B-Lactamasas plasmídicas de espectro ampliado en Enterobacteriaceae

Este trabajo, realizado prospectivamente durante 6 años (87-92) en el hospital Ramon y Cajal, analiza la evolución de la resistencia a b-lactámicos en 24.058 Enterobacteriaceae y establece un sistema de detección fenotípica de los mecanismos de resistencia basado en criterios interpretativos con especial énfasis en el determinado por las b-lactamasas plasmidicas de espectro ampliado (bipea). Como aportaciones fundamentales destacan: caracterización de fenotipos mediados por b1pea tem y shv e influencia de mutaciones ompf- en su expresión; conocimiento de la incidencia de estas enzimas (0,3%) y detección de portadores fecales (0,5%); descripción por primera vez en España de una epidemia intrahospitalaria por Enterobacteriaceae con b1pea (tem-6/8) y caracterización de la enzima shv-6; hallazgo de una b1pea en E. gergoviae; evidencia de una gran variación en la expresión de shv-2 en K.pneumoniae (relación lineal entre cmi y actividad enzimática). Asimismo se ha estudiado los marcadores asociados de resistencia (caracterización de enzimas modificantes de aminoglicósidos) y factores epidemiológicos asociados a las bipe

Ten Issues for Updating in Community-Acquired Pneumonia: An Expert Review

Aetiology; Community acquired pneumonia; Radiologic findingsEtiologia; Pneumònia adquirida a la comunitat; Troballes radiològiquesEtiología; Neumonía adquirida en la comunidad; Hallazgos radiológicosCommunity-acquired pneumonia represents the third-highest cause of mortality in industrialized countries and the first due to infection. Although guidelines for the approach to this infection model are widely implemented in international health schemes, information continually emerges that generates controversy or requires updating its management. This paper reviews the most important issues in the approach to this process, such as an aetiologic update using new molecular platforms or imaging techniques, including the diagnostic stewardship in different clinical settings. It also reviews both the Intensive Care Unit admission criteria and those of clinical stability to discharge. An update in antibiotic, in oxygen, or steroidal therapy is presented. It also analyzes the management out-of-hospital in CAP requiring hospitalization, the main factors for readmission, and an approach to therapeutic failure or rescue. Finally, the main strategies for prevention and vaccination in both immunocompetent and immunocompromised hosts are reviewed

A systematic literature review and expert consensus on risk factors associated to infection progression in adult patients with respiratory tract or rectal colonisation by carbapenem-resistant Gram-negative bacteria

Multi-drug resistance; Risk factor; ColonizationResistencia a múltiples fármacos; Factor de riesgo; ColonizaciónResistència a múltiples fàrmacs; Factor de risc; ColonitzacióObjective. Risk factors (RFs) associated with infection progression in patients already colonised by carbapenem-resistant Gram-negative bacteria (CRGNB) have been addressed in few and disperse works. The aim of this study is to identify the relevant RFs associated to infection progression in patients with respiratory tract or rectal colonisation. Material and methods. A systematic literature review was developed to identify RFs associated with infection progression in patients with CRGNB respiratory tract or rectal colonisation. Identified RFs were then evaluated and discussed by the expert panel to identify those that are relevant according to the evidence and expert’s experience. Results. A total of 8 articles were included for the CRGNB respiratory tract colonisation and 21 for CRGNB rectal colonisation, identifying 19 RFs associated with pneumonia development and 44 RFs associated with infection progression, respectively. After discussion, the experts agreed on 13 RFs to be associated with pneumonia development after respiratory tract CRGNB colonisation and 33 RFs to be associated with infection progression after rectal CRGNB colonisation. Respiratory tract and rectal colonisation, previous stay in the ICU and longer stay in the ICU were classified as relevant RF independently of the pathogen and site of colonisation. Previous exposure to antibiotic therapy or previous carbapenem use were also common relevant RF for patients with CRGNB respiratory tract and rectal colonisation. Conclusion. The results of this study may contribute to the early identification of CRGNB colonized patients at higher risk of infection development, favouring time-to-effective therapy and improving health outcomes.This study was funded by Shionogi S.L.U

Emerging insights into nitrogen assimilation in gymnosperms

Gymnosperms are a heterogeneous and ancient group of seed plants that includes conifers, ginkgos, cycads and gnetophytes. Molecular studies on extant gymnosperms have been constrained by some discouraging features for experimental research such as their long life cycles, large sizes, complex megagenomes and abundant phenolic compounds in their woody tissues. However, the development of high-throughput sequencing and refined multiomics technologies in the last few years has allowed to explore the molecular basis of essential processes in this ancient lineage of plants. Nitrogen is one of the main limiting factors determining vascular development and biomass production in woody plants. Therefore, nitrogen uptake, metabolism, storage and recycling are essential processes for fundamental gymnosperm biology. Here, recent progress in the molecular regulation of nitrogen assimilation in gymnosperms is reviewed and some future perspectives on this topic are outlined.This research was fnancially supported by Ministry of Science and Innovation (BIO2015-73512-JIN, RTI2018-094041-B-I00 and PID2021-125040OB-I00) and by Junta de Andalucía (P20-00036 PAIDI 2020/FEDER, UE). JMVM was supported by a Grant from the Spanish Ministry of Education (FPU17/03517). Funding for open access publishing: Universidad Málaga/CBUA

Time kill-assays of antibiotic combinations for multidrug resistant clinical isolates of OXA-48 carbapenemase producing Klebsiella pneumoniae

Treatment of infections caused by OXA-48 carbapenemase producing multidrug-resistant isolates often necessitates combination therapy. In vitro effect of different antibiotic combinations against multidrug-resistant (MDR) Klebsiella pneumoniae isolates were evaluated in this study.Meropenem-tobramycin (MER+TOB), meropenem-ciprofloxacin (MER+CIP), colistin-mer-openem (COL+MER), colistin-ciprofloxacin (COL+CIP) and colistin-tobramycin (COL+TOB) combinations were tested by time kill-assays. Each antibiotic alone and in combination at their Cmax values were tested against 4 clinical K. pneumoniae isolates at 1, 2, 4, 6, 8, 12 and 24 h. Effect of colistin and its associations were also assessed at 30 min. Bactericidal activity was defined as >= 3log10 CFU mL-1 decrease compared with initial inoculum. Synergy was defined as >= 2log10CFU mL-1 decrease by the combination compared with the most active single agent. Presence of blaOXA-48, blaNDM, blaVIM, blaIMP, blaKPC and blaCTX-M-1 genes was screened by PCR using specific primers.The blaOXA-48 gene was identified together with blaCTXM-1 group gene in all isolates. COL+MER demonstrated to be synergistic and bactericidal. MER+TOB showed synergistic and bactericidal effect on two strains although, regrowth was seen on other two strains at 24 h. MER+CIP exhibited indif-ferent effect on the strains.Combination therapy could be a potential alternative to treat MDR K. pneumoniae infections. This combination might prevent resistance development and secondary effects of colistin monotherapy. MER+TOB and MER+CIP might have an isolate-dependent effect, that may not always result in synergism

Algunos aspectos de la evolución de la familia génica de glutamina sintetasa en plantas

En las plantas, la actividad glutamina sintetasa reside en miembros de la superfamilia GSII, que forman dos grupos de enzimas GS funcionales: la GSIIb eubacteriana (GLN2) y la GSIIe eucariota (GLN1/GS). Los análisis filogenéticos han demostrado que el grupo GLN2 se originó mediante un proceso de transferencia horizontal desde bacterias tras la divergencia de procariotas y eucariotas2. En las plantas vasculares solo se encuentran genes GLN1/GS, lo que sugiere que la evolución a esta composición de isoformas de GS está asociada a la adaptación final de las plantas a la vida terrestre. El estudio filogenético que presentamos reclasifica las diferentes GS de las plantas con semilla en tres grupos: GS1a, GS1b y GS23. GS1b y GS2 corresponden a las formas citosólica y cloroplastídica ampliamente estudiadas en angiospermas. Mientras que GS1a corresponde a una isoforma de localización citosólica identificada anteriormente exclusivamente en coníferas y que se ha propuesto que reemplaza funcionalmente a la forma cloroplastídica ausente en este grupo. Nuestro trabajo ha permitido también ampliar la presencia de genes que codifican la isoforma cloroplastídica GS2 a las gimnospermas Cycadopsida, lo que sugiere el origen de este gen en un ancestro común de Cycadopsida, Ginkgoopsida y angiospermas. Además, genes que codifican GS1a se han identificado en todas las gimnospermas, las angiospermas basales y algunas especies de Magnoliidae. Los estudios previos en coníferas y los perfiles de expresión génica en ginkgo y magnolia que hemos realizado en este trabajo podrían explicar la ausencia de GS1a en especies de angiospermas más recientes (por ejemplo, monocotiledóneas y eudicotiledóneas), debido a las funciones redundantes de GS1a y GS2 en las células fotosintéticas. En conjunto, los resultados proporcionan una mejor comprensión de la evolución de la familia génica de la GS en plantas.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Assessing the best time interval between doses in a two-dose vaccination regimen to reduce the number of deaths in an ongoing epidemic of SARS-CoV-2

Funding: This work was supported by the Coordination of Superior Level Staff Improvement (CAPES), Brazil (Finance Code 001 to LSF and FMDM), National Council for Scientific and Technological Development (CNPq), Brazil (grant number: 315854/2020-0 to MEB, 141698/2018-7 to RLPS, 312559/2020-8 to MASMV and 311832/2017-2 to RAK), São Paulo Research Foundation (FAPESP), Brazil (grant #2019/26310-2 and #2017/26770-8 to CF, #2018/26512-1 to OC, #2018/24037-4 to SP, #2018/23984-0 to VS and contract #2016/01343-7 to RAK) and Swiss National Science Foundation (grant PCEFP3_181243 to VS). The Sound Foundation (Massachusetts, USA) provided financial support for the open-source publication of this work via a grant to The University of Oxford (UK) to support the work of members of the COVID-19 International Modeling (CoMo) Consortium. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Etest® versus broth microdilution for ceftaroline MIC determination with Staphylococcus aureus: results from PREMIUM, a European multicentre study

Objectives: To compare the concordance of ceftaroline MIC values 24 by reference broth microdilution (BMD) and Etest (BioMérieux, France) for MSSA and MRSA isolates, respectively, in isolates from PREMIUM (D372SL00001), a European multi-centre study.  Methods: Ceftaroline MICs were determined by reference BMD and by Etest for 1,242 MSSA and MRSA from adult patients with community-acquired pneumonia or complicated skin and soft tissue infections collected between February and May 2012; tests were performed across six European laboratories. Selected isolates with ceftaroline resistance in broth (MIC >1 mg/L) were retested in three central laboratories to confirm their behaviour.  Results: Overall concordance between BMD and Etest was good, with >97% essential agreement and >95% categorical agreement. Nevertheless, 12 of the 26 MRSA isolates found resistant by BMD scored as susceptible by Etest, with MICs ≤1 mg/L, thus counting as very major errors, whereas only five of 380 MRSA found ceftaroline susceptible in BMD were mis-categorised as resistant by Etest. Twenty-one of the 26 isolates with MICs of 2 mg/L by BMD were then re-tested twice by each of three central laboratories: BMD MICs of 2 mg/L were consistently found for 19 of the 21 isolates. Among 147 Etest results for these 21 isolates (original plus six repeats per isolate) 112 were >1 mg/L.  Conclusions: BMD and Etest have good overall agreement for ceftaroline against Staphylococcus aureus; nevertheless, reliable Etest-based discrimination of the minority of ceftaroline-resistant (MIC 2 mg/L) MRSA is extremely challenging, requiring careful reading of strips, ideally with duplicate testing