Pneumococcal serotypes in children, clinical presentation and antimicrobial susceptibility in the PCV13 era.

The aim was to analyse invasive pneumococcal disease (IPD) serotypes in children aged ⩽17 years according to clinical presentation and antimicrobial susceptibility. We conducted a prospective study (January 2012-June 2016). IPD cases were diagnosed by culture and/or real-time polymerase chain reaction (PCR). Demographic, microbiological and clinical data were analysed. Associations were assessed using the odds ratio (OR) and 95% confidence intervals (CI). Of the 253 cases, 34.4% were aged <2 years, 38.7% 2-4 years and 26.9% 5-17 years. Over 64% were 13-valent pneumococcal conjugate vaccine (PCV13) serotypes. 48% of the cases were diagnosed only by real-time PCR. Serotypes 3 and 1 were associated with complicated pneumonia (P < 0.05) and non-PCV13 serotypes with meningitis (OR 7.32, 95% CI 2.33-22.99) and occult bacteraemia (OR 3.6, 95% CI 1.56-8.76). Serotype 19A was more frequent in children aged <2 years and serotypes 3 and 1 in children aged 2-4 years and 5-17 years, respectively. 36.1% of cases were not susceptible to penicillin and 16.4% were also non-susceptible to cefotaxime. Serotypes 14, 24F and 23B were associated with non-susceptibility to penicillin (P < 0.05) and serotypes 11, 14 and 19A to cefotaxime (P < 0.05). Serotype 19A showed resistance to penicillin (P = 0.002). In conclusion, PCV13 serotypes were most frequent in children aged ⩽17 years, mainly serotypes 3, 1 and 19A. Non-PCV13 serotypes were associated with meningitis and occult bacteraemia and PCV13 serotypes with pneumonia. Non-susceptibility to antibiotics of non-PCV13 serotypes should be monitored.

Colossal barocaloric effects near room temperature in plastic crystals of neopentylglycol.

There is currently great interest in replacing the harmful volatile hydrofluorocarbon fluids used in refrigeration and air-conditioning with solid materials that display magnetocaloric, electrocaloric or mechanocaloric effects. However, the field-driven thermal changes in all of these caloric materials fall short with respect to their fluid counterparts. Here we show that plastic crystals of neopentylglycol (CH3)2C(CH2OH)2 display extremely large pressure-driven thermal changes near room temperature due to molecular reconfiguration, that these changes outperform those observed in any type of caloric material, and that these changes are comparable with those exploited commercially in hydrofluorocarbons. Our discovery of colossal barocaloric effects in a plastic crystal should bring barocaloric materials to the forefront of research and development in order to achieve safe environmentally friendly cooling without compromising performance.

Giant barocaloric effects at low pressure in ferrielectric ammonium sulphate.

Caloric effects are currently under intense study due to the prospect of environment-friendly cooling applications. Most of the research is centred on large magnetocaloric effects and large electrocaloric effects, but the former require large magnetic fields that are challenging to generate economically and the latter require large electric fields that can only be applied without breakdown in thin samples. Here we use small changes in hydrostatic pressure to drive giant inverse barocaloric effects near the ferrielectric phase transition in ammonium sulphate. We find barocaloric effects and strengths that exceed those previously observed near magnetostructural phase transitions in magnetic materials. Our findings should therefore inspire the discovery of giant barocaloric effects in a wide range of unexplored ferroelectric materials, ultimately leading to barocaloric cooling devices.

Impact of prompt catheter withdrawal and adequate antimicrobial therapy on the prognosis of hospital-acquired parenteral nutrition catheter-related bacteraemia.

Catheter-related bacteraemia (CRB) is a cause of death in hospitalized patients, and parenteral nutrition (PN) is a risk factor. We aim to describe the prognosis of PN-CRB and the impact of catheter extraction within 48 h from bacteraemia. All consecutive hospitalized adult patients with CRB (2007-2012) were prospectively enrolled. Factors associated with 30-day mortality were determined by logistic regression analysis. Among 847 episodes of CRB identified, 291 (34%) episodes were associated with short-term catheter use for PN. Cure was achieved in 236 (81%) episodes, 42 (14.5%) patients died within the first 30 days, 7 (2.5%) relapsed, and 6 (2%) had re-infection. On multivariate analysis, previous immunosuppressive therapy (OR 5.62; 95% CI 1.69-18.68; p 0.0048) and patient age (OR 1.05; 95% CI 1.02-1.07; p 0.0009) were predictors of 30-day mortality, whereas catheter removal within 48 h of bacteraemia onset (OR 0.26; 95% CI 0.12-0.58; p 0.0010) and adequate empirical antibiotic treatment (OR 0.36; 95% CI 0.17-0.77; p 0.0081) were protective factors. Incidence of PN-CRB decreased from 5.36 episodes/1000 days of PN in 2007 to 2.9 in 2012, yielding a 46.1% rate reduction (95% CI 15.7-65.5%), which may be attributable to implementation of a multifaceted prevention strategy. In conclusion, short-term PN-CRB accounted for one-third of all episodes of CRB in our setting, and 14.5% of patients died within 30 days following bacteraemia. Our findings suggest that prompt catheter removal and adequate empirical antibiotic treatment could be protective factors for 30-day mortality. Concomitantly with implementation of a multifaceted prevention strategy, PN-CRB incidence was reduced by half.

Impact of the emergence of non-vaccine pneumococcal serotypes on the clinical presentation and outcome of adults with invasive pneumococcal pneumonia.

The introduction of the 7-valent pneumococcal conjugate vaccine in children has led to a change in the pattern of pneumococcal serotypes causing pneumococcal disease. The aim of this study was to compare the clinical presentation and outcome of invasive pneumococcal pneumonia (IPP) in adults between the pre and post-vaccine era. We have conducted an observational study of all adults hospitalized with IPP, from 1996 to 2001 (pre-vaccine period), and from 2005 to 2009 (post-vaccine period). Incidence, serotype distribution and clinical data were compared between both periods. A total of 653 episodes of IPP were diagnosed. The overall incidence of IPP increased from 14.2 to 17.9 cases per 100 000 population-year (p 0.003). In the post-vaccine period IPP caused by vaccine serotypes decreased (-36%; 95% CI, -52 to -15) while IPP caused by non-vaccine serotypes increased (71%; 95% CI, 41-106). IPP in the post-vaccine period was associated with higher rates of septic shock (19.1% vs. 31.1%, p <0.001). Among patients aged 50-65 years there was a trend towards a greater proportion of case-fatalities (11.6-23.5%, p 0.087). Independent risk factors for septic shock were IPP caused by serotype 3 (OR 2.38; 95% CI, 1.16-4.87) and serotype 19A (OR 6.47, 95% CI, 1.55-27). Serotype 1 was associated with a lower risk of death (OR 0.1; 95% CI, 0.01-0.78). In conclusion, the incidence of IPP in the post-vaccine period has increased in our setting, it is caused mainly by non-vaccine serotypes and it is associated with higher rates of septic shock.

Immediate and long-term outcome of left-sided infective endocarditis. A 12-year prospective study from a contemporary cohort in a referral hospital.

The aim of this study was to describe the immediate and long-term prognosis of a contemporary cohort of patients with left-sided infective endocarditis (LSIE). A prospective observational cohort study was conducted in a referral centre. Between January 2000 and December 2011, all consecutive adult patients with LSIE were followed-up until death, relapse, recurrence, need for late surgery, or last control. During the active phase of IE, 174 of 438 patients underwent surgery (40% overall; 43% native valve (NVIE), 30% prosthetic valve (PVIE)) and 125 died (29% overall; 26% NVIE, 39% PVIE). The median follow-up in survivors was 3.2 years (interquartile range (IQR) 1.0-6.0 years). Relapses occurred in seven patients (2.2%; 95% CI, 1.1-4.5) and recurrences in eight (2.6%; 95% CI, 1.3-5.0), with an incidence density of 0.0067 per patient-year (95% CI, 0.0029-0.0133) and high mortality (75% of recurrences). Only four of 130 survivors (3.1%; 95% CI, 1.2-7.6) who were treated surgically during the active phase of the disease, and 14/183 (7.7%; 95% CI, 4.6-12.4) of those not undergoing surgery needed operation during follow-up (p 0.09). In the 313 survivors, actuarial survival was 86% at 1 year (87% NVIE, 83% PVIE), 79% at 2 years (81% NVIE, 72% PVIE) and 68% at 5 years (71% NVIE, 57% PVIE). At 1 year, 115 of 397 patients (29.0%; 95% CI, 24.7-33.6) remained alive, with no surgery requirement, relapse or recurrence. LSIE is associated with considerable in-hospital and long-term mortality, especially PVIE. However, relapses, recurrences and the need for late surgery are uncommon.

Serotype 3 is a common serotype causing invasive pneumococcal disease in children less than 5 years old, as identified by real-time PCR.

Serotype 3 is one of the most often detected pneumococcal serotypes in adults and it is associated with serious disease. In contrast, the isolation of serotype 3 by bacterial culture is unusual in children with invasive pneumococcal disease (IPD). The purpose of this study was to learn the serotype distribution of IPD, including culture-negative episodes, by using molecular methods in normal sterile samples. We studied all children<5 years of age with IPD admitted to two paediatric hospitals in Catalonia, Spain, from 2007 to 2009. A sequential real-time polymerase chain reaction (PCR) approach was added to routine methods for the detection and serotyping of pneumococcal infection. Among 257 episodes (219 pneumonia, 27 meningitis, six bacteraemia and five others), 33.5% were identified by culture and the rest, 66.5%, were detected exclusively by real-time PCR. The most common serotypes detected by culture were serotypes 1 (26.7%) and 19A (25.6%), and by real-time PCR, serotypes 1 (19.8%) and 3 (18.1%). Theoretical coverage rates by the PCV7, PCV10 and PCV13 vaccines were 10.5, 52.3 and 87.2%, respectively, for those episodes identified by culture, compared to 5.3, 31.6 and 60.2% for those identified only by real-time PCR. Multiplex real-time PCR has been shown to be useful for surveillance studies of IPD. Serotype 3 is underdiagnosed by culture and is important in paediatric IPD.

[Incidence of central line-associated bloodstream infection in an intensive care unit]. / Incidencia de bacteriemia asociada a catéter venoso central en una unidad de cuidados intensivos.

BACKGROUND: Central line-associated bloodstream infection (CLABSI) is one of the most common nosocomial infections. The incidence is higher in paediatric patients than in adults, especially in those admitted to Intensive Care Units (ICU). CLABSI-related morbidity makes it a major health problem; therefore it is necessary to develop prevention strategies against it. PATIENTS AND METHODS: An intervention study in a paediatric ICU (PICU) was performed, in order to assess the impact of the introduction of the program «Bacteraemia zero¼ in December 2007. This program aims to prevent CLABSI. Demographic data and variables related to hospitalisation and infection were collected from January to December 2007 (before the intervention) and from January to December 2008 (after the intervention), and were compared. In the first period, 497 patients were studied, and 495 in the second. RESULTS: A reduction of 30.4% in the incidence of CLABSI (P=0.49) in the second year was observed (5.5 to 3.8 episodes per 1000 catheter-days). The CVC use ratio was 0.59 and 0.64, respectively. The most frequently isolated organism was coagulase-negative Staphylococcus spp. CONCLUSIONS: The implementation of a «no bacteraemia¼ program, involving all staff in the PICU as well as the professionals in infection control, reduces the incidence of CLABSI.

Prognosis of left-sided infective endocarditis in patients transferred to a tertiary-care hospital--prospective analysis of referral bias and influence of inadequate antimicrobial treatment.

The aims of this study were to compare the characteristics of adult patients with left-sided infective endocarditis (LSIE) diagnosed and treated in a tertiary-care hospital with those of patients referred from a second-level community hospital, and to establish the accuracy of diagnosis and adequacy of treatment in referred patients and the influence of this factor on outcome. A prospective observational cohort study was conducted at Hospital Universitari Vall d'Hebron, a 1000-bed teaching hospital in Barcelona (Spain) and a referral centre for cardiac surgery. One hundred and fourteen of 337 (34%) episodes of LSIE treated in our hospital occurred in transferred patients. As compared with patients diagnosed in our hospital, transferred patients acquired LSIE within the healthcare system less often (16.7% vs. 38.1%, p <0.001), were in better health (Charlson index 3 (interquartile range (IQR)) 1-4) vs. 4 (IQR 2-6), p <0.001), had more complications (94.7% vs. 78.9%, p <0.001), underwent more operations (69.3% vs. 22.1%, p <0.001), and experienced similar mortality (22.8% vs. 31.4%, p 0.100). Only 52 of 114 (45.6%) referred patients received an antimicrobial regimen included in the American, European or Spanish guidelines at the hospital of origin. After adjustment for congestive heart failure and staphylococcal infection in multivariate logistic regression, inadequate or no antimicrobial treatment at origin was a risk factor for in-hospital mortality (OR 3.3, 95% CI 1.1-10.0, p 0.030). Errors in the initial antimicrobial treatment prescribed for LSIE are associated with greater mortality.

Impact of prior pneumococcal vaccination on clinical outcomes in HIV-infected adult patients hospitalized with invasive pneumococcal disease.

BACKGROUND: Recent studies in hospitalized patients with community-acquired pneumonia have found a lower risk of bacteraemia and better clinical outcomes in patients who had previously received the 23-valent pneumococcal polysaccharide vaccine (PPV) in comparison with unvaccinated individuals. The aim of this study was to assess the influence of prior PPV on clinical outcomes in HIV-infected adult patients hospitalized with invasive pneumococcal disease (IPD). METHODS: This was an observational study of all consecutive HIV-infected adults hospitalized with IPD from January 1996 to October 2007 in three hospitals in Spain. Baseline characteristics and clinical outcome-related variables were compared according to prior PPV vaccination status. RESULTS: A total of 162 episodes of IPD were studied. In 23 of these (14.2%), patients had previously received PPV. In both vaccinated and unvaccinated patients, most of the causal serotypes were included in the 23-valent PPV (76.9% and 84.1%, respectively). Overall, 25 patients (15.4%) died during hospitalization, 21 patients (13%) required admission to an intensive care unit (ICU) and 34 patients (21%) reached the composite outcome of death and/or admission to the ICU. None of the 23 patients who had previously received PPV died or required ICU admission, in comparison with 25 (18%; P=0.026) and 21 (15.1%; P=0.046), respectively, of the unvaccinated patients. The length of hospital stay for vaccinated patients was significantly shorter (8.48 vs. 13.27 days; P=0.011). CONCLUSIONS: Although 23-valent PPV failed to prevent IPD in some HIV-infected patients, vaccination produced beneficial effects on clinical outcomes by decreasing illness severity and mortality related to IPD.

Combined experimental and theoretical investigation of the premartensitic transition in Ni2MnGa.

Ultraviolet-photoemission (UPS) measurements and supporting specific-heat, thermal-expansion, resistivity, and magnetic-moment measurements are reported for the magnetic shape-memory alloy Ni2MnGa over the temperature range 100T(PM) is due to the Ni d minority-spin electrons. Below T(M) this peak disappears, resulting in an enhanced density of states at energies around 0.8 eV. This enhancement reflects Ni d and Mn d electronic contributions to the majority-spin density of states.

Impact of early central venous catheter removal on outcome in patients with candidaemia.

Removal of central venous catheters (CVCs) from candidaemic patients is considered the reference standard of care, although this practice is not always possible. The impact of prompt catheter removal on outcome was investigated by analysing data from an active population-based surveillance study in Barcelona, Spain. Patients with candidaemia and a CVC were identified between January 2002 and December 2003. Cases with CVC removal within 2 days were classified as having early CVC removal. Outcome, defined as in-hospital mortality 2-30 days after diagnosis of candidaemia, was determined among hospitalised adults using univariate, Kaplan-Meier and multivariate logistic regression analysis. Outpatients, paediatric patients and those who died or were discharged within 2 days were excluded. The study identified 265 patients with candidaemia and a CVC. Median time from diagnosis of candidaemia to catheter removal was 1 day (range 0-29 days). Overall, 172 patients met the criteria for inclusion in the outcome study. Patients with early CVC removal differed significantly from those with delayed CVC removal. According to univariate, Kaplan-Meier and multivariate analysis, the marker most predictive of in-hospital mortality among candidaemic patients with CVCs was severity of illness. These data suggest that timing of CVC removal may best be determined after carefully considering the risks and benefits to individual patients.

Deep-vein thrombosis rates after major orthopedic surgery in Asia. An epidemiological study based on postoperative screening with centrally adjudicated bilateral venography.

BACKGROUND: The incidence of postsurgical venous thromboembolism is thought to be low in Asian ethnic populations. OBJECTIVE: We studied the incidence of deep-vein thrombosis (DVT) in Asian patients undergoing major orthopedic surgery of the lower limbs. PATIENTS/METHODS: We performed a prospective epidemiological study in 19 centers across Asia (China, Indonesia, South Korea, Malaysia, Philippines, Taiwan, and Thailand) in patients undergoing elective total hip replacement (THR), total knee replacement (TKR) or hip fracture surgery (HFS) without pharmacological thromboprophylaxis. The primary endpoint was the rate of DVT of the lower limbs documented objectively with bilateral ascending venography performed 6-10 days after surgery using a standardized technique and evaluated by a central adjudication committee unaware of local interpretation. RESULTS: Overall, of 837 Asian patients screened for this survey, 407 (48.6%, aged 20-99 years) undergoing THR (n = 175), TKR (n = 136) or HFS (n = 96) were recruited in 19 centers. DVT was diagnosed in 121 of 295 evaluable patients [41.0%, (95% confidence interval (CI): 35.4-46.7)]. Proximal DVT was found in 30 patients [10.2% (7.0-14.2)]. Total DVT and proximal DVT rates were highest in TKR patients (58.1% and 17.1%, respectively), followed by HFS patients (42.0% and 7.2%, respectively), then THR patients (25.6% and 5.8%, respectively). DVT was more frequent in female patients aged at least 65 years. Pulmonary embolism was clinically suspected in 10 of 407 patients (2.5%) and objectively confirmed in two (0.5%). CONCLUSIONS: The rate of venographic thrombosis in the absence of thromboprophylaxis after major joint surgery in Asian patients is similar to that previously reported in patients in Western countries.

Origin of magnetic and magnetoelastic tweedlike precursor modulations in ferroic materials.

Based on experimental observations of modulated magnetic patterns in a Co0.5Ni0.205Ga0.295 alloy, we propose a model to describe a (purely) magnetic tweed and a magnetoelastic tweed. The former arises above the Curie (or Néel) temperature due to magnetic disorder. The latter results from compositional fluctuations coupling to strain and then to magnetism through the magnetoelastic interaction above the structural transition temperature. We discuss the origin of purely magnetic and magnetoelastic precursor modulations and their experimental thermodynamic signatures.

Management of catheter-related Staphylococcus aureus bacteremia: when may sonographic study be unnecessary?

This study reviews the outcome of patients with uncomplicated catheter-related Staphylococcus aureus bacteremia diagnosed in our hospital from January 1997 to December 1999 and treated with short-course antibiotic therapy. Our aim was to assess the effectiveness of this regimen for minimizing complications (relapses, endocarditis and metastatic foci). A total of 213 episodes of bacteremia were registered and 167 (78.4%) were nosocomial. Among these, 87 (52.1%) were catheter-related Staphylococcus aureus bacteremia and 20 were primary nosocomial bacteremia. Endocarditis was diagnosed during the acute episode in 7/107 of these patients (2 by persistent fever after catheter removal and 5 by metastatic foci; 3 of them also had cardiac risk factors) and confirmed with transesophageal echocardiography. Among the 84/87 catheter-related Staphylococcus aureus bacteremia and 16/20 primary nosocomial bacteremia patients who did not develop endocarditis, 31 patients died during the acute episode (16 due to sepsis despite initiation of antibiotic treatment and 15 due to the underlying disease) and five had osteoarticular foci. The remaining 64 episodes were considered to be uncomplicated bacteremia (no cardiac risk factors, persistent fever, metastatic foci, or clinical signs of endocarditis) and were treated with 10-14 days of high-dose antistaphylococcal antibiotics. Echocardiography was not mandatory in these patients. Of the 64 uncomplicated episodes, 62 were followed for at least 3 months and none relapsed or developed endocarditis. Even though some of the patients might have had subclinical endocarditis, short-course therapy with high doses of antistaphylococcal antibiotics was effective for treating uncomplicated catheter-related Staphylococcus aureus bacteremia. Transesophageal echocardiography may not be necessary in these cases.

Efficacy and safety of bemiparin compared with enoxaparin in the prevention of venous thromboembolism after total knee arthroplasty: a randomized, double-blind clinical trial.

In this randomized, multicenter, controlled, double-blind, sequential trial, 381 patients undergoing primary total knee replacement were randomly assigned to receive subcutaneous injections of either 3500 IU anti-factor Xa of bemiparin sodium, first dose 6 h after surgery, or 40 mg of enoxaparin, first dose 12 h before surgery, followed by daily doses for 10 +/- 2 days, for the prophylaxis of venous thromboembolism. The primary efficacy endpoint was venous thromboembolism up to postoperative day 10 +/- 2, defined as deep vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep vein thrombosis and/or documented symptomatic pulmonary embolism. The primary safety endpoint was major bleeding. Eighty-seven percent of all randomized patients (333 of 381 patients) were evaluable for efficacy. The incidence of venous thromboembolism was 32.1% (53 of 165 patients) in the bemiparin group and 36.9% (62 of 168 patients) in the enoxaparin group. The absolute risk difference was 4.8% in favor of bemiparin [95% confidence interval (CI), -15.1% to 5.6%; non-inferiority P-value: 0.02; superiority P-value: 0.36]. The incidence of proximal deep vein thrombosis was 1.8% (three of 165 patients) in the bemiparin group and 4.2% (seven of 168 patients) in the enoxaparin group. Major bleeding occurred in six patients (three in each group). There were no deaths during the study. This trial shows that bemiparin started postoperatively is as effective and safe as enoxaparin started preoperatively in the prevention of venous thromboembolism in patients undergoing total knee replacement.

[Evolution of perinatal Escherichia coli disease in the era of group B Streptococcus prophylaxis]. / Evolución de la sepsis perinatal por Escherichia coli en la era de la profilaxis del estreptococo del grupo B.

BACKGROUND: The aim of this study was to characterize perinatal Escherichia coli disease, and to analyze its possible correlation with the employment of prophylaxis for group B streptococcal (GBS)disease. PATIENTS AND METHOD: Between 1994 and 2000, 24 neonates born in our hospital were diagnosed of early-onset E. coli disease: 12 born to mothers who received prenatal care in our center and 12 born to mothers who were referred from other hospitals shortly before labor. Three further neonates born in other centers were also referred with the same diagnosis. RESULTS: The annual rate did not change significantly (RR:1.065; confidence interval [CI] 95% -0.873-1.301; p = 0.533):from 0.6 per 1,000 live births in 1994 to 1.7 per 1,000 in 1997 and 0.5 in 2000. Among mothers, 92% presented obstetric risk factors including 68% with prematurity (mean 32.9 gestation weeks, median 32), 64% with prolonged rupture of membranes (mean 184 hours,median 44), and 56% with intrapartum fever. Twelve percent of mothers received intrapartum ampicillin as prophylaxis against GBS and 80% received antibiotics: prophylaxis for rupture of membranes in 6 cases, treatment of urinary tract infection in 6 cases and treatment of probable chorioamnionitis in 8 cases. Ampicillin-resistant E. coli was isolated in 81% of neonates. No significant correlation was found between ampicillin resistance and prematurity(p = 0.57), rupture of membranes (p = 0.63), intrapartum fever(p = 0.24) or death (p = 0.53). CONCLUSIONS: Our results suggest that perinatal E. coli disease is not related with the employment of prophylaxis against GBS disease. Instead, it seems to be related with prematurity, prolonged gestation in premature rupture of membranes and exposure to antibiotics.