scholarly journals Megalin Contributes to Kidney Accumulation and Nephrotoxicity of Colistin

2013 ◽  
Vol 57 (12) ◽  
pp. 6319-6324 ◽  
Author(s):  
Takahiro Suzuki ◽  
Hiroaki Yamaguchi ◽  
Jiro Ogura ◽  
Masaki Kobayashi ◽  
Takehiro Yamada ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Proximal Tubules ◽  
Limiting Factor ◽  
Tubular Damage ◽  
Gram Negative Bacteria ◽  
Renal Tubular Damage ◽  
Gram Negative ◽  
Renal Tubular ◽  
And Control

ABSTRACTInterest has recently been shown again in colistin because of the increased prevalence of infections caused by multidrug-resistant Gram-negative bacteria. Although the potential for nephrotoxicity is a major dose-limiting factor in colistin use, little is known about the mechanisms that underlie colistin-induced nephrotoxicity. In this study, we focused on an endocytosis receptor, megalin, that is expressed in renal proximal tubules, with the aim of clarifying the role of megalin in the kidney accumulation and nephrotoxicity of colistin. We examined the binding of colistin to megalin by using a vesicle assay. The kidney accumulation, urinary excretion, and concentrations in plasma of colistin in megalin-shedding rats were also evaluated. Furthermore, we examined the effect of megalin ligands and a microtubule-depolymerizing agent on colistin-induced nephrotoxicity. We found that cytochromec, a typical megalin ligand, inhibited the binding of colistin to megalin competitively. In megalin-shedding rats, renal proximal tubule colistin accumulation was decreased (13.5 ± 1.6 and 21.3 ± 2.6 μg in megalin-shedding and control rats, respectively). Coadministration of colistin and cytochromecor albumin fragments resulted in a significant decrease in urinaryN-acetyl-β-d-glucosaminidase (NAG) excretion, a marker of renal tubular damage (717.1 ± 183.9 mU/day for colistin alone, 500.8 ± 102.4 mU/day for cytochromecwith colistin, and 406.7 ± 156.7 mU/day for albumin fragments with colistin). Moreover, coadministration of colistin and colchicine, a microtubule-depolymerizing agent, resulted in a significant decrease in urinary NAG excretion. In conclusion, our results indicate that colistin acts as a megalin ligand and that megalin plays a key role in the accumulation in the kidney and nephrotoxicity of colistin. Megalin ligands may be new targets for the prevention of colistin-induced nephrotoxicity.

scholarly journals Relationship Between Membrane Vesicles, Extracellular ATP and Biofilm Formation in Antarctic Gram-Negative Bacteria

2020 ◽  
Author(s):  
Nicolas Baeza ◽  
Elena Mercade
Keyword(s):  
Biofilm Formation ◽  
Membrane Vesicles ◽  
Metabolic Cost ◽  
Extracellular Atp ◽  
Gram Negative Bacteria ◽  
Bacterial Survival ◽  
Gram Negative ◽  
Two Factors ◽  
And Control

Abstract Biofilms offer a safe environment that favors bacterial survival; for this reason, most pathogenic and environmental bacteria live integrated in biofilm communities. The development of biofilms is complex and involves many factors, which need to be studied in order to understand bacterial behavior and control biofilm formation when necessary. We used a collection of cold-adapted Antarctic Gram-negative bacteria to study whether their ability to form biofilms is associated with a capacity to produce membrane vesicles and secrete extracellular ATP. In most of the studied strains, no correlation was found between biofilm formation and these two factors. Only Shewanella vesiculosa M7T secreted high levels of extracellular ATP, and its membrane vesicles caused a significant increase in the speed and amount of biofilm formation. In this strain, an important portion of the exogenous ATP was contained in membrane vesicles, where it was protected from apyrase treatment. These results confirm that ATP influences biofilm formation. Although the role of extracellular ATP in prokaryotes is still not well understood, the metabolic cost of its production suggests it has an important function, such as a role in biofilm formation. Thus, the liberation of extracellular ATP through membrane vesicles and its function deserve further study.

scholarly journals Phenotypic characterization of carbapenem non-susceptible gram-negative bacilli isolated from clinical specimens

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0256556
Author(s):  
Abera Abdeta ◽  
Adane Bitew ◽  
Surafel Fentaw ◽  
Estifanos Tsige ◽  
Dawit Assefa ◽  
...  
Keyword(s):  
Public Health ◽  
Prevention And Control ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Gram Negative ◽  
Extensively Drug Resistant ◽  
Gram Negative Organisms ◽  
And Control ◽  
Public Health Institute

Background Multidrug resistant, extremely drug-resistant, pan-drug resistant, carbapenem-resistant, and carbapenemase-producing gram-negative bacteria are becoming more common in health care settings and are posing a growing threat to public health. Objective The study was aimed to detect and phenotypically characterize carbapenem no- susceptible gram-negative bacilli at the Ethiopian Public Health Institute. Materials and methods A prospective cross-sectional study was conducted from June 30, 2019, to May 30, 2020, at the national reference laboratory of the Ethiopian Public Health Institute. Clinical samples were collected, inoculated, and incubated for each sample in accordance with standard protocol. Antimicrobial susceptibility testing was conducted using Kirby-Bauer disk diffusion method. Identification was done using the traditional biochemical method. Multidrug-resistant and extensively drug-resistant isolates were classified using a standardized definition established by the European Centre for Disease Prevention and Control and the United States Centers for Disease Prevention and Control. Gram-negative organisms with reduced susceptibility to carbapenem antibiotics were considered candidate carbapenemase producers and subjected to modified carbapenem inactivation and simplified carbapenem inactivation methods. Meropenem with EDTA was used to differentiate metallo-β-lactamase (MBL) from serine carbapenemase. Meropenem (MRP)/meropenem + phenylboronic acid (MBO) were used to differentiate Klebsiella pneumoniae carbapenemase (KPC) from other serine carbapenemase producing gram-negative organisms. Results A total of 1,337 clinical specimens were analyzed, of which 429 gram-negative bacterial isolates were recovered. Out of 429 isolates, 319, 74, and 36 were Enterobacterales, Acinetobacter species, and Pseudomonas aeruginosa respectively. In our study, the prevalence of multidrug-resistant, extensively drug-resistant, carbapenemase-producing, and carbapenem nonsusceptible gram-negative bacilli were 45.2%, 7.7%, 5.4%, and 15.4% respectively. Out of 429 isolates, 66 demonstrated reduced susceptibility to the antibiotics meropenem and imipenem. These isolates were tested for carbapenemase production of which 34.8% (23/66) were carbapenemase producers. Out of 23 carbapenemase positive gram-negative bacteria, ten (10) and thirteen (13) were metallo-beta-lactamase and serine carbapenemase respectively. Three of 13 serine carbapenemase positive organisms were Klebsiella pneumoniae carbapenemase. Conclusion This study revealed an alarming level of antimicrobial resistance (AMR), with a high prevalence of multidrug-resistant (MDR) and extremely drug-resistant, carbapenemase-producing gram-negative bacteria, particularly among intensive care unit patients at the health facility level. These findings point to a scenario in which clinical management of infected patients becomes increasingly difficult and necessitates the use of “last-resort” antimicrobials likely exacerbating the magnitude of the global AMR crisis. This mandates robust AMR monitoring and an infection prevention and control program.

scholarly journals Detection and phenotypic characterization of carbapenem non susceptible gram-negative bacilli isolated from clinical specimens

2021 ◽  
Author(s):  
Abera Abdeta ◽  
Adane Bitew ◽  
Surafel Fentaw ◽  
Estifanos Tsige ◽  
Dawit Assefa ◽  
...  
Keyword(s):  
Public Health ◽  
Prevention And Control ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Gram Negative ◽  
Clinical Specimens ◽  
Extensively Drug Resistant ◽  
And Control ◽  
Public Health Institute

Background Multi-drug resistant, extremely drug-resistant, pan-drug resistant, carbapenem-resistant, and carbapenemase-producing gram-negative bacteria are becoming more common in health care settings and are posing a growing threat to public health. Objective The study was aimed to determine the magnitude of multi-drug resistant, extremely drug-resistant, carbapenem non-susceptible, and carbapenemase-producing gram-negative bacilli at Ethiopian Public Health Institute. Materials and methods Prospective cross-sectional study was conducted from June 30, 2019, to May 30, 2020, at the national reference laboratory of the Ethiopian Public Health Institute. Clinical samples were collected, inoculated, and incubated in accordance to standard protocol for each sample. Antimicrobial susceptibility testing was done using Kirby Bauer disk diffusion. Identification was done using the traditional biochemical method. Multidrug-resistant and extensively drug-resistant were classified using a standardized definition established by European Centers for Disease prevention and control and the United States Centers for Disease prevention and control experts. Carbapenemase production was confirmed by modified carbapenem inactivation and a simplified carbapenem inactivation method. Meropenem with EDTA was used to differentiate serine carbapenemase and Metallo β-lactamase. Results A total of 1337 clinical specimens were analyzed, of which 429-gram negative bacilli isolates were recovered. Out of 429 isolates 319, 74, and 36 were Enterobacterales, Acinetobacter species, and P. aeruginosa respectively. In our study, the prevalence of Multidrug-resistant, extensively drug-resistant, Carbapenemase-producing, and carbapenem non-susceptible Gram-negative bacilli were, 45.2%, 7.7%, 5.4%, and 15.4% respectively. Out of 66 isolates screened for Carbapenemase, 34.8% (23/66) were Carbapenemase enzyme producers. Ten out of twenty-three Carbapenemase-positive organisms were Metallo-beta-lactamase producers. Thirteen out of twenty-three isolates were serine carbapenemase producers. Three out of 13 serine Carbapenemase positive organisms were Klebsiella pneumoniae Carbapenemase. Conclusion The finding from this study revealed a high prevalence of Multidrug-resistant, extremely drug-resistant, carbapenemase-producing gram-negative bacteria, particularly among Intensive care unit patients at the health facility level, this necessitates a robust laboratory-based antimicrobial resistance monitoring and infection prevention and control program.

scholarly journals Prevention and Control of Multidrug-Resistant Gram-Negative Bacteria in Adult Intensive Care Units: A Systematic Review and Network Meta-analysis

2017 ◽  
Vol 64 (suppl_2) ◽  
pp. S51-S60 ◽  
Author(s):  
Nattawat Teerawattanapong ◽  
Kirati Kengkla ◽  
Piyameth Dilokthornsakul ◽  
Surasak Saokaew ◽  
Anucha Apisarnthanarak ◽  
...  
Keyword(s):  
Systematic Review ◽  
Intensive Care ◽  
Intensive Care Units ◽  
Prevention And Control ◽  
Meta Analysis ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
And Control

scholarly journals Rapid Spread and Control of Multidrug-Resistant Gram-Negative Bacteria in COVID-19 Patient Care Units

2021 ◽  
Vol 27 (4) ◽  
Author(s):  
Ashka Patel ◽  
Michele Emerick ◽  
Marie K. Cabunoc ◽  
Michelle H. Williams ◽  
Michael Anne Preas ◽  
...  
Keyword(s):  
Patient Care ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Rapid Spread ◽  
And Control
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