Search

Objectives The COVID-19 pandemic has had a substantial impact on health systems. The WHO Antimicrobial Resistance (AMR) Surveillance and Quality Assessment Collaborating Centres Network conducted a survey to assess the effects of COVID-19 on AMR surveillance, prevention and control. Methods From October to December 2020, WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) national focal points completed a questionnaire, including Likert scales and open-ended questions. Data were descriptively analysed, income/regional differences were assessed and free-text questions were thematically analysed. Results Seventy-three countries across income levels participated. During the COVID-19 pandemic, 67% reported limited ability to work with AMR partnerships; decreases in funding were frequently reported by low- and middle-income countries (LMICs; P Conclusions This was the first survey to explore the global impact of COVID-19 on AMR among GLASS countries. Responses highlight important actions to help ensure that AMR remains a global health priority, including engaging with GLASS to facilitate reliable AMR surveillance data, seizing the opportunity to develop more sustainable IPC programmes, promoting integrated antibiotic stewardship guidance, leveraging increased laboratory capabilities and other system-strengthening efforts.

SynopsisObjectivesThe COVID-19 pandemic has had a substantial impact on health systems. The WHO Antimicrobial Resistance (AMR) Collaborating Centres Network conducted a survey to assess the effects of COVID-19 on AMR surveillance, prevention and control.MethodsFrom October-December 2020, WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) national focal points completed a questionnaire including Likert-scales and open-ended questions. Data were descriptively analysed, income/regional differences were assessed, and free-text questions were thematically analysed.ResultsSeventy-three countries across income levels participated. During the COVID-19 pandemic, 67% reported limited ability to work with AMR partnerships; decreases in funding were frequently reported by low- and middle-income countries (LMICs; pConclusionsThis was the first survey to explore the global impact of COVID-19 on AMR among GLASS countries. Responses revealed universal patterns but also captured country variability. Although focus is understandably on COVID-19, gains in detecting and controlling AMR, a global health priority, cannot afford to be lost.

IntroductionAntimicrobial resistance undermines our ability to treat bacterial infections, leading to longer hospital stays, increased morbidity and mortality, and a mounting burden to the healthcare system. Antimicrobial stewardship is increasingly important to safeguard the efficacy of existing drugs, as few new drugs are in the developmental pipeline. While significant progress has been made with respect to stewardship in hospitals, relatively little progress has been made in the primary care setting, where the majority of antimicrobials are prescribed. OPEN Stewardship is an international collaboration to develop an automated feedback platform to improve responsible antimicrobial prescribing among primary care physicians and capable of being deployed across heterogeneous healthcare settings. We describe the protocol for an evaluation of this automated feedback intervention with two main objectives: assessing changes in antimicrobial prescribing among participating physicians and determining the usability and usefulness of the reports.Methods and analysisA non-randomised evaluation of the automated feedback intervention (OPEN Stewardship) will be conducted among approximately 150 primary care physicians recruited from Ontario, Canada and Southern Israel, based on a series of targeted stewardship messages sent using the platform. Using a controlled interrupted time-series analysis and multilevel negative binomial modelling, we will compare the antimicrobial prescribing rates of participants before and after the intervention, and also to the prescribing rates of non-participants (from the same healthcare network) during the same period. We will examine outcomes targeted by the stewardship messages, including prescribing for antimicrobials with duration longer than 7 days and prescribing for indications where antimicrobials are typically unnecessary. Participants will also complete a series of surveys to determine the usability and usefulness of the stewardship reports.Ethics and disseminationAll sites have obtained ethics committee approval to recruit providers and access anonymised prescribing data. Dissemination will occur through open-access publication, stakeholder networks and national/international meetings.

IntroductionAntimicrobial resistance (AMR) impacts the health and well-being of animals, affects animal owners both socially and economically, and contributes to AMR at the human and environmental interface. The overuse and/or inappropriate use of antibiotics in animals has been identified as one of the most important drivers of the development of AMR in animals. Effective antibiotic stewardship interventions such as feedback can be adopted in veterinary practices to improve antibiotic prescribing. However, the provision of dedicated financial and technical resources to implement such systems are challenging. The newly developed web-based Online Platform for Expanding Antibiotic Stewardship (OPEN Stewardship) platform aims to automate the generation of feedback reports and facilitate wider adoption of antibiotic stewardship. This paper describes a protocol to evaluate the usability and usefulness of a feedback intervention among veterinarians and assess its impact on individual antibiotic prescribing.Methods and analysisApproximately 80 veterinarians from Ontario, Canada and 60 veterinarians from Israel will be voluntarily enrolled in a controlled interrupted time-series study and their monthly antibiotic prescribing data accessed. The study intervention consists of targeted feedback reports generated using the OPEN Stewardship platform. After a 3-month preintervention period, a cohort of veterinarians (treatment cohort, n=120) will receive three feedback reports over the course of 6 months while the remainder of the veterinarians (n=20) will be the control cohort. A survey will be administered among the treatment cohort after each feedback cycle to assess the usability and usefulness of various elements of the feedback report. A multilevel negative-binomial regression analysis of the preintervention and postintervention antibiotic prescribing of the treatment cohort will be performed to evaluate the impact of the intervention.Ethics and disseminationResearch ethics board approval was obtained at each participating site prior to the recruitment of the veterinarians. The study findings will be disseminated through open-access scientific publications, stakeholder networks and national/international meetings.

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 résistance bactérienne aux antibiotiques constituent un défi pour le développement et la santé mondiaux. Il est nécessaire de communiquer et de diffuser les initiatives qui parviennent à contenir ce problème. En Suède, la propagation rapide de pneumocoques résistants dans le sud du pays en 1995 a conduit à la formation du Programme stratégique suédois contre la résistance aux antibiotiques, également connu sous le nom de Strama. La création de ce programme a été un point de départ important pour coordonner des efforts sur le long terme afin de lutter contre la résistance aux antibiotiques dans le pays. Cet article décrit les principales stratégies du programme: engagement aux niveaux local et national; suivi de l'utilisation d'antibiotiques afin de prendre des décisions en connaissance de cause; objectif national de prescription d'antibiotiques; surveillance de la résistance aux antibiotiques pour agir au niveau local, national et mondial; observation des tendances de résistance; lutte contre les infections afin de limiter la progression de la résistance; communication afin d'inciter à l'action et au changement des comportements. L'adoption d'une démarche ascendante a été un élément clé pour favoriser les changements à long terme, notamment la collaboration étroite avec les prescripteurs au niveau local. Le travail qui est décrit ici et les enseignements tirés pourraient aider les pays à mettre en œuvre leur propre plan d'action national contre la résistance aux antibiotiques.El creciente uso de antibióticos y el aumento de los niveles de resistencia bacteriana a los antibióticos son un desafío para la salud y el desarrollo mundiales. Es necesario comunicar y difundir iniciativas de éxito para contener el problema. En Suecia, una rápida propagación de neumococos resistentes en el sur del país desencadenó la formación del programa estratégico sueco contra la resistencia a los antibióticos, también conocido como Strama, en 1995. La creación del programa fue un importante punto de partida de los esfuerzos coordinados a largo plazo para combatir la resistencia a los antibióticos en el país. En este artículo se describen las principales estrategias del programa: labores dedicadas a nivel local y nacional, supervisión del uso de antibióticos para tomar decisiones fundamentadas, un objetivo nacional para las recetas de antibióticos, vigilancia de la resistencia a los antibióticos para la acción local, nacional y global; seguimiento de las tendencias de resistencia, control de las infecciones para reducir la propagación de la resistencia y comunicación 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 médicos a nivel local. El trabajo aquí descrito y las lecciones aprendidas podrían ofrecer información a los países que implementan sus propios planes de medidas nacionales contra la resistencia a los antibióticos.يشكل الاستخدام المتزايد للمضادات الحيوية وارتفاع مستويات المقاومة البكتيرية للمضادات الحيوية تحديًا يواجه الصحة والتنمية العالمية. لذلك نحن بحاجة إلى توصيل ونشر مبادرات ناجحة لاحتواء المشكلة، حيث أدى الانتشار السريع في السويد لبكتريا المكورات الرئوية المقاومة في الجزء الجنوبي من البلد إلى تشكيل البرنامج الاستراتيجي السويدي ضد مقاومة المضادات الحيوية في عام 1995، والذي يُعرف كذلك باسم Strama. وقد مثّل إطلاق البرنامج نقطة انطلاق هامة للجهود المنسقة الطويلة الأجل لمواجهة مقاومة المضادات الحيوية في البلاد. ويصف التقرير الاستراتيجيات الأساسية للبرنامج كما يلي: الالتزام بالعمل على المستويات المحلية والوطنية، ومراقبة استخدام المضادات الحيوية لاتخاذ القرارات المستنيرة، واستهداف وطني للوصفات الطبية للمضادات المحلية، ومراقبة مقاومة المضادات الحيوية لاتخاذ إجراءات محلية ووطنية وعالمية، ورصد نزعات المقاومة، ومكافحة العدوى للحد من انتشار المقاومة، والتواصل لزيادة الوعي للعمل والتغير السلوكي. ويتمثل العنصر الرئيسي لتحقيق التغييرات على المدى الطويل في اتباع نهج تصاعدي، والعمل بشكل وثيق مع مقدمي الوصفات الطبية على المستوى المحلي. ويمكن للعمل الموضح في هذه الدراسة والدروس المستفادة أن تساعد البلدان على تنفيذ خططها للعمل الوطني ضد مقاومة المضادات الحيوية.抗生素用量的不断增加和细菌抗生素耐药性水平的不断增强已经成为威胁全球健康和发展的难题。我们需要交流和传播遏制该问题的成功举措。在瑞典南部迅速蔓延的耐药性肺炎双球菌推动了 1995 年瑞典抗生素耐药性应对战略计划（也称作 Strama）的制定。该计划的制定是长期协调努力解决该国抗生素耐药性问题的重要起点。本文描述了该计划的主要战略：致力于从地方和全国层面开展工作；监控抗生素的使用以制定明智的决策；设定抗生素处方的全国性目标；监督抗生素耐药性的地方、全国和全球措施；追踪耐药性发展趋势；控制感染以限制耐药性的传播；加强宣传以增强行动和行为转变意识。实现长期转变的关键因素是采取自下而上的方式，包括与地方层面的处方开具人员开展密切合作。本文描述的工作内容和经验教训可告知其他实施全国性应对抗生素耐药性行动计划的国家。.Все большее использование антибиотиков и повышение резистентности бактерий к антибиотикам являются проблемой для глобального здоровья и развития. Необходимо поддерживать взаимодействие с успешными инициативами по сдерживанию проблемы и распространять о них информацию. В Швеции быстрое распространение резистентных пневмококков в южной части страны послужило причиной формирования в 1995 году шведской стратегической программы по борьбе с резистентностью к антибиотикам, также известной как Strama. Создание программы стало важной отправной точкой для долгосрочных скоординированных усилий по борьбе с резистентностью к антибиотикам в этой стране. В этом документе описываются основные стратегии программы: целенаправленная работа на местном и национальном уровнях, мониторинг использования антибиотиков с целью принятия обоснованных решений, национальная цель по назначению антибиотиков, наблюдение за резистентностью к антибиотикам для принятия действий на местном, национальном и глобальном уровнях, отслеживание тенденций резистентности, контроль инфекций с целью ограничения распространения резистентности, взаимодействие для повышения осведомленности о действиях и изменение поведенческих схем. Ключевым элементом в достижении долгосрочных изменений был подход «снизу вверх» при тесном сотрудничестве на местном уровне с врачами, назначающими лекарственные препараты. Описанная здесь работа и полученный опыт могли бы помочь странам реализовать свои собственные национальные программы действий против резистентности к антибиотикам.

Objective To develop, evaluate, and implement a universal online platform - termed OPEN Stewardship - to promote responsible antimicrobial prescribing (antimicrobial stewardship). Introduction Antibiotic resistance is a mounting public health threat calling for action on global, national and local levels. Antibiotic use has been a major driver of increasing rates of antibiotic resistance. This has given rise to the practice of antibiotic stewardship, which seeks to reduce unnecessary antibiotic use across different care settings. Antibiotic stewardship has been increasingly applied in hospital settings, but adoption has been slow in many ambulatory care settings including primary care of humans. Uptake of antibiotic stewardship in veterinary care has been similarly limited. Audit and feedback systems of antibiotic use coupled with patterns of antibiotic use and best practice guidelines have proven useful in outpatient settings, but scale-up is limited by heterogeneous systems of care and limited resources. Methods A multi-sectoral team with partners from Canada, Israel and Sweden is developing a web-based platform for administering antibiotic stewardship across multiple care settings and sectors, for human and animal prescribers. There are several interventions which support behaviour change and can be applied to antibiotic stewardship programs. Systematic reviews have found beneficial effects of numerous behaviour change interventions for optimizing clinical practice such as computerized reminders [1], opinion leaders as champions for change [2], and audit and feedback [3]. A recent Cochrane review [4] found that interventions to enable correct use of antibiotics improved policy compliance, and that enabling interventions that included feedback were more likely to be effective. We will use antibiotic prescribing benchmarking, focused guidelines, and local patterns of antibiotic resistance as key components that can be deployed as feedback through this antibiotic stewardship platform. The OPEN Stewardship platform will be hosted on an AWS cloud-based server using industry standard encryption. The platform will function with a central administrator who will enroll and deliver feedback to participating prescribers. This platform will be evaluated prospectively in two countries (Canada and Israel) to evaluate user experience of the feedback as well as impact on antimicrobial prescribing. The evaluation will include prescribers from both human and animal health. After the prospective evaluation, the platform will be made available online for broad multi-sectoral use. Results We have designed the interface for a web-based platform for antibiotic stewardship which will be used in a multinational prospective primary care stewardship intervention in 2019 and 2020 and subsequently rolled out for broad public use (www.openasp.org). The platform layout can be seen in Figure 1. Data capture for aggregate prescriber level antibiotic use and local guidelines will be possible through both a manual graphical user interface and a dataset template upload. Antibiotic resistance data will be pulled from a companion database (www.resistanceopen.org). Administrators will be able to generate unique feedback forms containing visualizations and snapshots from antibiotic use, guidelines, and antibiotic resistance data (Figure 2). These can then be delivered by email on an individual or scheduled basis for one or multiple prescribers simultaneously. Participating prescribers will also have the option to login to view their own profile and browse antibiotic use, resistance and guidelines. Conclusions Antibiotic stewardship needs to be adopted in a fashion that is country and context specific and not administered from the top down. With our approach we seek to empower groups from any country or care setting to provide regional and tailored stewardship feedback through an open interface. We have here demonstrated the design of an web-based antibiotic stewardship platform which will be evaluated prospectively and subsequently made available for open and broad multi-sectoral use - in keeping with a One Health approach. References 1. Shojania KG, Jennings A, Mayhew A, Ramsay CR, Eccles MP, Grimshaw J. The effects of on-screen, point of care computer reminders on processes and outcomes of care. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD001096. 2. Flodgren G, Eccles MP, Shepperd S, Scott A, Parmelli E, Beyer FR. An overview of reviews evaluating the effectiveness of financial incentives in changing healthcare professional behaviours and patient outcomes. Cochrane Database Syst Rev. 2011 Jul 6;(7):CD009255. 3. Ivers N, Jamtvedt G, Flottorp S, Young JM, Odgaard-Jensen J, French SD, et al. Audit and feedback: effects on professional practice and healthcare outcomes. Cochrane Database Syst Rev. 2012 Jun 13;(6):CD000259. 4. Davey P, Brown E, Charani E, Fenelon L, Gould IM, Holmes A, et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev. 2013 Apr 30;(4):CD003543.

Objectives Community carriage of ESBL-producing Escherichia coli (EPE) is common worldwide and there is a need to understand the connection between carriage and infection. We compared the molecular characteristics of EPE among Swedish community carriers with those of EPE causing invasive infections. Methods We collected 2134 faecal samples from randomly selected Swedish inhabitants and examined them for the presence of EPE. All participating volunteers answered a questionnaire about putative risk factors for EPE carriage. Suspected EPE isolates (n = 418) from patients with bloodstream infection (BSI) were collected from Swedish laboratories. Isolates were genotypically and phenotypically characterized. Results Our results show that the EPE population found in carriers generally had lower pathogenicity compared with the isolates from BSIs, since carriers had a lower proportion of E. coli belonging to phylogroup B2, ST131 and ST131 subclone H30-Rx. Isolates from carriers also had lower levels of multiresistance. The Swedish carriage rate of EPE was 4.7% (101/2134) among healthy volunteers. Risk factors associated with carriage were travel to countries in Asia (OR = 3.6, 95% CI = 1.4-9.2) and Africa (OR = 3.6, 95% CI = 1.7-7.7) and a diet without pork (OR = 0.5, 95% CI = 0.3-0.8 for pork eaters). Conclusions E. coli host factors previously associated with higher pathogenicity were all more common in BSIs compared with carriers. This indicates that the risk of invasive infection with EPE may be relatively modest in many community carriers and that EPE carriage of high-risk strains should be the focus of attention for prevention.

Food is a limited source of these antimicrobial resistance genes for humans., Extended-spectrum β-lactamase (ESBL)– and plasmid-encoded ampC (pAmpC)–producing Enterobacteriaceae might spread from farm animals to humans through food. However, most studies have been limited in number of isolates tested and areas studied. We examined genetic relatedness of 716 isolates from 4,854 samples collected from humans, farm animals, and foods in Sweden to determine whether foods and farm animals might act as reservoirs and dissemination routes for ESBL/pAmpC-producing Escherichia coli. Results showed that clonal spread to humans appears unlikely. However, we found limited dissemination of genes encoding ESBL/pAmpC and plasmids carrying these genes from foods and farm animals to healthy humans and patients. Poultry and chicken meat might be a reservoir and dissemination route to humans. Although we found no evidence of clonal spread of ESBL/pAmpC-producing E. coli from farm animals or foods to humans, ESBL/pAmpC-producing E. coli with identical genes and plasmids were present in farm animals, foods, and humans.

Summary The constant shedding and renewal of epithelial cells maintain the protection of epithelial barriers. Interference with the processes of host cell-cycle regulation and barrier integrity permits the bacterial pathogen Neisseria gonorrhoeae to effectively colonize and invade epithelial cells. Here, we show that a gonococcal infection causes DNA damage in human non-tumor vaginal VK2/E6E7 cells with an increase of 700 DNA strand breaks per cell per hour as detected by an alkaline DNA unwinding assay. Infected cells exhibited elevated levels of DNA double-strand breaks, as indicated by a more than 50% increase in cells expressing DNA damage-response protein 53BP1-positive foci that co-localized with phosphorylated histone H2AX (γH2AX). Furthermore, infected cells abolished their expression of the tumor protein p53 and induced an increase in the expression of cyclin-dependent kinase inhibitors p21 and p27 to 2.6-fold and 4.2-fold of controls, respectively. As shown by live-cell microscopy, flow cytometry assays, and BrdU incorporation assays, gonococcal infection slowed the host cell-cycle progression mainly by impairing progression through the G2 phase. Our findings show new cellular players that are involved in the control of the human cell cycle during gonococcal infection and the potential of bacteria to cause cellular abnormalities.

Metronidazole has been used for the treatment of infections for >45 years and is still successfully used for the treatment of trichomoniasis, amoebiasis, and giardiasis. Anaerobic bacterial infections caused by Bacteroides species, fusobacteria, and clostridia respond favorably to metronidazole therapy. Good clinical results in the treatment of vaginosis due to Gardnerella vaginalis have also been reported. Rates of resistance to metronidazole are still generally low; however, several studies have reported decreased susceptibility among Bacteroides species, as well as different mechanisms of resistance. Metronidazole-resistant Helicobacter pylori strains have been described, but combination therapy (eg, metronidazole, amoxicillin, or clarithromycin plus omeprazole) is still recommended for eradication of this pathogen in patients with gastroduodenal ulcers. Metronidazole is considered to be a cost-effective drug because of its low cost, good activity against pathogenic anaerobic bacteria, favorable pharmacokinetic and pharmacodynamic properties, and minor adverse effects. Metronidazole is still the criterion standard for therapy of anaerobic infections, as was described by Tally and colleagues 35 years ago.

Acquired antibiotic resistance typically confers a cost to the bacteria, but these costs can be reduced by genetic compensation over time. The fitness of two Bacteroides thetaiotaomicron clones consecutively isolated in vivo was studied using an in vitro pair-wise competition method. The isolates derived from faecal samples of two clindamycin-exposed healthy volunteers and the two B. thetaiotaomicron clone types could be followed up to 18 months in these two subjects. The two clones were originally susceptible to clindamycin and lacked erm genes; however, after 7 days of clindamycin administration they carried the erm (erythromycin methylase)(G) or (F) gene, respectively, and expressed phenotypic clindamycin resistance. The initial cost of acquired resistance was high as seen in the in vitro pair-wise competition experiments. At 2 weeks post-administration, no growth disadvantage was detected for isolates of either of the two clones in the in vitro experiments and this regained fitness remained for isolates collected up to 18 months. Competition analysis of an in vitro isolated erm(G) positive transconjugant also demonstrated an initial reduction of fitness that was restored over time. The results indicate that the biological cost associated with a resistance gene can rapidly be compensated during in vivo growth. Thus, once the resistant clone has gained its resistance determinant it will be difficult to eliminate.

Antibiotic administration is known to cause short-term disturbances in the microbiota of the human gastrointestinal tract, but the potential long-term consequences have not been well studied. The aims of this study were to analyse the long-term impact of a 7-day clindamycin treatment on the faecal microbiota and to simultaneously monitor the ecological stability of the microbiota in a control group as a baseline for reference. Faecal samples from four clindamycin-exposed and four control subjects were collected at nine different time points over 2 years. Using a polyphasic approach, we observed highly significant disturbances in the bacterial community that persisted throughout the sampling period. In particular, a sharp decline in the clonal diversity of Bacteroides isolates, as assessed by repetitive sequence-based PCR (rep-PCR) and long-term persistence of highly resistant clones were found as a direct response to the antibiotic exposure. The Bacteroides community never returned to its original composition during the study period as assessed using the molecular fingerprinting technique, terminal restriction fragment length polymorphism (T-RFLP). Furthermore, using real-time PCR we found a dramatic and persistent increase in levels of specific resistance genes in DNA extracted from the faeces after clindamycin administration. The temporal variations in the microbiota of the control group were minor compared to the large and persistent shift seen in the exposed group. These results demonstrate that long after the selection pressure from a short antibiotic exposure has been removed, there are still persistent long term impacts on the human intestinal microbiota that remain for up to 2 years post-treatment.

The purpose of the study was to characterize the resistance mechanism of 36 clindamycin (CL) and erythromycin (EM) resistant Propionibacterium acnes strains and 27 tetracycline (TET) resistant P. acnes isolates, collected from nine European countries, both from acne patients and from patients with different infections. PCR and sequencing of the genes encoding domain V of 23S rRNA for CL and EM resistant strains and 16S rRNA for TET resistant strains were performed. Pulsed-field gel electrophoresis was used as a typing method to establish the relationship between resistance genotypes and pulsed-field types. Several unique resistant genotypes were found to be distributed throughout Europe. P. acnes CL and EM resistant strains carrying one of the mutations within the 23S rRNA were predominantly isolated from Swedish acne patients (64%) compared to other infections (43%), OR=2.33 [CI=1.16-4.69]. Of 36 P. acnes isolates tested, none was found to carry the erm(X) resistance gene. Forty-four percent of TET resistant strains were found to carry a G-C transition in the 16S rRNA of the small ribosomal subunit and all these strains were isolated from Swedish acne patients. MIC of TET among all strains carrying this G-C mutation (n=12) was 32 mg/L and the MIC range for the strains where no mutation was detected ranged from 2 to 8 mg/L. The MIC values of TET were unaffected by the presence of reserpine, a well-known inhibitor of efflux pumps. Those TET resistant strains harbouring the mutation at 16S rRNA were clustered in one pulsotype. For TET resistant strains where no mutation was found, greater variability was noticed. No correlation was noticed between different resistance genotypes of CL and EM resistant strains and pulsed-field types.

Nitroimidazole resistance ( nim ) genes were detected in 2% of 1,502 clinical Bacteroides fragilis group strains isolated from 19 European countries, and a novel nim gene was identified. High metronidazole resistance could be induced in nim -positive strains, which emphasizes the importance of acknowledging metronidazole resistance in the clinical setting.

We investigated cell cycle progression in epithelial cervical ME-180 cells during colonization of three different Lactobacillus species utilizing live cell microscopy, bromodeoxyuridine incorporation assays, and flow cytometry. The colonization of these ME-180 cells by L. rhamnosus and L. reuteri, originating from human gastric epithelia and saliva, respectively, was shown to reduce cell cycle progression and to cause host cells to accumulate in the G1 phase of the cell cycle. The G1 phase accumulation in L. rhamnosus-colonized cells was accompanied by the up-regulation and nuclear accumulation of p21. By contrast, the vaginal isolate L. crispatus did not affect cell cycle progression. Furthermore, both the supernatants from the lactic acid-producing L. rhamnosus colonies and lactic acid added to cell culture media were able to reduce the proliferation of ME-180 cells. In this study, we reveal the diversity of the Lactobacillus species to affect host cell cycle progression and demonstrate that L. rhamnosus and L. reuteri exert anti-proliferative effects on human cervical carcinoma cells.

Although it is known that antibiotics have short-term impacts on the human microbiome, recent evidence demonstrates that the impacts of some antibiotics remain for extended periods of time. In addition, antibiotic-resistant strains can persist in the human host environment in the absence of selective pressure. Both molecular- and cultivation-based approaches have revealed ecological disturbances in the microbiota after antibiotic administration, in particular for specific members of the bacterial community that are susceptible or alternatively resistant to the antibiotic in question. A disturbing consequence of antibiotic treatment has been the long-term persistence of antibiotic resistance genes, for example in the human gut. These data warrant use of prudence in the administration of antibiotics that could aggravate the growing battle with emerging antibiotic-resistant pathogenic strains.

Human intestinal Enterococcus spp. was monitored during a 2-y period after 7 d clindamycin treatment. Consecutive faecal samples were collected from 8 healthy volunteers, 4 of whom had received clindamycin. After treatment, the number of enterococcal colonies was diminished and species variation extended. Erythromycin and clindamycin resistance increased from 19% to 69% and 0% to 67%, respectively. Elevated resistance levels lasted up to 9 months and erm(B) was detected in samples up to 6 months. Our results show that the clindamycin treatment had a prolonged impact on resistance and species variation.

The aim of this study was to gain better knowledge of how the intestinal microbiota are affected over time after administration of an antimicrobial agent. This study monitored the prevalence and frequencies of antibiotic resistance in Enterobacteriaceae against 17 antimicrobial agents, during a 2-y period, in consecutive faecal samples collected from 8 healthy volunteers. Four subjects had received 150 mg clindamycin perorally for 7 d, while 4 non-exposed subjects served as a control group. The samples from both groups were cultured and screened for Enterobacteriaceae. The highest incidence of resistance observed was to ampicillin. The ampicillin resistance is due to production of the beta-lactamase TEM-1. The administration of clindamycin had a prolonged impact on the composition of the microbiota, even though enterobacteria are intrinsically resistant to clindamycin; the level of resistance in Escherichia coli isolates was elevated after administration and persisted up to 9 months after administration. After 9 months the susceptibility levels in the exposed group were similar to those at d 0.

Objectives: The aim was to study the long-term consequences of 1 week clindamycin administration regarding selection and persistence of resistance, resistance determinants and diversity of the Bacteroides spp. in the intestinal microflora. Methods: A total of 1306 Bacteroides isolates were collected from constitutively cultured faecal samples during a 2 year period from eight healthy volunteers. The strains were identified by biochemical and genotyping methods. MIC values were determined by the agar dilution method and presence of resistance genes was screened by real-time PCR. Results: Ecological changes in the intestinal microflora persisting up to 24 months were recorded after a 7 day clindamycin administration to four healthy volunteers. Compared to a control group, not exposed to clindamycin, an enrichment and stabilization of resistant Bacteroides strains and resistance determinants were discovered up to 2 years after clindamycin exposure. Conclusions: The results indicate that even a short-term antibiotic administration can cause long-term alterations in the commensal microbiota of individual subjects, detectable 2 years after dosing. The recorded selection and persistence of resistant strains and resistance genes, illustrates the importance of increasing our knowledge of the role of the abundant intestinal microbial community as a reservoir for spread of resistance.

Objectives Quinolone resistance in the opportunistic pathogen Pseudomonas aeruginosa is commonly caused by mutations that alter the target molecules DNA gyrase/topoisomerase IV, or cause activation of various efflux systems. We have analysed the effect of quinolone resistance caused by DNA gyrase/topoisomerase IV mutations on bacterial fitness. Methods Norfloxacin-resistant mutants were isolated and by DNA sequencing the mutations conferring resistance were identified. Mutant fitness was determined by measuring growth rates in vitro. Mutants with reduced growth rates were serially passaged to obtain growth-compensated mutants. The level of DNA supercoiling was determined by isolating plasmid DNA from the susceptible, resistant and compensated mutants and comparing the topoisomer distribution patterns by gel electrophoresis in the presence of chloroquine. Results Low-level resistance (4-48 mg/L) was caused by single mutations in gyrA or gyrB. Among these strains, three out of eight mutants showed lower fitness, whereas high-level resistant (>256 mg/L) mutants with double mutations in gyrA and parC, parE, nfxB or unknown genes all showed a reduced fitness. Slow-growing resistant mutants with a gyrA mutation had decreased DNA supercoiling. After serial passage in laboratory medium, mutant fitness was increased by compensatory mutation(s) that restored supercoiling to normal levels. The compensatory mutation(s) was not located in any of the genes (gyrAB, topA, parCE, hupB, fis, hupN, himAD or PA5348) that were expected to affect supercoiling. Conclusions Our results show that 'no cost' and compensatory mutations are common in quinolone-resistant P. aeruginosa.