Generic Recarbrio 500mg/500mg/250mg powder for solution for infusion vials

BackgroundMultiple randomized controlled studies have compared numerous antibiotic regimens, including new, recently commercialized antibiotics in the treatment of nosocomial pneumonia (NP). The objective of this Bayesian network meta-analysis (NMA) was to compare the efficacy and the safety of different antibiotic treatments for NP.MethodsWe conducted a systematic search of PubMed, Medline, Web of Science, EMBASE and the Cochrane Library databases from 2000 through 2021. The study selection included studies comparing antibiotics targeting Gram-negative bacilli in the setting of NP. The primary endpoint was 28 day mortality. Secondary outcomes were clinical cure, microbiological cure and adverse events.ResultsSixteen studies encompassing 4993 patients were included in this analysis comparing 13 antibiotic regimens. The level of evidence for mortality comparisons ranged from very low to moderate. No significant difference in 28 day mortality was found among all beta-lactam regimens. Only the combination of meropenem plus aerosolized colistin was associated with a significant decrease of mortality compared to using intravenous colistin alone (OR = 0.43; 95% credible interval [0.17-0.94]), based on the results of the smallest trial included. The clinical failure rate of ceftazidime was higher than meropenem with (OR = 1.97; 95% CrI [1.19-3.45]) or without aerosolized colistin (OR = 1.40; 95% CrI [1.00-2.01]), imipemen/cilastatin/relebactam (OR = 1.74; 95% CrI [1.03-2.90]) and ceftazidime/avibactam (OR = 1.48; 95% CrI [1.02-2.20]). For microbiological cure, no substantial difference between regimens was found, but ceftolozane/tazobactam had the highest probability of being superior to comparators. In safety analyses, there was no significant difference between treatments for the occurrence of adverse events, but acute kidney failure was more common in patients receiving intravenous colistin.ConclusionsThis network meta-analysis suggests that most antibiotic regimens, including new combinations and cefiderocol, have similar efficacy and safety in treating susceptible Gram-negative bacilli in NP. Further studies are necessary for NP caused by multidrug-resistant bacteria. Registration PROSPERO CRD42021226603.

Abstract licence: CC BY

BackgroundImipenem is a broad-spectrum carbapenem antibiotic for severe infections with significant pharmacokinetic (PK) variability. This review systematically synthesized published population pharmacokinetic (popPK) studies to identify key covariates and guide individualized dosing for patients with various conditions.MethodsA systematic PubMed and Web of Science search identified imipenem popPK models. Studies employing nonlinear mixed-effects modeling in patients with various conditions were included, and data were extracted independently by two reviewers via a standardized form. The study characteristics and PK parameter estimates were compared.ResultsThis systematic review of 18 popPK studies revealed that imipenem PKs were predominantly characterized by two-compartment models. The clearance of imipenem varied from 4.79 to 16.2 L/h in adults. Creatinine clearance (CLcr) was the most consistent and significant covariate for imipenem clearance, whereas body weight (BW) was frequently identified for volume of distribution. Other clinically relevant covariates, including the glomerular filtration rate (GFR), age, and serum ALB level, were also incorporated into the final models for specific patient subpopulations. All models applied internal validations, such as bootstrap and visual predicative check, but only three studies performed external validation.ConclusionThis review systematically integrates existing popPK models of imipenem, highlighting renal function and BW as key covariates. This study provides valuable insights for individualized dosing while identifying critical research gaps, particularly the need for external validation and focused studies in special populations.

Abstract licence: CC BY

BackgroundCarbapenem-resistant Gram-negative bacteria (CRGNB) pose a severe global health threat, yet comprehensive bibliometric analyses in this field remain limited. This systematic review employs a bibliometric methodology to identify research hotspots and emerging trends from 2020 to 2025.MethodLiterature published between January 1, 2020, and October 31, 2025, was retrieved from the Web of Science Core Collection (WoSCC), Scopus, and PubMed for bibliometric analysis. Analytical tools, including VOSviewer, CiteSpace, and the Bibliometrix package, were used to assess publications by number, country, institution, journal, author, and keywords.ResultsThe bibliometric analysis revealed that global CRGNB research has experienced a fluctuating growth trend. China was the leading contributor, with 2,950 publications (25.5% of the total), and demonstrated significant collaboration with the USA and the UK. Major research clusters encompassed hypervirulent CRGNB strains (particularly carbapenem-resistant Klebsiella pneumoniae and Escherichia coli), resistance mechanisms (particularly carbapenemase-producing), antibiotic resistance, emerging therapeutic strategies (such as novel β-lactam/β-lactamase inhibitors, siderophore antibiotics, phage therapy, and antimicrobial peptides) and One Health perspectives (addressing environmental reservoirs). Thematic analysis identified evolving research priorities, including hypervirulent CRGNB strains, artificial intelligence, and early diagnosis and rapid screening of carbapenem resistance, exemplified by clustered regularly interspaced short palindromic repeats-based detection and artificial intelligence-driven matrix assisted laser desorption ionization-time of flight analysis. Randomized controlled trials indicated promising outcomes for several new antimicrobial agents, such as cefiderocol, sulbactam-durlobactam, and imipenem-relebactam. However, safety concerns, particularly in critically ill patients, remain a significant challenge.ConclusionCRGNB research is increasingly directed toward elucidating resistance mechanisms, improving diagnostic tools, and exploring non-antibiotic therapeutic options. Strengthening international collaboration and fostering multidisciplinary approaches are imperative to advance high-quality research and address this growing threat.

Abstract licence: CC BY

Guideline-based combination therapy achieves sputum culture conversion rates in 23%-34% of patients with Mycobacterium abscessus-complex lung disease. Thus, new therapies are needed. We performed a systematic review to validate and benchmark the hollow fiber system model of M. abscessus lung disease for drug development. We performed a literature search to identify all published hollow fiber system pharmacokinetic-pharmacodynamic studies. Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used for bias minimization. A total of 12 studies were identified. The average quality score was 13.7 out of 21. Eight were monotherapy (exposure-effect and dose-fractionation), one double β-lactam, and three guideline-based therapy studies. For omadacycline and imipenem, hollow fiber system data were accompanied by clinical real-world evidence confirmation. Microbial kill was always terminated by antimicrobial resistance. We used quantitative analyses to rank drugs' efficacy based on CFU/mL kill below day 0 bacterial burden normalized to multi-drug guideline-based therapy kill. The highest-ranked drugs were sulbactam-durlobactam-ceftriaxone (177-fold), epetraborole (15-fold), and omadacycline (7-fold) better than guideline-based therapy. We used the target exposures identified in the systematic analysis in Monte Carlo experiments to identify optimal doses for inhaled formulations. The optimal inhalational dose of imipenem was 250 mg/day, for tigecycline 4 mg/day, for cefoxitin 50 mg/day, and for amikacin liposome inhalation suspension 590 mg once weekly. The hollow fiber system model of M. abscessus lung disease is tractable for exposure-effect, dose-fractionation, and factorial design combination studies. It could also be used to rank drugs and inform on which drugs to test in novel combinations.IMPORTANCECurrent treatments for Mycobacterium abscessus lung disease fail in 70%-80% of patients and are toxic. The hollow fiber system has been used to study old and new potential treatments for this disease. We performed a systematic review of this methodology, for lessons learned. We found 12 studies, which were of adequate quality. Efficacy was always terminated by antimicrobial resistance. The top three drugs in terms of efficacy were sulbactam-durlobactam-ceftriaxone, epetraborole, and omadacycline, which were 7 to 177 times better than standard of care. These drugs could be combined into a new treatment regimen better than current treatments. We also calculated new doses for imipenem, tigecycline, cefoxitin, and amikacin when administered as inhalational therapy. The inhaled doses were multiple-fold lower than intravenous ones, which could be less toxic. The hollow fiber system model is an easily managed system from drug development and dose finding for M. abscessus lung disease.

Abstract licence: CC BY