ArticleAntimicrobial agents and chemotherapy2004
Novel approach to characterization of combined pharmacodynamic effects of antimicrobial agents.
Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 36 citations in OpenAlex.
- Pulsed antibiotic release into the environment may foster the spread of antimicrobial resistance.FEMS microbiology ecology · 2025Article
- Synergistic Meropenem-Tobramycin Combination Dosage Regimens against Clinical Hypermutable Pseudomonas aeruginosa at Simulated Epithelial Lining Fluid Concentrations in a Dynamic Biofilm Model.Antimicrobial agents and chemotherapy · 2019Article
- Response envelope analysis for quantitative evaluation of drug combinations.Bioinformatics (Oxford, England) · 2019Article
- Aminoglycoside Concentrations Required for Synergy with Carbapenems against Pseudomonas aeruginosa Determined via Mechanistic Studies and Modeling.Antimicrobial agents and chemotherapy · 2017Article
- Optimization of Synergistic Combination Regimens against Carbapenem- and Aminoglycoside-Resistant Clinical Pseudomonas aeruginosa Isolates via Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling.Antimicrobial agents and chemotherapy · 2017Article
- Combination of Amphotericin B and Flucytosine against Neurotropic Species of Melanized Fungi Causing Primary Cerebral Phaeohyphomycosis.Antimicrobial agents and chemotherapy · 2016Article
- Tobramycin and bicarbonate synergise to kill planktonicNPJ biofilms and microbiomes · 2016Article
- The Natural Antimicrobial Subtilosin A Synergizes with Lauramide Arginine Ethyl Ester (LAE), ε-Poly-L-lysine (Polylysine), Clindamycin Phosphate and Metronidazole, Against the Vaginal Pathogen Gardnerella vaginalis.Probiotics and antimicrobial proteins · 2015Article
- In vitro activity of MK-7655, a novel β-lactamase inhibitor, in combination with imipenem against carbapenem-resistant Gram-negative bacteria.Antimicrobial agents and chemotherapy · 2012Article
- Article
- Two-drug antimicrobial chemotherapy: a mathematical model and experiments with Mycobacterium marinum.PLoS pathogens · 2012Article
- Carbapenems: past, present, and future.Antimicrobial agents and chemotherapy · 2011Review
- Quantitative assessment of combination antimicrobial therapy against multidrug-resistant Acinetobacter baumannii.Antimicrobial agents and chemotherapy · 2008Article
- Optimization of meropenem minimum concentration/MIC ratio to suppress in vitro resistance of Pseudomonas aeruginosa.Antimicrobial agents and chemotherapy · 2005Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is considerable need for new modeling approaches in the study of combined antimicrobial effects. Current methods based on the Loewe additivity and Bliss independence models are associated with implicit assumptions about the interacting system. To circumvent these limitations, we propose an alternative approach to the quantification of pharmacodynamic drug interaction (PDI). Pilot time-kill studies were performed with 10(8) CFU of Pseudomonas aeruginosa/ml at baseline with meropenem or tobramycin alone. The studies were repeated with 25 concentration combinations of meropenem (0 to 64 mg/liter) and tobramycin (0 to 32 mg/liter) in a five-by-five array. The data were modeled with a three-dimensional response surface using effect summation as the basis of null interaction. The interaction index (Ii) is defined as the ratio of the volumes under the planes (VUP) of the observed and expected surfaces: VUP(observed)/VUP(expected). Synergy and antagonism are defined as Ii values of <1 and >1, respectively. In all combinations, an enhanced killing effect was seen compared to that of either drug at the same concentration. The most significant synergism was observed between 1 and 5 mg/liter of meropenem and between 1 and 4 mg/liter of tobramycin; seven out of nine combinations had a >2-log drop compared to the more potent agent. The Ii was found to be 0.76 (95% confidence interval, 0.65 to 0.91) for the concentration ranges of the agents. The results corroborate previous data indicating that meropenem is synergistic with an aminoglycoside when used in combination against P. aeruginosa. Our parametric approach to quantifying PDI appears robust and warrants further investigations.
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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.