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José A Cornejo-García, Abderrahim Oussalah, Miguel Blanca, Rosa-María Guéant-Rodríguez, Cristobalina Mayorga, Julie Waton, Annick Barbaud, Francesco Gaeta, Antonino Romano, Jean-Louis Guéant
Our knowledge of genetic predisposing factors of drug hypersensitivity reactions (DHRs) is still scarce. The analysis of the genetic basis of these reactions may contribute to dissect the underlying mechanisms. We will outline current knowledge of the genetic predictors of most common DHRs, including reactions to betalactam antibiotics (BLs), nonsteroidal anti-inflammatory drugs (NSAIDs) and biological agents. The predictors of DHRs to BLs are mostly linked to IgE-class switching, IgE pathway and atopy (IL4R, NOD2, LGALS3) in replicated candidate gene studies, and to antigen presentation (HLA-DRA) in the single replicated GWAS performed so far...
September 27, 2016: Current Pharmaceutical Design
F Sörgel, R Höhl, R Glaser, C Stelzer, M Munz, M Vormittag, M Kinzig, J Bulitta, C Landersdorfer, A Junger, M Christ, M Wilhelm, U Holzgrabe
Optimized dosage regimens of antibiotics have remained obscure since their introduction. During the last two decades pharmacokinetic(PK)-pharmacodynamic(PD) relationships, originally established in animal experiments, have been increasingly used in patients. The action of betalactams is believed to be governed by the time the plasma concentration is above the minimum inhibitory concentration (MIC). Aminoglycosides act as planned when the peak concentration is a multiple of the MIC and vancomycin seems to work best when the area under the plasma vs...
October 24, 2016: Medizinische Klinik, Intensivmedizin und Notfallmedizin
Adriana Ariza, Cristobalina Mayorga, María Salas, Inmaculada Doña, Ángela Martín-Serrano, Ezequiel Pérez-Inestrosa, Dolores Pérez-Sala, Antonio E Guzmán, María I Montañez, María J Torres
The optimal recognition of penicillin determinants, including amoxicillin (AX), by specific IgE antibodies is widely believed to require covalent binding to a carrier molecule. The nature of the carrier and its contribution to the antigenic determinant is not well known. Here we aimed to evaluate the specific-IgE recognition of different AX-derived structures. We studied patients with immediate hypersensitivity reactions to AX, classified as selective or cross-reactors to penicillins. Competitive immunoassays were performed using AX itself, amoxicilloic acid, AX bound to butylamine (AXO-BA) or to human serum albumin (AXO-HSA) in the fluid phase, as inhibitors, and amoxicilloyl-poli-L-lysine (AXO-PLL) in the solid-phase...
October 12, 2016: Scientific Reports
Marie Gisselsson-Solen, Ann Hermansson, Åsa Melhus
BACKGROUND: Although there is evidence of an association between antibiotic consumption and resistant bacteria on a population level, the relationship on an individual level has been less well studied, particularly in terms of nasopharyngeal colonization. We have therefore analysed this association, using data from a closely followed cohort of children taking part in a vaccination trial. METHODS: 109 children with early onset of acute otitis media (AOM) were randomised to heptavalent pneumococcal conjugate vaccine (PCV7) or no vaccination...
September 2016: International Journal of Pediatric Otorhinolaryngology
Leila Azimi, Amirmorteza Ebrahimzadeh Namvar, Sadaf Jamali, Aida Rastegar Lari, Aslan Bijari, Abdolaziz Rastegar Lari
Pseudomonas aeruginosa is known as an important opportunistic pathogen, resistant to a high number of antibiotics. Efflux pumps are one of the main intrinsic antibiotics resistance mechanisms in P. aeruginosa. MexAB-OprM, MexCD-OprJ, and MexXY-OprM are the main efflux pumps involved in beta-lactam resistant strains which may cause cross resistance to different antimicrobial classes. The aim of this study was to detect relative gene expression in betalactam-resistant clinical P. aeruginosa strains. One hundred fourteen clinical strains of P...
July 2015: Roumanian Archives of Microbiology and Immunology
Kimberly G Blumenthal, James L Kuhlen, Ana A Weil, Christy A Varughese, David W Kubiak, Aleena Banerji, Erica S Shenoy
BACKGROUND: Ceftaroline fosamil is a cephalosporin approved for treating skin and soft tissue infections (SSTIs), including those caused by methicillin-resistant Staphylococcus aureus and community-acquired pneumonia (CAP). OBJECTIVES: We aimed to study ceftaroline use and associated adverse drug reactions (ADRs), including hypersensitivity reactions (HSRs), among inpatients. METHODS: We performed a retrospective electronic health record review of inpatients from Massachusetts General Hospital and Brigham and Women's Hospital who received ceftaroline between May 2012 and February 2015...
July 2016: Journal of Allergy and Clinical Immunology in Practice
A Oussalah, C Mayorga, M Blanca, A Barbaud, A Nakonechna, J Cernadas, M Gotua, K Brockow, J-C Caubet, A Bircher, M Atanaskovic, P Demoly, L K Tanno, I Terreehorst, J J Laguna, A Romano, J-L Guéant
Drug hypersensitivity includes allergic (AR) and nonallergic reactions (NARs) influenced by genetic predisposition. We performed a systematic review of genetic predictors of IgE-mediated AR and NAR with MEDLINE and PubMed search engine between January 1966 and December 2014. Among 3110 citations, the search selected 53 studies, 42 of which remained eligible. These eligible studies have evaluated genetic determinants of immediate reactions (IR) to beta-lactams (n = 19), NAR against aspirin (n = 12) and other nonsteroidal anti-inflammatory drugs (NSAIDs) (n = 8), and IR to biologics (n = 3)...
April 2016: Allergy
M J Torres, M I Montañez, A Ariza, M Salas, T D Fernandez, N Barbero, C Mayorga, M Blanca
Betalactam (BL) antibiotics are the drugs most frequently involved in IgE-mediated reactions. The culprit BL varies according to consumption patterns, with amoxicillin (AX) more prevalent in Southern Europe and penicillin V in Scandinavian countries. Nowadays, the combination of AX and clavulanic acid (CLV) is the most highly consumed BL containing medicine worldwide. Both BLs, AX and CLV, can independently be involved in reactions, which poses a diagnostic challenge. In patients with immediate allergic reactions to AX, two patterns of responses have been described, those responding to benzylpenicillin (cross-reactors) and those selective to AX...
February 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Cathérine L Steinbach, Christoph Töpper, Thomas Adam, Martin G Kees
BACKGROUND: Secondary peritonitis requires surgical source control and adequate antimicrobial treatment. Antimicrobial regimens are usually selected according to local susceptibility data of individual pathogens against single agents, but this neglects both the polymicrobial nature of the infection and the use of combination therapy. We analysed the probability of common regimens to cover all relevant pathogens isolated in one patient ("spectrum adequacy rate", SAR) in a real-life data set...
2015: Annals of Clinical Microbiology and Antimicrobials
Emine Alp, Tülay Orhan, Cemile Atalay Kürkcü, Safiye Ersoy, Mary-Louise McLaws
BACKGROUND: Patients in resourced-limited neonatal and pediatric intensive care units (NICU and PICU) are vulnerable to healthcare associated infections (HAI). We report the incidence of HAI, multidrug resistant microorganisms (MDROs) and the pattern of antibiotic usage in the first six years of a surveillance program in a teaching hospital in Turkey. METHODS: Between 2007 and 2012 surveillance data for HAI, MDROs and antibiotic usage were collected from the infection control department, pathology, hospital admissions and pharmacy...
2015: Antimicrobial Resistance and Infection Control
María Del C Valdivia-Tapia, Elizabeth Pinelo-Chumbe, Nilton Y Carreazo
Listeria meningoencephalitis is a rare condition, occurring mainly in immunocompromised patients. We present two cases of Listeria monocytogenes meningoencephalitis in immunocompetent children, with successful treatment with betalactam/aminoglycoside combination. Unpasteurized cheese was postulated as the source of infection.
August 2015: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
E R Gomes, K Brockow, S Kuyucu, F Saretta, F Mori, N Blanca-Lopez, H Ott, M Atanaskovic-Markovic, M Kidon, J-C Caubet, I Terreehorst
When questioned, about 10% of the parents report suspected hypersensitivity to at least one drug in their children. However, only a few of these reactions can be confirmed as allergic after a diagnostic workup. There is still a lack of knowledge on drug hypersensitivity (DH) epidemiology, clinical spectrum, and appropriate diagnostic methods particularly in children. Meanwhile, the tools used for DH management in adults are applied also for children. Whereas this appears generally acceptable, some aspects of DH and management differ with age...
February 2016: Allergy
Eda Karadağ Öncel, Yasemin Özsürekci, Yakut Akyön, Deniz Gür, Ali Bülent Cengiz, Ateş Kara
Kluyvera is a relatively newly described member of the Enterobacteriaceae family that rarely causes infections in humans. In the pediatric population, it is described in association with clinically significant infections ranging from urinary tract infections to sepsis with multiorgan failure. Our aim is to determine the clinical significance of K. ascorbata infections in the pediatric population at our institution. We retrospectively analyzed clinical microbiology data as from 2006 and identified four clinically significant isolates in this period...
June 2015: Türk Pediatri Arşivi
Corina Glanzmann, Bernhard Frey, Priska Vonbach, Christoph R Meier
BACKGROUND: Acute kidney injury (AKI) is a serious condition in critically ill children. Nephrotoxic medication exposure is a common contributing factor to AKI, but little literature is available in pediatrics. The aim of the present study was to assess potential associations between drugs and the risk of developing AKI. METHODS: We performed a retrospective case-control study in a pediatric intensive care unit (PICU). Cases were patients who developed AKI during PICU stay...
January 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Soledad Lopez, Enrique Gomez, Maria J Torres, David Pozo, Tahia D Fernandez, Adriana Ariza, Maria L Sanz, Miguel Blanca, Cristobalina Mayorga
The mechanisms leading to drug allergy in predisposed patients, especially those related to T-cell-mediated drug hypersensitivity, are not well understood. A key event in allergic reactions to drugs is the maturation process undergone by dendritic cells (DCs). Although amoxicillin (AX) has been reported to interact and maturate DCs from patients with AX-induced delayed-type hypersensitivity, the cell signaling pathways related to AX-mediated DC maturation have not been elucidated. We sought to determine the role of the MAPK and NF-κΒ pathways on AX-induced DC maturation and functional status...
November 1, 2015: Toxicology and Applied Pharmacology
Francisco Javier Candel, Elvira Baos, Mercedes Nieto, Juan José Picazo
INTRODUCTION: Coagulase negative Staphylococcus continues generating interest in critically ill patients, due to their infections in extended admissions, in instrumented patients and due to their described multidrug resistance, which include glycopeptide heterorresistance and the increase in oxazolidinone resistance. Ceftaroline is a new cephalosporin with activity against resistant gram-positives, which, being betalactam, may provide adequate safety profile in the critical ill patient...
August 2015: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
Vanessa da Costa Andrade, Bruna Del Busso Zampieri, Eliete Rodrigues Ballesteros, Aline Bartelochi Pinto, Ana Julia Fernandes Cardoso de Oliveira
Bacterial resistance is a rising problem all over the world. Many studies have showed that beach sands can contain higher concentration of microorganisms and represent a risk to public health. This paper aims to evaluate the densities and resistance to antimicrobials of Escherichia coli strains, isolated from seawater and samples. The hypothesis is that microorganisms show higher densities in contaminated beach sands and more antimicrobial resistance than the water column. Density, distribution, and antimicrobial resistance of bacteria E...
June 2015: Environmental Monitoring and Assessment
Zachary R Smith, Sharla K Tajchman, Brian M Dee, Jeffrey J Bruno, Wei Qiao, Frank P Tverdek
PURPOSE: Development of a combination antibiogram to identify combinations of antibiotics that have the highest likelihood of attaining one active agent in the empiric management of presumed Pseudomonas aeruginosa bacteremia. METHODS: Patients with cancer and P. aeruginosa bacteremia from January 1 to December 31, 2012 were included in this analysis. The primary outcome was identification of effective combinations of beta-lactam and non-betalactam agents. An effective combination was defined as one which achieved in-vitro activity to greater than or equal to 85% of isolates collected...
June 2016: Journal of Oncology Pharmacy Practice
Thomas Steinke, Stefan Moritz, Stefanie Beck, Carsten Gnewuch, Martin G Kees
BACKGROUND: In ICU patients, glomerular filtration is often impaired, but also supraphysiological values are observed ("augmented renal clearance", >130 mL/min/1.73 m(2)). Renally eliminated drugs (e.g. many antibiotics) must be adjusted accordingly, which requires a quantitative measure of renal function throughout all the range of clinically encountered values. Estimation from plasma creatinine is standard, but cystatin C may be a valuable alternative. METHODS: This was a secondary analysis of renal function parameters in 100 ICU patients from two pharmacokinetic studies on vancomycin and betalactam antibiotics...
2015: BMC Anesthesiology
Ngo Tat Trung, Tran Thi Thu Hien, Tran Thi Thanh Huyen, Dao Thanh Quyen, Mai Thanh Binh, Phan Quoc Hoan, Christian G Meyer, Thirumalaisamy P Velavan, Le Huu Song
UNLABELLED: Surgical site infection (SSI) is common in Vietnamese post-operative patients. It contributes to increased morbidity, mortality, hospitalization time and health care expenditure. Bacterial culture is considered the gold standard procedure to identify SSI pathogens and antibiotic resistant properties; however, it can detect microbes that can readily grow and is time-consuming. We propose optimized multiplex PCR assays to diagnose the most relevant microbes and associated genes encoding for acquired extended spectrum betalactamases (ESBL) or carbapenemases from Vietnamese patients with SSI in a hospital setting in Hanoi...
2015: Annals of Clinical Microbiology and Antimicrobials
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