ArticleAntimicrobial agents and chemotherapy2015
In vitro pharmacodynamics of various antibiotics in combination against extensively drug-resistant Klebsiella pneumoniae.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04202861 (A Randomised Controlled Trial Evaluating a Novel Individualised Treatment Strategy for Carbapenem-Resistant Gram-Negative Bacteria Infections), which is not on this map. Cited by 21 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.
A Randomised Controlled Trial Evaluating a Novel Individualised Treatment Strategy for Carbapenem-Resistant Gram-Negative Bacteria Infections (iACT)
Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- In vitro and in vivo synergistic effects of cyclizine and piroxicam in combination with linezolid against methicillin-resistant Staphylococcus aureus.Applied microbiology and biotechnology · 2026Article
- Addressing carbapenemase-producing extensively drug-resistant Pseudomonas aeruginosa: the potential of cefiderocol and ceftazidime/avibactam plus aztreonam therapy.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Article
- Doxorubicin PK/PD modeling in multiple myeloma: towards in silico trials.Biology direct · 2025Article
- ATP Bioluminescence Assay To Evaluate Antibiotic Combinations against Extensively Drug-Resistant (XDR) Pseudomonas aeruginosa.Microbiology spectrum · 2022Article
- Time-Kill Evaluation of Antibiotic Combinations Containing Ceftazidime-Avibactam against Extensively Drug-Resistant Pseudomonas aeruginosa and Their Potential Role against Ceftazidime-Avibactam-Resistant Isolates.Microbiology spectrum · 2021Article
- Losing the Battle but Winning the War: Can Defeated Antibacterials Form Alliances to Combat Drug-Resistant Pathogens?Antibiotics (Basel, Switzerland) · 2021Review
- Article
- Elimination of Extracellular Adenosine Triphosphate for the Rapid Prediction of Quantitative Plate Counts in 24 h Time-Kill Studies against Carbapenem-Resistant Gram-Negative Bacteria.Microorganisms · 2020Article
- Article
- Polymyxin Triple Combinations against Polymyxin-Resistant, Multidrug-Resistant, KPC-Producing Klebsiella pneumoniae.Antimicrobial agents and chemotherapy · 2020Article
- Efficacy of Ceftolozane-Tazobactam in Combination with Colistin against Extensively Drug-Resistant Pseudomonas aeruginosa, Including High-Risk Clones, in anAntimicrobial agents and chemotherapy · 2020Article
- When One Drug Is Not Enough: Context, Methodology, and Future Prospects in Antibacterial Synergy Testing.Clinics in laboratory medicine · 2019Review
- The Genetic Structures of an Extensively Drug Resistant (XDR)Frontiers in cellular and infection microbiology · 2018Article
- Substantial Impact of Altered Pharmacokinetics in Critically Ill Patients on the Antibacterial Effects of Meropenem Evaluated via the Dynamic Hollow-Fiber Infection Model.Antimicrobial agents and chemotherapy · 2017Article
- Review
- Evaluating Polymyxin B-Based Combinations against Carbapenem-Resistant Escherichia coli in Time-Kill Studies and in a Hollow-Fiber Infection Model.Antimicrobial agents and chemotherapy · 2017Article
- Extensively Drug-ResistantFrontiers in microbiology · 2017Article
- Synergistic combinations of polymyxins.International journal of antimicrobial agents · 2016Review
- In Vitro Activity of Polymyxin B in Combination with Various Antibiotics against Extensively Drug-Resistant Enterobacter cloacae with Decreased Susceptibility to Polymyxin B.Antimicrobial agents and chemotherapy · 2016Article
- Validation of a High-Throughput Screening Assay for Identification of Adjunctive and Directly Acting Antimicrobials Targeting Carbapenem-Resistant Enterobacteriaceae.Assay and drug development technologies · 2016Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extensively drug-resistant (XDR) Klebsiella pneumoniae is an emerging pathogen in Singapore. With limited therapeutic options available, combination antibiotics may be the only viable option. In this study, we aimed to elucidate effective antibiotic combinations against XDR K. pneumoniae isolates. Six NDM-1-producing and two OXA-181-producing K. pneumoniae strains were exposed to 12 antibiotics alone and in combination via time-kill studies. A hollow-fiber infection model (HFIM) with pharmacokinetic validation was used to simulate clinically relevant tigecycline-plus-meropenem dosing regimens against 2 XDR K. pneumoniae isolates over 240 h. The emergence of resistance against tigecycline was quantified using drug-free and selective (tigecycline at 3× the MIC) media. The in vitro growth rates were determined and serial passages on drug-free and selective media were carried out on resistant isolates obtained at 240 h. Both the polymyxin B and tigecycline MICs ranged from 1 to 4 mg/liter. In single time-kill studies, all antibiotics alone demonstrated regrowth at 24 h, except for polymyxin B against 2 isolates. Tigecycline plus meropenem was found to be bactericidal in 50% of the isolates. For the isolates that produced OXA-181-like carbapenemases, none of the 55 tested antibiotic combinations was bactericidal. Against 2 isolates in the HFIM, tigecycline plus meropenem achieved a >90% reduction in bacterial burden for 96 h before regrowth was observed until 10(9) CFU/ml at 240 h. Phenotypically stable and resistant isolates, which were recovered from tigecycline-supplemented plates post-HFIM studies, had lower growth rates than those of their respective parent isolates, possibly implying a substantial biofitness deficit in this population. We found that tigecycline plus meropenem may be a potential antibiotic combination for XDR K. pneumoniae infections, but its efficacy was strain specific.
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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.