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antibiotic development

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https://www.readbyqxmd.com/read/28102546/ataluren-and-similar-compounds-specific-therapies-for-premature-termination-codon-class-i-mutations-for-cystic-fibrosis
#1
REVIEW
Aisha A Aslam, Colin Higgins, Ian P Sinha, Kevin W Southern
BACKGROUND: Cystic fibrosis is a common life-shortening genetic disorder in the Caucasian population (less common in other ethnic groups) caused by the mutation of a single gene that codes for the production of the cystic fibrosis transmembrane conductance regulator protein. This protein coordinates the transport of salt (and bicarbonate) across cell surfaces and the mutation most notably affects the airways. In the lungs of people with cystic fibrosis, defective protein results in a dehydrated surface liquid and compromised mucociliary clearance...
January 19, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28102514/carbapenemase-producing-klebsiella-pneumoniae-bloodstream-infection-in-critically-ill-patients-risk-factors-and-predictors-of-mortality
#2
M Papadimitriou-Olivgeris, F Fligou, C Bartzavali, A Zotou, A Spyropoulou, K Koutsileou, S Vamvakopoulou, N Sioulas, V Karamouzos, E D Anastassiou, I Spiliopoulou, M Christofidou, M Marangos
A significant increase in carbapenemase-producing Klebsiella pneumoniae (CP-Kp) bacteraemias has been observed worldwide. The objective of the present work was to study the risk factors and predictors of mortality of CP-Kp bacteraemias among critically ill patients. During a 4-year period (2012-3015), a matched 1:2 case-control study was conducted. Klebsiella pneumoniae was identified by Vitek 2 technology. Antibiotic susceptibility was performed by the agar disc diffusion method and Etest. The presence of the bla KPC, bla VIM and bla NDM genes was confirmed by polymerase chain reaction (PCR)...
January 19, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28101041/endophthalmitis-following-27-gauge-pars-plana-vitrectomy-for-vitreous-floaters
#3
Zhong Lin, Rong Han Wu, Nived Moonasar
PURPOSE: To report a case of Staphylococcus epidermidis endophthalmitis following 27-gauge pars plana vitrectomy for symptomatic vitreous floaters. METHODS: The clinical course and imaging findings, including fundus optomap, and spectral domain optical coherence tomography of a 24-year-old male patient were documented. RESULTS: The patient, with a preoperative best-corrected visual acuity (BCVA) of 1.0, developed endophthalmitis following 27-gauge pars plana vitrectomy for symptomatic vitreous floaters...
September 2016: Case Reports in Ophthalmology
https://www.readbyqxmd.com/read/28100993/cdc-group-eo-4-and-candida-tropicalis-peritonitis-in-a-patient-on-peritoneal-dialysis-after-upper-endoscopy-colonoscopy-and-coil-embolization-of-the-gastroduodenal-artery
#4
Shameek Gayen, Yonah Ziemba, Shikha Jaiswal, Adam Frank, Yasmin Brahmbhatt
Peritoneal dialysis (PD) is an excellent form of renal replacement therapy for many patients with end-stage renal disease (ESRD). Over 10,000 patients receive PD in the United States [United States Renal Data System: 2015 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States, 2015]. PD has superior outcomes compared to hemodialysis in the first 2 years of ESRD [Sinnakirouchenan and Holley: Adv Chronic Kidney Dis 2011;18: 428-432]. However, peritonitis is a known complication and may result in significant morbidity and necessitate transition to hemodialysis, which increases medical costs [Holley and Piraino: Semin Dial 1990;3: 245-248]...
September 2016: Case Reports in Gastroenterology
https://www.readbyqxmd.com/read/28100903/rhodoccocus-equi-pneumonia-and-paradoxical-immune-reconstitution-inflammatory-syndrome-in-a-patient-with-acquired-immune-deficiency-syndrome-aids
#5
Ritika Zijoo, Ahmed Dirweesh, Nigahus Karabulut
BACKGROUND Pulmonary infections are a major cause of mortality and morbidity in patients infected with human immunodeficiency virus (HIV) and can progress rapidly to respiratory failure and death without appropriate therapy. Herein, we present a rare case of an advanced HIV infection and Rhodoccocus equi (R. equi) pneumonia in a young male who had severe paradoxical immune reconstitution inflammatory syndrome (IRIS). CASE REPORT A 47-year-old nonsmoking Hispanic man with advanced HIV infection presented with severe acute necrotizing pneumonia secondary to R...
January 19, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28100776/crystallographic-snapshots-of-class-a-%C3%AE-lactamase-catalysis-reveal-structural-changes-that-facilitate-%C3%AE-lactam-hydrolysis
#6
Xuehua Pan, Yunjiao He, Jinping Lei, Xuhui Huang, Yanxiang Zhao
β-lactamases confer resistance to β-lactam-based antibiotics. There is great interest in understanding their mechanisms to enable the development of β-lactamase-specific inhibitors. The mechanism of Class A β-lactamases has been studied extensively, revealing Lys73 and Glu166 as general bases that assist the catalytic residue Ser70. However, the specific roles of these two residues within the catalytic cycle remains not fully understood. To help resolve this question, we first identified a Glu166His mutant that is functional but kinetically slowed...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100714/the-dynamics-of-the-pulmonary-microbiome-during-mechanical-ventilation-in-the-intensive-care-unit-and-the-association-with-occurrence-of-pneumonia
#7
Tetyana Zakharkina, Ignacio Martin-Loeches, Sébastien Matamoros, Pedro Povoa, Antoni Torres, Janine B Kastelijn, Jorrit J Hofstra, B de Wever, Menno de Jong, Marcus J Schultz, Peter J Sterk, Antonio Artigas, Lieuwe D J Bos
RATIONALE: Ventilator-associated pneumonia (VAP) is the most common nosocomial infections in patients admitted to the ICU. The adapted island model predicts several changes in the respiratory microbiome during intubation and mechanical ventilation. OBJECTIVES: We hypothesised that mechanical ventilation and antibiotic administration decrease the diversity of the respiratory microbiome and that these changes are more profound in patients who develop VAP. METHODS: Intubated and mechanically ventilated ICU-patients were included...
January 18, 2017: Thorax
https://www.readbyqxmd.com/read/28100443/surveillance-of-antimicrobial-use-in-dutch-long-term-care-facilities
#8
Monique Roukens, Linda Verhoef, Ellen Stobberingh, Stephanie Natsch
OBJECTIVES: Residents living in a long-term care facility (LTCF) are more susceptible to infections. Treatment with antimicrobials is sometimes necessary; however, antibiotic use is considered one of the most important drivers of the development of antibiotic resistance. Surveillance data on antibiotic use in these LTCFs are necessary to get more insight into these patterns. The objective of this study was to describe antibiotic use in LTCFs in the Netherlands. METHODS: One hundred and seventy-seven LTCFs in the Netherlands were contacted and asked to participate in a study concerning antibiotic resistance and antibiotic use...
January 18, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28099198/osteomyelitis-of-the-navicular-bone-a-case-report
#9
Nobuyuki Kumahashi, Suguru Kuwata, Shinji Imade, Yuji Uchio
A 16-year-old boy developed left foot pain of unknown cause that was unresponsive to conservative treatment, associated with fever and difficulty walking. He was admitted to our hospital with osteomyelitis of the accessory and body of the navicular bone. Surgery could not be performed because the patient had been diagnosed with Wiskott-Aldrich syndrome. After antibiotic therapy, laboratory abnormalities and pain had resolved. One year after treatment, the patient had returned to his original level of sports activity...
January 17, 2017: Journal of Pediatric Orthopedics. Part B
https://www.readbyqxmd.com/read/28098447/the-stories-tryptophans-tell-exploring-protein-dynamics-of-heptosyltransferase-i-from-escherichia-coli
#10
Joy M Cote, Carlos Andres Ramirez-Mondragon, Zarek S Siegel, Daniel Joseph Czyzyk, Jiali Gao, Yuk Yin Sham, Ishita Mukerji, Erika A Taylor
Heptosyltransferase I (HepI) catalyzes the addition of a single L-glycero-β-D-manno-heptose sugar (heptose) onto the membrane incorporated Kdo2-Lipid A as part of the biosynthesis of the core region of lipopolysaccharide (LPS). Gram-negative bacteria with gene knockouts of HepI have reduced virulence with enhanced susceptibility to hydrophobic antibiotics, making design of inhibitors against HepI of interest. Previous studies have shown that HepI protein dynamics are partially rate limiting, and therefore disruption of protein dynamics might provide a new strategy for inhibiting HepI...
January 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28097747/a-literacy-sensitive-approach-to-improving-antibiotic-understanding-in-a-community-based-setting
#11
Crystal M David, Katherine S O'Neal, Michael J Miller, Jeremy L Johnson, Ann E Lloyd
OBJECTIVE: Antibiotic misuse contributes to antibiotic-resistant bacterial infections. Patient and prescriber knowledge and behaviors influence antibiotic use. Past research has focused on describing and influencing prescriber behavior with less attention to the patient role in antibiotic use. This study seeks to: (1) develop and deploy a program to enhance patient knowledge about antibiotic use; (2) evaluate whether providing patient education is associated with improvements in antibiotic knowledge in a community-based sample; and (3) explore whether health literacy may be associated with knowledge of appropriate antibiotic use...
January 18, 2017: International Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/28097714/photoantimicrobial-biohybrids-by-supramolecular-immobilization-of-cationic-phthalocyanines-onto-cellulose-nanocrystals
#12
Eduardo Anaya-Plaza, Eveline van de Winckel, Joona Mikkilä, Jani-Markus Malho, Olli Ikkala, Oscar Gulías, Roger Bresolí-Obach, Montserrat Agut, Santi Nonell, Tomás Torres, Mauri A Kostiainen, Andrés de la Escosura
The development of photoactive and biocompatible nanostructures is a highly desirable goal to address the current threat of antibiotic resistance. Here, we describe a novel supramolecular biohybrid nanostructure based on the non-covalent immobilization of cationic zinc phthalocyanine (ZnPc) derivatives onto unmodified cellulose nanocrystals (CNC), following an easy and straightforward protocol, in which binding is driven by electrostatic interactions. These non-covalent biohybrids show strong photodynamic activity against S...
January 18, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28097633/meropenem-dosing-based-on-a-population-pharmacokinetic-pharmacodynamic-model-in-elderly-patients-with-infection-of-the-lower-respiratory-tract
#13
Qing-Tao Zhou, Bei He, Ning Shen, Ying Liang, Li-Na Sun
BACKGROUND: Meropenem is used for the treatment of severe lower respiratory tract infections (LRTIs) caused by multidrug-resistant Gram-negative bacilli. OBJECTIVE: We evaluated the clinical benefits of a strategy of meropenem dosing based on a population pharmacokinetics/pharmacodynamics (PK/PD) model in elderly patients with an LRTI. METHODS: In this prospective single-center open-label randomized controlled trial, 79 elderly patients with an LRTI caused by Gram-negative bacilli were randomized to a study group (SG) or a control group (CG)...
January 17, 2017: Drugs & Aging
https://www.readbyqxmd.com/read/28097503/blended-chitosan-paste-for-infection-prevention-preliminary-and-preclinical-evaluations
#14
Joel M Berretta, Jessica A Jennings, Harry S Courtney, Karen E Beenken, Mark S Smeltzer, Warren O Haggard
BACKGROUND: Local drug delivery devices offer a promising method for delivering vancomycin and amikacin for musculoskeletal wounds. However, current local delivery devices such as beads and sponges do not necessarily allow for full coverage of a wound surface with eluted antibiotics and do not address the need for reducing the antibiotic diffusion distance to help prevent contamination by bacteria or other microorganisms. We blended chitosan/polyethylene glycol (PEG) pastes/sponges to increase biocompatibility and improve antibiotic coverage within the wound...
January 17, 2017: Clinical Orthopaedics and related Research
https://www.readbyqxmd.com/read/28097252/enterococcus-faecalis-causing-delayed-spondylodiscitis-in-a-case-with-retained-intraspinal-bullet
#15
Siddharth N Aiyer, Ajoy Prasad Shetty, Rishi Kanna, Srikanth Reddy, Shanmuganathan Rajasekaran
Delayed presentations have been reported following gunshot wounds (GSW) with retained intraspinal bullets due to migration of projectile or lead intoxication. We report on the rare occurrence of delayed pyogenic spondylodiscitis and neurological dysfunction following injury from low velocity GSW to the spine with a retained projectile. A 55-year-old male presented 4 months following GSW to the abdomen which resulted in colonic injury and L5 fracture. The patient was treated initially with ileo-transverse anastomosis, antibiotics, without retrieval of the bullet...
December 2016: Journal of Spine Surgery (Hong Kong)
https://www.readbyqxmd.com/read/28097195/rapidly-expanding-infectious-aortic-aneurysm-caused-by-perforated-colon-cancer
#16
Taufiek Konrad Rajab, Daniel E Rinewalt, Michael Belkin, Joel E Goldberg, Haiyang Zhou
A 50-year-old male smoker presented with a perforated colon cancer and underwent an extended right colectomy. Feculent peritonitis was treated with empiric antibiotics. Postoperatively he developed severe back pain and rising leukocytosis. Serial computed tomography revealed a rapidly expanding infrarenal aortic aneurysm. He was urgently treated with extra-anatomic bypasses and aortic resection. No organisms grew from the resected aortic wall. He was discharged in stable condition, and the ileostomy was reversed 9 months later...
August 2016: Aorta (Stamford, Conn.)
https://www.readbyqxmd.com/read/28096686/peptide-consensus-sequence-determination-for-the-enhancement-of-the-antimicrobial-activity-and-selectivity-of-antimicrobial-peptides
#17
Ammar Almaaytah, Ya'u Ajingi, Ahmad Abualhaijaa, Shadi Tarazi, Nizar Alshar'i, Qosay Al-Balas
The rise of multidrug-resistant bacteria is causing a serious threat to the world's human population. Recent reports have identified bacterial strains displaying pan drug resistance against antibiotics and generating fears among medical health specialists that humanity is on the dawn of entering a post-antibiotics era. Global research is currently focused on expanding the lifetime of current antibiotics and the development of new antimicrobial agents to tackle the problem of antimicrobial resistance. In the present study, we designed a novel consensus peptide named "Pepcon" through peptide consensus sequence determination among members of a highly homologous group of scorpion antimicrobial peptides...
2017: Infection and Drug Resistance
https://www.readbyqxmd.com/read/28096550/the-ups-and-downs-of-drug-discovery-the-early-history-of-fidaxomicin
#18
James B McAlpine
The path from antibiotic compound discovery to the market is marked by many potholes and its negotiation is often dependent on luck and persistence. Perhaps the prime example of this is the case of the development of tiacumicin B to Fidaxomicin, where both parameters were critical and the path was particularly circuitous.The Journal of Antibiotics advance online publication, 18 January 2017; doi:10.1038/ja.2016.157.
January 18, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28096548/the-synthesis-and-evaluation-of-the-antiproliferative-activity-of-deacidified-gex1a-analogues
#19
Takamichi Imaizumi, Hiroshi Nakagawa, Ran Hori, Yasuo Watanabe, Shiro Soga, Kyoichiro Iida, Hideyuki Onodera
GEX1A/herboxidiene (1) is a natural product isolated from Streptomyces sp. and has been reported to target the pre-mRNA splicing process. Although 1 was shown to have antitumor activity in vivo, weight loss was observed in mice when 1 was consecutively administered. We assumed that the carboxylic acid moiety was one of the causes of this toxicity. In this study, a series of amide, carbamate and urea analogues of 1 were synthesized and their antiproliferative activity was evaluated in vitro. The synthesis of urea analogues featured Curtius rearrangement following amine treatment with the one-pot procedure from 1...
January 18, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28096488/novel-superspreader-bacteriophages-promote-horizontal-gene-transfer-by-transformation
#20
Eric C Keen, Valery V Bliskovsky, Francisco Malagon, James D Baker, Jeffrey S Prince, James S Klaus, Sankar L Adhya
: Bacteriophages infect an estimated 10(23) to 10(25) bacterial cells each second, many of which carry physiologically relevant plasmids (e.g., those encoding antibiotic resistance). However, even though phage-plasmid interactions occur on a massive scale and have potentially significant evolutionary, ecological, and biomedical implications, plasmid fate upon phage infection and lysis has not been investigated to date. Here we show that a subset of the natural lytic phage population, which we dub "superspreaders," releases substantial amounts of intact, transformable plasmid DNA upon lysis, thereby promoting horizontal gene transfer by transformation...
January 17, 2017: MBio
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