Measuring antibiotic levels and their relationship with the microbiome in chronic rhinosinusitis

2019 ◽  
Vol 133 (10) ◽  
pp. 862-866
Author(s):  
J Siu ◽  
M D Tingle ◽  
R G Douglas
Keyword(s):  
Drug Therapy ◽  
Gut Microbiota ◽  
Antibiotic Therapy ◽  
Chronic Rhinosinusitis ◽  
Drug Distribution ◽  
The Body ◽  
Oral Antibiotics ◽  
Future Studies ◽  
Drug Concentrations ◽  
The Impact

AbstractBackgroundThe evidence supporting the efficacy of antibiotic therapy in the treatment of chronic rhinosinusitis is not compelling. A limited number of studies show that the changes in the nasal microbiome in patients following drug therapy are unpredictable and variable. The evidence for the impact of oral antibiotics on the gut microbiota is stronger, possibly as a result of differences in drug distribution to various sites around the body. There are few studies on sinus mucosal and mucus levels of oral antibiotics used in the treatment of chronic rhinosinusitis. The distribution dependent effects of antibiotics on the sinonasal microbiome is unclear.ConclusionThis review highlights that relative drug concentrations and their efficacy on microbiota at different sites is an important subject for future studies investigating chronic rhinosinusitis.

Contributions of Lactobacillus plantarum PC170 administration on the recovery of gut microbiota after short-term ceftriaxone exposure in mice

2020 ◽  
Vol 11 (5) ◽  
pp. 489-509
Author(s):  
R. Cheng ◽  
H. Liang ◽  
Y. Zhang ◽  
J. Guo ◽  
Z. Miao ◽  
...  
Keyword(s):  
Body Weight ◽  
Gut Microbiota ◽  
Lactobacillus Plantarum ◽  
Antibiotic Treatment ◽  
Recovery Phase ◽  
The Body ◽  
Faecal Microbiota ◽  
Short Term ◽  
Host Animal ◽  
The Impact

This study aimed to determine the impact of Lactobacillus plantarum PC170 concurrent with antibiotic treatment and/or during the recovery phase after antibiotic treatment on the body weight, faecal bacterial composition, short-chain fatty acids (SCFAs) concentration, and splenic cytokine mRNA expression of mice. Orally administrated ceftriaxone quantitatively and significantly decreased body weight, faecal total bacteria, Akkermansia muciniphila, and Lactobacillus plantarum, and faecal SCFAs concentration. Ceftriaxone treatment also dramatically altered the faecal microbiota with an increased Chao1 index, decreased species diversities and Bacteroidetes, and more Firmicutes and Proteobacteria. After ceftriaxone intervention, these changes all gradually started to recover. However, faecal microbiota diversities were still totally different from control by significantly increased α- and β-diversities. Bacteroidetes all flourished and became dominant during the recovery process. However, mice treated with PC170 both in parallel with and after ceftriaxone treatment encouraged more Bacteroidetes, Verrucomicrobia, and Actinobacteria, and the diversity by which to make faecal microbiota was very much closer to control. Furthermore, the expression of splenic pro-inflammatory cytokine tumour necrosis factor-α mRNA in mice supplemented with PC170 during the recovery phase was significantly lower than natural recovery. These results indicated that antibiotics, such as ceftriaxone, even with short-term intervention, could dramatically damage the structure of gut microbiota and their abilities to produce SCFAs with loss of body weight. Although such damages could be partly recovered with the cessation of antibiotics, the implication of antibiotics to gut microbiota might remain even after antibiotic treatment. The selected strain PC170 might be a potential probiotic because of its contributions in helping the host animal to remodel or stabilise its gut microbiome and enhancing the anti-inflammatory response as protection from the side effects of antibiotic therapy when it was administered in parallel with and after antibiotic treatment.

Mutual effects of free and nanoencapsulated phenolic compounds on human microbiota

2021 ◽  
Vol 28 ◽  
Author(s):  
Carina Cassini ◽  
Pedro Henrique Zatti ◽  
Valéria Weiss Angeli ◽  
Catia Santos Branco ◽  
Mirian Salvador
Keyword(s):  
Phenolic Compounds ◽  
Gut Microbiota ◽  
Oral Bioavailability ◽  
Polymeric Nanoparticles ◽  
The Body ◽  
Biological Targets ◽  
Chemical Structures ◽  
Metabolic Transformation ◽  
Biological Performance ◽  
The Impact

: Phenolic compounds (PC) have many health benefits such as antioxidant, anticarcinogenic, neuroprotective, and anti-inflammatory activities. All of these activities depend on their chemical structures and their interaction with biological targets in the body. PC occur naturally in polymerized form, linked to glycosides and requires metabolic transformation from their ingestion to their absorption. The gut microbiota can transform PC into more easily absorbed metabolites. The PC, in turn, have prebiotic and antimicrobial actions on the microbiota. Despite this, their low oral bioavailability still compromises biological performance. Therefore, the use of nanocarriers has been demonstrated to be a useful strategy to improve PC absorption and, consequently, their health effects. Nanotechnology is an excellent alternative able to overcome the limits of oral bioavailability of PC, since it offers protection from degradation during their passage through the gastrointestinal tract. Moreover, nanotechnology is also capable of promoting controlled PC release and modulating the interaction between PC and the microbiota. However, little is known about the impact of the nanotechnology on PC effects on the gut microbiota. This review highlights the use of nanotechnology for PC delivery on gut microbiota, focusing on the ability of such formulations to enhance oral bioavailability by applying nanocarriers (polymeric nanoparticles, nanostructured lipid carriers, solid lipid nanoparticles). In addition, the effects of free and nanocarried PC or nanocarriers per se on gut microbiota are also described.

scholarly journals The Application of Metabolomics to Probiotic and Prebiotic Interventions in Human Clinical Studies

Metabolites ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 120
Author(s):  
Thomas M. O’Connell
Keyword(s):  
Clinical Trials ◽  
Nucleic Acid ◽  
Gut Microbiota ◽  
Microbial Communities ◽  
Biochemical Mechanism ◽  
Beneficial Bacteria ◽  
Future Studies ◽  
Current State ◽  
Live Bacteria ◽  
The Impact

There is an ever-increasing appreciation for our gut microbiota that plays a crucial role in the maintenance of health, as well as the development of disease. Probiotics are live bacteria that are consumed to increase the population of beneficial bacteria and prebiotics are dietary substrates intended to promote the propagation of beneficial bacteria. In order to optimize the use of probiotics and prebiotics, a more complete biochemical understanding of the impact that these treatments have on the community and functioning of the gut microbiota is required. Nucleic acid sequencing methods can provide highly detailed information on the composition of the microbial communities but provide less information on the actual function. As bacteria impart much of their influence on the host through the production of metabolites, there is much to be learned by the application of metabolomics. The focus of this review is on the use of metabolomics in the study of probiotic and prebiotic treatments in the context of human clinical trials. Assessment of the current state of this research will help guide the design of future studies to further elucidate the biochemical mechanism by which probiotics and prebiotics function and pave the way toward more personalized applications.

scholarly journals Persistent Bacteremia in Rabbit Fetuses despite Maternal Antibiotic Therapy in a Novel Intrauterine-Infection Model

2003 ◽  
Vol 47 (7) ◽  
pp. 2125-2130 ◽  
Author(s):  
C. Gras-Le Guen ◽  
T. Debillon ◽  
C. Toquet ◽  
A. Jarry ◽  
N. Winer ◽  
...  
Keyword(s):  
Drug Therapy ◽  
Antibiotic Therapy ◽  
Rabbit Model ◽  
Blood Cultures ◽  
Maternal Outcome ◽  
Dramatic Improvement ◽  
Human Pharmacokinetics ◽  
Fetal Survival ◽  
Drug Concentrations ◽  
Persistent Bacteremia

ABSTRACT The effect of optimized maternal therapy by bactericidal agents was evaluated in a reproducible rabbit model of Escherichia coli maternofetal infection simulating human pharmacokinetics. Intravenous antibiotic therapy was begun in the pregnant rabbit 12 h after bacterial intrauterine inoculation, using a computer-controlled pump to simulate human pharmacokinetics of ceftriaxone (1 g/day) associated or not with gentamicin (3 mg/kg of body weight/day). Data were compared for fetal survival, quantitative blood cultures, fetal histology in treated versus untreated groups, and maternal and fetal antibiotic concentrations in plasma in treated animals. Antibiotic therapy led to dramatic improvement in maternal outcome (100% survival versus 100% death in the untreated group in association with maternal septicemia). Fetal survival also improved, with the two-drug combination providing a more potent effect. After 3 days of treatment, 32% of fetuses survived with one-drug therapy and 62% with two-drug therapy (Yates corrected χ2, P < 0.05). In untreated animals, bacterial counts in blood cultures increased rapidly during the first 24 h up to 8.1 ± 0.5 log CFU/ml, but remained relatively constant at all times with antibiotic treatment: 4.5 ± 0.7 log CFU/ml at the start of treatment and 6.2 ± 0.4 and 5.2 ± 0.9 log CFU/ml after 72 h for one- and two-drug therapy, respectively (data are means ± standard deviations). The failure of animals to be cured after 3 days of treatment was not due to an inadequate concentration of ceftriaxone, as the residual level in fetal serum at sacrifice was more than 1,000 times the MIC of the microbe. Unexpectedly, inflammation in fetal lung decreased in the treated group after as little as 24 h of antibiotic therapy, despite persistent bacteremia. Although maternal outcome improved and drug concentrations were above the MIC, the treatment did not achieve sterilization of fetuses in utero for this rabbit E. coli maternofetal infection. However, fetal survival showed some improvement, and the histologic features of lung inflammation were reduced.

scholarly journals Impact of a Moderately Hypocaloric Mediterranean Diet on the Gut Microbiota Composition of Italian Obese Patients

2020 ◽  
Author(s):  
Silvia Pisanu ◽  
Vanessa Palmas ◽  
Veronica Madau ◽  
Emanuela Casula ◽  
Andrea Deledda ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Mediterranean Diet ◽  
Illumina Miseq ◽  
Nutritional Intervention ◽  
The Body ◽  
Rrna Gene ◽  
Obese Patients ◽  
Dietary Interventions ◽  
The Impact ◽  
Gut Microbiota Composition

Although it is known that the gut microbiota (GM) can be modulated by diet, the efficacy of specific dietary interventions in determining its composition and diversity in obese patients remains to be ascertained. The present work aims to evaluate the impact of a moderately hypocaloric Mediterranean diet on the GM of obese and overweight patients (OB). The GM of 23 OB patients (F/M= 20/3) was compared before (T0) and after 3 months (T3) of the nutritional intervention (NI). Fecal samples were analyzed by Illumina MiSeq sequencing of the 16S rRNA gene. At baseline, the GM characterization confirmed the typical obesity-associated dysbiosis. After 3 months of NI, patients presented a statistically significant reduction of the body weight and fat mass, along with changes in the relative abundance of many microbial patterns. In fact, we observed an increased abundance in several Bacteroidetes taxa (i.e. Sphingobacteriaceae, Sphingobacterium, Bacteroides spp., Prevotella stercorea) and depletion of many Firmicutes taxa (i.e. Lachnospiraceae members, Ruminococcaceae and Ruminococcus, Veillonellaceae, Catenibacterium, Megamonas). In addition, the phylum Proteobacteria showed an increased abundance, while the genus Sutterella, within the same phylum, decreased after the intervention. Metabolic pathways, predicted by bioinformatic analyses, showed a decrease in membrane transport and cell motility after NI. The present study extends our knowledge of the GM profiles in OB, highlighting the potential benefit of a moderate caloric restriction in counteracting the gut dysbiosis.

scholarly journals Have You Heard That—“GOSSIP”? Gossip Spreads Rapidly and Influences Broadly

2021 ◽  
Vol 18 (24) ◽  
pp. 13389
Author(s):  
Rezwan Ullah ◽  
Muhammad Zada ◽  
Imran Saeed ◽  
Jawad Khan ◽  
Muhammad Shahbaz ◽  
...  
Keyword(s):  
Ego Depletion ◽  
Current Data ◽  
The Body ◽  
Theory And Practice ◽  
Public And Private ◽  
Future Studies ◽  
Single Region ◽  
Study Results ◽  
Time Lagged ◽  
The Impact

This study examines the impact of negative workplace gossip (NWG) on employee political acts (PA) and the role of ego depletion (ED) as a mediator. We also examined the indirect impact of NWG on PA through ED controlled by emotional intelligence (EI). A three-wave time-lagged study (paper-pencil based) was performed with 277 employees from various private organisations in Islamabad, Pakistan. The current data were gathered in three phases to reduce common method bias. Study results indicate that NWG positively affects employees’ PA. The authors also found ED as a potential mediator in the association between NWG and PA. In addition, the results also indicate the indirect effect of NWG on targets’ PA via ED is reduced by targets’ EI, with the result that this connection is weak when targets’ EI is high. Because this research is limited to a single region of Pakistan, particularly Islamabad, its findings cannot be comprehensive. Future studies should use a larger sample size to accomplish the same study. Future studies may include more organisations (that is, Public) to conduct a comparative analysis of the public and private sectors. This article, based on the affective events theory (AET), argues that EI should be utilised to mitigate the effects of NWG. Along with our significant and relevant theoretical contributions, we provide novel insights into the body of knowledge on how managers may prevent or minimise such PA. The current study results support all direct and indirect hypothesised connections, with important implications for theory and practice. A review of the existing literature indicates that EI may be associated with a reduction in employees’ ED; however, EI has not been used as a moderator in mitigating the influence of NWG, ED, and PA in the past.

Pharmacokinetics of Drug Distribution

Drug Delivery ◽  
2001 ◽  
Author(s):  
W. Mark Saltzman
Keyword(s):  
Time Course ◽  
Molecular Mechanisms ◽  
Drug Distribution ◽  
The Body ◽  
Drug Uptake ◽  
Pharmacokinetic Analysis ◽  
Model Parameters ◽  
Drug Concentrations ◽  
Uptake Rates ◽  
Tissue Compartments

Pharmacology, the study of agents and their actions, can be divided into two branches. Pharmacodynamics is concerned with the effects of a drug on the body and, therefore, encompasses dose–response relationships as well as the molecular mechanisms of drug activity. Pharmacokinetics, on the other hand, is concerned with the effect of the body on the drug. Drug metabolism, transport, absorption, and elimination are components of pharmacokinetic analysis. Physiology influences the distribution of drugs within the body; overall distribution depends on rates of drug uptake, rates of distribution between tissue compartments, and rates of drug elimination or biotransformation. Each of these phenomena potentially involves aspects of drug diffusion, permeation through membranes, and fluid movement that were introduced in the previous sections. The goal of pharmacokinetics is synthesis of these isolated basic mechanisms into a functional unit; this goal is most often achieved by development of a mathematical model that incorporates descriptions of the uptake, distribution, and elimination of a drug in humans or animals. This model can then be used to predict the outcome of different dosage regimens on the time course of drug concentrations in tissues. The development of a complete pharmacokinetic model for any given drug is a substantial undertaking, since the fate of any compound introduced into a whole organism is influenced by a variety of factors, and is usually complicated—in ways that are difficult to predict—by the presence of disease. In this section, pharamacokinetics will be introduced by first considering the simplest situation: an agent is introduced into a single body compartment from which it is also eliminated. While quite sophisticated compartmental models can be developed from this basic construct, it is frequently difficult to relate model parameters (such as the volume of specific compartments or the rate of transfer between compartments) to physiological or anatomical parameters. To avoid this difficulty, physiological pharmacokinetic models are frequently employed; in these models, the kinetics of drug uptake, distribution, and elimination from local tissue sites are predicted by constructing anatomically and biochemically accurate models of the tissue environment.

scholarly journals 578. Microbiology Laboratory-Driven Standardized Urine Culture Reporting Increases Aminopenicillin Prescribing in Vancomycin-Resistant Enterococci Urinary Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S273-S273
Author(s):  
Genevieve Cheung ◽  
Diane Javier ◽  
Farrnam Kachouei ◽  
Roxanne Pasiliao ◽  
Michelle Ta ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Medical Center ◽  
Primary Outcome Measure ◽  
Post Intervention ◽  
Urinary Infections ◽  
Drug Concentrations ◽  
Positive Urine ◽  
Vancomycin Resistant ◽  
Tract Infections ◽  
The Impact

Abstract Background Vancomycin-resistant Enterococcus (VRE) urinary tract infections (UTI) are traditionally treated with therapies like linezolid or daptomycin. Multiple recent studies have demonstrated that aminopencillins (APs) have equivalent clinical efficacy outcomes as these therapies are able to achieve high urinary drug concentrations and may also have favorable comparative safety profiles and lower costs. Our institution implemented a standardized microbiology report for urine cultures positive for VRE which encouraged prescribing of APs and blinded sensitivity results. Methods This was a single-center, retrospective, observational study evaluating the impact of this microbiology report on prescribing outcomes in patients being treated for VRE UTI at a community regional medical center. The study was conducted over 7.5 years with January 2011 to September 2014 representing the pre-intervention cohort and October 2014 to July 2018 representing the post-intervention cohort. Patients were included if they were 18 years or older and received antibiotic therapy for a diagnosed VRE UTI. The primary outcome measure was terminal antibiotic therapy. Results Out of 388 patients with VRE positive urine cultures, 102 were included for analysis, 38 in the pre-intervention cohort and 64 in the post-intervention cohort. Cohorts were similar in terms of age, Charlson Comorbidity Index (CCI), β-lactam allergy, ID consultation, and urologic abnormalities. AP prescribing significantly increased from 3% (1/38) in the pre-intervention cohort to 44% (28/64) in the post-intervention cohort both in univariate (OR 29.8, 95% CI 3.7–222.8) and multivariate (OR 38.7, 95% CI 4.8–312.3) analyses. In the post-intervention cohort, age, gender, CCI, β-lactam allergy, and urologic abnormalities were not significantly associated with differences in aminopenicillin prescribing. There was no difference in in-hospital mortality between cohorts. Conclusion The results from this study demonstrate that a simple microbiology report for VRE positive urine cultures encouraging AP prescribing is significantly associated with an increase in AP prescribing for diagnosed VRE UTI and should be considered as a supplementary antimicrobial stewardship intervention. Disclosures All authors: No reported disclosures.

scholarly journals Gut Microbiota, Antibiotic Therapy and Antimicrobial Resistance: A Narrative Review

2020 ◽  
Vol 8 (2) ◽  
pp. 269 ◽  
Author(s):  
Benoit Pilmis ◽  
Alban Le Monnier ◽  
Jean-Ralph Zahar
Keyword(s):  
Antimicrobial Resistance ◽  
Gut Microbiota ◽  
Antibiotic Therapy ◽  
Fecal Microbiota Transplantation ◽  
Ecological Impact ◽  
Antibiotic Consumption ◽  
Epidemiological Studies ◽  
Fecal Microbiota ◽  
Spectrum Activity ◽  
The Impact

Antimicrobial resistance is a major concern. Epidemiological studies have demonstrated direct relationships between antibiotic consumption and emergence/dissemination of resistant strains. Within the last decade, authors confounded spectrum activity and ecological effects and did not take into account several other factors playing important roles, such as impact on anaerobic flora, biliary elimination and sub-inhibitory concentration. The ecological impact of antibiotics on the gut microbiota by direct or indirect mechanisms reflects the breaking of the resistance barrier to colonization. To limit the impact of antibiotic therapy on gut microbiota, consideration of the spectrum of activity and route of elimination must be integrated into the decision. Various strategies to prevent (antimicrobial stewardship, action on residual antibiotics at colonic level) or cure dysbiosis (prebiotic, probiotic and fecal microbiota transplantation) have been introduced or are currently being developed.

scholarly journals A 3D brain unit model to further improve prediction of local drug distribution within the brain

2019 ◽  
Author(s):  
Esmée Vendel ◽  
Vivi Rottschäfer ◽  
Elizabeth C. M. de Lange
Keyword(s):  
Extracellular Fluid ◽  
Drug Distribution ◽  
Drug Binding ◽  
Brain Capillaries ◽  
Drug Concentrations ◽  
Unit Model ◽  
Quantitative Understanding ◽  
The Impact ◽  
The Brain ◽  
Excellent Tool

AbstractThe development of drugs targeting the brain still faces a high failure rate. One of the reasons is a lack of quantitative understanding of the complex processes that govern the pharmacokinetics (PK) of a drug within the brain. While a number of models on drug distribution into and within the brain is available, none of these addresses the combination of factors that affect local drug concentrations in brain extracellular fluid (brain ECF).Here, we develop a 3D brain unit model, which builds on our previous proof-of-concept 2D brain unit model, to understand the factors that govern local unbound and bound drug PK within the brain. The 3D brain unit is a cube, in which the brain capillaries surround the brain ECF. Drug concentration-time profiles are described in both a blood-plasma-domain and a brain-ECF-domain by a set of differential equations. The model includes descriptions of blood plasma PK, transport through the blood-brain barrier (BBB), by passive transport via paracellular and trancellular routes, and by active transport, and drug binding kinetics. The impact of all these factors on ultimate local brain ECF unbound and bound drug concentrations is assessed.In this article we show that all the above mentioned factors affect brain ECF PK in an interdependent manner. This indicates that for a quantitative understanding of local drug concentrations within the brain ECF, interdependencies of all transport and binding processes should be understood. To that end, the 3D brain unit model is an excellent tool, and can be used to build a larger network of 3D brain units, in which the properties for each unit can be defined independently to reflect local differences in characteristics of the brain.Author summaryInsights on how a drug distributes within the brain over both time and space are still limited. Here, we develop a ‘3D brain unit model’ in order to understand the factors that control drug concentrations within a small piece of brain tissue, the 3D brain unit. In one 3D brain unit, the brain capillaries, which are the smallest blood vessels of the brain, surround the brain extracellular fluid (ECF). The blood-brain barrier (BBB) is located between the brain capillaries and the brain ECF. The model describes the impact of brain capillary blood flow, transport across the BBB, diffusion, flow and drug binding on the distribution of a drug within the brain ECF. We distinguish between free (unbound) drug and drug that is bound to binding sites within the brain. We show that all of the above mentioned factors affect drug concentrations within brain ECF in an interdependent manner. The 3D brain unit model that we have developed is an excellent tool to increase our understanding of how local drug concentrations within the brain ECF are affected by brain transport and binding processes.

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