Strategies to Reduce Long-Term Drug Resistance by Considering Effects of Differential Selective Treatments

2021 ◽  
pp. 49-60
Author(s):  
Tina Ghodsi Asnaashari ◽  
Young Hwan Chang
Keyword(s):  
Drug Resistance

The importance of year-round flea and roundworm prevention in lockdown and beyond

2021 ◽  
Vol 12 (2) ◽  
pp. 54-57
Author(s):  
Ian Wright
Keyword(s):  
Drug Resistance ◽  
Environmental Impact ◽  
Pivotal Role ◽  
Parasite Control ◽  
Treatment Need ◽  
Zoonotic Risk ◽  
Control Protocols

Whether routine preventative deworming regimens for Toxocara spp. in cats and dogs should be used to reduce zoonotic risk, continues to be a subject of much debate. Nurses are on the frontline of giving preventative parasite control advice and it is vital that this is based on the latest evidence to minimise zoonotic risk while ensuring over treatment does not take place. The need for routine year-round flea treatment is also fundamental to parasite control protocols in cats and dogs. The benefits of routine flea treatment need to be considered against the possible environmental impact and drug resistance issues that may be associated with long-term use. Veterinary nurses play a pivotal role in giving accurate parasite control to clients and balancing these factors based on the latest evidence.

scholarly journals Predicting drug resistance in M. tuberculosis using a long-term recurrent convolutional network

2021 ◽  
Author(s):  
Amir Hosein Safari ◽  
Nafiseh Sedaghat ◽  
Hooman Zabeti ◽  
Alpha Forna ◽  
Leonid Chindelevitch ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Convolutional Network

scholarly journals Candida albicans exhibits distinct cytoprotective responses to anti-fungal drugs that facilitate the evolution of drug resistance

2020 ◽  
Author(s):  
V Bettauer ◽  
S Massahi ◽  
S Khurdia ◽  
ACBP Costa ◽  
RP Omran ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Candida Albicans ◽  
Drug Exposure ◽  
Fluorescent Imaging ◽  
Late Time ◽  
Transport Mechanisms ◽  
Short Term ◽  
Anti Fungal ◽  
Initial Drug

AbstractWe developed a modified protocol for nanolitre droplet-based single cell sequencing appropriate for fungal settings, and used it to transcriptionally profiled several thousands cells from a prototrophic Candida albicans population and several drug exposed colonies (incl. fluconazole, caspofungin and nystatin). Thousands of cells from each colony were profiled both at early and late time points post-treatment in order to infer survival trajectories from initial drug tolerance to drug resistance. We find that prototrophic C. albicans populations differentially and stochastically express cytoprotective epigenetic programs. For all drugs, there is evidence that tolerant individuals partition into distinct subpopulations, each with a unique survival strategy involving different regulatory programs. These responses are weakly related to changes in morphology (shift from white to opaque forms, or shift from yeast to filamentous forms). In turn, those subpopulations that successfully reach resistance each have a distinct multivariate epigenetic response that coordinates the expression of efflux pumps, chaperones, transport mechanisms, and cell wall maintenance. Live cell fluorescent imaging was used to validate predictions of which molecular responses most often led to survival after drug exposure. Together our findings provide evidence that C. albicans has a robust toolkit of short-term epigenetic cytoprotective responses designed to “buy time” and increase the chance of acquiring long-term resistance.

scholarly journals Stenotrophomonas Maltophilia Peritonitis in a Child: Case Report and Review of Literature

2020 ◽  
Author(s):  
Demet Alaygut ◽  
Caner Alparslan ◽  
Serdar Sarıtaş ◽  
Elif Perihan Öncel ◽  
Önder Yavaşcan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Peritoneal Dialysis ◽  
Case Report ◽  
Antibiotic Treatment ◽  
Stenotrophomonas Maltophilia ◽  
Multi Drug Resistance ◽  
Review Of Literature ◽  
Dysplastic Kidney ◽  
Success Of Treatment

Stenotrophomonas maltophilia peritonitis has been only occasionally reported in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Because this microorganism has multi-drug resistance, its treatment is hard and long-term. The treatment might not be successful despite all the efforts and the process of peritoneal dialysis, and may terminate with loss of the catheter. In the present paper, S. maltophilia peritonitis developed in a 6-year-old girl patient, who underwent peritoneal dialysis due to bilateral dysplastic kidney, suffered from episodes of peritonitis frequently and required hospitalization, was presented with literature data. Even though the case received multiple antibiotic treatment and underwent endoluminal brushing (EB), the success of treatment could not be achieved. To the best of our knowledge, this patient is the youngest case in the literature.

scholarly journals Intravenous Honokiol in Drug-Resistant Cancer: Two Case Reports

2020 ◽  
Vol 19 ◽  
pp. 153473542092261
Author(s):  
Isaac Eliaz ◽  
Elaine Weil
Keyword(s):  
Drug Resistance ◽  
Cancer Patients ◽  
Complete Blood Count ◽  
Case Reports ◽  
Clinical Results ◽  
Drug Resistant ◽  
Magnolia Officinalis

Context: Long-term patient survival in cancer is affected by drug resistance. Honokiol (HNK) is a small-molecule polyphenol isolated from the bark and seed cones of Magnolia officinalis. HNK has been shown to enhance the effects of chemotherapy and inhibit drug resistance in preclinical models. HNK was well tolerated in multiple animal models when administered orally, intravenously (IV), and via intraperitoneal route. However, there are limited human data on the use of HNK in general, and specifically via IV (HNK-IV) in cancer. Objective: We aim to assess the efficacy, safety, and tolerability of HNK-IV in patients with drug-resistant tumors. Methods: This is a case study of 2 cancer patients who utilized HNK-IV as part of their cancer treatment regimen. The initial infusion of HNK was 10 mg/kg body weight, and subsequent treatments were increased up to 50 mg/kg according to individual tolerance, over 2 weeks. Results: Positive clinical response was achieved in both patients, including improved symptoms and quality of life. No serious adverse side effects occurred, and there were no adverse effects on laboratory parameters (complete blood count, kidney, and liver function). Transient sedation and minor nausea were noted and resolved postinfusion. Conclusions: This is the first report of HNK-IV in human patients. Given the positive clinical results, safety, and tolerability, the use of HNK-IV warrants further investigation regarding optimum formulation, and its use as adjunctive therapy in cancer patients.

Long-term virological outcomes, failure and acquired resistance in a large cohort of Ugandan children

2019 ◽  
Vol 74 (10) ◽  
pp. 3035-3043
Author(s):  
M H W Huibers ◽  
C Kityo ◽  
R S Boerma ◽  
E Kaudha ◽  
K C E Sigaloff ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Viral Suppression ◽  
Acquired Resistance ◽  
Close Monitoring ◽  
Resistance Mutations ◽  
Second Line Therapy ◽  
Drug Resistance Mutations ◽  
Virological Outcomes ◽  
Susceptibility Score

Abstract Objectives To evaluate long-term virological failure (VF) and drug resistance among HIV-infected Ugandan children on first-line ART. Methods In a multicentre prospective cohort study, viral load (VL) and drug resistance mutations (DRMs) were investigated at baseline and 6 monthly intervals in children (age ≤ 12 years). VF (two consecutive VLs >1000 copies/mL or death after 6 months of ART) was defined as early VF (0–24 months of ART) or late VF (25–48 months of ART). An active regimen was defined as partially active if the genotypic susceptibility score (GSS) was <3. Results Between 2010 and 2011, 316 children were enrolled. Viral suppression was achieved in 75.8%, 71.5%, 72.6% and 69.2% at 12, 24, 36 and 48 months. VF occurred in 111/286 (38.8%), of which 67.6% was early and 32.4% late VF. Early VF was associated with a partially active regimen at baseline (OR 6.0, 95% CI 1.9–18.5), poor adherence (OR 3.1, 95% CI 1.3–7.4) and immunodeficiency (OR 3.3, 95% CI 1.1–10.2). Late VF was associated with age >3 years (OR 2.5, 95% CI 1.0–6.6) and WHO stage 3/4 (OR 4.2, 95% CI 1.4–13.4). Acquired DRMs were detected in 27.0% before 24 months, versus 14.4% after 24 months (P < 0.001). A total of 92.2% of the children with early VF, versus 56.2% with late VF, had a partially active regimen (P < 0.001). Conclusions VF rates were high, occurred predominantly in the first 24 months and appeared to increase again in year four. Risk factors and patterns of early VF/DRMs were different from those of late VF/DRMs. Virological control may improve by close monitoring and prompt switching to second-line therapy in the first 24 months. Late VF may be prevented by early start of ART.

scholarly journals Engagement in Care, Viral Suppression, Drug Resistance, and Reasons for Nonengagement After Home-Based Same-Day Antiretroviral Therapy Initiation in Lesotho: A Two-Year Follow-up of the CASCADE Trial

2019 ◽  
Vol 71 (10) ◽  
pp. 2608-2614 ◽  
Author(s):  
Alain Amstutz ◽  
Jennifer Anne Brown ◽  
Isaac Ringera ◽  
Josephine Muhairwe ◽  
Thabo Ishmael Lejone ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Viral Suppression ◽  
Human Immunodeficiency Virus Testing ◽  
Long Term Results ◽  
Absolute Difference ◽  
Engagement In Care ◽  
Resistance Mutations ◽  
Home Based

Abstract Background The CASCADE trial showed that compared with usual care (UC), offering same-day (SD) antiretroviral therapy (ART) during home-based human immunodeficiency virus testing improved engagement in care and viral suppression 12 months after diagnosis. However, questions remain regarding long-term outcomes and the risk of propagating drug resistance. Methods After completion of the primary endpoint at 12 months, participants not in care in both arms were traced and encouraged to access care. At 24 months, the following outcomes were assessed in both arms: engagement in care, viral suppression, and reasons for nonengagement. Furthermore, we explored the acquisition of drug resistance mutations (DRMs) among SD arm nonlinkers. Results At 24 months, 64% (88/137) in the SD arm vs 59% (81/137) in the UC arm were in care (absolute difference [AD], 5%; 95% confidence interval [CI], −6 to16; P = .38) and 57% (78/137) vs 54% (74/137) had documented viral suppression (AD, 3%; 95% CI, −9 to 15; P = .28). Among 36 participants alive and not in care at 24 months with ascertained status, the majority rejected contact with the health system or were unwilling to take ART. Among 8 interviewed SD arm nonlinkers, 6 had not initiated ART upon enrollment, and no acquired DRMs were detected. Two had taken the initial 30-day ART supply and acquired DRMs. Conclusions SD ART resulted in higher rates of engagement in care and viral suppression at 12 months but not at 24 months. Leveling off between both arms was driven by linkage beyond 12 months in the UC arm. We did not observe compensatory long-term disengagement in the SD arm. These long-term results endorse SD ART initiation policies. Clinical Trials Registration NCT02692027.

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