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Polymyxin B

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https://www.readbyqxmd.com/read/29149329/polymyxin-derivatives-nab739-and-nab815-are-more-effective-than-polymyxin-b-in-murine-escherichia-coli-pyelonephritis
#1
Martti Vaara, Timo Vaara, Carina Vingsbo Lundberg
Objectives: Extremely multiresistant strains of Enterobacteriaceae, such as those of Escherichia coli and Klebsiella pneumoniae, are emerging and spreading at a worrisome speed. Polymyxins (polymyxin B, colistin) are used as last-line therapy against such strains, in spite of their notable nephrotoxicity that may even require discontinuation of the therapy. We have previously developed polymyxin derivatives NAB739 and NAB815 that are better tolerated in cynomolgus monkeys than polymyxin B and are, in contrast to polymyxin B, excreted in the cynomolgus urine to a very significant degree...
November 14, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29149294/pharmacokinetics-pharmacodynamics-of-systemically-administered-polymyxin-b-against-klebsiella-pneumoniae-in-mouse-thigh-and-lung-infection-models
#2
Cornelia B Landersdorfer, Jiping Wang, Veronika Wirth, Ke Chen, Keith S Kaye, Brian T Tsuji, Jian Li, Roger L Nation
Background: The pharmacokinetic/pharmacodynamic (PK/PD) relationship for polymyxin B against Klebsiella pneumoniae infections is not known. Methods: Dose-fractionation studies with subcutaneous polymyxin B were conducted in neutropenic mice in which infection with three strains of K. pneumoniae had been produced in thighs or lungs. Dosing (thigh infection 0.5-120 mg/kg/day; lung infection 5-120 mg/kg/day) commenced 2 h after inoculation, and bacterial burden was measured 24 h later...
November 14, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29137129/design-and-evaluation-of-novel-polymyxin-fluorescent-probes
#3
Bo Yun, Kade D Roberts, Philip E Thompson, Roger L Nation, Tony Velkov, Jian Li
Polymyxins (polymyxin B and colistin) are cyclic lipopeptide antibiotics that serve as a last-line defence against Gram-negative "superbugs". In the present study, two novel fluorescent polymyxin probes were designed through regio-selective modifications of the polymyxin B core structure at the N-terminus and the hydrophobic motif at positions 6 and 7. The resulting probes, FADDI-285 and FADDI-286 demonstrated comparable antibacterial activity (MICs 2-8 mg/L) to polymyxin B and colistin (MICs 0.5-8 mg/L) against a panel of gram-negative clinical isolates of Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa...
November 11, 2017: Sensors
https://www.readbyqxmd.com/read/29123880/efficacy-of-direct-hemoperfusion-with-a-polymyxin-b-immobilized-fiber-column-in-miliary-tuberculosis
#4
Yasumasa Kawano, Ryotaro Nagashima, Shinichi Morimoto, Yoshito Izutani, Reiko Yamasaki, Takeshi Nishida, Mitsutoshi Iwaasa, Hiroyasu Ishikura
Case: A 75-year-old woman presented with a 10-day history of intermittent fever, general fatigue, and progressive dyspnea. Although she had a low PaO2/FIO2 ratio, the cause of acute respiratory distress syndrome was not clear until day 9 in hospital. Outcome: We treated the patient with direct hemoperfusion with a polymyxin B-immobilized fiber column incidentally; the PaO2/FIO2 ratio improved following this therapy. Acid-fast bacilli, which were not seen in the sputum on admission, were detected in cultures from sputum, urine, bone marrow, liver biopsy, and blood samples, with a real-time polymerase chain reaction assay confirming tuberculosis...
July 2017: Acute Medicine & Surgery
https://www.readbyqxmd.com/read/29120716/cost-comparison-of-commonly-used%C3%A2-postoperative-topical-ophthalmic%C3%A2-antibiotics
#5
Eric L Crowell, Vivek A Koduri, R Scott Groat, David A Lee
PURPOSE: To provide information on the actual fill level and cost of currently available antibiotic drops used perioperatively. DESIGN: Prospective laboratory investigation. SETTING: Robert Cizik Eye Clinic, Houston, Texas USA. METHODS: The following 9 medications were tested: moxifloxacin, gatifloxacin (branded and generic), besifloxacin, levofloxacin, ciprofloxacin, ofloxacin, trimethoprim/polymyxin B, tobramycin, and gentamicin...
October 2017: Journal of Cataract and Refractive Surgery
https://www.readbyqxmd.com/read/29117525/membrane-cholesterol-reduces-polymyxin-b-nephrotoxicity-in-renal-membrane-analogs
#6
Adree Khondker, Richard J Alsop, Alexander Dhaliwal, Sokunthearath Saem, Jose M Moran-Mirabal, Maikel C Rheinstädter
Polymyxin B (PmB) is a "last-line" antibiotic scarcely used due to its nephrotoxicity. However, the molecular basis for antibiotic nephrotoxicity is not clearly understood. We prepared kidney membrane analogs of detergent-susceptible membranes, depleted of cholesterol, and cholesterol enriched, resistant membranes. In both analogs, PmB led to membrane damage. By combining x-ray diffraction, molecular dynamics simulations, and electrochemistry, we present evidence for two populations of PmB molecules: peptides that lie flat on the membranes, and an inserted state...
November 7, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29107079/clonal-spread-of-carbapenem-resistant-acinetobacter-baumannii-in-neonatal-intensive-care-unit
#7
Wirlaine Glauce Maciel, Kesia Esther da Silva, Julio Croda, Rodrigo Cayô, Ana Carolina Ramos, Romário Oliveira de Sales, Gleyce Hellen de Almeida de Souza, José Victor Bortolotto Bampi, Leticia Cristina Limiere, Junior César Casagrande, Ana Cristina Gales, Simone Simionatto
Acinetobacter baumannii has been frequently associated with colonization and/or infection in neonatal intensive care units (NICU). In this study, we describe a clonal spread of carbapenem-resistant A. baumannii (CRAB) isolates in a NICU. A total of 21 CRAB isolates were collected from premature newborns. Only polymyxin B was active against such isolates. Nineteen CRAB isolates were clonally related (cluster C that belonged to worldwide-disseminated ST1). All newborns had peripheral access and previously received β-lactams therapy...
October 26, 2017: Journal of Hospital Infection
https://www.readbyqxmd.com/read/29093381/the-serum-ferritin-level-is-associated-with-the-treatment-responsivity-for-rapidly-progressive-interstitial-lung-disease-with-amyopathic-dermatomyositis-irrespective-of-the-anti-mda5-antibody-level-a-case-report
#8
Takeshi Osawa, Kozo Morimoto, Yuka Sasaki, Shuichi Matsuda, Kazunari Yamana, Ryozo Yano, Takashi Uchiyama, Hajime Goto
We herein report he case of a 61-year-old woman with rapidly progressive interstitial lung disease caused by clinically amyopathic dermatomyositis. Both the serum ferritin and anti-MDA5 antibody levels were elevated at the time of admission. Despite intensive treatment with corticosteroids, immunosuppressants, immunoglobulins and polymyxin B direct hemoperfusion, the patient died 75 days after symptom onset. Over the course of treatment, the anti-MDA5 antibody level continually decreased, while the serum ferritin level increased, suggesting that sequential measurements of the serum ferritin level might be useful for evaluating the treatment responsivity, irrespective of the anti-MDA5 antibody level...
November 1, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29091192/modifications-in-the-pmrb-gene-are-the-primary-mechanism-for-the-development-of-chromosomally-encoded-resistance-to-polymyxins-in-uropathogenic-escherichia-coli
#9
Minh-Duy Phan, Nguyen Thi Khanh Nhu, Maud E S Achard, Brian M Forde, Kar Wai Hong, Teik Min Chong, Wai-Fong Yin, Kok-Gan Chan, Nicholas P West, Mark J Walker, David L Paterson, Scott A Beatson, Mark A Schembri
Objectives: Polymyxins remain one of the last-resort drugs to treat infections caused by MDR Gram-negative pathogens. Here, we determined the mechanisms by which chromosomally encoded resistance to colistin and polymyxin B can arise in the MDR uropathogenic Escherichia coli ST131 reference strain EC958. Methods: Two complementary approaches, saturated transposon mutagenesis and spontaneous mutation induction with high concentrations of colistin and polymyxin B, were employed to select for mutations associated with resistance to polymyxins...
October 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29079699/substrate-analog-interaction-with-mcr-1-offers-insight-into-the-rising-threat-of-the-plasmid-mediated-transferable-colistin-resistance
#10
Pengcheng Wei, Guangji Song, Mengyang Shi, Yafei Zhou, Yang Liu, Jun Lei, Peng Chen, Lei Yin
Colistin is considered a last-resort antibiotic against most gram-negative bacteria. Recent discoveries of a plasmid-mediated, transferable colistin-resistance gene (mcr-1) on all continents have heralded the imminent emergence of pan-drug-resistant superbacteria. The inner-membrane protein MCR-1 can catalyze the transfer of phosphoethanolamine (PEA) to lipid A, resulting in colistin resistance. However, little is known about the mechanism, and few drugs exist to address this issue. We present crystal structures revealing the MCR-1 catalytic domain (cMCR-1) as a monozinc metalloprotein with ethanolamine (ETA) and d-glucose, respectively, thus highlighting 2 possible substrate-binding pockets in the MCR-1-catalyzed PEA transfer reaction...
October 27, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29077917/characterization-of-ornithobacterium-rhinotracheale-from-commercial-layer-chickens-in-eastern-japan
#11
D V Umali, K Shirota, K Sasai, H Katoh
From a total of 72 commercial layer and pullet farms that were monitored in the eastern Japan area, 4 farms had mild to severe respiratory disease accompanied by decreased feed intake and drop in egg production. Microbiological analysis showed that 3 of the 4 farms, particularly from Fukushima, Tochigi, and Ibaraki prefectures, were positive for Ornithobacterum rhinotracheale (ORT). Out of 65 birds examined, ORT was isolated in 21 birds (32.31%). All isolates were Gram-negative pleomorphic rods with a colony size of 0...
October 25, 2017: Poultry Science
https://www.readbyqxmd.com/read/29065861/clinical-effects-of-direct-hemoperfusion-using-a-polymyxin-b-immobilized-fiber-column-in-clinically-amyopathic-dermatomyositis-associated-rapidly-progressive-interstitial-pneumonias
#12
Hiroko Okabayashi, Hidenori Ichiyasu, Sayuri Hirooka, Kimitaka Akaike, Keisuke Kojima, Takayuki Jodai, Yasumiko Sakamoto, Hideharu Ideguchi, Shohei Hamada, Chieko Yoshida, Susumu Hirosako, Shinichiro Okamoto, Hirotsugu Kohrogi
BACKGROUND: Rapidly progressive interstitial pneumonias (RPIPs) associated with clinically amyopathic dermatomyositis (CADM) are highly resistant to therapy and have a poor prognosis. Multimodal therapies, including direct hemoperfusion using a polymyxin B-immobilized fiber column (PMX-DHP), have a protective effect on RPIPs. We evaluated the effects of PMX-DHP on CADM-associated RPIPs. METHODS: We retrospectively enrolled 14 patients with CADM-associated RPIPs and acute respiratory failure treated with PMX-DHP, corticosteroids, and immunosuppressive agents...
October 24, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29061752/methionine-ameliorates-polymyxin-induced-nephrotoxicity-by-attenuating-cellular-oxidative-stress
#13
Mohammad A K Azad, Sivashangarie Sivanesan, Jiping Wang, Ke Chen, Roger L Nation, Philip E Thompson, Kade D Roberts, Tony Velkov, Jian Li
Polymyxins are a last-line defence against multidrug-resistant Gram-negative pathogens. Recent pharmacological data show that intravenous polymyxins can cause nephrotoxicity in up to 60% of patients, and plasma concentrations of polymyxins are suboptimal in a large proportion of patients with the currently recommended dosage regimens. Simply increasing the daily dose of polymyxins is not possible due to nephrotoxicity. This study aimed to examine the protective effect of methionine against polymyxin-induced nephrotoxicity...
October 23, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29058126/time-kill-analysis-of-ceftolozane-tazobactam-efficacy-against-mucoid-pseudomonas-aeruginosa-strains-from-cystic-fibrosis-patients
#14
Hana Rac, Kayla R Stover, Jamie L Wagner, S Travis King, Henderson D Warnock, Katie E Barber
INTRODUCTION: Mucoid Pseudomonas aeruginosa (MP) strains in cystic fibrosis (CF) patients are thought to initiate the chronic infection stage of CF and are associated with pulmonary function decline. OBJECTIVES: The purpose of this study was to assess the susceptibility of MP strains to ceftolozane/tazobactam and the efficacy of ceftolozane/tazobactam against MP strains compared with those for standard-of-care antipseudomonal antibiotics. METHODS: Ten clinical isolates of MP from CF patients were tested for susceptibility with Etest and time-kill analysis with ceftolozane/tazobactam compared with ceftazidime, cefepime, ciprofloxacin, meropenem, tobramycin, and polymyxin B...
October 20, 2017: Infectious Diseases and Therapy
https://www.readbyqxmd.com/read/29058043/synergistic-antimicrobial-activity-between-the-broad-spectrum-bacteriocin-garvicin-ks-and-nisin-farnesol-and-polymyxin-b-against-gram-positive-and-gram-negative-bacteria
#15
Hai Chi, Helge Holo
The increasing emergence of antibiotics resistance is of global concern. Finding novel antimicrobial agents and strategies based on synergistic combinations are essential to combat resistant bacteria. We evaluated the activity of garvicin KS, a new bacteriocin produced by Lactococcus garvieae. The bacteriocin has a broad inhibitory spectrum, inhibiting members of all the 19 species of Gram-positive bacteria tested. Unlike other bacteriocins from Gram-positive bacteria, garvicin KS inhibits Acinetobacter but not other Gram-negative bacteria...
October 20, 2017: Current Microbiology
https://www.readbyqxmd.com/read/29046251/mycobacterium-tuberculosis-esat6-induces-ifn-%C3%AE-gene-expression-in-macrophages-via-tlrs-mediated-signaling
#16
Ah-Ra Jang, Joo-Hee Choi, Sung Jae Shin, Jong-Hwan Park
Mycobacterium tuberculosis is a highly virulent bacterium that causes tuberculosis. It infects about one third of the world's population. Type I interferons (IFNs) play a detrimental role in host defense against M. tuberculosis infection. Proteins secreted by M. tuberculosis through ESX-1 secretion system contribute to type I IFNs production. However, the precise mechanism by which 6-kDa early secretory antigen target (ESAT6), one of ESX-1-mediated secretory proteins, induces type I IFNs production in host cells is currently unclear...
October 15, 2017: Cytokine
https://www.readbyqxmd.com/read/29038262/severe-infusion-related-adverse-events-and-renal-failure-in-patients-receiving-high-dose-intravenous-polymyxin-b
#17
Josiane F John, Diego R Falci, Maria Helena Rigatto, Renata D Oliveira, Thaysa G Kremer, Alexandre P Zavascki
Very high doses of polymyxin B (PMB) have been addressed in in vitro experiments against carbapenem-resistant Gram-negative bacilli as a strategy to improve bacterial killing and suppress resistance emergence. However, the toxicities of very high doses in patients are unknown. This is a retrospective cohort study assessing patients receiving >3mg/kg/day or a total dose ≥250mg/day of PMB. The main outcomes were severe infusion-related adverse event according to Common Terminology Criteria for Adverse Criteria and renal failure category of RIFLE criteria for acute kidney injury (AKI) during treatment...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29030025/emerge-of-blandm-1-and-blaoxa-48-like-harboring-carbapenem-resistant-klebsiella-pneumoniae-isolates-from-hospitalized-patients-in-southwestern-iran
#18
Zahra Hosseinzadeh, Hadi Sedigh Ebrahim-Saraie, Jamal Sarvari, Jalal Mardaneh, Behzad Dehghani, Seyed Mohammad Hossein Rokni-Hosseini, Mohammad Motamedifar
BACKGROUND: One of the most important emerging carbapenem-resistant bacteria is Klebsiella pneumoniae (K. pneumoniae). The present study aimed to investigate the antibiotic susceptibility pattern of K. pneumoniae isolates and detection of carbapenemase producing K. pneumoniae obtained from Iranian hospitalized patients. METHODS: This cross-sectional study was performed on 211 K. pneumoniae isolates which were recovered from different clinical specimens from 2014 to 2015...
October 10, 2017: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/29028568/virulence-genotypes-and-antimicrobial-susceptibility-patterns-of-arcobacter-butzleri-isolated-from-seafood-and-its-environment
#19
Srinu Rathlavath, Vandita Kohli, Asem Sanjit Singh, Manjusha Lekshmi, Gayatri Tripathi, Sanath Kumar, Binaya Bhusan Nayak
Arcobacter butzleri is an emerging pathogen isolated from animals, food and the environment. In this study, 147 A. butzleri isolated from seafood and the coastal environment were tested for the presence of ten putative virulence genes (cadF, cj1349, ciaB, mviN, pldA, tlyA, hecA, hecB, irgA, iroE) and antimicrobial susceptibilities. Majority of the isolates harbored mviN (100%), cj1349 (97.2%), ciaB (95.9%), tlyA (91.8%), pldA (91.1%) and cadF (89.7%). Lower detection rates were observed for hecA (10.8%), hecB (19%), iroE (12...
October 3, 2017: International Journal of Food Microbiology
https://www.readbyqxmd.com/read/29026662/intrathecal-and-intraventricular-antibiotics-for-postoperative-gram-negative-meningitis-and-ventriculitis
#20
Saad Akhtar Khan, Muhammad Waqas, Usman T Siddiqui, Muhammad Shahzad Shamim, Karim Rizwan Nathani, Rashid Jooma, Faisal Mehmood
BACKGROUND: Postoperative meningitis is a growing cause of concern, especially with the evolution of multidrug-resistant organism. The authors evaluate the use of intraventricular/intrathecal (IVT/IT) antibiotics for postoperative gram-negative meningitis in patients whom intravenous antibiotics were ineffective. METHODS: Medical records were retrospectively reviewed and neurosurgery patients with gram-negative postoperative infection meningitis/ventriculitis were enrolled in the study...
2017: Surgical Neurology International
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