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Sustainable access to effective antibiotics is a foundational need for functioning health care that is increasingly threatened by antibiotic resistance. Although resistance has been known as long as antibiotics have been in clinical use, there are still multiple gaps in the global and local responses. One often cited cause for this complacency is the language that is used to describe the problem and its consequences. In this paper, we survey some examples of the current discussions around antibiotic resistance and seek to offer a path towards unified and understandable messaging that is relevant both to the public and policymakers by using narratives that highlight the individual and societal consequences of antibiotic resistance. Major shortcomings in the current language that hamper both the understanding of antibiotic resistance and needed behaviour change have been identified in scientific papers and special reports. These shortcomings range from terminology that is difficult to understand, through a lack of personal relevance, to a fragmented response in the policy field. We propose that scientists, including behaviour change experts, and other key stakeholders that are engaged in the issue take lead to agreement on the core scientific facts and to formulate a vision that can be a foundation for creation of consistent global narratives. These narratives must in turn be adapted to local contexts. Development of such narratives should be viewed as an essential component in national action plans on AMR to raise awareness, empower citizens and incentivise societal behaviour change, policy development and implementation of governance structures. [ABSTRACT FROM AUTHOR]

Increasing use of antibiotics and rising levels of bacterial resistance to antibiotics are a challenge to global health and development. Successful initiatives for containing the problem need to be communicated and disseminated. In Sweden, a rapid spread of resistant pneumococci in the southern part of the country triggered the formation of the Swedish strategic programme against antibiotic resistance, also known as Strama, in 1995. The creation of the programme was an important starting point for long-term coordinated efforts to tackle antibiotic resistance in the country. This paper describes the main strategies of the programme: committed work at the local and national levels; monitoring of antibiotic use for informed decision-making; a national target for antibiotic prescriptions; surveillance of antibiotic resistance for local, national and global action; tracking resistance trends; infection control to limit spread of resistance; and communication to raise awareness for action and behavioural change. A key element for achieving long-term changes has been the bottom-up approach, including working closely with prescribers at the local level. The work described here and the lessons learnt could inform countries implementing their own national action plans against antibiotic resistance. L'utilisation croissante d'antibiotiques et l'augmentation de la resistance bacterienne aux antibiotiques constituent un defi pour le developpement et la sante mondiaux. Il est necessaire de communiquer et de diffuser les Initiatives qui parviennent a contenir ce probleme. En Suede, la propagation rapide de pneumocoques resistants dans le sud du pays en 1995 a conduit a la formation du Programme strategique suedois contre la resistance aux antibiotiques, egalement connu sous le nom de Strama. La creation de ce programme a ete un point de depart important pour coordonner des efforts sur le long terme afin de lutter contre la resistance aux antibiotiques dans le pays. Cet article decrit les principales strategies du programme: engagement aux niveaux local et national; suivi de l'utilisation d'antibiotiques afin de prendre des decisions en connaissance de cause; objectif national de prescription d'antibiotiques; surveillance de la resistance aux antibiotiques pour agir au niveau local, national et mondial; observation des tendances de. resistance; lutte contre les infections afin de limiter la progression de la resistance; communication afin d'Inciter a l'action et au changement des comportements. L'adoption d'une demarche ascendante a ete un element cle pour favoriser les changements a long terme, notamment la collaboration etroite avec les prescripteurs au niveau local. Le travail qui est decrit ici et les enseignements tires pourraient aider les pays a mettre en oeuvre leur propre plan d'action national contre la resistance aux antibiotiques. El creciente uso de antibioticos y el aumento de los niveles de resistencia bacteriana a los antibioticos son un desafio para la salud y el desarrollo mundiales. Es necesario comunicar y difundir iniciativas de exito para contener el problema. En Suecia, una rapida propagacion de neumococos resistentes en el sur del pais desencadeno la formacion del programa estrategico sueco contra la resistencia a los antibioticos, tambien conocido como Strama, en 1995. La creacion del programa fue un importante punto de partida de los esfuerzos coordinados a largo plazo para combatir la resistencia a los antibioticos en el pais. En este articulo se describen las principales estrategias del programa: labores dedicadas a nivel local y nacional, supervision del uso de antibioticos para tomar decisiones fundamentadas, un objetivo nacional para las recetas de antibioticos, vigilancia de la resistencia a los antibioticos para la accion local, nacional y global; seguimiento de las tendencias de resistencia, control de las infecciones para reducir la propagacion de la resistencia y comunicacion para sensibilizar sobre las medidas y el cambio de comportamiento. Un elemento clave para conseguir cambios a largo plazo ha sido en enfoque ascendente, que Incluye trabajar estrechamente con los medicos a nivel local. El trabajo aqui descrito y las lecciones aprendidas podrian ofrecer Informacion a los paises que implementan sus propios planes de medidas nacionales contra la resistencia a los antibioticos, Introduction The high global use of antibiotics, the rapid spread of multidrug-resistant bacteria and the lack of new, effective antibiotics has led to an imminent threat to health systems and [...]

Securing equitable antibiotic access as an essential component for health system resilience and pandemic preparedness requires a systems perspective. This article discusses key components that need to be coordinated and paired with adequate financing and resources to ensure antibiotic effectiveness as a global public good, which should be central while discussing a new global agreement. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.tips.2010.08.002 Byline: Liselotte Diaz Hogberg, Andreas Heddini, Otto Cars Abstract: The emerging problem of antibiotic resistance is a serious threat to global public health. The situation is aggravated by a substantial decline in the research and development of antibacterial agents. Hence, very few new antibacterial classes are brought to market when older classes lose their efficacy. There has been renewed and growing attention within policy groups to: (i) address the problem; (ii) discuss incentives for the development of urgently needed new treatments; (iii) preserve the efficacy of existing therapeutic options. We briefly review the basic principles of antibiotic resistance, and contrast the increasing resistance to the dwindling antibacterial 'pipeline'. We also highlight some recent policy initiatives aiming to secure the future need of effective antibiotics. Author Affiliation: Department of Medical Sciences, Uppsala University, Box 256, 751 05 Uppsala, Sweden, and ReAct (Action on Antibiotic Resistance), Box 256, 751 05 Uppsala, Sweden

In Europe, antimicrobial resistance has been monitored since 1998 by the European Antimicrobial Resistance Surveillance System (EARSS). We examined the relationship between penicillin nonsusceptibility of invasive isolates of Streptococcus pneumoniae [...]

Antimicrobial resistance is recognized as a grave threat to global health. (1,2) It already causes an estimated 700000 deaths annually and--without effective action--is predicted to cause 10 million deaths annually [...]

Background:In view of the paucity of clinical evidence,in vitrostudies are needed to find antibiotic combinations effective against multidrug-resistant Gram-negative bacteria. Interpretation ofin vitroeffects is usually based on bacterial growth after 24 h in time-kill and checkerboard experiments. However, the clinical relevance of the effects observedin vitrois not established. In this study we explored alternative output parameters to assess the activities of colistin and meropenem againstPseudomonas aeruginosaandAcinetobacter baumannii. Methods:Four strains each ofP. aeruginosaandA. baumanniiwere exposed to colistin and meropenem, alone and in combination, in 8 h dynamic time-kill experiments. Initial (1 h), maximum and 8 h bacterial reductions and the area under the bacterial time-kill curve were evaluated. Checkerboards, interpreted based on fractional inhibitory concentration indices after 24 h, were performed for comparison. Results:In the time-kill experiments, the combination resulted in enhanced 1 h, maximum and 8 h bacterial reductions against 2, 3 and 5 of 8 strains, respectively, as compared to the single drugs. A statistically significant reduction in the area under the time-kill curve was observed for three strains. In contrast, the checkerboards did not identify synergy for any of the strains. Conclusions:Combination effects were frequently found with colistin and meropenem againstP. aeruginosaand A.baumanniiin time-kill experiments but were not detected with the checkerboard method. We propose that the early dynamics of bacterial killing and growth, which may be of great clinical importance, should be considered in futurein vitrocombination studies. [ABSTRACT FROM PUBLISHER]

Background: Appropriate antibiotic therapy is critical in the management of severe sepsis and septic shock to reduce mortality, morbidity and health costs. New methods for rapid antibiotic susceptibility testing are needed because of increasing resistance rates to standard treatment. Aims: The purpose of this study was to evaluate the performance of a novel microfluidic method and the potential to directly apply this method on positive blood cultures. Methods: Minimum inhibitory concentrations (MICs) of ciprofloxacin, ceftazidime, tigecycline and/or vancomycin for Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus were determined using a linear antibiotic concentration gradient in a microfluidic assay. Bacterial growth along the antibiotic gradient was monitored using automated time-lapse photomicrography and growth inhibition was quantified by measuring greyscale intensity changes in the images. In addition to pure culture MICs, vancomycin MICs were determined for S. aureus from spiked and clinical blood cultures following a short centrifugation step. The MICs were compared with those obtained with the Etest and for S. aureus and vancomycin also with macrodilution. Results: The MICs obtained with the microfluidic assay showed good agreement internally as well as with the Etest and macrodilution assays, although some minor differences were noted between the methods. The time to possible readout was within the range of 2 to 5 h. Conclusions: The examined microfluidic assay has the potential to provide rapid and accurate MICs using samples from positive clinical blood cultures and will now be tested using other bacterial species and antibiotics. [ABSTRACT FROM AUTHOR]

This commentary examines how specific sustainable development goals (SDGs) are affected by antimicrobial resistance and suggests how the issue can be better integrated into international policy processes. Moving beyond the importance of effective antibiotics for the treatment of acute infections and health care generally, we discuss how antimicrobial resistance also impacts on environmental, social, and economic targets in the SDG framework. The paper stresses the need for greater international collaboration and accountability distribution, and suggests steps towards a broader engagement of countries and United Nations agencies to foster global intersectoral action on antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Objectives: Combination therapy can be a strategy to ensure effective bacterial killing when treating Pseudomonas aeruginosa, a Gram-negative bacterium with high potential for developing resistance. The aim of this study was to develop a pharmacokinetic/pharmacodynamic (PK/PD) model that describes the in vitro bacterial time-kill curves of colistin and meropenem alone and in combination for one WT and one meropenem-resistant strain of P. aeruginosa.Methods: In vitro time-kill curve experiments were conducted with a P. aeruginosa WT (ATCC 27853) (MICs: meropenem 1 mg/L; colistin 1 mg/L) and a meropenem-resistant type (ARU552) (MICs: meropenem 16 mg/L; colistin 1.5 mg/L). PK/PD models characterizing resistance were fitted to the observed bacterial counts in NONMEM. The final model was applied to predict the bacterial killing of ARU552 for different combination dosages of colistin and meropenem.Results: A model with compartments for growing and resting bacteria, where the bacterial killing by colistin reduced with continued exposure and a small fraction (0.15%) of the start inoculum was resistant to meropenem, characterized the bactericidal effect and resistance development of the two antibiotics. For a typical patient, a loading dose of colistin combined with a high dose of meropenem (2000 mg q8h) was predicted to result in a pronounced kill of the meropenem-resistant strain over 24 h.Conclusions: The developed PK/PD model successfully described the time course of bacterial counts following exposures to colistin and meropenem, alone and in combination, for both strains, and identified a dynamic drug interaction. The study illustrates the application of a PK/PD model and supports high-dose combination therapy of colistin and meropenem to overcome meropenem resistance. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this study were to study the presence of mutators in a set of Acinetobacter baumannii isolates and to explore whether there is a correlation between mutation rates and antibiotic resistance.Methods: The variation in mutation rate was evaluated for 237 clinical A. baumannii isolates by determining the frequency of their mutation to rifampicin resistance. For each isolate, the antibiotic resistance profile was determined by disc diffusion and/or Etest. Isolates were divided into susceptible, resistant and MDR groups according to their resistance to five groups of different antibiotics. A comparison between differences in mutation frequency (f) and strain-specific factors was performed.Results: Of the 237 isolates 32%, 18% and 50% were classified as susceptible, resistant and MDR, respectively. The f of rifampicin resistance varied between 2.2 × 10(-10) and 1.2 × 10(-6). Of the strains under investigation, 16% had an ≥2.5- to 166-fold higher f. The presence of mutators (definition ≥2.5-fold increase in f compared with ATCC 19606) in the MDR group (22%) was significantly higher (P < 0.05) than that in the susceptible and resistant groups (11% and 7%, respectively). Furthermore, f was significantly higher in the MDR group compared with that in the susceptible and resistant groups.Conclusions: The facts that 26 of 37 mutator isolates (70%) in the population were MDR and that there was a significantly higher general f in isolates exhibiting an MDR profile suggest that hypermutability can be of advantage for the organism in a selective environment with extensive exposure to antimicrobials. [ABSTRACT FROM AUTHOR]