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Objectives: Optimal treatment of carbapenem-resistant Gram-negative bacteria (CR-GNB) infections is uncertain because of the lack of good-quality evidence and the limited effectiveness of available antibiotics. The aim of this survey was to investigate clinicians' prescribing strategies for treating CR-GNB infections worldwide. Methods: A 36-item questionnaire was developed addressing the following aspects of antibiotic prescribing: respondent's background, diagnostic and therapeutic availability, preferred antibiotic strategies and rationale for selecting combination therapy. Prescribers were recruited following the snowball sampling approach, and a post-stratification correction with inverse proportional weights was used to adjust the sample's representativeness. Results: A total of 1012 respondents from 95 countries participated in the survey. Overall, 298 (30%) of the respondents had local guidelines for treating CR-GNB at their facility and 702 (71%) had access to Infectious Diseases consultation, with significant discrepancies according to country economic status: 85% (390/502) in high-income countries versus 59% (194/283) in upper-medium-income countries and 30% (118/196) in lower-middle-income countries/lower-income-countries). Targeted regimens varied widely, ranging from 40 regimens for CR-Acinetobacter spp. to more than 100 regimens for CR-Enterobacteriaceae. Although the majority of respondents acknowledged the lack of evidence behind this choice, dual combination was the preferred treatment scheme and carbapenem-polymyxin was the most prescribed regimen, irrespective of pathogen and infection source. Respondents noticeably disagreed around the meaning of ‘combination therapy’ with 20% (150/783) indicating the simple addition of multiple compounds, 42% (321/783) requiring the presence of in vitro activity and 38% (290/783) requiring in vitro synergism. Conclusions: Management of CR-GNB infections is far from being standardized. Strategic public health focused randomized controlled trials are urgently required to inform evidence-based treatment guidelines.

Additional material: Online Supplementary Document available at http://jogh.org/documents/2021/jogh-11-05011-s001.pdf . Copyright © 2021 The Author(s). Background: Variation in the approaches taken to contain the SARS-CoV-2 (COVID-19) pandemic at country level has been shaped by economic and political considerations, technical capacity, and assumptions about public behaviours. To address the limited application of learning from previous pandemics, this study aimed to analyse perceived facilitators and inhibitors during the pandemic and to inform the development of an assessment tool for pandemic response planning. Methods A cross-sectional electronic survey of health and non-health care professionals (5 May - 5 June 2020) in six languages, with respondents recruited via email, social media and website posting. Participants were asked to score inhibitors (−10 to 0) or facilitators (0 to +10) impacting country response to COVID-19 from the following domains - Political, Economic, Sociological, Technological, Ecological, Legislative, and wider Industry (the PESTELI framework). Participants were then asked to explain their responses using free text. Descriptive and thematic analysis was followed by triangulation with the literature and expert validation to develop the assessment tool, which was then compared with four existing pandemic planning frameworks. Results 928 respondents from 66 countries (57% health care professionals) participated. Political and economic influences were consistently perceived as powerful negative forces and technology as a facilitator across high- and low-income countries. The 103-item tool developed for guiding rapid situational assessment for pandemic planning is comprehensive when compared to existing tools and highlights the interconnectedness of the 7 domains. Conclusions The tool developed and proposed addresses the problems associated with decision making in disciplinary silos and offers a means to refine future use of epidemic modelling. This study did not receive any external funding.

BackgroundHealthcare professionals are increasingly expected to lead antimicrobial stewardship (AMS) initiatives. This role in complex healthcare environments requires specialized training.ObjectivesLittle is known about the types of AMS training programmes available to clinicians seeking to play a lead role in AMS. We aimed to identify clinicians’ awareness of AMS training programmes, characteristics of AMS training programmes available and potential barriers to participation.MethodsAMS training programmes available were identified by members of the ESCMID Study Group for Antimicrobial Stewardship (ESGAP) via an online survey and through an online search in 2018. Individual training programme course coordinators were then contacted (September–October 2018) for data on the target audience(s), methods of delivery, intended outcomes and potential barriers to accessing the training programme.ResultsA total of 166/250 ESGAP members (66%) responded to the survey, nominating 48 unique AMS training programmes. An additional 32 training programmes were identified through an online search. AMS training programmes were from around the world. Less than half (44.4%) of respondents were aware of one or more AMS training programmes available, with pharmacists more aware compared with medical doctors and other professionals (73% versus 46% and 25%, respectively). AMS training programmes were most commonly delivered online (59%) and aimed at medical doctors (46%). Training costs and a lack of recognition by health professional societies were the most frequently cited barriers to participation in AMS training programmes.ConclusionsThe development of a systematic inventory of AMS training programmes around the globe identifies opportunities and limitations to current training available. Improving access and increasing awareness amongst target participants will support improved education in AMS.

Background Inappropriate antibiotic use represents a major global threat. Sepsis and bacterial lower respiratory tract infections (LRTIs) have been linked to antimicrobial resistance, carrying important consequences for patients and health systems. Procalcitonin-guided algorithms may represent helpful tools to reduce antibiotic overuse but the financial burden is unclear. The aim of this study was to estimate the healthcare and budget impact in Argentina of using procalcitonin-guided algorithms to guide antibiotic prescription. Methods A decision tree was used to model health and cost outcomes for the Argentinean health system, over a one-year duration. Patients with suspected sepsis in the intensive care unit and hospitalized patients with LRTI were included. Model parameters were obtained from a focused, non-systematic, local and international bibliographic search, and validated by a panel of local experts. Deterministic and probabilistic sensitivity analyses were performed to analyze the uncertainty of parameters. Results The model predicted that using procalcitonin-guided algorithms would result in 734.5 [95% confidence interval (CI): 1,105.2;438.8] thousand fewer antibiotic treatment days, 7.9 [95% CI: 18.5;8.5] thousand antibiotic-resistant cases avoided, and 5.1 [95% CI: 6.7;4.2] thousand fewer Clostridioides difficile cases. In total, this would save $422.4 US dollars (USD) [95% CI: $935;$267] per patient per year, meaning cost savings of $83.0 [95% CI: $183.6;$57.7] million USD for the entire health system and $0.4 [95% CI: $0.9;$0.3] million USD for a healthcare provider with 1,000 cases per year of sepsis and LRTI patients. The sensitivity analysis showed that the probability of cost-saving for the sepsis patient group was lower than for the LRTI patient group (85% vs. 100%). Conclusions Healthcare and financial benefits can be obtained by implementing procalcitonin-guided algorithms in Argentina. Although we found results to be robust on an aggregate level, some caution must be used when focusing only on sepsis patients in the intensive care unit.

To examine published antimicrobial stewardship (AMS) initiatives in hospitals in Latin America and the Caribbean (LAC) in order to characterize AMS terminology usage, geotemporality, and elements of structure (human resources), process (interventions), and outcomes, and to set priority areas for improving AMS reporting.This was a scoping review that searched PubMed, LILACS, EMBASE, and 12 other databases, along with a manual search for academic and grey literature to identify documents on AMS initiatives in hospitals in 33 countries of LAC, up to August 2019. Keywords included 'antibiotic' or 'antimicrobial' AND 'stewardship, policy, strategies, management, control, rational use, appropriate use, surveillance, or interventions' and 33 country names.Selected articles totalled 147 studies published in 1985 - 2019; of those, 22% used 'antimicrobial stewardship' in the title. Eighteen countries published AMS hospital initiatives, one-half of which were implemented in capital cities. Brazil, Argentina, Colombia, Cuba, Mexico, and Chile, in descending frequency, made up59% of published initiatives. Educational interventions were the most frequently reported, followed by persuasive and restrictive strategies. Antimicrobial consumption was the most common outcome measure reported. About one-third of the studies (35%) referred to baseline measures-only in preparation for AMS interventions. Fifty-nine studies from 6 countries reported AMS comprehensively, using structure, process, and outcome (SPO) elements.Published hospital AMS initiatives have increased over time and have expanded across LAC. However, more programs need to be developed. Complete reporting of SPO elements is imperative to evaluating and replicating AMS actions.Examinar las iniciativas publicadas sobre optimización del uso de antimicrobianos (OUA) en hospitales de América Latina y el Caribe para caracterizar el uso de la terminología, la geotemporalidad y algunos elementos de la estructura (recursos humanos), el proceso (intervenciones) y los resultados, así como para establecer las áreas prioritarias para mejorar la información sobre este tema.En esta revisión exploratoria se realizaron búsquedas en PubMed, LILACS, Embase y otras doce bases de datos, además de una búsqueda manual de la bibliografía académica y gris, con el fin de encontrar documentos acerca de las iniciativas de optimización del uso de antimicrobianos en hospitales de 33 países de América Latina y el Caribe hasta agosto del 2019. Algunas de las palabras clave fueron “antibiótico” o “antimicrobiano” Y “rectoría”, “política”, “estrategias”, “gestión”, “control”, “uso racional”, “uso apropiado”, “vigilancia” o “intervenciones”, además de los nombres de los 33 países.Los artículos seleccionados sumaron 147 estudios publicados entre 1985 y el 2019, de los que en un 22 % se mencionó la optimización del uso de antimicrobianos (‘antimicrobial stewardship’) en su título. Dieciocho países publicaron iniciativas de optimización del uso de antimicrobianos para hospitales, la mitad de las cuales se ejecutaron en sus ciudades capitales. Brasil, Argentina, Colombia, Cuba, México y Chile, en orden descendente según la frecuencia, constituyeron más del 59% de las iniciativas publicadas. Las intervenciones educativas fueron las que se informaron con mayor frecuencia, seguidas por las estrategias persuasivas y restrictivas. La medida de resultado notificada más comúnmente fue el consumo de antimicrobianos. Cerca de un tercio de los estudios (35%) se refirió únicamente a las mediciones de base en preparación para las intervenciones de optimización del uso de antimicrobianos. Cincuenta y nueve estudios de seis países informaron exhaustivamente sobre las iniciativas de optimización del uso de antimicrobianos mediante elementos relativos a la estructura, el proceso y los resultados (EPR).Las iniciativas publicadas sobre la optimización del uso de antimicrobianos en los hospitales han aumentado con el transcurso del tiempo y se han ampliado en América Latina y el Caribe. Sin embargo, se necesitan más programas. Es esencial suministrar información completa de los elementos relativos a la EPR para evaluar y replicar las medidas de optimización del uso de antimicrobianos.Examinar iniciativas publicadas sobre a otimização do uso de antimicrobianos em hospitais da América Latina e Caribe (ALC), caracterizar o uso da terminologia sobre iniciativas de otimização do uso de antimicrobianos, geotemporalidade e elementos das estruturas (recursos humanos), processos (intervenções) e resultados, bem como estabelecer áreas prioritárias para melhorar a publicação de estudos sobre iniciativas de otimização do uso de antimicrobianos.Realizamos uma revisão exploratória pesquisando as bases de dados PubMed, LILACS, EMBASE e outras 12, juntamente com uma pesquisa manual da literatura acadêmica e cinzenta para identificar artigos sobre iniciativas de otimização do uso de antimicrobianos em hospitais de 33 países da ALC, até agosto de 2019. Os termos de busca foram ‘antibiótico’ ou ‘antimicrobiano’ E ‘gestão, políticas, estratégias, gerenciamento, controle, uso racional, uso apropriado, vigilância ou intervenções’, bem como os nomes de 33 países.Os artigos selecionados totalizaram 147 estudos publicados entre 1985 e 2019; desses, 22% utilizaram a expressão ‘iniciativas de otimização do uso de antimicrobianos’ (‘As iniciativas publicadas sobre a otimização do uso de antimicrobianos em hospitais têm aumentado ao longo do tempo, expandindo-se em toda a ALC. No entanto, é preciso desenvolver mais programas. A descrição completa de elementos de EPR é fundamental para avaliar e reproduzir as ações de otimização do uso de antimicrobianos.

Background: Variation in the approaches taken to contain the SARS-CoV-2 (COVID-19) pandemic at country level has been shaped by economic and political considerations, technical capacity, and assumptions about public behaviours. To address the limited application of learning from previous pandemics, this study aimed to analyse perceived facilitators and inhibitors during the pandemic and to inform the development of an assessment tool for pandemic response planning. Methods: A cross-sectional electronic survey of health and non-healthcare professionals (5 May - 5 June 2020) in six languages, with respondents recruited via email, social media and website posting. Participants were asked to score inhibitors (-10 to 0) or facilitators (0 to +10) impacting country response to COVID-19 from the following domains – Political, Economic, Sociological, Technological, Ecological, Legislative, and wider Industry (the PESTELI framework). Participants were then asked to explain their responses using free text. Descriptive and thematic analysis was followed by triangulation with the literature and expert validation to develop the assessment tool, which was then compared with four existing pandemic planning frameworks. Findings: 928 respondents from 66 countries (57% healthcare professionals) participated. Political and economic influences were consistently perceived as powerful negative forces and technology as a facilitator across high- and low-income countries. The 103-item tool developed for guiding rapid situational assessment for pandemic planning is comprehensive when compared to existing tools and highlights the interconnectedness of the 7 domains. Interpretation: The tool developed and proposed addresses the problems associated with decision making in disciplinary silos and offers a means to refine future use of epidemic modelling. Funding Statement: This study did not receive any external funding. Declaration of Interests: None to declare. Ethics Approval Statement: The study was approved by the Joint Research Compliance Office, Imperial College London (ICREC reference: 20IC5947).

[Objectives/purpose] The costs attributable to antimicrobial resistance (AMR) remain theoretical and largely unspecified. Current figures fail to capture the full health and economic burden caused by AMR across human, animal, and environmental health; historically many studies have considered only direct costs associated with human infection from a hospital perspective, primarily from high-income countries. The Global Antimicrobial Resistance Platform for ONE-Burden Estimates (GAP-ON€) network has developed a framework to help guide AMR costing exercises in any part of the world as a first step towards more comprehensive analyses for comparing AMR interventions at the local level as well as more harmonized analyses for quantifying the full economic burden attributable to AMR at the global level., [Methods] GAP-ON€ (funded under the JPIAMR 8th call (Virtual Research Institute) is composed of 19 international networks and institutions active in the field of AMR. For this project, the Network operated by means of Delphi rounds, teleconferences and face-to-face meetings. The resulting costing framework takes a bottom-up approach to incorporate all relevant costs imposed by an AMR bacterial microbe in a patient, in an animal, or in the environment up through to the societal level., [Results] The framework itemizes the epidemiological data as well as the direct and indirect cost components needed to build a realistic cost picture for AMR. While the framework lists a large number of relevant pathogens for which this framework could be used to explore the costs, the framework is sufficiently generic to facilitate the costing of other resistant pathogens, including those of other aetiologies., [Conclusion] In order to conduct cost-effectiveness analyses to choose amongst different AMR-related interventions at local level, the costing of AMR should be done according to local epidemiological priorities and local health service norms. Yet the use of a common framework across settings allows for the results of such studies to contribute to cumulative estimates that can serve as the basis of broader policy decisions at the international level such as how to steer R&D funding and how to prioritize AMR amongst other issues. Indeed, it is only by building a realistic cost picture that we can make informed decisions on how best to tackle major health threats., The creation of the GAP-ONE Network was supported under the framework of the Joint Programming Initiative on Antimicrobial Resistance and funded by the Italian Ministry of Health, within the JPIAMR 8th call, Virtual Research Initiative, 2018.

Background The World Health Organization Essential Medicines List (WHO-EML) includes ‘access’ antibiotics, judged essential to treat common infections. The European Society of Clinical Microbiology and Infectious Diseases Study Group for Antimicrobial Stewardship defined a list of ‘forgotten’ antibiotics, some old and often off-patent antibiotics, which have particular value for specific indications. Objective To investigate which WHO-EML ‘access’ and ‘forgotten’ antibiotics are approved at national level in a sample of low- to middle-income countries (LMICs). Methods The Scientific Committee used a consensus procedure to select 26 WHO-EML ‘access’ and 15 ‘forgotten’ antibiotics. Paediatric formulations were explored for 14 antibiotics. An internet-based questionnaire was circulated to 40 LMIC representatives. Antibiotics were defined as approved if an official drug regulatory agency and/or the national ministry of health licensed their use, making them, at least theoretically, available on the market. Results Twenty-eight LMICs (11 in Africa, 11 in Asia and six in America) were surveyed. Nine WHO-EML ‘access’ antibiotics (amoxicillin, ampicillin, benzylpenicillin, ceftriaxone, clarithromycin, ciprofloxacin, doxycycline, gentamicin and metronidazole) were approved in all countries, and all 26 ‘access’ antibiotics were approved in more than two-thirds of countries. Among the 15 ‘forgotten’ antibiotics, only one was approved in more than two-thirds of countries. The median number of approved antibiotics per country was 30 (interquartile range 23–35). Six of 14 paediatric formulations (amoxicillin, amoxicillin-clavulanic acid, oral antistaphylococcal penicillin, cotrimoxazole, erythromycin and metronidazole) were approved in more than two-thirds of countries. Conclusions WHO-EML ‘access’ antibiotics and the most frequently used formulations for paediatrics were approved in the vast majority of the 28 surveyed LMICs. This was not the case for many of the ‘forgotten’ antibiotics, despite their important role, particularly in areas with high prevalence of multi-drug-resistant bacteria.

Dear Editor, Myeloproliferative neoplasms (MPNs) are rare diseases in children [1] when compared to adults [2]. Targeted sequencing revealed differences in the mutational landscape of pediatric and adult MPNs [1]. Children exhibit a lower frequency of mutations in the MPN driver genes JAK2, MPL, and CALR, and a much higher proportion of children exhibit no mutation among the 104 classically involved genes; these children exhibiting a trend towards essential thrombocythemia (ET) [1]. We were surprised to read about an activating thrombopoietin receptor (TpoR/Mpl) S505A transmembrane domain (TM) mutation in childhood hereditary thrombocytosis (HT) and ET [3–5]. [...]

Cranial radiotherapy in children has detrimental effects on cognition, mood, and social competence in young cancer survivors. Treatments harnessing hippocampal neurogenesis are currently of great relevance in this context. Lithium, a well-known mood stabilizer, has both neuroprotective, pro-neurogenic as well as antitumor effects, and in the current study we introduced lithium treatment 4 weeks after irradiation. Female mice received a single 4 Gy whole-brain radiation dose on postnatal day (PND) 21 and were randomized to 0.24% Li2CO3 chow or normal chow from PND 49 to 77. Hippocampal neurogenesis was assessed on PND 77, 91, and 105. We found that lithium treatment had a pro-proliferative effect on neural progenitors, but neuronal integration occurred only after it was discontinued. Also, the treatment ameliorated deficits in spatial learning and memory retention observed in irradiated mice. Gene expression profiling and DNA methylation analysis identified two novel factors related to the observed effects, Tppp, associated with microtubule stabilization, and GAD2/65, associated with neuronal signaling. Our results show that lithium treatment reverses irradiation-induced loss of hippocampal neurogenesis and cognitive impairment even when introduced long after the injury. We propose that lithium treatment should be intermittent in order to first make neural progenitors proliferate and then, upon discontinuation, allow them to differentiate. Our findings suggest that pharmacological treatment of cognitive so-called late effects in childhood cancer survivors is possible.

Unavailability of old antibiotics threatens effective treatment for common bacterial infections

Summary Background The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Due to its large public health and societal implications, multidrug-resistant tuberculosis has been long regarded by WHO as a global priority for investment in new drugs. In 2016, WHO was requested by member states to create a priority list of other antibiotic-resistant bacteria to support research and development of effective drugs. Methods We used a multicriteria decision analysis method to prioritise antibiotic-resistant bacteria; this method involved the identification of relevant criteria to assess priority against which each antibiotic-resistant bacterium was rated. The final priority ranking of the antibiotic-resistant bacteria was established after a preference-based survey was used to obtain expert weighting of criteria. Findings We selected 20 bacterial species with 25 patterns of acquired resistance and ten criteria to assess priority: mortality, health-care burden, community burden, prevalence of resistance, 10-year trend of resistance, transmissibility, preventability in the community setting, preventability in the health-care setting, treatability, and pipeline. We stratified the priority list into three tiers (critical, high, and medium priority), using the 33rd percentile of the bacterium's total scores as the cutoff. Critical-priority bacteria included carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa , and carbapenem-resistant and third-generation cephalosporin-resistant Enterobacteriaceae. The highest ranked Gram-positive bacteria (high priority) were vancomycin-resistant Enterococcus faecium and meticillin-resistant Staphylococcus aureus . Of the bacteria typically responsible for community-acquired infections, clarithromycin-resistant Helicobacter pylori , and fluoroquinolone-resistant Campylobacter spp, Neisseria gonorrhoeae , and Salmonella typhi were included in the high-priority tier. Interpretation Future development strategies should focus on antibiotics that are active against multidrug-resistant tuberculosis and Gram-negative bacteria. The global strategy should include antibiotic-resistant bacteria responsible for community-acquired infections such as Salmonella spp, Campylobacter spp, N gonorrhoeae , and H pylori . Funding World Health Organization.

Few biologists have studied the evolutionary processes at work in indoor environments. Yet indoor environments comprise approximately 0.5% of ice-free land area--an area as large as the subtropical coniferous forest biome. Here we review the emerging subfield of 'indoor biome' studies. After defining the indoor biome and tracing its deep history, we discuss some of its evolutionary dimensions. We restrict our examples to the species found in human houses--a subset of the environments constituting the indoor biome--and offer preliminary hypotheses to advance the study of indoor evolution. Studies of the indoor biome are situated at the intersection of evolutionary ecology, anthropology, architecture, and human ecology and are well suited for citizen science projects, public outreach, and large-scale international collaborations.

Infections caused by multidrug-resistant and extensively drug-resistant Gram-negative bacilli are increasingly challenging to manage in hospitals and long term-care facilities worldwide. As the therapeutic options are limited, the International Society of Chemotherapy in collaboration with the Asia-Pacific Society of Clinical Microbiology and Immunology organised a consensus conference as part of the 13th Asia-Pacific Congress of Clinical Microbiology and Infection. A panel of international experts from Europe, the Americas and Asia were convened to discuss the issues of therapeutic options for the management of these difficult-to-treat pathogens.

A new independent trade union, set up to represent employees in higher education, is challenging wide-ranging reforms proposed by the Russian government.

International audience; The Antibiotic Stewardship and Resistance Working Groups of the International Society for Chemotherapy propose ten key points for the appropriate use of antibiotics in hospital settings. (i) Get appropriate microbiological samples before antibiotic administration and carefully interpret the results: in the absence of clinical signs of infection, colonisation rarely requires antimicrobial treatment. (ii) Avoid the use of antibiotics to ‘treat’ fever: use them to treat infections, and investigate the root cause of fever prior to starting treatment. (iii) Start empirical antibiotic treatment after taking cultures, tailoring it to the site of infection, risk factors for multidrug-resistant bacteria, and the local microbiology and susceptibility patterns. (iv) Prescribe drugs at their optimal dosing and for an appropriate duration, adapted to each clinical situation and patient characteristics. (v) Use antibiotic combinations only where the current evidence suggests some benefit. (vi) When possible, avoid antibiotics with a higher likelihood of promoting drug resistance or hospital-acquired infections, or use them only as a last resort. (vii) Drain the infected foci quickly and remove all potentially or proven infected devices: control the infection source. (viii) Always try to de-escalate/streamline antibiotic treatment according to the clinical situation and the microbiological results. (ix) Stop unnecessarily prescribed antibiotics once the absence of infection is likely. And (x) Do not work alone: set up local teams with an infectious diseases specialist, clinical microbiologist, hospital pharmacist, infection control practitioner or hospital epidemiologist, and comply with hospital antibiotic policies and guidelines. © 2016

The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed. volumen 13; número 12

Polymyxins (polymyxin B and colistin) are older bactericidal antibiotics that are increasingly used to treat infections caused by multidrug-resistant (MDR) Gram-negative bacteria. However, dosing and clinical use of these drugs vary widely. This survey was undertaken to reveal how polymyxins are used worldwide. Data were collected through a structured online questionnaire consisting of 24 questions regarding colistin usage patterns and indications as well as colistin dosage for adult patients. The questionnaire was disseminated in 2011 to relevant experts worldwide and was completed by 284 respondents from 56 different countries. Respondents from 11/56 countries (20%) had no access to colistin; 58/284 respondents (20.4%) reported that in 2010 they experienced that colistin was not available when needed. Formulations of polymyxins used were reported as: colistimethate sodium (48.6%); colistin sulfate (14.1%); both (1.4%); polymyxin B (1.4%); and unknown. Intravenous formulations were used by 84.2%, aerosolised or nebulised colistin by 44.4% and oral colistin for selective gut decontamination by 12.7%. Common indications for intravenous colistin were ventilator-associated pneumonia, sepsis and catheter-related infections with MDR Gram-negative bacteria. Only 21.2% of respondents used a colistin-loading dose, mainly in Europe and North America. This survey reveals that the majority of respondents use colistin and a few use polymyxin B. The survey results show that colistin is commonly underdosed. Clear guidance is needed on indications, dosing and antibiotic combinations to improve clinical outcomes and delay the emergence of resistance. Colistin should be considered a last-resort drug and its use should be controlled. International guidelines are urgently needed. (C) 2013 International Society for Chemotherapy of Infection and Cancer.

The role of fluoroquinolones (FQs) as empirical therapy for community-acquired pneumonia (CAP) remains controversial in countries with high tuberculosis (TB) endemicity owing to the possibility of delayed TB diagnosis and treatment and the emergence of FQ resistance in Mycobacterium tuberculosis. Although the rates of macrolide-resistant Streptococcus pneumoniae and amoxicillin/clavulanic acid-resistant Haemophilus influenzae have risen to alarming levels, the rates of respiratory FQ (RFQ) resistance amongst these isolates remain relatively low. It is reported that ca. 1–7% of CAP cases are re-diagnosed as pulmonary TB in Asian countries. A longer duration (≥7 days) of symptoms, a history of night sweats, lack of fever (>38 °C), infection involving the upper lobe, presence of cavitary infiltrates, opacity in the lower lung without the presence of air, low total white blood cell count and the presence of lymphopenia are predictive of pulmonary TB. Amongst patients with CAP who reside in TB-endemic countries who are suspected of having TB, imaging studies as well as aggressive microbiological investigations need to be performed early on. Previous exposure to a FQ for >10 days in patients with TB is associated with the emergence of FQ-resistant M. tuberculosis isolates. However, rates of M. tuberculosis isolates with FQ resistance are significantly higher amongst multidrug-resistant M. tuberculosis isolates than amongst susceptible isolates. Consequently, in Taiwan and also in other countries with TB endemicity, a short-course (5-day) regimen of a RFQ is still recommended for empirical therapy for CAP patients if the patient is at low risk for TB.