Epidemiological interpretation of antibiotic resistance studies - what are we missing?

Antimicrobial resistance is an emerging public-health threat. Studies of the relationship between antibiotic use and resistance, as well as surveillance programmes, examine changes in the proportion of isolates that are resistant. Although proportions are helpful to the clinician prescribing empirical therapy, proportion-based analyses can be misleading to the public-health professional as they can yield biased estimates. Proportions do not adequately reflect the burden of resistance, a measure often of interest in public health. A more appropriate measure of this burden is the rate of isolation of resistant organisms, that is, the absolute number of resistant isolates in a population over time.     

Epidemiology of Japanese Encephalitis in the Philippines: A Systematic Review

BackgroundJapanese encephalitis virus (JEV) is an important cause of encephalitis in most of Asia, with high case fatality rates and often significant neurologic sequelae among survivors. The epidemiology of JE in the Philippines is not well defined. To support consideration of JE vaccine for introduction into the national schedule in the Philippines, we conducted a systematic literature review and summarized JE surveillance data from 2011 to 2014.MethodsWe conducted searches on Japanese encephalitis and the Philippines in four databases and one library. Data from acute encephalitis syndrome (AES) and JE surveillance and from the national reference laboratory from January 2011 to March 2014 were tabulated and mapped.ResultsWe identified 29 published reports and presentations on JE in the Philippines, including 5 serologic surveys, 18 reports of clinical cases, and 8 animal studies (including two with both clinical cases and animal data). The 18 clinical studies reported 257 cases of laboratory-confirmed JE from 1972 to 2013. JE virus (JEV) was the causative agent in 7% to 18% of cases of clinical meningitis and encephalitis combined, and 16% to 40% of clinical encephalitis cases. JE predominantly affected children under 15 years of age and 6% to 7% of cases resulted in death. Surveillance data from January 2011 to March 2014 identified 73 (15%) laboratory-confirmed JE cases out of 497 cases tested.SummaryThis comprehensive review demonstrates the endemicity and extensive geographic range of JE in the Philippines, and supports the use of JE vaccine in the country. Continued and improved surveillance with laboratory confirmation is needed to systematically quantify the burden of JE, to provide information that can guide prioritization of high risk areas in the country and determination of appropriate age and schedule of vaccine introduction, and to measure the impact of preventive measures including immunization against this important public health threat.     

Parasites and biosecurity--the example of Australia

Biosecurity issues as they impact on agriculture, health and the environment are becoming increasingly important. Surveillance is crucial in maintaining a country's biosecurity and this article looks at some of the issues in the context of Australia and its neighbors in the Asia-Pacific region, and emerging threats from parasitic diseases. The important threats to agriculture, public health and wildlife are highlighted, and attention is given to how future surveillance activities must be undertaken on a regional basis and involve neighboring countries if they are to be effective and lead to the protection of both the trade and health of the population.     

Antibiotic resistance in surface water ecosystems: Presence in the aquatic environment,prevention strategies,and risk assessment

Antibiotic-resistant bacteria (ARB) have gained increased notoriety due to their continued detection in environmental media and consequently their threat to human and animal health. The continuing spread of antibiotic resistance throughout the environment is of growing environmental and public health concern, making it difficult to treat harmful resistant diseases. This paper examines the presence of antibiotics, ARB, and antibiotic-resistant genes (ARGs) in aquatic environments; the effectiveness of current water treatment strategies to remove them; and risk assessment methods available that can be used to evaluate the risk from antibiotic resistance. Antibiotics, ARB, and ARGs have been reported at varying levels in wastewater treatment plants, hospital wastewater, irrigation water, recreational water, and drinking water. There are many different water treatments capable of reducing antibiotic resistance (including chlorination, UV, and ozone); however, no one method can fully eliminate it with much variation in the reported effects. Risk assessment models can be used for interpreting field data into the risk to human health from antibiotic resistance. Currently, there is no gold standard risk assessment method for evaluating antibiotic resistance. Methods in this area need further development to reflect evolving risk assessment methodologies and dynamic data as it emerges.     

Multiple antibiotic resistance of Vibrio cholerae serogroup O139 in China from 1993 to 2009

Regarded as an emerging diarrheal micropathogen, Vibrio cholerae serogroup O139 was first identified in 1992 and has become an important cause of cholera epidemics over the last two decades. O139 strains have been continually isolated since O139 cholera appeared in China in 1993, from sporadic cases and dispersed foodborne outbreaks, which are the common epidemic types of O139 cholera in China. Antibiotic resistance profiles of these epidemic strains are required for development of clinical treatments, epidemiological studies and disease control. In this study, a comprehensive investigation of the antibiotic resistance of V. cholerae O139 strains isolated in China from 1993 to 2009 was conducted. The initial O139 isolates were resistant to streptomycin, trimethoprim-sulfamethoxazole and polymyxin B only, while multidrug resistance increased suddenly and became common in strains isolated after 1998. Different resistance profiles were observed in the isolates from different years. In contrast, most V. cholerae O1 strains isolated in the same period were much less resistant to these antibiotics and no obvious multidrug resistance patterns were detected. Most of the non-toxigenic strains isolated from the environment and seafood were resistant to four antibiotics or fewer, although a few multidrug resistant strains were also identified. These toxigenic O139 strains exhibited a high prevalence of the class I integron and the SXT element, which were rare in the non-toxigenic strains. Molecular subtyping of O139 strains showed highly diverse pulsed-field gel electrophoresis patterns, which may correspond to the epidemic state of sporadic cases and small-scale outbreaks and complex resistance patterns. Severe multidrug resistance, even resistance transfers based on mobile antibiotic resistance elements, increases the probability of O139 cholera as a threat to public health. Therefore, continual epidemiological and antibiotic sensitivity surveillance should focus on the occurrence of multidrug resistance and frequent microbial population shifts in O139 strains.     

Emerging High-Level Tigecycline Resistance: Novel Tetracycline Destructases Spread via the Mobile Tet(X)

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.     

Collection, use, and protection of population-based birth defects surveillance data in the united states

Birth defects surveillance systems collect population-based birth defects data from multiple sources to track trends in prevalence, identify risk factors, refer affected families to services, and evaluate prevention efforts. Strong state and federal public health and legal mandates are in place to govern the collection and use of these data. Despite the prima facie appeal of "opt-in" and similar strategies to those who view data collection as a threat to privacy, the use of these strategies in lieu of population-based surveillance can severely limit the ability of public health agencies to accurately access the health status of a group within a defined geographical area. With the need for population-based data central to their mission, birth defects programs around the country take their data stewardship role seriously, recognizing both moral and legal obligations to protect the data by employing numerous safeguards. Birth defects surveillance systems are shaped by the needs of the community they are designed to serve, with the goal of preventing birth defects or alleviating the burdens associated with them.     

Clinical significance of the emergence of bacterial resistance in the hospital environment

Antibiotic resistance is an increasing threat in hospitals and both morbidity and mortality from infections are greater when caused by drug-resistant organisms. Whilst hospitals are universally blamed for this increase, there is an insufficient appreciation of external sources of resistance, such as when patients are admitted to hospitals from long-term care facilities in the community. The use of antibiotics in family practice and animal husbandry has also been linked to drug resistance being encountered in the hospital setting. Justifiable hospital antibiotic use, which can be life saving, may lead to 'collateral damage' with the emergence of resistance in non-target bacteria in the bowel, for example, with subsequent spread by cross-infection. At a management level, antibiotic resistance can have a significant impact on the ability of hospitals to maintain services since cohorting of patients and ward closures from outbreaks add to continuing bed shortages and waiting lists. Hospital laboratories must review their standard operating procedures since some resistance mechanisms may be missed by current methods of antibiotic susceptibility testing. With increasing public concern from press reports of 'multiresistant Staphylococcus aureus killer virus' and other drug-resistant organisms, there will inevitably be a push by national authorities for more surveillance data on antibiotic resistance; however, the cost-effectiveness of different surveillance strategies should be considered. Clinical governance and risk management are dominant themes in the National Health Service and hospital hygiene and antibiotic resistance are likely to feature prominently in audits related to these themes in the near future.     

Combining Healthcare-Based and Participatory Approaches to Surveillance: Trends in Diarrheal and Respiratory Conditions Collected by a Mobile Phone System by Community Health Workers in Rural Nepal

BackgroundSurveillance systems are increasingly relying upon community-based or crowd-sourced data to complement traditional facilities-based data sources. Data collected by community health workers during the routine course of care could combine the early warning power of community-based data collection with the predictability and diagnostic regularity of facility data. These data could inform public health responses to epidemics and spatially-clustered endemic diseases. Here, we analyze data collected on a daily basis by community health workers during the routine course of clinical care in rural Nepal. We evaluate if such community-based surveillance systems can capture temporal trends in diarrheal diseases and acute respiratory infections.MethodsDuring the course of their clinical activities from January to December 2013, community health workers recorded healthcare encounters using mobile phones. In parallel, we accessed condition-specific admissions from 2011–2013 in the hospital from which the community health program was based. We compared diarrhea and acute respiratory infection rates from both the hospital and the community, and assigned three categories of local disease activity (low, medium, and high) to each week in each village cluster with categories determined by tertiles. We compared condition-specific mean hospital rates across categories using ANOVA to assess concordance between hospital and community-collected data.ResultsThere were 2,710 cases of diarrhea and 373 cases of acute respiratory infection reported by community health workers during the one-year study period. At the hospital, the average weekly incidence of diarrhea and acute respiratory infections over the three-year period was 1.8 and 3.9 cases respectively per 1,000 people in each village cluster. In the community, the average weekly rate of diarrhea and acute respiratory infections was 2.7 and 0.5 cases respectively per 1,000 people. Both diarrhea and acute respiratory infections exhibited significant differences between the three categories of disease rate burden (diarrhea p = 0.009, acute respiratory infection p = 0.001) when comparing community health worker-collected rates to hospital rates.ConclusionCommunity-level data on diarrhea and acute respiratory infections modestly correlated with hospital data for the same condition in each village each week. Our experience suggests that community health worker-collected data on mobile phones may be a feasible adjunct to other community- and healthcare-related data sources for surveillance of such conditions. Such systems are vitally needed in resource-limited settings like rural Nepal.     

Prevalence and Risk Factors for Intestinal Protozoan Infections with Cryptosporidium,Giardia, Blastocystis and Dientamoeba among Schoolchildren in Tripoli,Lebanon

BackgroundIntestinal protozoan infections are confirmed as major causes of diarrhea, particularly in children, and represent a significant, but often neglected, threat to public health. No recent data were available in Lebanon concerning the molecular epidemiology of protozoan infections in children, a vulnerable population at high risk of infection.ConclusionsThis is the first study performed in Lebanon reporting the prevalence and the clinical and molecular epidemiological data associated with intestinal protozoan infections among schoolchildren in Tripoli. A high prevalence of protozoan parasites was found, with Blastocystis spp. being the most predominant protozoans. Although only 50% of children reported digestive symptoms, asymptomatic infection was observed, and these children may act as unidentified carriers. This survey provides necessary information for designing prevention and control strategies to reduce the burden of these protozoan infections, especially in children.     

The Effectiveness of Public Health Interventions to Reduce the Health Impact of Climate Change: A Systematic Review of Systematic Reviews

Background

Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases.

Methods and Findings

For each disease, we performed a systematic search with no restriction on date or language of publication on Medline, Web of Knowledge, Cochrane CENTRAL and SCOPUS up to December 2010 to identify systematic reviews of public health interventions. We retrieved some 3176 records of which 85 full papers were assessed and 33 included in the review. The included papers investigated the effect of public health interventions on various outcome measures. All interventions were GRADE assessed to determine the strength of evidence. In addition we developed a systematic review quality score. The interventions included environmental interventions to control vectors, chemoprophylaxis, immunization, household and community water treatment, greening cities and community advice. For most reviews, GRADE showed low quality of evidence because of poor study design and high heterogeneity. Also for some key areas such as floods, droughts and other weather extremes, there are no adequate systematic reviews of potential public health interventions.

Conclusion

In conclusion, we found the evidence base to be mostly weak for environmental interventions that could have the most value in a warmer world. Nevertheless, such interventions should not be dismissed. Future research on public health interventions for climate change adaptation needs to be concerned about quality in study design and should address the gap for floods, droughts and other extreme weather events that pose a risk to health.     

食品动物养殖环境中细菌耐药性研究进展

抗生素耐药性被世界卫生组织认为是21世纪人类面临的最大的公共卫生安全问题之一。近年来,抗生素耐药基因作为一种新型污染物而受到广泛关注。养殖场现已成为耐药基因的一个重要储库,耐药菌及耐药基因随着动物排泄物进入环境,从而加速了耐药基因在环境中的传播。畜禽养殖环境中耐药基因和耐药菌可能经食物链、空气等途径传至人类,给人类健康带来巨大威胁。文中结合最新文献,主要介绍了动物养殖场抗菌药物耐药菌和耐药基因的分布特点、耐药基因的持留和传播扩散、研究方法等方面的研究进展,为食品动物养殖环境的抗菌药物耐药性风险评估提供一定支持。     

Heavy metal-induced selection and proliferation of antibiotic resistance: A review

Antibiotic resistance is recognized as a global threat to public health. The selection and evolution of antibiotic resistance in clinical pathogens were believed to be majorly driven by the imprudent use of antibiotics. However, concerns regarding the same, through selection pressure by a multitude of other antimicrobial agents, such as heavy metals, are also growing. Heavy metal contamination co-selects antibiotic and metal resistance through numerous mechanisms, such as co-resistance and cross-resistance. Here, we have reviewed the role of heavy metals as antimicrobial resistance driving agents and the underlying concept and mechanisms of co-selection, while also highlighting the scarcity of studies explicitly inspecting the process of co-selection in clinical settings. Prospective strategies to manage heavy metal-induced antibiotic resistance have also been deliberated, underlining the need to find specific inhibitors so that alternate medicinal combinations can be added to the existing therapeutic armamentarium.     

Integrating Culture-based Antibiotic Resistance Profiles with Whole-genome Sequencing Data for 11,087 Clinical Isolates

Emerging antibiotic resistance is a major global health threat. The analysis of nucleic acid sequences linked to susceptibility phenotypes facilitates the study of genetic antibiotic resistance determinants to inform molecular diagnostics and drug development. We collected genetic data(11,087 newly-sequenced whole genomes) and culture-based resistance profiles(10,991 out of the11,087 isolates comprehensively tested against 22 antibiotics in total) of clinical isolates including18 main species spanning a time period of 30 years. Species and drug specific resistance patterns were observed including increased resistance rates for Acinetobacter baumannii to carbapenems and for Escherichia coli to fluoroquinolones. Species-level pan-genomes were constructed to reflect the genetic repertoire of the respective species, including conserved essential genes and known resistance factors. Integrating phenotypes and genotypes through species-level pan-genomes allowed to infer gene–drug resistance associations using statistical testing. The isolate collection and the analysis results have been integrated into GEAR-base, a resource available for academic research use free of charge at https://gear-base.com.     

Bacterial multidrug efflux pumps: Mechanisms,physiology and pharmacological exploitations

Multidrug resistance (MDR) refers to the capability of bacterial pathogens to withstand lethal doses of structurally diverse drugs which are capable of eradicating non-resistant strains. MDR has been identified as a major threat to the public health of human being by the World Health Organization (WHO). Among the four general mechanisms that cause antibiotic resistance including target alteration, drug inactivation, decreased permeability and increased efflux, drug extrusion by the multidrug efflux pumps serves as an important mechanism of MDR. Efflux pumps not only can expel a broad range of antibiotics owing to their poly-substrate specificity, but also drive the acquisition of additional resistance mechanisms by lowering intracellular antibiotic concentration and promoting mutation accumulation. Over-expression of multidrug efflux pumps have been increasingly found to be associated with clinically relevant drug resistance. On the other hand, accumulating evidence has suggested that efflux pumps also have physiological functions in bacteria and their expression is subject tight regulation in response to various of environmental and physiological signals. A comprehensive understanding of the mechanisms of drug extrusion, and regulation and physiological functions of efflux pumps is essential for the development of anti-resistance interventions. In this review, we summarize the development of these research areas in the recent decades and present the pharmacological exploitation of efflux pump inhibitors as a promising anti-drug resistance intervention.     

Increasing Awareness about Antibiotic Use and Resistance: A Hands-On Project for High School Students

Background

Health-promoting education is essential to foster an informed society able to make decisions about socio-scientific issues based on scientifically sustained criteria. Antibiotic resistance is currently a major public health issue. Considering that irrational antibiotic use has been associated with the development and widespread of antibiotic resistant bacteria, educational interventions to promote prudent antibiotic consumption are required.

Methodology/Principal Findings

This study focuses on the outcomes of an interventional program implemented at the University of Porto, Portugal, to promote awareness about antibiotic resistance at high school levels (15–17 year old). The project Microbiology recipes: antibiotics à la carte articulates a set of wet and dry lab activities designed to promote the participants’ understanding of concepts and processes underlying antibiotics’ production and activity, such as the notion of mechanisms of action of antibiotics. Following a mix-method approach based on a pre−/post design, the effectiveness of this project was assessed by gathering data from surveys, direct observation and analysis of artifacts of 42 high school students (aged 15 and 16 years). The results indicate that the participants developed a more comprehensive picture of antibiotic resistance. The project was shown to promote more sophisticated conceptualizations of bacteria and antibiotics, increased awareness about the perils of antibiotic resistance, and enhanced consciousness towards measures that can be undertaken to mitigate the problem. The participants regarded their experiences as enjoyable and useful, and believed that the project contributed to improve their understanding and raise their interest about the issues discussed. Furthermore, there were also improvements in their procedural skills concerning the laboratory techniques performed.

Conclusions/Significance

This study evidences the possibility of increasing high school students’ awareness about the consequences of antibiotic resistance and the importance of judicious antibiotic use. The findings inform about the educational benefits of incorporating hands-on activities in science education programs.     

The human gut resistome

In recent decades, the emergence and spread of antibiotic resistance among bacterial pathogens has become a major threat to public health. Bacteria can acquire antibiotic resistance genes by the mobilization and transfer of resistance genes from a donor strain. The human gut contains a densely populated microbial ecosystem, termed the gut microbiota, which offers ample opportunities for the horizontal transfer of genetic material, including antibiotic resistance genes. Recent technological advances allow microbiota-wide studies into the diversity and dynamics of the antibiotic resistance genes that are harboured by the gut microbiota (‘the gut resistome’). Genes conferring resistance to antibiotics are ubiquitously present among the gut microbiota of humans and most resistance genes are harboured by strictly anaerobic gut commensals. The horizontal transfer of genetic material, including antibiotic resistance genes, through conjugation and transduction is a frequent event in the gut microbiota, but mostly involves non-pathogenic gut commensals as these dominate the microbiota of healthy individuals. Resistance gene transfer from commensals to gut-dwelling opportunistic pathogens appears to be a relatively rare event but may contribute to the emergence of multi-drug resistant strains, as is illustrated by the vancomycin resistance determinants that are shared by anaerobic gut commensals and the nosocomial pathogen Enterococcus faecium.     

Research progress on distribution,migration, transformation of antibiotics and antibiotic resistance genes (ARGs) in aquatic environment

Antimicrobial and antibiotics resistance caused by misuse or overuse of antibiotics exposure is a growing and significant threat to global public health. The spread and horizontal transfer of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) by the selective pressure of antibiotics in an aquatic environment is a major public health issue. To develop a better understanding of potential ecological risks die to antibiotics and ARGs, this study mainly summarizes research progress about: (i) the occurrence, concentration, fate, and potential ecological effects of antibiotics and ARGs in various aquatic environments, (ii) the threat, spread, and horizontal gene transfer (HGT) of ARGs, and (iii) the relationship between antibiotics, ARGs, and ARB. Finally, this review also proposes future research direction on antibiotics and ARGs.