scholarly journals Microevolution of acquired colistin resistance in Enterobacteriaceae from ICU patients receiving selective decontamination of the digestive tract

2020 ◽  
Author(s):  
Axel B. Janssen ◽  
Denise van Hout ◽  
Marc J.M. Bonten ◽  
Rob J.L. Willems ◽  
Willem van Schaik
Keyword(s):  
Digestive Tract ◽  
Response Regulator ◽  
Multidrug Resistant ◽  
Selective Decontamination ◽  
Opportunistic Pathogens ◽  
Colistin Resistance ◽  
Gram Negative ◽  
Routine Surveillance ◽  
Resistant Strains ◽  
Prophylactic Use

AbstractColistin is an antibiotic that targets the lipopolysaccharides present in the membranes of Gram-negative bacteria. It is used as last-resort drug to treat infections with multidrug-resistant strains. Colistin is also used in selective decontamination of the digestive tract (SDD), a prophylactic therapy used in patients hospitalised in intensive care units (ICUs) to selectively eradicate opportunistic pathogens in the oropharyngeal and gut microbiota. In this study, we aimed to unravel the mechanisms of acquired colistin resistance in Gram-negative opportunistic pathogens obtained from SDD-treated patients.Routine surveillance of 428 SDD-treated patients resulted in thirteen strains with acquired colistin resistance (Escherichia coli n=9; Klebsiella aerogenes, n=3; Enterobacter asburiae, n=1) from five patients. Genome sequence analysis showed that these isolates represented multiple distinct colistin-resistant clones, but that within the same patients, colistin-resistant strains were clonally related. We identified previously described mechanisms that lead to colistin resistance, i.e. a G53 substitution in the response regulator PmrA/BasR, and the acquisition of the mobile colistin resistance gene mcr-1.1, but we also observed novel variants of basR with an 18-bp deletion, and a G19E substitution in the sensor histidine kinase BasS. We experimentally confirmed these variants to contribute to reduced colistin susceptibility. In a single patient, we observed that colistin resistance in a single E. coli clone evolved through two unique variants in basRS.We show that prophylactic use of colistin during SDD can select for colistin resistance in species that are not intrinsically colistin-resistant. This highlights the importance of continued surveillance for the emergence of colistin resistance in patients treated with SDD.

scholarly journals Microevolution of acquired colistin resistance in Enterobacteriaceae from ICU patients receiving selective decontamination of the digestive tract

2020 ◽  
Vol 75 (11) ◽  
pp. 3135-3143
Author(s):  
Axel B Janssen ◽  
Denise van Hout ◽  
Marc J M Bonten ◽  
Rob J L Willems ◽  
Willem van Schaik
Keyword(s):  
Digestive Tract ◽  
Response Regulator ◽  
Selective Decontamination ◽  
Opportunistic Pathogens ◽  
Colistin Resistance ◽  
Gram Negative ◽  
Routine Surveillance ◽  
Novel Variants ◽  
Prophylactic Use ◽  
Enterobacter Asburiae

Abstract Background Colistin is an antibiotic that targets the LPS molecules present in the membranes of Gram-negative bacteria. It is used as a last-resort drug to treat infections with MDR strains. Colistin is also used in selective decontamination of the digestive tract (SDD), a prophylactic therapy used in patients hospitalized in ICUs to selectively eradicate opportunistic pathogens in the oropharyngeal and gut microbiota. Objectives To unravel the mechanisms of acquired colistin resistance in Gram-negative opportunistic pathogens obtained from SDD-treated patients. Results Routine surveillance of 428 SDD-treated patients resulted in 13 strains with acquired colistin resistance (Escherichia coli, n = 9; Klebsiella aerogenes, n = 3; Enterobacter asburiae, n = 1) from 5 patients. Genome sequence analysis showed that these isolates represented multiple distinct colistin-resistant clones but that colistin-resistant strains within the same patient were clonally related. We identified previously described mechanisms that lead to colistin resistance, i.e. a G53 substitution in the response regulator PmrA/BasR and the acquisition of the mobile colistin resistance gene mcr-1.1, but we also observed novel variants of basR with an 18 bp deletion and a G19E substitution in the sensor histidine kinase BasS. We experimentally confirmed that these variants contribute to reduced colistin susceptibility. In a single patient, we observed that colistin resistance in a single E. coli clone evolved through two unique variants in basRS. Conclusions We show that prophylactic use of colistin during SDD can select for colistin resistance in species that are not intrinsically colistin resistant. This highlights the importance of continued surveillance for strains with acquired colistin resistance in patients treated with SDD.

scholarly journals Detection of Colistin Resistance in Pseudomonas aeruginosa Using the MALDIxin Test on the Routine MALDI Biotyper Sirius Mass Spectrometer

2021 ◽  
Vol 12 ◽  
Author(s):  
Katy Jeannot ◽  
Katheryn Hagart ◽  
Laurent Dortet ◽  
Markus Kostrzewa ◽  
Alain Filloux ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Lipid A ◽  
Response Regulator ◽  
Multidrug Resistant ◽  
Positive Control ◽  
Colistin Resistance ◽  
Clinical Strains ◽  
Efficient Detection ◽  
Maldi Biotyper ◽  
Resistant Strains

Colistin is frequently a last resort treatment for Pseudomonas aeruginosa infections caused by multidrug-resistant (MDR) and extensively drug resistant (XDR) strains, and detection of colistin resistance is essential for the management of infected patients. Therefore, we evaluated the recently developed MALDIxin test for the detection of colistin resistance in P. aeruginosa clinical strains using the routine matrix-assisted laser desorption ionization (MALDI) Biotyper Sirius system. The test is based on the detection by mass spectrometry of modified lipid A by the addition of 4-amino-l-arabinose (l-ara4N) molecules on one or two phosphate groups, in strains resistant to colistin. Overproduction of l-Ara4N molecules is mainly due to the constitutive activation of the histidine kinase (PmrB) or the response regulator (PmrA) following an amino-acid substitution in clinical strains. The performance of the test was determined on a panel of 14 colistin-susceptible and 14 colistin-resistant P. aeruginosa clinical strains, the reference strain PAO1 and positive control mutants PmrB (V28G), PmrB (D172), PhoQ (D240–247), and ParR (M59I). In comparison with the broth microdilution (BMD) method, all the susceptible strains (n=14) and 8/14 colistin-resistant strains were detected in less than 1h, directly on whole bacteria. The remaining resistant strains (n=6) were all detected after a short pre-exposure (4h) to colistin before sample preparation. Validation of the method on a larger panel of strains will be the next step before its use in diagnostics laboratories. Our data showed that the MALDIxin test offers rapid and efficient detection of colistin resistant P. aeruginosa and is thus a valuable diagnostics tool to control the spread of these emerging resistant strains.

Oral, nasopharyngeal, and gut decontamination in the ICU

2016 ◽  
Author(s):  
Evelien Oostdijk ◽  
Marc Bonten
Keyword(s):  
Digestive Tract ◽  
Antibiotic Use ◽  
Multidrug Resistant ◽  
Selective Decontamination ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Detailed Data ◽  
Multidrug Resistant Bacteria ◽  
Gram Negative ◽  
Selective Oropharyngeal Decontamination

Many infections are caused by enteric bacilli, presumably from endogenous origin. Selective decontamination of the digestive tract (SDD) was developed to selectively eliminate the aerobic Gram-negative bacilli from the digestive tract, leaving the anaerobic flora unaffected. As an alternative to SDD, investigators have evaluated the effects of selective oropharyngeal decontamination (SOpD) alone. Most detailed data on the effects of SDD and SOpD in ICU-patients come from two studies performed in Dutch ICUs. The Dutch studies provide strong evidence that SDD and SOpD reduce ICUmortality, ICU-acquired bacteraemia with Gram-negative bacteria, and systemic antibiotic use. Although successful application has been reported from several solitary ICUs across Europe, it is currently unknown to what extent these effects can be achieved in settings with different bacterial ecology. More studies are needed on the use of SDD or SOpD as a measure to control outbreaks with multidrug resistant bacteria.

scholarly journals Emergence of multidrug-resistant Gram-negative bacteria during selective decontamination of the digestive tract on an intensive care unit—authors' response

2007 ◽  
Vol 60 (2) ◽  
pp. 446-446
Author(s):  
Nashwan al Naiemi ◽  
Edou R. Heddema ◽  
Aldert Bart ◽  
Evert de Jonge ◽  
Christina M. Vandenbroucke-Grauls ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Digestive Tract ◽  
Multidrug Resistant ◽  
Selective Decontamination ◽  
Gram Negative Bacteria ◽  
Gram Negative

scholarly journals Effects of Efflux Pump Inhibitors on Colistin Resistance in Multidrug-Resistant Gram-Negative Bacteria

2016 ◽  
Vol 60 (5) ◽  
pp. 3215-3218 ◽  
Author(s):  
Wentao Ni ◽  
Yanjun Li ◽  
Jie Guan ◽  
Jin Zhao ◽  
Junchang Cui ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Colistin Resistance ◽  
Gram Negative ◽  
Content Type ◽  
Resistant Strains ◽  
Efflux Pump Inhibitors ◽  
Time Kill

ABSTRACTWe tested the effects of various putative efflux pump inhibitors on colistin resistance in multidrug-resistant Gram-negative bacteria. Addition of 10 mg/liter cyanide 3-chlorophenylhydrazone (CCCP) to the test medium could significantly decrease the MICs of colistin-resistant strains. Time-kill assays showed CCCP could reverse colistin resistance and inhibit the regrowth of the resistant subpopulation, especially inAcinetobacter baumanniiandStenotrophomonas maltophilia. These results suggest colistin resistance in Gram-negative bacteria can be suppressed and reversed by CCCP.

scholarly journals Multidrug-Resistant Gram-Negative Bacilli: A Retrospective Study of Trends in a Tertiary Healthcare Unit

Medicina ◽  
2018 ◽  
Vol 54 (6) ◽  
pp. 92 ◽  
Author(s):  
Delia Muntean ◽  
Florin-George Horhat ◽  
Luminița Bădițoiu ◽  
Victor Dumitrașcu ◽  
Iulia-Cristina Bagiu ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Metabolic Diseases ◽  
Treatment Options ◽  
Acquired Resistance ◽  
Multidrug Resistant ◽  
Trend Test ◽  
Gram Negative ◽  
Increasing Trend ◽  
Tertiary Healthcare ◽  
Resistant Strains

Background and objective: Bacterial multidrug resistance is particularly common in Gram-negative bacilli (GNB), with important clinical consequences regarding their spread and treatment options. The aim of this study was to investigate the trend of multidrug-resistant GNB (MDR-GNB) in high-risk hospital departments, between 2000–2015, in intervals of five years, with the intention of improving antibiotic therapy policies and optimising preventive and control practices. Materials and methods: This is an observational, retrospective study performed in three departments of the most important tertiary healthcare unit in the southwestern part of Romania: the Intensive Care Unit (ICU), the General Surgery Department (GSD), and the Nutrition and Metabolic Diseases Department (NMDD). MDR was defined as acquired resistance to at least one agent in three or more antimicrobial categories. Trends over time were determined by the Cochran–Armitage trend test and linear regression. Results: During the study period, a total of 2531 strains of MDR-GNB were isolated in 1999 patients: 9.20% in 2000, 18.61% in 2005, 37.02% in 2010, and 35.17% in 2015. The most significant increasing trend was recorded in the ICU (gradient = 7.63, R² = 0.842, p < 0.001). The most common MDR-GNB in the ICU was isolated from bronchoalveolar aspiration samples. Concerning the proportion of different species, most of the changes were recorded in the ICU, where a statistically significant increasing trend was observed for Proteus mirabilis (gradient = 2.62, R2 = 0.558, p < 0.001) and Acinetobacter baumannii (gradient = 2.25, R2 = 0.491, p < 0.001). Analysis of the incidence of the main resistance phenotypes proportion identified a statistically significant increase in carbapenem resistance in the ICU (Gradient = 8.27, R² = 0.866, p < 0.001), and an increased proportion of aminoglycoside-resistant strains in all three departments, but more importantly in the ICU and GSD. Conclusion: A statistically significant increasing trend was observed in all three departments; the most significant one was recorded in the ICU, where after 2010, carbapenem-resistant strains were isolated.

scholarly journals In Vitro Properties of BAL30072, a Novel Siderophore Sulfactam with Activity against Multiresistant Gram-Negative Bacilli

2010 ◽  
Vol 54 (6) ◽  
pp. 2291-2302 ◽  
Author(s):  
Malcolm G. P. Page ◽  
Clothilde Dantier ◽  
Eric Desarbre
Keyword(s):  
Multidrug Resistant ◽  
Unusual Property ◽  
Gram Negative ◽  
Penicillin Binding Proteins ◽  
High Affinity ◽  
Class A ◽  
Carbapenem Resistant ◽  
Lactam Antibiotic ◽  
Resistant Strains

ABSTRACT BAL30072 is a new monocyclic β-lactam antibiotic belonging to the sulfactams. Its spectrum of activity against significant Gram-negative pathogens with β-lactam-resistant phenotypes was evaluated and was compared with the activities of reference drugs, including aztreonam, ceftazidime, cefepime, meropenem, imipenem, and piperacillin-tazobactam. BAL30072 showed potent activity against multidrug-resistant (MDR) Pseudomonas aeruginosa and Acinetobacter sp. isolates, including many carbapenem-resistant strains. The MIC90s were 4 μg/ml for MDR Acinetobacter spp. and 8 μg/ml for MDR P. aeruginosa, whereas the MIC90 of meropenem for the same sets of isolates was >32 μg/ml. BAL30072 was bactericidal against both Acinetobacter spp. and P. aeruginosa, even against strains that produced metallo-β-lactamases that conferred resistance to all other β-lactams tested, including aztreonam. It was also active against many species of MDR isolates of the Enterobacteriaceae family, including isolates that had a class A carbapenemase or a metallo-β-lactamase. Unlike other monocyclic β-lactams, BAL30072 was found to trigger the spheroplasting and lysis of Escherichia coli rather than the formation of extensive filaments. The basis for this unusual property is its inhibition of the bifunctional penicillin-binding proteins PBP 1a and PBP 1b, in addition to its high affinity for PBP 3, which is the target of monobactams, such as aztreonam.

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