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1.
Braz. j. biol ; 82: e231838, 2022. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1153467

RESUMEN

Abstract Use of antibiotics inevitably leads to antimicrobial resistance. Selection for resistance occurs primarily within the gut of humans and animals as well as in the environment through natural resistance and residual antibiotics in streams and soil. We evaluated antimicrobial resistance in Gram negative bacteria from a river system in a rural community in Bahia, Brazil. Water was collected from the Jiquiriçá and Brejões rivers and the piped water supply. Additionally, stools were collected from a random sample of residents, cows, pigs and horses near the river. The samples were screened for bacteria resistant to ciprofloxacin, cefotaxime, and meropenem and identified biochemically at the genus and species levels. Microbial source tracking demonstrated that ruminant and human fecal contamination increased as the rivers neared the village center and decreased after the last residence. Antibiotic bacteria were identified from all samples (n = 32). No bacteria were resistant to carbapenems, but the majority of the enterobacteria were resistant to ciprofloxacin, even though this class of antibiotics is not commonly used in food animals in this region. Considering these facts, together with the pattern of human fecal contamination, a human source was considered most likely for these resistant isolates.


Resumo O uso de antibióticos inevitavelmente leva à resistência antimicrobiana. A seleção para resistência antimicrobiana ocorre principalmente no intestino de seres humanos e animais, bem como no meio ambiente, através da resistência natural e resíduos de antibióticos nos esgotos e no solo. Avaliamos a resistência antimicrobiana em bactérias Gram-negativas de um sistema fluvial em uma comunidade rural da Bahia, Brasil. A água foi coletada nos rios Jiquiriçá e Brejões e no abastecimento de água encanada. Além disso, foram coletadas amostras randomizadas de fezes de moradores, vacas, porcos e cavalos próximos ao rio. As amostras foram triadas para bactérias resistentes à ciprofloxacina, cefotaxima e meropenem e identificadas bioquimicamente nos níveis de gênero e espécie. O rastreamento de fontes microbianas demonstrou que a contaminação fecal de ruminantes e humanos aumentou à medida que os rios se aproximavam do centro da vila e diminuía após a última residência. Bactérias resistentes a antibióticos foram identificadas em todas as amostras (n = 32). Nenhuma bactéria demonstrou ser resistente aos carbapenêmicos testados, contudo, foi encontrado enterobactérias resistentes à ciprofloxacina, ainda que essa classe de antibióticos não seja comumente usada na medicina veterinária dos animais dessa região. Considerando esses fatos, juntamente com o padrão de contaminação fecal avaliado, a fonte de contaminação humana foi considerada a mais provável na interação desses isolados resistentes.

2.
Rev. enferm. UERJ ; 29: e52508, jan.-dez. 2021.
Artículo en Inglés, Portugués | LILACS-Express | LILACS | ID: biblio-1254203

RESUMEN

Objetivo: identificar, na literatura científica, estratégias assistenciais para o controle da tuberculose drogarresistente. Método: revisão integrativa da literatura, com análise de pesquisas relevantes sobre a questão nortedora: Quais são as evidências científicas sobre as estratégias assistenciais para o controle da tuberculose drogarresistente? Busca realizada nas bases Literatura Latino-Americana e do Caribe em Ciências da Saúde, Medical Literature Analysis, Índice Bibliográfico Espanhol em Ciências da Saúde e Banco de Dados em Enfermagem, entre janeiro e março de 2020. Foram incluídos dez artigos para discussão dos resultados que responderam à questão da pesquisa, atendendo aos critérios de inclusão e exclusão. Resultados: nos estudos publicados nos últimos cinco anos, 80% abordaram estratégias assistenciais para o controle da tuberculose drogarresistente e 20% evidenciaram falhas na assistência aos portadores da doença. Conclusão: a revisão da literatura identificou várias estratégias assistenciais para o controle da tuberculose drogarresistente, com destaque para a descentralização do diagnóstico e tratamento compartilhado, possibilitando uma atenção ampliada e integral aos pacientes.


Objective: from the scientific literature, to identify care strategies for controlling drug-resistant tuberculosis. Method: this integrative literature review examined relevant research on the research question ­ What is the scientific evidence on care strategies for controlling drug-resistant tuberculosis? ­ by searching Latin American and Caribbean Health Sciences Information, Medical Literature Analysis, Índice Bibliográfico Español en Ciencias de la Salud and Banco de Dados em Enfermagem, between January and March 2020. Ten articles were included in order to discuss findings that answered the research question, after meeting the inclusion and exclusion criteria. Results: of studies published in the past five years, 80% addressed care strategies for controlling drug-resistant tuberculosis and 20% revealed shortcomings in care for patients with the disease. Conclusion: the literature review identified several care strategies for controlling drug-resistant tuberculosis, particularly by decentralized diagnosis and shared treatment, allowing expanded, comprehensive patient care.


Objetivo: identificar, en la literatura científica, estrategias de asistencia para el control de la tuberculosis farmacorresistente. Método: se trata de una revisión integradora de la literatura, con análisis de investigaciones relevantes sobre la cuestión rectora: ¿Cuáles son las evidencias científicas sobre las estrategias de asistencia para el control de la tuberculosis farmacorresistente? La búsqueda fue realizada en las bases Literatura Latinoamericana y del Caribe en Ciencias de la Salud, Medical Literature Analysis, Índice Bibliográfico Español en Ciencias de la Salud y Banco de Datos en Enfermería, de enero a marzo de 2020. Se incluyeron diez artículos para discutir los resultados que respondieron a la pregunta de la investigación, cumpliendo con los criterios de inclusión y exclusión. Resultados: en los estudios publicados en los últimos cinco años, el 80% abordó estrategias de atención para el control de la tuberculosis farmacorresistente y el 20% mostró fallas en la atención de los pacientes con la enfermedad. Conclusión: la revisión de la literatura identificó varias estrategias asistenciales para el control de la tuberculosis farmacorresistente, con énfasis en la descentralización del diagnóstico y tratamiento compartido, permitiendo una atención ampliada e integral a los pacientes.

3.
Artículo en Inglés | MEDLINE | ID: mdl-34508865

RESUMEN

OBJECTIVES: Aeromonas veronii can cause infection in humans and a wide variety of aquatic and terrestrial animals, has caused serious economic losses in aquaculture worldwide. We isolated a A. veronii from an infected common carp in a fish pond in Jilin Province, named it JC529, identified the multi-drug resistant genes and traced the source of the strain in order to lay the foundation for research on the resistance mechanism of other Aeromonas. METHODS: The isolated stain was sequenced by PacBio RS II and Illumina HiSeq 4000 platforms. The corrected reads were assembled by Celera and Falcon software and predicted by Glimmer software. Seven databases are used for general function annotation. Virulence factors and resistance genes were identified based on the core dataset in VFDB and ARDB database. At the same time, 68 public available A. veronii genomes (including A.veronii JC529) were compared to reveal the clustering relationship of JC529. RESULTS: The JC529 is a 4,834,659 bp circular chromosome with a GC content of 59.64%, including 4,264 protein-coding genes, 2 prophages, 482 virulence factors and 27 antibiotic resistance genes which indicated that the JC529 is a multi-drug resistant strain of A. veronii. The phylogenetic tree showed that trains JC529 and NS, PDB, AG5.28.6, VCK1 appear to be inherited from a common ancestor and affect aquaculture in both China and Greece. CONCLUSION: The JC529 stain is a multidrug-resistant strain A. veronii and be inherited from a common ancestor with Greece.

4.
Int J Mol Sci ; 22(17)2021 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-34502290

RESUMEN

BACKGROUND: Salmonella Kentucky belongs to zoonotic serotypes that demonstrate that the high antimicrobial resistance and multidrug resistance (including fluoroquinolones) is an emerging problem. To the best of our knowledge, clinical S. Kentucky strains isolated in Poland remain undescribed. METHODS: Eighteen clinical S. Kentucky strains collected in the years 2018-2019 in Poland were investigated. All the strains were tested for susceptibility to 11 antimicrobials using the disc diffusion and E-test methods. Whole genome sequences were analysed for antimicrobial resistance genes, mutations, the presence and structure of SGI1-K (Salmonella Genomic Island and the genetic relationship of the isolates. RESULTS: Sixteen of 18 isolates (88.9%) were assigned as ST198 and were found to be high-level resistant to ampicillin (>256 mg/L) and quinolones (nalidixic acid MIC ≥ 1024 mg/L, ciprofloxacin MIC range 6-16 mg/L). All the 16 strains revealed three mutations in QRDR of GyrA and ParC. The substitutions of Ser83 → Phe and Asp87 → Tyr of the GyrA subunit and Ser80→Ile of the ParC subunit were the most common. One S. Kentucky isolate had qnrS1 in addition to the QRDR mutations. Five of the ST198 strains, grouped in cluster A, had multiple resistant determinants like blaTEM1-B, aac(6')-Iaa, sul1 or tetA, mostly in SGI1 K. Seven strains, grouped in cluster B, had shorter SGI1-K with deletions of many regions and with few resistance genes detected. CONCLUSION: The results of this study demonstrated that a significant part of S. Kentucky isolates from humans in Poland belonged to ST198 and were high-level resistant to ampicillin and quinolones.

5.
Sci Rep ; 11(1): 17951, 2021 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-34504243

RESUMEN

Most Mycobacterium tuberculosis (Mtb) resistant to rifampicin (RIF) has mutations in the rpoB gene, while most Mtb resistant to isoniazid (INH) has mutations in the katG gene or inhA promoter. We used gene chip technology to detect mutations in these genes to determine the resistance of Mtb to RIF and INH. A total of 4148 clinical specimens with sputum smear positivity for acid-fast bacilli (AFB) were detected. Then, taking the results of the drug sensitivity test (DST) as the reference standard, the detection efficiency of sputum samples from different grades of positive smears was compared in detail. We found that the sensitivity of the gene chip method for detecting sputum samples with a grade ≥ AFB 2 + was higher than that of sputum samples with a grade ≤ AFB 1 + (P < 0.05). When the grade of the sample was ≤ AFB 1 +, the sensitivity of the gene chip method was 72.6% for RIF, 67.3% for INH, and 60.0% for MDR-TB. When the grade of the sample was ≥ AFB 2 +, the sensitivity of the gene chip method was 84.5% for RIF, 78.2% for INH, and 73.9% for MDR-TB. The results show that gene chip technology can be directly used to diagnose drug-resistant tuberculosis in clinical specimens, and the diagnostic efficiency for the detection of sputum specimens with a grade ≥ AFB 2 + is better than that of other sputum specimens.

6.
Nat Commun ; 12(1): 5384, 2021 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-34508079

RESUMEN

Antimicrobial resistance (AMR) is a growing threat to human and animal health. However, in aquatic animals-the fastest growing food animal sector globally-AMR trends are seldom documented, particularly in Asia, which contributes two-thirds of global food fish production. Here, we present a systematic review and meta-analysis of 749 point prevalence surveys reporting antibiotic-resistant bacteria from aquatic food animals in Asia, extracted from 343 articles published in 2000-2019. We find concerning levels of resistance to medically important antimicrobials in foodborne pathogens. In aquaculture, the percentage of antimicrobial compounds per survey with resistance exceeding 50% (P50) plateaued at 33% [95% confidence interval (CI) 28 to 37%] between 2000 and 2018. In fisheries, P50 decreased from 52% [95% CI 39 to 65%] to 22% [95% CI 14 to 30%]. We map AMR at 10-kilometer resolution, finding resistance hotspots along Asia's major river systems and coastal waters of China and India. Regions benefitting most from future surveillance efforts are eastern China and India. Scaling up surveillance to strengthen epidemiological evidence on AMR and inform aquaculture and fisheries interventions is needed to mitigate the impact of AMR globally.

7.
Med J Malaysia ; 76(5): 698-705, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34508377

RESUMEN

INTRODUCTION: Antibiotic resistance is a burgeoning problem worldwide. The trend of bacterial resistance has increased over the past decade in which more common bacteria are becoming resistant to almost all the antibiotics currently in use, posing a threat to humans and even livestock. METHODS: The databases used to search for the relevant articles for this review include PubMed, Science Direct, and Scopus. The following keywords were used in the search: Antimicrobial resistance, Malaysian action plan, antibioticresistant bacteria, and Malaysian National Surveillance on Antimicrobial Resistance (NSAR). The relevant articles published in English were considered. RESULTS: The antibiotic-resistant bacteria highlighted in this review showed an increase in resistance patterns to the majority of the antibiotics tested. The Malaysian government has come up with an action plan to create public awareness and to educate them regarding the health implications of antibiotic resistance. CONCLUSION: Antimicrobial resistance in Malaysia continues to escalate and is attributed to the overuse and misuse of antibiotics in various fields. As this crisis impacts the health of both humans and animals, therefore a joined continuous effort from all sectors is warranted to reduce the spread and minimize its development.

8.
Epilepsia ; 2021 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-34510448

RESUMEN

OBJECTIVE: This study was undertaken to determine whether the vertical parasagittal approach or the lateral peri-insular/peri-Sylvian approach to hemispheric surgery is the superior technique in achieving long-term seizure freedom. METHODS: We conducted a post hoc subgroup analysis of the HOPS (Hemispheric Surgery Outcome Prediction Scale) study, an international, multicenter, retrospective cohort study that identified predictors of seizure freedom through logistic regression modeling. Only patients undergoing vertical parasagittal, lateral peri-insular/peri-Sylvian, or lateral trans-Sylvian hemispherotomy were included in this post hoc analysis. Differences in seizure freedom rates were assessed using a time-to-event method and calculated using the Kaplan-Meier survival method. RESULTS: Data for 672 participants across 23 centers were collected on the specific hemispherotomy approach. Of these, 72 (10.7%) underwent vertical parasagittal hemispherotomy and 600 (89.3%) underwent lateral peri-insular/peri-Sylvian or trans-Sylvian hemispherotomy. Seizure freedom was obtained in 62.4% (95% confidence interval [CI] = 53.5%-70.2%) of the entire cohort at 10-year follow-up. Seizure freedom was 88.8% (95% CI = 78.9%-94.3%) at 1-year follow-up and persisted at 85.5% (95% CI = 74.7%-92.0%) across 5- and 10-year follow-up in the vertical subgroup. In contrast, seizure freedom decreased from 89.2% (95% CI = 86.3%-91.5%) at 1-year to 72.1% (95% CI = 66.9%-76.7%) at 5-year to 57.2% (95% CI = 46.6%-66.4%) at 10-year follow-up for the lateral subgroup. Log-rank test found that vertical hemispherotomy was associated with durable seizure-free progression compared to the lateral approach (p = .01). Patients undergoing the lateral hemispherotomy technique had a shorter time-to-seizure recurrence (hazard ratio = 2.56, 95% CI = 1.08-6.04, p = .03) and increased seizure recurrence odds (odds ratio = 3.67, 95% CI = 1.05-12.86, p = .04) compared to those undergoing the vertical hemispherotomy technique. SIGNIFICANCE: This pilot study demonstrated more durable seizure freedom of the vertical technique compared to lateral hemispherotomy techniques. Further studies, such as prospective expertise-based observational studies or a randomized clinical trial, are required to determine whether a vertical approach to hemispheric surgery provides superior long-term seizure outcomes.

9.
Artículo en Inglés | MEDLINE | ID: mdl-34511310

RESUMEN

PURPOSE: This paper explores inclusion of topics on antimicrobial resistance (AMR) and antimicrobial stewardship (AMS) in pre-service human and animal healthcare professional curricula as mandated in the first strategic objective of National Action Plan on Antimicrobial Resistance. METHODS: Online versions of pre-service medical [Bachelor of Medicine, Bachelor of Surgery (MBBS)], dental [Bachelor of dental sciences (BDS)], pharmacy [Bachelor of Pharmacy (B Pharm)], veterinary [Bachelor of veterinary science and animal husbandry (B.V.Sc. & A.H.)] and post graduate medical [Doctor of medicine (MD), Master of surgery (MS) and post graduate (PG) medical diploma courses] curricula and hardcopy of nursing (Bachelor of science (BSc) Nursing-Basic) curricula were assessed. Validated search terms were used for identifying individual learning topics, domains of learning and number of hours of learning related to AMS and AMR. Recent edition of commonly referred medical textbooks were manually checked for inclusion of chapters or separate sections on AMR and AMS. RESULTS: Low coverage and poor depth with no mention of required duration of learning for AMR and AMS was observed across the majority of curricula. MS, BDS, B Pharm and BSc nursing curricula did not include AMR and AMS. Out of twenty-three textbooks assessed, only six textbooks included AMS. Gynecology, Obstetrics, Orthopedic and Surgery textbooks did not include separate section on AMR or AMS. CONCLUSIONS: Our study documented inadequate inclusion of AMR and AMS in pre-service medical, dental, nursing, pharmacy and veterinary curricula and post graduate medical curriculum. Standardized education regarding AMR and AMS in multi-professional curricula by educational councils across sectors and updating of medical textbooks of all the subjects by authors/publishers for adequate emphasis on these topics is urgently needed for success of 'One health' in combating AMR.

10.
Curr Med Chem ; 2021 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-34514979

RESUMEN

The unique features of the tumor microenvironment (TME) govern the biological properties of many cancers, including hematological malignancies. TME factors can trigger invasion, and protect against drug cytotoxicity by inhibiting apoptosis and activating specific signaling pathways (e.g. NF-ΚB). TME remodeling is facilitated due to the high self-renewal ability of the bone marrow. Progressing tumor cells can alter some extracellular matrix (ECM) components which act as a barrier to drug penetration in the TME. The initial progression of the cell cycle is controlled by the MAPK pathway (Raf/MEK/ERK) and Hippo pathway, while the final phase is regulated by the PI3K/Akt /mTOR and WNT pathways. In this review we summarize the main signaling pathways involved in drug resistance (DR) and some mechanisms by which DR can occur in the bone marrow. The relationship between autophagy, endoplasmic reticulum stress, and cellular signaling pathways in DR and apoptosis are covered in relation to the TME.

11.
Curr HIV Res ; 2021 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-34515004

RESUMEN

BACKGROUND: HIV drug resistance poses a major challenge for anti-retroviral treatment (ART) and the prevention and control of HIV epidemic. OBJECTIVE: The study aims to establish a novel in-house assay with high efficiency, named AP in-house method, that would be suitable for HIV-1 drug resistance detection in China. METHODS: An in-house HIV-1 genotyping method was used to sequence the partial pol gene from 60 clinical plasma samples; the results of our test were compared with a commercial ViroSeq HIV-1 genotyping system. RESULTS: Among sixty samples, 58(96.7%) were successfully amplified by AP in-house method, five of them harbored viral load below 1,000 copies/ml. The genotype distribution was 43.1% CRF07_BC (25/58), 39.7% CRF01_AE (23/58), 6.9% CRF55_01B (4/58), 5.2% subtype B (3/58) and 5.2% CRF08_BC (3/58). Compared with that of the ViroSeq system, the consistent rate of these nucleotides and amino acids obtained by AP in-house method was up to 99.5 ± 0.4% and 99.5 ± 0.4%, respectively. A total of 290 HIV-1 drug resistance mutations were identified by two methods, including 126 nucleoside reverse transcriptase inhibitors (NRTIs), 145 non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 19 protease inhibitors (PIs) resistance mutations. Out of them, 94.1% (273/290) were completely concordant between the AP in-house method and the ViroSeq system. CONCLUSION: Overall, the evaluation of AP in-house method provided comparable results to those of the ViroSeq system on diversified HIV-1 subtypes in China.

12.
BMC Infect Dis ; 21(1): 914, 2021 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-34488673

RESUMEN

OBJECTIVES: Antimicrobial resistance (AMR) is a significant threat to global public health. Many medical curricula have limited clinical cases and materials focused on AMR, yet enhanced AMR education and training are needed to support antimicrobial stewardship programmes. We used crowdsourcing methods to develop open-access, learner-centred AMR resources. Crowdsourcing is the process of having a large group, including experts and non-experts, solve a problem and then share solutions with the public. METHODS: We organised a global crowdsourcing contest soliciting AMR-related multiple-choice questions, infographics, and images. First, we convened a diverse steering committee group to finalise a call for entries. Second, we launched the contest and disseminated the call for entries using social media, blog posts, email, and an in-person event. Partner institutions included two digital healthcare platforms: Figure 1® and Ding Xiang Yuan. Both organizations serve as online communities for healthcare specialists and professionals to report and comment on clinical information. At the end of the call, solicited entries were screened for eligibility and judged on merit and relevance to AMR learning and education. Exceptional entries were recognised, awarded prizes, and further reviewed for sharing with the public via open-access platforms. RESULTS: We received 59 entries from nine countries. These included 54 multiple-choice questions, four infographics, and one image. Eligible entries (n = 56) were reviewed and assigned a score on a 1-10 scale. Eight entries received mean scores greater than 6.0 and were selected as finalists. The eight finalist entries consisted of three infographics and five multiple-choice questions. They were disseminated through open-access publications and online medical communities. Although we launched a global call, we relied heavily on medical student groups and the entries received were not entirely globally representative. CONCLUSIONS: We demonstrate that crowdsourcing challenge contests can be used to identify infectious disease teaching materials. Medical educators and curriculum developers can adapt this method to solicit additional teaching content for medical students.

13.
Syst Rev ; 10(1): 242, 2021 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-34488879

RESUMEN

BACKGROUND: Antimicrobial resistance (AMR) is accelerated by the widespread and often indiscriminate use of antimicrobials in humans, animals, and the environment. In 2015, the World Health Organization recognised AMR as one of the top ten global health threats, due to its potential to neutralise humanity's advancements in western medicine by enabling the emergence of new strains of existing pathogens, many of which have no available treatments. Over the past decade, several countries, including those in low- and middle-income contexts, have started implementing interventions to tackle AMR. However, economic evidence regarding the cost-effectiveness of these interventions remains weak. To address this evidence gap, we will conduct a systematic literature review to provide a comprehensive summary on the value for money of different AMR interventions. METHODS: We aim to conduct a systematic literature review of all available economic evaluations on interventions addressing AMR and will provide a narrative synthesis of our findings. Systematic searches for relevant studies will be performed across all suitable databases as well as in grey literature sources such as unpublished studies, reports, and other relevant documents. All economic evaluation studies will be included as long as they report an economic outcome and have stated that the analysed intervention will reduce antimicrobial resistance or antimicrobial use in the abstract. Those studies reporting clinical endpoints alone will be excluded. Selection for final inclusion and data extraction will be performed by two independent reviewers. DISCUSSION: The review will be one of the first of its kind, and the most recent, to systematically review literature on the cost-effectiveness of AMR interventions, an important evidence gap in the economics of AMR. The findings will enable policy and decision-makers, particularly in resource-constrained settings, to better use available resources when selecting interventions to address AMR burdens, SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020190310.

14.
Antimicrob Resist Infect Control ; 10(1): 131, 2021 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-34488891

RESUMEN

BACKGROUND: Escherichia coli is an important pathogen in humans and is the most common cause of bacterial bloodstream infections (BSIs). The objectives of our study were to determine factors associated with E. coli BSI incidence rate and third-generation cephalosporin resistance in a multinational population-based cohort. METHODS: We included all incident E. coli BSIs (2014-2018) from national (Finland) and regional (Australia [Canberra], Sweden [Skaraborg], and Canada [Calgary, Sherbrooke, and western interior]) surveillance. Incidence rates were directly age and sex standardized to the European Union 28-country 2018 population. Multivariable negative binomial and logistic regression models estimated factors significantly associated with E. coli BSI incidence rate and third-generation cephalosporin resistance, respectively. The explanatory variables considered for inclusion in both models were year (2014-2018), region (six areas), age (< 70-years-old and ≥ 70-years-old), and sex (female and male). RESULTS: We identified 31,889 E. coli BSIs from 40.7 million person-years of surveillance. Overall and third-generation cephalosporin-resistant standardized rates were 87.1 and 6.6 cases/100,000 person-years, respectively, and increased 14.0% and 40.1% over the five-year study. Overall, 7.8% (2483/31889) of E. coli BSIs were third-generation cephalosporin-resistant. Calgary, Canberra, Sherbrooke, and western interior had significantly lower E. coli BSI rates compared to Finland. The significant association between age and E. coli BSI rate varied with sex. Calgary, Canberra, and western interior had significantly greater odds of third-generation cephalosporin-resistant E. coli BSIs compared to Finland. Compared to 2014, the odds of third-generation cephalosporin-resistant E. coli BSIs were significantly increased in 2016, 2017, and 2018. The significant association between age and the odds of having a third-generation cephalosporin-resistant E. coli BSI varied with sex. CONCLUSIONS: Increases in overall and third-generation cephalosporin-resistant standardized E. coli BSI rates were clinically important. Overall, E. coli BSI incidence rates were 40-104% greater than previous investigations from the same study areas. Region, sex, and age are important variables when analyzing E. coli BSI rates and third-generation cephalosporin resistance in E. coli BSIs. Considering E. coli is the most common cause of BSIs, this increasing burden and evolving third-generation cephalosporin resistance will have an important impact on human health, especially in aging populations.

15.
Elife ; 102021 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-34473060

RESUMEN

Triple-drug therapies have transformed HIV from a fatal condition to a chronic one. These therapies should prevent HIV drug resistance evolution, because one or more drugs suppress any partially resistant viruses. In practice, such therapies drastically reduced, but did not eliminate, resistance evolution. In this article, we reanalyze published data from an evolutionary perspective and demonstrate several intriguing patterns about HIV resistance evolution - resistance evolves (1) even after years on successful therapy, (2) sequentially, often via one mutation at a time and (3) in a partially predictable order. We describe how these observations might emerge under two models of HIV drugs varying in space or time. Despite decades of work in this area, much opportunity remains to create models with realistic parameters for three drugs, and to match model outcomes to resistance rates and genetic patterns from individuals on triple-drug therapy. Further, lessons from HIV may inform other systems.

16.
Cancer Genomics Proteomics ; 18(5): 637-643, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34479916

RESUMEN

BACKGROUND/AIM: Osteosarcoma is a recalcitrant heterogenous malignancy. The aim of the present study was to compare a series of multikinase inhibitors (MKIs) for efficacy on two drug-resistant osteosarcoma patient-derived orthotopic xenograft (PDOX) models in order to identify a clinical candidate. MATERIALS AND METHODS: The two osteosarcoma PDOX models were tested for response to the following MKIs: pazopanib, sunitinib, sorafenib, crizotinib, and regorafenib, in comparison to first-line treatment with cisplatinum and an untreated control. RESULTS: Regorafenib led to regression of osteosarcoma in both PDOXs. Total necrosis was observed pathologically in the regorafenib-treated tumors. Sorafenib arrested growth, without inducing regression, in one osteosarcoma model but not the other, and the other MKIs only slowed tumor growth. CONCLUSION: The present study demonstrated that regorafenib is much more effective than the other MKIs tested and has clinical potential against recalcitrant osteosarcoma.

17.
Biosci Trends ; 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34483225

RESUMEN

Community-acquired pneumonia (CAP) refers to infectious inflammation of the lung parenchyma developing outside of a hospital. CAP has quite a high mortality and morbidity rate worldwide, and especially among elderly patients. The increasing burden of CAP is due to antibiotic resistance, the growth of the elderly population, and underlying comorbidities. Streptococcus pneumoniae remains the most common bacterial pathogen causing CAP, but multi-drug resistance bacteria and potential pathogens have increased the difficulty and challenges of managing CAP. Although preventive measures, diagnostic techniques, and treatment strategies are constantly advancing and improving, the susceptibility of multi-drug resistant pathogens, such as including Methicillin-Resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, and Pseudomonas aeruginosa, has not improved significantly in recent decades, thus highlighting the importance and necessity of developing new antibiotics for the treatment of CAP. New antimicrobials have been approved over the past few years that will expand treatment options for CAP, and especially for patients with potential comorbidities. This situation also offers the chance to reduce the abuse of antibiotics, their toxicities, and their adverse reactions and to provide effective personalized antibiotic treatment.

18.
J Infect Dev Ctries ; 15(8): 1155-1166, 2021 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-34516424

RESUMEN

INTRODUCTION: A cross-sectional study was conducted to determine the prevalence and AMR pattern of Salmonella isolated from broiler chickens, farm sewage, and farm workers. This study also aimed at identifying the risk factors for Salmonella infection in chickens. METHODOLOGY: Cloacal swabs (n = 50) from broiler chickens, farm sewage (n = 50), and hand washed water of farm workers (n = 50) were collected along with data on farm management and antimicrobial usage from 50 broiler farms of Mymensingh and Gazipur districts. All samples were analysed for the presence of Salmonella using selective media and PCR assay. Antimicrobial susceptibility test was done for ten antimicrobials by disk diffusion test. Risk factor analyses were carried out by multivariable logistic regression using SPSS. RESULTS: The overall Salmonella prevalence was 66% (99/150). Salmonella prevalence were 82% and 72% in cloacal swabs and farm sewage samples, respectively. From hand washed water, 44% of the samples were positive for Salmonella. Salmonella infection in broiler chickens was significantly associated with farming experience (≤ 5 years) and age of birds (≥ 11 days). Similar pattern of antimicrobial resistance was observed in Salmonella isolated from three types of samples, and high resistances were observed to colistin, doxycycline, ciprofloxacin and ceftazidime. Moreover, isolates from all the three sources showed high percentage of multidrug-resistance (80.6% to 97.6%). CONCLUSIONS: The findings of this study reveal that antimicrobial-resistant Salmonella are prevailing at animal-human-environment interface, which needs an integrated approach to limit further spread of AMR.

19.
BMC Biol ; 19(1): 191, 2021 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-34493269

RESUMEN

BACKGROUND: Antimicrobial resistance (AMR) is among the gravest threats to human health and food security worldwide. The use of antimicrobials in livestock production can lead to emergence of AMR, which can have direct effects on humans through spread of zoonotic disease. Pigs pose a particular risk as they are a source of zoonotic diseases and receive more antimicrobials than most other livestock. Here we use a large-scale genomic approach to characterise AMR in Streptococcus suis, a commensal found in most pigs, but which can also cause serious disease in both pigs and humans. RESULTS: We obtained replicated measures of Minimum Inhibitory Concentration (MIC) for 16 antibiotics, across a panel of 678 isolates, from the major pig-producing regions of the world. For several drugs, there was no natural separation into 'resistant' and 'susceptible', highlighting the need to treat MIC as a quantitative trait. We found differences in MICs between countries, consistent with their patterns of antimicrobial usage. AMR levels were high even for drugs not used to treat S. suis, with many multidrug-resistant isolates. Similar levels of resistance were found in pigs and humans from regions associated with zoonotic transmission. We next used whole genome sequences for each isolate to identify 43 candidate resistance determinants, 22 of which were novel in S. suis. The presence of these determinants explained most of the variation in MIC. But there were also interesting complications, including epistatic interactions, where known resistance alleles had no effect in some genetic backgrounds. Beta-lactam resistance involved many core genome variants of small effect, appearing in a characteristic order. CONCLUSIONS: We present a large dataset allowing the analysis of the multiple contributing factors to AMR in S. suis. The high levels of AMR in S. suis that we observe are reflected by antibiotic usage patterns but our results confirm the potential for genomic data to aid in the fight against AMR.

20.
Tuberculosis (Edinb) ; 130: 102122, 2021 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-34517268

RESUMEN

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a major cause of death worldwide. Diverse genotypes have been demonstrated to drive the epidemiology of drug resistant (DR-) TB globally. Currently, there is limited knowledge on the genotypes and transmission dynamics of M. tuberculosis in Zambia. This study aimed to describe the genotypes of DR-TB from the Copperbelt and Northern regions of Zambia. Molecular typing tools of insertion sequence 6110-restriction fragment length polymorphism (IS6110-RFLP) and spacer oligonucleotide typing (spoligotyping) were applied. We demonstrate that diverse genotypes are associated with DR-TB in Zambia. The predominant genotype was lineage 4; other strains belonged to lineage 2 and 3. Genotypes previously identified as driving the epidemiology of drug susceptible TB have been identified as drivers of DR-TB. Genotyping analysis showed clustering of strains among patients from different regions of the country; suggesting that DR-TB is widespread. Molecular findings combined with phenotypic and epidemiologic findings play a critical role in identifying circulating genotypes and possible transmission chains. Clustering of drug resistant strains was demonstrated to be 48% and 86% according to IS6110-RFLP and spoligotyping, respectively. However, gaps in clinical and demographic data skew the interpretation, and call for data collection policy improvements.

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