AI Article Synopsis

  • The ASPECT-NP trial compared the effectiveness of ceftolozane/tazobactam (C/T) and meropenem in treating adults with hospital or ventilator-associated bacterial pneumonia, focusing on those with normal and augmented renal clearance (ARC).
  • The trial used Monte Carlo simulations to assess the probability of reaching effective drug concentrations in the bloodstream and lung fluids, measuring outcomes like mortality and cure rates over a 28-day period.
  • Results showed comparable 28-day mortality and clinical cure rates between C/T and meropenem treatment groups, regardless of whether participants had normal renal function or ARC, indicating similar treatment effectiveness across kidney function levels.

Article Abstract

Background: The randomized, double-blind, phase 3 ASPECT-NP trial evaluated the efficacy of 3 g of ceftolozane/tazobactam (C/T) versus 1 g of meropenem infused every 8 h for 8 to 14 days for treatment of adults with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP). We assessed the probability of target attainment and compared efficacy outcomes from ASPECT-NP in participants with augmented renal clearance (ARC) versus those with normal renal function.

Methods: Baseline renal function was categorized as normal renal function (creatinine clearance 80-130 mL/min) or ARC (creatinine clearance > 130 mL/min). Population pharmacokinetic models informed Monte Carlo simulations to assess probability of target attainment in plasma and pulmonary epithelial lining fluid. Outcomes included 28-day all-cause mortality and clinical cure and per-participant microbiologic cure rates at the test-of-cure visit.

Results: A > 99% and > 80% probability of target attainment was demonstrated for ceftolozane and tazobactam, respectively, in simulated plasma and epithelial lining fluid. Within treatment arms, 28-day all-cause mortality rates in participants with normal renal function (C/T, n = 131; meropenem, n = 123) and ARC (C/T, n = 96; meropenem, n = 113) were comparable (data comparisons presented as rate; treatment difference [95% CI]) (C/T: normal renal function, 17.6%; ARC, 17.7%; 0.2 [- 9.6 to 10.6]; meropenem: normal renal function, 20.3%; ARC, 17.7%; - 2.6 [- 12.6 to 7.5]). Clinical cure rates at test-of-cure were also comparable across renal function groups within treatment arms (C/T: normal renal function, 57.3%; ARC, 59.4%; - 2.1 [- 14.8 to 10.8]; meropenem: normal renal function, 59.3%; ARC, 57.5%; 1.8 [- 10.6 to 14.2]). Per-participant microbiologic cure rates at test-of-cure were consistent across renal function groups within treatment arms (C/T: normal renal function, 72.2% [n/N = 70/97]; ARC, 71.4% [n/N = 55/77]; 0.7 [- 12.4 to 14.2]; meropenem: normal renal function, 75.0% [n/N = 66/88]; ARC, 70.0% [n/N = 49/70]; 5.0 [- 8.7 to 19.0]).

Conclusions: C/T and meropenem resulted in 28-day all-cause mortality, clinical cure, and microbiologic cure rates that were comparable between participants with ARC or normal renal function. In conjunction with high probability of target attainment, these results confirm that C/T (3 g) every 8 h is appropriate in patients with HABP/VABP and ARC. Trial registration ClinicalTrials.gov identifier: NCT02070757, registered February 25, 2014; EudraCT: 2012-002862-11.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487337PMC
http://dx.doi.org/10.1186/s13054-021-03773-5DOI Listing

Publication Analysis

Top Keywords

renal function
48
normal renal
40
probability target
20
target attainment
20
cure rates
16
renal
15
function
12
28-day all-cause
12
all-cause mortality
12
clinical cure
12

Similar Publications

The kidney plays an important role in iron homeostasis and mesangial cells (MCs) are phagocytic cells important for glomerular homeostasis. Sickle hemoglobin (HbS) modulators are promising clinical candidates for treatment of sickle cell disease. Although they prevent disease pathophysiology of HbS polymerization and red blood cell (RBC) sickling by increasing hemoglobin oxygen affinity, higher oxygen affinity can also cause transient tissue hypoxia with compensatory increases in erythropoiesis and subsequent increases in RBC turnover.

View Article and Find Full Text PDF

: Prior experimental investigations have highlighted the beneficial effects of flavonoid consumption on renal function. However, a comprehensive evaluation of their impact on modulating albuminuria risk within population-based epidemiological studies is still limited. This study aimed to fill this gap by examining the correlation between flavonoid intake and albuminuria risk, while also shedding light on the potential mediating influence of inflammation in this association.

View Article and Find Full Text PDF

Angiopoeitin-2 (Ang2) is a vascular growth factor involved in regulating angiogenesis and endothelial remodeling. Higher Ang2 levels have been associated with mortality in the general population and among male hemodialysis patients, but its effects on concomitant heart failure with reduced ejection fraction (HFrEF) and end-stage renal disease (ESRD) are unknown. Plasma samples from 73 ESRD patients and 40 healthy patients were analyzed for Ang2 concentrations using ELISA.

View Article and Find Full Text PDF

Background And Objective: Vancomycin is a glycopeptide antibiotic used for the treatment of severe gram-positive infections. Despite decades of clinical experience, optimized dosing for vancomycin in pediatric populations still warrants further investigation. Patients admitted to the pediatric intensive care unit (PICU) after cardiac surgery are often treated with vancomycin in case of (suspected) infection.

View Article and Find Full Text PDF

Background And Aim: Recent Mendelian randomization and meta analysis suggest a controversial causality between C3-epimer of 25 hydroxyvitamin D3 (C3-epi-D3) and type 2 diabetes mellitus (T2DM). The clinical evidence regarding the impact of C3-epi-D3 on the progression of T2DM is currently insufficient. This study aims to investigate whether C3-epi-D3 has any effect on metabolic disorders of T2DM patients.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!