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Gregory G Stone, Paul Newell, Leanne B Gasink, Helen Broadhurst, Angela Wardman, Katrina Yates, Zhangjing Chen, Jie Song, Joseph W Chow
Objectives: This analysis evaluated the clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa isolates pooled from the adult Phase III clinical trials in patients with complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI) or nosocomial pneumonia (NP) including ventilator-associated pneumonia (VAP). Methods: Baseline isolates from five Phase III randomized controlled trials of ceftazidime/avibactam versus predominantly carbapenem comparators in patients with cIAI (RECLAIM 1 and 2; NCT01499290 and RECLAIM 3; NCT01726023), cUTI (RECAPTURE 1 and 2; NCT01595438 and NCT01599806), NP including VAP (REPROVE; NCT01808092) and cIAI or cUTI caused by ceftazidime-non-susceptible Gram-negative pathogens (REPRISE; NCT01644643) were tested for MDR status and susceptibility to ceftazidime/avibactam and carbapenem-based comparators using CLSI broth microdilution methodology...
June 14, 2018: Journal of Antimicrobial Chemotherapy
Lu Liu, Yu Feng, Alan McNally, Zhiyong Zong
Objectives: New Delhi MBL (NDM) is a type of carbapenemase; 20 variants of NDM have been identified to date. We have found a new variant of NDM, NDM-21, and describe it here. Methods: A carbapenem-resistant Escherichia coli was subjected to WGS using an Illumina X10 sequencer to identify the antimicrobial resistance genes and its ST. The gene encoding the new variant of NDM was cloned into E. coli DH5α, with blaNDM-5 being cloned as the control. Transformants were tested for susceptibility to carbapenems...
June 14, 2018: Journal of Antimicrobial Chemotherapy
Bao-Tao Liu, Xiao-Yan Zhang, Shu-Wei Wan, Jun-Jie Hao, Rui-De Jiang, Feng-Jing Song
Vegetables harboring bacteria resistant to antibiotics are a growing food safety issue. However, data concerning carbapenem-resistant Enterobacteriaceae (CRE) in ready-to-eat fresh vegetables is still rare. In this study, 411 vegetable samples from 36 supermarkets or farmer's markets in 18 cities in China, were analyzed for CRE. Carbapenemase-encoding genes and other resistance genes were analyzed among the CRE isolates. Plasmids carrying carbapenemase genes were studied by conjugation, replicon typing, S1-PFGE southern blot, restriction fragment length polymorphism (RFLP), and sequencing...
2018: Frontiers in Microbiology
Zishuo Cheng, Pei W Thomas, Lincheng Ju, Alexander Bergstrom, Kelly Mason, Delaney Clayton, Callie Miller, Christopher R Bethel, Jamie VanPelt, David L Tierney, Richard C Page, Robert A Bonomo, Walter Fast, Michael W Crowder
Infections by carbapenem-resistant Enterobacteriaceae (CRE) are difficult to manage owing to broad antibiotic resistance profiles and because of the inability of clinically-used β-lactamase inhibitors to counter the activity of metallo-β-lactamases often harbored by these pathogens. Of particular importance is New Delhi metallo-β-lactamase (NDM), which requires a dinuclear zinc ion cluster for catalytic activity. Here, we compare the structures and functions of clinical NDM variants 1-17. The impact of NDM variants on structure is probed by comparing comparing melting temperature and refolding efficiency and also by spectroscopy (UV-Vis, 1 H-NMR, and EPR) of di-cobalt metalloforms...
June 16, 2018: Journal of Biological Chemistry
Olfa Dziri, Carla Andrea Alonso, Raoudha Dziri, Haythem Gharsa, Abderrahmen Maraoub, Carmen Torres, Chedly Chouchani
Carbapenem resistance in Gram-negative bacteria constitutes a major clinical problem. We propose to characterize molecular features among carbapenem-resistant Gram-negative clinical isolates collected from Southeastern Tunisian Island Hospital. Eighteen carbapenem-resistant clinical isolates (13 Klebsiella pneumoniae, 1 Proteus mirabilis, 1 Enterobacter cloacae, 3 Acinetobacter baumannii) were recovered during April 2015-August 2016. Molecular characterization of antimicrobial resistance was performed by PCR and sequencing...
June 14, 2018: International Journal of Antimicrobial Agents
Kazuhiko Nakaharai, Kojiro Morita, Taisuke Jo, Hiroki Matsui, Kiyohide Fushimi, Hideo Yasunaga
OBJECTIVES: Previous studies evaluating the clinical benefits of prophylactic antibiotics for severe acute pancreatitis (SAP) have generated inconsistent results due to heterogeneities among the study settings. We determined if early prophylactic antibiotics improved the outcomes of SAP patients using a study designed to overcome these previous methodological weaknesses. METHODS: We conducted a retrospective cohort study of SAP patients discharged between July 2010 and March 2016, using a Japanese nationwide inpatient database...
June 13, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
Chia-Yi Lien, Jun-Jun Lee, Chun-Chih Chien, Chi-Ren Huang, Cheng-Hsien Lu, Wen-Neng Chang
Adult bacterial meningitis (ABM) caused by Citrobacter (C.) infection is very uncommon and the clinical characteristics of this specific infectious syndrome have not been analyzed in the literature. The clinical characteristics of six Citrobacter ABM patients collected during a study period of 30 years (1986-2015) were enrolled, and they accounted for 1.1% (6/540) of our ABM patients. In this study, a total of 14 patients with Citrobacter ABM (six collected from our hospital and eight from the literature) were included for analysis...
June 12, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Michael A Noble, Robert Rennie
BACKGROUND: Reporting on the presence of antimicrobial resistance is of considerable concern both for individual patient care and for understanding the underlying health status within the community at large. Antimicrobial resistance is solely dependent upon clinical laboratory detection and thus can be impacted upon by the quality and competence of medical laboratories. Proficiency testing or external quality assessment (PT/EQA) is the international standard for the direct measurement of medical laboratory performance on critical testing...
June 15, 2018: Diagnosis
Rafael De León-Borrás, Julio Álvarez-Cardona, Jorge A Vidal, Humberto M Guiot
A 36-year-old man was admitted to the intensive care unit due to diabetic ketoacidosis and pneumonia requiring mechanical ventilation. Three weeks after admission, he developed a refractory bacteremia with Klebsiella pneumoniae carbapenemase-producing bacteria (KPC). He remained febrile and with bacteremia for six weeks despite therapy with polymyxin B, carbapenems, and amikacin. Imaging studies looking for deep-seated infection revealed vertebral L1-L2 diskitis and osteomyelitis with pre-vertebral abscess and bilateral psoas pyomyositis that were not amenable for drainage...
June 2018: Puerto Rico Health Sciences Journal
Maroya S Walters, Medora Witwer, Yeon-Kyeng Lee, Valerie Albrecht, David Lonsway, J Kamile Rasheed, Melissa Anacker, Paula Snippes-Vagnone, Ruth Lynfield, Alexander J Kallen
No abstract text is available yet for this article.
June 15, 2018: MMWR. Morbidity and Mortality Weekly Report
Helio S Sader, Robert K Flamm, Glenn E Dale, Paul R Rhomberg, Mariana Castanheira
Background: Murepavadin (POL7080) represents the first member of a novel class of outer membrane protein-targeting antibiotics. Murepavadin acts by binding to LPS transport protein D and is being developed for the treatment of hospital-acquired and ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Objectives: To evaluate the antimicrobial activity of murepavadin against XDR P. aeruginosa. Methods: A total of 785 clinical isolates of XDR P...
June 12, 2018: Journal of Antimicrobial Chemotherapy
Matteo Bassetti, Alessandro Russo, Alessia Carnelutti, Alessandro La Rosa, Elda Righi
Introduction Infections due to multidrug-resistant (MDR) bacteria are burdened by high mortality rates. The development of new compounds to face the global threat of resistance is urgently needed. Combination regimens including "old" high-dose antimicrobials are currently limited by the risk of toxicity, resistance selection, and reduced efficacy. Following the Infectious Diseases Society of America call to develop 10 new antibacterials by 2020, new molecules are currently under development or have become available for use in clinical practice...
June 13, 2018: Expert Opinion on Drug Safety
Felix Lange, Niels Pfennigwerth, Rainer Hartl, Heidrun Kerschner, Dagmar Achleitner, Sören G Gatermann, Martin Kaase
Objectives: To identify and characterize a novel MBL gene conferring carbapenem resistance to an isolate of Enterobacter cloacae from Austria. Methods: The novel MBL gene was heterologously expressed in Escherichia coli TOP10 to conduct comparative MIC studies and biochemical assays. Furthermore, WGS was performed using Illumina MiSeq and Oxford Nanopore MinION instruments to analyse the genetic environment of the novel MBL gene. Results: The novel MBL showed highest sequence homology to a predicted MBL precursor from the marine bacterium Rheinheimera pacifica and hence belongs to Ambler subgroup B3...
June 11, 2018: Journal of Antimicrobial Chemotherapy
Zhiyong Zong, Samuel Fenn, Christopher Connor, Yu Feng, Alan McNally
Objectives: The increase in infections as a result of MDR strains of Escherichia coli is a global health crisis. The emergence of globally disseminated lineages of E. coli carrying ESBL genes has been well characterized. An increase in strains producing carbapenemase enzymes and mobile colistin resistance is now being reported, but to date there is little genomic characterization of such strains. Methods: Routine screening of patients within an ICU of West China Hospital identified a number of E...
June 11, 2018: Journal of Antimicrobial Chemotherapy
Supeng Yin, Ping Chen, Bo You, Yulong Zhang, Bei Jiang, Guangtao Huang, Zichen Yang, Yu Chen, Jing Chen, Zhiqiang Yuan, Yan Zhao, Ming Li, Fuquan Hu, Yali Gong, Yizhi Peng
Pseudomonas aeruginosa is the leading cause of infection in burn patients. The increasing carbapenem resistance of P. aeruginosa has become a serious challenge to clinicians. The present study investigated the molecular typing and carbapenem resistance mechanisms of 196 P. aeruginosa isolates from the bloodstream and wound surface of patients in our burn center over a period of 6 years. By multilocus sequence typing (MLST), a total of 58 sequence types (STs) were identified. An outbreak of ST111, a type that poses a high international risk, occurred in 2014...
2018: Frontiers in Microbiology
Elizabeth Diago-Navarro, Michael P Motley, Gonzalo Ruiz-Peréz, Winnie Yu, Julianne Austin, Bruna M S Seco, Guozhi Xiao, Aniska Chikhalya, Peter H Seeberger, Bettina C Fries
No abstract text is available yet for this article.
June 12, 2018: MBio
S Maham, F Fallah, Z Gholinejad, A Seifi, S M Hoseini-Alfatemi
BACKGROUND: Due to the diverse nature of bloodstream infections etiology and to the antibiotic resistance patterns in periodic intervals, rational and accurate use of antibiotics requires an understanding of common causative agents of septicemia and their susceptibility patterns. The present study aimed to determine the bacterial etiology of the neonate and pediatric septicemia, and their antibiotic resistance pattern in Tehran, North of Iran. MATERIAL AND METHODS: This retrospective cross-sectional study was conducted along two years, from October 2014 to November 2016 among children with suspected bloodstream infection...
July 2018: Annali di Igiene: Medicina Preventiva e di Comunità
Wen Bin Jin, Chen Xu, Qipeng Cheng, Xiao Lin Qi, Wei Gao, Zhiwei Zheng, Edward W C Chan, Yun-Chung Leung, Tak Hang Chan, Kwok-Yin Wong, Sheng Chen, Kin-Fai Chan
The worldwide prevalence of NDM-1-producing bacteria has drastically undermined the clinical efficacy of the last line antibiotic of carbapenems, prompting a need to devise effective strategy to preserve their clinical value. Our previous studies have shown that ebselen can restore the efficacy of meropenem against a laboratory strain that produces NDM-1. Here we report the construction of a focused compound library of 1,2-benzisoselenazol-3(2H)-one derivatives which comprise a total of forty-six candidate compounds...
June 6, 2018: European Journal of Medicinal Chemistry
Takashi Okanda, Anwarul Haque, Tomoko Ehara, Qumrul Huda, Kiyofumi Ohkusu, Ruhul Amin Miah, Tetsuya Matsumoto
The aim of this study was to characterize the fluoroquinolone (FQ) resistance mechanism of Salmonella enterica serovar Typhi and Paratyphi A in Bangladesh. Salmonella Typhi isolates were classified into sequence type (ST) 1, ST2, and ST2209 and Salmonella Paratyphi A isolates were classified into ST85 and ST129. The most common STs of the FQ-nonsusceptible strain were ST1 (44.4%) and ST129 (66.6%). Thirty-nine percent of Salmonella Typhi isolates were multidrug resistant, and these were all ST1, which is the type prevalent in the Indian subcontinent...
June 12, 2018: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
Fangyou Yu, Jingnan Lv, Siqiang Niu, Hong Du, Yi-Wei Tang, Robert A Bonomo, Barry N Kreiswirth, Liang Chen
Carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKp) strains have emerged while antimicrobial treatment options remain limited. Herein, we tested the in vitro activity of ceftazidime-avibactam and other comparator antibiotics against 65 CR-hvKp isolates. Ceftazidime-avibactam, colistin and tigecycline are highly active in vitro against CR-hvKp isolates (MIC90 ≤ 1μg/ml), including KPC-2-producing ST11 CR-hvKp. Based upon previous clinical experience and the in vitro data presented herein, we posit that ceftazidime-avibactam is a considered therapeutic option against CR-hvKp infections...
June 11, 2018: Antimicrobial Agents and Chemotherapy
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