ArticleClinical pharmacology and therapeutics2021
Evaluation Strategies for Triple-Drug Combinations against Carbapenemase-Producing Klebsiella Pneumoniae in an In Vitro Hollow-Fiber Infection Model.
Article in Clinical pharmacology and therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Real-World Data on the Effectiveness and Use of Intravenous Fosfomycin for the Treatment of Difficult-to-Treat Infections Caused by Carbapenem-Resistant Gram-Negative Bacteria-A Subgroup Analysis from the FORTRESS Study.Infectious diseases and therapy · 2026Article
- A mechanism-based pharmacokinetic/pharmacodynamic analysis of polymyxin B-based combination therapy against carbapenem-resistantAntimicrobial agents and chemotherapy · 2026Article
- Co-evolution of resistance and virulence inFrontiers in cellular and infection microbiology · 2026Review
- Population Pharmacokinetic/Toxicodynamic Model for Polymyxin B in Critically Ill Patients to Identify the Risk of Nephrotoxicity.Clinical pharmacology and therapeutics · 2025Observational
- Emerging Concepts for the Treatment of Biofilm-Associated Bone and Joint Infections with IV Fosfomycin: A Literature Review.Microorganisms · 2025Review
- Real-World Use, Effectiveness, and Safety of Intravenous Fosfomycin: The FORTRESS Study.Infectious diseases and therapy · 2025Article
- Breaking the resistance: integrative approaches with novel therapeutics against Klebsiella pneumoniae.Archives of microbiology · 2024Review
- Proof-of-concept for incorporating mechanistic insights from multi-omics analyses of polymyxin B in combination with chloramphenicol against Klebsiella pneumoniae.CPT: pharmacometrics & systems pharmacology · 2023Article
- Applications of the hollow-fibre infection model (HFIM) in viral infection studies.The Journal of antimicrobial chemotherapy · 2022Review
- Losing the Battle but Winning the War: Can Defeated Antibacterials Form Alliances to Combat Drug-Resistant Pathogens?Antibiotics (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Mounting antimicrobial resistance to carbapenemase-producing Klebsiella pneumoniae (CPKP) highlights the need to optimize currently available treatment options. The objective of this study was to explore alternative dosing strategies that limit the emergence of resistance to preserve the utility of last-line antibiotics by: (i) evaluating the pharmacodynamic (PD) killing activity of simulated humanized exposures to monotherapy and two-drug and three-drug combinations against CPKP bacterial isolates with different resistance mechanisms; and (ii) optimizing polymyxin B (PMB) exposure simulated in the three-drug combination regimens to maximize the killing activity. Two CPKP clinical isolates (BAA2146 (NDM-1) and BRKP76 (KPC-2)) were evaluated over 168 hours using a hollow-fiber infection model simulating clinically relevant PMB, fosfomycin, and meropenem dosing regimens. PMB-based three-drug combinations were further optimized by varying the initial exposure (0-24 hours) or maintenance dose received over the duration of treatment. The area under the bacterial load-versus-time curve (AUCFU) was used to determine PD activity. Overall reductions in PMB exposure ranged from 2 to 84%. BAA2146 and BRKP76 had median (range) AUCFUs of 11.0 (10.6-11.6) log
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.