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https://www.readbyqxmd.com/read/27872078/polymyxin-b-in-combination-with-rifampin-and-meropenem-against-polymyxin-b-resistant-kpc-producing-klebsiella-pneumoniae
#1
John Diep, David M Jacobs, Rajnikant Sharma, Jenna Covelli, Dana R Bowers, Thomas A Russo, Gauri G Rao
Safe and effective therapies are urgently needed to treat polymyxin-resistant KPC-producing K. pneumoniae and suppress the emergence of resistance. We investigated the pharmacodynamics of polymyxin B, rifampin, and meropenem alone and as polymyxin B-based double and triple combinations against KPC-producing K. pneumoniae The rate and extent of killing with polymyxin B (1-128mg/L), rifampin (2-16mg/L), and meropenem (10-120mg/L) were evaluated against polymyxin B-susceptible (PB(S)) and -resistant (PB(R)) clinical isolates using 48h static time-kills...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27834322/a-structural-epidemiological-genetic-overview-of-klebsiella-pneumoniae-carbapenemases-kpcs
#2
REVIEW
C H Swathi, Rosy Chikala, K S Ratnakar, V Sritharan
Klebsiella pneumoniae carbapenemases (KPCs) are plasmid encoded carbapenem hydrolyzing enzymes which have the potential to spread widely through gene transfer. The instability of upstream region of blaKPC accelerates emergence of different isoforms. Routine antibiotic susceptibility testing failed to detect KPC producers and some commercial kits have been launched for early identification of KPC producers. Notable among the drugs under development against KPC are mostly derivatives of polymixin; ß-lactamase inhibitor NXL104 with combination of oxyimino cephalosporin as well as with ceftazidime; a novel tricyclic carbapenem, LK-157, potentially useful against class A and class C enzymes; BLI-489-a bicyclic penem derivative; PTK-0796, a tetracycline derivative and ACHN-490...
July 2016: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/27832961/emergence-of-colistin-resistance-in-the-largest-university-hospital-complex-of-s%C3%A3-o-paulo-brazil-over-five-years
#3
Flávia Rossi, Raquel Girardello, Ana Paula Cury, Thais Sabato Romano Di Gioia, João Nóbrega de Almeida, Alberto José da Silva Duarte
Colistin resistance involving Gram-negative bacilli infections is a challenge for health institutions around of the world. Carbapenem-resistance among these isolates makes colistin the last therapeutic option for this treatment. Colistin resistance among Enterobacteriaceae, Acinetobacter spp., and Pseudomonas spp. was evaluated between 2010 and 2014 years, at Hospital das Clínicas, São Paulo, Brazil. Over five years 1346 (4.0%) colistin resistant Gram-negative bacilli were evaluated. Enterobacteriaceae was the most frequent (86...
November 7, 2016: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27809803/a-prospective-study-of-treatment-of-carbapenem-resistant-enterobacteriaceae-infections-and-risk-factors-associated-with-outcome
#4
Claudia M D de Maio Carrilho, Larissa Marques de Oliveira, Juliana Gaudereto, Jamile S Perozin, Mariana Ragassi Urbano, Carlos H Camargo, Cintia M C Grion, Anna Sara S Levin, Silvia F Costa
BACKGROUND: To describe the clinical and microbiological data of carbapenem-resistant Enterobacteriaceae (CRE) infections, the treatment used, hospital- and infection-related mortality, and risk factors for death. METHODS: A prospective cohort conducted from March 2011 to December 2012. Clinical, demographic, and microbiological data such as in vitro sensitivity, clonality, carbapenemase gene mortality related to infection, and overall mortality were evaluated. Data were analyzed using Epi Info version 7...
November 3, 2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27800140/detection-of-kpc-carbapenemase-in-pseudomonas-aeruginosa-isolated-from-clinical-samples-using-modified-hodge-test-and-boronic-acid-phenotypic-methods-and-their-comparison-with-the-polymerase-chain-reaction
#5
Saeed Falahat, Mana Shojapour, Abdorrahim Sadeghi
BACKGROUND: Bacterial resistance to antibiotics has become a major source of concern for public health. Pseudomonas aeruginosa strains are important opportunistic pathogens. These bacteria have a high resistance to a wide range of existing antimicrobials and antibiotics. OBJECTIVES: The present study was performed to evaluate the frequency of KPC in P. aeruginosa isolated from clinical samples of educational hospitals of Arak University of Medical Sciences, using the mentioned phenotypic and genotypic methods...
September 2016: Jundishapur Journal of Microbiology
https://www.readbyqxmd.com/read/27797936/il-6-and-pd-l1-antibody-blockade-combination-therapy-reduces-tumour-progression-in-murine-models-of-pancreatic-cancer
#6
Thomas A Mace, Reena Shakya, Jason R Pitarresi, Benjamin Swanson, Christopher W McQuinn, Shannon Loftus, Emily Nordquist, Zobeida Cruz-Monserrate, Lianbo Yu, Gregory Young, Xiaoling Zhong, Teresa A Zimmers, Michael C Ostrowski, Thomas Ludwig, Mark Bloomston, Tanios Bekaii-Saab, Gregory B Lesinski
OBJECTIVE: Limited efficacy of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) has prompted investigation into combination therapy. We hypothesised that interleukin 6 (IL-6) blockade would modulate immunological features of PDAC and enhance the efficacy of anti-programmed death-1-ligand 1 (PD-L1) checkpoint inhibitor therapy. DESIGN: Transcription profiles and IL-6 secretion from primary patient-derived pancreatic stellate cells (PSCs) were analyzed via Nanostring and immunohistochemistry, respectively...
October 21, 2016: Gut
https://www.readbyqxmd.com/read/27795336/informing-antibiotic-treatment-decisions-evaluating-rapid-molecular-diagnostics-rmds-to-identify-susceptibility-and-resistance-to-carbapenems-against-acinetobacter-spp-primers-iii
#7
Scott R Evans, Andrea M Hujer, Hongyu Jiang, Carol B Hill, Kristine M Hujer, Jose R Mediavilla, Claudia Manca, Thuy Tien T Tran, T Nicholas Domitrovic, Paul G Higgins, Harald Seifert, Barry N Kreiswirth, Robin Patel, Michael R Jacobs, Liang Chen, Rangarajan Sampath, Thomas Hall, Christine Marzan, Vance G Fowler, Henry F Chambers, Robert A Bonomo
The widespread dissemination of carbapenem-resistant Acinetobacter spp. has created significant therapeutic challenges. At present, rapid molecular diagnostics (RMDs) that can identify this phenotype are not commercially available. Two RMD platforms, polymerase chain reaction combined with electrospray ionization mass spectrometry (PCR/ESI-MS) and molecular beacons (MB), for detecting genes conferring resistance/susceptibility to carbapenems in Acinetobacter spp. were evaluated. An archived collection of 200 clinical Acinetobacter spp...
October 26, 2016: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/27779106/targeted-delivery-of-chemotherapy-using-hsp90-inhibitor-drug-conjugates-is-highly-active-against-pancreatic-cancer-models
#8
Egor Bobrov, Natalia Skobeleva, Diana Restifo, Natalya Beglyarova, Kathy Q Cai, Elizabeth Handorf, Kerry Campbell, David A Proia, Vladimir Khazak, Erica A Golemis, Igor Astsaturov
The lack of effective treatment modalities is a major problem in pancreatic cancer (PCa), a devastating malignancy that is nearly universally driven by the "undruggable" KRAS and TP53 cancer genes. Poor tumor tissue penetration is the major source of resistance in pancreatic cancer where chemotherapy is the mainstay of treatment. In this study we exploited the selective tumor-targeting properties of the heat shock 90 protein inhibitors as the vehicle for drug delivery to pancreatic tumor tissues. STA-12-8666 is a novel esterase-cleavable conjugate of an HSP90i and a topoisomerase I inhibitor, SN-38...
October 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27739023/bacteriological-assessment-of-pneumonia-caused-by-gram-negative-bacteria-in-patients-hospitalized-in-intensive-care-unit
#9
A Guzek, Krzysztof Korzeniewski, D Tomaszewski, Z Rybicki, E Zwolińska
The article presents the results of 11-year study (2005-2015) of Gram-negative bacteria responsible for pneumonia in 2033 mechanically ventilated patients hospitalized in Intensive Care Unit. Of 8796 biological samples, consisting mainly of bronchial aspirate (97.9 %), 2056 bacterial strains were isolated and subjected to identification. VITEK 2 was used to determine drug susceptibility (classified according to the EUCAST criteria). ESBL, MBL and KPC-producing strains were identified by means of phenotypic methods using appropriate discs...
October 14, 2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27630840/a-pilot-study-on-carbapenemase-detection-do-we-see-the-same-level-of-agreement-as-with-the-clsi-observations
#10
Agila Kumari Pragasam, Rani Diana Sahni, Shalini Anandan, Archa Sharma, Radha Gopi, Noorjahan Hadibasha, Priya Gunasekaran, Balaji Veeraraghavan
INTRODUCTION: Rapid identification of carbapenemase producing organisms is of great importance for timely detection, treatment and implementation of control measures to prevent the spread. The Modified Hodge Test (MHT) and Carba NP test is recommended by CLSI for the detection of carbapenemases in Enterobacteriaceae. However, MHT may give false positive results or fail to detect metallo β-lactamases (MBLs). In the US, MHT is the most widely used test for detection of carbapenemases and has been found to have a sensitivity and specificity of >90% for bla KPC producers...
July 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/27602425/clostridium-difficile-ribotype-033-colitis-in-a-patient-following-broad-spectrum-antibiotic-treatment-for-kpcproducing-klebsiella-pneumoniae-infection-italy
#11
Stefano Grandesso, Fabio Arena, Franklin Esoka Eseme, Sandro Panese, Lucia Henrici De Angelis, Patrizia Spigaglia, Fabrizio Barbanti, Gian Maria Rossolini
This report describes a case of Clostridium difficile ribotype 033 colitis in a patient treated with multiple antibiotics for KPC-producing Klebsiella pneumoniae pancreatitis. Diagnostic, clinical and therapeutic features are discussed. To the best of our knowledge, this is the first case of C. difficile ribotype 033 clinical infection reported from Italy.
September 2016: New Microbiologica
https://www.readbyqxmd.com/read/27594855/tigecycline-amikacin-combination-effectively-suppresses-the-selection-of-resistance-in-clinical-isolates-of-kpc-producing-klebsiella-pneumoniae
#12
Wentao Ni, Chuanqi Wei, Chufei Zhou, Jin Zhao, Beibei Liang, Junchang Cui, Rui Wang, Youning Liu
By far, only tigecycline, colistin, and some aminoglycosides still show favorable in vitro activities against carbapenem-resistant Enterobacteriaceae. However, rapid emergence of resistance often occurs during long-term treatment in clinic, challenging these last resort antimicrobials. In this study, we measured mutant prevention concentration (MPC) and mutant selection window (MSW) of tigecycline, colistin and amikacin alone and in combination for clinical isolates of KPC-producing K. pneumoniae, and characterized the resistant mutants recovered...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27585707/molecular-epidemiology-of-carbapenem-resistant-gram-negative-bacilli-from-infected-pediatric-population-in-tertiary-care-hospitals-in-medell%C3%A3-n-colombia-an-increasing-problem
#13
Johanna M Vanegas, O Lorena Parra, J Natalia Jiménez
BACKGROUND: Gram-negative bacilli are a cause of serious infections in the pediatric population. Carbapenem are the treatment of choice for infections caused by multidrug-resistant Gram-negative bacilli, but the emergence of carbapenem resistance has substantially reduced access to effective antimicrobial regimens. Children are a population vulnerable to bacterial infections and the emergence of resistance can worsen prognosis. The aim of this study is to describe the clinical and molecular characteristics of infections caused by carbapenem-resistant Gram-negative bacilli in pediatric patients from five tertiary-care hospitals in Medellín, Colombia...
2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27545397/matrix-metalloproteinase-9-mmp-9-as-an-activator-of-nanosystems-for-targeted-drug-delivery-in-pancreatic-cancer
#14
Barbara Grünwald, Jennifer Vandooren, Erica Locatelli, Pierre Fiten, Ghislain Opdenakker, Paul Proost, Achim Krüger, Jean Paul Lellouche, Liron Limor Israel, Louis Shenkman, Mauro Comes Franchini
Specific cancer cell targeting is a pre-requisite for efficient drug delivery as well as for high-resolution imaging and still represents a major technical challenge. Tumor-associated enzyme-assisted targeting is a new concept that takes advantage of the presence of a specific activity in the tumor entity. MMP-9 is a protease found to be upregulated in virtually all malignant tumors. Consequently, we hypothesized that its presence can provide a de-shielding activity for targeted delivery of drugs by nanoparticles (NPs) in pancreatic cancer...
October 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27544976/-carbapenem-resistant-enterobacteriaceae-cre-a-menace-to-the-public-and-the-mechanisms-of-antimicrobial-resistance
#15
REVIEW
Ryuichi Nakano
Dissemination of carbapenem-resistant Enterobacteriaceae (CRE) poses a considerable threat to public health. Infections caused by CRE have limited treatment options and have been associated with high mortality rates. This resistance is largely the consequence of acquisition of carbapenemase genes. The genotypes in the geographical areas were initially different, as the Japanese epidemic was related to the IMP type (Class B), whereas the US epidemic was related to the KPC type (Class A). Thus, clinical detection of carbapenemase producers remains difficult based on each genotypes has specific screening method...
April 2016: Japanese Journal of Antibiotics
https://www.readbyqxmd.com/read/27494911/oral-decontamination-with-aminoglycosides-is-associated-with-lower-risk-of-mortality-and-infections-in-high-risk-patients-colonized-with-colistin-resistant-kpc-producing-klebsiella-pneumoniae
#16
Isabel Machuca, Belén Gutiérrez-Gutiérrez, Salvador Pérez Cortés, Irene Gracia-Ahufinger, Josefina Serrano, María Dolores Madrigal, José Barcala, Fernando Rodríguez-López, Jesús Rodríguez-Baño, Julián Torre-Cisneros
OBJECTIVES: Invasive infections caused by KPC-producing Klebsiella pneumoniae (KPCKP) are associated with very high mortality. Because infection is usually preceded by rectal colonization, we investigated if decolonization therapy (DT) with aminoglycosides had a protective effect in selected patients. METHODS: Patients with rectal colonization by colistin-resistant KPCKP who were at high risk of developing infection (because of neutropenia, surgery, previous recurrent KPCKP infections or multiple comorbidities) were followed for 180 days...
November 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27477421/bloodstream-infections-caused-by-klebsiella-pneumoniae-carbapenemase-2-producing-k-pneumoniae-at-a-hematology-department-in-wenzhou-china
#17
Chongyun Xing, Bei Ge, Kang Yu, Shenmeng Gao, Bin Liang, Haige Ye
The increasing prevalence of Klebsiella pneumoniae carbapenemase 2-producing K. pneumoniae (KPC-2-KP) infections can become a new life-threatening complication for hematological patients. Five cases of KPC-2-KP bloodstream infections have been identified in our hematology department over the past 10 years. The current treatment options do not show satisfactory efficacy, especially for bloodstream infections. The treatment of these five cases was unsuccessful, mainly due to the high minimum inhibitory concentrations of carbapenem, fosfomycin resistance, or the inaccessibility of polymyxin...
2016: Internal Medicine
https://www.readbyqxmd.com/read/27472388/microenvironment-mediated-alterations-to-metabolic-pathways-confer-increased-chemo-resistance-in-cd133-tumor-initiating-cells
#18
Alice Nomura, Patricia Dauer, Vineet Gupta, Olivia McGinn, Nivedita Arora, Kaustav Majumdar, Charles Uhlrich Iii, Joseph Dalluge, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee
Chemoresistance in pancreatic cancer has been attributed to tumor-initiating cells (TICs), a minor sub-population of tumor cells. However, the mechanism of chemo-resistance in these cells is still unclear.In the current study, immunohistochemical analysis of LSL-KrasG12D; LSL-Trp53R172H;PdxCre (KPC) murine tumors indicated that hypoxic regions developed through tumor progression. This hypoxic "niche" correlated with increased CD133+ population that had an increased HIF1A activity. Consistent with this observation, CD133+ cells had increased glucose uptake and activity of glycolytic pathway enzymes compared to CD133- cells...
July 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27471630/evaluation-of-innate-and-adaptive-immunity-contributing-to-the-antitumor-effects-of-pd1-blockade-in-an-orthotopic-murine-model-of-pancreatic-cancer
#19
Marcela D'Alincourt Salazar, Edwin R Manuel, Weimin Tsai, Massimo D'Apuzzo, Leanne Goldstein, Bruce R Blazar, Don J Diamond
Despite the clinical success of anti-PD1 antibody (α-PD1) therapy, the immune mechanisms contributing to the antineoplastic response remain unclear. Here, we describe novel aspects of the immune response involved in α-PD1-induced antitumor effects using an orthotopic Kras (G12D)/p53(R172H)/Pdx1-Cre (KPC) model of pancreatic ductal adenocarcinoma (PDA). We found that positive therapeutic outcome involved both the innate and adaptive arms of the immune system. Adoptive transfer of total splenocytes after short-term (3 d) but not long-term (28 d) PD1 blockade significantly extended survival of non-treated tumor-bearing recipient mice...
June 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27432599/spotlight-on-ceftazidime-avibactam-a-new-option-for-mdr-gram-negative-infections
#20
REVIEW
Marco Falcone, David Paterson
During the last decade infections caused by MDR Gram-negative bacteria (GNB) have become increasingly prevalent. Because of their high morbidity and mortality rates, these infections constitute a serious threat to public health worldwide. Ceftazidime/avibactam is a new approved agent combining ceftazidime and a novel β-lactamase inhibitor with activity against various β-lactamases produced by MDR GNB. Avibactam has a spectrum of inhibition of class A and C β-lactamases, including ESBLs, AmpC and Klebsiella pneumoniae carbapenemase (KPC) enzymes...
October 2016: Journal of Antimicrobial Chemotherapy
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