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Satoshi Inoue, Yuichiro Sakamoto, Hiroyuki Koami, Kosuke Yamada C, Futoshi Nagashima, Toru Miike, Takashi Iwamura, Toru Obata
PURPOSE: The aim of this study was to identify a useful biomarker to predict the efficacy of polymyxin B-immobilized fiber direct hemoperfusion (PMX-DHP) in patients with septic shock. METHODS: The 44 patients included in this study were divided into two groups. Group A had an increase in systolic blood pressure (SBP) over 30 mmHg after PMX-DHP treatment. Group B had an increase in SBP less than 30 mmHg after PMX-DHP treatment. We evaluated the clinical characteristics and demographics of both groups...
2018: Journal of Nippon Medical School, Nippon Ika Daigaku Zasshi
Sinosh Skariyachan, Meghna Manjunath, Nikhil Bachappanavar
Acinetobacter baumannii, an opportunistic pathogen, has become multi-drug resistant (MDR) to major classes of antibacterial and poses grave threat to public health. The current study focused to screen novel phytotherapeutics against prioritized targets of Acinetobacter baumannii by computational investigation. Fourteen potential drug targets were screened based on their functional role in various biosynthetic pathways and the three dimensional structures of nine targets were retrieved from Protein Data Bank and others were computationally predicted...
March 12, 2018: Journal of Biomolecular Structure & Dynamics
Jian Sun, Huimin Zhang, Ya-Hong Liu, Youjun Feng
Antibiotic resistance has become a global public health priority. Polymyxins, a family of cationic polypeptide antibiotics, act as a final line of refuge against severe infections by Gram-negative pathogens with pan-drug resistance. Unfortunately, this last-resort antibiotic has been challenged by the emergence and global spread of mobilized colistin resistance determinants (mcr). Given the fact that it has triggered extensive concerns worldwide, we present here an updated view of MCR-like colistin resistance...
March 7, 2018: Trends in Microbiology
William Gustavo Lima, Mara Cristina Alves, Waleska Stephanie Cruz, Magna Cristina Paiva
Acinetobacter baumannii is an opportunistic pathogen associated with nosocomial and community infections of great clinical relevance. Its ability to rapidly develop resistance to antimicrobials, especially carbapenems, has re-boosted the prescription and use of polymyxins. However, the emergence of strains resistant to these antimicrobials is becoming a critical issue in several regions of the world because very few of currently available antibiotics are effective in these cases. This review summarizes the most up-to-date knowledge about chromosomally encoded and plasmid-mediated polymyxins resistance in A...
March 9, 2018: European Journal of Clinical Microbiology & Infectious Diseases
Konrad Gwozdzinski, Saina Azarderakhsh, Can Imirzalioglu, Linda Falgenhauer, Trinad Chakraborty
The plasmid-located colistin resistance gene ( mcr - 1 ) confers low-level resistance to colistin, a last-line antibiotic against multidrug-resistant Gram-negative bacteria. Current EUCAST/CLSI recommendations require the use of a broth microdilution (BMD) method in cation-adjusted Mueller-Hinton (CA-MH) for colistin susceptibility testing, but approximately 15% of all MCR-1-producers classify as sensitive in this medium. Here we report on an improved calcium-enhanced Mueller-Hinton (CE-MH) medium that permits simple and reliable determination of mcr-1 -producing Enterobacteriaceae Colistin susceptibility for 50 mcr-1 -encoding isolates of E...
March 7, 2018: Journal of Clinical Microbiology
Sue C Nang, Faye C Morris, Michael J McDonald, Mei-Ling Han, Jiping Wang, Richard A Strugnell, Tony Velkov, Jian Li
Objectives: The discovery of mobile colistin resistance mcr-1, a plasmid-borne polymyxin resistance gene, highlights the potential for widespread resistance to the last-line polymyxins. In the present study, we investigated the impact of mcr-1 acquisition on polymyxin resistance and biological fitness in Klebsiella pneumoniae. Methods: K. pneumoniae B5055 was used as the parental strain for the construction of strains carrying vector only (pBBR1MCS-5) and mcr-1 recombinant plasmids (pmcr-1)...
March 5, 2018: Journal of Antimicrobial Chemotherapy
Victor I Band, Sarah W Satola, Eileen M Burd, Monica M Farley, Jesse T Jacob, David S Weiss
Antibiotic resistance is a growing crisis and a grave threat to human health. It is projected that antibiotic-resistant infections will lead to 10 million annual deaths worldwide by the year 2050. Among the most significant threats are carbapenem-resistant Enterobacteriaceae (CRE), including carbapenem-resistant Klebsiella pneumoniae (CRKP), which lead to mortality rates as high as 40 to 50%. Few treatment options are available to treat CRKP, and the polymyxin antibiotic colistin is often the "last-line" therapy...
March 6, 2018: MBio
Yue Li, Liqiang Liu, Shanshan Song, Hua Kuang, Chuanlai Xu
Increasing attention is now being directed to the utilization of polymyxin B (PMB) as a last-line treatment for life-threatening infections caused by multidrug resistant Gram-negative bacteria. Unfortunately, polymyxins resistance is also increasingly reported, leaving a serious threat to human health. Therefore, the establishment of rapid detection methods for PMB residues is highly essential to ensure public health. In this study, two monoclonal antibodies (mAb; 2A2 and 3C6) were obtained using PMB-bovine serum albumin as the immunogen and PMB-ovalbumin as the coating antigen, which were prepared with N -(γ-maleimidobutyryloxy) succinimide ester and glutaraldehyde as cross-linking agents, respectively...
March 5, 2018: Nanomaterials
Sybil Obuobi, Zhi Xiang Voo, Mei W Low, Bertrand Czarny, Vanitha Selvarajan, Nor L Ibrahim, Yi Yan Yang, Pui Lai Rachel Ee
While physically crosslinked polycarbonate hydrogels are effective drug delivery platforms, their hydrophobic nature and lack of side chain functionality or affinity ligands for controlled release of hydrophilic drugs underscore the importance of their chemical compositions. This study evaluates an array of anionic hydrogel systems of phenylboronic acid functionalized triblock copolymers prepared via reversible physical interactions. Variation of key chemical functionalities while maintaining similar core structural features demonstrates the influence of the substitution position and protection of the boronic acid functionality on gel viscoelasticity and mechanical strength at physiological pH...
March 6, 2018: Advanced Healthcare Materials
Robin K Kuriakose, Lorna W Grant, Eric K Chin, David R P Almeida
Purpose: Conjunctival adherence of a tick is an uncommon event with few reports previously cited in the literature. We report a unique case of tick penetration, specifically a black-legged deer tick ( Ixodes scapularis ), into the conjunctiva. Observations: This patient experienced a 3-week history of unilateral mild ocular pain, decreased vision, and pigmented lesion of her right eye. Slit lamp examination demonstrated a tick attached to the conjunctiva. Pathology confirmed the insect exoskeleton...
April 2017: American Journal of Ophthalmology Case Reports
Qiuxia Ma, Yong Huang, Jian Wang, Xuebin Xu, Jane Hawkey, Chaojie Yang, Beibei Liang, Xiaofeng Hu, Fuli Wu, Xiaoxia Yang, Jinyan Wang, Rongrui Li, Peng Li, Jing Xie, Leili Jia, Ligui Wang, Rongzhang Hao, Yigang Tong, Kathryn E Holt, Shaofu Qiu, Yansong Sun, Hongbin Song
Since the plasmid-mediated polymyxin resistance gene mcr-1 was first reported in Escherichia coli and Klebsiella pneumoniae in China, only one mcr-1-positive isolate of Shigella sonnei, containing inactivated mcr-1, has been reported worldwide. Here, we screened 1650 historical S. sonnei strains isolated from 2003 to 2015 in China for mcr-1. We determined the antimicrobial susceptibilities and resistance genes of mcr-1-positive isolates and investigated the transferability of polymyxin resistance by plasmid conjugation...
February 28, 2018: International Journal of Antimicrobial Agents
Manjulika Shukla, Isha Soni, Karen Matsuyama, Tran Tran, Mary Tanga, Leyi Gong, Sidharth Chopra
INTRODUCTION: Multidrug-resistant Acinetobacter baumannii (MDR-AB) is one of the most significant nosocomial pathogens, that is increasingly being isolated in healthcare settings worldwide. Owing to its inherent drug-resistant nature, coupled with its ability to readily acquire resistance to other antibiotic classes, there is a real dearth of antibiotics available to treat infections with MDR-AB. MATERIALS AND METHODS: A commercially available library was screened against MDR-AB BAA-1605 to identify novel inhibitory molecules...
February 28, 2018: International Journal of Antimicrobial Agents
Eduardo C Gomes, Diego R Falci, Pedro Bergo, Alexandre P Zavascki, Maria Helena Rigatto
OBJECTIVES: To evaluate the impact of polymyxin B (PMB)- associated Acute Kidney Injury (AKI) in 1-year mortality and renal function recovery. METHODS: Patients >18 years old who survived the first 30-days after PMB therapy were followed for 1-year. The impact of AKI and Renal Failure (using RIFLE score) in 1-year mortality was analyzed, along with other confounding variables. Variables with a P value ≤0.2 were included in a forward stepwise Cox regression model...
March 1, 2018: International Journal of Antimicrobial Agents
Willy Chin, Guansheng Zhong, Qinqin Pu, Chuan Yang, Weiyang Lou, Paola Florez De Sessions, Balamurugan Periaswamy, Ashlynn Lee, Zhen Chang Liang, Xin Ding, Shujun Gao, Collins Wenhan Chu, Simone Bianco, Chang Bao, Yen Wah Tong, Weimin Fan, Min Wu, James L Hedrick, Yi Yan Yang
Polymyxins remain the last line treatment for multidrug-resistant (MDR) infections. As polymyxins resistance emerges, there is an urgent need to develop effective antimicrobial agents capable of mitigating MDR. Here, we report biodegradable guanidinium-functionalized polycarbonates with a distinctive mechanism that does not induce drug resistance. Unlike conventional antibiotics, repeated use of the polymers does not lead to drug resistance. Transcriptomic analysis of bacteria further supports development of resistance to antibiotics but not to the macromolecules after 30 treatments...
March 2, 2018: Nature Communications
Vincenzo Pota, Maria Beatrice Passavanti, Pasquale Sansone, Maria Caterina Pace, Filomena Peluso, Alfonso Fiorelli, Caterina Aurilio
BACKGROUND: Descending necrotizing mediastinitis is a common and progressive polymicrobial infection involving the neck and chest with a high death rate (10 to 40%). From a microbiological point of view, descending necrotizing mediastinitis is sustained by Gram-positive bacteria (43-62%), anaerobes (46-78%), and, rarely, Gram-negative bacteria. Data collected during the Antibiotic Resistance-Istituto Superiore di Sanità project confirmed that Italy is positioned among the countries with the highest levels of resistance in most pathogenic species under surveillance...
March 3, 2018: Journal of Medical Case Reports
Zackery P Bulman, Miao Zhao, Michael J Satlin, Liang Chen, Barry N Kreiswirth, Thomas J Walsh, Roger L Nation, Jian Li, Brian T Tsuji
Polymyxin B and fosfomycin are two 'old' antibiotics that consistently maintain activity against Klebsiella pneumoniae carbapenemase (KPC)-producing organisms based on in vitro susceptibility testing. However, each antibiotic's use in monotherapy has been associated with high rates of treatment failure. Therefore, our objective was to investigate the combinatorial pharmacodynamics of polymyxin B and fosfomycin against KPC-producing K. pneumoniae. Polymyxin B front-loading (3.33 mg/kg for 1 dose followed by 1...
February 24, 2018: International Journal of Antimicrobial Agents
Martti Vaara
Polymyxin B and colistin (polymyxin E) are bactericidal pentacationic lipopeptides that act specifically on Gram-negative bacteria, first by disrupting their outermost permeability barrier, the outer membrane (OM), and then damaging the cytoplasmic membrane. The discovery of both polymyxin B and colistin was published independently by three laboratories as early as in 1947. They were subsequently used in intravenous therapy. Unfortunately, they also exhibit significant and dose-limiting nephrotoxicity. Therefore, polymyxins were reserved as agents of last-line defense...
February 27, 2018: Medicinal Research Reviews
Yong-Xin Li, Zheng Zhong, Peng Hou, Wei-Peng Zhang, Pei-Yuan Qian
Nonribosomal peptide antibiotics, including polymyxin, vancomycin, and teixobactin, most of which contain D-amino acids, are highly effective against multidrug-resistant bacteria. However, overusing antibiotics while ignoring the risk of resistance arising has inexorably led to widespread emergence of resistant bacteria. Therefore, elucidation of the emerging mechanisms of resistance to nonribosomal peptide antibiotics is critical to their implementation. Here we describe a networking-associated genome-mining platform for linking biosynthetic building blocks to resistance components associated with biosynthetic gene clusters...
February 26, 2018: Nature Chemical Biology
Pavithra Srinivas, Lauren N Hunt, Stephanie M Pouch, Keelie Thomas, Debra A Goff, Preeti Pancholi, Joan-Miquel Balada-Llasat, Karri A Bauer
Polymyxins are one of the last-line antibiotics for multidrug-resistant Acinetobacter baumannii. Reports have demonstrated the emergence of colistin heteroresistance in A. baumannii, which can complicate assessment of minimum inhibitory concentrations and promote resistance to colistin. We aimed to determine the presence of colistin heteroresistance in A. baumannii isolates and correlate the results with clinical and microbiological outcomes via a retrospective study of 24 adult patients: 12 blood and 12 invasive respiratory cultures positive for colistin-susceptible A...
February 4, 2018: Diagnostic Microbiology and Infectious Disease
Aiko Okubo, Ayumu Nakashima, Shigehiro Doi, Toshinori Ueno, Kensuke Sasaki, Takashi Esaki, Takao Masaki
BACKGROUND: The definition of sepsis was updated to sepsis-3 in February 2016. Currently, direct hemoperfusion therapy using the polymyxin B-immobilized fiber cartridge (PMX-DHP) is widely performed to treat sepsis and septic shock. However, the prognostic factors of PMX-DHPs in patients with sepsis using the new definition are unclear. We retrospectively assessed prognostic factors in patients who had received PMX-DHP therapy for sepsis and septic shock. METHODS: We included 71 patients with severe infection who underwent PMX-DHP treatment from January 2006 to August 2015 in this study...
February 24, 2018: Clinical and Experimental Nephrology
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