Long-Term Exposure to Antibiotics Has Caused Accumulation of Resistance Determinants in the Gut Microbiota of Honeybees

ABSTRACT Antibiotic treatment can impact nontarget microbes, enriching the pool of resistance genes available to pathogens and altering community profiles of microbes beneficial to hosts. The gut microbiota of adult honeybees, a distinctive community dominated by eight bacterial species, provides an opportunity to examine evolutionary responses to long-term treatment with a single antibiotic. For decades, American beekeepers have routinely treated colonies with oxytetracycline for control of larval pathogens. Using a functional metagenomic screen of bacteria from Maryland bees, we detected a high incidence of tetracycline/oxytetracycline resistance. This resistance is attributable to known resistance loci for which nucleotide sequences and flanking mobility genes were nearly identical to those from human pathogens and from bacteria associated with farm animals. Surveys using diagnostic PCR and sequencing revealed that gut bacteria of honeybees from diverse localities in the United States harbor eight tetracycline resistance loci, including efflux pump genes (tetB, tetC, tetD, tetH, tetL, and tetY) and ribosome protection genes (tetM and tetW), often at high frequencies. Isolates of gut bacteria from Connecticut bees display high levels of tetracycline resistance. Resistance genes were ubiquitous in American samples, though rare in colonies unexposed for 25 years. In contrast, only three resistance loci, at low frequencies, occurred in samples from countries not using antibiotics in beekeeping and samples from wild bumblebees. Thus, long-term antibiotic treatment has caused the bee gut microbiota to accumulate resistance genes, drawn from a widespread pool of highly mobile loci characterized from pathogens and agricultural sites. IMPORTANCE We found that 50 years of using antibiotics in beekeeping in the United States has resulted in extensive tetracycline resistance in the gut microbiota. These bacteria, which form a distinctive community present in healthy honeybees worldwide, may function in protecting bees from disease and in providing nutrition. In countries that do not use antibiotics in beekeeping, bee gut bacteria contained far fewer resistance genes. The tetracycline resistance that we observed in American samples reflects the capture of mobile resistance genes closely related to those known from human pathogens and agricultural sites. Thus, long-term treatment to control a specific pathogen resulted in the accumulation of a stockpile of resistance capabilities in the microbiota of a healthy gut. This stockpile can, in turn, provide a source of resistance genes for pathogens themselves. The use of novel antibiotics in beekeeping may disrupt bee health, adding to the threats faced by these pollinators.

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Abstract P44: Does Race Influence Disability and Hospital Disposition After Cerebral Hemorrhage? Results From a Community Wide Stroke Registry

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.4.suppl_1.ap44 ◽

2011 ◽

Vol 4 (suppl_1) ◽

Author(s):

Dilip K Pandey ◽

Venkatesh Aiyagari

Keyword(s):

Hospital Mortality ◽

Racial Differences ◽

The United States ◽

Term Treatment ◽

Severe Disability ◽

Stroke Registry ◽

Discharge Disposition ◽

Long Term Treatment ◽

Mortality Incidence

Background: Compared to Non-Hispanic whites (NHW), intracerebral hemorrhage (ICH) has a higher incidence among African Americans (AA) where it also occurs at a younger age. Previous studies have concluded that there are no racial differences in hospital mortality after ICH, but the influence of race on disability and discharge disposition after ICH has not been studied. Methods: The Illinois Capture-Stroke registry is a prospectively collected database of patients admitted with a stroke to 56 acute care hospitals in Illinois. We performed a retrospective analysis of the association between race, and in-hospital mortality, modified Rankin Scale (mRS) score at discharge and discharge disposition in 804 patients with ICH enrolled in the registry between 2005 and 2007. Results: We studied 530 NHW and 175 AA patients with radiologically proven ICH. Compared to NHW, AA patients were younger (mean age NHW: 73±14 vs AA: 58±12 yrs, p <0.001) and had a higher incidence of hypertension, smoking and coronary artery disease. Although there was no racial difference in hospital mortality, incidence of moderate to severe disability (mRS 4-5) was significantly higher in NHW (69%) compared to AA (55%). Among patients <65 years old, a trend (p=0.102) towards a higher disability in NHW was observed (60% in NHW vs. 45% in AA). In this age group, 41% of NHW and 33% of AA were discharged to rehabilitation facilities while 37% of NHW and 44% of AA were discharged home. Conclusion: A very large proportion of patients with ICH are discharged from hospitals with moderate or severe disability. Compared to NHW, a higher proportion of younger AA patients are discharged home after ICH. The long term outcomes of survivors after ICH in the United States is not well studied, and the influence of racial and socioeconomic factors on long-term treatment and outcome after ICH needs to be explored.

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Atezolizumab (atezo) in patients with metastatic urothelial carcinoma (mUC): A 2-year clinical update from a phase Ia study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.290 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 290-290 ◽

Cited By ~ 7

Author(s):

Daniel Peter Petrylak ◽

Thomas Powles ◽

Joaquim Bellmunt ◽

Fadi S. Braiteh ◽

Yohann Loriot ◽

...

Keyword(s):

Objective Response ◽

The United States ◽

Term Treatment ◽

Long Term Results ◽

Platinum Based Chemotherapy ◽

Long Term Treatment ◽

Previously Treated ◽

Ecog Ps

290 Background: Atezo (anti–PD-L1) has demonstrated safety and efficacy in a broad range of cancers and is approved in the United States for mUC previously treated with platinum-based chemotherapy. Here we report long-term results in mUC from Phase Ia study NCT01375842 (PCD4989g). Methods: Previously treated mUC patients received atezo 15 mg/kg or 1200 mg IV q3w. Enrollment in this Phase Ia expansion cohort initially required PD-L1–selected status and later opened to patients regardless of PD-L1 expression on tumor-infiltrating immune cells. The primary endpoint was safety/tolerability. Secondary endpoints included investigator-assessed RECIST v1.1 ORR (confirmed), DOR and OS. Results: 95 patients were safety evaluable (Table). Median age was 66 years, 76% were male and 80% had primary bladder tumors. 61% had ECOG PS 1. 52% received ≥ 3 prior systemic therapies for mUC (70% platinum). Median treatment duration was 3 months (range: 0-32 months); 24% were treated for ≥ 1 year. Treatment-related AEs occurred in 66% (all Grade) and 8% (Grade 3-4) of patients. No treatment-related deaths were reported. In 94 objective response–evaluable patients (follow-up ≥ 12 weeks), the ORR was 27% (95% CI: 18, 37%), and the CR rate was 10%; the SD rate was 19%. mDOR was 22.1 months (95% CI: 12.1, NE months) in all patients; 56% of responses (7/9 CRs and 7/16 PRs) were ongoing at the December 15, 2015 data cutoff. With a 24-month median follow-up duration (range: 1+ to 32 months), the 1-year OS rate was 47% (95% CI: 36, 58%), and the 2-year rate was 29% (19, 40%); mOS is in the Table. Updated clinical data with further follow-up and analyses by PD-L1 status will be presented. Conclusions: Long-term treatment with atezo was well tolerated, without new safety signals in heavily pre-treated mUC patients. The durability of responses, including CRs, along with extended OS, confirm atezo as a new standard for previously treated mUC patients. Clinical trial information: NCT01375842. [Table: see text]

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Hypnotic agents and controlled substances

10.1093/med/9780199360574.003.0029 ◽

2015 ◽

Author(s):

Ingrid Li ◽

Arthur Brewer ◽

Rusty Reeves

Keyword(s):

Treatment Decision ◽

The United States ◽

Term Treatment ◽

Health Concern ◽

Correctional Setting ◽

Controlled Substances ◽

Sleep Complaints ◽

Long Term Treatment ◽

Correctional Settings

Sleep medications are among the most frequently prescribed medications in the community. Many other Class II controlled substances, such as benzodiazepines and opiate medications, have become a major public health concern through overuse and abuse. Within correctional settings, these concerns are heightened and special considerations must be included in any treatment decision. Inmates abuse drugs at a prevalence many times higher than in the general population. A survey of practitioners in jails and prisons in the United States expresses the concern that sleep, opiate, and benzodiazepine medications can be abused or diverted. There has been little published as to the best correctional practice for the prescription of these medications. In general, sleep medications and controlled substances should be prescribed cautiously in a correctional setting, and wherever possible should be avoided as first-line treatment or as long-term treatment. Sleep medications are the most difficult to control since the quest for medications to treat sleep complaints is ubiquitous in corrections. Guidelines, thoughtful use of formulary controls, and a measure of flexibility will assist in the appropriate prescription of these medications. This chapter evaluates best practices in this arena of prescription practice.

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Clinical outcomes of EUS-guided drainage of debris-containing pancreatic pseudocysts: a large multicenter study

Endoscopy International Open ◽

10.1055/s-0042-121666 ◽

2017 ◽

Vol 05 (02) ◽

pp. E130-E136 ◽

Cited By ~ 2

Author(s):

Dennis Yang ◽

Sunil Amin ◽

Susana Gonzalez ◽

Daniel Mullady ◽

Steven Edmundowicz ◽

...

Keyword(s):

Treatment Outcomes ◽

Clinical Outcomes ◽

The United States ◽

Term Treatment ◽

Pancreatic Pseudocysts ◽

Endoscopic Drainage ◽

Technical Success ◽

Long Term Treatment

Abstract Background and study aims Data on clinical outcomes of endoscopic drainage of debris-free pseudocysts (PDF) versus pseudocysts containing solid debris (PSD) are very limited. The aims of this study were to compare treatment outcomes between patients with PDF vs. PSD undergoing endoscopic ultrasound (EUS)-guided drainage via transmural stents. Patients and methods Retrospective review of 142 consecutive patients with pseudocysts who underwent EUS-guided transmural drainage (TM) from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TM technical success, treatment outcomes (symptomatic and radiologic resolution), need for endoscopic re-intervention at follow-up, and adverse events (AEs). Results TM was performed in 90 patients with PDF and 52 with PSD. Technical success: PDF 87 (96.7 %) vs. PSD 51 (98.1 %). There was no difference in the rates for endoscopic re-intervention (5.5 % in PDF vs. 11.5 % in PSD; P = 0.33) or AEs (12.2 % in PDF vs. 19.2 % in PSD; P = 0.33). Median long-term follow-up after stent removal was 297 days (interquartile range [IQR]: 59 – 424 days) for PDF and 326 days (IQR: 180 – 448 days) for PSD (P = 0.88). There was a higher rate of short-term radiologic resolution of PDF (45; 66.2 %) vs. PSD (21; 51.2 %) (OR = 0.30; 95 % CI: 0.13 – 0.72; P = 0.009). There was no difference in long-term symptomatic resolution (PDF: 70.4 % vs. PSD: 66.7 %; P = 0.72) or radiologic resolution (PDF: 68.9 % vs. PSD: 78.6 %; P = 0.72) Conclusions There was no difference in need for endoscopic re-intervention, AEs or long-term treatment outcomes in patients with PDF vs. PSD undergoing EUS-guided drainage with transmural stents. Based on these results, the presence of solid debris in pancreatic fluid collections does not appear to be associated with a poorer outcome.

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Stable Colonization of Orally Administered Lactobacillus casei SY13 Alters the Gut Microbiota

BioMed Research International ◽

10.1155/2020/5281639 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Yuanchun Yue ◽

Xiaoxi Xu ◽

Baoyu Yang ◽

Jing Lu ◽

Shuwen Zhang ◽

...

Keyword(s):

Gut Microbiota ◽

Oral Administration ◽

Lactobacillus Casei ◽

Illumina Miseq ◽

Term Treatment ◽

Short Term ◽

Short Term Treatment ◽

Long Term Treatment ◽

Colonization Ability

The gut microbiota plays an important role in intestinal health. Probiotics such as Lactobacillus are known to regulate gut microbes and prevent diseases. However, most of them are unable to colonize their stability in hosts’ intestinal tracts. In this study, we investigated the ability of Lactobacillus casei SY13 (SY13) to colonize the intestinal tract of BALB/c mice, after its oral administration for a short-term (once for a day) and long-term (once daily for 27 days) duration. Furthermore, we also evaluated the influence of its administration on the gut microbial structure and diversity in mice. Male BALB/c mice were gavaged with 108 colony-forming units (CFU) of SY13, and TaqMan-MGB probe and Illumina MiSeq sequencing were performed to assess the colonization ability and bacterial community structure in the cecum contents. The results showed that long-term treatment with SY13 enhanced its ability to form a colony in the intestine tract in contrast to the short-term treatment group, whose colony was retained for only 3 days. Oral administration of SY13 also significantly enhanced the gut microbial diversity. Short-term treatment with SY13 (SSY13) elevated Firmicutes and diminished Bacteroidetes phyla compared with long-term treatment (LSY13) and controls. The findings laid the foundation for the study of probiotic colonization ability and improvement of microbiota for the prevention of gut diseases.

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Time trends and treatment pathways in the prescribing of individual oral anticoagulants in patients with non-valvular atrial fibrillation: an observational study of more than three million patients from Europe and the United States

10.22541/au.161932997.71916310/v1 ◽

2021 ◽

Author(s):

Pareen Vora ◽

Henry Morgan Stewart ◽

Beth Russell ◽

Alex Asiimwe ◽

Gunnar Brobert

Keyword(s):

United States ◽

Atrial Fibrillation ◽

Time Trends ◽

Oral Anticoagulants ◽

The United States ◽

Common Data Model ◽

Long Term Treatment ◽

The Us ◽

The Uk

Background: Data directly comparing trends in the use of different oral anticoagulants (OACs) among patients with atrial fibrillation (AF) from different countries are limited. We addressed this using a large-scale network cohort study in the United States (US), Belgium, France, Germany and United Kingdom (UK). Methods: We used nine databases (claims or electronic health records) that had been converted into the Observational Medical Outcomes Partnership Common Data Model with analysis performed using open-source analytical tools. We identified adults with AF and a first OAC prescription, either vitamin K antagonist (VKA) or direct oral anticoagulant (DOAC) from 2010–2017. We described time-trends in use, continuation and switching. Results: In 2010, 87.5%–99.8% of patients started on a VKA. By 2017, the majority started on a DOAC: 87.0% (US), 88.3% (Belgium), 93.1% (France), 88.4% (Germany), 86.1%–86.7% (UK). In the UK, DOACs became the most common starting OAC in 2015, 2–3 years later than elsewhere. Apixaban was the most common starting OAC by 2017: 50.2%–57.8% (US), 31.4% (Belgium), 45.9% (France), 39.5% (Germany), 49.8%– 50.5% (UK), followed by rivaroxaban; 24.8%–32.5% (US), 25.7% (Belgium), 38.4% (France), 24.9% (Germany), 30.2%– 31.2% (UK). Long-term treatment was less common in the US than in Europe, especially the UK. A minority of patients switched from their index OAC, both in the short- and long-term. Conclusions: From 2010–2017, VKA use had significantly declined and DOAC use had significantly increased in the US and Europe; apixaban was the most prescribed OAC in 2017 followed by rivaroxaban.

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Benzodiazepines and Pain Management

The Benzodiazepines Crisis ◽

10.1093/med/9780197517277.003.0009 ◽

2020 ◽

pp. 149-159

Author(s):

John F. Peppin ◽

Steven L. Wright

Keyword(s):

Chronic Pain ◽

Sleep Disturbances ◽

Muscle Relaxation ◽

The United States ◽

Term Treatment ◽

Muscle Spasm ◽

The European Union ◽

Long Term Treatment ◽

Few Data

Chronic pain is widespread and the use of opioids for chronic pain is also common. Frequently benzodiazepines are concomitantly prescribed in these patients, for anxiety, sleep disorders, and muscle pain and spasm. In the United States, Canada, and the European Union, increases in benzodiazepine prescribing has been seen, in some cases over 16% over the last decade. Unfortunately, the combination of opioids and benzodiazepines is correlated with overdose and overdose death. Few data exist to support the use of benzos for sleep, muscle spasm, or the long-term treatment of anxiety in the context of pain. It has been further shown that the use of benzodiazepines carries other adverse events and issues. It is estimated that the elimination of benzodiazepines would decrease overdoses by over 15%. The deprescribing of benzodiazepines should become common practice in the professional pain community and their use drastically limited. The authors suggest an approach to the discontinuation of benzodiazepines that includes extensive patient involvement. Other options for anxiety, sleep disturbances, and muscle relaxation are available and should be considered. For those already on these agents (legacy patients), tapering with the goal of discontinuation in a safe and person-centered process should be undertaken.

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A Report from the International Collaborative Gaucher Group (ICGG) Gaucher Registry

Blood ◽

10.1182/blood.v112.11.3549.3549 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3549-3549 ◽

Cited By ~ 1

Author(s):

Neal J. Weinreb ◽

Stephan vom Dahl

Keyword(s):

Bone Pain ◽

Liver Volume ◽

The United States ◽

Rare Allele ◽

Term Treatment ◽

Severe Thrombocytopenia ◽

Long Term Effects ◽

Long Term Treatment ◽

History Of

Abstract Objective: To report the latest data on patients with Gaucher disease (GD) enrolled in the ICGG Gaucher Registry. Methods: Data from all patients enrolled in the ICGG Gaucher Registry from 1991 through 2007 were analyzed. Results: As of December 31, 2007, 4,936 GD patients were enrolled in the ICGG Gaucher Registry by 772 physicians in 60 countries. The countries with the largest numbers of patients were the United States (36%), Israel (14%) and Brazil (10%). The majority of patients were diagnosed with GD between 4 and 30 years (mean age, 19 years). The most common genotypes were N370S/N370S (31%), N370S/L444P (16%), N370S/Rare Allele (13%), and N370S/unknown (11%). The most frequent genotype for patients with neuronopathic GD was L444P/L444P (68%). At diagnosis, anemia was reported in 37% of patients and moderate to severe thrombocytopenia in 60%. Splenomegaly was reported in 86% of patients (>5 multiples of normal [MN]) and hepatomegaly in 65% (liver volume >1.25 MN). Bone pain was present in 34% of patients and radiologic bone disease was reported in 83%. Long-term treatment with imiglucerase resulted in improved haematological parameters, decreased visceral involvement, decreased bone pain and abolition of bone crises. Conclusions: For GD and other rare “ultra-orphan” diseases, a large longitudinal international disease registry provides the best means to investigate the natural history of the disease and the long-term effects of therapy. The strength of the ICGG Gaucher Registry data is the inclusion of a large, worldwide patient population with long periods of follow-up data, allowing for studies not otherwise possible.

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Laxative effect of repeated Daiokanzoto is attributable to decrease in aquaporin-3 expression in the colon

Journal of Natural Medicines ◽

10.1007/s11418-018-1174-1 ◽

2018 ◽

Vol 72 (2) ◽

pp. 493-502 ◽

Cited By ~ 7

Author(s):

Risako Kon ◽

Miho Yamamura ◽

Yukari Matsunaga ◽

Hiroshi Kimura ◽

Moe Minami ◽

...

Keyword(s):

Gut Microbiota ◽

Chronic Constipation ◽

Term Treatment ◽

Control Treatment ◽

Colonic Inflammation ◽

Aquaporin 3 ◽

Laxative Effect ◽

Long Term Treatment ◽

Repeated Use

Abstract Daiokanzoto (DKT) exerts its laxative effect via colonic inflammation caused by sennoside A in Daio (rhubarb). Previously, we showed that the laxative effect of sennoside A is related to decreased aquaporin-3 (AQP3) expression in mucosal epithelial cells due to colonic inflammation. We also found that a combination of glycyrrhizin, an ingredient in Kanzo (glycyrrhiza), and sennoside A attenuates the inflammatory response induced by sennoside A and reduces its laxative effect. These findings indicate that DKT may be a long-term treatment for chronic constipation, but there is no evidence supporting this hypothesis. In this study, we analyzed the laxative effect of repeated DKT administration, focusing on AQP3 expression in the colon. After rats were treated for 7 days, decreased AQP3 expression and the onset of diarrhea were observed in the DKT group, but were not seen in the Daio group either. Although the relative abundance of gut microbiota after repeated DKT administration was similar to that after control treatment, Daio reduced Lactobacillaceae, Bifidobacteriaceae, and Bacteroidaceae levels and markedly increased Lachnospiraceae levels. In this study, we show that DKT has a sustained laxative effect, even upon repeated use, probably because it maintains decreased AQP3 expression and gut microbiota homeostasis. This outcome therefore indicates that DKT can be used as a long-term treatment for chronic constipation.

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WCA Recommendations for the Long-Term Treatment of Generalized Anxiety Disorder

CNS Spectrums ◽

10.1017/s1092852900006945 ◽

2003 ◽

Vol 8 (S1) ◽

pp. 53-61 ◽

Cited By ~ 61

Author(s):

Christer Allgulander ◽

Borwin Bandelow ◽

Eric Hollander ◽

Stuart A. Montgomery ◽

David J. Nutt ◽

...

Keyword(s):

Anxiety Disorder ◽

Generalized Anxiety Disorder ◽

Selective Serotonin Reuptake Inhibitors ◽

Physical Dependence ◽

The United States ◽

Term Treatment ◽

Generalized Anxiety ◽

Treatment Trials ◽

Long Term Treatment

ABSTRACTWhat are the current recommendations for the long-term treatment of generalized anxiety disorder (GAD)? GAD is a common disorder with a lifetime prevalence of 4% to 7% in the general population. GAD is characterized by excessive, uncontrollable worry or anxiety about a number of events or activities that the individual experiences on more days than not over a 6-month period. Onset of GAD symptoms usually occurs during an individual's early twenties; however, high rates of GAD have also been seen in children and adolescents. The clinical course of GAD is often chronic, with 40% of patients reporting illness lasting >5 years. GAD is associated with pronounced functional impairment, resulting in decreased vocational function and reduced quality of life. Patients with GAD tend to be high users of outpatient medical care, which contributes significantly to healtcare costs. Currently, benzodiazepines and buspirone are prescribed frequently to treat GAD. Although both show efficacy in acute treatment trials, few long-term studies have been perform Benzodiazepines are not recommended for long-term treatment of GAD, due to associated development of tolerance, psychomotor impairment, cognitive and memory changes, physical dependence, and a withdrawal reaction on discontinuation. The antidepressant venlafaxine extended-release (XR) has received approval for the treatment of GAD in the United States and many other countries. Venlafaxine XR has demonstrated efficacy over placebo in two randomized treatment trials of 6 months' duration as well as in other acute trials. Paroxetine is the first of the selective serotonin reuptake inhibitors (SSRIs) to receive US approval for the treatment of GAD. Paroxetine demonstrated superiority to placebo in short-term trials, and investigations into the use of other SSRIs are ongoing. This suggests that other SSRIs, and serotonin and noradrenaline reuptake inhibitors, are likely to be effective in the treatment of GAD. Of the psychological therapies, cognitive-behavioral therapy (CBT) shows the greatest benefit in treating GAD patients. Treatment gains after a 12-week course of CBT may be maintained for up to 1 year. Currently, no guidelines exist for the long-term treatment of GAD.

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