ArticleAntimicrobial agents and chemotherapy2012
In vitro activity of MK-7655, a novel β-lactamase inhibitor, in combination with imipenem against carbapenem-resistant Gram-negative bacteria.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
72 citing papers in PubMed.
- Intrapulmonary Pharmacokinetics of Relebactam, a Novel β-Lactamase Inhibitor, Dosed in Combination with Imipenem-Cilastatin in Healthy Subjects.Antimicrobial agents and chemotherapy · 2018Trial
- Phase 2, Dose-Ranging Study of Relebactam with Imipenem-Cilastatin in Subjects with Complicated Intra-abdominal Infection.Antimicrobial agents and chemotherapy · 2016Trial
- Molecular determinants associated with resistance to imipenem and imipenem-relebactam in clinical Pseudomonas aeruginosa isolates.BMC genomics · 2026Article
- Current and future options for the treatment of serious infections due to carbapenem-resistantClinical microbiology reviews · 2025Review
- Clinical efficacy, safety and pharmacokinetics of novel β-lactam/β-lactamase inhibitor combinations: a systematic review.JAC-antimicrobial resistance · 2025Review
- Efficacy of Imipenem/Cilastatin/Relebactam in infections caused by Difficult-to-Treat Gram-Negative Bacteria: A Retrospective Analysis of Real-world data in Greece.Le infezioni in medicina · 2025Article
- Activities of aztreonam in combination with several novel β-lactam-β-lactamase inhibitor combinations against carbapenem-resistantFrontiers in microbiology · 2024Article
- Molecular mechanisms underlying bacterial resistance to ceftazidime/avibactam.WIREs mechanisms of disease · 2022Review
- New Perspectives on Antimicrobial Agents: Imipenem-Relebactam.Antimicrobial agents and chemotherapy · 2022Review
- Review
- Development of Peptide-based Metallo-β-lactamase Inhibitors as a New Strategy to Combat Antimicrobial Resistance: A Mini-review.Current pharmaceutical design · 2022Review
- Predicting Antimicrobial Activity at the Target Site: Pharmacokinetic/Pharmacodynamic Indices versus Time-Kill Approaches.Antibiotics (Basel, Switzerland) · 2021Review
- Imipenem/Relebactam Ex Vivo Clearance during Continuous Renal Replacement Therapy.Antibiotics (Basel, Switzerland) · 2021Article
- High-Throughput Crystallography Reveals Boron-Containing Inhibitors of a Penicillin-Binding Protein with Di- and Tricovalent Binding Modes.Journal of medicinal chemistry · 2021Article
- Review
- New β-Lactam-β-Lactamase Inhibitor Combinations.Clinical microbiology reviews · 2020Review
- New Carbapenemase Inhibitors: Clearing the Way for the β-Lactams.International journal of molecular sciences · 2020Review
- Resistance to Novel β-Lactam-β-Lactamase Inhibitor Combinations: The "Price of Progress".Infectious disease clinics of North America · 2020Review
- Imipenem/Cilastatin/Relebactam Alone and in Combination againstAntimicrobial agents and chemotherapy · 2020Article
- Emerging Strategies to Combat β-Lactamase Producing ESKAPE Pathogens.International journal of molecular sciences · 2020Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Carbapenem-resistant bacteria represent a significant treatment challenge due to the lack of active antimicrobials available. MK-7655 is a novel β-lactamase inhibitor under clinical development. We investigated the combined killing activity of imipenem and MK-7655 against four imipenem-resistant bacterial strains, using a mathematical model previously evaluated in our laboratory. Time-kill studies (TKS) were conducted with imipenem and MK-7655 against a KPC-2-producing Klebsiella pneumoniae isolate (KP6339) as well as 3 Pseudomonas aeruginosa isolates (PA24226, PA24227, and PA24228) with OprD porin deletions and overexpression of AmpC. TKS were performed using 25 clinically achievable concentration combinations in a 5-by-5 array. Bacterial burden at 24 h was determined in triplicate by quantitative culture and mathematically modeled using a three-dimensional response surface. Mathematical model assessments were evaluated experimentally using clinically relevant dosing regimens of imipenem, with or without MK-7655, in a hollow-fiber infection model (HFIM). The combination of imipenem and MK-7655 was synergistic for all strains. Interaction indices were as follows: for KP6339, 0.50 (95% confidence interval [CI], 0.42 to 0.58); for PA24226, 0.60 (95% CI, 0.58 to 0.62); for PA24227, 0.70 (95% CI, 0.66 to 0.74); and for PA24228, 0.55 (95% CI, 0.49 to 0.61). In the HFIM, imipenem plus MK-7655 considerably reduced the bacterial burden at 24 h, while failure with imipenem alone was seen against all isolates. Sustained suppression of bacterial growth at 72 h was achieved with simulated doses of 500 mg imipenem plus 500 mg MK-7655 in 2 (KP6339 and PA24227) strains, and it was achieved in an additional strain (PA24228) when the imipenem dose was increased to 1,000 mg. Additional studies are being conducted to determine the optimal dose and combinations to be used in clinical investigations.
Indexed as
Identifiers
What OpenQuestion holds
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.