“Antibiotic resistance is usually associated with a fitness cost” is frequently accepted as common knowledge in the field of infectious diseases. However, with the advances in high‐throughput DNA sequencing that allows for a comprehensive analysis of bacterial pathogenesis at the genome scale, including antibiotic resistance genes, it appears that this paradigm might not be as solid as previously thought. Recent studies indicate that antibiotic resistance is able to enhance bacterial fitness in vivo with a concomitant (...) increase in virulence during infections. As a consequence, strategies to minimize antibiotic resistance turn out to be not as simple as initially believed. Indeed, decreased antibiotic use may not be sufficient to let susceptible strains outcompete the resistant ones. Here, we put in perspective these findings and review alternative approaches, such as preventive and therapeutic anti‐bacterial immunotherapies that have the potential to by‐pass the classic antibiotics. (shrink)

Antibiotic resistance in bacteria has become a great threat to global public health. Tigecycline is a next‐generation tetracycline that is the final line of defense against severe infections by pan‐drug‐resistant bacterial pathogens. Unfortunately, this last‐resort antibiotic has been challenged by the recent emergence of the mobile Tet(X) orthologs that can confer high‐level tigecycline resistance. As it is reviewed here, these novel tetracycline destructases represent a growing threat to the next‐generation tetracyclines, and a basic framework for understanding the (...) molecular epidemiology and resistance mechanisms of them is presented. However, further large‐scale epidemiological and functional studies are urgently needed to better understand the prevalence and dissemination of these newly discovered Tet(X) orthologs among Gram‐negative bacteria in both human and veterinary medicine. (shrink)

For over a century, scientists have run experiments using phage viruses to treat bacterial infections. Until recently, the results were inconclusive because the mechanisms viruses use to attack bacteria were poorly understood. With the development of molecular biology, scientists now have a better sense of how phage work, and how they can be used to target infections. As resistance to traditional antibiotics continues to spread around the world, there is a moral imperative to facilitate research into phage therapy as (...) an alternative treatment. This essay reviews ethical questions raised by phage therapy, and discusses regulatory challenges associated with phage research, and phage treatments. (shrink)

Bacterial plasmids are ubiquitous ‘minichromosomes’ that have major importance in clinical microbiology, as agents of pathogenicity and as carriers of antibiotic resistance, and in molecular genetics, through their role as vectors in gene manipulation. Plasmids carry a wide range of dispensable, transiently useful and often bizarre functions.1 Naturally occurring plasmids, in addition to modifying the host cell phenotype, carry genes involved in the control of their own vegetative replication, plasmid copy number2 and stable inheritance. They (...) may also carry determinants for the conjugal transfer of DNA between bacteria.3 Whereas low‐copy‐number plasmids must be partitioned by some active process during cell division, the evidence suggests that multicopy plasmids are distributed randomly between daughter cells. Two independent determinants are necessary for the stable inheritance of multicopy plasmids, and both of these appear to act by maximizing the number of independent plasmid molecules. (shrink)

The 1940s and 1950s were marked by intense debates over the origin of drug resistance in microbes. Bacteriologists had traditionally invoked the notions of ‘training’ and ‘adaptation’ to account for the ability of microbes to acquire new traits. As the field of bacterial genetics emerged, however, its participants rejected ‘Lamarckian’ views of microbial heredity, and offered statistical evidence that drug resistance resulted from the selection of random resistant mutants. Antibiotic resistance became a key issue among those disputing physiological (...) vs. genetic explanations of variation in bacteria. Postwar developments connected with the Lysenko affair gave this debate a new political valence.Proponents of the neo-Darwinian synthesis weighed in with support for the genetic theory. However, certain features of drug resistance seemed inexplicable by mutation and selection, particularly the phenomenon of ‘multiple resistance’—the emergence of resistance in a single strain against several unrelated antibiotics. In the late 1950s, Tsutomu Watanabe and his collaborators solved this puzzle by determining that resistance could be conferred by cytoplasmic resistance factors rather than chromosomal mutation. These R factors could carry resistance to many antibiotics and seemed able to promote their own dissemination in bacterial populations. In the end, the vindication of the genetic view of drug resistance was accompanied by a recasting of the ‘gene’ to include extrachromosomal hereditary units carried on viruses and plasmids. (shrink)

Bacterial resistance mechanisms to the antibiotics known as β‐lactams, which include the penicillins and cephalosporins, can take several forms but frequently involve the production of β‐lactamases from either plasmid‐ or chromosomally‐encoded loci. Gram negative bacteria express a β‐lactamase from evolutionarily related chromosomal ampC genes. Genetic analysis of both inducible and constitutively expressed AmpC β‐lactamases provide insights into the mechanisms regulating production of the enzyme. Evolutionary relationships between the genes of different species are discussed, as well as the regulatory mechanisms (...) that in both laboratory mutants and clinical isolates lead to overproduction of β‐lactamase. (shrink)

Antibiotic resistance threatens the capacity to treat life-threatening infections. If it is accepted that it will be many years until the production of new antibiotics overcomes current concerns with antibiotic resistance then ways to conserve the effectiveness of current antibiotics will have to be found. For many bacterial agents of infection levels of antibiotic resistance are directly dependent on the quantity of antibiotic prescribed. Antibiotics are currently underutilised in many parts of the world. If a (...) just distribution of access to antibiotics requires equal access for individuals with equal need irrespective of wealth then responding to this requirement of justice has the potential to shorten the effective life of currently available antibiotics. Increasing the range and numbers of individuals treated with antibiotics would seem to threaten sustainability and also potentially undermine the access of future generations to cost-effective treatments for bacterial infection. The control of antibiotic resistance requires that the determinants of infectious disease transmission are addressed, such as poor housing, education and nutrition as well as the provision of antibiotics. The apparent tension between intragenerational justice and sustainability diminishes when the account of distributive justice extends beyond access to antibiotics and includes plural entitlements. Controlling antibiotic resistance requires more than the redistribution or reduction of antibiotics. (shrink)

Antibiotic resistance poses an urgent public health risk. High rates of ABR have been noted in all regions of the globe by the World Health Organization. ABR develops when bacteria are exposed to antibiotics either during treatments in humans or animals or through environmental sources contaminated with antibiotic residues. Spread beyond those administered antibiotics occurs through direct contact with the infected or colonized person or animal, through contact or ingestion of retail meat or agricultural products contaminated with ABR (...) organisms, or through the environment. ABR bacteria spread from individuals to populations and across countries. (shrink)

To the extent that antibiotic resistance (ABR) is accelerated by antibiotic consumption and that it represents a serious public health emergency, it is imperative to drastically reduce antibiotic consumption, particularly in high‐income countries. I present the problem of ABR as an instance of the collective action problem known as ‘tragedy of the commons’. I propose that there is a strong ethical justification for taxing certain uses of antibiotics, namely when antibiotics are required to treat minor and self‐limiting (...) infections, such as respiratory tract infections, in otherwise healthy individuals. Taxation would allow a reduction in consumption (given certain behavioural economics assumptions) and/or ensure that individuals internalize or compensate for their contribution to the erosion of the common good of antibiotic effectiveness. I suggest that revenue from the tax could be used to fund conservation and innovation strategies. Taxation might be a coercive policy, especially for certain individuals, but the ethical case for coercive policies is very strong when the good to be preserved is important enough and when they force individuals to do something they have a moral obligation to do anyway. I argue that, in the case of mild and self‐limiting infections, individuals have a moral duty of easy rescue and a moral duty of fairness to make their contribution to the preservation of the common good of antibiotic effectiveness by foregoing antibiotics. I also suggest that taxing antibiotics in such cases is an all things considered ethically justified policy even if it would introduce inequalities in access to healthcare. (shrink)

Antibiotic resistance presents a classic example of the “tragedy of the commons.” In this eponymous tragedy, the commons — shared, public access lands — are overgrazed because farmers can send their livestock onto the land at a zero price. The “tragedy” occurs because overgrazing destroys the land and reduces its ability to provide fodder. The application to antibiotics is obvious: the use of antibiotics creates selection pressure leading to increased proportions of resistant bacteria in the patient and the environment. (...) The increase in frequency of resistant organisms diminishes the effectiveness of antibiotics in treating future infections; thus, the long-term value of the antimicrobial resource is reduced. (shrink)

Beginning in the 1940s, mass production of antibiotics involved the industrial-scale growth of microorganisms to harvest their metabolic products. Unfortunately, the use of antibiotics selects for resistance at answering scale. The turn to the study of antibiotic resistance in microbiology and medicine is examined, focusing on the realization that individual therapies targeted at single pathogens in individual bodies are environmental events affecting bacterial evolution far beyond bodies. In turning to biological manifestations of antibiotic use, sciences fathom material (...) outcomes of their own previous concepts. Archival work with stored soil and clinical samples produces a record described here as ‘the biology of history’: the physical registration of human history in bacterial life. This account thus foregrounds the importance of understanding both the materiality of history and the historicity of matter in theories and concepts of life today. (shrink)

Antimicrobial resistance is a critical public health challenge, and the contribution of the widespread use of antimicrobials in food animals to bacterial drug resistance and human infection demands greater policymaker attention. Global consumption of antimicrobials in food animal production by 2030 is projected to rise by two-thirds due to increases in both food animal production and demand for animal products. In the United States, the volume of antibiotics sold for use in food-producing animals is at least three times greater (...) than that sold for human use. A One Health approach that emphasizes the connections among the health of humans, animals, and the environment is needed to address antibiotic resistance in an integrated manner. This approach holds the promise of collaboration across multiple disciplines, including doctors, veterinarians, food safety professionals, and environmental health experts. (shrink)

Background: Increasing resistance of Pseudomonas aeruginosa to ciprofloxacin in ICU/burn units has created a problem in the treatment of infections caused by this microorganism. -/- Methods: Fifty P. aeruginosa strains were isolated from burn patients hospitalized in the Kerman Hospital during May 1999-April 2000 and were tested for in-vitro sensitivity to different antibiotics by disc diffusion breakpoint assay. The isolates were subjected to minimum inhibitory concentration (MIC) test by agar dilution method. Existence of the plasmids was also investigated in (...) the isolates. -/- Results: Thirty-four patients infected with ciprofloxacin strains showed MIC of 8 mg/ml [p<0.001]. Sixteen patients were infected with sensitive strains exhibiting MIC range of 0.0125-0.125 ± 0.033 mg/ml. The isolates were also also resistant to other antibiotics [p<0.001]. Plasmid isolation and agarose gel electrophoresis (0.7%) revealed three plasmid bands in strains 8 and 16, and one band in strain 35. -/- Conclusion: The emergence of ciprofloxacin resistance of P. aeruginosa in burn patients is alarming since this antibiotic has only recently been introduced onto the market in Iran. One important observation was that some isolates exhibited cross resistance to other antibiotics. Furthermore, some strains were carriers of plasmids which might have acted as the potential source of acquired resistance in the hospital setting. -/- . (shrink)

The use of subtherapeutic doses of antibiotics in food-producing animals has been linked to antibiotic resistant infections in humans. Although this practice has been banned in Europe, the U.S. regulatory authorities have been slow to act. This paper discusses the regulatory hurdles and ethical dilemmas of banning this practice within the context of the risk analysis model (risk assessment, risk management, and risk communication). Specific issues include unethical use of scientific uncertainty during the risk assessment phase, the rejection of (...) the precautionary principle leading to ineffective risk management, and the criticality of risk communication to build consensus and force action. The underlying root cause is a conflict of values (Type I ethical problem) among key stakeholders, which is examined in depth along with an ethical analysis using public health ethical values. (shrink)

Antibiotic-resistant bacteria pose a serious threat to our health. Our ability to destroy deadly bacteria by using antibiotics have not only improved our lives by curing infections, it also allows us to undertake otherwise dangerous treatments from chemotherapies to invasive surgeries. The emergence of antibiotic resistance, I argue, is a consequence of various iterations of prisoner’s dilemmas. To wit, each participant (from patients to nations) has rational self-interest to pursue a course of action that is suboptimal for all (...) of us. The standard solutions to prisoner’s dilemma look to realign cost-benefit such that individuals’ interests match those of the collective. However, the lack of a global organization to enforce an effective carrot-and-stick system makes it unlikely that we can solve the antibiotic resistance problem this way. I argue that our best chance might be an attempt to teach altruism and convince individuals to act not out of their self-interests. (shrink)

Staphylococcus aureus is an opportunistic pathogen capable of causing a variety of diseases including osteomyelitis, endocarditis, infections of indwelling devices and wound infections. These infections are often chronic and highly recalcitrant to antibiotic treatment. Persister cells appear to be central to this recalcitrance. A multitude of factors contribute to S. aureus virulence and high levels of treatment failure. These include its ability to colonize the skin and nares of the host, its ability to evade the host immune system and (...) its development of resistance to a variety of antibiotics. Less understood is the phenomenon of persister cells and their role in S. aureus infections and treatment outcome. Persister cells occur as a sub‐population of phenotypic variants that are tolerant to antibiotic treatment. This review examines the importance of persisters in chronic and relapsing S. aureus infections and proposes methods for their eradication. (shrink)

Individuals are at risk of acquiring untreatable agents of infection when they travel to countries where antibiotic-resistant agents of infection are prevalent, and particularly when they travel for healthcare. Uncertainty with respect to the overall political and economic consequences seems to underlie the reluctance of public health authorities to issue relevant travel advisories. The conditions of choice, the act of choice and the consequences of choice can each be a primary focus of ethical appraisal of public health policy. The (...) ‘value of choice’ account provided by Scanlon draws attention to the value of the choices that individuals are given, and the potential for reasonable rejection of policies that do not give adequate emphasis to the conditions of individual choice. There is both instrumental and symbolic value in informing people of the risk of acquisition of antibiotic-resistant microbes associated with health tourism. We cannot reasonably reject a principle of actively informing unless there are insurmountable countervailing reasons. These reasons should be explicit and subject to review. If health tourism is a concern then we might also consider how best to facilitate alternative choices. (shrink)

The development of bacterial resistance to antibiotics is one of the best documented examples of contemporary biological evolution. Variability in the mechanisms of resistance depends on the diversity of genotypes in the huge bacterial populations, and also on the diversity of selective pressures that are produced along the antibiotic concentration gradients formed in the highly compartmentalized human body during therapy. These antibiotic gradients can be conceived as comprising selective compartments, each one of them defined as the (...) concentration able to select a particular genetic variant. In vitro experimental models confirm that some antibiotic resistant variants are selected only at certain selective concentrations of antibiotics. The correspondence between selective compartments and selectable variants could offer a way of describing more accurately the antibiotic selective landscapes and for taking measures to prevent the development of a major threat to the future of modern medicine. (shrink)

The development of bacterial resistance to antibiotics is one of the best documented examples of contemporary biological evolution. Variability in the mechanisms of resistance depends on the diversity of genotypes in the huge bacterial populations, and also on the diversity of selective pressures that are produced along the antibiotic concentration gradients formed in the highly compartmentalized human body during therapy. These antibiotic gradients can be conceived as comprising selective compartments, each one of them defined as the (...) concentration able to select a particular genetic variant. In vitro experimental models confirm that some antibiotic resistant variants are selected only at certain selective concentrations of antibiotics. The correspondence between selective compartments and selectable variants could offer a way of describing more accurately the antibiotic selective landscapes and for taking measures to prevent the development of a major threat to the future of modern medicine. (shrink)

Decisions to use antibiotics require that patient interests are balanced against the public good, that is, control of antibiotic resistance. Patients carry the risks of suboptimal antibiotic treatment and many physicians are reluctant to impose even small avoidable risks on patients. At the same time, antibiotics are overused and antibiotic-resistant microbes are contributing an increasing burden of adverse patient outcomes. It is the criteria that we can use to reject the use of antibiotics that is the focus (...) of this paper. Scanlon's contractualism explains why antibiotics should not be used to gain small benefits, even when the direct costs of antibiotics are low. We know that some individuals now (and probably more in the future will) carry a burden of irretrievable harm as a consequence of treatment- (antibiotic-) resistant infection. If we accept that the dominant justification for use of antibiotics is to prevent irretrievable harm to an individual or contact, then the use of antibiotics for self-limiting conditions, or for the treatment of individuals with conditions for which antibiotics do not substantially impact on outcomes (eg, in the latter stages of terminal illness), or for access based on preference or willingness to pay (internet or over-the-counter access), or the use of antibiotics as animal growth promoters can be rejected. Scanlon's approach also suggests that, with few new antibiotics in the pipeline and an increasing burden of disease attributable to resistant microbes, control of the spread of antibiotic-resistant microbes should be given increasing priority. (shrink)

The dangers presented by antibiotic resistance have now established themselves as a global health security issue. From an international policy perspective, three key pillars have been established: responsible access, conservation, and innovation. These pillars are intrinsically linked, meaning that any attempt to address one must take into account the implications for the other two.An urgent need exists to address the innovation failure in ABR. In the field of anti-bacterials, the pipeline remains anemic in terms of therapeutics with novel mechanisms (...) of action, new drug classes and strategies involving radically different, innovative approaches. The key reasons for this failure have already been well established. The slow development of new antibiotics is the result of a poor and uncertain commercial market and scientific challenges in research and development. (shrink)

Individual bacterial cells can communicate via quorum sensing, cooperate to harvest nutrients from their environment, form multicellular biofilms, compete over resources and even kill one another. When the environment that bacteria inhabit is an animal host, these social behaviours mediate virulence. Over the last decade, much attention has focussed on the ecology, evolution and pathology of bacterial cooperation, and the possibility that it could be exploited or destabilised to treat infections. But how far can we really extrapolate from (...) theoretical predictions and laboratory experiments to make inferences about ‘cooperative’ behaviours in hosts and reservoirs? To determine the likely importance and evolution of cooperation ‘in the wild’, several questions must be addressed. A recent paper that reports the dynamics of bacterial cooperation and virulence in a field experiment provides an excellent nucleus for bringing together key empirical and theoretical results which help us to frame – if not completely to answer – these questions. (shrink)

Cell‐wall‐less bacterial variants, or L‐forms, have been described in many bacterial species under laboratory conditions, in infected eukaryotic cell cultures and inside animals. Of special interest for human health is the formation of L‐forms as a consequence of specific antibiotic treatments, and the potential involvement of L‐forms in persistent and relapsing infections. An old enigma about L‐forms is how they can divide in the absence of cell wall synthesis, since septum formation is an essential requisite for cell (...) division. However, the classical definition of L‐forms as cell‐wall‐less bacterial variants may need a revision to accomodate recent observations by Richard d'Ari and coworkers:1 genetic and biochemical evidence indicates that E. coli L‐forms induced by β‐lactam antibiotics do contain small amounts of peptidoglycan, essential for their growth and probably required for septum formation. If these observations are extrapolated to all known L‐forms, the very concept of cell‐wall‐less bacteria may need revision, and be restricted to mycoplasmas and their relatives. BioEssays 29:1189–1191, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The discovery, made in Oxford, that crude penicillin could cure systemic and life‐threatening bacterial infections was followed by attempts to purify penicillin, to determine its structure and then to produce it by total chemical synthesis. The β‐lactam structure of the molecule, first proposed in October 1943, was a source of controversy until 1945. However, no useful chemical synthesis was achieved and fermentation became the commercial source of the antibiotic.In 1953, one of the products of a Cephalosporium sp. from (...) Sardinia was shown to be a new and hydrophilic penicillin (penicillin N). This was contaminated with a substance having the same side‐chain but a characteristic absorption spectrum. The latter, cephalosporin C, showed antibacterial activity but was not inactivated by a penicillinase. The determination of its β‐lactam structure and isolation of its nucleus enabled pharmaceutical companies to produce many semisynthetic cephalosporins.A new tripeptide was later found to be an intermediate in the biosynthesis of both penicillin N and cephalosporin C, and this was followed by the complete elucidation of the biosynthetic pathways leading to these compounds and to benzylpenicillin. (shrink)

Antimicrobial resistance (AMR) in bacterial infections is a growing threat to humanity and a challenge to healthcare systems worldwide. Healthcare professionals have an important role in preventing AMR and the spreading of infections. This article focuses on trade union financed journals for nurses in Scandinavia studying how the journals articulate AMR to its readership. A systematic literature search over an eleven‐year period was conducted, using web‐based national trade union financed journals, searching for ‘bacteria’ and ‘resistance’. A thematic analysis, inspired (...) by Foucault's concepts of power and governmentality, was made of 131 texts to understand, which kind of practices, strategies and policies the journals frame regarding AMR. The time period studied resulted in the recognition of four separate themes: the horror scenario, the ‘dangerous’ other, healthcare professionals as a source of resistance development and AMR as a field of research and producer of research qualifications. The study concludes that the journals tend: to present AMR in apocalyptic terms with more research and pharmaceutical industries needed for avoidance; to point out problems in other countries, populations, and sometimes nurses’ working conditions, but primarily with other professionals’ behaviour; and lastly, to present the nurse as a good fairy and disciplinator of doctors. (shrink)

Antimicrobial resistance kills people. According to a recent estimate, ‘7 00 000 people die of resistant infections every year’, and ‘by 2050 10 million lives a year are at risk due to drug resistant infections, as are 100 trillion USD of economic output’.1 Today, ‘bacteria are resistant to nearly all antibiotics that were earlier active against them’.2 For all these reasons, antimicrobial resistance is considered a ‘slowly emerging disaster’3 and a ‘global health security issue’.4 The prospect we are facing is (...) that of a ‘post antibiotic era’,5 in which we risk losing the availability of effective antibiotics and, with them, of medical interventions that require effective antibiotics, such as chemotherapy, transplantation and major surgery. One of the causes of antimicrobial resistance is antimicrobial consumption. As put by the Centers for Disease Control and Prevention, ‘the use of antibiotics is the single most important factor leading to antibiotic resistance around the world: simply using antibiotics creates resistance’.6 According to the 2016 Review on Antimicrobial Resistance commissioned by the UK Government, ‘more consumption of antibiotics directly leads to more resistance’.1 This is because microbes that are not killed by antimicrobials are more likely to reproduce and proliferate and to pass their resistance genes on to other microbes. Thus, exactly like the consumption of many other finite resources, antibiotic and antimicrobial consumption gives rise to the collective action problem known as ‘tragedy of the commons’: consuming a certain resource, such as antimicrobials, is in an individual’s best short-term interest, but many instances of individual consumption erode the resource and therefore conflict with the collective interest in preserving the good. How to solve a tragedy of the commons? As is the case with the consumption of other finite resources, the answer is quite simple: by rationing the resource. Simon Oczkowski’s article …. (shrink)

Antibiotic use triggers evolutionary and ecological responses from bacteria, leading to antibiotic resistance and harmful patient outcomes. Two complementary strategies support long-term antibiotic effectiveness: conservation of existing therapies and production of novel antibiotics. Conservation encompasses infection control, antibiotic stewardship, and other public health interventions to prevent infection, which reduce antibiotic demand. Production of new antibiotics allows physicians to replace existing drugs rendered less effective by resistance.In recent years, physicians and policymakers have raised concerns about the (...) pipeline for new antibiotics, pointing to a decline in the number of antibiotics approved since the 1980s. This trend has been attributed to high research and development costs, low reimbursement for antibiotics, and regulatory standards for review and approval. Professional societies and researchers around the world have called for renewed emphasis on antimicrobial stewardship, while also supporting antibiotic research and development through grants, changes to intellectual property laws to extend market exclusivity periods, and modification of premarket testing regulations to reduce antibiotic development time and expenses. (shrink)

Effectiveness is a key criterion in assessing the justification of antibiotic resistance interventions. Depending on an intervention’s effectiveness, burdens and costs will be more or less justified, which is especially important for large scale population-level interventions with high running costs and pronounced risks to individuals in terms of wellbeing, integrity and autonomy. In this paper, we assess the case of routine hospital screening for multi-drug-resistant Gram-negative bacteria (MDRGN) from this perspective. Utilizing a comparison to screening programs for Methicillin-Resistant Staphylococcus (...) aureus (MRSA) we argue that current screening programmes for MDRGN in low endemic settings should be reconsidered, as its effectiveness is in doubt, while general downsides to screening programs remain. To accomplish justifiable antibiotic stewardship, MDRGN screening should not be viewed as a separate measure, but rather as part of a comprehensive approach. The program should be redesigned to focus on those at risk of developing symptomatic infections with MDRGN rather than merely detecting those colonised. (shrink)

Drug‐resistant bacterial infections constitute a major threat to global public health. Several key bacteria that are becoming increasingly resistant are among those that are ubiquitously carried by human beings and usually cause no symptoms (i.e. individuals are asymptomatic carriers) until and/or unless a precipitating event leads to symptomatic infection (and thus disease). Carriers of drug‐resistant bacteria can also transmit resistant pathogens to others, thus putting the latter at risk of resistant infections. Accumulating evidence suggests that such transmission occurs not (...) only in hospital settings but also in the general community, although considerably more data are needed to assess the extent of this problem. Asymptomatic carriage of drug‐resistant bacteria raises important ethical questions regarding the appropriate public health response, including the degree to which it would be justified to impose burdens on asymptomatic carriers (and others) in order to prevent transmission. In this paper, we (i) summarize current evidence regarding the carriage of key drug‐resistant bacteria, noting important knowledge gaps; and (ii) explore the particular implications of existing public health ethics frameworks for policy‐making regarding asymptomatic carriers. Inter alia, we argue that the relative burdens imposed by public health measures on healthy carriers (as opposed to sick individuals) warrant careful consideration and should be proportionate to the expected public health benefits in terms of risks averted. We conclude that more surveillance and research regarding community transmission will be needed in order to clarify relevant risks and design proportionate policies, although extensive community surveillance itself would also require careful ethical consideration. (shrink)

Antibiotic resistance is one of the most pressing public health problems humanity faces. Research into new classes of antibiotics and new kinds of treatments – including risky experimental treatments such as phage therapy and vaccines – is an important part of improving our ability to treat infectious diseases. In order to aid this research, we will argue that we should permit researchers to pay people any amount of money to compensate for the risks of participating in clinical trials, including (...) ‘challenge studies’ that involve deliberately infecting patients. We think that standard worries about paying for participation in risky research are reducible to concerns that can be addressed with the right screening mechanisms. (shrink)

Recent research has suggested that Staphylococcus epidermidis is a reservoir of genes that, after horizontal transfer, facilitate the potential of Staphylococcus aureus to colonize, survive during infection, or resist antibiotic treatment, traits that are notably manifest in methicillin‐resistant S. aureus (MRSA). S. aureus is a dangerous human pathogen and notorious for acquiring antibiotic resistance. MRSA in particular is one of the most frequent causes of morbidity and death in hospitalized patients. S. aureus is an extremely versatile pathogen with (...) a multitude of mechanisms to cause disease and circumvent immune defenses. In contrast, most other staphylococci, such as S. epidermidis, are commonly benign commensals and only occasionally cause disease. Recent findings highlight the key importance of efforts to better understand how genes of staphylococci other than S. aureus contribute to survival in the human host, how they are transferred to S. aureus, and why this exchange appears to be uni‐directional. (shrink)

Upon entering clinical medicine in the 1940s, antibiotic therapy seemed to complete a transformation of hospitals that originated in the late nineteenth century. Former death sinks had become harbingers of therapeutic progress. Yet this triumph was short-lived. The arrival of pathologies caused by resistant bacteria, and of nosocomial infections whose spread was helped by antibiotic therapies, seemed to be intimately related to modern anti-infective therapy. The place where such problems culminated were hospitals, which increasingly appeared as dangerous environments (...) where attempts to combat infectious diseases had instead created hothouses of disease evolution. This paper will focus on one aspect of that history. It caused clinical medicine and hospital hygiene in particular to pay attention to a dimension of infectious disease it had previously paid little attention to thus far: The evolution of infectious disease—previously a matter of mostly theoretical interest—came to be useful in explaining many phenomena observed. This did not turn hospital hygienists into geneticists, though it did give them an awareness that the evolution of infectious disease in a broad sense was something that did matter to them. The paper advances its argument by looking at three phases: The growing awareness of the hospital as a dangerous environment in the 1950s, comprehensive attempts at improving antibiotic therapy and hospital hygiene that followed from the 1960s and lastly the framing of such challenges as risk factors from the 1970s. In conclusion, I will argue that hospital hygiene, being inspired in particular by epidemiology and risk factor analysis, discussed its own specific version of disease emergence and therefore contributed to the 1980s debates around such topics. Being loosely connected to more specialized studies, it consisted of a re-interpretation of infectious disease centred around the temporality of such phenomena as they were encountered in day-to-day dealings of clinical wards. (shrink)

The Diagnosis Confirmation Model includes a dual-pricing mechanism designed to support value-based pricing of novel antibiotics while improving the alignment of financial incentives with their optimal use in patients at high risk of drug-resistant infections. DCM is a market-based model and complementary to delinked models. Policymakers interested in stimulating antibiotic innovation could consider tailoring the DCM to their reimbursement systems and incorporating it into the suite of incentives to improve the economics of antibiotics.

Upon entering clinical medicine in the 1940s, antibiotic therapy seemed to complete a transformation of hospitals that originated in the late nineteenth century. Former death sinks had become harbingers of therapeutic progress. Yet this triumph was short-lived. The arrival of pathologies caused by resistant bacteria, and of nosocomial infections whose spread was helped by antibiotic therapies, seemed to be intimately related to modern anti-infective therapy. The place where such problems culminated were hospitals, which increasingly appeared as dangerous environments (...) where attempts to combat infectious diseases had instead created hothouses of disease evolution. This paper will focus on one aspect of that history. It caused clinical medicine and hospital hygiene in particular to pay attention to a dimension of infectious disease it had previously paid little attention to thus far: The evolution of infectious disease—previously a matter of mostly theoretical interest—came to be useful in explaining many phenomena observed. This did not turn hospital hygienists into geneticists, though it did give them an awareness that the evolution of infectious disease in a broad sense was something that did matter to them. The paper advances its argument by looking at three phases: The growing awareness of the hospital as a dangerous environment in the 1950s, comprehensive attempts at improving antibiotic therapy and hospital hygiene that followed from the 1960s and lastly the framing of such challenges as risk factors from the 1970s. In conclusion, I will argue that hospital hygiene, being inspired in particular by epidemiology and risk factor analysis, discussed its own specific version of disease emergence and therefore contributed to the 1980s debates around such topics. Being loosely connected to more specialized studies, it consisted of a re-interpretation of infectious disease centred around the temporality of such phenomena as they were encountered in day-to-day dealings of clinical wards. (shrink)

In February, the Food and Drug Administration announced a rule imposing new manufacturer labeling requirements for antibiotics. The aim of the new standards is to educate physicians and patients about the dangers of improper antibiotic use. Overprescription of antibiotics, as well as patient failure to comply with treatment regimens, has led to the development of drug-resistant bacteria. “Antibacterial resistance is a serious and growing public health problem in the United States and worldwide,” FDA Commissioner Mark McClellan said in a (...) press release accompanying the rule. “Without effective antibiotic drugs, common infections, that were once easily treated, can create a serious health threat to children and adults alike.”The FDA regulates foods, drugs, and cosmetics introduced into interstate commerce for safety and effectiveness. Currently, the agency requires drug labels to provide “adequate directions for use,” including indications, quantity of dose, frequency, duration, route, and preparation. (shrink)

In February, the Food and Drug Administration announced a rule imposing new manufacturer labeling requirements for antibiotics. The aim of the new standards is to educate physicians and patients about the dangers of improper antibiotic use. Overprescription of antibiotics, as well as patient failure to comply with treatment regimens, has led to the development of drug-resistant bacteria. “Antibacterial resistance is a serious and growing public health problem in the United States and worldwide,” FDA Commissioner Mark McClellan said in a (...) press release accompanying the rule. “Without effective antibiotic drugs, common infections, that were once easily treated, can create a serious health threat to children and adults alike.”The FDA regulates foods, drugs, and cosmetics introduced into interstate commerce for safety and effectiveness. Currently, the agency requires drug labels to provide “adequate directions for use,” including indications, quantity of dose, frequency, duration, route, and preparation. (shrink)

Most proposals for new international agreements aim to address important global challenges. If the goal is to solve problems, then the value of these agreements depends on their ability to influence the world — to shape norms, constrain behavior, facilitate cooperation, and mobilize action. A recent review of empirical studies has suggested that many international agreements fail to achieve their aspirations. The review indicates that the form in which states make commitments to each other — through an international legal agreement (...) or through other means — may not be as important as commonly thought. It is the content of the commitments and how these are supported by mechanisms to encourage implementation that matter the most. When developing proposals for new international agreements, like the one that has recently been proposed to address antibiotic resistance, attention to implementation mechanisms should therefore be equal to if not greater than the attention paid to its form. (shrink)

The rate of human health care-associated infections caused by Acinetobacter baumannii has increased significantly in recent years for its remarkable resistance to desiccation and most antibiotics. Phospholipases, capable of destroying a phospholipid substrate, are heterologous group of enzymes which are believed to be the bacterial virulence determinants. There is a need for in silico studies to identify potential vaccine candidates. A. baumannii phospholipase D role has been proved in increasing organism’s resistance to human serum, destruction of host epithelial cell (...) and pathogenesis in murine model. In this in silico study high potentials of A. baumannii PLD in elicitation of humoral and cellular immunities were elucidated. Thermal stability, long half-life, non-similarity to human and gut flora proteome and non-allergenicity were in a list of A. baumannii PLD positive properties. Potential epitopic sequences were also identified that could be used as peptide vaccines against A. baumannii and various other human bacterial pathogens. (shrink)

Antibiotic resistance (AR) is a major threat to public health and healthcare worldwide. In this article, we analyse and discuss the claim that taking actions to minimize AR is everyone's responsibility, focusing on individual moral responsibility. This should not be merely interpreted as a function of knowledge of AR and the proper use of antibiotics. Instead, we suggest a circumstantial account of individual responsibility for AR, where individuals do or do not engage in judicious antibiotic behaviour with different (...) degrees of voluntariness. Furthermore, we suggest a notion of responsibility as a virtue, in which individuals have the opportunity to develop a sensitivity towards the AR theme and, consequently, are capable of engaging, actively and voluntarily, in judicious antibiotic behaviour. The development of such sensitivity depends on the creation of adequate circumstances, that is individual capacities and availability of resources. (shrink)

1. This paper investigates the viability of the harm principle (HP) to justify restricting consumer freedom regarding the purchase of products, such as meat, that require intense use of antibiotics...

This Open Access volume provides in-depth analysis of the wide range of ethical issues associated with drug-resistant infectious diseases. Antimicrobial resistance is widely recognized to be one of the greatest threats to global public health in coming decades; and it has thus become a major topic of discussion among leading bioethicists and scholars from related disciplines including economics, epidemiology, law, and political theory. Topics covered in this volume include responsible use of antimicrobials; control of multi-resistant hospital-acquired infections; privacy and data (...) collection; antibiotic use in childhood and at the end of life; agricultural and veterinary sources of resistance; resistant HIV, tuberculosis, and malaria; mandatory treatment; and trade-offs between current and future generations. As the first book focused on ethical issues associated with drug resistance, it makes a timely contribution to debates regarding practice and policy that are of crucial importance to global public health in the 21st century. (shrink)

This article assesses which policies for addressing antibiotic resistance as part of a multi-pronged approach would benefit from legalization through an international legal agreement. Ten candidate policies were identified based on a review of existing literature, especially The Lancet Series on Antimicrobial Resistance, The Lancet Infectious Diseases Commission on AMR, and the World Health Organization Global Action Plan for AMR. These policies were then grouped under the headings of access, conservation, and innovation.Each of the ten policies were assessed using (...) four criteria developed by Hoffman, Røttingen, and Frenk to help consider why their legalization may be helpful, necessary and/or justified. These criteria are: the problem has a significant transnational dimension; the goal justifies the coercive nature of law; the outcome is likely to be beneficial; and legalization represents the best commitment mechanism among competing alternatives. (shrink)

There are substantial inequalities associated with antibiotics and the determinants of their effectiveness, including the risk of exposure to antibiotic‐resistant microbes, access to relevant treatment advice, diagnostic facilities, risk of life‐threatening infectious disease, and access to antibiotics. Current arrangements (social, political, economic) allow inequalities in the distribution of antibiotic benefits and burdens. This article focuses on the justification of relevant inequalities from a contractualist perspective.

ZusammenfassungDieser Artikel beschreibt die ethischen Herausforderungen, die sich durch das Problem der Antibiotikaresistenz ergeben. Wir legen die Ursachen für ABR dar und argumentieren, dass eine effektive Bekämpfung der ABR es erforderlich macht, den derzeitigen Antibiotikagebrauch drastisch zu reduzieren. Allerdings müssen hierbei auch die ethischen Probleme, die durch ABR entstehen, berücksichtigt werden. ABR führt zum einen zur Verstärkung bereits bestehender Herausforderungen im Infektionsschutz, zum anderen wirft sie neue ethische Probleme auf. Wir argumentieren, dass sich diese Probleme vor allem in Bezug auf (...) kollektive Handlungsentscheidungen und gerechte Ressourcenverteilung ergeben. Um den Konsum von Antibiotika fair zu reduzieren, entwickeln wir anschließend sowohl ein kontraktualistisches Prinzip für die Rationierung, als auch erste Vorschläge zu dessen Implementierung. Hierbei skizzieren wir Risikogrenzen für die Patienten, bei denen ein Verzicht auf Antibiotikatherapie gerechtfertigt werden kann. (shrink)

The nature and effectiveness of any international legal agreement is heavily shaped by the forum in which it is negotiated and implemented. This includes both the substantive content that global policymakers agree upon and the subsequent state compliance with those provisions. Forums differ in their institutional characteristics, thereby providing unique opportunities and costs for participating actors. Forums may have different mandates, capacities, cultures, members, and legal processes — all of which ultimately affect distributions of power and influence. These differences then (...) shape how issues are framed, the content of agreements as they are negotiated, and the incentives states have to comply with any obligations. (shrink)