Dataset Information

Efficacy of Antibiotic Combinations against Multidrug-Resistant Pseudomonas aeruginosa in Automated Time-Lapse Microscopy and Static Time-Kill Experiments.

ABSTRACT: Antibiotic combination therapy is used for severe infections caused by multidrug-resistant (MDR) Gram-negative bacteria, yet data regarding which combinations are most effective are lacking. This study aimed to evaluate the in vitro efficacy of polymyxin B in combination with 13 other antibiotics against four clinical strains of MDR Pseudomonas aeruginosa We evaluated the interactions of polymyxin B in combination with amikacin, aztreonam, cefepime, chloramphenicol, ciprofloxacin, fosfomycin, linezolid, meropenem, minocycline, rifampin, temocillin, thiamphenicol, or trimethoprim by automated time-lapse microscopy using predefined cutoff values indicating inhibition of growth (?106 CFU/ml) at 24 h. Promising combinations were subsequently evaluated in static time-kill experiments. All strains were intermediate or resistant to polymyxin B, antipseudomonal ?-lactams, ciprofloxacin, and amikacin. Genes encoding ?-lactamases (e.g., bla PAO and bla OXA-50) and mutations associated with permeability and efflux were detected in all strains. In the time-lapse microscopy experiments, positive interactions were found with 39 of 52 antibiotic combination/bacterial strain setups. Enhanced activity was found against all four strains with polymyxin B used in combination with aztreonam, cefepime, fosfomycin, minocycline, thiamphenicol, and trimethoprim. Time-kill experiments showed additive or synergistic activity with 27 of the 39 tested polymyxin B combinations, most frequently with aztreonam, cefepime, and meropenem. Positive interactions were frequently found with the tested combinations, against strains that harbored several resistance mechanisms to the single drugs, and with antibiotics that are normally not active against P. aeruginosa Further study is needed to explore the clinical utility of these combinations.

SUBMITTER: Olsson A

PROVIDER: S-EPMC7269485 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Efficacy of Antibiotic Combinations against Multidrug-Resistant Pseudomonas aeruginosa in Automated Time-Lapse Microscopy and Static Time-Kill Experiments.

Olsson Anna A Wistrand-Yuen Pikkei P Nielsen Elisabet I EI Friberg Lena E LE Sandegren Linus L Lagerbäck Pernilla P Tängdén Thomas T

Antimicrobial agents and chemotherapy 20200521 6

Antibiotic combination therapy is used for severe infections caused by multidrug-resistant (MDR) Gram-negative bacteria, yet data regarding which combinations are most effective are lacking. This study aimed to evaluate the <i>in vitro</i> efficacy of polymyxin B in combination with 13 other antibiotics against four clinical strains of MDR <i>Pseudomonas aeruginosa</i> We evaluated the interactions of polymyxin B in combination with amikacin, aztreonam, cefepime, chloramphenicol, ciprofloxacin, ...[more]

PMID: 32179531

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Project description:Time-lapse imaging of cell colonies in microfluidic chambers provides time series of bioimages, i.e., biomovies. They show the behavior of cells over time under controlled conditions. One of the main remaining bottlenecks in this area of research is the analysis of experimental data and the extraction of cell growth characteristics, such as lineage information. The extraction of the cell line by human observers is time-consuming and error-prone. Previously proposed methods often fail because of their reliance on the accurate detection of a single cell, which is not possible for high density, high diversity of cell shapes and numbers, and high-resolution images with high noise. Our task is to characterize subpopulations in biomovies. In order to shift the analysis of the data from individual cell level to cellular groups with similar fluorescence or even subpopulations, we propose to represent the cells by two new abstractions: the particle and the patch. We use a three-step framework: preprocessing, particle tracking, and construction of the patch lineage. First, preprocessing improves the signal-to-noise ratio and spatially aligns the biomovie frames. Second, cell sampling is performed by assuming particles, which represent a part of a cell, cell or group of contiguous cells in space. Particle analysis includes the following: particle tracking, trajectory linking, filtering, and color information, respectively. Particle tracking consists of following the spatiotemporal position of a particle and gives rise to coherent particle trajectories over time. Typical tracking problems may occur (e.g., appearance or disappearance of cells, spurious artifacts). They are effectively processed using trajectory linking and filtering. Third, the construction of the patch lineage consists in joining particle trajectories that share common attributes (i.e., proximity and fluorescence intensity) and feature common ancestry. This step is based on patch finding, patching trajectory propagation, patch splitting, and patch merging. The main idea is to group together the trajectories of particles in order to gain spatial coherence. The final result of CYCASP is the complete graph of the patch lineage. Finally, the graph encodes the temporal and spatial coherence of the development of cellular colonies. We present results showing a computation time of less than 5?min for biomovies and simulated films. The method, presented here, allowed for the separation of colonies into subpopulations and allowed us to interpret the growth of colonies in a timely manner.

Dataset Information

Efficacy of Antibiotic Combinations against Multidrug-Resistant Pseudomonas aeruginosa in Automated Time-Lapse Microscopy and Static Time-Kill Experiments.

Publications

Efficacy of Antibiotic Combinations against Multidrug-Resistant Pseudomonas aeruginosa in Automated Time-Lapse Microscopy and Static Time-Kill Experiments.

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