Antimicrobial resistance 1979–2009 at Karolinska hospital, Sweden: normalized resistance interpretation during a 30‐year follow‐up on <i>Staphylococcus aureus</i> and <i>Escherichia coli</i> resistance development

Kronvall, Göran

doi:10.1111/j.1600-0463.2010.02660.x

Cited by 31 publications

(26 citation statements)

References 81 publications

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“…NRI thus represents an objective method for estimating the WT population in both MIC distributions and inhibition zone histograms. NRI was recently used in a retrospective 30-year follow-up on S. aureus and E. coli resistance development at a university hospital (9). Several changes in the methodology during these 30 years made a direct comparison of the susceptibility interpretations invalid, but with NRI-generated zone diameter cutoff values, such a comparison was made possible.…”

Section: Discussionmentioning

confidence: 99%

Normalized Resistance Interpretation as a Tool for Establishing Epidemiological MIC Susceptibility Breakpoints

Kronvall

2010

J Clin Microbiol

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Normalized resistance interpretation (NRI) utilizes the fact that the wild-type population on the sensitive side is not affected by resistance development, and therefore a normalized reconstruction of the peak can be performed Traditional concepts for setting interpretive breakpoints in antimicrobial susceptibility testing were challenged by J. D. Williams in 1990 when he proposed the setting of so-called microbiological guidelines in relation to the distribution of inhibition zone diameter values (or MIC values) of the susceptible population, for instance two standard deviations (SD) below the mode inhibition zone size (24). This would require a species-related aspect which was not yet accepted, although some reports on this issue had been published (2,12,14). Earlier, O'Brien had shown that an adjustment of interpretive breakpoints in relation to the susceptible peak in zone diameter histograms made results from different laboratories comparable and thereby foresaw later developments (17). In recent years, the term epidemiological breakpoints or epidemiological cutoff (ECOFF), has been proposed by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) to describe the upper MIC limit of the susceptible peak in an MIC distribution, the wild-type (WT) population. MIC distributions of WT isolates species-wise for many antimicrobials have been published on the internet by EUCAST and are publicly available (http://www.eucast.org/mic_distributions/) (5, 6).Normalized resistance interpretation (NRI) is an objective method to define the WT population in inhibition zone diameter histograms (4,8,10). The method has been used for setting interpretive breakpoints in an 18-year resistance surveillance, and also in an investigation of meropenem susceptibility in Pseudomonas aeruginosa (3,22). It was recently used extensively in marine microbiology by P. . NRI was also used successfully to analyze Etest MIC data to set epidemiological breakpoints for tigecycline (11). However, a direct application of NRI to regular 2-fold dilution MIC results has not been possible because the mathematical calculations will be based on too few data points. The use of NRI has been extended in the present investigations to regular MIC values by the introduction of helper variables, and NRI has been evaluated as a method for the objective estimation of epidemiological breakpoints using the EUCAST MIC distributions as the material and as the reference (http://www.eucast .org/mic_distributions/). MATERIALS AND METHODSMIC distributions. The publicly available EUCAST MIC distributions include a large number of bacterial species and antimicrobials (http://www.eucast.org /mic_distributions/). For the purpose of testing the NRI method for MIC distributions in the present studies, results for Staphylococcus aureus and Escherichia coli were used. EUCAST claim on their website that the "Histograms display WT organisms." It is not clear, however, which method is used to ensure this selection in the published materials, which can include as ...

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Section: Discussionmentioning

confidence: 99%

Normalized Resistance Interpretation as a Tool for Establishing Epidemiological MIC Susceptibility Breakpoints

Kronvall

2010

J Clin Microbiol

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“…In a survey covering 30 years of isolates in Sweden (194), the prevalence of isolates showing "non-wild-type" MICs of ciprofloxacin increased from 0% to 40% in 2009. Drugs that have become essentially useless in recent years include ampicillin (70% showing non-wild-type MIC values), tetracyclines, and trimethoprim (up to 60%).…”

Section: E Colimentioning

confidence: 99%

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

2015

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SUMMARY The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps.

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“…A number of these organisms have acquired mechanisms that make them resistant to nearly all currently available antimicrobial agents, compromising the clinical utility of these agents (3,19). A more comprehensive understanding of the resistance development process could help overcome resistance emergence.…”

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Temporal Interplay between Efflux Pumps and Target Mutations in Development of Antibiotic Resistance in Escherichia coli

Singh

Swick

Ledesma

et al. 2012

Antimicrob Agents Chemother

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The emergence of resistance presents a debilitating change in the management of infectious diseases. Currently, the temporal relationship and interplay between various mechanisms of drug resistance are not well understood. A thorough understanding of the resistance development process is needed to facilitate rational design of countermeasure strategies. Using an in vitro hollow-fiber infection model that simulates human drug treatment, we examined the appearance of efflux pump (acrAB) overexpression and target topoisomerase gene (gyrA and parC) mutations over time in the emergence of quinolone resistance in Escherichia coli. Drug-resistant isolates recovered early (24 h) had 2-to 8-fold elevation in the MIC due to acrAB overexpression, but no point mutations were noted. In contrast, high-level (>64؋ MIC) resistant isolates with target site mutations (gyrA S83L with or without parC E84K) were selected more readily after 120 h, and regression of acrAB overexpression was observed at 240 h. Using a similar dosing selection pressure, the emergence of levofloxacin resistance was delayed in a strain with acrAB deleted compared to the isogenic parent. The role of efflux pumps in bacterial resistance development may have been underappreciated. Our data revealed the interplay between two mechanisms of quinolone resistance and provided a new mechanistic framework in the development of high-level resistance. Early low-level levofloxacin resistance conferred by acrAB overexpression preceded and facilitated high-level resistance development mediated by target site mutation(s). If this interpretation is correct, then these findings represent a paradigm shift in the way quinolone resistance is thought to develop.

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Antimicrobial resistance 1979–2009 at Karolinska hospital, Sweden: normalized resistance interpretation during a 30‐year follow‐up on Staphylococcus aureus and Escherichia coli resistance development

Cited by 31 publications

References 81 publications

Normalized Resistance Interpretation as a Tool for Establishing Epidemiological MIC Susceptibility Breakpoints

Normalized Resistance Interpretation as a Tool for Establishing Epidemiological MIC Susceptibility Breakpoints

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

Temporal Interplay between Efflux Pumps and Target Mutations in Development of Antibiotic Resistance in Escherichia coli

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