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Polymyxin resistance

Konstantinos Z Vardakas, Konstantinos Rellos, Nikolaos A Triarides, Matthew E Falagas
Colistin (polymyxin E) has been widely used since the beginning of the century as a last-option antibiotic for the treatment of patients with multidrug-resistant and extensively-drug resistant bacterial infections. However, colistin dosing is troublesome because each batch of the drug contains a mixture of components and because it is administered as the inactive pro-drug colistimethate sodium (CMS), which has different pharmacokinetic (PK) properties from the active drug. Significant inter-individual and intra-individual variability in colistin plasma concentrations have been observed in all available studies...
September 28, 2016: International Journal of Antimicrobial Agents
A A Carvalho, L L Cardoso, H S Nogueira, E V Menezes, M A S Xavier, N A P Barreto, L F Fernandes, A R E O Xavier
Acinetobacter sp isolates deserve special attention once they have emerged globally in healthcare institutions because they display numerous intrinsic and acquired drug-resistance mechanisms. This study assessed the antibiotic susceptibility profile, the presence of the genetic marker blaOXA-23, and the clonal relationship among 34 nosocomial isolates of Acinetobacter spp obtained at a hospital in southeastern Brazil. Antibiotic sensitivity analysis was performed by the standard disc-diffusion method. All isolates were found to be extensively resistant to several drugs, but sensitive to polymyxin B...
August 19, 2016: Genetics and Molecular Research: GMR
Pooja Manchandani, Yanina Dubrovskaya, Song Gao, Vincent H Tam
Polymyxin B is increasingly used as a treatment of last resort for multidrug-resistant Gram-negative infections. Despite available as a mixture of several structurally-related analogues, the properties are commonly reported as an aggregate of the individual components. We compared the pharmacokinetics of individual polymyxin B components in an animal model and in humans. There were no considerable differences observed in the pharmacokinetics among major components of polymyxin B. Combining different components for pharmacokinetic analysis appeared reasonable...
October 3, 2016: Antimicrobial Agents and Chemotherapy
Lívia Viganor, Orla Howe, Pauraic McCarron, Malachy McCann, Michael Devereux
The "antibiotic era", characterized by the overuse and misuse of antibiotics, over the last half-century has culminated in the present critical "era of resistance". The treatment of bacterial infections is challenging because of a decline in the current arsenal of useful antibiotics and the slow rate of new drug development. The discovery of a new gene (mcr-1) in 2015, which enables bacteria to be highly resistant to polymyxins (such as colistin), the last line of antibiotic defence left, heralds a new level of concern as this gene is susceptible to horizontal gene transfer, with alarming potential to be spread between different bacterial populations, suggesting that the progression from "extensive drug resistance" to "pan-drug resistance" may be inevitable...
October 3, 2016: Current Topics in Medicinal Chemistry
Konstantinos Z Vardakas, Matthew E Falagas
Colistin and polymyxin B (PMB) have different pharmacokinetic profiles and minor differences in antimicrobial activities that may result in discrepancies in mortality and nephrotoxicity. A systematic review and meta-analysis was conducted. PubMed, Scopus and Cochrane Library databases were searched. There was no significant difference in unadjusted mortality between patients treated with colistin and PMB [risk ratio (RR) = 0.71, 95% confidence interval (CI) 0.45-1.13]. Adjusted data were not available. Unadjusted nephrotoxicity was more common in patients treated with colistin than PMB (RR = 1...
September 16, 2016: International Journal of Antimicrobial Agents
Kevin Bihan, Qin Lu, Manon Enjalbert, Maxime Apparuit, Olivier Langeron, Jean-Jacques Rouby, Christian Funck-Brentano, Noel Zahr
BACKGROUND: Colistin is a polypeptide antibiotic from the polymyxin E group used for the treatment of infections caused by multidrug resistant gram-negative bacteria. The main constituents, accounting for approximately 85% of this mixture, are colistinA (polymyxin E1) and colistin B (polymyxin E2). The aim of this study was to develop and validate new and fast methods of quantification of colistin A&B and its precursors (CMS A&B) by Liquid Chromatography-tandem Mass Spectrometry (UPLC-MS) in plasma and urine with short pre-treatment and run times...
September 27, 2016: Therapeutic Drug Monitoring
Jocelyn Qi Min Teo, Yiying Cai, Tze-Peng Lim, Thuan Tong Tan, Andrea Lay-Hoon Kwa
Singapore is an international travel and medical hub and faces a genuine threat for import and dissemination of bacteria with broad-spectrum resistance. In this review, we described the current landscape and management of carbapenem resistance in Gram-negative bacteria (GNB) in Singapore. Notably, the number of carbapenem-resistant Enterobacteriaceae has exponentially increased in the past two years. Resistance is largely mediated by a variety of mechanisms. Polymyxin resistance has also emerged. Interestingly, two Escherichia coli isolates with plasmid-mediated mcr-1 genes have been detected...
February 16, 2016: Microorganisms
Akinori Kato
Recombineering has been used to facilitate the development of in vivo cloning methods. However, the method relies heavily on PCR, which still generates a much higher error rate than DNA replication in vivo, even when amplifying large DNA inserts. Here, a precise technique is reported in Salmonella enterica that enables the cloning of up to at least 19 kb target chromosomal DNA segments that had been marked by FRTs, which were derived from two consecutive lambda Red-mediated recombination events. P22 phage was utilized to transduce the target DNA segments from donor strains to recipient strains harboring a derivative of bacterial artificial chromosome (BAC) containing a FRT and a plasmid expressing Flp recombinase...
September 23, 2016: Journal of General and Applied Microbiology
Cheng Kao, Xiaoyan Lin, Guanghui Yi, Yunliang Zhang, Dean A Rowe-Magnus, Karen Bush
UNLABELLED: The world is at the precipice of a postantibiotic era in which medical procedures and minor injuries can result in bacterial infections that are no longer effectively treated by antibiotics. Cathelicidins are peptides produced by animals to combat bacterial infections and to regulate innate immune responses. However, cathelicidins are potent activators of the inflammatory response. Cathelicidins with reduced proinflammatory activity and potent bactericidal activity in the low micromolar range against Gram-negative bacteria have been identified...
2016: MBio
Polly Soo Xi Yap, Azanna Ahmad Kamar, Chun Wie Chong, Ivan Kok Seng Yap, Kwai Lin Thong, Yao Mun Choo, Mohd Yasim Md Yusof, Cindy Shuan Ju Teh
The prevalence and antibiotic susceptibility of intestinal carriage of Gram-negative bacteria among preterm infants admitted to the neonatal intensive care unit (NICU) in a tertiary teaching hospital in Malaysia were determined. A total of 34 stool specimens were obtained from preterm infants upon admission and once weekly up to two weeks during hospitalization. The presumptive colonies of Escherichia coli and Klebsiella pneumoniae were selected for identification, antibiotic susceptibility testing, and subtyping by using pulsed-field gel electrophoresis (PFGE)...
September 2016: Pathogens and Global Health
Vahid R Adineh, Ross K W Marceau, Tony Velkov, Jian Li, Jing Fu
Emergence of multidrug resistant Gram-negative bacteria has caused a global health crisis and last-line class of antibiotics such as polymyxins are increasingly used. The chemical composition at the cell surface plays a key role in antibiotic resistance. Unlike imaging the cellular ultrastructure with well-developed electron microscopy, the acquisition of a high-resolution chemical map of the bacterial surface still remains a technological challenge. In this study, we developed an atom probe tomography (APT) analysis approach to acquire mass spectra in the pulsed-voltage mode and reconstructed the 3D chemical distribution of atoms and molecules in the subcellular domain at the near-atomic scale...
October 14, 2016: Nano Letters
Y L Gong, Z C Yang, S P Yin, M X Liu, C Zhang, X Q Luo, Y Z Peng
Objective: To analyze the distribution and drug resistance of pathogen isolated from severely burned patients with bloodstream infection, so as to provide reference for the clinical treatment of these patients. Methods: Blood samples of 162 severely burned patients (including 120 patients with extremely severe burn) with bloodstream infection admitted into our burn ICU from January 2011 to December 2014 were collected. Pathogens were cultured by fully automatic blood culture system, and API bacteria identification panels were used to identify pathogen...
September 20, 2016: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
Shamshul Ansari, Rabindra Dhital, Sony Shrestha, Sangita Thapa, Ram Puri, Niraj Chaudhary, Suresh Khatiwada, Rajendra Gautam
Introduction. Pseudomonas aeruginosa is the most frequently isolated organism as it acts as the opportunistic pathogen and can cause infections in immunosuppressed patients. The production of different types of beta-lactamases renders this organism resistant to many commonly used antimicrobials. Therefore, the aim of this study was to document the antibiotic resistance rate in Pseudomonas aeruginosa isolated from different clinical specimens. Methods. Pseudomonas aeruginosa recovered was identified by standard microbiological methods...
2016: BioMed Research International
Justin R Lenhard, Jürgen B Bulitta, Terry D Connell, Natalie King-Lyons, Cornelia B Landersdorfer, Soon-Ee Cheah, Visanu Thamlikitkul, Beom Soo Shin, Gauri Rao, Patricia N Holden, Thomas J Walsh, Alan Forrest, Roger L Nation, Jian Li, Brian T Tsuji
OBJECTIVES: The pharmacodynamics of polymyxin/carbapenem combinations against carbapenem-resistant Acinetobacter baumannii (CRAB) are largely unknown. Our objective was to determine whether intensified meropenem regimens in combination with polymyxin B enhance killing and resistance suppression of CRAB. METHODS: Time-kill experiments for meropenem and polymyxin B combinations were conducted against three polymyxin B-susceptible (MIC of polymyxin B = 0.5 mg/L) CRAB strains with varying meropenem MICs (ATCC 19606, N16870 and 03-149-1; MIC of meropenem = 4, 16 and 64 mg/L, respectively) at 10(8) cfu/mL...
September 15, 2016: Journal of Antimicrobial Chemotherapy
Daria Van Tyne, Joseph B Ciolino, Jay Wang, Marlene L Durand, Michael S Gilmore
Importance: Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are highly antibiotic resistant, and primary ocular infection by ESBL E coli has rarely been reported. A novel mutation conferring phagocytosis resistance would position a strain well to infect the cornea. Observations: A woman with recurrent keratitis presented with a corneal ulcer, which was culture positive for ESBL E coli. Resistant to nearly all other antimicrobials, the infection was treated with amikacin and polymyxin B-trimethoprim, and the ulcer resolved over 3 weeks...
September 15, 2016: JAMA Ophthalmology
Amber M Vasquez, Noelisa Montero, Mark Laughlin, Ehren Dancy, Russell Melmed, Lynn Sosa, Louise Francois Watkins, Jason P Folster, Nancy Strockbine, Heather Moulton-Meissner, Uzma Ansari, Matthew L Cartter, Maroya Spalding Walters
The mcr-1 gene confers resistance to the polymyxins, including the antibiotic colistin, a medication of last resort for multidrug-resistant infections. The mcr-1 gene was first reported in 2015 in food, animal, and patient isolates from China (1) and is notable for being the first plasmid-mediated colistin resistance mechanism to be identified. Plasmids can be transferred between bacteria, potentially spreading the resistance gene to other bacterial species. Since its discovery, the mcr-1 gene has been reported from Africa, Asia, Europe, South America, and North America (2,3), including the United States, where it has been identified in Escherichia coli isolated from three patients and from two intestinal samples from pigs (2,4-6)...
2016: MMWR. Morbidity and Mortality Weekly Report
Tony Velkov, Bo Yun, Elena K Schneider, Mohammad A K Azad, Olan Dolezal, Faye C Morris, Roger L Nation, Jiping Wang, Ke Chen, Heidi H Yu, Lv Wang, Philip E Thompson, Kade D Roberts, Jian Li
Polymyxins B and E (i.e., colistin) are a family of naturally occurring lipopeptide antibiotics that are our last line of defense against multidrug resistant (MDR) Gram-negative pathogens. Unfortunately, nephrotoxicity is a dose-limiting factor for polymyxins that limits their clinical utility. Our recent studies demonstrate that polymyxin-induced nephrotoxicity is a result of their extensive accumulation in renal tubular cells. The design and development of safer, novel polymyxin lipopeptides is hampered by our limited understanding of their complex structure-nephrotoxicity relationships...
May 13, 2016: ACS Infectious Diseases
Elena K Schneider, Mohammad A K Azad, Mei-Ling Han, Qi Tony Zhou, Jiping Wang, Johnny X Huang, Matthew A Cooper, Yohei Doi, Mark A Baker, Phillip J Bergen, Mark T Muller, Jian Li, Tony Velkov
Novel combination therapies are desperately needed for combating lung infections caused by bacterial "superbugs". This study aimed to investigate the synergistic antibacterial activity of polymyxin B in combination with the cystic fibrosis (CF) drugs KALYDECO (ivacaftor) and ORKAMBI (ivacaftor + lumacaftor) against Gram-negative pathogens that commonly colonize the CF lung, in particular, the problematic Pseudomonas aeruginosa. The in vitro synergistic activity of polymyxin B combined with ivacaftor or lumacaftor was assessed using checkerboard and static time-kill assays against a panel of polymyxin-susceptible and polymyxin-resistant P...
July 8, 2016: ACS Infectious Diseases
Oren Zusman, Sergey Altunin, Fidi Koppel, Yael Dishon Benattar, Habip Gedik, Mical Paul
OBJECTIVES: The objective of this study was to summarize available data on polymyxin-based combination therapy or monotherapy for carbapenem-resistant Gram-negative bacteria. METHODS: This is a systematic review. We included observational studies and randomized controlled trials (RCTs) comparing polymyxin monotherapy versus polymyxin-based combination therapy in adult patients with infections caused by carbapenem-resistant or carbapenemase-producing Gram-negative bacteria...
September 13, 2016: Journal of Antimicrobial Chemotherapy
Katherine A Rhodes, Herbert P Schweizer
The genus Burkholderia comprises metabolically diverse and adaptable Gram-negative bacteria, which thrive in often adversarial environments. A few members of the genus are prominent opportunistic pathogens. These include Burkholderia mallei and Burkholderia pseudomallei of the B. pseudomallei complex, which cause glanders and melioidosis, respectively. Burkholderia cenocepacia, Burkholderia multivorans, and Burkholderia vietnamiensis belong to the Burkholderia cepacia complex and affect mostly cystic fibrosis patients...
September 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
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