Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 48.319
Filtrar
2.
Ann Palliat Med ; 10(9): 10005-10012, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34628924

RESUMO

BACKGROUND: To analyze the pathogenic bacteria, drug resistance, and risk factors of postoperative infection in patients with non-small cell lung cancer (NSCLC). METHODS: A total of 119 patients with NSCLC who were admitted to our hospital from January 2017 to March 2020 were selected. The patients' clinical data were collected to evaluate the postoperative infection. The pathogenic bacteria, drug resistance, and risk factors of postoperative infections in patients with NSCLC were analyzed. RESULTS: Among 119 patients, 33 cases (27.73%) had postoperative infection, and 86 cases (72.28%) had no infection. In total, 81 pathogens were isolated from the secretions via bacterial culture from the infected sites of the 33 patients. Of these, 43 (53.09%) were gram-negative bacteria, 34 (41.98%) were Gram-positive bacteria, and four (4.94%) were fungi. Postoperative gram-negative infection showed the highest resistance rate to ciprofloxacin (81.39%), and the drug resistance rate to imipenem and meropenem was low (9.30% and 4.65%, respectively). Postoperative gram-positive infection exhibited the highest resistance rate to erythromycin (82.35%), and the drug resistance rate to vancomycin was low (5.88%). According to the univariate analysis, there were differences between the two groups in age, length of hospitalization, combined diseases, operation time, invasive procedures, hemoglobin, and serum albumin (P<0.05). However, there were no differences in terms of gender, TNM staging, and pathological classification (P<0.05). Based on the unconditional multivariate logistic regression model analysis, age ≥60 years, hospitalization time >30 d, combined diseases, operation time ≥3 h, hospitalization time >30 d, invasive operation, hemoglobin ≤90 g/L, and serum albumin ≤30 g/L were independent risk factors leading to postoperative infection in patients with NSCLC (P<0.05). CONCLUSIONS: The postoperative infection rate of patients with NSCLC is high. gram-negative bacteria infection is the primary infection in patients. There are many factors that cause postoperative infections in patients, and it is necessary to strictly control these risk factors in clinical practice, which is an effective means to prevent postoperative infection.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Bactérias , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Resistência a Medicamentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Fatores de Risco
3.
Washington, D.C.; PAHO; 2021-10-14.
Não convencional em Inglês | PAHO-IRIS | ID: phr-54995

RESUMO

The acquisition of antimicrobials without a prescription is a global concern. This practice is thriving in countries that lack adequate legislation or where regulations are not properly enforced. The Pan American Health Organization (PAHO) and its member states in the Region of the Americas approved the Global Action Plan on Antimicrobial Resistance, which recognizes antimicrobial resistance as a threat to global public health that requires a multisectoral response. To tackle antimicrobial resistance, a worldwide change in behavior is needed in terms of how these drugs are used and acquired. National approaches are required to address the indiscriminate use and over-prescription of antimicrobials, and to enforce regulations on prescription and acquisition practices. The objective of this communication handbook is to help communication professionals and health program officials develop strategies to raise awareness and promote the importance of the appropriate use of antimicrobials among different stakeholders; raise public awareness about the importance of obtaining antimicrobials with a prescription in order to achieve multisectoral collaboration to ensure compliance with laws and regulations on this issue; and promote a change in behavior regarding the appropriate use and acquisition of antimicrobials by everyone involved. The target audiences for this handbook are the general population (including adolescents, children, and child caregivers/parents of children), healthcare professionals (including pharmacists and pharmacy staff), and various stakeholders (government officials, professional societies, medical organizations, the private sector, local leaders, and health-influencers, among others).


Assuntos
Resistência a Medicamentos , Resistência Microbiana a Medicamentos , Medicina , Acesso a Medicamentos Essenciais e Tecnologias em Saúde , Gestão de Ciência, Tecnologia e Inovação em Saúde , Sistemas de Saúde , Saúde Pública , Programas Nacionais de Saúde
4.
Pan Afr Med J ; 39: 118, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34512854

RESUMO

Introduction: from a genetic point of view P. falciparumis extremely polymorphic. There is a variety of parasite strains infesting individuals living in malaria endemic areas. The purpose of this study is to investigate the relationship between polymorphisms in Plasmodium falciparum parasites and Pfcrt and Pfmdr1 gene mutations in Nanoro area, Burkina Faso. Methods: blood samples from plasmodium carriers residing in the Nanoro Health District were genotyped using nested PCR. Parasite gene mutations associated with resistance to antimalarial drugs were detected by PCR-RFLP. Results: samples of 672 patients were successfully genotyped. No msp1and msp2allelic families exhibited an increase in developing mutations in resistance genes. However, mutant strains of these genes were present at greater levels in monoclonal infections than in multi-clonal infections. Conclusion: this study provides an overview of the relationship between polymorphisms in Plasmodium falciparum parasites and mutations in resistance genes. These data will undoubtedly contribute to improving knowledge of the parasite´s biology and its mechanisms of resistance to antimalarial drugs.


Assuntos
Antimaláricos/farmacologia , Malária Falciparum/parasitologia , Plasmodium falciparum/genética , Burkina Faso , Resistência a Medicamentos , Genótipo , Humanos , Malária Falciparum/tratamento farmacológico , Proteínas de Membrana Transportadoras/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Mutação , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/isolamento & purificação , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Proteínas de Protozoários/genética
5.
Front Cell Infect Microbiol ; 11: 673194, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568082

RESUMO

Background: Sulfadoxine-pyrimethamine (SP) is recommended for intermittent preventive treatment in Africa against Plasmodium falciparum infection. However, increasing SP resistance (SPR) of P. falciparum affects the therapeutic efficacy of SP, and pfdhfr (encoding dihydrofolate reductase) and pfdhps (encoding dihydropteroate synthase) genes are widely used as molecular markers for SPR surveillance. In the present study, we analyzed single nucleotide polymorphisms (SNPs) of pfdhfr and pfdhps in P. falciparum isolated from infected Chinese migrant workers returning from Africa. Methods: In total, 159 blood samples from P. falciparum-infected workers who had returned from Africa to Anhui, Shangdong, and Guangxi provinces were successfully detected and analyzed from 2017 to 2019. The SNPs in pfdhfr and pfdhps were analyzed using nested PCR. The genotypes and linkage disequilibrium (LD) were analyzed using Haploview. Results: High frequencies of the Asn51Ile (N51I), Cys59Arg(C59R), and Ser108Asn(S108N) mutant alleles were observed, with mutation frequencies of 97.60, 87.43, and 97.01% in pfdhfr, respectively. A triple mutation (IRN) in pfdhfr was the most prevalent haplotype (86.83%). Six point mutations were detected in pfdhps DNA fragment, Ile431Val (I431V), Ser436Ala (S436A), Ala437Gly (A437G), Lys540Glu(K540E), Ala581Gly(A581G), Ala613Ser(A613S). The pfdhps K540E (27.67%) was the most predominant allele, followed by S436A (27.04%), and a single mutant haplotype (SGKAA; 62.66%) was predominant in pfdhps. In total, 5 haplotypes of the pfdhfr gene and 13 haplotypes of the pfdhps gene were identified. A total of 130 isolates with 12 unique haplotypes were found in the pfdhfr-pfdhps combined haplotypes, most of them (n = 85, 65.38%) carried quadruple allele combinations (CIRNI-SGKAA). Conclusion: A high prevalence of point mutations in the pfdhfr and pfdhps genes of P. falciparum isolates was detected among Chinese migrant workers returning from Africa. Therefore, continuous in vitro molecular monitoring of Sulfadoxine-Pyrimethemine combined in vivo therapeutic monitoring of artemisinin combination therapy (ACT) efficacy and additional control efforts among migrant workers are urgently needed.


Assuntos
Antimaláricos , Malária Falciparum , África , Antimaláricos/farmacologia , China , Estudos Transversais , Combinação de Medicamentos , Resistência a Medicamentos/genética , Humanos , Mutação , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Pirimetamina , Sulfadoxina , Tetra-Hidrofolato Desidrogenase/genética
6.
Int J Mol Sci ; 22(17)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34502313

RESUMO

During DNA replication, the WEE1 kinase is responsible for safeguarding genomic integrity by phosphorylating and thus inhibiting cyclin-dependent kinases (CDKs), which are the driving force of the cell cycle. Consequentially, wee1 mutant plants fail to respond properly to problems arising during DNA replication and are hypersensitive to replication stress. Here, we report the identification of the polα-2 mutant, mutated in the catalytic subunit of DNA polymerase α, as a suppressor mutant of wee1. The mutated protein appears to be less stable, causing a loss of interaction with its subunits and resulting in a prolonged S-phase.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/efeitos dos fármacos , DNA Polimerase I/genética , Resistência a Medicamentos/genética , Hidroxiureia/farmacologia , Mutação , Proteínas Serina-Treonina Quinases/deficiência , Antidrepanocíticos/farmacologia , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Ciclo Celular , Dano ao DNA , Fosforilação
7.
AIDS Res Ther ; 18(1): 58, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496848

RESUMO

OBJECTIVE: The DUALIS study showed that switching to boosted darunavir (bDRV) plus dolutegravir (DTG; 2DR) was non-inferior to continuous bDRV plus 2 nucleoside/nucleotide reverse-transcriptase inhibitors (NRTIs; 3DR) in treatment-experienced virologically suppressed people living with HIV (PLWH). We analyzed virologic outcomes with respect to treatment history and HIV drug resistance. DESIGN: Post hoc analysis of a randomized trial. METHODS: Main inclusion criteria were an HIV RNA level < 50 copies/mL for ≥ 24 weeks and no resistance to integrase strand transfer inhibitors or bDRV. Resistance-associated mutations (RAMs) were interpreted using the Stanford HIVdb mutation list. Outcomes measures were 48-week virologic response (HIV RNA < 50 copies/mL, FDA snapshot) and HIV RNA ≥ 50 copies/mL (including discontinuation due to a lack of efficacy or reasons other than adverse events and HIV RNA ≥ 50 copies/mL, referred to as snapshot non-response). RESULTS: The analysis population included 263 patients (2DR: 131, 3DR: 132): 90.1% males; median age, 48 years; CD4 + T-cell nadir < 200/µl, 47.0%; ≥ 2 treatment changes, 27.4%; NRTI, non-NRTI (NNRTI), and major protease inhibitor (PI) RAMs in 9.5%, 14.4%, and 3.4%, respectively. In patients with RAMs in the 2DR and 3DR groups, virologic response rates were 87.8% and 96.0%, respectively; the corresponding rates in those without RAMs were 85.7% and 81.8%. RAMs were unrelated to virologic non-response in either group. No treatment-emergent RAMs were observed. CONCLUSIONS: DTG + bDRV is an effective treatment option without the risk of treatment-emergent resistance for PLWH on suppressive first- or further-line treatment with or without evidence of pre-existing NRTI, NNRTI, or PI RAMs. TRIAL REGISTRATION: EUDRA-CT Number 2015-000360-34; registered 07 April 2015; https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-000360-34/DE .


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Fármacos Anti-HIV/uso terapêutico , Darunavir/uso terapêutico , Resistência a Medicamentos , Feminino , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Compostos Heterocíclicos com 3 Anéis , Humanos , Masculino , Pessoa de Meia-Idade , Oxazinas , Piperazinas , Piridonas
8.
Biomed Res Int ; 2021: 5539544, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497848

RESUMO

Since 2000, a good deal of progress has been made in malaria control. However, there is still an unacceptably high burden of the disease and numerous challenges limiting advancement towards its elimination and ultimate eradication. Among the challenges is the antimalarial drug resistance, which has been documented for almost all antimalarial drugs in current use. As a result, the malaria research community is working on the modification of existing treatments as well as the discovery and development of new drugs to counter the resistance challenges. To this effect, many products are in the pipeline and expected to be marketed soon. In addition to drug and vaccine development, mass drug administration (MDA) is under scientific scrutiny as an important strategy for effective utilization of the developed products. This review discusses the challenges related to malaria elimination, ongoing approaches to tackle the impact of drug-resistant malaria, and upcoming antimalarial drugs.


Assuntos
Antimaláricos/uso terapêutico , Erradicação de Doenças/métodos , Malária/terapia , Resistência a Medicamentos , Drogas em Investigação/uso terapêutico , Humanos , Malária/tratamento farmacológico , Malária/epidemiologia , Malária/prevenção & controle
9.
J Clin Psychiatry ; 82(5)2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34496461

RESUMO

Treatment-resistant schizophrenia (TRS) represents a major clinical challenge. The broad definition of TRS requires nonresponse to at least 2 sequential antipsychotic trials of sufficient dose, duration, and adherence. Several demographic, clinical, and neurologic predictors are associated with TRS. Primary (or early) TRS is present from the beginning of therapy, while patients with secondary (or later-onset) TRS initially respond to antipsychotics but become resistant over time, often after relapses. Guidelines worldwide recognize clozapine as the most effective treatment option for TRS, but clozapine is underused due to various barriers. Importantly, studies indicate that response rates are higher when clozapine is initiated earlier in the treatment course. Side effects are common with clozapine, particularly in the first few weeks, but can mostly be managed without discontinuation; they do require proactive assessment, intervention, and reassurance for patients. Furthermore, plasma leucocyte and granulocyte levels must be monitored weekly during the first 18-26 weeks of treatment, and regularly thereafter, according to country regulations. Therapeutic drug monitoring of clozapine trough plasma levels is helpful to guide dosing, with greatest efficacy at plasma clozapine levels ≥350 µg/L, although this level is not universal. Notably, plasma clozapine levels are generally greater at lower doses in nonsmokers, patients with heavy caffeine consumption, in women, in obese people, in those with inflammation (including COVID-19 infection), and in older individuals. Earlier and broader use of clozapine in patients with TRS is an important measure to improve outcomes of patients with this most severe form of the illness.


Assuntos
Antipsicóticos/administração & dosagem , Clozapina/administração & dosagem , Esquizofrenia/tratamento farmacológico , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Resistência a Medicamentos/efeitos dos fármacos , Tolerância a Medicamentos , Feminino , Humanos , Masculino
10.
Anal Chim Acta ; 1181: 338920, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34556207

RESUMO

Drug resistance poses an enormous challenge for successful chemotherapy. Glutathione S-transferase (GST) has been confirmed to be involved in the progression of drug resistance to some anticancer drugs, thus revealing that the role of GST in anticancer drug resistance is necessary. Herein, by taking advantage of frequency upconversion luminescence (FUCL) technology, we reported an FUCL probe (NRh-NDs) that can detect GST based on a rhodamine derivative structure decorated with a 2,4-dinitrobenzenesulfonyl group (NDs). The NRh-NDs showed excellent sensitivity and high selectivity for GST and released the emissive dye NRh-NH2, which showed emission and excitation wavelengths in vitro of 820 nm and 850 nm, respectively. The NRh-NDs probe successfully tested endogenic GST in U87, MCF-7 and A549 cells. The cell data showed that the increased levels of GST were positively related to cisplatin resistance but not to 5-fluorouracil resistance. These results suggested that the probe could be used as a visual tool to reveal the cause of drug resistance for cisplatin resistance in cancer treatment. Furthermore, it may serve as an effective tool to confirm the mechanism of antitumor drug resistance.


Assuntos
Antineoplásicos , Preparações Farmacêuticas , Células A549 , Antineoplásicos/farmacologia , Cisplatino/farmacologia , Resistência a Medicamentos , Glutationa , Glutationa Transferase , Humanos , Células MCF-7
11.
Rev Bras Parasitol Vet ; 30(3): e010921, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34550213

RESUMO

The effectiveness of four anthelmintic classes on cattle gastrointestinal nematodes in the semi-arid region of Paraiba State, Brazil, was evaluated. Twenty farms were used, testing 40 animals in each one, totaling 800 animals. Cattle were divided into four groups composed with ten animals: I, treated with albendazole sulfoxide 15%; II, treated with ivermectin 1%; III, treated with closantel 25%; IV, treated with levamisole hydrochloride 7.5%. All treatments were administered subcutaneously. For the Fecal Egg Count Reduction Test (FECRT), individual fecal samples were collected on days 0 and 14, and sent for analysis of egg count per gram of feces (EPG) and larval cultures. It was observed that multiresistance was present in 95% (19/20) of the farms. Resistance to ivermectin and albendazole was observed in 95% (19/20), to closantel in 75% (15/20) and to levamisole in 20% (4/20). The most used management system was semi-intensive (75%; 15/20) and the ivermectin was the most reported drug for controlling helminths (65%; 13/20). Haemonchus spp. was the most prevalent helminth genus. It was concluded that the anthelmintic resistance of bovine gastrointestinal nematodes is high in the semi-arid of Paraíba State, Brazil, with multiresistance observed mainly to ivermectin, albendazole and closantel.


Assuntos
Anti-Helmínticos , Haemonchus , Nematoides , Doenças dos Ovinos , Animais , Anti-Helmínticos/farmacologia , Brasil , Bovinos , Resistência a Medicamentos , Fezes , Ivermectina/uso terapêutico , Contagem de Ovos de Parasitas/veterinária , Ovinos , Doenças dos Ovinos/tratamento farmacológico
12.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 33(4): 396-400, 2021 Aug 19.
Artigo em Chinês | MEDLINE | ID: mdl-34505447

RESUMO

OBJECTIVE: To investigate the genetic polymorphisms of Plasmodium falciparum multidrug resistance protein 1 (PfMDR1), chloroquine resistance transporter (PfCRT) and Kelch 13 (PfK13) genes in Bioko Island, Equatorial Guinea, so as to provide insights into the development of the malaria control strategy in local areas. METHODS: A total of 85 peripheral blood samples were collected from patients with Plasmodium falciparum infections in Bioko Island, Equatorial Guinea in 2018 and 2019, and genomic DNA was extracted. The PfMDR1, PfCRT and PfK13 genes were amplified using a nested PCR assay. The amplification products were sequenced, and the gene sequences were aligned. RESULTS: There were no mutations associated with artemisinin resistance in PfK13 gene in Bioko Island, Equatorial Guinea, while drug-resistant mutations were detected in PfMDR1 and PfCRT genes, and the proportions of PfMDR1_N86Y, PfMDR1_Y184F and PfCRT_K76T mutations were 35.29% (30/85), 72.94% (62/85) and 24.71% (21/85), respectively. CONCLUSIONS: There are mutations in PfMDR1, PfCRT and PfK13 genes in P. falciparum isolates from Bioko Island, Equatorial Guinea.


Assuntos
Antimaláricos , Malária Falciparum , Preparações Farmacêuticas , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Resistência a Medicamentos/genética , Guiné Equatorial/epidemiologia , Humanos , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/genética , Polimorfismo Genético , Proteínas de Protozoários/genética
13.
Talanta ; 235: 122771, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34517629

RESUMO

Intracellular cysteine and glutathione was deemed as the most important reductants in the cell and played significant roles in the cellular homeostasis and redox adjustment. Here we developed a NIR fluorescent probe (HI) to detect and report the intracellular cysteine and glutathione, and monitor the development of the drug resistance of tumor. HI with both excited wavelength and emitting wavelength located within near infrared area showed no fluorescence in the normal physiological environment. However, when HI responded to cysteine and glutathione, strong NIR fluorescence could be turned on, which was linear dependent to the cysteine concentrations and the limited of detection was 0.18 µM. The response between HI and cysteine/glutathione demonstrated high specificity and no other amino acids showed influence or competition. The HPLC identification of the recognition results confirmed the response of acryloyloxy on the HI and active sulfhydryl on the cysteine/glutathione. DFT calculation of the HOMO and LUMO energy before and after response revealed the intramolecular charge transfer mechanism that induced the generation of the fluorescence. When HI was incubated with PATU-8988 and PATU-8988/Fu cell, the intracellular cysteine and glutathione could be clearly imaged and monitored by the enhanced fluorescence. Meanwhile, when HI was applied to the tumor-bearing mice, the drug resistance of tumor could be monitored and reported.


Assuntos
Cisteína , Corantes Fluorescentes , Animais , Resistência a Medicamentos , Corantes Fluorescentes/farmacologia , Glutationa , Camundongos , Espectrometria de Fluorescência
14.
Parasite ; 28: 63, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34468310

RESUMO

A questionnaire was distributed to 5487 farmers throughout Norway in order to obtain information about management practices regarding helminth infections in sheep. In addition, the farmers' perceptions of helminths and anthelmintic efficacy were investigated. Most farmers (80%) treated prophylactically against nematodes, and 24% also used prophylactic treatment against Fasciola hepatica. Overall, few farmers (11%) used parasitological analysis as a tool to assess the timing of treatment, but rather based it on other factors such as previous experience (70%). In the surveyed sheep flocks, the use of benzimidazoles was reduced from 2018 (52%) to 2019 (47%) (p < 0.01), whereas the use of macrocyclic lactones increased from 2017 (23%) to 2019 (36%) (p < 0.001). Poor anthelmintic efficacy was suspected by 10% of the farmers, and 11% reported that helminths were an increasing problem in their flocks. The majority of farmers (72%) considered their veterinarian as the most important advisor for treatment of parasites, but reported a high level of uncertainty regarding which parasites were present in their flocks, with unknown status most frequently reported for Haemonchus contortus (71.5%). This is probably related to the fact that very few farmers (15%) regularly test their animals for parasites. The present study provides up-to-date information on treatment practices for helminths in Norwegian sheep flocks.


Assuntos
Anti-Helmínticos , Helmintos , Doenças dos Ovinos , Animais , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Resistência a Medicamentos , Fezes , Ovinos , Doenças dos Ovinos/tratamento farmacológico , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/prevenção & controle , Inquéritos e Questionários
15.
Braz J Biol ; 83: e247061, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34468524

RESUMO

The objective of this study was to evaluate the effectiveness of common antibiotics against different microorganisms in apparently healthy cattle in Shandong province and its suburb. A total of 220 nasal swab samples were collected and cultured for bacteriological evaluation. All the bacteria isolates after preliminary identification were subjected to antibiogram studies following disc diffusion method. It was found in the study that E. coli is the most commonly associated isolate (21%), followed by Klebsiella spp. (18%), Pseudomonas aeruginosa (13%), Salmonella spp. (15%), Shigella spp (12%), and Proteus spp (11%). While the antibiogram studies reveled that highest number of bacterial isolates showed resistance to Ampicillin (95%), followed by Augmentin (91%), Cefuroxime (85%) and Tetracycline (95%) of (Escherichia coli and Klebsiella spp). In the case of pseudomonas spp. and Salmonella the highest resistance was showed by Ampicillin (90%) followed by Amoxicillin + Clavulanic Acid (80%), Cefixime (90%), and Erythromycin (80%). In Shigella spp and Salmonella spp highest resistance was showed by Amoxicillin, Ceftazidime, Augmentin (60%), and Amoxicillin + Clavulanic Acid (50%). It is concluded that in vitro antibiogram studies of bacterial isolates revealed higher resistance for Ampicillin, Augmentin, Cefuroxime, Cefixime, Tetracycline, Erythromycin, and Amoxicillin + Clavulanic Acid. The high multiple Antibiotics resistance indexes (MARI) observed in all the isolates in this study ranging from 0.6 to 0.9. MARI value of >0.2 is suggests multiple antibiotic resistant bacteria and indicate presence of highly resistant bacteria.


Assuntos
Escherichia coli , Bactérias Gram-Negativas , Animais , Bovinos , Resistência a Medicamentos , Lactamas , Fenótipo
16.
Antimicrob Agents Chemother ; 65(10): e0077121, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34339273

RESUMO

Among novel compounds under recent investigation as potential new antimalarial drugs are three independently developed inhibitors of the Plasmodium falciparum P-type ATPase (PfATP4): KAE609 (cipargamin), PA92, and SJ733. We assessed ex vivo susceptibilities to these compounds of 374 fresh P. falciparum isolates collected in Tororo and Busia districts, Uganda, from 2016 to 2019. Median IC50s were 65 nM for SJ733, 9.1 nM for PA92, and 0.5 nM for KAE609. Sequencing of pfatp4 for 218 of these isolates demonstrated many nonsynonymous single nucleotide polymorphisms; the most frequent mutations were G1128R (69% of isolates mixed or mutant), Q1081K/R (68%), G223S (25%), N1045K (16%), and D1116G/N/Y (16%). The G223S mutation was associated with decreased susceptibility to SJ733, PA92, and KAE609. The D1116G/N/Y mutations were associated with decreased susceptibility to SJ733, and the presence of mutations at both codons 223 and 1116 was associated with decreased susceptibility to PA92 and SJ733. In all of these cases, absolute differences in susceptibilities of wild-type (WT) and mutant parasites were modest. Analysis of clones separated from mixed field isolates consistently identified mutant clones as less susceptible than WT. Analysis of isolates from other sites demonstrated the presence of the G223S and D1116G/N/Y mutations across Uganda. Our results indicate that malaria parasites circulating in Uganda have a number of polymorphisms in PfATP4 and that modestly decreased susceptibility to PfATP4 inhibitors is associated with some mutations now present in Ugandan parasites.


Assuntos
Antimaláricos , Malária Falciparum , Adenosina Trifosfatases , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Resistência a Medicamentos/genética , Genótipo , Humanos , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Proteínas de Protozoários/uso terapêutico , Uganda
17.
N Engl J Med ; 385(7): 595-608, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34379922

RESUMO

BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).


Assuntos
Infecções por HIV/prevenção & controle , Inibidores de Integrase de HIV/administração & dosagem , Profilaxia Pré-Exposição , Piridonas/administração & dosagem , Tenofovir/uso terapêutico , Administração Oral , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Preparações de Ação Retardada/administração & dosagem , Método Duplo-Cego , Esquema de Medicação , Resistência a Medicamentos/genética , Feminino , Inibidores de Integrase de HIV/efeitos adversos , Homossexualidade Masculina , Humanos , Injeções Intramusculares/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Piridonas/efeitos adversos , Pessoas Transgênero , Adulto Jovem
18.
Elife ; 102021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34372970

RESUMO

Background: National Malaria Control Programmes (NMCPs) currently make limited use of parasite genetic data. We have developed GenRe-Mekong, a platform for genetic surveillance of malaria in the Greater Mekong Subregion (GMS) that enables NMCPs to implement large-scale surveillance projects by integrating simple sample collection procedures in routine public health procedures. Methods: Samples from symptomatic patients are processed by SpotMalaria, a high-throughput system that produces a comprehensive set of genotypes comprising several drug resistance markers, species markers and a genomic barcode. GenRe-Mekong delivers Genetic Report Cards, a compendium of genotypes and phenotype predictions used to map prevalence of resistance to multiple drugs. Results: GenRe-Mekong has worked with NMCPs and research projects in eight countries, processing 9623 samples from clinical cases. Monitoring resistance markers has been valuable for tracking the rapid spread of parasites resistant to the dihydroartemisinin-piperaquine combination therapy. In Vietnam and Laos, GenRe-Mekong data have provided novel knowledge about the spread of these resistant strains into previously unaffected provinces, informing decision-making by NMCPs. Conclusions: GenRe-Mekong provides detailed knowledge about drug resistance at a local level, and facilitates data sharing at a regional level, enabling cross-border resistance monitoring and providing the public health community with valuable insights. The project provides a rich open data resource to benefit the entire malaria community. Funding: The GenRe-Mekong project is funded by the Bill and Melinda Gates Foundation (OPP11188166, OPP1204268). Genotyping and sequencing were funded by the Wellcome Trust (098051, 206194, 203141, 090770, 204911, 106698/B/14/Z) and Medical Research Council (G0600718). A proportion of samples were collected with the support of the UK Department for International Development (201900, M006212), and Intramural Research Program of the National Institute of Allergy and Infectious Diseases.


Assuntos
Controle de Doenças Transmissíveis/estatística & dados numéricos , Erradicação de Doenças/estatística & dados numéricos , Resistência a Medicamentos/genética , Malária/prevenção & controle , Plasmodium/genética , Animais , Ásia Sudeste , Bangladesh , República Democrática do Congo , Índia , Plasmodium/efeitos dos fármacos
19.
J Photochem Photobiol B ; 223: 112286, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34416476

RESUMO

Plasmodium falciparum, the causative organism of Malaria is a mosquito-borne parasitic disease which infects red blood cells (RBCs), where it multiplies rapidly and goes through different stages of its life cycle. When the parasite load exceeds >3% in the blood, malaria transforms into severe malaria which requires immediate attention as death occurs within hours to days. The increase in people traveling to malaria-endemic areas and resistance/partial resistance to most known antimalarial drugs has put the current management scheme in jeopardy. To improve the patient outcome at this point, the physician may opt to perform exchange transfusions from another individual as an adjunct therapy to reduce parasitized RBCs, but the strategy has many drawbacks, including chances of infection. These limitations can be mitigated if the patient's own blood is withdrawn/extracted, sterilized from the parasitic load and then re-transfused almost similar to what is done in extracorporeal blood treatment for sepsis, poisoning and graft versus host disease. Thus, in the present study a light-based photochemical approach, Photodynamic Therapy (PDT) built on delta-aminolevulinic acid-protoporphyrin IX (ALA-PpIX) synthesis is exploited. This modality was effective at destruction of both resistant and susceptible strains of parasites, including at a high load mimicking severe drug resistant malaria. The current findings have set the stage for concept of an ALA-PpIX based PDT platform, "the REAP (Rapid Elimination of Active Plasmodium) strategy". This approach provides an additional tool towards the defense against multi-drug resistant severe malaria, and other intracellular blood pathogens, dependent on heme-synthesis.


Assuntos
Antimaláricos/farmacologia , Luz , Malária/patologia , Fármacos Fotossensibilizantes/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Ácido Aminolevulínico/química , Antimaláricos/química , Antimaláricos/uso terapêutico , Resistência a Medicamentos/efeitos dos fármacos , Eritrócitos/parasitologia , Humanos , Cinética , Malária/tratamento farmacológico , Malária/parasitologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Plasmodium falciparum/isolamento & purificação , Protoporfirinas/química , Índice de Gravidade de Doença
20.
Vet Parasitol ; 298: 109535, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34340009

RESUMO

The equine roundworm Parascaris univalens has developed resistance to the three anthelmintic substances most commonly used in horses. The mechanisms responsible for resistance are believed to be multi-genic, and transport proteins such as the P-glycoprotein (Pgp) family have been suggested to be involved in resistance in several parasites including P. univlaens. To facilitate further research into the mechanisms behind drug metabolism and resistance development in P. univalens we aimed to develop an in vitro model based on larvae. We developed a fast and easy protocol for hatching P. univalens larvae for in vitro studies, resulting in a hatching rate of 92 %. The expression of transport protein genes pgp-2, pgp-9, pgp-11.1, pgp-16.1 and major facilitator superfamily (MFS) genes PgR006_g137 and PgR015_g078 were studied in hatched larvae exposed to the anthelmintic drugs ivermecin (IVM) 10-9 M, pyrantel citrate (PYR) 10-6 M and thiabendazole (TBZ) 10-5 M for 24 h. In comparison, the expression of these transport protein genes was studied in the anterior end and intestinal tissues of adult worms in vitro exposed to IVM, TBZ and PYR, at the same concentrations as larvae, for 3 h, 10 h and 24 h. Larval exposure to sub-lethal doses of IVM for 24 h did not affect the expression levels of any of the investigated genes, however larvae exposed to PYR and TBZ for 24 h showed significantly increased expression of pgp-9. In vitro drug exposure of adult worms did not result in any significant increases in expression of transport protein genes. Comparisons of constitutive expression between larvae and adult worm tissues showed that pgp-9, pgp-11.1, pgp-16.1 and MFS gene PgR015_g078 were expressed at lower levels in larvae than in adult tissues, while pgp-2 and MFS gene PgR006_g137 had similar expression levels in larvae and adult worms. All investigated transport protein genes were expressed at higher rates in the intestine than in the anterior end of adult worms, except pgp-11.1 where the expression was similar between the two tissues. This high constitutive expression in the intestine suggests that this is an important site for xenobiotic efflux in P. univalens. Despite the fact that the results of this study show differences in expression of transport protein genes between larvae and adult tissues, we believe that the larval assay system described here will be an important tool for further research into the molecular mechanisms behind anthelmintic resistance development and for other in vitro studies.


Assuntos
Anti-Helmínticos , Ascaridoidea , Proteínas de Transporte , Regulação da Expressão Gênica , Animais , Anti-Helmínticos/farmacologia , Ascaridoidea/efeitos dos fármacos , Ascaridoidea/genética , Proteínas de Transporte/genética , Resistência a Medicamentos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Ivermectina/farmacologia , Larva/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...