Dalbavancin in clinical practice in Spain: a 2 year retrospective study

Objectives Dalbavancin is approved for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) in adults. Its unique pharmacokinetic properties allow daily dosing to be avoided. The objective was to describe the sociodemographic and clinical characteristics of patients treated with dalbavancin in Spain, and to evaluate its effectiveness and safety in real-world settings. Patients and methods This non-interventional, retrospective, observational and multicentre study included patients who received at least one dose between 2018 and 2019 in seven Spanish hospitals. Results In total, 187 patients were included. The most common comorbidities were cardiovascular disease (27.4%) and diabetes mellitus (23.5%). Dalbavancin was used to treat osteoarticular infections (28.3%), ABSSSIs (22.5%), cardiovascular infections (20.9%) and catheter-related infections (18.2%). The most prevalent pathogens were Staphylococcus aureus (34.2%), CoNS (32.6%), and enterococci (12.8%). The main reason for use was early hospital discharge (65.8%). Most patients were treated with 1500 mg in a single dose (35.3%) and the median duration of treatment was 2 weeks. The treatment was clinically successful in 91.4% of cases. Six patients (3.2%) reported adverse events. Physicians agreed on the potential reduction of hospitalization days (85.3%). A subanalysis of patient characteristics and type of pathogen showed similar results in terms of efficacy and safety. Conclusions Dalbavancin seems to be effective and safe as second-line treatment in severe Gram-positive infections. It improves treatment adherence and allows outpatient management. Furthermore, the effectiveness and safety profile are maintained against diverse microorganisms in Gram-positive infections and regardless of the patients' comorbidities at baseline, or age

Prosthetic joint infection by Bordetella holmesii: Case report and a review of the literature

Introduction: Bordetella holmesii is a Gram-negative coccobacillus involved in different infections mostly described in case reports. Prosthetic joint infections in relation to this pathogen are rare. Here, we present the third case of B. holmesii in a patient without anatomical or functional spleen dysfunction. Case report: The patient was a 62-year-old female with a total knee prosthesis implanted in 1997 that required multiple replacements of the femoral component due to aseptic loosening in the past years. The patient was admitted to our hospital for an elective replacement surgery due to new radiological signs of loosening. B. holmesii was isolated from synovial fluid obtained during surgery. The identification was performed by matrix-assisted laser desorption ionization-time of flight mass spectrometry and confirmed by 16S rRNA gene amplification and sequencing. Antibiotic treatment was started but 14 days after surgery the patient presented pain and joint effusion. An arthrocentesis was performed and synovial fluid culture was positive again for B. holmesii. Surgical debridement including polyethylene replacement was performed and antibiotic treatment was continued for 3 months. After a 2-year follow-up period, the patient remained asymptomatic and physical examination showed normal function of the prosthesis. Conclusion: B. holmesii is an uncommon cause of bone and joint infections. This case indicates that this microorganism is a potential pathogen of prosthetic or native arthritis, and it should be considered when cultures are negative and in cases presenting torpid evolution

Dalbavancin in clinical practice in Spain: a 2 year retrospective study

Dalbavancin; Acute bacterial skin; Gram-positive infectionsDalbavancina; Pell bacteriana aguda; Infeccions gram-positivesDalbavancina; Piel bacteriana aguda; Infecciones gram-positivasObjectives Dalbavancin is approved for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) in adults. Its unique pharmacokinetic properties allow daily dosing to be avoided. The objective was to describe the sociodemographic and clinical characteristics of patients treated with dalbavancin in Spain, and to evaluate its effectiveness and safety in real-world settings. Patients and methods This non-interventional, retrospective, observational and multicentre study included patients who received at least one dose between 2018 and 2019 in seven Spanish hospitals. Results In total, 187 patients were included. The most common comorbidities were cardiovascular disease (27.4%) and diabetes mellitus (23.5%). Dalbavancin was used to treat osteoarticular infections (28.3%), ABSSSIs (22.5%), cardiovascular infections (20.9%) and catheter-related infections (18.2%). The most prevalent pathogens were Staphylococcus aureus (34.2%), CoNS (32.6%), and enterococci (12.8%). The main reason for use was early hospital discharge (65.8%). Most patients were treated with 1500 mg in a single dose (35.3%) and the median duration of treatment was 2 weeks. The treatment was clinically successful in 91.4% of cases. Six patients (3.2%) reported adverse events. Physicians agreed on the potential reduction of hospitalization days (85.3%). A subanalysis of patient characteristics and type of pathogen showed similar results in terms of efficacy and safety. Conclusions Dalbavancin seems to be effective and safe as second-line treatment in severe Gram-positive infections. It improves treatment adherence and allows outpatient management. Furthermore, the effectiveness and safety profile are maintained against diverse microorganisms in Gram-positive infections and regardless of the patients’ comorbidities at baseline, or age.This work was supported by Angelini Pharma España, S.L.U

Intraoperative Transfusion of Red Blood Cell Units Stored >14 Days is Associated with an Increased Risk of Prosthetic Joint Infection.

Background: The aim of the present study was to evaluate the association between prosthetic joint infection (PJI) after joint arthroplasty and the length of red blood cell (RBC) storage, timing of RBC transfusion, and the number of RBC units transfused. Study design and Methods: All patients who underwent a primary or revision joint artrhoplasty between January 2000 and December 2012 were retrospectively reviewed. For this study, only patients who received RBC transfusions during the day of the surgery (early transfusion group) or within the first 4 days after surgery (late transfusion group) were included. Results: A total of 9906 patients were reviewed. In the early transfusion group (n=1153, 11.6%), patients receiving 1 or 2 RBC units (3.5% vs 6.3%, P=0.041), 3 or 4 RBC (1.3% vs 13.3%, P=0.004) or ≥5 RBC units (5.0% vs 37.5%, P=0.026) had a higher PJI rate only when >50% of RBC units transfused had been stored >14 days. In the late transfusion group (n=920, 9.3%) these differences were not significant. Early transfusion of RBCs stored >14 days was an independent variable associated with an increased risk of PJI (OR:2.50, 95%CI:1.44-4.33) Conclusion: Transfusion of RBC within the first 6h after joint arthroplasty was an independent variable associated with PJI risk when RBC units are stored >14 days. The rate of PJI increased with the number of old RBC units transfused within this critical period

Schizosaccharomyces selective differential media

This study discusses the optimisation of a selectiv e and differential medium which would facilitate the isolation of Schizosaccharomyces (a genus with a low incidence compared to other microorganisms) to select individuals from this genus for industrial purposes, especially in light of the recent approval of the use of yeasts from this genus in the wine industry by the International Organisation of Vine and Wine, or to detect the presence of such yeasts, for those many authors who consider them food spoilers. To this end, we studied various selective differential agents based on the main thephysiological characteristics of this species, such as its high resistance to high concentrations of sugar, sulfur dioxide, sorbic acid, benzoic acid, acetic acid or malo ethanolic fermentation. This selective medium is based on the resistance of the genus to the antibiotic actidione and its high resistance to inhibitory agents such as benzoic acid compared to possible microorganisms which can give rise to false positive results. Malic acid was used as a differential fact or due to the ability of this genus to metabolise it to ethanol, which allows detecting of the degradation of this compound. Lastly, the medium was successfully used to isolate strains of Schizosaccharomyces pombe from honey

Long-Term Use of Tedizolid in Osteoarticular Infections: Benefits among Oxazolidinone Drugs

Background: To evaluate the efficacy and safety of long-term use of tedizolid in osteoarticular infections. Methods: Multicentric retrospective study (January 2017–March 2019) of osteoarticular infection cases treated with tedizolid. Failure: clinical worsening despite antibiotic treatment or the need of suppressive treatment. Results: Cases (n = 51; 59% women, mean age of 65 years) included osteoarthritis (n = 27, 53%), prosthetic joint infection (n = 17, 33.3%), and diabetic foot infections (n = 9, 18%); where, 59% were orthopedic device-related. Most frequent isolates were Staphylococcus spp. (65%, n = 47; S. aureus, 48%). Reasons for choosing tedizolid were potential drug-drug interaction (63%) and cytopenia (55%); median treatment duration was 29 days (interquartile range -IQR- 15–44), 24% received rifampicin (600 mg once daily) concomitantly, and adverse events were scarce (n = 3). Hemoglobin and platelet count stayed stable throughout treatment (from 108.6 g/L to 116.3 g/L, p = 0.079; and 240 × 109/L to 239 × 109/L, p = 0.942, respectively), also in the subgroup of cases with cytopenia. Among device-related infections, 33% were managed with implant retention. Median follow-up was 630 days and overall cure rate 83%; among failures (n = 8), 63% were device-related infections. Conclusions: Long-term use of tedizolid was effective, showing a better safety profile with less myelotoxicity and lower drug-drug interaction than linezolid. Confirmation of these advantages could make tedizolid the oxazolidinone of choice for most of osteoarticular infections

The Arabidopsis Transcription Factor CDF3 Is Involved in Nitrogen Responses and Improves Nitrogen Use Efficiency in Tomato

Nitrate is an essential macronutrient and a signal molecule that regulates the expression of multiple genes involved in plant growth and development. Here, we describe the participation of Arabidopsis DNA binding with one finger (DOF) transcription factor CDF3 in nitrate responses and shows that CDF3 gene is induced under nitrate starvation. Moreover, knockout cdf3 mutant plants exhibit nitrate-dependent lateral and primary root modifications, whereas CDF3 overexpression plants show increased biomass and enhanced root development under both nitrogen poor and rich conditions. Expression analyses of 35S::CDF3 lines reveled that CDF3 regulates the expression of an important set of nitrate responsive genes including, glutamine synthetase-1, glutamate synthase-2, nitrate reductase-1, and nitrate transporters NRT2.1, NRT2.4, and NRT2.5 as well as carbon assimilation genes like PK1 and PEPC1 in response to N availability. Consistently, metabolite profiling disclosed that the total amount of key N metabolites like glutamate, glutamine, and asparagine were higher in CDF3-overexpressing plants, but lower in cdf3-1 in N limiting conditions. Moreover, overexpression of CDF3 in tomato increased N accumulation and yield efficiency under both optimum and limiting N supply. These results highlight CDF3 as an important regulatory factor for the nitrate response, and its potential for improving N use efficiency in crops

The targeted overexpression of SlCDF4 in the fruit enhances tomato size and yield involving gibberellin signalling

[EN] Tomato is one of the most widely cultivated vegetable crops and a model for studying fruit biology. Although several genes involved in the traits of fruit quality, development and size have been identified, little is known about the regulatory genes controlling its growth. In this study, we characterized the role of the tomato SlCDF4 gene in fruit development, a cycling DOF-type transcription factor highly expressed in fruits. The targeted overexpression of SlCDF4 gene in the fruit induced an increased yield based on a higher amount of both water and dry matter accumulated in the fruits. Accordingly, transcript levels of genes involved in water transport and cell division and expansion during the fruit enlargement phase also increased. Furthermore, the larger amount of biomass partitioned to the fruit relied on the greater sink strength of the fruits induced by the increased activity of sucrose-metabolising enzymes. 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Multifaceted role of cycling DOF factor 3 (CDF3) in the regulation of flowering time and abiotic stress responses in Arabidopsis

[EN] DNA-binding with one finger (DOF)-type transcription factors are involved in many fundamental processes in higher plants, from responses to light and phytohormones to flowering time and seed maturation, but their relation with abiotic stress tolerance is largely unknown. Here, we identify the roles of CDF3, an Arabidopsis DOF gene in abiotic stress responses and developmental processes like flowering time. CDF3 is highly induced by drought, extreme temperatures and abscisic acid treatment. The CDF3 T-DNA insertion mutant cdf3-1 is much more sensitive to drought and low temperature stress, whereas CDF3 overexpression enhances the tolerance of transgenic plants to drought, cold and osmotic stress and promotes late flowering. Transcriptome analysis revealed that CDF3 regulates a set of genes involved in cellular osmoprotection and oxidative stress, including the stress tolerance transcription factors CBFs, DREB2A and ZAT12, which involve both gigantea-dependent and independent pathways. Consistently, metabolite profiling disclosed that the total amount of some protective metabolites including -aminobutyric acid, proline, glutamine and sucrose were higher in CDF3-overexpressing plants. Taken together, these results indicate that CDF3 plays a multifaceted role acting on both flowering time and abiotic stress tolerance, in part by controlling the CBF/DREB2A-CRT/DRE and ZAT10/12 modules.We thank Dr Pablo Gonzalez-Melendi and Dr Jan Zouhar for technical handling of the confocal microscope and Dr Rafael Catala for the assistance with the low temperature stress assays. This work was supported by grants from Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria (INIA; projects 2009-0004-C01, 2012-0008-C01), Spanish Ministry of Science and Innovation (projects BIO2010-1487, BFU2013-49665-EXP). A.R.C. and J.D.F. were supported by INIA pre-doctoral fellowshipsCorrales, AR.; Carrillo, L.; Lasierra, P.; Nebauer, SG.; Dominguez-Figueroa, J.; Renau-Morata, B.; Pollmann, S.... (2017). Multifaceted role of cycling DOF factor 3 (CDF3) in the regulation of flowering time and abiotic stress responses in Arabidopsis. Plant Cell & Environment. 40(5):748-764. https://doi.org/10.1111/pce.12894S748764405Achard, P., Gong, F., Cheminant, S., Alioua, M., Hedden, P., & Genschik, P. (2008). The Cold-Inducible CBF1 Factor–Dependent Signaling Pathway Modulates the Accumulation of the Growth-Repressing DELLA Proteins via Its Effect on Gibberellin Metabolism. The Plant Cell, 20(8), 2117-2129. doi:10.1105/tpc.108.058941Ahuja, I., de Vos, R. C. H., Bones, A. 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Gambling disorder duration and cognitive behavioural therapy outcome considering gambling preference and sex

Gambling Disorder (GD) is a behavioural addiction that leads to high level of clinical distress and, in general, it is characterized by enduring symptomatology that presents high rates of chronicity. However, there is high variability of illness duration among patients who seek treatment for GD. Previous studies reported mixed results about the relevance of illness duration in GD treatment outcome. However, there are different profiles of patients who are diagnosed with GD. For this reason, this study aimed to evaluate the effect of illness duration in the treatment outcome of different profiles of GD patients according to their gambling preference and sex. The sample were 1699 patients diagnosed with GD. All patients received cognitive-behavioural therapy in a group format. Treatment outcome was evaluated in terms of relapsing to gambling behaviours and dropout from treatment. Results showed higher probability of poor outcome in the first years of the disorder for strategic gambling compared to non-strategic or mixed forms of gambling. Moreover, women also showed higher probability of poor outcomes than men since the first stages of the disorder. This study draws attention to the relevance of illness duration in the treatment outcome of specific profiles of GD patients. In particular, patients who presented a preference for strategic forms of gambling and women who are diagnosed with GD would have a higher risk of poor treatment outcomes since the first stages of the disorder. These results highlight the importance of an early intervention in these patients in order to prevent the chronicity of the disorder