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Rising antimicrobial resistance (AMR) is a global health crisis for countries of all economic levels, alongside the broader challenge of access to antibiotics. As a result, development goals for child survival, healthy ageing, poverty reduction, and food security are at risk. Preserving antimicrobial effectiveness, a global public good, requires political will, targets, accountability frameworks, and funding. The upcoming second high-level meeting on AMR at the UN General Assembly (UNGA) in September, 2024, is evidence of political interest in addressing the problem of AMR, but action on targets, accountability, and funding, absent from the 2016 UNGA resolution, is needed. We propose ambitious yet achievable global targets for 2030 (relative to a prepandemic 2019 baseline): a 10% reduction in mortality from AMR; a 20% reduction in inappropriate human antibiotic use; and a 30% reduction in inappropriate animal antibiotic use. Given national variation in current levels of antibiotic use, these goals (termed the 10–20–30 by 2030) should be met within a framework of universal access to effective antibiotics. The WHO Access, Watch, Reserve (AWARE) system can be used to define, monitor, and evaluate appropriate levels of antibiotic use and access. Some countries should increase access to narrow-spectrum, safe, and affordable (Access) antibiotics, whereas others should discourage the inappropriate use of broader-spectrum (Watch) and last-resort (Reserve) antibiotics; AWARE targets should use a risk-based, burden-adjusted approach. Improved infection prevention and control, access to clean water and sanitation, and vaccination coverage can offset the selection effects of increased antibiotic use in low-income settings. To ensure accountability and global scientific guidance and consensus, we call for the establishment of the Independent Panel on Antimicrobial Access and Resistance and the support of leaders from low-income and middle-income countries. [ABSTRACT FROM AUTHOR]

COVID-19 demanded urgent and immediate global attention, during which other public health crises such as antimicrobial resistance (AMR) increased silently, undermining patient safety and the life-saving ability of several antimicrobials. In 2019, WHO declared AMR a top ten global public health threat facing humanity, with misuse and overuse of antimicrobials as the main drivers in the development of antimicrobial-resistant pathogens. AMR is steadily on the rise, especially in low-income and middle-income countries across south Asia, South America, and Africa. Extraordinary circumstances often demand an extraordinary response as did the COVID-19 pandemic, underscoring the fragility of health systems across the world and forcing governments and global agencies to think creatively. The key strategies that helped to contain the increasing SARS-CoV-2 infections included a focus on centralised governance with localised implementation, evidence-based risk communication and community engagement, use of technological methods for tracking and accountability, extensive expansion of access to diagnostics, and a global adult vaccination programme. The extensive and indiscriminate use of antimicrobials to treat patients, particularly in the early phase of the pandemic, have adversely affected AMR stewardship practices. However, there were important lessons learnt during the pandemic, which can be leveraged to strengthen surveillance and stewardship, and revitalise efforts to address the AMR crisis. [ABSTRACT FROM AUTHOR]

To investigate the drivers for infection management and antimicrobial stewardship (AMS) across high-infection-risk surgical pathways. A qualitative study—ethnographic observation of clinical practices, patient case studies, and face-to-face interviews with healthcare professionals (HCPs) and patients—was conducted across cardiovascular and thoracic and gastrointestinal surgical pathways in South Africa (SA) and India. Aided by Nvivo 11 software, data were coded and analysed until saturation was reached. The multiple modes of enquiry enabled cross-validation and triangulation of findings. Between July 2018 and August 2019, data were gathered from 190 hours of non-participant observations (138 India, 72 SA), interviews with HCPs (44 India, 61 SA), patients (six India, eight SA), and case studies (four India, two SA). Across the surgical pathway, multiple barriers impede effective infection management and AMS. The existing implicit roles of HCPs (including nurses and senior surgeons) are overlooked as interventions target junior doctors, bypassing the opportunity for integrating infection-related care across the surgical team. Critically, the ownership of decisions remains with the operating surgeons, and entrenched hierarchies restrict the inclusion of other HCPs in decision-making. The structural foundations to enable staff to change their behaviours and participate in infection-related surgical care are lacking. Identifying the implicit existing HCP roles in infection management is critical and will facilitate the development of effective and transparent processes across the surgical team for optimized care. Applying a framework approach that includes nurse leadership, empowering pharmacists and engaging surgical leads, is essential for integrated AMS and infection-related care. [ABSTRACT FROM AUTHOR]

COVID-19 has highlighted the worldwide inequities in access to the tools needed to tackle the pandemic. The same is the case for antibiotic resistance (ABR), which is projected to cause far greater devastation. The truth is that unless we tackle the burden of infectious diseases in low- and middle-income countries (LMICs), we will not impact ABR worldwide. Despite valiant efforts we have largely failed to address antibiotic conservation. We have directed millions of dollars into developing new antibiotics and surveillance systems and mostly ignored interventions such as infection prevention. Insufficient resources are dedicated to interventions such as sanitation and clean water, vaccination and changes in agricultural practice to reduce reliance on antimicrobials. Large-scale public health interventions are required. Funding mechanisms must be found to support LMICs in making these changes. Action is required at the highest levels. [ABSTRACT FROM AUTHOR]

Access to quality-assured antimicrobials is regarded as part of the human right to health, yet universal access is often undermined in low-income and middle-income countries. Lack of access to the instruments necessary to make the correct diagnosis and prescribe antimicrobials appropriately, in addition to weak health systems, heightens the challenge faced by prescribers. Evidence-based interventions in community and health-care settings can increase access to appropriately prescribed antimicrobials. The key global enablers of sustainable financing, governance, and leadership will be necessary to achieve access while preventing excess antimicrobial use. [ABSTRACT FROM AUTHOR]

To understand geographic variation in travel-related illness acquired in distinct African regions, we used the GeoSentinel Surveillance Network database to analyze records for 16,893 ill travelers returning from Africa over a 14-year period. Travelers to northern Africa most commonly reported gastrointestinal illnesses and dog bites. Febrile illnesses were more common in travelers returning from sub-Saharan countries. Eleven travelers died, 9 of malaria; these deaths occurred mainly among male business travelers to sub-Saharan Africa. The profile of illness varied substantially by region: malaria predominated in travelers returning from Central and Western Africa; schistosomiasis, strongyloidiasis, and dengue from Eastern and Western Africa; and loaisis from Central Africa. There were few reports of vaccine-preventable infections, HIV infection, and tuberculosis. Geographic profiling of illness acquired during travel to Africa guides targeted pretravel advice, expedites diagnosis in ill returning travelers, and may influence destination choices in tourism. [ABSTRACT FROM AUTHOR]

The WHO Model List of Essential Medicines (EML) prioritizes medicines that have significant global public health value. The EML can also deliver important messages on appropriate medicine use. Since 2017, in response to the growing challenge of antimicrobial resistance, antibiotics on the EML have been reviewed and categorized into three groups: Access, Watch, and Reserve, leading to a new categorization called AWaRe. These categories were developed taking into account the impact of different antibiotics and classes on antimicrobial resistance and the implications for their appropriate use. The 2023 AWaRe classification provides empirical guidance on 41 essential antibiotics for over 30 clinical infections targeting both the primary health care and hospital facility setting. A further 257 antibiotics not included on the EML have been allocated an AWaRe group for stewardship and monitoring purposes. This article describes the development of AWaRe, focussing on the clinical evidence base that guided the selection of Access, Watch, or Reserve antibiotics as first and second choices for each infection. The overarching objective was to offer a tool for optimizing the quality of global antibiotic prescribing and reduce inappropriate use by encouraging the use of Access antibiotics (or no antibiotics) where appropriate. This clinical evidence evaluation and subsequent EML recommendations are the basis for the AWaRe antibiotic book and related smartphone applications. By providing guidance on antibiotic prioritization, AWaRe aims to facilitate the revision of national lists of essential medicines, update national prescribing guidelines, and supervise antibiotic use. Adherence to AWaRe would extend the effectiveness of current antibiotics while helping countries expand access to these life-saving medicines for the benefit of current and future patients, health professionals, and the environment. [ABSTRACT FROM AUTHOR]

Background: Infections due to resistant bacteria are associated with severe illness, increased risk for complications, hospital admissions, and higher mortality. Inappropriate use of antibiotics, which contributes to increased antibiotic resistance (ABR), is common in healthcare settings across the globe. In Cameroon, antibiotics have been reported as high as 45-70% of prescriptions. We sought to investigate the knowledge, attitudes, and perceptions regarding appropriate antibiotic use and ABR of medical doctors practicing in tertiary hospitals in Yaoundé, Cameroon.Methods: We conducted a cross-sectional survey using a 54-item self-administered questionnaire sent via email to medical doctors working in the four major tertiary hospitals of Yaoundé. The questionnaire recorded socio-demographics, perceptions on antibiotic use and ABR, sources and usefulness of education on ABR, and clinical scenarios to appraise knowledge.Results: A total of 98/206 (48%) doctors responded. Years of experience ranged between 1 and 17 years. Most participants agreed that ABR is a problem nationwide (93%) and antibiotics are overused (96%), but only one third (32%) thought that ABR was a problem in their wards. Most respondents (65%) were confident that they use antibiotics appropriately. We found a mean knowledge score of 56% (± 14), with prescribers not influenced by patient-exerted pressure for antibiotic prescribing scoring better compared to those influenced by patients (67% vs 53%, p = 0.01). Overall, most participants (99%) expressed interest for further education on both appropriate antibiotic use and ABR.Conclusion: Confidence of prescribers in their ability to appropriately use antibiotics conflicts with the low level of knowledge on antibiotic use in this group of doctors. Moreover, the opinion of the majority, that ABR is not a problem in their own backyard is in keeping with similar studies in other countries and is of significant concern. Introduction of formal antibiotic stewardship programmes in Cameroon may be a useful intervention. [ABSTRACT FROM AUTHOR]

The link between healthcare worker (HCW) communication, teamwork and patient safety is well-established. Infection prevention and control (IPC) and antimicrobial stewardship (AMS) require multidisciplinary teamwork and communication. We conducted a scoping review of published evidence on effective mechanisms of HCW team communication in hospitals with the intention of transferring and tailoring learning to IPC and AMS team communication. PubMed, Scopus, Web of Science, and CINAHL were searched for studies that investigated HCW team communication across in-hospital patient pathways. Studies published between 2000 and 2021 that provided evidence on/or described the effect of communication on team and patient outcomes in hospital were included. Through a process of inductive qualitative content analysis, key themes in the included studies were identified. Of 537 studies identified, 53 (from high-income countries) were included in the data extraction. Fifty one percent (27/53) of studies were conducted in high acuity settings e.g., intensive care units. Standardizing or structuring the content and/or process of team communication was the most common goal of interventions (34/53, 64%). The key outcome measures were either team communication focused (25/34,74%) or patient and process outcome focused (8/34, 24%), such as reduced length of mechanical ventilation days, length of hospital stay, and shorter empiric antibiotic duration. Four studies (4/53, 8%) associated improved communication with positive IPC and AMS outcome measures. Mixed method intervention studies primarily facilitated collaborative input from HCWs and applied structures to standardize the content of patient care discussions, whereas observational studies describe component of team communication. A communication strategy that formalizes input from multidisciplinary team members can lead to optimized and consistent clinical discussion including in IPC and AMS-related care. Although we were unable to assess the effectiveness of interventions, the existing evidence suggests that optimizing team communication can have a positive effect on infection-related patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Empiric antibiotic strategies in the treatment of fracture-related infections, chronic osteomyelitis, prosthetic joint infection, and septic arthritis should be based on local microbiological antibiograms. This study aims to describe the microbiology and review the antibiogram profiles of bacterial isolates from patients undergoing surgical treatment for non-spinal orthopaedic infections, to identify the most appropriate empiric antibiotic strategy. Methods: A retrospective review was performed of all cases of non-spinal orthopaedic infections treated surgically from 1 January 2018 to 31 December 2018. The National Health Laboratory Service microbiology database was used to identify all intra-operative microbiological specimens obtained from orthopaedic patients, and data were correlated with the orthopaedic surgical database. Cases were divided into fracture-related infections, chronic osteomyelitis, prosthetic joint infection, and septic arthritis. Antibiotic susceptibility data were used to predict the efficacy of different empiric antibiotic regimens. Results: A total of 107 cases were included in the study; 184 organisms were cultured. Overall, the most common organism cultured was Staphylococcus aureus (25%) followed by Acinetobacter baumannii (9%), Enterococcus faecalis (7%) and Enterobacter cloacae (5%). Across all categories the oral antibiotic combination with the highest effectiveness (81%) would have been a combination of co-trimoxazole, ciprofloxacin and amoxicillin. The most effective intravenous antibiotic combination would have been either piperacillin–tazobactam, amikacin and vancomycin or meropenem and vancomycin; 90% of tested isolates were susceptible to either of these combinations. Conclusion: Antibiogram profiles can serve to guide to empiric antibiotic choice in the management of different categories of non-spinal orthopaedic infections. [ABSTRACT FROM AUTHOR]

Increasing reliance on antibiotics of last resort to treat the rising numbers of multidrug-resistant bacterial infections in people has focused attention on how shared-use antibiotics are managed and regulated across human and animal health. Discussions at international and national levels have intensified since the identification of new plasmid-mediated genes for colistin resistance in 2016, first in China and subsequently in many other countries, removing the last line of defense against multidrug-resistant Gram-negative bacterial infections with carbapenem resistance. South Africa has reacted to this threat by doing a situational analysis and review of the existing legislation concerning colistin use in animals and people, to inform which course of action to take. The experiences shared in this Personal View outline the process, institution of governance with widespread stakeholder engagement, surveillance, and interventions that South Africa has taken towards optimising the shared use of colistin. The instigation of stewardship guided by the principles of the One Health concept for shared-use antibiotics at the country level is a crucial component of any action plan to combat antibiotic resistance, and is as relevant to other existing antibiotics and new chemical entities that will be forthcoming from an invigorated antibiotic pipeline as it is to colistin. [ABSTRACT FROM AUTHOR]

Introduction: While a large proportion of people with HIV (PWH) have experienced SARS‐CoV‐2 infections, there is uncertainty about the role of HIV disease severity on COVID‐19 outcomes, especially in lower‐income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH. Methods: We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS‐CoV‐2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID‐19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period. Results: Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first‐diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults. Conclusions: Mortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID‐19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimized. [ABSTRACT FROM AUTHOR]

Objective: The irrational use of antibiotics is a leading contributor to antibiotic resistance. Antibiotic stewardship (AS) interventions predominantly focus on prescribers. This study investigated the influence and participation of inpatients in infection‐related care, including antibiotic decision‐making, within and across two tertiary hospitals in South Africa (Cape Town) and India (Kerala). Methods: Through ethnographic enquiry of clinical practice in surgical pathways, including direct nonparticipant observation of clinical practices, healthcare worker (HCW), patient and carer interactions in surgical ward rounds and face‐to‐face interviews with participants (HCWs and patients), we sought to capture the implicit and explicit influence that patients and carers have in infection‐related care. Field notes and interview transcripts were thematically coded, aided by NVivo 12® Pro software. Results: Whilst observational data revealed the nuanced roles that patients/carers play in antibiotic decision‐making, HCWs did not recognize these roles. Patients and carers, though invested in patient care, are not routinely involved, nor are they aware of the opportunities for engagement in infection‐related decision‐making. Patients associated clinical improvement with antibiotic use and did not consider hospitalization to be associated with infection acquisition or transmission, highlighting a lack of understanding of the threat of infection and antibiotic resistance. Patients' economic and cultural positionalities may influence their infection‐related behaviours. In the study site in India, cultural norms mean that carers play widespread but unrecognized roles in inpatient care, participating in infection prevention activities. Conclusion: For patients to have a valuable role in AS and make informed decisions regarding their infection‐related care, a mutual understanding of their role in this process among HCWs and patients is crucial. The observed differences between the two study sites indicate the critical need for understanding and addressing the contextual drivers that impact effective patient‐centred healthcare delivery. Patient or Public Contribution: Ethnographic observations and interviews conducted in this study involved patients as participants. Patients were recruited for interviews after obtaining signed informed consent forms. Patients' identities were completely anonymized when presenting the study findings. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance (AMR) is a recognized threat to global public health. Increasing AMR and a dry pipeline of novel antimicrobial drugs have put AMR in the international spotlight. One strategy to combat AMR is to reduce antimicrobial drug consumption. Governments around the world have been experimenting with different policy interventions, such as regulating where antimicrobials can be sold, restricting the use of last-resort antimicrobials, funding AMR stewardship programs, and launching public awareness campaigns. To inform future action, governments should have access to synthesized data on the effectiveness of large-scale AMR interventions. This planned systematic review will (1) identify and describe previously evaluated government policy interventions to reduce human antimicrobial use and (2) estimate the effectiveness of these different strategies. Methods: An electronic search strategy has been developed in consultation with two research librarians. Seven databases (MEDLINE, CINAHL, EMBASE, CENTRAL, PAIS Index, Web of Science, and PubMed excluding MEDLINE) will be searched, and additional studies will be identified using several gray literature search strategies. To be included, a study must (1) clearly describe the government policy and (2) use a rigorous design to quantitatively measure the impact of the policy on human antibiotic use. The intervention of interest is any policy intervention enacted by a government or government agency in any country to change human antimicrobial use. Two independent reviewers will screen for eligibility using criteria defined a priori. Data will be extracted with Covidence software using a customized extraction form. If sufficient data exists, a meta-analysis by intervention type will be conducted as part of the effectiveness review. However, if there are too few studies or if the interventions are too heterogeneous, data will be tabulated and a narrative synthesis strategy will be used. Discussion: This evidence synthesis is intended for use by policymakers, public health practitioners, and researchers to inform future government policies aiming to address antimicrobial resistance. This review will also identify gaps in the evidence about the effectiveness of different policy interventions to inform future research priorities. [ABSTRACT FROM AUTHOR]

Summary Objective The widespread use of antibiotics in humans and animals has contributed to growing rates of antibiotic resistance. Previously treatable bacterial infections now require the last line of antibiotics or are untreatable. The current antibiotic of last resort for carbapenem-resistant Gram-negative bacterial infections is often colistin. Evidence for the shifting pattern of colistin resistance and how the international community should respond are discussed in this review. Methods The literature on colistin resistance was reviewed. Results Plasmid-mediated colistin resistance encoded by mcr-1 was first documented in China during the routine surveillance of food animals. This has been followed by similar reports across a wide geographic area, in humans, animals, and the environment. The mcr-1 gene has been reported among human isolates in 29 countries, related to environmental samples in four countries, and in food animals and other animals in 28 countries. More recently, a second gene encoding resistance, mcr-2 , has been isolated from porcine and bovine Escherichia coli . Conclusion The emergence and horizontal transmission of colistin resistance highlights the need for heightened stewardship efforts across the One Health platform for this antibiotic of last resort, and indeed for all antibiotics used in animals and humans. [ABSTRACT FROM AUTHOR]

The article discusses the risk of needlestick injuries due to the improper disposal of blunt items in sharps bins. The author explains that limiting occupational needlestick and sharps injuries is a priority for infection control in hospitals. He reports the results of an audit of waste disposal practices at a hospital in Cape Town, South Africa, where a sharps bin was found to contain a banana skin and apple core.

A joke is presented about a doctor questioning a patient and mistaking her for a prostitute when she was a prosecutor.

• The diagnostic gap hides the true extent of antimicrobial resistance in Africa. • Conventional laboratory diagnostics are unlikely to bridge this gap. • Various point-of-care assays for antimicrobial resistance applications are in development. • Implementation strategies for point-of-care assays are needed to close the diagnostic gap. Sub-Saharan African (SSA) countries are severely impacted by antimicrobial resistance (AMR). Due to gaps in access to diagnostics in SSA, the true extent of AMR remains unknown. This diagnostic gap affects patient management and leads to significant antimicrobial overuse. This review explores how point-of-care (POC) testing for pathogen identification and AMR may be used to close the diagnostic gap in SSA countries. A narrative review exploring current clinical practice and novel developments in the field of POC testing for infectious diseases and AMR. POC assays for identification of various pathogens have been successfully rolled out in SSA countries. While implementation studies have mostly highlighted impressive test performance of POC assays, there is limited data on the impact of implementation on clinical outcomes and cost-effectiveness. We did not encounter local studies of host-directed POC assays relevant to AMR. Novel POC assays using real-time polymerase chain reaction, isothermal amplification, microfluidics, and other technologies are in various stages of development. Available literature shows that POC testing for AMR applications is implementable in SSA and holds the potential to reduce the diagnostic gap. Implementation will require effective regulatory pathways, incorporation of POC testing in clinical and laboratory guidelines, and adequate value capture in existing health financing models. [ABSTRACT FROM AUTHOR]

Background: There is still a paucity of evidence on the outcomes of coronavirus disease 2019 (COVID-19) among people living with human immunodeficiency virus (PWH) and those co-infected with tuberculosis (TB), particularly in areas where these conditions are common. We describe the clinical features, laboratory findings and outcome of hospitalised PWH and human immunodeficiency virus (HIV)-uninfected COVID-19 patients as well as those co-infected with tuberculosis (TB).Methods: We conducted a multicentre cohort study across three hospitals in Cape Town, South Africa. All adults requiring hospitalisation with confirmed COVID-19 pneumonia from March to July 2020 were analysed.Results: PWH comprised 270 (19%) of 1434 admissions. There were 47 patients with active tuberculosis (3.3%), of whom 29 (62%) were PWH. Three-hundred and seventy-three patients (26%) died. The mortality in PWH (n = 71, 26%) and HIV-uninfected patients (n = 296, 25%) was comparable. In patients with TB, PWH had a higher mortality than HIV-uninfected patients (n = 11, 38% vs n = 3, 20%; p = 0.001). In multivariable survival analysis a higher risk of death was associated with older age (Adjusted Hazard Ratio (AHR) 1.03 95%CI 1.02-1.03, p < 0.001), male sex (AHR1.38 (95%CI 1.12-1.72, p = 0.003) and being "overweight or obese" (AHR 1.30 95%CI 1.03-1.61 p = 0.024). HIV (AHR 1.28 95%CI 0.95-1.72, p 0.11) and active TB (AHR 1.50 95%CI 0.84-2.67, p = 0.17) were not independently associated with increased risk of COVID-19 death. Risk factors for inpatient mortality in PWH included CD4 cell count < 200 cells/mm3, higher admission oxygen requirements, absolute white cell counts, neutrophil/lymphocyte ratios, C-reactive protein, and creatinine levels.Conclusion: In a population with high prevalence of HIV and TB, being overweight/obese was associated with increased risk of mortality in COVID-19 hospital admissions, emphasising the need for public health interventions in this patient population. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The objective was to compare COVID‐19 outcomes in the Omicron‐driven fourth wave with prior waves in the Western Cape, assess the contribution of undiagnosed prior infection to differences in outcomes in a context of high seroprevalence due to prior infection and determine whether protection against severe disease conferred by prior infection and/or vaccination was maintained. METHODS: In this cohort study, we included public sector patients aged ≥20 years with a laboratory‐confirmed COVID‐19 diagnosis between 14 November and 11 December 2021 (wave four) and equivalent prior wave periods. We compared the risk between waves of the following outcomes using Cox regression: death, severe hospitalisation or death and any hospitalisation or death (all ≤14 days after diagnosis) adjusted for age, sex, comorbidities, geography, vaccination and prior infection. RESULTS: We included 5144 patients from wave four and 11,609 from prior waves. The risk of all outcomes was lower in wave four compared to the Delta‐driven wave three (adjusted hazard ratio (aHR) [95% confidence interval (CI)] for death 0.27 [0.19; 0.38]. Risk reduction was lower when adjusting for vaccination and prior diagnosed infection (aHR: 0.41, 95% CI: 0.29; 0.59) and reduced further when accounting for unascertained prior infections (aHR: 0.72). Vaccine protection was maintained in wave four (aHR for outcome of death: 0.24; 95% CI: 0.10; 0.58). CONCLUSIONS: In the Omicron‐driven wave, severe COVID‐19 outcomes were reduced mostly due to protection conferred by prior infection and/or vaccination, but intrinsically reduced virulence may account for a modest reduction in risk of severe hospitalisation or death compared to the Delta‐driven wave. [ABSTRACT FROM AUTHOR]

• The COVID-19 pandemic has helped challenge the usual way of doing research. • A prolonged on-site presence at the early stage of projects is critical. • Research should rely on a capacity-building strategy to provide local skills. • Funding should be proportionate to the cost of resources and gaps in each low middle income countries setting. This article summarizes the consequences of the COVID-19 pandemic, on an international project to tackle antimicrobial resistance (AMR). The research leadership and process, the access to data, and stakeholders were deeply disrupted by the national and international response to the pandemic, including the interruption of healthcare delivery, lockdowns, and quarantines. The key principles to deliver the research through the pandemic were mainly the high degree of interdisciplinary engagement with integrated teams, and equitable partnership across sites with capacity building and leadership training. The level of preexisting collaboration and partnership were also keys to sustaining connections and involvements throughout the pandemic. The pandemic offered opportunities for realigning research priorities. Flexibility in funding timelines and projects inputs are required to accommodate variance introduced by external factors. The current models for research collaboration and funding need to be critically evaluated and redesigned to retain the innovation that was shown to be successful through this pandemic. [ABSTRACT FROM AUTHOR]

An editorial is presented in which the authors discuss several aspects of the Paris Agreement under the United Nations Framework Convention on Climate Change that may be significant and applicable in global governance of antimicrobial resistance (AMR), particularly in the wake of the COVID-19 pandemic. The authors call for an international treaty concerning pandemics.

Background: The outcome of kidney transplantation in human immunodeficiency virus (HIV)-positive patients who receive organs from HIV-negative donors has been reported to be similar to the outcome in HIV-negative recipients. We report the outcomes at 3 to 5 years in HIV-positive patients who received kidneys from HIV-positive deceased donors. Methods: We conducted a prospective, nonrandomized study of kidney transplantation in HIV-infected patients who had a CD4 T-cell count of 200 per cubic millimeter or higher and an undetectable plasma HIV RNA level. All the patients were receiving antiretroviral therapy (ART). The patients received kidneys from deceased donors who tested positive for HIV with the use of fourth-generation enzyme-linked immunosorbent assay at the time of referral. All the donors either had received no ART previously or had received only first-line ART. Results: From September 2008 through February 2014, a total of 27 HIV-positive patients underwent kidney transplantation. Survivors were followed for a median of 2.4 years. The rate of survival among the patients was 84% at 1 year, 84% at 3 years, and 74% at 5 years. The corresponding rates of graft survival were 93%, 84%, and 84%. (If a patient died with a functioning graft, the calculation was performed as if the graft had survived.) Rejection rates were 8% at 1 year and 22% at 3 years. HIV infection remained well controlled, with undetectable virus in blood after the transplantation. Conclusions: Kidney transplantation from an HIV-positive donor appears to be an additional treatment option for HIV-infected patients requiring renal-replacement therapy. (Funded by Sanofi South Africa and the Roche Organ Transplantation Research Foundation.). [ABSTRACT FROM AUTHOR]

The article presents a study on the outcome of kidney transplantation from human immunodeficiency virus (HIV)-negative donors to HIV-positive patients from September 2008 through February 2014. The patients had a CD4 T-cell count of 200 per cubic millimeter or higher and an undetectable plasma HIV RNA level, in which they were receiving antiretroviral therapy. It also suggests that the outcome was the same for an HIV-positive donor and HIV-infect patients needing renal-replacement therapy.

Antibiotics are often prescribed inappropriately, either when they are not necessary or with an unnecessarily broad spectrum of activity. AWaRe (AccessWatchReserve) is a system developed by WHO to classify antibiotics based on their spectrum of activity and potential for favouring the development of antibiotic resistance (Access: narrow spectrum/low potential for resistance; Watch: broader spectrum/higher potential for resistance; Reserve: last resort antibiotics to use very selectively). The WHO target is that by 2023, at least 60% of prescribed antibiotics globally should be from the Access category. The WHO AWaRe Book aims to improve empiric antibiotic prescribing by providing simple guidance for common infections based on the principles of AWaRe in alignment with the Model Lists of Essential Medicines for adults and children. [ABSTRACT FROM AUTHOR]

• Patient participation in surgical care is associated with improved outcomes. • Opportunities exist for patient engagement in infection care in the surgical pathway. • Effective patient engagement is needed, particularly in antimicrobial stewardship. To explore the existing evidence on patient understanding of and/or participation in infection-related care in surgical specialties. A scoping review of the literature was conducted. PubMed, Web of Science, Scopus, and grey literature sources were searched using predefined search criteria for policies, guidelines, and studies in the English language. Data synthesis was done through content and thematic analysis to identify key themes in the included studies. The initial search identified 604 studies, of which 41 (36 from high-income and five from low- and middle-income countries) were included in the final review. Most of the included studies focused on measures to engage patients in infection prevention and control (IPC) activities, with few examples of antimicrobial stewardship (AMS) engagement strategies. While patient engagement interventions in infection-related care varied depending on study goals, surgical wound management was the most common intervention. AMS engagement was primarily limited to needs assessment, without follow-up to address such needs. Existing evidence highlights a gap in patient participation in infection-related care in the surgical pathway. Standardization of patient engagement strategies is challenging, particularly in the context of surgery, where several factors influence how the patient can engage and retain information. Infection-related patient engagement and participation strategies in surgery need to be inclusive and contextually fit. [ABSTRACT FROM AUTHOR]

Though women increasingly make up the majority of medical-school and other science graduates, they remain a minority in academic biomedical settings, where they are less likely to hold leadership positions or be awarded research funding. A major factor is the career breaks that women disproportionately take to see to familial duties. They experience a related, but overlooked, hurdle upon their return: they are often too old to be eligible for 'early-career researcher' grants and 'career-development' awards, which are stepping stones to leadership positions in many institutions and which determine the demographics of their hierarchies for decades to come. Though age limits are imposed to protect young applicants from more experienced seniors, they have an unintended side effect of excluding returning workers, still disproportionately women, from the running. In this joint effort by the European Society of Clinical Microbiology and Infectious Diseases, the Federation of European Microbiological Societies, the Infectious Disease Society of America, the International Society for Infectious Diseases and the Swiss Society for Infectious Diseases, we invited all European Congress of Clinical Microbiology and Infectious Diseases-affiliated medical societies and funding bodies to participate in a survey on current 'early-career' application restrictions and measures taken to provide protections for career breaks. The following simple consensus recommendations are geared to funding bodies, academic societies and other organizations for the fair handling of eligibility for early-career awards: 1. Apply a professional, not physiological, age limit to applicants. 2. State clearly in the award announcement that career breaks will be factored into applicants' evaluations such that: • Time absent is time extended : for every full-time equivalent of career break taken, the same full-time equivalent will be extended to the professional age limit. • Opportunity costs will also be taken into account : people who take career breaks risk additional opportunity costs, with work that they did before the career break often being forgotten or poorly documented, particularly in bibliometric accounting. Although there is no standardized metric to measure additional opportunity costs, organizations should (a) keep in mind their existence when judging applicants' submissions, and (b) note clearly in the award announcement that opportunity costs of career breaks are also taken into account. 3. State clearly that further considerations can be undertaken, using more individualized criteria that are specific to the applicant population and the award in question. The working group welcomes feedback so that these recommendations can be improved and updated as needed. [ABSTRACT FROM AUTHOR]

In 2013, a Lancet Infectious Diseases Commission described the state of antimicrobial resistance worldwide. Since then, greater awareness of the public health ramifications of antimicrobial resistance has led to national actions and global initiatives, including a resolution at the high-level meeting of the UN General Assembly in 2016. Progress in addressing this issue has ranged from a ban on irrational drug combinations in India to commitments to ban colistin as a growth promoter in animals, improve hospital infection control, and implement better antimicrobial stewardship. Funds have been mobilised, and regulatory barriers to new antibiotic development have been relaxed. These efforts have been episodic and uneven across countries, however. Sustained funding for antimicrobial resistance and globally harmonised targets to monitor progress are still urgently needed. Except for in a few leading countries, antimicrobial resistance has not captured the sustained focus of national leaders and country-level actors, including care providers. [ABSTRACT FROM AUTHOR]

Background There are limited data on the etiology of respiratory infections in human immunodeficiency virus (HIV)–infected patients in resource-limited settings. Methods We performed quantitative multiplex real-time polymerase chain reaction (PCR) for Pneumocystis jirovecii and common bacterial and viral respiratory pathogens on sputum samples (spontaneous or induced) from a prospective cohort study of HIV-infected inpatients with World Health Organization danger signs and cough. Mycobacterial culture was done on 2 sputum samples, blood cultures, and relevant extrapulmonary samples. Results We enrolled 284 participants from 2 secondary-level hospitals in Cape Town, South Africa: median CD4 count was 97 cells/μL, 64% were women, and 38% were on antiretroviral therapy. One hundred forty-eight had culture-positive tuberculosis, 100 had community-acquired pneumonia (CAP), 26 had P. jirovecii pneumonia (PJP), and 64 had other diagnoses. Probable bacterial infection (>105 copies/mL) was detected in 133 participants; the prevalence was highest in those with CAP (52%). Haemophilus influenzae and Streptococcus pneumoniae were the commonest bacterial pathogens detected; atypical bacteria were uncommon. Viruses were detected in 203 participants; the prevalence was highest in those with PJP (85%). Human metapneumovirus was the commonest virus detected. Multiple coinfections were commonly detected. Conclusions Sputum multiplex PCR could become a useful diagnostic tool for bacterial respiratory infections in HIV-infected inpatients, but its value is limited as quantitative cutoffs have only been established for a few bacterial pathogens and validation has not been done in this patient population. We found a high prevalence of respiratory viruses, but it is unclear whether these viruses were causing infection as there are no accepted quantitative PCR cutoffs for diagnosing respiratory viral infections. [ABSTRACT FROM AUTHOR]

'Superbugs', bacteria that have become resistant to antibiotics, have been in numerous media headlines, raising awareness of antibiotic resistance and leading to multiple action plans from policymakers worldwide. However, many commonly used terms, such as 'the war against superbugs', risk misleading people to request 'new' or 'stronger' antibiotics from their doctors, veterinary surgeons or pharmacists, rather than addressing a fundamental issue: the misuse and overuse of antibiotics in humans and animals. Simple measures of antibiotic consumption are needed for mass communication. In this article, we describe the concept of the 'antibiotic footprint' as a tool to communicate to the public the magnitude of antibiotic use in humans, animals and industry, and how it could support the reduction of overuse and misuse of antibiotics worldwide. We propose that people need to make appropriate changes in behaviour that reduce their direct and indirect consumption of antibiotics. [ABSTRACT FROM AUTHOR]

Background: Growing political attention to antimicrobial resistance (AMR) offers a rare opportunity for achieving meaningful action. Many governments have developed national AMR action plans, but most have not yet implemented policy interventions to reduce antimicrobial overuse. A systematic evidence map can support governments in making evidence-informed decisions about implementing programs to reduce AMR, by identifying, describing, and assessing the full range of evaluated government policy options to reduce antimicrobial use in humans.Methods and Findings: Seven databases were searched from inception to January 28, 2019, (MEDLINE, CINAHL, EMBASE, PAIS Index, Cochrane Central Register of Controlled Trials, Web of Science, and PubMed). We identified studies that (1) clearly described a government policy intervention aimed at reducing human antimicrobial use, and (2) applied a quantitative design to measure the impact. We found 69 unique evaluations of government policy interventions carried out across 4 of the 6 WHO regions. These evaluations included randomized controlled trials (n = 4), non-randomized controlled trials (n = 3), controlled before-and-after designs (n = 7), interrupted time series designs (n = 25), uncontrolled before-and-after designs (n = 18), descriptive designs (n = 10), and cohort designs (n = 2). From these we identified 17 unique policy options for governments to reduce the human use of antimicrobials. Many studies evaluated public awareness campaigns (n = 17) and antimicrobial guidelines (n = 13); however, others offered different policy options such as professional regulation, restricted reimbursement, pay for performance, and prescription requirements. Identifying these policies can inform the development of future policies and evaluations in different contexts and health systems. Limitations of our study include the possible omission of unpublished initiatives, and that policies not evaluated with respect to antimicrobial use have not been captured in this review.Conclusions: To our knowledge this is the first study to provide policy makers with synthesized evidence on specific government policy interventions addressing AMR. In the future, governments should ensure that AMR policy interventions are evaluated using rigorous study designs and that study results are published.Protocol Registration: PROSPERO CRD42017067514. [ABSTRACT FROM AUTHOR]

Highlights • Sputum induction maximizes the yield of the Xpert MTB/RIF test in patients with advanced HIV. • The urine lateral flow lipoarabinomannan (LAM) test decreases costs when diagnosing tuberculosis in patients with advanced HIV. • Sputum culture adds little to the diagnostic yield of Xpert MTB/RIF. Abstract Background Tuberculosis is a major cause of mortality among HIV-infected inpatients, and the World Health Organization (WHO) recommends an algorithm to improve diagnosis. The urine lateral flow lipoarabinomannan (LAM) and sputum Xpert MTB/RIF tests are promising tools, but the optimal diagnostic algorithm is unclear. Methods This prospective cohort study enrolled HIV-positive inpatients with cough and WHO danger signs. The Xpert MTB/RIF test and mycobacterial culture were performed on sputum using sputum induction when necessary, and the LAM test was performed on stored urine. Tuberculosis was diagnosed by culture from any site. The diagnostic accuracy and costs of testing were determined for single and combined tests. Results Tuberculosis was confirmed in 169 of 332 patients (50.9%). The yield of LAM, Xpert MTB/RIF on spontaneous sputum (Xpert Spot), and Xpert MTB/RIF on spontaneous or induced sputum (Xpert SI) was 35.5%, 23.1%, and 90.5%, respectively. When LAM was placed before Xpert Spot and Xpert SI in an algorithm, the yield was 50.9% and 92.3%, respectively. Adding culture to Xpert MTB/RIF only increased the yield by 1.2% and 2.7%, respectively. Use of the LAM test reduced costs. Conclusions Sputum induction is important to increase the yield of Xpert MTB/RIF for seriously ill patients with HIV and cough. LAM testing has little effect on yield when sputum induction is available, but reduces costs and may have other benefits. [ABSTRACT FROM AUTHOR]

Importance: Extended-spectrum β-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective "carbapenem-sparing" option to treat extended-spectrum β-lactamase producers.Objectives: To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae.Design, Setting, and Participants: Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study.Interventions: Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician.Main Outcomes and Measures: The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used.Results: Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, -∞ to 14.5%]; P = .90 for noninferiority). Effects were consistent in an analysis of the per-protocol population. Nonfatal serious adverse events occurred in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group.Conclusions and relevance: Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality. These findings do not support use of piperacillin-tazobactam in this setting.Trial Registration: anzctr.org.au Identifiers: ACTRN12613000532707 and ACTRN12615000403538 and ClinicalTrials.gov Identifier: NCT02176122. [ABSTRACT FROM AUTHOR]