Paracetamol absorption test to detect poor enteric absorption of oseltamivir in intensive care unit patients with severe influenza: a pilot study.
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ABSTRACT:
SUBMITTER: May F
PROVIDER: S-EPMC7094964 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
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Paracetamol absorption test to detect poor enteric absorption of oseltamivir in intensive care unit patients with severe influenza: a pilot study.
May Faten F Peytavin Gilles G Fourati Slim S Pressiat Claire C Carteaux Guillaume G Razazi Keyvan K Mekontso Dessap Armand A de Prost Nicolas N
Intensive care medicine 20190722 10
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Project description:BackgroundWhether the enteric absorption of the neuraminidase inhibitor oseltamivir is impaired in critically ill patients is unknown. We documented the pharmacokinetic profile of oseltamivir in patients admitted to intensive care units (ICUs) with suspected or confirmed pandemic (H1N1) influenza.MethodsWe included 41 patients 18 years of age and older with suspected or confirmed pandemic (H1N1) influenza who were admitted for ventilatory support to nine ICUs in three cities in Canada and Spain. Using tandem mass spectrometry, we assessed plasma levels of oseltamivir free base and its active metabolite carboxylate at baseline (before gastric administration of the drug) and at 2, 4, 6, 9 and 12 hours after the fourth or later dose.ResultsAmong the 36 patients who did not require dialysis, the median concentration of oseltamivir free base was 10.4 (interquartile range [IQR] 4.8-14.9) microg/L; the median concentration of the carboxylate metabolite was 404 (IQR 257-900) microg/L. The volume of distribution of the carboxylate metabolite did not increase with increasing body weight (R2=0.00, p=0.87). The rate of elimination of oseltamivir carboxylate was modestly correlated with estimations of creatinine clearance (R2=0.27, p<0.001). Drug clearance in the five patients who required continuous renal replacement therapy was about one-sixth that in the 36 patients with relatively normal renal function.InterpretationOseltamivir was well absorbed enterically in critically ill patients admitted to the ICU with suspected or confirmed pandemic (H1N1) influenza. The dosage of 75 mg twice daily achieved plasma levels that were comparable to those in ambulatory patients and were far in excess of concentrations required to maximally inhibit neuraminidase activity of the virus. Adjustment of the dosage in patients with renal dysfunction requiring continuous renal replacement therapy is appropriate; adjustment for obesity does not appear to be necessary.
| S-EPMC2831695 | biostudies-literature
Project description:In March 2013, the cases of human infection with influenza A of H7N9 subtype were first reported. Preliminary data suggested that the H7N9 isolates are sensitive to neuraminidase inhibitors, such as oseltamivir, which is the recommended choice of treatment. On April 2(nd), a 56-year-old male patient was presented with fever and cough to our hospital. He had previous history of close contact with another H7N9 patient. After caring for his wife (a confirmed H7N9 infection case died on April 3(rd)), this patient showed flu like symptoms on April 2(nd). On the same day, oseltamivir (75 mg bid) treatment was started. Throat swab specimens were screened for H7N9 virus by real-time reverse transcriptase-polymerase chain reaction. The patient was hospitalized on April 4(th). Initial specimens on April 4(th) and April 5(th) were negative for H7N9. But the specimen collected on April 10(th) was tested positive for H7N9. The result was confirmed by Shanghai Municipal Center of Disease Control and Prevention. By April 25(th) when we submitted this report, swab specimens of this patient were still positive for H7N9. This case calls for increased awareness of potential resistance of H7N9 to oseltamivir.
| S-EPMC3675405 | biostudies-other
Project description:Mutations in the influenza virus neuraminidase (NA) that cause reduced susceptibility to the NA inhibitor (NAI) oseltamivir may occur naturally or following antiviral treatment. Currently, detection uses either a traditional NA inhibition assay or gene sequencing to identify known markers associated with reduced inhibition by oseltamivir. Both methods are laborious and require trained personnel. The influenza antiviral resistance test (iART), a prototype system developed by Becton, Dickinson and Company for research use only, offers a rapid and simple method to identify such viruses. This study investigated application of iART to influenza A viruses isolated from non-human hosts with a variety of NA subtypes (N1-N9).
| S-EPMC6692545 | biostudies-literature
Project description:Critically ill patients are admitted to an intensive care unit (ICU) for multiple reasons. In this study, we aim to analyze the current evidence and findings associated with influenza and other emergent viral infections, namely, herpes simplex virus type 1 (HSV-1), Epstein-Barr virus (EBV), and cytomegalovirus (CMV).Among medical conditions, community-acquired respiratory infections are the most frequent reason for ventilatory support in ICUs. Community-acquired pneumonia in a severe form including the need of invasive mechanical ventilation and/or vasopressors is associated with high mortality rates. However, after the pandemic that occurred in 2009 by H1N1 influenza, the number of cases being admitted to ICUs with viral infections is on the rise. Patients in whom an etiology would not have been identified in the past are currently being tested with more sensitive viral molecular diagnostic tools, and patients being admitted to ICUs have more preexisting medical conditions that can predispose to viral infections. Viral infections can trigger the dysregulation of the immune system by inducing a massive cytokine response. This cytokine storm can cause endothelial damage and dysfunction, deregulation of coagulation, and, consequently, alteration of microvascular permeability, tissue edema, and shock. In severe influenza, this vascular hyperpermeability can lead to acute lung injury, multiorgan failure, and encephalopathy. In immunocompetent patients, the most common viral infections are respiratory, and influenza should be considered in patients with severe respiratory failure being admitted to ICU. Seasonality and coinfection are two important features when considering influenza as a pathogen in critically ill patients.Herpesviridae (HSV, CMV, and EBV) may reactivate in ICU patients, and their reactivation is associated with morbidity/mortality. However, whether a specific treatment may impact on outcome remains to be determined.
| S-EPMC7117087 | biostudies-literature
Project description:Despite continued efforts to optimize vaccination composition, severe influenza disease requiring intensive care unit (ICU) admission remains a clinical issue. Influenza epidemics and pandemics worldwide continue to challenge clinicians with managing infected patients requiring ICU care. While routine use of antiviral therapy is deployed in ambulatory outpatients, their use in the ICU in patients with hypoxemic respiratory failure is less well established. Additionally, these therapies primarily target the neuraminidase protein, while contemporary research is increasingly demonstrating potential therapeutic benefits of targeting the hemagglutinin protein. These data have given rise to a growing interest in the use of immune modulating therapies for treatment of severe influenza. Additionally, pandemic outbreaks have revealed the growing need for salvage management, wherein lies the potential role for venovenous extracorporeal membrane oxygenation therapy in refractory respiratory failure. In this report, we review the contemporary ICU care of the severe influenza patient.
| S-EPMC7127549 | biostudies-literature
Project description:BackgroundInfluenza virus predictably causes an annual epidemic resulting in a considerable burden of illness in Australia. Children are disproportionately affected and can experience severe illness and complications, which occasionally result in death.MethodsWe conducted a retrospective descriptive study using data collated in the Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry of influenza-related intensive care unit (ICU) admissions over a 17-year period (1997-2013, inclusive) in children <16 years old. National laboratory-confirmed influenza notifications were used for comparison.ResultsBetween 1997 and 2013, a total of 704 influenza-related ICU admissions were recorded, at a rate of 6.2 per 1,000 all-cause ICU admissions. Age at admission ranged from 0 days and 15.9 years (median = 2.1 years), with 135 (19.2%) aged <6 months. Pneumonia/pneumonitis and bronchiolitis were the most common primary diagnoses among influenza-related admissions (21.9% and 13.6%, respectively). More than half of total cases (59.2%) were previously healthy (no co-morbidities recorded), and in the remainder, chronic lung disease (16.7%) and asthma (12.5%) were the most common co-morbidities recorded. Pathogen co-detection occurred in 24.7% of cases, most commonly with respiratory syncytial virus or a staphylococcal species. Median length of all ICU admissions was 3.2 days (range 2.0 hours- 107.4 days) and 361 (51.3%) admissions required invasive respiratory support for a median duration of 4.3 days (range 0.2 hours- 107.5 days). There were 27 deaths recorded, 14 (51.9%) in children without a recorded co-morbidity.ConclusionInfluenza causes a substantial number of ICU admissions in Australian children each year with the majority occurring in previously healthy children.
| S-EPMC4811543 | biostudies-literature
Project description:RationaleExisting real-time surveillance of influenza morbidity, based primarily on time-trended U.S. hospitalization and death data, is inadequate. These surveillance methods do not accurately predict hospital resource requirements or sufficiently capture the public health impact of the current influenza season.ObjectivesTo determine the feasibility and potential usefulness of tracking surrogate markers of influenza morbidity among patients hospitalized with influenza.MethodsWe performed a pilot study at three tertiary care referral hospitals and retrospectively collected and analyzed data on patients admitted with influenza during the 2013-2014 influenza season. We analyzed traditional influenza surveillance metrics, including weekly statistics on admissions and deaths, as well as weekly rates and trends of intensive care unit (ICU), mechanical ventilation, and extracorporeal membrane oxygenation (ECMO) utilization.ResultsIn our three-hospital cohort, 431 patients were hospitalized with influenza and spent a total of 1,520 days in ICUs. Eighty-six (20%) of these patients required 1,080 days of mechanical ventilation, and 17 patients (4%) received 229 days of ECMO. Trends of ICU and mechanical ventilation use were similar but differed notably from trends of ECMO use, hospitalization, and death. In particular, at two hospitals, increases in utilization of ICU and mechanical ventilation among patients with influenza occurred several weeks after increases in hospitalization rates. Furthermore, ICU, mechanical ventilation, and ECMO utilization rates at the three-hospital network remained elevated for several weeks after the influenza-associated hospitalization rate declined.ConclusionsSurrogate markers of influenza severity were feasible to collect and revealed trends of ICU resource utilization that differed notably from trends of hospitalization and death given by traditional influenza surveillance metrics. A national network of sentinel hospitals that prospectively collects, time-trends, and reports additional influenza morbidity data would be useful to hospital administrators, hospital epidemiologists, infection preventionists, and public health officials.
| S-EPMC5711258 | biostudies-literature
Project description:Avian influenza A viruses continue to cause disease outbreaks in humans, and extrapulmonary infection is characteristic. In vitro studies demonstrate the activity of oseltamivir against avian viruses of the H5, H7 and H9 subtypes. In animal models of lethal infection, oseltamivir treatment and prophylaxis limit viral replication and improve survival. Outcomes are influenced by the virulence of the viral strain, dosage regimen and treatment delay; it is also critical for the compound to act systemically. Observational data on oseltamivir treatment in the early stages of disease suggest it is useful for improving survival in patients infected with H5 viruses, and drug-selected resistance has only rarely been reported. The WHO strongly recommends oseltamivir for the treatment of confirmed or suspected cases of human H5 infection and prophylaxis of those at high risk of infection. In addition to oral dosing, nasogastric administration appears to be a viable option for the management of severely ill patients, as is the use of higher doses and prolonged schedules. F. Hoffmann-La Roche Ltd, the manufacturer of oseltamivir, is developing a mathematical model to allow rapid prediction of appropriate dosage regimens for any future pandemic. Roche is also funding the Avian Influenza Registry, an online database that aims to collect information from clinicians worldwide on the course of avian influenza in humans.
| S-EPMC2835509 | biostudies-literature
Project description:We describe the first confirmed person-to-person transmission of oseltamivir-resistant pandemic influenza A(H1N1) 2009 virus that occurred in a hematology unit in the United Kingdom. Eleven cases of (H1N1) 2009 virus infection were identified, of which, ten were related as shown by sequence analysis of the hemagglutinin and neuraminidase genes. H275Y analysis demonstrated that 8 of 10 case patients had oseltamivir-resistant virus, with 4 of 8 case patients infected by direct transmission of resistant virus. Zanamivir should be considered as first-line therapy for influenza in patients with lymphopenic hematological conditions and uptake of influenza vaccination encouraged to further reduce the number of susceptible individuals.
| S-EPMC3086444 | biostudies-literature