Dosificación de ceftriaxona en el paciente crítico hipoproteinémico: un factor más a tener en cuenta / Dosage of ceftriaxone in the critical hypoproteinemic patient: another factor to take into account

Introducción: El objetivo principal del estudio fue evaluar la necesidad de ajuste posológico de ceftriaxona en pacientes críticos hipoproteinémicos. Pacientes y métodos: Estudio observacional y retrospectivo, llevado a cabo en la unidad de cuidados intensivos (UCI) del Hospital General Universitario de Ciudad Real (médico-quirúrgica de 21 camas), en el que se incluyeron pacientes tratados con ceftriaxona en la UCI desde enero de 2014 a diciembre de 2019 y se clasificaron en dos grupos al inicio del tratamiento: pacientes normoproteinémicos (proteínas totales >5,5g/dl) e hipoproteinémicos (proteínas totales ≤5,5g/dl).Variables principales: Edad, sexo, APACHE II, diagnóstico-localización del foco infeccioso, estancia en UCI, dosis de ceftriaxona, pauta posológica, tratamiento antibiótico concomitante, empírico o dirigido, necesidad de cambio de tratamiento, días de antibioterapia y mortalidad. Resultados: Se incluyeron 98 pacientes (44 normoproteinémicos y 54 hipoproteinémicos). No se obtuvieron diferencias estadísticamente significativas entre las características basales de ambos grupos, exceptuando la localización del foco, siendo respiratorio con mayor frecuencia en el grupo de pacientes normoproteinémicos (p=0,044). Se obtuvieron diferencias estadísticamente significativas a favor del grupo de pacientes normoproteinémicos para: estancia en UCI (p=0,001), necesidad de cambio de tratamiento antibiótico (p=0,004), días de antibioterapia (p=0,007) y mortalidad (p=0,046). Conclusión: Los resultados terapéuticos obtenidos en el grupo de pacientes críticos hipoproteinémicos tratados con ceftriaxona ponen en evidencia la necesidad de considerar la hipoproteinemia como un factor que podría condicionar dicho resultado si se emplean las pautas posológicas de tratamiento habituales. (AU)

Introduction: The main objective of the study was to evaluate the need for posologic adjustment of ceftriaxone in critical hypoproteinemic patients. Patients and methods: Observational and retrospective study, carried out in the intensive care unit (ICU) of the General University Hospital of Ciudad Real (21-bed medical-surgical), which included patients treated with ceftriaxone in the ICU from January 2014 to December 2019 and classified into two groups at the beginning of treatment: normoproteinemic (total proteins >5.5 g/dl) and hypoproteinemic (total proteins ≤5.5g/dl) patients.Main variables: Age, sex, APACHE II, diagnosis-location of the infectious site, ICU stay, ceftriaxone dose, dosage regimen, concomitant antibiotic treatment, empirical or targeted antibiotic treatment, need to change treatment, days of antibiotic therapy and mortality. Results: 98 patients were included (44 normoproteinemics and 54 hypoproteinemics).No statistically significant differences were obtained between the basal characteristics of both groups, except for the location of the infectious site, being respiratory more frequently in the group of normoproteinemic patients (p=0.044).Statistically significant differences were obtained in favour of the group of normoproteinemic patients for: stay in ICU (p=0.001), need for change of antibiotic treatment (p=0.004), days of antibiotherapy (p=0.007) and mortality (p=0.046). Conclusion: The therapeutic results obtained in the group of critical hypoproteinemic patients treated with ceftriaxone show the need to consider hypoproteinemia as a factor that could condition such result if the usual treatment dosage guidelines are used.

Electroless controllable growth of ZnO films and their morphology-dependent antimicrobial properties.

An electroless deposition process was used to synthesize with a controlled morphology, polycrystalline ZnO on glass substrates as antimicrobial coatings. The influence of deposition temperature (Tdep) on the physicochemical and antimicrobial properties of the ZnO films was analyzed. The results indicated that a change in deposition temperature greatly affected the morphology and the degree of crystallinity of the films. Scanning electron microscope images show that the film surface is porous at a deposition temperature of 40 and 50 °C, whereas hexagonal-plate shaped morphology predominated at 60 °C and finally at 70 and 80 °C the films consisted of rod-like particles. The films showed good transparency in the visible region. All ZnO films presented notable antimicrobial activity against the gram-negative bacteria Escherichia coli (E. coli) and the gram-positive Staphylococcus aureus (S. aureus). It was found that the antimicrobial efficiency is strongly dependent on morphology and structural properties. The best antimicrobial performance was recorded for the films consisting of rod-like morphology with a high degree of crystallinity. The procedure used in this investigation is strongly recommended for the development of functional surfaces.

Endemic caseous lymphadenitis in a wild Caprinae population.

Between 2010 and 2013, an outbreak of caseous lymphadenitis (CLA) occurred in a captive stock of Iberian ibexes (Capra pyrenaica, Schinz 1838) maintained for conservation purposes in the National Game Reserve 'Ports de Tortosa i Beseit' (PTB), northeastern Spain. The aim of this study was to assess the CLA status in the free-ranging donor population of ibexes. An ELISA test to detect antibodies to CLA was performed in 360 hunter-harvested ibexes between 2007 and 2013. A spatial analysis and recursive partitioning approaches with regression tree models were used to explore CLA-associated risk factors. Nineteen per cent of ibexes had antibodies to CLA. Significant differences in seroprevalence were observed among game management areas but no clear trends of CLA occurrence were observed over the study period. Ibexes from areas of higher population density and living close to aggregation points displayed a higher probability of testing positive to CLA. These results suggest that CLA is endemic in the Iberian ibex population inhabiting PTB and density-dependent risk factors. To the best of our knowledge, this is the first record of CLA maintenance in a free-ranging wild Caprinae population.

Post-Natal Persistent Infection With Classical Swine Fever Virus in Wild Boar: A Strategy for Viral Maintenance?

In this study, fifteen wild boar piglets were intranasally inoculated <10 h after birth with the moderately virulent classical swine fever virus (CSFV) strain Catalonia 01. At 5 days post-inoculation, seven other animals within 48 h of birth were put in contact with them. Viral replication and innate and specific immune responses were evaluated. Of the inoculated animals, 46.67% remained post-natally persistently infected and were apparently healthy with neither humoral nor cellular immunological responses specific to CSFV and with high viral loads in their blood, organs and body secretions. Moreover, the present data extend the time period to 48 h after birth when a moderately virulent CSFV strain could lead to post-natal persistent infection given the generation of persistently infected wild boars in the contact group (33.33%). The innate immune response to the virus, as measured by type I IFN-α in serum, was mostly not impaired in the persistently infected wild boars. Interestingly, a decrease and lack of IFN-γ-producing cells against CSFV and PHA was observed. In endemic countries where wild swine species are increasing and low and moderate virulence CSFV strains are prevalent, the possible generation of this form of disease cannot be ruled out.

The European hare (Lepus europaeus) as a potential wild reservoir for ruminant pestiviruses.

Ruminant pestiviruses cause important economic losses in livestock and the epidemiological role of free-ranging sympatric wildlife is of special interest for the implementation of pestivirus eradication plans. Moreover, the emergence of high mortality outbreaks of pestivirus in Pyrenean chamois (Rupicapra pyrenaica pyrenaica) since 2001 in the border between Spain and France has increased the value of knowing the hosts that role pestivirus infection. In the present study, pestivirus infection was assessed in 94 sera from wild hunted European hares (Lepus europaeus) collected in two different areas: Pyrenees (alpine and subalpine ecosystems) versus Non Pyrenees (non alpine and subalpine ecosystems). The presence of antibodies against Border Disease Virus (BDV) and Bovine Viral Diarrhea Virus (BVDV) was evaluated by means of the Virus Neutralization Test and the presence of viral RNA in sera samples was assessed by Reverse transcription-polymerase chain reaction (RT-PCR). A total of 34 out of 94 (36.2%; CI95 0.26-0.46) sera presented neutralizing antibodies against ruminant pestiviruses, and significant differences between BDV4 and BVDV1 titres were found in 7 hares. In the Pyrenean area not statistically significant seroprevalence was observed when comparing with the Non Pyrenean area. RT-PCR analysis of sera samples resulted all negative. The results of the present study indicate that the European hare is susceptible to pestivirus infection and that could be involved in the epidemiology of ruminant pestiviruses. To the authors' knowledge, this is the third wild non-artiodactyl with reported antibodies against ruminant pestivirus after the rabbit and Bennet's wallaby.

Immune-system-dependent anti-tumor activity of a plant-derived polyphenol rich fraction in a melanoma mouse model.

Recent findings suggest that part of the anti-tumor effects of several chemotherapeutic agents require an intact immune system. This is in part due to the induction of immunogenic cell death. We have identified a gallotannin-rich fraction, obtained from Caesalpinia spinosa (P2Et) as an anti-tumor agent in both breast carcinoma and melanoma. Here, we report that P2Et treatment results in activation of caspase 3 and 9, mobilization of cytochrome c and externalization of annexin V in tumor cells, thus suggesting the induction of apoptosis. This was preceded by the onset of autophagy and the expression of immunogenic cell death markers. We further demonstrate that P2Et-treated tumor cells are highly immunogenic in vaccinated mice and induce immune system activation, clearly shown by the generation of interferon gamma (IFN-γ) producing tyrosine-related protein 2 antigen-specific CD8+ T cells. Moreover, the tumor protective effects of P2Et treatment were abolished in immunodeficient mice, and partially lost after CD4 and CD8 depletion, indicating that P2Et's anti-tumor activity is highly dependent on immune system and at least in part of T cells. Altogether, these results support the hypothesis that the gallotannin-rich fraction P2Et's anti-tumor effects are mediated to a great extent by the endogenous immune response following to the exposure to immunogenic dying tumor cells.

Pestivirus in alpine wild ruminants and sympatric livestock from the Cantabrian Mountains, Spain.

Bovine viral diarrhoea virus (BVDV) and Border disease virus (BDV) were investigated at the wildlife-livestock interface in the distribution area of chamois in the Cantabrian Mountains, North-Western Spain. From 2010 to 2014, sera from sympatric wild (n=167) and domestic (n=272) ruminants were analysed for pestivirus antibodies by cELISA, virus neutralisation test (VNT) and for the presence of pestiviral RNA using a reverse transcription (RT)-PCR. Results showed a higher seroprevalence in cattle (59.4 per cent, 13/13 of herds) than in domestic small ruminants (5.9 per cent sheep, 2/8 of flocks; 0 per cent goats of 4 flocks) and wildlife (10.8 per cent in red deer, 0 per cent in roe deer and 0 per cent in Cantabrian chamois). High VNT titres were detected in two cattle herds, suggesting the circulation of BVDV-1 and BVDV-2 strains. BVDV-1 RNA was detected in one cattle calf by RT-PCR and sequencing. Conversely to other similar grazing systems, sheep flocks did not play a relevant role in the pestivirus epidemiology in this region. Pestivirus infections in wild ruminants were sporadic and most probably dependent on a domestic source.

Cálculos biliares asociados al uso de ceftriaxona en niños / Gallstones in association with the use of ceftriaxone in children

INTRODUCCIÓN: La pseudocolelitiasis asociada a ceftriaxona en niños es un evento frecuente pero pocas veces tenido en cuenta; ocurre en el 15 al 57% de los que la reciben y en la mayoría de los casos cursa asintomática y autorresolutiva. PACIENTES Y MÉTODOS: Estudio prospectivo, observacional y descriptivo. Se incluyeron pacientes de 1 mes a 18 años que recibieron ceftriaxona. Se realizó ecografía de hígado y vesícula biliar al inicio del tratamiento y cada 5 días hasta finalizarlo. A los pacientes con anormalidades ecográficas se les realizó seguimiento clínico y ecográfico semanalmente hasta la resolución completa. Se buscó asociación con los factores de riesgo descritos en la literatura. RESULTADOS: Fueron incluidos 73 pacientes, 57,5% femeninos, con edad entre 4 meses y 17 años (x = 4,2 años). Se presentó pseudocolelitiasis en 31 pacientes (42,5%) y en este grupo se documentó al día 5 en el 96,8% (n = 30). El tamaño de los cálculos estuvo entre 4 y 14 mm (x = 8,1). La duración de la pseudocolelitiasis estuvo entre 9 y 55 días (x = 24,1 días). El 22,6% (n = 7) presentó síntomas y se presentó una complicación grave. En el análisis multivariado el lactato de Ringer como líquido de dilución tuvo 1,86 veces más riesgo (p = 0,019). No se encontró relación con la edad, duración ni dosis del antibiótico, ayuno, uso de suplementos de calcio, nutrición parenteral o uso de otros antibióticos. CONCLUSIÓN: Se presenta pseudocolelitiasis asociado a ceftriaxona en 4 de cada 10 niños que la reciben, sin relación con factores de riesgo tradicionales. La evolución es hacia la auto resolución aunque cerca del 20% presentan síntomas

INTRODUCTION: Ceftriaxone associated pseudolithiasis is fairly frequent in children, but rarely taken into account. It occurs in 15% to 57% of children, and in most cases is asymptomatic and resolves spontaneously. PATIENTS AND METHODS: A prospective, observational, and descriptive study was conducted that included patients aged 1 month to 18 years-old who received ceftriaxone. Liver and gallbladder ultrasound was performed at the start of treatment, and every 5 days until it was completed. Patients with abnormal ultrasound findings were followed up clinically every week until they were resolved. The findings were compared with risk factors described in the literature. RESULTS: A total of 73 patients aged between 4 months and 17 years (mean = 4.2 years) were included, of whom 57.5% were female. Pseudolithiasis was present in 31 patients (42.5%) and was documented in 96.8% (n = 30) of this group on day 5. The stone size was between 4 and 14 mm (mean = 8.1 mm). The duration of pseudolithiasis was between 9 and 55 days (mean = 24.1 days).Symptoms were present in 22.6% (n = 7) and 1 had a serious complication. In the multivariate analysis, Ringer's Lactate as fluid dilution was 1.86 times higher risk (P = 0.019). No relationship was found with age, duration and dose of antibiotic, fasting, use of calcium supplements, parenteral nutrition, or use of other antibiotics. CONCLUSION: Pseudocolelitiasis associated with ceftriaxone take place in 4 of 10 children who receive, unrelated to traditional risk factors. The trend is towards self resolution although about20% have symptoms

[Gallstones in association with the use of ceftriaxone in children]. / Cálculos biliares asociados al uso de ceftriaxona en niños.

INTRODUCTION: Ceftriaxone associated pseudolithiasis is fairly frequent in children, but rarely taken into account. It occurs in 15% to 57% of children, and in most cases is asymptomatic and resolves spontaneously. PATIENTS AND METHODS: A prospective, observational, and descriptive study was conducted that included patients aged 1 month to 18 years-old who received ceftriaxone. Liver and gallbladder ultrasound was performed at the start of treatment, and every 5 days until it was completed. Patients with abnormal ultrasound findings were followed up clinically every week until they were resolved. The findings were compared with risk factors described in the literature. RESULTS: A total of 73 patients aged between 4 months and 17 years (mean=4.2 years) were included, of whom 57.5% were female. Pseudolithiasis was present in 31 patients (42.5%) and was documented in 96.8% (n=30) of this group on day 5. The stone size was between 4 and 14mm (mean=8.1mm). The duration of pseudolithiasis was between 9 and 55 days (mean=24.1 days). Symptoms were present in 22.6% (n=7) and 1 had a serious complication. In the multivariate analysis, Ringer's Lactate as fluid dilution was 1.86 times higher risk (P=.019). No relationship was found with age, duration and dose of antibiotic, fasting, use of calcium supplements, parenteral nutrition, or use of other antibiotics. CONCLUSION: Pseudocolelitiasis associated with ceftriaxone take place in 4 of 10 children who receive, unrelated to traditional risk factors. The trend is towards self resolution although about 20% have symptoms.

Treatment of vitamin D deficiency in CKD patients with ergocalciferol: are current K/DOQI treatment guidelines adequate?

BACKGROUND: Vitamin D deficiency/insufficiency (VDDI) is common in CKD patients and may be associated with abnormal mineral metabolism. It is not clear whether the K/DOQI recommended doses of ergocalciferol are adequate for correction of VDDI and hyperparathyroidism. METHODS: Retrospective study of 88 patients with CKD Stages 1 - 5 and baseline 25-hydroxyvitamin D level < 30 ng/ml (< 75 nmol/l). Patients treated with ergocalciferol as recommended by K/DOQI guidelines. Only 53 patients had elevated baseline PTH level for the CKD stage. Patients were excluded if they received vitamin D preparations other than ergocalciferol or phosphate binders. 25-hydroxyvitamin D level, intact PTH level (iPTH), and other parameters of mineral metabolism were measured at baseline and after completion of ergocalciferol course. RESULTS: 88 patients with CKD were treated with ergocalciferol. Mean age 56.8 +/- 9.5 years and 41% were males. The mean (+/- SD) GFR was 28.3 +/- 16.6 ml/min. At the end of the 6-month period of ergocalciferol treatment, the mean 25-hydroxyvitamin D level increased from 15.1 +/- 5.8 to 23.3 +/- 11.8 ng/ml (37.75 +/- 14.5 to 58.25 +/- 29.5 nmol/l) (p < 0.001). Treatment led to > or = 5 ng/ml (12.5 nmol/l) increases in 25-hydroxyvitamin D level in 54% of treated patients, and only 25% achieved levels > or = 30 ng/ml (75 nmol/l). Mean iPTH level decreased from 157.9 +/- 125.9 to 150.7 +/- 127.5 pg/ml (p = 0.5). Only 26% of patients had > or = 30% decrease in their iPTH level after treatment with ergocalciferol. CONCLUSIONS: Current K/DOQI guidelines are inadequate for correcting VDDI or secondary hyperparathyroidism in CKD patients. Future studies should examine the effects of higher or more frequent dosing of ergocalciferol on these clinical endpoints.

Qualitative and quantitative determination of a humic model compound in microbial cultures by cyclic voltammetry.

The humic model compound, anthraquinone-2,6-disulfonate (AQDS), was characterized and measured in microbial cultures by cyclic voltammetry (CV). Under the experimental conditions, the formal reduction potential (E(o')) of the couple AQDS/AHQDS was found to be of -0.520 V vs. SCE (standard calomel electrode) at pH value of 7.0. Control experiments showed that there were no interferences of the culture medium or the microbial consortium on the quantitative determination of the quinone. The linear equation E(o') = -0.294 - 0.032 pH was found, showing that the pH used (7.0-7.8) did not affect significantly the AQDS determination by CV and AHQDS was the predominant hydroquinone formed. A calibration curve was obtained by plotting current response versus AQDS concentration with a linear correlation (r = 0.999) from 0.2 to 10 mM of AQDS. This technique was applied in a denitrifying culture to establish kinetic profiles for AHQDS formation coupled to acetate and p-cresol oxidation. CV results showed that organic matter oxidation by the denitrifying sludge was stoichiometrically associated to AQDS reduction into AHQDS-. CV was shown to be a useful tool for monitoring oxidation/reduction processes of quinones occurring in complex microbial media.

Randomized double-blind comparison of short-term itraconazole and terbinafine therapy for toenail onychomycosis.

Previous studies evaluating short-term itraconazole and terbinafine therapy for onychomycosis have varied in protocol and size; this double-blind study enabled a large-scale, standardized, direct comparison. Patients with toenail onychomycosis were randomized to itraconazole 200 mg daily (n = 146) or terbinafine 250 mg daily (n = 146) for 12 weeks, with a 36-week follow-up. Mycological cure rates at the follow-up end-point were significantly equivalent (61% with itraconazole vs. 67% with terbinafine). A similar proportion of patients in each group experienced adverse events during treatment (itraconazole, 22%; terbinafine, 23%). More patients receiving terbinafine stopped treatment permanently because of treatment-related adverse events (8% vs. 1%).

Transcriptional analysis of the 5'-noncoding region of the human involucrin gene.

Human involucrin whose gene transcription is directed by a 2456-nucleotide (nt) 5'-noncoding region is a structural component of the epithelial cornified layer. Transient transfection assays demonstrated that this region is transcriptionally active in multiplying keratinocytes and is enhanced by 2 mM CaCl2 treatment. Calcium-independent transcriptional activity and the interaction with the AP-1 transcriptional factor was located on the proximal part (nt -159 to -1) of the 5'-noncoding region. However, CaCl2 responsiveness was mapped to a distal 1185-nt fragment (nt -2456 to -1272). Moreover, this fragment potentiated the Herpes simplex thymidine kinase promoter in normal keratinocytes and is responsive to calcium treatment in a cell type-specific manner. Interestingly, the absence of a 491-nt fragment located between the two enhancer domains (nt -651 to -160) resulted in transcriptional activation in multiplying keratinocytes. This fragment interacts with AP-1 and the YY1 transcriptional silencer. It is concluded that human involucrin 5'-noncoding region contains at least three regulatory domains, a distal CaCl2-responsive enhancer, a putative transcriptional silencer (that interacts with AP-1 and YY1), and a proximal enhancer/promoter (that interacts with AP-1). Thus, this study demonstrates the presence of particular transcriptional factors can potentially regulate the human involucrin expression.

Evidence of a new antigen-antibody system (anti-Mic-1) in patients with systemic lupus erythematosus and hyperthyroidism.

Autoimmune thyroid diseases may occur in association with systemic rheumatic disorders, and usually they show a high prevalence of antithyroglobulin and antimicrosomal antibodies. We report 6 patients with the clinical association of systemic lupus erythematosus (SLE) and hyperthyroidism. Of interest, in 5 of the 6 patients (83%), we found an antibody directed against a microsomal extract of human thyroid gland which was different than previous microsomal antibodies in that it was a precipitating antibody; we have called it anti-Mic-1 antibody. We investigated the prevalence of this specific autoimmune reaction in 58 patients with idiopathic SLE, 30 with hyperthyroidism, 15 with Hashimoto's thyroiditis, 25 with insulin dependent diabetes mellitus, 45 with rheumatoid arthritis, and 25 healthy controls. No control had anti-Mic-1 antibody. In addition, this antibody was shown to be organ specific. We suggest that patients with the combined association of SLE and hyperthyroidism may represent a different subset in the spectrum of SLE. The high prevalence of this antigen-antibody reaction in these cases may serve as a serological marker of this association.