Database : MEDLINE
Search on : polymyxin and b [Words]
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[PMID]: 29411661
[Au] Autor:Kidd JM; Kuti JL; Nicolau DP
[Ad] Address:a Center for Anti-Infective Research and Development , Hartford Hospital , Hartford , CT , USA.
[Ti] Title:Novel pharmacotherapy for the treatment of hospital-acquired and ventilator-associated pneumonia caused by resistant gram-negative bacteria.
[So] Source:Expert Opin Pharmacother;19(4):397-408, 2018 Mar.
[Is] ISSN:1744-7666
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:INTRODUCTION: Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are among the most prevalent infections in hospitalized patients, particularly those in the intensive care unit. Importantly, the frequency of multidrug resistant (MDR) Gram-negative (GN) bacteria as the bacteriologic cause of HABP/VABP is increasing. These include MDR Pseudomonas aeruginosa, Acinetobacter baumannii, and carbapenem resistant Enterobacteriaceae (CRE). Few antibiotics are currently available when such MDR Gram-negatives are encountered and older agents such as polymyxin B, colistin (polymyxin E), and tigecycline have typically performed poorly in HABP/VABP. Areas covered: In this review, the authors summarize novel antibiotics which have reached phase 3 clinical trials including patients with HABP/VABP. For each agent, the spectrum of activity, pertinent pharmacological characteristics, clinical trial data, and potential utility in the treatment of MDR-GN HABP/VABP is discussed. Expert opinion: Novel antibiotics currently available, and those soon to be, will expand opportunities to treat HABP/VABP caused by MDR-GN organisms and minimize the use of more toxic, less effective drugs. However, with sparse clinical data available, defining the appropriate role for each of the new agents is challenging. In order to maximize the utility of these antibiotics, combination therapy and the role of therapeutic drug monitoring should be investigated.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Process
[do] DOI:10.1080/14656566.2018.1438408

  2 / 6276 MEDLINE  
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[PMID]: 29514208
[Au] Autor:Nang SC; Morris FC; McDonald MJ; Han ML; Wang J; Strugnell RA; Velkov T; Li J
[Ad] Address:Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Victoria, Australia.
[Ti] Title:Fitness cost of mcr-1-mediated polymyxin resistance in Klebsiella pneumoniae.
[So] Source:J Antimicrob Chemother;, 2018 Mar 05.
[Is] ISSN:1460-2091
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract: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). Plasmid stability was determined by serial passaging for 10 consecutive days in antibiotic-free LB broth, followed by patching on gentamicin-containing and antibiotic-free LB agar plates. Lipid A was analysed using LC-MS. The biological fitness was examined using an in vitro competition assay analysed with flow cytometry. The in vivo fitness cost of mcr-1 was evaluated in a neutropenic mouse thigh infection model. Results: Increased polymyxin resistance was observed following acquisition of mcr-1 in K. pneumoniae B5055. The modification of lipid A with phosphoethanolamine following mcr-1 addition was demonstrated by lipid A profiling. The plasmid stability assay revealed the instability of the plasmid after acquiring mcr-1. Reduced in vitro biological fitness and in vivo growth were observed with the mcr-1-carrying K. pneumoniae strain. Conclusions: Although mcr-1 confers a moderate level of polymyxin resistance, it is associated with a significant biological fitness cost in K. pneumoniae. This indicates that mcr-1-mediated resistance in K. pneumoniae could be attenuated by limiting the usage of polymyxins.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:Publisher
[do] DOI:10.1093/jac/dky061

  3 / 6276 MEDLINE  
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[PMID]: 29412662
[Au] Autor:Cui AL; Hu XX; Gao Y; Jin J; Yi H; Wang XK; Nie TY; Chen Y; He QY; Guo HF; Jiang JD; You XF; Li ZR
[Ad] Address:Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China.
[Ti] Title:Synthesis and Bioactivity Investigation of the Individual Components of Cyclic Lipopeptide Antibiotics.
[So] Source:J Med Chem;61(5):1845-1857, 2018 Mar 08.
[Is] ISSN:1520-4804
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:In this paper, 26 natural polymyxin components and a new derivative S were synthesized, and their differences in efficacy and toxicity have been investigated. Almost all of the synthesized components showed strong activity against both susceptible and resistant strains of E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii. The toxicities were obviously different between the components. Only some of the components were tested for toxicity in vivo. Compounds E , E -Val, A , M , D , and S showed obviously lower renal cytotoxicity and acute toxicity than polymyxins B and E. The in vivo nephrotoxicity of E , M , and S was similar to that of polymyxin E. Compound S , with four positive charges, was especially interesting as it possessed both increased efficacy and decreased toxicity. The SAR and toxicity studies indicated that further structural modification could concentrate on polymyxin S. The results also indicated that S could be a new drug candidate.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:In-Data-Review
[do] DOI:10.1021/acs.jmedchem.7b01367

  4 / 6276 MEDLINE  
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[PMID]: 29406023
[Au] Autor:Song X; Xie J; Zhang M; Zhang Y; Li J; Huang Q; He L
[Ad] Address:National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
[Ti] Title:Simultaneous determination of eight cyclopolypeptide antibiotics in feed by high performance liquid chromatography coupled with evaporation light scattering detection.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1076:103-109, 2018 Feb 15.
[Is] ISSN:1873-376X
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:A high throughput, reliable and reproducible analysis strategy based on high performance liquid chromatography combined to evaporative light scattering detector (HPLC-ELSD) was developed for simultaneous determination of eight cyclopolypeptide antibiotics including vancomycin, polymyxin B (polymyxin B1 and polymyxin B2), polymyxin E (colistin A and colistin B), teicoplanin, bacitracin A, daptomycin and virginiamycin M1 in animal Feed. Feed samples were extracted with methanol-2% formic acid aqueous solution, followed by a solid-phase extraction step using a HLB cartridge. Under the optimum chromatographic conditions and ELSD parameters, target compounds were separated well on a short column filled with biphenyl stationary phase. The method was developed in accordance with pig complete feed and then extended to detect polypeptide antibiotics in piglet premix, pig feed additive, poultry complete feed and fattening pig premix. The results showed that logarithmic calibration curves of eight analytes were linear (r > 0.99) within the concentration range of 5-200 mg mL . The developed method provided good accuracy and precision for quantification of eight polypeptides in five kinds of feeds with recoveries ranging from 72.0% to 105.4% with relative standard deviations <9.5%. The limits of detection ranged from 2 to 5 mg kg . Finally, the method was successfully applied to analyze polypeptide antibiotics in commercial feed.
[Mh] MeSH terms primary: Animal Feed/analysis
Anti-Bacterial Agents/analysis
Chromatography, High Pressure Liquid/methods
Drug Residues/analysis
Peptides, Cyclic/analysis
[Mh] MeSH terms secundary: Animals
Anti-Bacterial Agents/chemistry
Drug Residues/chemistry
Light
Limit of Detection
Linear Models
Peptides, Cyclic/chemistry
Reproducibility of Results
Scattering, Radiation
Solid Phase Extraction
Swine
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Anti-Bacterial Agents); 0 (Peptides, Cyclic)
[Em] Entry month:1803
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[Js] Journal subset:IM
[Da] Date of entry for processing:180207
[St] Status:MEDLINE

  5 / 6276 MEDLINE  
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[PMID]: 29186402
[Au] Autor:Nath S; Moussavi F; Abraham D; Landman D; Quale J
[Ad] Address:Department of Medicine and Division of Infectious Diseases, SUNY Downstate Medical Center, Brooklyn, NY, USA.
[Ti] Title:In vitro and in vivo activity of single and dual antimicrobial agents against KPC-producing Klebsiella pneumoniae.
[So] Source:J Antimicrob Chemother;73(2):431-436, 2018 Feb 01.
[Is] ISSN:1460-2091
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Objectives: Options for treatment of infections due to KPC-producing Klebsiella pneumoniae are limited and combination therapy is often recommended. In this report, the in vitro and in vivo activity of potential therapeutic agents and combinations was assessed against four KPC-producing K. pneumoniae isolates. Methods: Using clinically relevant concentrations, time-kill experiments and the Galleria mellonella model of infection were used to examine the activity of polymyxin B, ceftazidime/avibactam, meropenem, rifampicin and amikacin alone and in combination. Results: Two K. pneumoniae isolates were resistant to polymyxin B and had ceftazidime/avibactam MICs of 8/4 mg/L. When ceftazidime/avibactam was combined with either amikacin or meropenem, synergy was observed in vitro, and these combinations were associated with improved survival in the in vivo model. Improved survival was also observed using higher doses of ceftazidime/avibactam. The other two K. pneumoniae isolates were susceptible to polymyxin B and had lower (1/4 mg/L) MICs of ceftazidime/avibactam. For these two isolates, bactericidal activity was observed in vitro at ceftazidime/avibactam concentrations four times the MIC. At one-quarter of the MIC, synergy was observed when ceftazidime/avibactam was combined with meropenem. In the in vivo model with the two susceptible isolates, improved survival rates were observed following therapy with ceftazidime/avibactam monotherapy. For all four isolates, polymyxin B with or without rifampicin or meropenem performed poorly in the in vivo model. Conclusions: Pending clinical studies, combining ceftazidime/avibactam with another agent (e.g. a carbapenem) should be considered when treating serious infections due to these pathogens, particularly for isolates with ceftazidime/avibactam MICs near the susceptibility breakpoint.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1711
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:In-Data-Review
[do] DOI:10.1093/jac/dkx419

  6 / 6276 MEDLINE  
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[PMID]: 29499757
[Au] Autor:Pota V; Passavanti MB; Sansone P; Pace MC; Peluso F; Fiorelli A; Aurilio C
[Ad] Address:Department of Women, Infant and Surgical and Specialist Surgery, University of Campania "L. Vanvitelli", Piazza Miraglia 2, 80138, Naples, Italy. Vincenzo.pota@unicampania.it.
[Ti] Title:Septic shock from descending necrotizing mediastinitis - combined treatment with IgM-enriched immunoglobulin preparation and direct polymyxin B hemoperfusion: a case report.
[So] Source:J Med Case Rep;12(1):55, 2018 Mar 03.
[Is] ISSN:1752-1947
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract: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 Sanit project confirmed that Italy is positioned among the countries with the highest levels of resistance in most pathogenic species under surveillance. In particular, 32.9% of Klebsiella pneumoniae isolates were resistant to carbapenem, 33.6% of Staphylococcus aureus to methicillin, and 28.7% and 43.9% of Escherichia coli isolates to third-generation cephalosporins and fluoroquinolones, respectively. CASE PRESENTATION: We describe the case of a 38-year-old white man with septic shock due to descending necrotizing mediastinitis sustained by multidrug-resistant Gram-negative and Gram-positive bacteria treated after surgery with an IgM-enriched immunoglobulin preparation and polymyxin B hemoperfusion therapy. CONCLUSION: Despite the contrasting data on the use of immunoglobulins and polymyxin B hemoperfusion in septic shock and the lack of literature in cases of acute mediastinitis caused by both Gram-negative and Gram-positive multidrug-resistant bacteria, we obtained an improvement in clinical conditions and the survival of our patient, against all odds.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:In-Process
[do] DOI:10.1186/s13256-018-1611-5

  7 / 6276 MEDLINE  
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[PMID]: 29508561
[Au] Autor:Obuobi S; Voo ZX; Low MW; Czarny B; Selvarajan V; Ibrahim NL; Yang YY; Ee PLR
[Ad] Address:Department of Pharmacy National University of Singapore, 18 Science Drive 4, 117543, Singapore.
[Ti] Title:Phenylboronic Acid Functionalized Polycarbonate Hydrogels for Controlled Release of Polymyxin B in Pseudomonas Aeruginosa Infected Burn Wounds.
[So] Source:Adv Healthc Mater;, 2018 Mar 06.
[Is] ISSN:2192-2659
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract: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. The optimum gel systems obtained from the meta-substituted copolymers (m-PAP) are stable at physiological pH and nontoxic to mammalian dermal cells. The polymyxin B loaded m-PAP hydrogels demonstrate controlled in vitro drug release kinetics and in vitro antimicrobial activity against Pseudomonas aeruginosa over 48 h. In vivo antimicrobial efficacy of the drug loaded hydrogels further corroborates the in vitro results, demonstrating sustained antimicrobial activity against P. aeruginosa burn wound infections. The current strategy described in this study demonstrates a straightforward approach in designing physiologically relevant boronic acid hydrogel systems for controlled release of cationic antimicrobials for future clinical applications.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180306
[Lr] Last revision date:180306
[St] Status:Publisher
[do] DOI:10.1002/adhm.201701388

  8 / 6276 MEDLINE  
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[PMID]: 29501823
[Au] Autor:Ma Q; Huang Y; Wang J; Xu X; Hawkey J; Yang C; Liang B; Hu X; Wu F; Yang X; Wang J; Li R; Li P; Xie J; Jia L; Wang L; Hao R; Tong Y; Holt KE; Qiu S; Sun Y; Song H
[Ad] Address:Navy's Center for Disease Control and Prevention, Beijing, China; Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
[Ti] Title:Multidrug-resistant Shigella sonnei carrying plasmid-mediated mcr-1 gene in China.
[So] Source:Int J Antimicrob Agents;, 2018 Feb 28.
[Is] ISSN:1872-7913
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract: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. Pulsed-field gel electrophoresis, plasmid profiles, and Southern blot were used to analyze genetic relationships and plasmid characteristics, and mcr-1-positive plasmids were sequenced. In total, we identified six mcr-1-positive S. sonnei isolates from Shanghai (2010-2012) with polymyxin B resistance (MIC 4-8 g/mL). Four of these exhibited multidrug resistance (MDR), including resistance to azithromycin and third-generation cephalosporins, and co-harbored bla , mph (A), and bla on different plasmids. Mcr-1-positive plasmids shared highly similar IncI2 backbones that resembled reference plasmids, although some differences were observed, including various and abundant insertion sequences/patterns (IS1294, IS1, and ISApl1) and a diverse recombination shufflon region. Mcr-1 in S. sonnei may date back to mid-2006. For the first time, we report the presence of active mcr-1 in MDR S. sonnei in China, which has existed since at least 2010. Our study highlights the diverse mobile genetic elements on mcr-1-harboring plasmids, potentially resulting in high rates of mcr-1 horizontal transfer among Enterobacteriaceae. Our findings emphasize the importance of continuous national and international surveillance of mcr-1-positive Shigella and changes in antibiotic resistance patterns.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180304
[Lr] Last revision date:180304
[St] Status:Publisher

  9 / 6276 MEDLINE  
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[PMID]: 29501820
[Au] Autor:Shukla M; Soni I; Matsuyama K; Tran T; Tanga M; Gong L; Chopra S
[Ad] Address:Department of Microbiology, CSIR-Central Drug Research Institute, Lucknow-226021, Uttar Pradesh, India.
[Ti] Title:Identification and bio-evaluation of SRI-12742 as a antimicrobial agent against multi-drug resistant Acinetobacter baumannii.
[So] Source:Int J Antimicrob Agents;, 2018 Feb 28.
[Is] ISSN:1872-7913
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract: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. The selectivity index of hit was tested against Vero cells and it's in vitro efficacy was profiled against a panel of clinical multi-drug resistant A. baumannii. The bacteriostatic or bactericidal nature was determined by time kill experiments and its synergy with approved drugs was determined by chequerboard method. In addition, it's in vivo efficacy was measured in a murine neutropenic A. baumannii thigh infection model. RESULTS: SRI-12742 was identified as a potent hit active with an MIC of 4 mg/L. Its activity was then profiled against a MDR clinical strain panel (MIC 4-64 mg/L). SRI-12742 exhibited concentration dependent bactericidal activity and reduced ∼16 log CFU, which is comparable to minocycline. In the murine model of A. baumannii infection, SRI-12742 reduced CFU by ∼0.9 log CFU, which is comparable to polymyxin B. Additionally, SRI-12742 synergized with all the classes of antibiotics tested. CONCLUSION: SRI-12742 exhibits all the criteria to be positioned as a novel lead with potential to be deployed for the treatment of infections caused by MDR-AB.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180304
[Lr] Last revision date:180304
[St] Status:Publisher

  10 / 6276 MEDLINE  
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[PMID]: 29501603
[Au] Autor:Gomes EC; Falci DR; Bergo P; Zavascki AP; Rigatto MH
[Ad] Address:Infectious Diseases Service, Hospital de Clnicas de Porto Alegre, 2350 Ramiro Barcelos St., Porto Alegre, 90.035-903, Brazil.
[Ti] Title:Impact of Polymyxin B Associated Acute Kidney Injury in 1-Year Mortality and Renal Function Recovery.
[So] Source:Int J Antimicrob Agents;, 2018 Mar 01.
[Is] ISSN:1872-7913
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract: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. In the subgroup of patients who developed AKI, we evaluated renal function recovery. RESULTS: A total of 234 patients were included for analyses. Of these, 108 (46.1%) died, in a median time of 63 (38.3-102.5) days. The use of other nephrotoxic drugs along with PMB (P=0.05), renal failure (P=0.03), dialysis (P<0.01) and re-exposure to PMB (P<0.01), were all significantly related to 1-year mortality, while male gender had a protective effect (P=0.01). Independent factors related to death were age (aHR 1.02, 95%CI 1.00-1.03, P=0.02), re-exposure to PMB (aHR 2.69, 95%CI 1.82-3.95, P<0.01), and male gender (aHR0.6, 95%CI 0.41-0.87, P=0.01), when controlled for renal failure (aHR 1.28, 95%CI 0.78-2.10, P=0.34).Thirty one of 94 (33%) patients who developed AKI had renal function recovery within one-year. CONCLUSIONS: Mortality rates were high in the first year after PMB use and only one third of patients who develop AKI return to baseline renal function. Strategies to reduce renal toxicity are urgently needed in these patients.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180304
[Lr] Last revision date:180304
[St] Status:Publisher


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