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https://www.readbyqxmd.com/read/29897796/antimicrobial-resistance-and-treatment-an-unmet-clinical-safety-need
#1
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
https://www.readbyqxmd.com/read/29891602/clonal-background-resistance-gene-profile-and-porin-gene-mutations-modulate-in-vitro-susceptibility-to-imipenem-relebactam-in-diverse-enterobacteriaceae
#2
Angela Gomez-Simmonds, Stephania Stump, Marla J Giddins, Medini K Annavajhala, Anne-Catrin Uhlemann
Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) are limited. While Klebsiella pneumoniae harboring bla KPC account for most CRE, recent evidence points to increasing diversification of CRE. We determined whether CRE species and antibiotic resistance genotype influence response to relebactam (REL), a novel beta-lactamase inhibitor with class A/C activity, combined with imipenem(IMI)/cilastatin. We carried out broth microdilution testing to IMI alone or in the presence of 4 μg/mL REL in 154 clinical isolates collected at a New York City hospital with high prevalence of bla KPC including Enterobacter spp...
June 11, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29882610/in-silico-design-and-enantioselective-synthesis-of-functionalized-monocyclic-3-amino-1-carboxymethyl-%C3%AE-lactams-as-inhibitors-of-penicillin-binding-proteins-of-resistant-bacteria
#3
Lena Decuyper, Sari Deketelaere, Lore Vanparys, Marko Jukic, Izidor Sosic, Eric Sauvage, Ana Maria Amoroso, Olivier Verlaine, Bernard Joris, Stanislav Gobec, Matthias D'hooghe
As a complement to the renowned bicyclic beta-lactam antibiotics, monocyclic analogues provide a breath of fresh air in the battle against resistant bacteria. In that framework, the present study discloses the in silico design and unprecedented ten-step synthesis of eleven nocardicin-like enantiomerically pure 2-{3-[2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-2-oxoazetidin-1-yl}acetic acids starting from serine as a readily accessible precursor. The capability of this novel class of monocyclic 3-amino-beta-lactams to inhibit penicillin-binding proteins (PBPs) of various (resistant) bacteria was assessed, revealing the potential of alfa-benzylidenecarboxylates as interesting leads in the pursuit of novel PBP inhibitors...
June 8, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29864485/proton-pump-inhibitor-use-as-a-risk-factor-for-enterobacteriaceal-infection-a-case-control-study
#4
Richard Cunningham, Lewis Jones, Doyo Gragn Enki, Robert Tischhauser
BACKGROUND: Gastric acid suppressants increase the risk of gastroenteritis by allowing ingested pathogens to survive passage through the stomach. It is not known whether the same mechanism affects transmission of Enterobacteriacae. We carried out a case-control study to answer this question. AIM: To determine whether use of Proton Pump Inhibitors (PPIs) increases the risk of infection with Enterobacteriacae in hospital patients. METHODS: Retrospective case-control study in a teaching hospital in South West England...
June 1, 2018: Journal of Hospital Infection
https://www.readbyqxmd.com/read/29798080/-the-bacteriologic-features-of-recurrent-acute-rhinosinusitis
#5
H Q Wei, Z W Zhu, Zy Cao, J W Mo, H Y Xing
Objective: To investigate the bacteriologic characteristics of recurrent acute rhinosinusitis(RAR). Method: Twenty-nine patients (29 with RAR) from outpatient clinic in our hospital between June 2010 and May 2016 were enrolled in the study. Specimens of the middle meatus or olfactory cleft area using the sinus endoscopy through were transported to the laboratory for bacterial culture. Result: Twenty-five specimens out of 29 were bacterial culture positive (culture positive rate was 86.2%).A total of 32 isolates (25 aerobic or facultative and 7 anaerobic) were recovered from the 29 cases of RAR...
April 2018: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
https://www.readbyqxmd.com/read/29783881/lemierre-s-syndrome-a-case-study-with-a-short-review-of-literature
#6
Ken De Smet, Paul-Emile Claus, Gudrun Alliet, An Simpelaere, Geert Desmet
Objective and Importance Lemierre's syndrome (LS) is a rare condition that typically starts with a bacterial oropharyngeal infection complicated by a thrombophlebitis of the internal jugular vein and septic emboli to the lungs or other organs. The most common organism isolated is Fusobacterium necrophorum, although other causative organisms are isolated in rare cases. Case presentation We discuss a case of LS in a 44-year-old, previously healthy man presenting with an oropharyngeal infection. F. necrophorum was isolated from blood cultures and Computed tomography of the chest demonstrated septic emboli in the lungs...
May 21, 2018: Acta Clinica Belgica
https://www.readbyqxmd.com/read/29730830/the-epidemiology-evolution-and-treatment-of-kpc-producing-organisms
#7
REVIEW
Ann Marie Porreca, Kaede V Sullivan, Jason C Gallagher
PURPOSE OF REVIEW: The purpose of this review is to investigate the evolution and epidemiology of Klebsiella pneumoniae carbapenemase (KPC)-producing organisms and the current and future treatment options for infections caused by KPC-producing isolates. RECENT FINDINGS: The emergence of resistance in Enterobacteriaceae producing carbapenemases globally has increased the challenges in treating infections caused by these organisms. One of the prominent mechanisms of resistance is the production of KPC enzymes...
May 5, 2018: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/29675787/meropenem-vaborbactam-a-carbapenem-and-beta-lactamase-inhibitor-with-activity-against-carbapenem-resistant-enterobacteriaceae
#8
REVIEW
Young R Lee, Nathaniel T Baker
Meropenem-vaborbactam is a carbapenem and β-lactamase inhibitor combination that is newly indicated for the treatment of complicated urinary tract infections (cUTI), including adult pyelonephritis. Vaborbactam was developed due to emergence of carbapenem-resistant strains of Enterobacteriaceae. In a phase I trial, patients that received meropenem-vaborbactam 2-2 g intravenously over 3 h every 8 h, Cmax was 58.2 ± 10.8 μg/mL for meropenem and 59.0 ± 8.4 μg/mL for vaborbactam. AUC0-8 was 186 ± 33...
April 19, 2018: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/29615167/pseudomonas-aeruginosa-evaluation-of-pathogen-burden-and-drug-resistance-trends-in-a-tertiary-care-hospital
#9
Muhammad Saeed, Farhan Rasheed, Raja Kamran Afzal, Shahida Hussain, Saba Riaz, Adeel Ahmad
OBJECTIVE: To evaluate the pathogen burden and antibiotic-resistance trends of Pseudomonas aeruginosa among hospitalised patients at a tertiary care hospital. STUDY DESIGN: Retrospective, hospital record-based, cross-sectional study. PLACE AND DURATION OF STUDY: Microbiology Laboratory, Allama Iqbal Medical College/Jinnah Hospital, Lahore, from January 2014 to December 2016. METHODOLOGY: A total of 5,960 samples were collected from clinically suspected cases of bacterial infections, admitted to the hospital...
April 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/29596815/therapeutic-drug-monitoring-of-piperacillin-and-tazobactam-by-rp-hplc-of-residual-blood-specimens
#10
Sylvia M Verhoven, Joseph J Groszek, William H Fissell, Adam Seegmiller, Jennifer Colby, Pratish Patel, Alain Verstraete, Matthew Shotwell
BACKGROUND: Sepsis is a common diagnosis in critical care with inpatient mortality rates up to 50%. Sepsis care is organized around source control, antibiotics, and supportive care. Drug disposition is deranged by changes in volume of distribution and regional blood flow, as well as multiple organ failure. Thus, assuring that each patient with sepsis attains pharmacokinetic targets is challenging. There is currently no commercially available FDA-approved assay to measure piperacillin-tazobactam, very commonly used as a beta-lactam/beta-lactamase inhibitor combination antibiotic in the intensive care unit (ICU)...
July 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29559421/in-vitro-antimicrobial-activity-of-ceftolozane-tazobactam-against-p-aeruginosa-and-other-non-fermenting-gram-negative-organisms-in-adults-with-cystic-fibrosis
#11
A Gramegna, B C Millar, F Blasi, J S Elborn, D G Downey, J E Moore
INTRODUCTION: Pulmonary exacerbations in people with Cystic Fibrosis (CF), with chronic Gram-negative pathogens, are associated with reduced survival. These pathogens are usually treated with repeated courses of systemic antibiotics. However there is a linked emergence of multidrug resistant (MDR) pathogens. Ceftolozane/tazobactam is a new cephalosporin/beta-lactamase inhibitor combination that has been demonstrated to have good activity against MDR Pseudomonas aeruginosa. MATERIAL & METHODS: In this study ceftolozane/tazobactam was compared to other commonly used intravenous antibiotics against 193 non-fermenting Gram-negative bacteria isolated from CF sputum specimens, including P...
March 17, 2018: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/29531825/magnolol-restores-the-activity-of-meropenem-against-ndm-1-producing-escherichia-coli-by-inhibiting-the-activity-of-metallo-beta-lactamase
#12
Shui Liu, Yonglin Zhou, Xiaodi Niu, Tingting Wang, Jiyun Li, Zhongjie Liu, Jianfeng Wang, Shusheng Tang, Yang Wang, Xuming Deng
The emergence of plasmid-mediated New Delhi metallo-β-lactamase-1 (NDM-1) in carbapenem-resistant Gram-negative pathogens is an increasing clinical threat. Here we report the discovery of an NDM-1 inhibitor, magnolol, through enzyme inhibition screening. We showed that magnolol significantly inhibited NDM enzyme activity (IC50  = 6.47 µg/mL), and it restored the activity of meropenem against Escherichia coli ZC-YN3, an NDM-1-producing E. coli isolate, in in vitro antibacterial activity assays. Magnolol lacked direct antibacterial activity, but compared with meropenem alone, it reduced the MICs of meropenem against E...
December 2018: Cell Death Discovery
https://www.readbyqxmd.com/read/29521242/ceftazidime-avibactam-and-ceftolozane-tazobactam-novel-therapy-for-multidrug-resistant-gram-negative-infections-in-children
#13
Brittany A Rodriguez, Jennifer E Girotto, David P Nicolau
The rise in multidrug-resistant (MDR) infections has become a significant problem in both the developing countries and in the United States (U.S.). Specifically, MDR gram-negative infections are emerging, affecting not only adults but children as well. The specific gram-negative organisms that have been most concerning within the pediatric population include MDR P. aeruginosa, Enterobacteriaceae, and Acinetobacter spp. The increase in antimicrobial resistance rates are associated with various mechanisms, with, one of the most common being the production of beta-lactamases...
March 8, 2018: Current Pediatric Reviews
https://www.readbyqxmd.com/read/29511909/resistance-trends-and-treatment-options-in-gram-negative-ventilator-associated-pneumonia
#14
REVIEW
Nathaniel J Rhodes, Caroline E Cruce, J Nicholas O'Donnell, Richard G Wunderink, Alan R Hauser
PURPOSE OF REVIEW: Hospital-acquired and ventilator-associated pneumonia (VAP) are frequent causes of infection among critically ill patients. VAP is the most common hospital-acquired bacterial infection among mechanically ventilated patients. Unfortunately, many of the nosocomial Gram-negative bacteria that cause VAP are increasingly difficult to treat. Additionally, the evolution and dissemination of multi- and pan-drug resistant strains leave clinicians with few treatment options. VAP patients represent a dynamic population at risk for antibiotic failure and under-dosing due to altered antibiotic pharmacokinetic parameters...
March 6, 2018: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/29493397/ceftolozane-tazobactam-place-in-therapy
#15
Daniele Roberto Giacobbe, Matteo Bassetti, Francesco Giuseppe De Rosa, Valerio Del Bono, Paolo Antonio Grossi, Francesco Menichetti, Federico Pea, Gian Maria Rossolini, Mario Tumbarello, Pierluigi Viale, Claudio Viscoli
Ceftolozane/tazobactam (C/T) is a new antibiotic resulting from the combination of a novel cephalosporin, structurally similar to ceftazidime, with tazobactam, a well-known beta-lactamase inhibitor. C/T remains active against extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and multi-drug resistant (MDR) P. aeruginosa, and has been recently approved for the treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI). A trial on hospital-acquired pneumonia is ongoing...
April 2018: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/29486041/effect-of-meropenem-vaborbactam-vs-piperacillin-tazobactam-on-clinical-cure-or-improvement-and-microbial-eradication-in-complicated-urinary-tract-infection-the-tango-i-randomized-clinical-trial
#16
RANDOMIZED CONTROLLED TRIAL
Keith S Kaye, Tanaya Bhowmick, Symeon Metallidis, Susan C Bleasdale, Olexiy S Sagan, Viktor Stus, Jose Vazquez, Valerii Zaitsev, Mohamed Bidair, Erik Chorvat, Petru Octavian Dragoescu, Elena Fedosiuk, Juan P Horcajada, Claudia Murta, Yaroslav Sarychev, Ventsislav Stoev, Elizabeth Morgan, Karen Fusaro, David Griffith, Olga Lomovskaya, Elizabeth L Alexander, Jeffery Loutit, Michael N Dudley, Evangelos J Giamarellos-Bourboulis
Importance: Meropenem-vaborbactam is a combination carbapenem/beta-lactamase inhibitor and a potential treatment for severe drug-resistant gram-negative infections. Objective: To evaluate efficacy and adverse events of meropenem-vaborbactam in complicated urinary tract infection (UTI), including acute pyelonephritis. Design, Setting, and Participants: Phase 3, multicenter, multinational, randomized clinical trial (TANGO I) conducted November 2014 to April 2016 and enrolling patients (≥18 years) with complicated UTI, stratified by infection type and geographic region...
February 27, 2018: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/29444952/treatment-of-infections-caused-by-extended-spectrum-beta-lactamase-ampc-and-carbapenemase-producing-enterobacteriaceae
#17
REVIEW
Jesús Rodríguez-Baño, Belén Gutiérrez-Gutiérrez, Isabel Machuca, Alvaro Pascual
Therapy of invasive infections due to multidrug-resistant Enterobacteriaceae (MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum β-lactamase and AmpC producers, carbapenems are the drugs of choice, but alternatives are needed because the rate of carbapenem resistance is rising. Potential active drugs include classic and newer β-lactam-β-lactamase inhibitor combinations, cephamycins, temocillin, aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or trimethoprim-sulfamethoxazole...
April 2018: Clinical Microbiology Reviews
https://www.readbyqxmd.com/read/29442147/-urosepsis
#18
Mathias W Pletz, Sebastian Weis, Christina Forstner, Florian Wagenlehner
Urosepsis is defined as a severe disease due to organ failure caused by a urinary tract infection. An empirical antibiotic therapy should be instigated within the first hour after diagnosis. Urine cultures and blood cultures should be performed before antibiotic treatment. Further diagnostics should be carried out at an early stage to enable an interventional focus control in the case of urinary tract obstruction or abscess formation, if necessary. Gram-negative pathogens are most frequently isolated. Extended spectrum beta-lactamase (ESBL) forming bacteria as a cause of urosepsis are increasing...
March 2018: Medizinische Klinik, Intensivmedizin und Notfallmedizin
https://www.readbyqxmd.com/read/29437306/clinical-predictors-of-ceftriaxone-resistance-in-microorganisms-causing-febrile-urinary-tract-infections-in-men
#19
Javier Ramos Lázaro, Alex Smithson, Neus Jovè Vidal, María Teresa Batida Vila
OBJECTIVES: Because of high rates of resistance to fluoroquinolones, ceftriaxone has become one of the main options for treating febrile urinary tract infection (FUTI). This study aimed to identify predictors of ceftriaxone resistance in community-acquired FUTIs in men. MATERIAL AND METHODS: Cross-sectional ambispective study enrolling men with FUTIs treated in the emergency department of a local area hospital in Spain. RESULTS: A total of 552 FUTI episodes were studied; 103 (18...
February 2018: Emergencias: revista de la Sociedad Española de Medicina de Emergencias
https://www.readbyqxmd.com/read/29427523/meropenem-and-vaborbactam-stepping-up-the-battle-against-carbapenem-resistant-enterobacteriaceae
#20
REVIEW
Sarah Christina Jane Jorgensen, Michael Joseph Rybak
Vaborbactam (VAB; formerly RPX7009) is a novel beta-lactamase inhibitor based on a cyclic boronic acid pharmacophore with potent inhibitory activity against Ambler class A and C beta-lactamases. It has been co-formulated with meropenem to restore its activity against Klebsiella pneumoniae carbapenemases (KPC). VAB does not inhibit class B or D carbapenemases, nor does it improve the activity of meropenem against multidrug-resistant nonfermenting gram-negative bacilli, notably Acinetobacter spp. and Pseudomonas aeruginosa...
April 2018: Pharmacotherapy
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