Browse
Submit Data
Databases
API
Help

Dataset Information

23 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Inhaled amikacin for severe Gram-negative pulmonary infections in the intensive care unit: current status and future prospects.

ABSTRACT: Recently, the use of nebulized antibiotics in the intensive care unit, in particular amikacin, has been the subject of much discussion, owing to unconvincing results from the latest randomized clinical trials. Here, we examine and reappraise the evidence in favor and against this therapeutic strategy; we then discuss the potential factors that might have played a role in the negative findings of recent clinical trials. Also, we call attention to several factors that are seldom considered by study developers and regulatory agencies, to promote translational research in this field and improve the design of future randomized clinical trials.

SUBMITTER: Torres A

PROVIDER: S-EPMC6297966 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Inhaled amikacin for severe Gram-negative pulmonary infections in the intensive care unit: current status and future prospects.

Torres Antoni A Motos Anna A Battaglini Denise D Li Bassi Gianluigi G

Critical care (London, England) 20181217 1

Recently, the use of nebulized antibiotics in the intensive care unit, in particular amikacin, has been the subject of much discussion, owing to unconvincing results from the latest randomized clinical trials. Here, we examine and reappraise the evidence in favor and against this therapeutic strategy; we then discuss the potential factors that might have played a role in the negative findings of recent clinical trials. Also, we call attention to several factors that are seldom considered by stud ...[more]

PMID: 30558658

Similar Datasets

Inhaled Antibiotics for Gram-Negative Respiratory Infections.

Project description:Gram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects, in vitro and microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena.

| S-EPMC4978611 | biostudies-literature

Treatment of infections caused by Gram-negative pathogens: current status on the pharmacokinetics/pharmacodynamics of parenteral and inhaled polymyxins in patients.

Project description:Polymyxins are increasingly used as a last resort for the treatment of infections caused by multidrug-resistant Gram-negative bacteria in patients. Over the last decade, significant progress has been made in understanding the pharmacokinetics/pharmacodynamics/toxicodynamics (PK/PD/TD) of parenteral and inhaled polymyxins. This mini-review provides an overview of polymyxin chemistry, different dose definitions, and the latest research on their clinical use, toxicities, and PK/PD after intravenous and inhalation administration. Optimising the PK/PD/TD of polymyxins in patients is critical to maximise their efficacy while minimising toxicities and the emergence of resistance.

| S-EPMC7723449 | biostudies-literature

Amikacin pharmacokinetic/pharmacodynamic in intensive care unit: a prospective database.

Project description:BACKGROUND:Aminoglycosides have a concentration-dependent therapeutic effect when peak serum concentration (Cmax) reaches eight to tenfold the minimal inhibitory concentration (MIC). With an amikacin MIC of 8 mg/L, the Cmax should be 64-80 mg/L. This objective is based on clinical breakpoints and not on measured MIC. This study aimed to assess the proportion of patients achieving the pharmacokinetic/pharmacodynamic (PK/PD) target Cmax/MIC???8 using the measured MIC in critically ill patients treated for documented Gram-negative bacilli (GNB) infections. METHODS:Retrospective analysis from February 2016 to December 2017 of a prospective database conducted in 2 intensive care units (ICU). All patients with documented severe GNB infections treated with amikacin (single daily dose of 25 mg/kg of total body weight (TBW)) with both MIC and Cmax measurements at first day of treatment (D1) were included. Results are expressed in n (%) or median [min-max]. RESULTS:93 patients with 98 GNB-documented infections were included. The median Cmax was 55.2 mg/L [12.2-165.7] and the median MIC was 2 mg/L [0.19-16]. Cmax/MIC ratio???8 was achieved in 87 patients (88.8%) while a Cmax???64 mg/L was achieved in only 38 patients (38.7%). Overall probability of PK/PD target attainment was 93%. No correlation was found between Cmax/MIC ratio and clinical outcome at D8 and D28. CONCLUSION:According to PK/PD parameters observed in our study, single daily dose of amikacin 25 mg/kg of TBW appears to be sufficient in most critically ill patients treated for severe GNB infections.

| S-EPMC7276966 | biostudies-literature

Pneumoconiosis: current status and future prospects.

Project description:AbstractPneumoconiosis refers to a spectrum of pulmonary diseases caused by inhalation of mineral dust, usually as the result of certain occupations. The main pathological features include chronic pulmonary inflammation and progressive pulmonary fibrosis, which can eventually lead to death caused by respiratory and/or heart failure. Pneumoconiosis is widespread globally, seriously threatening global public health. Its high incidence and mortality lie in improper occupational protection, and in the lack of early diagnostic methods and effective treatments. This article reviews the epidemiology, safeguard procedures, diagnosis, and treatment of pneumoconiosis, and summarizes recent research advances and future research prospects.

| S-EPMC8078400 | biostudies-literature

Antimicrobial-resistant Gram-negative colonization in infants from a neonatal intensive care unit in Thailand.

Project description:Antimicrobial-resistant Gram-negative bacteria are a major cause of morbidity and mortality in hospitalized neonates in South and South-East Asia. This study aimed to determine the dynamics of colonization with antimicrobial-resistant Gram-negative bacteria amongst patients in a neonatal intensive care unit (NICU) in Thailand. From 97 enrolled patients, 52% were colonized by an extended-spectrum β-lactamase (ESBL) organism at some point during their stay and 64% were colonized by a carbapenem-resistant organism. Rapid acquisition of ESBL-positive and carbapenem-resistant organisms was found. Once colonized with an antibiotic-resistant organism, patients remained colonized for the remainder of their NICU stay.

| S-EPMC6863035 | biostudies-literature

Gram-negative infections in adult intensive care units of latin america and the Caribbean.

Project description:This review summarizes recent epidemiology of Gram-negative infections in selected countries from Latin American and Caribbean adult intensive care units (ICUs). A systematic search of the biomedical literature (PubMed) was performed to identify articles published over the last decade. Where appropriate, data also were collected from the reference list of published articles, health departments of specific countries, and registries. Independent cohort data from all countries (Argentina, Brazil, Chile, Colombia, Cuba, Mexico, Trinidad and Tobago, and Venezuela) signified a high rate of ICU infections (prevalence: Argentina, 24%; Brazil, 57%). Gram-negative pathogens, predominantly Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli, accounted for >50% of ICU infections, which were often complicated by the presence of multidrug-resistant strains and clonal outbreaks. Empirical use of antimicrobial agents was identified as a strong risk factor for resistance development and excessive mortality. Infection control strategies utilizing hygiene measures and antimicrobial stewardship programs reduced the rate of device-associated infections. To mitigate the poor health outcomes associated with infections by multidrug-resistant Gram-negative bacteria, urgent focus must be placed on infection control strategies and local surveillance programs.

| S-EPMC4265515 | biostudies-literature

Mumps Vaccines: Current Challenges and Future Prospects.

Project description:Five decades have passed since the first mumps vaccine was licensed. Over this period, a resurgence of mumps infections has been recorded worldwide. Although global mumps infections have been controlled through vaccination, outbreaks are still on the rise, including in populations with high vaccination coverage. Several epidemiological studies suggest that this infectious virus continues to be a worldwide public health threat. The development and deployment of an improved, prophylactic mumps vaccine that provides long-lasting protection is indeed a priority. The purpose of this review is to provide an immuno-biological perspective on mumps vaccines. Here, we review the virology of mumps, licensed mumps vaccines, and the typical immune responses elicited following mumps vaccination. Furthermore, we discuss the limitations and challenges of the currently licensed mumps vaccines and provide strategies for the development of an improved mumps vaccine.

| S-EPMC7468195 | biostudies-literature

Cytomegalovirus Vaccines: Current Status and Future Prospects.

Project description:Congenital human cytomegalovirus (HCMV) infection can result in severe and permanent neurological injury in newborns, and vaccine development is accordingly a major public health priority. HCMV can also cause disease in solid organ transplant (SOT) and hematopoietic stem-cell transplant (HSCT) recipients, and a vaccine would be valuable in prevention of viremia and end-organ disease in these populations. Currently there is no licensed HCMV vaccine, but progress toward this goal has been made in recent clinical trials. A recombinant HCMV glycoprotein B (gB) vaccine has been shown to have some efficacy in prevention of infection in young women and adolescents, and has provided benefit to HCMV-seronegative SOT recipients. Similarly, DNA vaccines based on gB and the immunodominant T-cell target, pp65 (ppUL83), have been shown to reduce viremia in HSCT patients. This review provides an overview of HCMV vaccine candidates in various stages of development, as well as an update on the current status of ongoing clinical trials. Protective correlates of vaccine-induced immunity may be different for pregnant woman and transplant patients. As more knowledge emerges about correlates of protection, the ultimate licensure of HCMV vaccines may reflect the uniqueness of the target populations being immunized.

| S-EPMC5628252 | biostudies-literature

Hepatic encephalopathy: current challenges and future prospects.

Project description:Hepatic encephalopathy (HE) is a common complication of liver dysfunction, including acute liver failure and liver cirrhosis. HE presents as a spectrum of neuropsychiatric symptoms ranging from subtle fluctuating cognitive impairment to coma. It is a significant contributor of morbidity in patients with liver disease. HE is observed in acute liver failure, liver bypass procedures, for example, shunt surgry and transjugular intrahepatic portosystemic shunt, and cirrhosis. These are classified as Type A, B and C HE, respectively. HE can also be classified according to whether its presence is overt or covert. The pathogenesis is linked with ammonia and glutamine production, and treatment is based on mechanisms to reduce the formation and/or removal of these compounds. There is no specific diagnostic test for HE, and diagnosis is based on clinical suspicion, excluding other causes and use of clinical tests that may support its diagnosis. Many tests are used in trials and experimentally, but have not yet gained universal acceptance. This review focuses on the definitions, pathogenesis and treatment of HE. Consideration will be given to existing treatment, including avoidance of precipitating factors and novel therapies such as prebiotics, probiotics, antibiotics, laxatives, branched-chain amino acids, shunt embolization and the importance of considering liver transplant in appropriate cases.

| S-EPMC5868572 | biostudies-literature

Diabetic gastroparesis: current challenges and future prospects.

Project description:Diabetic gastroparesis (DMGP) is a condition of delayed gastric emptying after gastric outlet obstruction has been excluded. Symptoms of nausea, vomiting, early satiety, bloating, and abdominal pain are associated with DMGP. Uncontrolled symptoms can lead to overall poor quality of life and financial burdens on the healthcare system. A combination of antiemetics and prokinetics is used in symptom control; metoclopramide is the main prokinetic available for clinical use and is the only U.S. Food and Drug Administration-approved agent in the United States. However, a black box warning in 2009 reporting its association with tardive dyskinesia and recommending caution in chronically using this agent beyond 3 months has decreased its role in clinical practice. There is an unmet need for new prokinetics with good efficacy and safety profiles. Currently, there are several new drugs with different mechanisms of action in the pipeline that are under investigation and show promising preliminary results. Surgically combining gastric electrical stimulation with pyloroplasty is considered "gold" standard. Advances in therapeutic endoscopic intervention with gastric per-oral endoscopic pyloromyotomy have also been shown to improve gastric emptying and gastroparesis (GP) symptoms. In this review, we will comment on the challenges encountered when managing patients with DMGP and provide an update on advances in drug development and endoscopic and surgical interventions.

| S-EPMC6165730 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data