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beta lactamase inhibitor

Makoto Miura, Akiko Kuwahara, Akinori Tomozawa, Naoki Omae, Motohiro Yamamori, Kaori Kadoyama, Toshiyuki Sakaeda
Objectives: A retrospective examination was conducted to identify risk factors for in-hospital mortality of elderly patients (65 years or older) treated with the beta-lactam/beta-lactamase inhibitor combination antibiotic, ampicillin/sulbactam (ABPC/SBT). Methods: Clinical data from 96 patients who were hospitalized with infectious diseases and treated with ABPC/SBT (9 g/day or 12 g/day) were analyzed. Risk factors examined included demographic and clinical laboratory parameters. Parameter values prior to treatment and changes after treatment were compared between survivors and non-survivors...
2016: International Journal of Medical Sciences
Abdolaziz Rastegar Lari, Leila Azimi, Malihe Talebi, Fatemeh Fallah, Aslan Bijari, Elnaz Rastegar Lari
BACKGROUND: Multi-drug resistant P. aeruginosa is being increasing worldwide. Various mechanisms create this cross resistance in this bacterium including, acquisition beta-lactamases and intrinsic mechanisms such as presence of multidrug efflux pumps. Generally, multidrug efflux pumps inhibitor is used as a phenotypic method for detection of active efflux pump systems. METHODS: In this study 100 P. aeruginosa were collected from burn patients. Cefepime and imipenem resistant strains were isolated by disc diffusion agar and MIC...
August 29, 2016: Infectious Disorders Drug Targets
Jose A Hidalgo, Celeste M Vinluan, Nishaal Antony
There has been greater interest in developing additional antimicrobial agents due to the increasing health care costs and resistance resulting from bacterial pathogens to currently available treatment options. Gram-negative organisms including Enterobacteriaceae and Pseudomonas aeruginosa are some of the most concerning threats due to their resistance mechanisms: extended-spectrum beta-lactamase production and Klebsiella pneumoniae carbapenemase enzymes. Ceftazidime is a third-generation broad-spectrum cephalosporin with activity against P...
2016: Drug Design, Development and Therapy
Jorgelina Morán-Barrio, María-Natalia Lisa, Nicole Larrieux, Salvador I Drusin, Alejandro M Viale, Diego M Moreno, Alejandro Buschiazzo, Alejandro J Vila
Metallo-beta-lactamases (MBLs) are broad-spectrum, Zn(II)-dependent lactamases able to confer resistance to virtually every β-lactam antibiotic currently available. The large diversity of active-site structures and metal content among MBLs from different sources has limited the design of a pan-MBL inhibitor. GOB-18 is a divergent MBL from subclass B3 that is expressed by the opportunistic Gram-negative pathogen Elizabethkingia meningoseptica This MBL is atypical, since several residues conserved in B3 enzymes (such as a metal ligand His) are substituted in GOB enzymes...
October 2016: Antimicrobial Agents and Chemotherapy
J A García-Rodríguez, J E García Sánchez, I Trujillano, J L Muñoz-Bellido
Bacteroides fragilis group are the most common anaerobic bacteria isolated in clinical specimens. The use of a beta-lactam with a β-lactamase inhibitor should result in a marked increase in the group's sensitivity to the β-lactams. Since the activity (MIC) shown by the amoxicillin + clavulanic acid combination against Bacteroides fragilis group is good, other parameters of in vitro activity have been studied. This study was also done with metronidazole. The minimum inhibitory concentration (MIC) was determined in 26 strains of Bacteroides fragilis group (14 B...
February 1990: Journal of Chemotherapy
Fatma Gizem Avci, Fatma Ece Altinisik, Didem Vardar Ulu, Elif Ozkirimli Olmez, Berna Sariyar Akbulut
Declining efficiency of antibiotic-inhibitor combinatorial therapies in treating beta-lactamase mediated resistance necessitates novel inhibitor development. Allosteric inhibition offers an alternative to conventional drugs that target the conserved active site. Here, we show that the evolutionarily conserved PWP triad located at the N-terminus of the H10 helix directly interacts with the allosteric site in TEM-1 beta-lactamase and regulates its activity. While point mutations in the PWP triad preserve the overall secondary structures around the allosteric site, they result in a more open and dynamic global structure with decreased chemical stability and increased aggregation propensity...
June 28, 2016: Journal of Enzyme Inhibition and Medicinal Chemistry
P Tattevin, J-L Mainardi
The optimal management of infective endocarditis requires a broad range of expertise (infectious disease specialists, cardiologists, microbiologists, cardiac surgeons, and intensivists). Given the low level of evidence currently available to support the management of infective endocarditis, international guidelines have always been particularly awaited and rather well implemented. Their cautious analysis of the medical literature and the range of expertise combined within the groups in charge of these guidelines are usually broadly acknowledged and respected...
June 10, 2016: Médecine et Maladies Infectieuses
Ertugrul Guclu, Aziz Ogutlu, Oguz Karabay, Tuna Demirdal, Ibrahim Erayman, Salih Hosoglu, Vedat Turhan, Serpil Erol, Nefise Oztoprak, Ayse Batirel, Fatma Aybala Altay, Gulsum Kaya, Mustafa Karahocagil, Hamdi Sozen, Mustafa Yildirim, Funda Kocak, Bahri Teker
This multi-centre study aimed to determine the antibiotic consumption in Turkish hospitals by point prevalence. Antibiotic consumption of 14 centres was determined using the DDD method. Among hospitalized patients, 44.8% were using antibiotics and the total antibiotic consumption was 674.5 DDD/1000 patient-days (DPD). 189.6 (28%) DPD of the antibiotic consumption was restricted while 484.9 (72%) DPD was unrestricted. Carbapenems (24%) and beta lactam/beta lactamase inhibitors (ampicillin-sulbactam or amoxicillin-clavulanate; 22%) were the most commonly used restricted and unrestricted antibiotics...
May 30, 2016: Journal of Chemotherapy
Ochoa-Aguilar Abraham, Ventura-Martinez Rosa, Sotomayor-Sobrino Marco Antonio, Gómez-Acevedo Claudia, Morales-Espinosa María Del Rosario
BACKGROUND: Beta-lactam molecules are a family of drugs commonly used for their antibiotic properties; however, recent research has shown that several members of this group present a large number of other effects such as neuroprotective, antioxidant, analgesic or immunomodulatory capabilities. These properties have been used in both preclinical and clinical studies in different diseases such as hypoxic neuronal damage or acute and chronic pain. The present work briefly reviews the antibiotic effect of these molecules, and will then focus specially on the non-antibiotic effects of three beta-lactam subfamilies: penicillins, cephalosporins and beta lactamase inhibitors, each of which have different molecular structure and pharmacokinetics and therefore have several potential clinical applications...
May 17, 2016: Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry
Faruk Pehlivanoglu, Hulya Turutoglu, Dilek Ozturk
In the present study, 3 quarter milk samples from 3 cows showing clinical signs of mastitis were investigated. Three Escherichia coli were isolated and were found resistant to ceftiofur and cefquinome. The isolates were detected as extended-spectrum beta-lactamase (ESBL) producers by the Clinical and Laboratory Standards Institute (CLSI) ESBL screening test and combined disc method. CTX-M- and TEM-type beta-lactamase genes (blaCTX-M blaTEM) were detected by polymerase chain reaction in the isolates. Sequencing of blaCTX-M and blaTEM genes showed that the isolates were both TEM-1- and CTX-M-15-type beta-lactamase producers...
September 2016: Foodborne Pathogens and Disease
David van Duin, Robert A Bonomo
Ceftolozane/tazobactam and ceftazidime/avibactam are 2 novel β-lactam/β-lactamase combination antibiotics. The antimicrobial spectrum of activity of these antibiotics includes multidrug-resistant (MDR) gram-negative bacteria (GNB), including Pseudomonas aeruginosa. Ceftazidime/avibactam is also active against carbapenem-resistant Enterobacteriaceae that produce Klebsiella pneumoniae carbapenemases. However, avibactam does not inactivate metallo-β-lactamases such as New Delhi metallo-β-lactamases. Both ceftolozane/tazobactam and ceftazidime/avibactam are only available as intravenous formulations and are dosed 3 times daily in patients with normal renal function...
July 15, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Jordan R Smith, Anu Arya, Juwon Yim, Katie E Barber, Jessica Hallesy, Nivedita B Singh, Michael J Rybak
Ceftolozane-tazobactam (TOL-TAZ) is a novel cephalosporin/beta-lactamase inhibitor with activity against several Gram-negative pathogens. Daptomycin (DAP) has demonstrated synergistic activity with beta-lactams against methicillin-resistant Staphylococcus aureus (MRSA) isolates with reduced lipopeptide and glycopeptide susceptibilities. Our objective was to determine if DAP and TOL-TAZ possess synergy in hollow-fiber pharmacokinetic/pharmacodynamic (PK/PD) models. One isogenic pair of daptomycin-susceptible and daptomycin-nonsusceptible MRSA strains was evaluated...
July 2016: Antimicrobial Agents and Chemotherapy
Yumei Guo, Haijian Zhou, Liyun Qin, Zhizhao Pang, Tian Qin, Hongyu Ren, Zhuo Pan, Jikun Zhou
This study aimed to assess the frequency of Klebsiella pneumoniae in food samples and to detect antibiotic resistance phenotypes, antimicrobial resistance genes and the molecular subtypes of the recovered isolates. A total of 998 food samples were collected, and 99 (9.9%) K. pneumoniae strains were isolated; the frequencies were 8.2% (4/49) in fresh raw seafood, 13.8% (26/188) in fresh raw chicken, 11.4% (34/297) in frozen raw food and 7.5% (35/464) in cooked food samples. Antimicrobial resistance was observed against 16 antimicrobials...
2016: PloS One
Charles Hoffmann, Matthew Zak, Lisa Avery, Jack Brown
Antimicrobial stewardship programs (ASPs) focus on improving the utilization of broad spectrum antibiotics to decrease the incidence of multidrug-resistant Gram positive and Gram negative pathogens. Hospital admission for both medical and surgical intra-abdominal infections (IAIs) commonly results in the empiric use of broad spectrum antibiotics such as fluoroquinolones, beta-lactam beta-lactamase inhibitors, and carbapenems that can select for resistant organisms. This review will discuss the management of uncomplicated and complicated IAIs as well as highlight stewardship initiatives focusing on the proper use of broad spectrum antibiotics...
2016: Antibiotics
Ali M Somily, Ghada A Garaween, Norah Abukhalid, Muhammad M Absar, Abiola C Senok
In recent years, there has been a rapid dissemination of carbapenem resistant Enterobacteriaceae (CRE). This study aimed to compare phenotypic and molecular methods for detection and characterization of CRE isolates at a large tertiary care hospital in Saudi Arabia. This study was carried out between January 2011 and November 2013 at the King Khalid University Hospital (KKUH) in Saudi Arabia. Determination of presence of extended-spectrum beta-lactamases (ESBL) and carbapenem resistance was in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines...
March 2016: Acta Microbiologica et Immunologica Hungarica
Brian D VanScoy, Michael Trang, Jennifer McCauley, Haley Conde, Sujata M Bhavnani, Lawrence V Friedrich, Dylan C Alexander, Paul G Ambrose
The usefulness of β-lactam antimicrobial agents is threatened as never before by β-lactamase-producing bacteria. For this reason, there has been renewed interest in the development of broad-spectrum β-lactamase inhibitors. Herein we describe the results of dose fractionation and dose-ranging studies carried out using a one-compartment in vitro infection model to determine the exposure measure for CB-618, a novel β-lactamase inhibitor, most predictive of the efficacy when given in combination with meropenem...
July 2016: Antimicrobial Agents and Chemotherapy
H J Heppner, F Yapan, A Wiedemann
Due to the demographic shift, increasing numbers of geriatric patients are admitted to acute care hospitals of all levels of care. This means that special challenges must be met in the medical care and management of these patients.Immunosenescence and multimorbidity make elderly patients vulnerable to infectious diseases. Urinary tract infections range from "simple" cystitis to pyelonephritis and urosepsis and, at 25%, are the second most common form of infection in geriatric patients. It is often difficult to make a diagnosis because typical symptoms do not always occur...
February 2016: Aktuelle Urologie
Iman Dandachi, Elie Salem Sokhn, Elie Najem, Eid Azar, Ziad Daoud
BACKGROUND: Multidrug-resistant (MDR) Enterobacteriaceae can cause severe infections with high morbidity, mortality, and health care costs. Individuals can be fecal carriers of these resistant organisms. Data on the extent of MDR Enterobacteriaceae fecal carriage in the community setting in Lebanon are very scarce. The aim of this study was to investigate the fecal carriage of MDR Enterobacteriaceae among the elderly residents of two nursing homes located in north Lebanon. METHODS: Over a period of 4 months, five fecal swab samples were collected from each of 68 elderly persons at regular intervals of 3-4 weeks...
April 2016: International Journal of Infectious Diseases: IJID
Tomoyuki Yunoki, Yasufumi Matsumura, Satoshi Nakano, Karin Kato, Go Hotta, Taro Noguchi, Masaki Yamamoto, Miki Nagao, Shunji Takakura, Satoshi Ichiyama
The accuracies of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and the phenotypic method using VITEK 2 were compared to the accuracy of 16S rRNA sequence analysis for the identification of 170 clinically isolated anaerobes. The antimicrobial susceptibility of the isolates was also evaluated. Genetic analysis identified 21 Gram-positive species in 14 genera and 29 Gram-negative species in 11 genera. The most frequently isolated genera were Prevotella spp. (n = 46), Bacteroides spp...
May 2016: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
Antonino Romano, Francesco Gaeta, Maria Francisca Arribas Poves, Rocco Luigi Valluzzi
Penicillins and cephalosporins are the major classes of beta-lactam (BL) antibiotics in use today and one of the most frequent causes of hypersensitivity reactions to drugs. Monobactams, carbapenems, oxacephems, and beta-lactamase inhibitors constitute the four minor classes of BLs. This review takes into account mainly the prospective studies which evaluated cross-reactivity among BLs in subjects with a well-demonstrated hypersensitivity to a certain class of BLs by performing allergy tests with alternative BLs and, in case of negative results, administering them...
March 2016: Current Allergy and Asthma Reports
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