peramivir and Critical-Illness

To describe the peramivir (PRV) pharmacokinetics in critically ill children treated for influenza A or B viral infections.. Retrospective electronic medical record review of prospectively collected data from critically ill children receiving peramivir for influenza A or B viral infections in the pediatric intensive care unit (PICU).. A 189-bed, freestanding children's tertiary care teaching hospital in Philadelphia, PA.. Critically ill children admitted to the PICU who were infected with influenza between January 1, 2016 and March 31, 2018.. None.. Eleven patients, two females (18%) and nine males (82%), accounted for 24 peramivir samples for therapeutic drug management. The median age was 5 years (interquartile range 1.5-6.5 yrs) with a median weight of 16.4 kg (interquartile range 14-24 kg). Ten (91%) patients demonstrated a larger volume of distribution, 11 (100%) patients demonstrated an increase in clearance, and 11 (100%) patients demonstrated a shorter half-life estimate as compared with the package insert and previous pediatric trial data for peramivir. Eight (73%) patients tested positive for a strain of influenza A and 3 (27%) patients tested positive for influenza B; 4 of 11 (36%) patients tested positive for multiple viruses. All patients had adjustments made to their dosing interval to a more frequent interval. Ten (91%) patients were adjusted to an every-12-hour regimen and 1 (9%) patient was adjusted to an every-8-hour regimen. No adverse events were associated with peramivir treatment.. The pharmacokinetics of PRV demonstrated in this PICU cohort differs in comparison to healthy pediatric and adult patients, and alterations to dosing regimens may be needed in PICU patients to achieve pharmacodynamic exposures. Additional investigations in the PICU population are needed to confirm these findings.

Topics: Acids, Carbocyclic; Antiviral Agents; Child; Child, Preschool; Cohort Studies; Critical Illness; Cyclopentanes; Drug Administration Schedule; Female; Guanidines; Half-Life; Hospitalization; Humans; Infant; Influenza A virus; Influenza B virus; Influenza, Human; Intensive Care Units, Pediatric; Male; Retrospective Studies; Tissue Distribution

The clinical efficacy of peramivir in the treatment of severe seasonal influenza in critically ill patients admitted to an intensive care unit (ICU) is not well established. The aim of this study was to compare the clinical efficacy of peramivir with that of oseltamivir in such critically ill patients. From September 2010 through March 2014, sixty patients with influenza confirmed by RT-PCR and hospitalized in our ICU were enrolled and reviewed retrospectively. Thirty-four and twenty-six patients received initial peramivir and oseltamivir, respectively. The median sequential organ failure assessment score was higher in the patients treated with peramivir (11 vs. 8.5, P= 0.029). There was no significant difference between the two groups in the median duration of use of antiviral agents. There were also no significant differences between the groups in 14-day (17.6% in peramivir vs. 7.7% in oseltamivir, P = 0.446), or 28-day mortality (35.3% in peramivir vs. 34.6% in oseltamivir, P = 0.813) or in the median length of ICU stay (11 days in peramivir vs. 12 days in oseltamivir, P=0.852). Peramivir has the similar clinical efficacy to oseltamivir in the treatment of severe seasonal influenza in the critically ill patients admitted to ICU.

Topics: Acids, Carbocyclic; Administration, Oral; Adult; Aged; Aged, 80 and over; Antiviral Agents; Critical Illness; Cyclopentanes; Guanidines; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Intensive Care Units; Length of Stay; Middle Aged; Organ Dysfunction Scores; Oseltamivir; Retrospective Studies; Seasons; Time Factors; Treatment Outcome; Young Adult

Timely treatment with neuraminidase inhibitor (NAI) drugs appears to improve survival in adults hospitalized with influenza. We analyzed California surveillance data to determine whether NAI treatment improves survival in critically ill children with influenza.. We analyzed data abstracted from medical records to characterize the outcomes of patients aged 0 to 17 years hospitalized in ICUs with laboratory-confirmed influenza from April 3, 2009, through September 30, 2012.. Seven hundred eighty-four influenza cases aged <18 years hospitalized in ICUs had information on treatment. Ninety percent (532 of 591) of cases during the 2009 H1N1 pandemic (April 3, 2009-August 31, 2010) received NAI treatment compared with 63% (121 of 193) of cases in the postpandemic period (September 1, 2010-September 30, 2012; P < .0001). Of 653 cases NAI-treated, 38 (6%) died compared with 11 (8%) of 131 untreated cases (odds ratio = 0.67, 95% confidence interval: 0.34-1.36). In a multivariate model that included receipt of mechanical ventilation and other factors associated with disease severity, the estimated risk of death was reduced in NAI-treated cases (odds ratio 0.36, 95% confidence interval: 0.16-0.83). Treatment within 48 hours of illness onset was significantly associated with survival (P = .04). Cases with NAI treatment initiated earlier in illness were less likely to die.. Prompt treatment with NAIs may improve survival of children critically ill with influenza. Recent decreased frequency of NAI treatment of influenza may be placing untreated critically ill children at an increased risk of death.

Topics: Acids, Carbocyclic; Adolescent; Betainfluenzavirus; California; Child; Child, Preschool; Critical Care; Critical Illness; Cyclopentanes; Drug Administration Schedule; Enzyme Inhibitors; Guanidines; Hospitalization; Humans; Infant; Infant, Newborn; Influenza A Virus, H1N1 Subtype; Influenza, Human; Logistic Models; Multivariate Analysis; Neuraminidase; Odds Ratio; Oseltamivir; Pandemics; Population Surveillance; Treatment Outcome; Zanamivir

Oral antiviral agents to treat influenza are challenging to administer in the intensive care unit (ICU). We describe 57 critically ill patients treated with the investigational intravenous neuraminidase inhibitor drug peramivir for influenza A (H1N1)pdm09 [pH1N1]. Most received late peramivir treatment following clinical deterioration in the ICU on enterically-administered oseltamivir therapy. The median age was 40 years (range 5 months-81 years). Common clinical complications included pneumonia or acute respiratory distress syndrome requiring mechanical ventilation (54; 95%), sepsis requiring vasopressor support (34/53; 64%), acute renal failure requiring hemodialysis (19/53; 36%) and secondary bacterial infection (14; 25%). Over half (29; 51%) died. When comparing the 57 peramivir-treated cases with 1627 critically ill cases who did not receive peramivir, peramivir recipients were more likely to be diagnosed with pneumonia/acute respiratory distress syndrome (p = 0.0002) or sepsis (p = <0.0001), require mechanical ventilation (p = <0.0001) or die (p = <0.0001). The high mortality could be due to the pre-existing clinical severity of cases prior to request for peramivir, but also raises questions about peramivir safety and effectiveness in hospitalized and critically ill patients. The use of peramivir merits further study in randomized controlled trials, or by use of methods such as propensity scoring and matching, to assess clinical effectiveness and safety.

Topics: Acids, Carbocyclic; Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; California; Child; Child, Preschool; Critical Illness; Cyclopentanes; Female; Guanidines; Humans; Infant; Infant, Newborn; Influenza A Virus, H1N1 Subtype; Influenza, Human; Male; Middle Aged; Pandemics; Retrospective Studies; Severity of Illness Index; Young Adult

Peramivir, an investigational intravenous neuraminidase inhibitor in Phase 3 trials for hospitalized patients, was made available during the 2009 H1N1 influenza pandemic under the Emergency Investigational New Drug (eIND) regulations. We describe the clinical characteristics and outcomes of all patients for whom peramivir was requested under the eIND.. After obtaining eIND approval from the Food and Drug Administration and local institutional review board approval, clinicians caring for hospitalized patients with influenza administered intravenous peramivir and collected information on demographic characteristics, clinical characteristics, and outcomes.. From April through October 2009, peramivir was requested for 42 patients and administered to 20 adults and 11 children. At hospitalization, all patients had rapidly progressing, radiographically confirmed viral pneumonia with respiratory failure, and all but 1 patient required mechanical ventilation. In most patients, including 1 person with documented oseltamivir-resistant infection, the illness had progressed despite oseltamivir treatment. Peramivir was administered for 1-14 days (median duration, 10 days). The 14-day, 28-day, and 56-day survival rates were 76.7%, 66.7%, and 59.0%, respectively. Peramivir was generally well tolerated.. Intravenous peramivir was well tolerated and was associated with recovery in most patients hospitalized with severe 2009 H1N1 influenza viral pneumonia and treated under an eIND.

Topics: Acids, Carbocyclic; Adolescent; Adult; Aged; Antiviral Agents; Child; Child, Preschool; Critical Illness; Cyclopentanes; Drugs, Investigational; Female; Guanidines; Humans; Infant; Influenza A Virus, H1N1 Subtype; Influenza, Human; Male; Middle Aged; Pregnancy; Survival Analysis; Treatment Outcome; United States; Young Adult

Topics: Acids, Carbocyclic; C-Reactive Protein; Critical Illness; Cyclopentanes; Diabetic Nephropathies; Female; Guanidines; Humans; Influenza A virus; Influenza, Human; Middle Aged; Neuraminidase; Respiratory Insufficiency