Burden and risk factors for Pseudomonas aeruginosa community-acquired pneumonia:a Multinational Point Prevalence Study of Hospitalised Patients

Pseudornonas aeruginosa is a challenging bacterium to treat due to its intrinsic resistance to the antibiotics used most frequently in patients with community-acquired pneumonia (CAP). Data about the global burden and risk factors associated with P. aeruginosa-CAP are limited. We assessed the multinational burden and specific risk factors associated with P. aeruginosa-CAP. We enrolled 3193 patients in 54 countries with confirmed diagnosis of CAP who underwent microbiological testing at admission. Prevalence was calculated according to the identification of P. aeruginosa. Logistic regression analysis was used to identify risk factors for antibiotic-susceptible and antibiotic-resistant P. aeruginosa-CAP. The prevalence of P. aeruginosa and antibiotic-resistant P. aeruginosa-CAP was 4.2% and 2.0%, respectively. The rate of P. aeruginosa CAP in patients with prior infection/colonisation due to P. aeruginosa and at least one of the three independently associated chronic lung diseases (i.e. tracheostomy, bronchiectasis and/or very severe chronic obstructive pulmonary disease) was 67%. In contrast, the rate of P. aeruginosa-CAP was 2% in patients without prior P. aeruginosa infection/colonisation and none of the selected chronic lung diseases. The multinational prevalence of P. aeruginosa-CAP is low. The risk factors identified in this study may guide healthcare professionals in deciding empirical antibiotic coverage for CAP patients

Prevalence and etiology of community-acquired pneumonia in immunocompromised patients

Background. The correct management of immunocompromised patients with pneumonia is debated. We evaluated the prevalence, risk factors, and characteristics of immunocompromised patients coming from the community with pneumonia. Methods. We conducted a secondary analysis of an international, multicenter study enrolling adult patients coming from the community with pneumonia and hospitalized in 222 hospitals in 54 countries worldwide. Risk factors for immunocompromise included AIDS, aplastic anemia, asplenia, hematological cancer, chemotherapy, neutropenia, biological drug use, lung transplantation, chronic steroid use, and solid tumor. Results. At least 1 risk factor for immunocompromise was recorded in 18% of the 3702 patients enrolled. The prevalences of risk factors significantly differed across continents and countries, with chronic steroid use (45%), hematological cancer (25%), and chemotherapy (22%) the most common. Among immunocompromised patients, community-acquired pneumonia (CAP) pathogens were the most frequently identified, and prevalences did not differ from those in immunocompetent patients. Risk factors for immunocompromise were independently associated with neither Pseudomonas aeruginosa nor non\u2013community-acquired bacteria. Specific risk factors were independently associated with fungal infections (odds ratio for AIDS and hematological cancer, 15.10 and 4.65, respectively; both P = .001), mycobacterial infections (AIDS; P = .006), and viral infections other than influenza (hematological cancer, 5.49; P < .001). Conclusions. Our findings could be considered by clinicians in prescribing empiric antibiotic therapy for CAP in immunocompromised patients. Patients with AIDS and hematological cancer admitted with CAP may have higher prevalences of fungi, mycobacteria, and noninfluenza viruses

Microbiological testing of adults hospitalised with community-acquired pneumonia: An international study

This study aimed to describe real-life microbiological testing of adults hospitalised with community-acquired pneumonia (CAP) and to assess concordance with the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) and 2011 European Respiratory Society (ERS) CAP guidelines. This was a cohort study based on the Global Initiative for Methicillin-resistant Staphylococcus aureus Pneumonia (GLIMP) database, which contains point-prevalence data on adults hospitalised with CAP across 54 countries during 2015. In total, 3702 patients were included. Testing was performed in 3217 patients, and included blood culture (71.1%), sputum culture (61.8%), Legionella urinary antigen test (30.1%), pneumococcal urinary antigen test (30.0%), viral testing (14.9%), acute-phase serology (8.8%), bronchoalveolar lavage culture (8.4%) and pleural fluid culture (3.2%). A pathogen was detected in 1173 (36.5%) patients. Testing attitudes varied significantly according to geography and disease severity. Testing was concordant with IDSA/ATS and ERS guidelines in 16.7% and 23.9% of patients, respectively. IDSA/ATS concordance was higher in Europe than in North America (21.5% versus 9.8%; p&lt;0.01), while ERS concordance was higher in North America than in Europe (33.5% versus 19.5%; p&lt;0.01). Testing practices of adults hospitalised with CAP varied significantly by geography and disease severity. There was a wide discordance between real-life testing practices and IDSA/ATS/ERS guideline recommendations

Gold nanoparticle-coated capillaries for protein and peptide analysis on open-tubular capillary electrochromatography

We report a new method of immobilization of gold nanoparticles (AuNPs) on a fused-silica capillary through covalent binding. The resulting modified capillary was applied to electrophoretic systems to improve the efficiency of separation and the selectivity of selected solutes. The immobilization of AuNPs on the capillary wall was performed in a very simple and fast way without requiring heating. The surface features of an AuNP-coated capillary column were determined using the scanning electron microscopy. The chromatographic properties of AuNP-coated capillaries were investigated through variation of the buffer pH and separation voltage. Effective separations of synthetic peptides mixture were obtained on the AuNP-coated capillaries. The method shows a remarkable stability since it was reused about 900 times. The capacity factor was duplicated. Therefore, this modification is stable and can be applied to different separation purposes. A complex mixture of tryptic peptide fragments of HSA was analyzed in both the bare- and the AuNP-coated capillaries. Better electrophoretic peptide profile was observed when using the AuNP-coated capillary.Fil: Hamer, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; ArgentinaFil: Yone, Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; ArgentinaFil: Rezzano, Irene Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; Argentin

Influence of dietary protein intake on body composition in chronic kidney disease patients in stages 3–5: A cross-sectional study

Introduction: A controlled protein intake has shown beneficial effects to preserve renal function and nutritional status in chronic kidney disease (CKD) patients. This study aimed to analyze usual dietary protein intake and its potential contribution to body composition in CKD patients in stages 3–5. Method: Cross-sectional study in 134 CKD patients in stages 3–5 (mean e-GFR: 19.4 ± 8.7 ml/min/1.73 m2; males 68.7% and primary CKD etiology was diabetes mellitus, 35.8%). Demographic, clinical and nutritional parameters were evaluated. Normalized protein nitrogen appearance (nPNA), was used as a surrogate marker of dietary protein intake. The sample was classified into three nPNA groups (Gn): G1: <0.8 g/kg/day; G2: 0.8–1 g/kg/day and, G3: ≥1 g/kg/day. Assessment of nutritional status using the malnutrition-inflammation score (MIS), anthropometric measures and laboratory parameters. Analysis of body composition and hydration status by bioelectrical impedance analysis (BIVA-101-RJL system). Statistical analysis by SPSS v.20. Results: Overall mean nPNA values were 0.91 ± 0.23 g of protein/kg BW/day and only 32.1% had a dietary protein intake <0.8 g of protein/kg BW/day. Most of the CKD patients (65.5%) were in stages 4 or 5. Prevalence of protein–energy–wasting (PEW) syndrome measured by MIS was 15%. By analyzing differences between nPNA groups, body weight (BW), BMI and triceps-skinfold (TSF) thickness were significantly higher in the group with nPNA ≥1 g/kg BW/day (G3), whereas a significant inverse relationship was found with the percentages of body cell mass (BCM%), fat-free mass (FFM%), muscle mass (MM%) and phase angle (PA) in the group with the lowest nPNA (G1). Analysis of gender among subjects showed significant differences with BW, FFM%, TSF and mid-arm muscle circumference (MAMC%). Linear regression analysis showed that resistance, BCM%, MM%, and serum albumin were significant predictors of nPNA as a surrogate marker of daily protein intake (R = 0.51; R2 = 0.29; R2 adjusted = 0.23; p < 0.001). Conclusion: Controlled protein intake is one of the cornerstones of treatment in CKD patients. A low protein intake in patients with CKD stages 3 and 4–5 was associated with loss of muscle mass in the advanced-CKD unit. The loss of muscle mass appears as an early indicator of nutritional comprised. Factors such, elderly age and loss of eGFR, showed lower protein intake and were associated with muscle loss, especially in women. Further longitudinal studies are required to evaluate the contribution of different protein intakes to uremic symptoms, nutritional status, body composition and CKD progression. Resumen: Introducción: El control de la ingesta proteica ha mostrado efectos beneficiosos preservando la función renal y el estado nutricional en pacientes con enfermedad renal crónica (ERC). El objetivo del estudio fue analizar la ingesta habitual de proteína, y su potencial contribución en la composición corporal en los pacientes con ERC estadios 3-5. Método: Estudio observacional transversal en 134 pacientes con ERC estadios 3-5 (media e-TFG: 19,4 ± 8,7 ml/min/1,73 m2; varones: 68,7% y etiología primaria de la ERC, diabetes mellitus: 35,8%). Se evaluaron parámetros demográficos, clínicos y nutricionales. La aparición de nitrógeno proteico normalizado (nPNA) se utilizó como marcador sustituto de la ingesta proteica. La muestra fue clasificada según el nPNA en 3 grupos (Gn): G1: < 0,8 g/kg/día; G2: 0,8-1 g/kg/día y G3: ≥ 1 g/kg/día. Valoración nutricional por la escala de malnutrición-inflamación (MIS), medidas antropométricas y parámetros de laboratorio. Análisis de composición corporal y del patrón de hidratación mediante bioimpedancia eléctrica (BIVA-101®, RJL System). Análisis estadístico por SPSS® v.20. Resultados: Globalmente los valores medios de nPNA fueron 0,91 ± 0,23 g proteína/kg peso corporal/día, y tan solo el 32,1% tenían una ingesta proteica < 0,8 g de proteína/kg peso corporal/día. El 65,5% de los pacientes con ERC estaban en estadios 4 y 5. La prevalencia de síndrome de desgaste proteico-energético (SDP) medido por MIS era del 15%. Analizando las diferencias con el nPNA entre los grupos, el peso corporal, el índice de masa corporal y el pliegue tricipital (PCT), eran significativamente mayores en el grupo con nPNA ≥ 1 g/kg peso corporal/día (G3), mientras que se encontró relación inversa significativa con los porcentajes de la masa celular (MC%), de la masa magra (MMagra%), de la masa muscular (MM%) y del ángulo de fase (AF) en el grupo con menor nPNA (G1). El análisis del género entre los sujetos mostró diferencias significativas con el peso corporal, MMagra%, PCT y la circunferencia muscular del brazo (CMB%). El análisis de regresión lineal demostró que la resistencia MC%, MM% y la albúmina sérica eran predictores significativos del nPNA como marcador de la ingesta proteica habitual (R = 0,51; R2 = 0,29; R2 ajustado = 0,23; p < 0,001). Conclusión: El control de la ingesta proteica es uno de los pilares del tratamiento en los pacientes con ERC. La dieta hipoproteica en pacientes con ERC estadios 3-5 se asoció con una pérdida de la masa muscular en la unidad de ERC avanzada. La pérdida de masa muscular aparece como un indicador temprano de compromiso nutricional. La edad avanzada y la pérdida de TFG-e se asociaron con menor ingesta proteica y pérdida de masa muscular asociada, especialmente en mujeres. Nuevos estudios longitudinales, son necesarios para evaluar la contribución de la ingesta de proteínas en los síntomas urémicos, el estado nutricional, la composición corporal y la progresión de la ERC. Keywords: Protein intake, Normalized protein nitrogen appearance, Muscle mass, Protein-energy wasting, Body composition, Bioelectrical impedance, Chronic kidney disease, Palabras clave: Ingesta de proteínas, Aparición de nitrógeno proteico normalizado, Masa muscular, Pérdida de energía proteica, Composición corporal, Impedancia bioeléctrica, Enfermedad renal crónic

Study of peptide–ligand interactions in open-tubular capillary columns covalently modified with porphyrins

The inner surface of fused silica capillaries has been covalently modified with different porphyrins (deuteroporphyrin, complexes of deuteroporphyrin with metal ions Fe(III), Cu(II), Zn(II), Ni(II), and Cu(II)–meso–tetra (carboxyphenyl) porphyrin) and it was applied for the separation of biologically active peptides by open-tubular capillary electrochromatography. Separations were performed in a mobile phase composed of 25 mM potassium phosphate, pH 4.0, 5% v/v ACN and 10 mM hydroquinone. Changes in the effective electrophoretic mobility of peptides were studied concerning porphyrin central metal atom, attachment geometry, and the presence of coordinating or aromatic amino acid residues in the peptide sequence. The results showed that differences in metal core on the porphyrin and the spatial conformation of attached porphyrin result in changes in the analyte interaction with the stationary phase.Fil: Yone, Angel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica. Cátedra de Química Analítica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carballo, Romina Raquel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica. Cátedra de Química Analítica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Grela, Denise Agata. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica. Cátedra de Química Analítica; ArgentinaFil: Rezzano, Irene Noemí. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica. Cátedra de Química Analítica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vizioli, Nora Matilde. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica. Cátedra de Química Analítica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

A helix-coil transition induced by the metal ion interaction with a grafted iron-binding site of the CyaY protein family

Iron-protein interactions are involved in electron transfer reactions. Alterations of these processes are present in a number of human pathologies; among them, in Friedreich's ataxia, in which a deficiency of functional frataxin, an iron-binding protein, leads to progressive neuromuscular degenerative disease. The putative iron-binding motif of acidic residues EExxED was selected from the first α-helical stretch of the frataxin protein family and grafted onto a foreign peptide scaffold corresponding to the C-terminal α-helix from E. coli thioredoxin. The resulting grafted peptide named GRAP was studied by applying experimental (circular dichroism, isothermal titration calorimetry, capillary zone electrophoresis, thermal denaturation, NMR) and computational approaches (docking, molecular dynamics simulations). Although isolated GRAP lacks a stable secondary structure in solution, when iron is added, the peptide acquires an α-helical structure. Here we have shown that the designed peptide is able to specifically bind Fe(3+) with a moderate affinity (KD = 1.9 ± 0.2 μM) and a 1 : 1 stoichiometry. Remarkably, the GRAP/Fe(3+) interaction is entropically driven (ΔH° = -1.53 ± 0.03 kcal mol(-1) and TΔS° = 6.26 kcal mol(-1)). Experiments and simulations indicate that Fe(3+) interacts with the peptide through three acidic side chains, inducing an α-helical conformation of the grafted motif. In addition, the acidic side chains involved undergo significant conformational rearrangements upon binding, as judged by the analysis of MDs. Altogether, these results contribute to an understanding of the iron-binding mechanisms in proteins and, in particular, in the case of human frataxin.Fil: Vázquez, Diego S.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Agudelo Suarez, William Armando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Yone, Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Vizioli, Nora Matilde. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Aran, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Gonzalez Flecha, Francisco Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: González Lebrero, Mariano Camilo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Santos, Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentin

International prevalence and risk factors evaluation for drug-resistant Streptococcus pneumoniae pneumonia

Objective: Streptococcus pneumoniae is the most frequent bacterial pathogen isolated in subjects with Community-acquired pneumonia (CAP) worldwide. Limited data are available regarding the current global burden and risk factors associated with drug-resistant Streptococcus pneumoniae (DRSP) in CAP subjects. We assessed the multinational prevalence and risk factors for DRSP-CAP in a multinational point-prevalence study. Design: The prevalence of DRSP-CAP was assessed by identification of DRSP in blood or respiratory samples among adults hospitalized with CAP in 54 countries. Prevalence and risk factors were compared among subjects that had microbiological testing and antibiotic susceptibility data. Multivariate logistic regressions were used to identify risk factors independently associated with DRSP-CAP. Results: 3,193 subjects were included in the study. The global prevalence of DRSP-CAP was 1.3% and continental prevalence rates were 7.0% in Africa, 1.2% in Asia, and 1.0% in South America, Europe, and North America, respectively. Macrolide resistance was most frequently identified in subjects with DRSP-CAP (0.6%) followed by penicillin resistance (0.5%). Subjects in Africa were more likely to have DRSP-CAP (OR: 7.6; 95%CI: 3.34-15.35, p<0.001) when compared to centres representing other continents. Conclusions: This multinational point-prevalence study found a low global prevalence of DRSP-CAP that may impact guideline development and antimicrobial policies

Prevalence and etiology of community-acquired pneumonia in immunocompromised patients

Background. The correct management of immunocompromised patients with pneumonia is debated. We evaluated the prevalence, risk factors, and characteristics of immunocompromised patients coming from the community with pneumonia. Methods. We conducted a secondary analysis of an international, multicenter study enrolling adult patients coming from the community with pneumonia and hospitalized in 222 hospitals in 54 countries worldwide. Risk factors for immunocompromise included AIDS, aplastic anemia, asplenia, hematological cancer, chemotherapy, neutropenia, biological drug use, lung transplantation, chronic steroid use, and solid tumor. Results. At least 1 risk factor for immunocompromise was recorded in 18% of the 3702 patients enrolled. The prevalences of risk factors significantly differed across continents and countries, with chronic steroid use (45%), hematological cancer (25%), and chemotherapy (22%) the most common. Among immunocompromised patients, community-acquired pneumonia (CAP) pathogens were the most frequently identified, and prevalences did not differ from those in immunocompetent patients. Risk factors for immunocompromise were independently associated with neither Pseudomonas aeruginosa nor non–community-acquired bacteria. Specific risk factors were independently associated with fungal infections (odds ratio for AIDS and hematological cancer, 15.10 and 4.65, respectively; both P = .001), mycobacterial infections (AIDS; P = .006), and viral infections other than influenza (hematological cancer, 5.49; P &lt; .001). Conclusions. Our findings could be considered by clinicians in prescribing empiric antibiotic therapy for CAP in immunocompromised patients. Patients with AIDS and hematological cancer admitted with CAP may have higher prevalences of fungi, mycobacteria, and noninfluenza viruses