystic fibrosis: A Delphi approach to defining best practices.

BACKGROUND: Antimicrobial susceptibility testing (AST) is a cornerstone of infection management in cystic fibrosis. However, there is little evidence that AST predicts the clinical outcome of CF antimicrobial treatment. It has been suggested there is a need for careful consideration of current AST use by the CF community. METHODS: We engaged a group of experts consisting of pulmonary (adult and pediatric) and infectious disease clinicians, microbiologists, and pharmacists representing a broad international experience. We conducted an iterative systematic survey (Delphi) to determine and quantify consensus regarding key questions facing CF clinicians in the use of respiratory culture results including what tests to order, when to obtain them, and how to act upon the results of the testing. RESULTS: Consensus was reached for many questions but there was not universal agreement to the questions that were addressed. There were some differences with respect to cultures obtained for surveillance compared to when there is clinical worsening. Areas of general consensus include when and how respiratory cultures should be performed, what information should be reported, and when AST should be performed. A key finding is that clinical response to treatment is used to guide treatment decisions rather than AST results. CONCLUSIONS: Recommendations are presented regarding questions related to microbiology testing for patients with CF. We have also offered recommendations for priority research questions.

The New Hampshire Ten Steps to Successful Breastfeeding Collaborative: A Statewide QI Initiative.

BACKGROUND AND OBJECTIVE: Despite national recognition for their breastfeeding-friendly practices, many New Hampshire hospitals are still not achieving the Ten Steps to Successful Breastfeeding. To increase achievement of the Ten Steps in New Hampshire's birthing hospitals, facilitate Baby-Friendly Hospital Initiative (BFHI) designation for interested hospitals, and improve rates of in-hospital any and exclusive breastfeeding. METHODS: After a 2010 needs assessment, we conducted 2 statewide workshops targeting 6 of the Ten Steps found to be most deficient among New Hampshire birthing hospitals. Eighteen of 20 hospitals attended at least 1 workshop, and 6 participated in an intensive collaborative. In 2013, we analyzed interval Ten Step achievement and in-hospital breastfeeding trends. RESULTS: Staff education showed the greatest improvement, increasing step 2 achievement from 1 to 6 hospitals (P=.05). Although the number of hospitals implementing step 6 (breast milk only) and step 9 (no artificial nipples) increased, differences were not statistically significant. Intensive collaborative hospitals achieved an average of 1.5 new steps, whereas non-Baby Friendly hospitals lost 0.7 steps (P=.05). In-hospital breastfeeding rates increased in intensive collaborative hospitals and were significantly higher than those in non-Baby Friendly hospitals by the end of the study (any breastfeeding, 89% vs 73%, P=.03; exclusive breastfeeding, 84% vs 61%, P<.001). CONCLUSIONS: A statewide improvement collaborative facilitated increases in Ten Step achievement and in-hospital breastfeeding for hospitals participating in an intensive collaborative. Active work in Ten Step implementation, including staff education, appears to be more effective in increasing in-hospital breastfeeding than does BFHI designation alone.

Transmission of hepatitis C from a midwife to a patient through non-exposure prone procedures.

A woman developed acute hepatitis C (HCV) infection 2 months after delivering her baby at a London Hospital. The other patients who had been on the unit at the same time all had negative HCV serology antenatally. Testing of the healthcare workers who had been involved in this patient's care revealed that one of the midwives who only worked on the postnatal unit was chronically infected with the same viral genotype. Sequencing and phylogenetic analysis revealed close identity between the viruses from the two individuals. Although, the midwife had only performed non-exposure prone procedures including venepuncture and cannulation, our findings indicate that transmission of the virus had occurred from the healthcare worker to the patient. The potential implications of this case within the setting of national policy on blood borne viruses and healthcare workers are discussed.

Making sense of evidence in management decisions: the role of research-based knowledge on innovation adoption and implementation in healthcare. study protocol.

BACKGROUND: We know that patient care can be improved by implementing evidence-based innovations and applying research findings linked to good practice. Successfully implementing innovations in complex organisations, such as the UK's National Health Service (NHS), is often challenging as multiple contextual dynamics mediate the process. Research studies have explored the challenges of introducing innovations into healthcare settings and have contributed to a better understanding of why potentially useful innovations are not always implemented in practice, even if backed by strong evidence. Mediating factors include health policy and health system influences, organisational factors, and individual and professional attitudes, including decision makers' perceptions of innovation evidence. There has been limited research on how different forms of evidence are accessed and utilised by organisational decision makers during innovation adoption. We also know little about how diverse healthcare professionals (clinicians, administrators) make sense of evidence and how this collective sensemaking mediates the uptake of innovations. METHODS: The study will involve nine comparative case study sites of acute care organisations grouped into three regional clusters across England. Each of the purposefully selected sites represents a variety of trust types and organisational contexts. We will use qualitative methods, in-depth interviews, observation of key meetings, and systematic analysis of relevant secondary data to understand the rationale and challenges involved in sourcing and utilising innovation evidence in the empirical setting of infection prevention and control. We will use theories of innovation adoption and sensemaking in organisations to interpret the data. The research will provide lessons for the uptake and continuous use of innovations in the English and international health systems. DISCUSSION: Unlike most innovation studies, which involve single-level analysis, our study will explore the innovation-adoption process at multiple embedded levels: micro (individual), meso (organisational), and macro (interorganisational). By comparing and contrasting across the nine sites, each with different organisational contexts, local networks, leadership styles, and different innovations considered for adoption, the findings of the study will have wide relevance. The research will produce actionable findings responding to the political and economic need for healthcare organisations to be innovation-ready.

Impact on and use of an inner-city London Infectious Diseases Department by international migrants: a questionnaire survey.

BACKGROUND: The UK has witnessed a considerable increase in immigration in the past decade. Migrant may face barriers to accessing appropriate health care on arrival and the current focus on screening certain migrants for tuberculosis on arrival is considered inadequate. We assessed the implications for an inner-city London Infectious Diseases Department in a high migrant area. METHODS: We administered an anonymous 20-point questionnaire survey to all admitted patients during a 6 week period. Questions related to sociodemographic characteristics and clinical presentation. Analysis was by migration status (UK born vs overseas born). RESULTS: 111 of 133 patients completed the survey (response rate 83.4%). 58 (52.2%) were born in the UK; 53 (47.7%) of the cohort were overseas born. Overseas-born were over-represented in comparison to Census data for this survey site (47.7% vs 33.6%; proportional difference 0.142 [95% CI 0.049-0.235]; p = 0.002): overseas born reported 33 different countries of birth, most (73.6%) of whom arrived in the UK pre-1975 and self-reported their nationality as British. A smaller number (26.4%) were new migrants to the UK (< or =10 years), mostly refugees/asylum seekers. Overseas-born patients presented with a broad range and more severe spectrum of infections, differing from the UK-born population, resulting in two deaths in this group only. Presentation with a primary infection was associated with refugee/asylum status (n = 8; OR 6.35 [95% CI 1.28-31.50]; p = 0.023), being a new migrant (12; 10.62 [2.24-50.23]; p = 0.003), and being overseas born (31; 3.69 [1.67-8.18]; p = 0.001). Not having registered with a primary-care physician was associated with being overseas born, being a refugee/asylum seeker, being a new migrant, not having English as a first language, and being in the UK for < or =5 years. No significant differences were found between groups in terms of duration of illness prior to presentation or duration of hospitalisation (mean 11.74 days [SD 12.69]). CONCLUSION: Migrants presented with a range of more severe infections, which suggests they face barriers to accessing appropriate health care and screening both on arrival and once settled through primary care services. A more organised and holistic approach to migrant health care is required.