The clinical correlation of fluconazole antifungal susceptibility testing (AST) for Candida isolates and its integration with pharmacokinetics/pharmacodynamics (PK/PD) parameters is unclear. We ...analysed the impact of fluconazole minimum inhibitory concentration (MIC) values, 24-hour area under the concentration–time curve (AUC24) and AUC24/MIC ratio on the outcome of candidemic patients.
We included 257 episodes of candidaemia treated with fluconazole monotherapy for ≥72 hours from a population-based surveillance conducted in 29 hospitals (CANDIPOP Project). AST was centrally performed by European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) microdilution methods. Primary outcome was clinical failure (30-day mortality and/or persistent candidaemia for ≥72 hours from initiation of therapy). Secondary outcomes included early (3–7 days) and late (3–30 days) mortality.
Rates of clinical failure, early and late mortality among evaluable episodes were 32.3% (80/248), 3.1% (8/257) and 23.4% (59/248). There was no relationship between fluconazole MIC values or PK/PD parameters and clinical failure. Although MIC values ≥2 mg/L by EUCAST (positive predictive value 32.1%, negative predictive value 68.7%) and ≥0.5 mg/L by CLSI (positive predictive value 34.8%, negative predictive value 74.4%) appeared to be optimal for predicting clinical failure, no significant associations remained after multivariate adjustment (odds ratio 1.67; 95% confidence interval 0.48–5.79; p 0.423). Lack of association was consistent for alternative thresholds (including proposed clinical breakpoints). The only association found for secondary outcomes was between an AUC24/MIC ratio >400 h by CLSI and early mortality (odds ratio 0.18; 95% confidence interval 0.04–0.98; p 0.026).
High fluconazole MIC values did not negatively impact outcome of patients with candidaemia treated with fluconazole. No effect of PK/PD targets on the risk of clinical failure was found.
Abstract The in vitro activity of penicillin, ampicillin, cefditoren, cefotaxime, erythromycin, clarithromycin, and levofloxacin against 763 clinical isolates of Streptococcus pyogenes was ...determined. Clinically significant isolates collected from November 2005 to December 2006 in the Czech Republic, Slovakia, Hungary, Poland, Romania, Estonia, Latvia, and Lithuania (the latter 3 analyzed as Baltic countries) were studied. No resistance to β-lactams and levofloxacin was found. The rate of erythromycin resistance in S. pyogenes varied among countries, being low (<10%) in Romania and Baltic countries, intermediate (10–20%) in Poland and Czech Republic, and high (>25%) in Hungary and Slovakia. The predominant (75.0%) erythromycin-resistant phenotype among S. pyogenes isolates was MLSB . The identification of the prevalence of erythromycin resistance mechanism could have impact on the choice of empiric antibiotic therapy for the clinicians in such countries.
Objective. Premature atherosclerosis in patients with SLE is partially explained by traditional risk factors; therefore, we aimed to identify lupus-related risk factors for coronary artery ...calcifications.
Methods. An inception cohort of 139 lupus patients (93% females) was screened for coronary artery calcifications using Multidetector CT, after 5.1 years of follow-up. Clinical and immunological variables and cardiovascular risk factors were assessed longitudinally. Also, 100 age- and sex-matched healthy subjects were studied. Correlates for calcifications were analysed in lupus patients, including levels of lipids and inflammatory molecules in samples obtained at enrolment, mid-term follow-up and at screening.
Results. At enrolment, lupus patients were 27.2 (9.1) years of age and with a disease duration of 5.4 (3.8) months. Calcifications were detected in 7.2% of patients and 1% of controls unadjusted odds ratio (OR) 7.7, 95% CI 1.05, 336.3, P = 0.02. In lupus, calcifications were detected since the age of 23 years and from 3 years of diagnosis. Patients with calcifications were older, post-menopausal, and had higher levels of serum apolipoprotein B and Framingham risk scores (P < 0.05). Lupus-related factors identified included age at diagnosis, IgG aCLs, cumulative lupus activity, length of moderate/severe activity and cumulative dose of prednisone and CYC (P < 0.05). Use of anti-malarials was protective (P = 0.006). Logistic regression analysis showed as predictors of calcification: disease duration (OR 15.1, 95% CI 2.6, 87.2), age at enrolment (OR 8.5, 95% CI 1.7, 43.0) and SLEDAI 2000 update (SLEDAI-2K) mean area under the curve (OR 12.3, 95% CI 2.5, 61.8). Longitudinal analyses of lipids and inflammatory molecules did not differ between patients.
Conclusions. Disease activity is a potentially modifiable risk factor for coronary artery calcifications in SLE. Therefore, management of traditional risk factors plus tight control of lupus activity, including the use of anti-malarials, is recommended.
Noninvasive ventilation (NIV) is increasingly used in patients with acute respiratory distress syndrome (ARDS). The evidence supporting NIV use in patients with ARDS remains relatively sparse.
To ...determine whether, during NIV, the categorization of ARDS severity based on the Pa
/Fi
Berlin criteria is useful.
The LUNG SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) study described the management of patients with ARDS. This substudy examines the current practice of NIV use in ARDS, the utility of the Pa
/Fi
ratio in classifying patients receiving NIV, and the impact of NIV on outcome.
Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on Days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severity based on Pa
/Fi
ratio was associated with an increase in intensity of ventilatory support, NIV failure, and intensive care unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate, and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1% and 45.4%, respectively. NIV use was independently associated with increased ICU (hazard ratio, 1.446 95% confidence interval, 1.159-1.805), but not hospital, mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a Pa
/Fi
lower than 150 mm Hg.
NIV was used in 15% of patients with ARDS, irrespective of severity category. NIV seems to be associated with higher ICU mortality in patients with a Pa
/Fi
lower than 150 mm Hg. Clinical trial registered with www.clinicaltrials.gov (NCT 02010073).
In situ anionic homo- and copolymerization of caprolactam (CL) and laurolactam (LL) with sodium montmorillonite clay (NaMMT) was carried out using two different initiators, sodium caprolactamate ...(CLNa) and caprolactam magnesium bromide (CLMgBr). Degree of conversion and final molecular weight were used to assess the advancement and efficiency of the polymerization reaction and X-ray diffraction and electron microscopy were used to evaluate the sodium montmorillonite clay intercalation/exfoliation. The use of CLNa as initiator produced a higher conversion degree and molecular weight than the use of CLMgBr. Through DSC, it was observed that CLNa and CLMgBr tended to produce random and block copolymer structures, respectively, and either random or block, this eventually has an effect on the clay dispersion within the polymer matrix. In all cases, increasing the LL content produced a decrease in the conversion degree and in the molecular weight of the resulting polymer.
Paradoxical growth (PG) and trailing effect (TE) are frequently observed during antifungal susceptibility testing (AFST). These two phenomena interfere with the determination of the minimal ...inhibitory concentration (MIC). The aim of this study was to assess the clinical impact of TE and PG.
We analysed the frequency of TE and PG of 690 Candida isolates collected from a population-based study performed in Spain (CANDIPOP) and correlated the results with clinical outcome of the patients.
Around 70% (484/690) of the isolates exhibited TE to azoles. Candida tropicalis showed the highest presence of TE (39/53 isolates exhibited residual growth >25% of control). No TE was seen in most of the isolates from the psilosis complex. PG was mainly associated with echinocandins. In patients treated with fluconazole within the first 48 hours after blood sampling (n = 221), the presence of TE to azoles tended to be associated with lower 30-day mortality (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.25–1.00) but not with clinical failure (OR 0.85, 95% CI 0.45–1.54). In the subgroup of 117 patients treated with echinocandins, the presence of PG was not associated with patient's response to antifungal treatment (OR for 30-day mortality 1.63, 95% CI 0.76–4.03; OR for clinical failure 1.17, 95% CI 0.53–2.70).
TE or PG are widely expressed among Candida spp., although they do not seem to influence clinical outcome.
Scientific interest in iron-oxides and in particular magnetite has been renewed due to the broad scope of their fascinating properties, which are finding applications in electronics and biomedicine. ...Specifically, iron oxide nanoparticles (IONPs) are gathering attraction in biomedicine. Their cores are usually constituted by a mixture of maghemite and magnetite phases. In view of this, to fine-tune the properties of an ensemble of IONPs towards their applications, it is essential to enhance mass fabrication processes towards the production of monodisperse IONPs with controlled size, shape, and stoichiometry. We exploit the vacancy sensitivity of the Verwey transition to detect the presence of magnetite. Here we provide direct evidence for the Verwey transition in an ensemble of IONPs through neutron diffraction. This transition is observed as a variation in the Fe magnetic moment at octahedral sites and, in turn, gives rise to a change of the net magnetic moment. Finally, we show this variation as the microscopic ingredient driving the characteristic kink that hallmarks the Verwey transition in thermal variation of magnetization.
We exploit the Verwey transition to detect the presence of magnetite in an ensemble of IONPs by using the thermal evolution value of the magnetic moment obtained by neutron diffraction in a mixture of maghemite and magnetite phases in their cores.
OBJECTIVETo determine the incidence and impact of Aspergillus spp. isolation (AI) on ICU mortality in critically ill patients with severe influenza pneumonia during the first 24h of admission. ...DESIGNSecondary analysis of an observational and prospective cohort study. SETTINGICUs voluntary participating in the Spanish severe Influenza pneumonia registry, between June 2009 and June 2019. PATIENTSConsecutive patients admitted to the ICU with diagnosis of severe influenza pneumonia, confirmed by real-time polymerase chain reaction. INTERVENTIONSNone. MAIN VARIABLES OF INTERESTIncidence of AI in respiratory samples. Demographic variables, comorbidities, need for mechanical ventilation and the presence of shock according at admission. Acute Physiology and Chronic Health Evaluation II (APACHE II) scale calculated on ICU admission. RESULTS3702 patients were analyzed in this study. AI incidence was 1.13% (n=42). Hematological malignancies (OR 4.39, 95% CI 1.92-10.04); HIV (OR 3.83, 95% CI 1.08-13.63), and other immunosuppression situations (OR 4.87, 95% CI 1.99-11.87) were factors independently associated with the presence of Aspergillus spp. The automatic CHAID decision tree showed that hematologic disease with an incidence of 3.3% was the most closely AI related variable. Hematological disease (OR 2.62 95% CI 1.95-3.51), immunosuppression (OR 2.05 95% CI 1.46-2.88) and AI (OR 3.24, 95% CI 1.60-6.53) were variables independently associated with ICU mortality. CONCLUSIONSEmpirical antifungal treatment in our population may only be justified in immunocompromised patients. In moderate-high risk cases, active search for Aspergillus spp. should be implemented.
Abstract
The differential stomatal regulation of transpiration among plant species in response to water deficit is not fully understood, although several hydraulic traits have been reported to ...influence it. This knowledge gap is partly due to a lack of direct and concomitant experimental data on transpiration, stomatal conductance, and hydraulic traits. We measured sap flux density (Js), stomatal conductance (gs), and different hydraulic traits in five crop species. Our aim was to contribute to establishing the causal relationship between water consumption and its regulation using a hydraulic trait-based approach. The results showed that the species-specific regulation of Js by gs was overall coordinated with the functional hydraulic traits analysed. Particularly relevant was the negative and significant relationship found between the Huber value (Hv) and its functional analogue ratio between maximum Js and gs (Jsmax/gsmax) which can be understood as a compensation to maintain the hydraulic supply to the leaves. The Hv was also significantly related to the slope of the relationship between gs and Js response to vapour pressure deficit and explained most of its variability, adding up to evidence recognizing Hv as a major trait in plant water relations. Thus, a hydraulic basis for regulation of tree water use should be considered.
We found coordination between stomatal regulation of tree transpiration and hydraulic traits, with the Huber value being the trait with the most predominant role in the stomatal control–water use relationship.
OBJECTIVETo determine whether the prior usage of the flu vaccine is a risk factor for bacterial co-infection in patients with severe influenza. DESIGNThis was a retrospective observational cohort ...study of subjects admitted to the ICU. A propensity score matching, and logistic regression adjusted for potential confounders were carried out to evaluate the association between prior influenza vaccination and bacterial co-infection. SETTINGS184 ICUs in Spain due to severe influenza. PATIENTSPatients included in the Spanish prospective flu registry. INTERVENTIONSFlu vaccine prior to the hospital admission. RESULTSA total of 4175 subjects were included in the study. 489 (11.7%) received the flu vaccine prior to develop influenza infection. Prior vaccinated patients were older 71 61-78, and predominantly male 65.4%, with at least one comorbid condition 88.5%. Prior vaccination was not associated with bacterial co-infection in the logistic regression model (OR: 1.017; 95%CI 0.803-1.288; p=0.885). After matching, the average treatment effect of prior influenza vaccine on bacterial co-infection was not statistically significant when assessed by propensity score matching (p=0.87), nearest neighbor matching (p=0.59) and inverse probability weighting (p=0.99). CONCLUSIONSNo association was identified between prior influenza vaccine and bacterial coinfection in patients admitted to the ICU due to severe influenza. Post influenza vaccination studies are necessary to continue evaluating the possible benefits.
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