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James Albiero, Sherwin K B Sy, Josmar Mazucheli, Silvana Martins Caparroz-Assef, Bruno Buranello Costa, Janio Leal Borges Alves, Ana Cristina Gales, Maria Cristina Bronharo Tognim
KPC-producing Klebsiella pneumoniae causes serious infections associated with high death rates worldwide. Combination therapy consisting of fosfomycin and a carbapenem is better than monotherapy to combat multidrug-resistant microorganisms, but no dosages for the combination have been defined. The MICs of meropenem and fosfomycin were evaluated against 18 clinical isolates of KPC-2-producing K. pneumoniae The activities of combination antimicrobials were also determined by the checkerboard method. The MIC50 and MIC90 of each agent alone and in combination were challenged against short (1...
July 2016: Antimicrobial Agents and Chemotherapy
Chad R Marion, Jianmiao Wang, Lokesh Sharma, Ashley Losier, Wei Lui, Nathaniel Andrews, Jack A Elias, Barbara I Kazmierczak, Craig R Roy, Charles S Dela Cruz
Pseudomonas aeruginosa causes hospital-acquired pneumonia and is associated with high mortality. An effective response to such an infection includes efficient clearance of pathogenic organisms while limiting collateral damage from the host inflammatory response, known as host resistance and host tolerance, respectively. P. aeruginosa expresses a type III secretion system (T3SS) needle complex that induces NLRC4 (NOD-like receptor C4) activation, interleukin-1β (IL-1β) production, and host tissue damage. Chitinase 3-like-1 (Chil1) is expressed during infection and binds to its receptor, IL-13 receptor α2 (IL-13Rα2), to regulate the pathogen-host response during Streptococcus pneumoniae infection, but the role Chil1 plays in balancing the host resistance and host tolerance during P...
July 2016: Infection and Immunity
Itzhak Brook
Anaerobes are the most predominant components of the normal human skin and mucous membranes bacterial flora, and are a frequent cause of endogenous bacterial infections. Anaerobic infections can occur in all body locations: the central nervous system, oral cavity, head and neck, chest, abdomen, pelvis, skin, and soft tissues. Treatment of anaerobic infection is complicated by their slow growth in culture, by their polymicrobial nature and by their growing resistance to antimicrobials. Antimicrobial therapy is frequently the only form of therapy needed, whereas in others it is an important adjunct to drainage and surgery...
January 2016: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
David van Duin, Robert A Bonomo
Ceftolozane/tazobactam and ceftazidime/avibactam are 2 novel β-lactam/β-lactamase combination antibiotics. The antimicrobial spectrum of activity of these antibiotics includes multidrug-resistant (MDR) gram-negative bacteria (GNB), including Pseudomonas aeruginosa. Ceftazidime/avibactam is also active against carbapenem-resistant Enterobacteriaceae that produce Klebsiella pneumoniae carbapenemases. However, avibactam does not inactivate metallo-β-lactamases such as New Delhi metallo-β-lactamases. Both ceftolozane/tazobactam and ceftazidime/avibactam are only available as intravenous formulations and are dosed 3 times daily in patients with normal renal function...
July 15, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Bruno Adler Maccagnan Pinheiro Besen, Marcelo Park
No abstract text is available yet for this article.
January 2016: Revista da Associação Médica Brasileira
Kevin S Gregg, Carol A Kauffman
Invasive aspergillosis remains an often fatal, difficult-to treat infection in immunocompromised patients. Patients not classically defined as immunocompromised, especially those in an intensive care unit setting, also develop invasive aspergillosis. Clinical clues suggesting angioinvasion and radiographic modalities, especially computed tomographic scans, combined with newer non-culture-based diagnostic techniques, have allowed earlier recognition of invasive aspergillosis. Although mortality remains high, it has greatly decreased over the past 15 years...
October 2015: Seminars in Respiratory and Critical Care Medicine
Stephen J Wood, Josef W Goldufsky, Daniella Bello, Sara Masood, Sasha H Shafikhani
Pseudomonas aeruginosa is the most common cause of hospital-acquired pneumonia and a killer of immunocompromised patients. We and others have demonstrated that the type III secretion system (T3SS) effector protein ExoT plays a pivotal role in facilitating P. aeruginosa pathogenesis. ExoT possesses an N-terminal GTPase-activating protein (GAP) domain and a C-terminal ADP-ribosyltransferase (ADPRT) domain. Because it targets multiple non-overlapping cellular targets, ExoT performs several distinct virulence functions for P...
November 27, 2015: Journal of Biological Chemistry
Odilo Engel, Levent Akyüz, Andrey C da Costa Goncalves, Katarzyna Winek, Claudia Dames, Mareike Thielke, Susanne Herold, Chotima Böttcher, Josef Priller, Hans Dieter Volk, Ulrich Dirnagl, Christian Meisel, Andreas Meisel
BACKGROUND AND PURPOSE: Temporary immunosuppression has been identified as a major risk factor for the development of pneumonia after acute central nervous system injury. Although overactivation of the sympathetic nervous system was previously shown to mediate suppression of systemic cellular immune responses after stroke, the role of the parasympathetic cholinergic anti-inflammatory pathway in the antibacterial defense in lung remains largely elusive. METHODS: The middle cerebral artery occlusion model in mice was used to examine the influence of the parasympathetic nervous system on poststroke immunosuppression...
November 2015: Stroke; a Journal of Cerebral Circulation
A M Thompson, S E Thomas, S J Schafers, A P Hartmann, W B Call, J Bushwitz, E N Deal
WHAT IS KNOWN AND OBJECTIVE: Healthcare-associated pneumonia (HCAP) is an important presentation among hospitalized patients. Standardized definitions of this entity are almost a decade old, and practice patterns have shifted from published guidelines to include empiric coverage with a macrolide, such as azithromycin. Azithromycin is oftentimes included in the empiric treatment regimen for HCAP because of the importance of appropriate empiric antimicrobial coverage, the perceived concern regarding atypical organisms, potential anti-inflammatory effects of the medication, and positive clinical data among patients with Streptococcal bacteremia...
October 2015: Journal of Clinical Pharmacy and Therapeutics
Ghalia Sabbagh, Noura Berakdar
Escherichia coli is one of the most frequent causes of many common bacterial infections, including cholecystitis, bacteremia, cholangitis, urinary tract infection (UTI), traveler's diarrhea and other clinical infections such as neonatal meningitis and pneumonia. The fatty acid biosynthesis is essential for the bacterial viability and growth. There are three types of β-ketoacyl acyl carrier protein synthase (KAS) which are important for overcoming the bacterial resistance problem. β-ketoacyl acyl carrier protein synthase I (KAS I) is member of the condensing enzyme family, which is a key catalyst in bacterial fatty acid biosynthesis, and thus an attractive target for novel antibioticsis related to the elongation of unsaturated fatty acids in bacterial fatty acid synthesis and can be a good therapeutic target of designing novel antibiotics...
September 2015: Journal of Molecular Graphics & Modelling
Hao-Yuan Lee, Chyi-Liang Chen, Shu-Ying Liu, Yu-Shan Yan, Chee-Jen Chang, Cheng-Hsun Chiu
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was associated with high mortality, but the risk factors associated with mortality remain controversial. METHODS: A retrospective cohort study was designed. All patients with MRSA bacteremia admitted were screened and collected for their clinical presentations and laboratory characteristics. Minimum inhibitory concentration (MIC) and staphylococcal cassette chromosome mec (SCCmec) type of bacterial isolates were determined...
2015: PloS One
Jared L Crandon, David P Nicolau
We evaluated the in vitro potency of cefepime combined with AAI101, a novel extended-spectrum β-lactamase inhibitor, against a population of clinical Escherichia coli and Klebsiella pneumoniae collected from USA hospitals. Of the 223 cefepime non-susceptible isolates, 95% were ceftazidime non-susceptible, 49% ertapenem non-susceptible, 57% piperacillin/tazobactam non-susceptible, 90% were multidrug-resistant (resistant to ≥3 drug classes), 22% produced carbapenemases, and 67% produced ESBLs. Addition of AAI101 restored the activity of cefepime such that the MIC50 was reduced from >64 mg/L for cefepime to 0...
2015: Pathogens
Yasir Alhamdi, Daniel R Neill, Simon T Abrams, Hesham A Malak, Reham Yahya, Richard Barrett-Jolley, Guozheng Wang, Aras Kadioglu, Cheng-Hock Toh
Streptococcus pneumoniae accounts for more deaths worldwide than any other single pathogen through diverse disease manifestations including pneumonia, sepsis and meningitis. Life-threatening acute cardiac complications are more common in pneumococcal infection compared to other bacterial infections. Distinctively, these arise despite effective antibiotic therapy. Here, we describe a novel mechanism of myocardial injury, which is triggered and sustained by circulating pneumolysin (PLY). Using a mouse model of invasive pneumococcal disease (IPD), we demonstrate that wild type PLY-expressing pneumococci but not PLY-deficient mutants induced elevation of circulating cardiac troponins (cTns), well-recognized biomarkers of cardiac injury...
May 2015: PLoS Pathogens
Angela R Branche, Edward E Walsh, Roberto Vargas, Barbara Hulbert, Maria A Formica, Andrea Baran, Derick R Peterson, Ann R Falsey
BACKGROUND: Viral lower respiratory tract illness (LRTI) frequently causes adult hospitalization and is linked to antibiotic overuse. European studies suggest that the serum procalcitonin (PCT) level may be used to guide antibiotic therapy. We conducted a trial assessing the feasibility of using PCT algorithms with viral testing to guide antibiotic use in a US hospital. METHODS: Three hundred patients hospitalized with nonpneumonic LRTI during October 2013-April 2014 were randomly assigned at a ratio of 1:1 to receive standard care or PCT-guided care and viral PCR testing...
December 1, 2015: Journal of Infectious Diseases
Mbiye A Mpenge, Alasdair P MacGowan
Ceftaroline is a new parenteral cephalosporin approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of complicated skin and soft tissue infections (cSSTIs) including those due to methicillin-resistant Staphylococcus aureus (MRSA), and community-acquired pneumonia (CAP). Ceftaroline has broad-spectrum activity against gram-positive and gram-negative bacteria and exerts its bactericidal effects by binding to penicillin-binding proteins (PBPs), resulting in inhibition of bacterial cell wall synthesis...
2015: Therapeutics and Clinical Risk Management
Rodney Dawson, Andreas H Diacon, Daniel Everitt, Christo van Niekerk, Peter R Donald, Divan A Burger, Robert Schall, Melvin Spigelman, Almari Conradie, Kathleen Eisenach, Amour Venter, Prudence Ive, Liesl Page-Shipp, Ebrahim Variava, Klaus Reither, Nyanda E Ntinginya, Alexander Pym, Florian von Groote-Bidlingmaier, Carl M Mendel
BACKGROUND: New antituberculosis regimens are urgently needed to shorten tuberculosis treatment. Following on from favourable assessment in a 2 week study, we investigated a novel regimen for efficacy and safety in drug-susceptible and multidrug-resistant (MDR) tuberculosis during the first 8 weeks of treatment. METHODS: We did this phase 2b study of bactericidal activity--defined as the decrease in colony forming units (CFUs) of Mycobacterium tuberculosis in the sputum of patients with microscopy smear-positive pulmonary tuberculosis-at eight sites in South Africa and Tanzania...
May 2, 2015: Lancet
Andreas H Diacon, Rodney Dawson, Florian von Groote-Bidlingmaier, Gregory Symons, Amour Venter, Peter R Donald, Christo van Niekerk, Daniel Everitt, Jane Hutchings, Divan A Burger, Robert Schall, Carl M Mendel
RATIONALE: New regimens to shorten tuberculosis treatment and manage patients with drug-resistant tuberculosis who are infected with HIV are urgently needed. Experimental and clinical evidence suggests that the new drugs bedaquiline (B) and pretomanid (Pa), combined with an existing drug, pyrazinamide (Z), and a repurposed drug, clofazimine (C), may assist treatment shortening of drug-susceptible and drug-resistant tuberculosis. OBJECTIVES: To evaluate the 14-day bactericidal activity of C and Z in monotherapy and in combinations with Pa and B...
April 15, 2015: American Journal of Respiratory and Critical Care Medicine
Keith C Meyer, Ganesh Raghu, Geert M Verleden, Paul A Corris, Paul Aurora, Kevin C Wilson, Jan Brozek, Allan R Glanville
Bronchiolitis obliterans syndrome (BOS) is a major complication of lung transplantation that is associated with poor survival. The International Society for Heart and Lung Transplantation, American Thoracic Society, and European Respiratory Society convened a committee of international experts to describe and/or provide recommendations for 1) the definition of BOS, 2) the risk factors for developing BOS, 3) the diagnosis of BOS, and 4) the management and prevention of BOS. A pragmatic evidence synthesis was performed to identify all unique citations related to BOS published from 1980 through to March, 2013...
December 2014: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Daniel M Musher, Anna R Thorner
New England Journal of Medicine, Volume 372, Issue 3, Page 292-294, January 2015.
January 15, 2015: New England Journal of Medicine
Antonio DiGiandomenico, Ashley E Keller, Cuihua Gao, Godfrey J Rainey, Paul Warrener, Mareia M Camara, Jessica Bonnell, Ryan Fleming, Binyam Bezabeh, Nazzareno Dimasi, Bret R Sellman, Jamese Hilliard, Caitlin M Guenther, Vivekananda Datta, Wei Zhao, Changshou Gao, Xiang-Qing Yu, JoAnn A Suzich, C Kendall Stover
Widespread drug resistance due to empiric use of broad-spectrum antibiotics has stimulated development of bacteria-specific strategies for prophylaxis and therapy based on modern monoclonal antibody (mAb) technologies. However, single-mechanism mAb approaches have not provided adequate protective activity in the clinic. We constructed multifunctional bispecific antibodies, each conferring three mechanisms of action against the bacterial pathogen Pseudomonas aeruginosa by targeting the serotype-independent type III secretion system (injectisome) virulence factor PcrV and persistence factor Psl exopolysaccharide...
November 12, 2014: Science Translational Medicine
2014-11-21 06:41:42
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