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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
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
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
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
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
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
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
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...
July 26, 2016: Journal of Antimicrobial Chemotherapy
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
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
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
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
Ana Ramírez, Melina Ruggiero, Carlos Aranaga, Angel Cataldi, Gabriel Gutkind, Jacobus H de Waard, María Araque, Pablo Power
The objectives of this study were to determine the kinetic parameters of purified recombinant BlaMab and BlaMmas by spectrophotometry, analyze the genetic environment of the blaMab and blaMmas genes in both species by polymerase chain reaction and sequencing, furthermore, in silico models of both enzymes in complex with imipenem were obtained by modeling tools. Our results showed that BlaMab and BlaMmas have a similar hydrolysis behavior, displaying high catalytic efficiencies toward penams, cephalothin, and nitrocefin; none of the enzymes are well inhibited by clavulanate...
July 18, 2016: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
Najla Mathlouthi, Charbel Al-Bayssari, Sofiane Bakour, Jean Marc Rolain, Chedly Chouchani
The emergence and the global spread of carbapenemases concern to health services worldwide. Their celestial rise among Gram-negative bacilli has challenged both the scientific and pharmaceutical sectors. Indeed, infections caused by these bacteria have limited treatment options and have been associated with high mortality and morbidity rates. Carbapenemase producers are mainly identified among Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii and still mostly in hospital settings and rarely in the community...
July 7, 2016: Critical Reviews in Microbiology
Hyunsoo Kim, Ji Yeon Sung, Dongeun Yong, Seok Hoon Jeong, Wonkeun Song, Kyungwon Lee, Yunsop Chong
BACKGROUND: Rapid detection of carbapenemase-producing gram-negative bacilli (GNB) is required for optimal treatment of infected patients. We developed and assessed a new disk carbapenemase test (DCT). METHODS: Paper disks containing 0.3 mg of imipenem and bromothymol blue indicator were developed, and the performance of the DCT were evaluated by using 742 strains of GNB with or without carbapenemases. RESULTS: The paper disks were simple to prepare, and the dried disks were stable at -20°C and at 4°C...
September 2016: Annals of Laboratory Medicine
Jian Wang, Peijun He, Matthias Gaida, Shouhui Yang, Aaron J Schetter, Jochen Gaedcke, B Michael Ghadimi, Thomas Ried, Harris Yfantis, Dong Lee, Jonathan M Weiss, Jimmy Stauffer, Nader Hanna, H Richard Alexander, S Perwez Hussain
Pancreatic cancer is one of the most lethal malignancies and is refractory to the available treatments. Pancreatic ductal adenocarcinoma (PDAC) expresses high level of inducible nitric oxide synthase (NOS2), which causes sustained production of nitric oxide (NO). We tested the hypothesis that an aberrantly increased NO-release enhances the development and progression of PDAC. Enhanced NOS2 expression in tumors significantly associated with poor survival in PDAC patients (N = 107) with validation in independent cohorts...
June 29, 2016: Oncotarget
Yunliang Zhang, Xiaoyan Lin, Karen Bush
Eravacycline is a novel, fully synthetic fluorocycline antibiotic of the tetracycline class being developed for the treatment of complicated urinary tract infections and complicated intra-abdominal infections. Eravacycline has activity against many key Gram-negative pathogens, including Enterobacteriaceae resistant to carbapenems, cephalosporins, fluoroquinolones and β-lactam/β-lactamase inhibitor combinations, including strains that are multidrug-resistant. Carbapenem-resistant Enterobacteriaceae (CRE) isolates from 2010 to 2013 (n=110) were characterized for carbapenemase genes by PCR and sequencing...
August 2016: Journal of Antibiotics
Amy Mathers
There has been a dramatic increase in the last decade in the number of carbapenem-resistant Enterobacteriaceae, often leaving patients and their providers with few treatment options and resultant poor outcomes when an infection develops. The majority of the carbapenem resistance is mediated by bacterial acquisition of one of three carbapenemases (Klebsiella pneumoniae carbapenemase [KPC], oxacillinase-48-like [OXA-48], and the New Delhi metallo-β-lactamase [NDM]). Each of these enzymes has a unique global epidemiology and microbiology...
June 2016: Microbiology Spectrum
Carmine G Monteferrante, Sadaf Sultan, Marian T Ten Kate, Lennard J M Dekker, Katrin Sparbier, Markus Peer, Markus Kostzrewa, Theo M Luider, Wil H F Goessens, Peter C Burgers
OBJECTIVES: Carbapenemase-resistant bacteria are increasingly spreading worldwide causing public concern due to their ability to elude antimicrobial treatment. Early identification of these bacteria is therefore of high importance. Here, we describe the development of a simple and robust protocol for the detection of carbapenemase activity in clinical isolates of Enterobacteriaceae, suitable for routine and clinical applications. METHODS: The final protocol involves cellular lysis and enzyme extraction from a defined amount of bacterial cells followed by the addition of a benchmark drug (e...
October 2016: Journal of Antimicrobial Chemotherapy
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.
June 10, 2016: New Microbiologica
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