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Xiqi Li, Cesar A Arias, Samuel L Aitken, Jessica Galloway Peña, Diana Panesso, Michael Chang, Lorena Diaz, Rafael Rios, Yazan Numan, Sammi Ghaoui, Sruti DebRoy, Micah M Bhatti, Dawn E Simmons, Isaam Raad, Ray Hachem, Stephanie A Folan, Pranoti Sahasarabhojane, Awdhesh Kalia, Samuel A Shelburne
Background: Pathobionts, bacteria that are typically human commensals but can cause disease, contribute significantly to antimicrobial resistance. Staphylococcus epidermidis is a prototypical pathobiont as it is a ubiquitous human commensal but also a leading cause of healthcare-associated bacteremia. We sought to determine the etiology of a recent increase in invasive S. epidermidis isolates resistant to linezolid. Methods: Whole-genome sequencing (WGS) was performed on 176 S...
March 12, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Bhupesh Bagga, Savitri Sharma, Sai Jeevan Madhuri Guda, Ritu Nagpal, Joveeta Joseph, Kodiganti Manjulatha, Ashik Mohamed, Prashant Garg
BACKGROUND: Pythium insidiosum is a parafungus that causes keratitis resembling fungal keratitis. This study compares outcome in a large cohort of patients with P insidiosum keratitis treated with antifungal drugs, to a pilot group treated with antibacterial antibiotics. METHODS: Between January 2014 and December 2016, 114 patients with culture positive P insidiosum keratitis were included in the study. A subset of culture isolates was tested in vitro for response to nine antibacterial antibiotics by disc diffusion and E test...
March 15, 2018: British Journal of Ophthalmology
Cheon Tae Kim, Tae-Ok Kim, Hong-Joon Shin, Young Chun Ko, Yeong Hun Choe, Hak-Ryul Kim, Yong-Soo Kwon
Relatively little is known about the efficacy and safety of the programmatic use of bedaquiline and delamanid in multidrug-resistant tuberculosis (MDR-TB) treatment. This study evaluated 61 patients with MDR-TB treated with bedaquiline (n=39), delamanid (n=11), or both, either sequentially (n=10) or in co-administration (n=1), for more than 1 month, combined with a World Health Organization-recommended regimen. Of these, 49 (80.3%) were men and 12 (19.7%) were women. The median age was 53 years (interquartile range [IQR]=38...
March 15, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
P Ioannou, M Stavroulaki, V Mavrikaki, I Papakitsou, S Panagiotakis
WHAT IS KNOWN AND OBJECTIVE: Hyponatremia is the most common electrolyte disorder. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the main cause of euvolemic hyponatremia and is often associated with medications or underlying diseases. Linezolid is a potent antibiotic against resistant Gram-positive microorganisms that has been associated with mild hyponatremia, yet with a mechanism different from SIADH. CASE SUMMARY: We present the case of a patient who developed severe hyponatremia during treatment with linezolid for an ampicillin-resistant E...
March 14, 2018: Journal of Clinical Pharmacy and Therapeutics
Shuaishuai Ni, Baoli Li, Feifei Chen, Hanwen Wei, Fei Mao, Yifu Liu, Yixiang Xu, Xiaoxi Qiu, Xiaokang Li, Wenwen Liu, Linghao Hu, Dazheng Ling, Manjiong Wang, Xinyu Zheng, Jin Zhu, Lefu Lan, Jian Li
Diapophytoene desaturase (CrtN) is a potential novel target for intervening in the biosynthesis of the virulence factor staphyloxanthin. In this study, 38 1,4-benzodioxan-derived CrtN inhibitors were designed and synthesized to overwhelm the defects of leading compound 4a . Derivative 47 displayed superior pigment inhibitory activity, better hERG inhibitory properties and water solubility, and significantly sensitized MRSA strains to immune clearance in vitro. Notably, 47 displayed excellent efficacy against pigmented S...
March 8, 2018: ACS Medicinal Chemistry Letters
Megumi Yazaki, Takehiko Oami, Kazuya Nakanishi, Ryota Hase, Hiroyuki Watanabe
Although vancomycin administration is recommended for the treatment of infective endocarditis (IE) caused by methicillin-resistant Staphylococcus aureus (MRSA), it is unclear whether an alternative agent, daptomycin, can be used to treat IE with pulmonary complications. A 26-year-old female who had undergone surgical repair of a ventricular septal defect as an early teenager presented with fever, headache, and vomiting. She was admitted to our hospital and diagnosed with right-sided IE with septic pulmonary embolism caused by MRSA...
March 10, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
John Pham, Talal Asif, Majdi S Hamarshi
Methicillin-resistant S taphylococcus aureus (MRSA) was previously considered a purely nosocomial pathogen. However, community-acquired MRSA has recently emerged as an important cause of severe necrotizing community-acquired pneumonia (CA-MRSA) in previously healthy individuals. This new pathogen exhibits antibiotic resistance and is linked to extended hospital stay and higher mortality. CA-MRSA has presented new therapeutic challenges due to high vancomycin treatment failure and lack of specificity of clinical findings...
January 3, 2018: Curēus
Hiroshige Mikamo, Yoshio Takesue, Yuji Iwamoto, Takahiko Tanigawa, Masaharu Kato, Yoko Tanimura, Shigeru Kohno
The objective of this open-label, randomised (i.e. 2:1 ratio), Phase 3 study was to compare the efficacy and safety of tedizolid phosphate 200 mg, once-daily treatment with that of linezolid 600 mg, twice-daily treatment for 7-14 days in Japanese adult patients (N = 125) with skin and soft tissue infections (SSTIs) and/or for 7-21 days for those with SSTI-related bacteraemia, caused by confirmed or highly suspected methicillin-resistant Staphylococcus aureus (MRSA). Primary outcome was clinical cure rate at test-of-cure (TOC, in SSTI: 7-14 days, in bacteraemia: 4-6 weeks after end-of-therapy [EOT]) time point in the microbiologically evaluable MRSA (ME-MRSA) population (N = 39)...
March 9, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
Cathy Hardalo, Thomas P Lodise, Monique Bidell, Shawn Flanagan, Carisa De Anda, Steven Anuskiewicz, Philippe Prokocimer
BACKGROUND: We evaluated safety and tolerability of tedizolid phosphate at the 200-mg once-daily dose approved for 6-day treatment of skin and skin-structure infections. RESEARCH DESIGN AND METHODS: Clinical adverse event (AE) and laboratory data were pooled across completed clinical studies (13 phase 1, two phase 2, and two phase 3), for all participants who received ≥1 dose of tedizolid 200 mg, linezolid 600 mg (phase 3 only), or placebo (phase 1 only). RESULTS: 1280 participants received tedizolid (phase 1: n = 355; phase 2/3: n = 925)...
March 12, 2018: Expert Opinion on Drug Safety
Alexander Q Cusumano, Joshua G Pierce
Herein, we report the synthesis and evaluation of 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones as antibacterial agents against methicillin-resistant S. aureus (MRSA) and methicillin-resistant S. epidermidis (MRSE). Lead compound 38 showed minimum inhibitory concentrations (MICs) of 8 and 4 μg/mL against MRSA and MRSE, respectively. Furthermore, compound 38 displayed a MIC of 8-16 μg/mL against linezolid-resistant MRSA. These molecules, previously underexplored as antibacterial agents, serve as a new scaffold for antimicrobial development...
February 27, 2018: Bioorganic & Medicinal Chemistry Letters
Faidad Khan, Mohsin Ahmad Khan, Nadeem Ahmed, Muhammad Islam Khan, Hamid Bashir, Saad Tahir, Ahmad Usman Zafar
INTRODUCTION: Pakistan has one of the highest burdens of pneumococcal diseases in the world, but unfortunately studies in this demanding research area are limited in the region. Pneumococcal surface protein A (PspA) is the next generation pneumococcal vaccine candidate as the protein locates on the Streptococcus pneumoniae surface. Its gene, pspA, might be encoded by all pneumococci, and the protein has proven immunogenicity. The molecular characterization of PspA, pneumococcal serotype distribution and antibiotic susceptibility are important for regional diversity studies...
March 9, 2018: Infectious Diseases and Therapy
Vladimír Kmeť, Anna Čuvalová, Michal Stanko
A total of 39 coagulase-negative staphylococci and seven Staphylococcus aureus strains were isolated from small mammal feces, i.e., the striped field mouse (Apodemus agrarius) and the yellow-necked mouse (A. flavicollis) in two sampling areas, deciduous forest and karst plains. MALDI-TOF analysis revealed five species of coagulase-negative staphylococci: S. sciuri, S. hominis, S. warneri, S. haemolyticus, and S. xylosus. All strains were susceptible to tetracycline, linezolid, vancomycin, and teicoplanin. Three MRSA strains with the mecA gene were detected...
March 9, 2018: Folia Microbiologica
Katarzyna Talaga, Dalma Odrowąż-Konduracka, Beata Paradowska, Barbara Jagiencarz-Starzec, Zdzisław Wolak, Małgorzata Bulanda, Anna Szczypta
BACKGROUND: In the Małopolska province, the first case of vancomycin resistant enterococci (VRE) occurrence was an outbreak in 2001 caused by strains of the genus E. faecium carrying the vanA operon. OBJECTIVES: The aim of this study is to determine the antimicrobial resistance and the occurrence of virulence determinants among Enterococcus spp. in patients hospitalized in the Małopolska region in 2015. MATERIAL AND METHODS: Antimicrobial susceptibility was determined by disc diffusion and the E test...
January 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Anno de Jong, Shabbir Simjee, Farid El Garch, Hilde Moyaert, Markus Rose, Myriam Youala, Magdalena Dry
The European Antimicrobial Susceptibility Surveillance in Animals (EASSA) program collects zoonotic and commensal bacteria from food-producing animals at slaughter and tracks their susceptibility to medically important antibiotics. Results of commensal enterococci species (2013-2014) are presented here. Intestinal content from cattle, pigs and chickens were randomly sampled (5-6 countries/host; ≥4 abattoirs/country; 1 sample/animal/farm) for isolation of enterococci, MICs of 9 antibiotics were assessed by CLSI agar dilution in a central laboratory...
March 2018: Veterinary Microbiology
Whittney A Warren, Domingo Franco-Palacios, Christopher S King, Oksana A Shlobin, Steven D Nathan, Shalika B Katugaha, Haresh Mani, A Whitney Brown
A 24-year-old woman with ΔF508/Y1092X cystic fibrosis (CF) complicated by severe obstructive lung disease (FEV1 of 30% predicted) was admitted for IV antibiotics for planned sinus surgery resulting from severe chronic sinusitis causing frequent exacerbations and declining lung function. She had persistent airway infection with multidrug-resistant Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and growth of a fungus presumed to be an airway colonizer, identified as Stephanoascus ciferrii 1 year before presentation...
March 2018: Chest
Glen P Carter, Jitendra R Harjani, Lucy Li, Noel P Pitcher, Yi Nong, Thomas V Riley, Deborah A Williamson, Timothy P Stinear, Jonathan B Baell, Benjamin P Howden
Background: Enterococcus faecium is an important nosocomial pathogen. It has a high propensity for horizontal gene transfer, which has resulted in the emergence of MDR strains that are difficult to treat. The most notorious of these, vancomycin-resistant E. faecium, are usually treated with linezolid or daptomycin. Resistance has, however, been reported, meaning that new therapeutics are urgently needed. The 1,2,4-oxadiazoles are a recently discovered family of antimicrobials that are active against Gram-positive pathogens and therefore have therapeutic potential for treating E...
March 6, 2018: Journal of Antimicrobial Chemotherapy
Victoria Thwaites, Julia Colston, Jose Lomas-Cabeza, Zsolt Orosz
We report a case of an 88-year-old man with osteomyelitis of the right ankle, with histopathology demonstrating a Mycobacterium spindle cell pseudotumor. The Mycobacterium contained in this spindle cell pseudotumor was Mycobacterium chelonae. M. chelonae spindle cell pseudotumors are rare and have only been reported twice previously in the literature. Similarly, M. chelonae presenting as the pathogen in bone infection is rare. Due to this unusual presentation of M. chelonae, the antibiotic rationale was based largely on case reports and consisted of imipenem, clarithromycin, and linezolid...
January 2018: International Journal of Mycobacteriology
D Raszka, S Popelka, J Heřt, D Jahoda, I Landor, P Vavřík
Nocardiosis is a rare infection caused by the aerobic actinomycete of the Nocardia genus. In most cases, nocardiosis manifests as a lung infection or a bone lesion. Due to the nonspecific and mild clinical manifestations of nocardiosis, the establishment of definite diagnosis can be difficult. When antibiotic therapy is incorrectly targeted, only the symptoms of the disease are suppressed. The mainstay in the treatment of Nocardia osteomyelitis has so far been the combined surgical debridement with long-term, initially intravenous, antibiotic administration...
March 5, 2018: Folia Microbiologica
Diego B Nobrega, Sohail Naushad, S Ali Naqvi, Larissa A Z Condas, Vineet Saini, John P Kastelic, Christopher Luby, Jeroen De Buck, Herman W Barkema
Emergence and spread of antimicrobial resistance is a major concern for the dairy industry worldwide. Objectives were to determine: (1) phenotypic and genotypic prevalence of drug-specific resistance for 25 species of non-aureus staphylococci, and (2) associations between presence of resistance determinants and antimicrobial resistance. Broth micro-dilution was used to determine resistance profiles for 1,702 isolates from 89 dairy herds. Additionally, 405 isolates were sequenced to screen for resistance determinants...
2018: Frontiers in Microbiology
Chih-Ning Cheng, Shu-Wen Lin, Chien-Chih Wu
Linezolid, an oxazolidinone antibiotic, does not required dose adjustment in patients with Child's class A and B liver cirrhosis. The dose adjustment data for Child's class C liver cirrhosis is inadequate. We reported a case of Child's class C liver cirrhosis, in which lactic acidosis, an adverse effect related to prolonged use, occurred only after two weeks of linezolid treatment. A 63-year old male had underlying diseases, such as end-stage renal disease (ESRD) and Child's class C liver cirrhosis, and was admitted for hepatic encephalopathy management and liver transplantation evaluation...
March 1, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
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