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https://www.readbyqxmd.com/read/28102514/carbapenemase-producing-klebsiella-pneumoniae-bloodstream-infection-in-critically-ill-patients-risk-factors-and-predictors-of-mortality
#1
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/28089736/antibacterial-activity-of-limonium-brasiliense-baicuru-against-multidrug-resistant-bacteria-using-a-statistical-mixture-design
#2
Andressa Blainski, Barbara Gionco, Admilton G Oliveira, Galdino Andrade, Ieda S Scarminio, Denise B Silva, Norberto P Lopes, João C P Mello
ETHNOPHARMACOLOGICAL RELEVANCE: Limonium brasiliense (Boiss.) Kuntze (Plumbaginaceae) is commonly known as "baicuru" or "guaicuru" and preparations of its dried rhizomes have been populary used in the treatment of premenstrual syndrome and menstrual disorder, and as an antiseptic in genito-urinary infections. This study evaluated the potential antibacterial activity of rhizome extracts against multidrug-resistant bacterial strains using statistical mixture design. MATERIALS AND METHODS: The statistical design of four components (water, methanol, acetone and ethanol) produced 15 different extracts and also a confirmatory experiment, which was performed using water:acetone (3:7, v/v)...
January 13, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28077438/fibroblast-drug-scavenging-increases-intratumoural-gemcitabine-accumulation-in-murine-pancreas-cancer
#3
E Hessmann, M S Patzak, L Klein, N Chen, V Kari, I Ramu, T E Bapiro, K K Frese, A Gopinathan, F M Richards, D I Jodrell, C Verbeke, X Li, R Heuchel, J M Löhr, S A Johnsen, T M Gress, V Ellenrieder, A Neesse
OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28065546/discharge-of-kpc-2-genes-from-the-wwtps-contributed-to-their-enriched-abundance-in-the-receiving-river
#4
Fengxia Yang, Liang Huang, Linyun Li, Yang Yang, Daqing Mao, Yi Luo
At present, very little is known about the persistence and spread pathway of KPC-2 genes in the environment. Our previous study reported the prevalence and persistence of KPC-2 genes in wastewater treatment plants (WWTPs). In the present work, we investigated the occurrence and fate of KPC-2 genes in a WWTP discharge-receiving river and studied the effect of WWTP discharges on the prevalence of KPC-2 genes and host bacteria in the receiving river. It is observed that a considerable level of KPC-2 genes occurred in the receiving river, and a significant increase of blaKPC-2 abundance in the downstream following WWTP discharge was observed compared to the upstream...
January 5, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28040408/polymyxin-b-in-combination-with-meropenem-against-carbapenemase-producing-klebsiella-pneumoniae-pharmacodynamics-and-morphological-changes
#5
Rajnikant Sharma, Saloni Patel, Cely Abboud, John Diep, Neang S Ly, Jason M Pogue, Keith S Kaye, Jian Li, Gauri G Rao
Combination therapy provides a useful therapeutic approach to overcome resistance until new antibiotics become available. In this study, the pharmacodynamics, including the morphological effects, of polymyxin B (PMB) and meropenem alone and in combination against KPC-producing Klebsiella pneumoniae clinical isolates was examined. Ten clinical isolates were obtained from patients undergoing treatment for mediastinitis. KPCs were identified and MICs were measured using microbroth dilution. Time-kill studies were conducted over 24 h with PMB (0...
December 23, 2016: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28031201/emergence-of-ceftazidime-avibactam-resistance-due-to-plasmid-borne-blakpc-3-mutations-during-treatment-of-carbapenem-resistant-klebsiella-pneumoniae-infections
#6
Ryan K Shields, Liang Chen, Shaoji Cheng, Kalyan D Chavda, Ellen G Press, Avin Snyder, Ruchi Pandey, Yohei Doi, Barry N Kreiswirth, M Hong Nguyen, Cornelius J Clancy
Ceftazidime-avibactam is a novel β-lactam/β-lactamase inhibitor with activity against carbapenem-resistant Enterobacteriaceae (CRE) that produce Klebsiella pneumoniae carbapenemase (KPC). We report the first cases of ceftazidime-avibactam resistance to develop during treatment of CRE infections, and identify resistance mechanisms. Ceftazidime-avibactam resistant K. pneumoniae emerged in three patients after ceftazidime-avibactam treatment for 10-19 days. Whole genome sequencing (WGS) of longitudinal ceftazidime-avibactam susceptible and resistant K...
December 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28031200/low-frequency-of-ceftazidime-avibactam-resistance-among-enterobacteriaceae-isolates-carrying-blakpc-collected-in-hospitals-from-the-united-states-from-2012-to-2015
#7
Mariana Castanheira, Rodrigo E Mendes, Helio S Sader
KPC-producing Enterobacteriaceae isolates have been increasingly reported worldwide and therapeutic options to treat infections caused by these organisms are limited. We evaluated the activity of ceftazidime-avibactam and comparators against 456 Enterobacteriaceae isolates carrying blaKPC collected from 79 United States hospitals during 2012-2015. Overall, ceftazidime-avibactam (MIC50/90, 0.5/2 μg/mL; 99.3% susceptible) and tigecycline (MIC50/90, 0.5/1 μg/mL; 98.9% at ≤2 μg/mL) were the most active agents...
December 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28013264/comparing-the-outcomes-of-patients-with-carbapenemase-producing-and-non-carbapenemase-producing-carbapenem-resistant-enterobacteriaceae-bacteremia
#8
Pranita D Tamma, Katherine E Goodman, Anthony D Harris, Tsigereda Tekle, Ava Roberts, Abimbola Taiwo, Patricia J Simner
BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) are associated with considerable mortality. As mechanisms of carbapenem resistance are heterogeneous, it is unclear if mortality differs based on resistance mechanisms. We sought to determine whether CRE resistance mechanism determination is prognostically informative. METHODS: We conducted an observational study comparing 14-day mortality between patients with carbapenemase-producing (CP)-CRE compared with non-CP-CRE bacteremia...
February 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28012683/might-real-time-pharmacokinetic-pharmacodynamic-optimisation-of-high-dose-continuous-infusion-meropenem-improve-clinical-cure-in-infections-caused-by-kpc-producing-klebsiella-pneumoniae
#9
Federico Pea, Paola Della Siega, Piergiorgio Cojutti, Assunta Sartor, Massimo Crapis, Claudio Scarparo, Matteo Bassetti
The effect of real-time pharmacokinetic/pharmacodynamic (PK/PD) optimisation of high-dose continuous-infusion meropenem on the clinical outcome of patients receiving combination antimicrobial therapy for treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections was retrospectively assessed. Data for all patients with KPC-Kp-related infections who received antimicrobial combination therapy containing high-dose continuous-infusion meropenem optimised by means of therapeutic drug monitoring (TDM) were retrieved...
December 8, 2016: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/27942042/faecal-carriage-of-gram-negative-multidrug-resistant-bacteria-among-patients-hospitalized-in-two-centres-in-ulaanbaatar-mongolia
#10
Bayaraa Baljin, Ganbaatar Baldan, Battogtokh Chimeddorj, Khosbayar Tulgaa, Batbaatar Gunchin, Tsogtsaikhan Sandag, Klaus Pfeffer, Colin R MacKenzie, Andreas F Wendel
Gram-negative multidrug-resistant organisms (GN-MDRO) producing β-lactamases (ESBL, plasmid-mediated AmpC β-lactamases and carbapenemases) are increasingly reported throughout Asia. The aim of this surveillance study was to determine the rate of bacterial colonization in patients from two hospitals in the Mongolian capital Ulaanbaatar. Rectal swabs were obtained from patients referred to the National Traumatology and Orthopaedics Research Centre (NTORC) or the Burn Treatment Centre (BTC) between July and September 2014, on admission and again after 14 days...
2016: PloS One
https://www.readbyqxmd.com/read/27932443/pd-l1-blockade-enhances-response-of-pancreatic-ductal-adenocarcinoma-to-radiotherapy
#11
Abul Azad, Su Yin Lim, Zenobia D'Costa, Keaton Jones, Angela Diana, Owen J Sansom, Philipp Kruger, Stanley Liu, W Gillies McKenna, Omer Dushek, Ruth J Muschel, Emmanouil Fokas
Pancreatic ductal adenocarcinoma (PDAC) is considered a non-immunogenic tumor, and immune checkpoint inhibitor monotherapy lacks efficacy in this disease. Radiotherapy (RT) can stimulate the immune system. Here, we show that treatment of KPC and Pan02 murine PDAC cells with RT and gemcitabine upregulated PD-L1 expression in a JAK/Stat1-dependent manner. In vitro, PD-L1 inhibition did not alter radio- and chemosensitivity. In vivo, addition of anti-PD-L1 to high (12, 5 × 3, 20 Gy) but not low (6, 5 × 2 Gy) RT doses significantly improved tumor response in KPC and Pan02 allografts...
December 8, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27872078/polymyxin-b-in-combination-with-rifampin-and-meropenem-against-polymyxin-b-resistant-kpc-producing-klebsiella-pneumoniae
#12
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
#13
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
#14
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 8, 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
#15
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
#16
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
#17
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-to-identify-susceptibility-and-resistance-to-carbapenems-against-acinetobacter-spp-in-primers-iii
#18
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, PCR 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 sp...
January 2017: 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
#19
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
#20
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
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