scholarly journals Meropenem vs standard of care for treatment of neonatal late onset sepsis (NeoMero1): a randomised controlled trial

2018 ◽  
Author(s):  
Irja Lutsar ◽  
Corine Chazallon ◽  
Ursula Trafojer ◽  
Vincent Meiffredy de Cabre ◽  
Cinzia Auriti ◽  
...  
Keyword(s):  
Adverse Events ◽  
Broad Spectrum ◽  
Late Onset ◽  
Standard Of Care ◽  
Phase Iii ◽  
Successful Outcome ◽  
Broad Spectrum Antibiotic ◽  
Gram Negative ◽  
Late Onset Sepsis ◽  
Full Analysis

AbstractBackgroundThe early use of broad-spectrum antibiotics remains the cornerstone for the treatment of neonatal late onset sepsis (LOS). However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, were single centre or country, insufficiently powered, evaluated antibiotics not in clinical use anymore and had variable inclusion/exclusion criteria and outcome measures. Moreover, antibiotic-resistant bacteria have become a major problem in many countries worldwide. We hypothesized that efficacy of meropenem as a broad spectrum antibiotic is superior to standard of care regimen (SOC) in empiric treatment of LOS and thus aimed to compare the efficacy and safety of meropenem to SOC in infants aged <90 days with LOS.Methods and findingsNeoMero-1 was a randomized, open-label, phase III superiority trial conducted in 18 neonatal units in 6 countries. Infants with post-menstrual age (PMA) of ≤44 weeks with positive blood culture and one, or those with negative culture and at least with two predefined clinical and laboratory signs suggestive of LOS, or those with PMA >44 weeks meeting the Goldstein criteria of sepsis, were randomized in a 1:1 ratio to receive meropenem or SOC (ampicillin+gentamicin or cefotaxime+gentamicin) for 8-14 days. The primary outcome was treatment success (survival, no modification of allocated therapy, resolution/improvement of clinical and laboratory markers, no need of additional antibiotics and presumed/confirmed eradication of pathogens) at test-of-cure visit (TOC) in full analysis set. Stool samples were tested at baseline and day 28 for meropenem-resistant Gram-negative organisms (CRGNO).The primary analysis was performed in all randomised patients (full analysis set) and in patients with culture confirmed LOS. Proportions of participants with successful outcome were compared by using a logistic regression model adjusted for the stratification factors.From September 3rd 2012 to November 30th 2014, in total 136 patients in each arm were randomized; 140 (52%) were culture positive. Success at TOC was achieved in 44/136 (32%) in the meropenem arm vs. 31/135 (23%) in the SOC arm (p=0.087); 17/63 (27%) vs. 10/77 (13%) in patients with positive cultures (p=0.022). The main reason of failure was modification of allocated therapy. Adverse events occurred in 72% and serious adverse events in 17% of patients, the mortality rate was 6% with no differences between study arms. Cumulative acquisition of CRGNO by day 28 occurred in 4% in the meropenem and 12% in the SOC arm (p=0.052).ConclusionsMeropenem was not superior to SOC in terms of success at TOC, short term hearing disturbances, safety or mortality and did not outselect colonization with CRGNOs. Meropenem as broad-spectrum antibiotic should be reserved for neonates who are more likely to have Gram-negative LOS, especially in NICUs where microorganisms producing ESBL and AmpC beta-lactamases are circulating.

scholarly journals Lesinurad in combination with allopurinol: a randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study)

2016 ◽  
Vol 76 (5) ◽  
pp. 811-820 ◽  
Author(s):  
Thomas Bardin ◽  
Robert T Keenan ◽  
Puja P Khanna ◽  
Jeff Kopicko ◽  
Maple Fung ◽  
...  
Keyword(s):  
Adverse Events ◽  
Laboratory Data ◽  
Standard Of Care ◽  
Phase Iii ◽  
Controlled Study ◽  
Inadequate Response ◽  
Double Blind ◽  
Significant Treatment ◽  
End Points ◽  
Registration Number

ObjectivesDetermine the efficacy and safety of daily lesinurad (200 or 400 mg orally) added to allopurinol in patients with serum uric acid (sUA) above target in a 12-month, randomised, phase III trial.MethodsPatients on allopurinol ≥300 mg (≥200 mg in moderate renal impairment) had sUA level of ≥6.5 mg/dL (≥387 µmol/L) at screening and two or more gout flares in the prior year. Primary end point was the proportion of patients achieving sUA level of <6.0 mg/dL (<357 µmol/L) (month 6). Key secondary end points were mean gout flare rate requiring treatment (months 7 through 12) and proportions of patients with complete resolution of one or more target tophi (month 12). Safety assessments included adverse events and laboratory data.ResultsPatients (n=610) were predominantly male, with mean (±SD) age 51.2±10.90 years, gout duration 11.5±9.26 years and baseline sUA of 6.9±1.2 mg/dL (410±71 µmol/L). Lesinurad at 200 and 400 mg doses, added to allopurinol, significantly increased proportions of patients achieving sUA target versus allopurinol-alone therapy by month 6 (55.4%, 66.5% and 23.3%, respectively, p<0.0001 both lesinurad+allopurinol groups). In key secondary end points, there were no statistically significant treatment-group differences favouring lesinurad. Lesinurad was generally well tolerated; the 200 mg dose had a safety profile comparable with allopurinol-alone therapy. Renal-related adverse events occurred in 5.9% of lesinurad 200 mg+allopurinol, 15.0% of lesinurad 400 mg+allopurinol and 4.9% of allopurinol-alone groups, with serum creatinine elevation of ≥1.5× baseline in 5.9%, 15.0% and 3.4%, respectively. Serious treatment-emergent adverse events occurred in 4.4% of lesinurad 200 mg+allopurinol, in 9.5% of lesinurad 400 mg+allopurinol and in 3.9% of allopurinol-alone groups, respectively.ConclusionLesinurad added to allopurinol demonstrated superior sUA lowering versus allopurinol-alone therapy and lesinurad 200 mg was generally well tolerated in patients with gout warranting additional therapy.Trial registration numberNCT01493531.

Conventional Versus Prolonged Infusion of Meropenem in Neonates With Gram-negative Late-onset Sepsis

2017 ◽  
Vol 36 (4) ◽  
pp. 358-363 ◽  
Author(s):  
Abd Elazeez Shabaan ◽  
Islam Nour ◽  
Heba Elsayed Eldegla ◽  
Nehad Nasef ◽  
Basma Shouman ◽  
...  
Keyword(s):  
Late Onset ◽  
Prolonged Infusion ◽  
Gram Negative ◽  
Late Onset Sepsis

scholarly journals Fournier Syndrome-Surgical and Intensive Care Treatment

2021 ◽  
Vol 1 (2) ◽  
Author(s):  
Paoliello V
Keyword(s):  
Intensive Care ◽  
Soft Tissue ◽  
Antibiotic Therapy ◽  
Broad Spectrum ◽  
Normal Skin ◽  
Acute Infection ◽  
Intensive Care Treatment ◽  
Broad Spectrum Antibiotic ◽  
Gram Negative ◽  
Complementary Actions

Fournier’s Gangrene, also referred to as necrotising fasciitis, Mellene Syndrome or Fournier Syndrome (FS), is a soft-tissue acute infection of the perinium with secondary necrotising cellulitis caused by anaerobic germs or gram-negative bacilli or both. This infection may develop in apparently normal skin, affects the tegumentary and fascial planes but it affects the muscle - aponeurotic plane very rarely dissecting the necrotic tissues, as it rapidly moves towards sepsis, with multiple failure of the organs and death. Treatment consists of agressive surgical debridement, broad spectrum antibiotic therapy, hyperbaric oxiygen therapy (OHB) and other complementary actions.

scholarly journals Patient characteristics, Bacteriological profile & outcome of Neonatal Sepsis: A Hospital Based Study

2013 ◽  
Vol 2 (1) ◽  
pp. 49-54
Author(s):  
Nasim Jahan ◽  
Zabrul SM Haque ◽  
Md Abdul Mannan ◽  
Morsheda Akhter ◽  
Sabina Yasmin ◽  
...  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Neonatal Sepsis ◽  
Early Onset ◽  
Late Onset ◽  
Female Ratio ◽  
Gram Negative ◽  
Common Pathogen ◽  
Late Onset Sepsis ◽  
Early Onset Sepsis

Neonatal sepsis is a major cause of mortality and morbidity in newborn. The spectrum of bacteria which causes neonatal sepsis varies in different parts of the world. The organisms responsible for early onset and late onset sepsis are different. The objective of the study was undertaken to determine the pattern of bacterial isolates responsible for early and late onset neonatal sepsis. A prospective descriptive study over the period of one year was conducted at the Department of Neonatal Intensive care unit of Ad-din Women’s Medical College and Hospital, Dhaka, Bangladesh.Organisms were isolated from 8.7% of collected blood samples. The male female ratio of culture proven sepsis was 1.7:1. More than half (52.8%) of the evaluated neonates were preterm. & 56.3% had low birth weight. The gram positive and gram negative bacteria accounted for 24.1% and 75.9% of the isolates respectively. Around three fourth of the neonates (75.8%) presented with early onset sepsis, while 24.2% presented with late onset sepsis. Acinetobacter was the most common pathogen both in early onset (70%) and late onset (30%) sepsis. Pseudomonas (89.4%) was the second most common pathogen in early onset sepsis. Total mortality rate was 5.7%. Pre term, low birth weight and gram negative sepsis contributes majority of mortality.Gram negative organism especially Acinetobacter found to be commonest cause of sepsis. Pseudomonas was second most common but contributed highest in late onset sepsis and neonatal death due to sepsis. DOI: http://dx.doi.org/10.3329/cbmj.v2i1.14184 Community Based Medical Journal Vol.2(1) 2013 49-54

scholarly journals Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E–Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study

2021 ◽  
Vol 39 (4) ◽  
pp. 273-284 ◽  
Author(s):  
Josep Tabernero ◽  
Axel Grothey ◽  
Eric Van Cutsem ◽  
Rona Yaeger ◽  
Harpreet Wasan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Standard Of Care ◽  
Braf V600e ◽  
Phase Iii ◽  
Primary Analysis ◽  
Metastatic Setting ◽  
Previously Treated Patients ◽  
Previously Treated

PURPOSE BEACON CRC evaluated encorafenib plus cetuximab with or without binimetinib versus investigators' choice of irinotecan or FOLFIRI plus cetuximab in patients with BRAFV600E–mutant metastatic colorectal cancer (mCRC), after progression on 1-2 prior regimens. In the previously reported primary analysis, encorafenib, binimetinib plus cetuximab (ENCO/BINI/CETUX; triplet) and encorafenib plus cetuximab (ENCO/CETUX; doublet) regimens improved overall survival (OS) and objective response rate (ORR; by blinded central review) versus standard of care. The purpose of this analysis was to report updated efficacy and safety data. METHODS In this open-label, phase III trial, 665 patients with BRAF V600E–mutant mCRC were randomly assigned 1:1:1 to receive triplet, doublet, or control. Primary end points were OS and independently reviewed ORR comparing triplet to control. OS for doublet versus control was a key secondary end point. Updated analyses include 6 months of additional follow-up and ORR for all randomized patients. RESULTS Patients received triplet (n = 224), doublet (n = 220), or control (n = 221). Median OS was 9.3 months (95% CI, 8.2 to 10.8) for triplet and 5.9 months (95% CI, 5.1 to 7.1) for control (hazard ratio [HR], 0.60 [95% CI, 0.47 to 0.75]). Median OS for doublet was 9.3 months (95% CI, 8.0 to 11.3) (HR v control, 0.61 [95% CI, 0.48 to 0.77]). Confirmed ORR was 26.8% (95% CI, 21.1% to 33.1%) for triplet, 19.5% (95% CI, 14.5% to 25.4%) for doublet, and 1.8% (95% CI, 0.5% to 4.6%) for control. Adverse events were consistent with the prior primary analysis, with grade ≥ 3 adverse events in 65.8%, 57.4%, and 64.2% for triplet, doublet, and control, respectively. CONCLUSION In the BEACON CRC study, encorafenib plus cetuximab improved OS, ORR, and progression-free survival in previously treated patients in the metastatic setting compared with standard chemotherapy. Based on the primary and updated analyses, encorafenib plus cetuximab is a new standard care regimen for previously treated patients with BRAF V600E mCRC.

Neonatal gram-negative bacillary late-onset sepsis: A case-control-control study on a prospectively collected database of 5,233 admissions

2016 ◽  
Vol 44 (2) ◽  
pp. 146-153 ◽  
Author(s):  
Ming-Horng Tsai ◽  
I. Hsyuan Wu ◽  
Chiang-Wen Lee ◽  
Shih-Ming Chu ◽  
Reyin Lien ◽  
...  
Keyword(s):  
Late Onset ◽  
Case Control ◽  
Gram Negative ◽  
Late Onset Sepsis ◽  
Control Study
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