Successful treatment of postsurgical meningitis caused by Bacillus cereus: a case report and literature review.

Bacillus cereus is a spore-forming, gram-positive bacterium that is ubiquitous in the environment. Central nervous system involvement with B. cereus is rare. Despite aggressive treatment with broad-spectrum antibiotics and using them appropriately, the mortality is high. A 72-year-old patient suffered a central nervous system infection associated with postsurgical meningitis and was successfully treated with a novel antibiotic therapy. This study includes the first case report of postsurgical B. cereus meningitis in the last ten years. It provides a different line of treatment to the previous ones.

A national survey of out-of-hours working and fatigue in consultants in anaesthesia and paediatric intensive care in the UK and Ireland.

The tragic death of an anaesthetic trainee driving home after a series of night shifts prompted a national survey of fatigue in trainee anaesthetists. This indicated that fatigue was widespread, with significant impact on trainees' health and well-being. Consultants deliver an increasing proportion of patient care resulting in long periods of continuous daytime duty and overnight on-call work, so we wished to investigate their experience of out-of-hours working and the causes and impact of work-related fatigue. We conducted a national survey of consultant anaesthetists and paediatric intensivists in the UK and Ireland between 25 June and 6 August 2018. The response rate was 46% (94% of hospitals were represented): 84% of respondents (95%CI 83.1-84.9%) contribute to a night on-call rota with 32% (30.9-33.1%) working 1:8 or more frequently. Sleep disturbance on-call is common: 47% (45.6-48.4%) typically receive two to three phone calls overnight, and 48% (46.6-49.4%) take 30 min or more to fall back to sleep. Only 15% (14.0-16.0%) reported always achieving 11 h of rest between their on-call and their next clinical duty, as stipulated by the European Working Time Directive. Moreover, 24% (22.8-25.2%) stated that there is no departmental arrangement for covering scheduled clinical duties following a night on-call if they have been in the hospital overnight. Overall, 91% (90.3-91.7%) reported work-related fatigue with over half reporting a moderate or significantly negative impact on health, well-being and home life. We discuss potential explanations for these results and ways to mitigate the effects of fatigue among consultants.

Outcomes by sex following treatment initiation with darunavir/cobicistat in a large Spanish cohort of the CODAR study (GeSIDA 9316).

BACKGROUND: Few women have been included in darunavir/cobicistat clinical development studies, and hardly any of them were antiretroviral experienced or treated with anything other than triple-based therapies. OBJECTIVES: Our aim was to increase our knowledge about women living with HIV undergoing darunavir/cobicistat-based regimens. METHODS: A multicentre (21 hospitals), retrospective study including a centrally selected random sample of HIV-1 patients starting a darunavir/cobicistat-based regimen from June 2014 to March 2017 was planned. Baseline characteristics, 24 and 48 week viral load response (<50 copies/mL), CD4+ lymphocyte count increase, time to change darunavir/cobicistat and adverse event occurrence were all compared by sex. The study was approved by each of the 21 ethics committees, and patients signed informed consent. RESULTS: Out of 761 participants, 193 were women. Similar characteristics were found for both sexes, except that the women had a longer duration of HIV infection (P = 0.001), and were less frequently pre-treated with darunavir/cobicistat in their previous regimen (P = 0.02). The main reason for using a darunavir/cobicistat-based regimen was simplification, without differences by sex, while monotherapy seems to be more frequently prescribed in women than in men (P = 0.067). The main outcomes, HIV viral load response, CD4+ lymphocyte count increase at 24 or 48 weeks, occurrence of adverse events, main reasons for changing and time to the modify darunavir/cobicistat regimen, did not show differences between the sexes. CONCLUSIONS: No sex disparities were found in the main study outcomes. These results support the use of a darunavir/cobicistat-based regimen in long-term pre-treated women. Clinical Trial.gov No. NCT03042390.

Carbon dots, a powerful non-toxic support for bioimaging by fluorescence nanoscopy and eradication of bacteria by photothermia.

Carbon Dots (CDs) are innovative materials which have potential applications in many fields, including nanomedicine, energy and catalysis. Here CDs were produced by the alkali-assisted ultrasonic route and characterized by several techniques to determine their composition and properties. Fluorescence nanoscopy using single-molecule localization microscopy shows that they have very good photophysical properties and a remarkable blinking behaviour at 405 nm. Moreover, these CDs are a safe material, non-toxic towards different cell lines (cancer and non-cancer cells) even at very high concentration, reflecting an excellent biocompatibility. Photothermia, i.e. their heating capacity under laser irradiation, was evaluated at two wavelengths and at several power densities. The resulting temperature increment was high (5 < ΔT < 45 °C) and appropriate for biomedical applications. Bioimaging and photothermia were then performed on E. coli, a Gram(-) bacterium, incubated with CDs. Remarkably, by photothermia at 680 nm (0.3, 1 and 1.9 W cm-2) or 808 nm (1.9 W cm-2), CDs are able to eradicate bacteria in their exponential and stationary phases. Images obtained by 3D super-resolution microscopy clearly show the different CD distributions in surviving bacteria after mild photothermal treatment. These results confirm that CDs are multifunctional materials with a wide range of biomedical applications.

A pragmatic approach for mortality prediction after surgery in infective endocarditis: optimizing and refining EuroSCORE.

OBJECTIVE: To simplify and optimize the ability of EuroSCORE I and II to predict early mortality after surgery for infective endocarditis (IE). METHODS: Multicentre retrospective study (n = 775). Simplified scores, eliminating irrelevant variables, and new specific scores, adding specific IE variables, were created. The performance of the original, recalibrated and specific EuroSCOREs was assessed by Brier score, C-statistic and calibration plot in bootstrap samples. The Net Reclassification Index was quantified. RESULTS: Recalibrated scores including age, previous cardiac surgery, critical preoperative state, New York Heart Association >I, and emergent surgery (EuroSCORE I and II); renal failure and pulmonary hypertension (EuroSCORE I); and urgent surgery (EuroSCORE II) performed better than the original EuroSCOREs (Brier original and recalibrated: EuroSCORE I: 0.1770 and 0.1667; EuroSCORE II: 0.2307 and 0.1680). Performance improved with the addition of fistula, staphylococci and mitral location (EuroSCORE I and II) (Brier specific: EuroSCORE I 0.1587, EuroSCORE II 0.1592). Discrimination improved in specific models (C-statistic original, recalibrated and specific: EuroSCORE I: 0.7340, 0.7471 and 0.7728; EuroSCORE II: 0.7442, 0.7423 and 0.7700). Calibration improved in both EuroSCORE I models (intercept 0.295, slope 0.829 (original); intercept -0.094, slope 0.888 (recalibrated); intercept -0.059, slope 0.925 (specific)) but only in specific EuroSCORE II model (intercept 2.554, slope 1.114 (original); intercept -0.260, slope 0.703 (recalibrated); intercept -0.053, slope 0.930 (specific)). Net Reclassification Index was 5.1% and 20.3% for the specific EuroSCORE I and II. CONCLUSIONS: The use of simplified EuroSCORE I and EuroSCORE II models in IE with the addition of specific variables may lead to simpler and more accurate models.

A national survey of the effects of fatigue on trainees in anaesthesia in the UK.

Long daytime and overnight shifts remain a major feature of working life for trainees in anaesthesia. Over the past 10 years, there has been an increase in awareness and understanding of the potential effects of fatigue on both the doctor and the patient. The Working Time Regulations (1998) implemented the European Working Time Directive into UK law, and in August 2009 it was applied to junior doctors, reducing the maximum hours worked from an average of 56 per week to 48. Despite this, there is evidence that problems with inadequate rest and fatigue persist. There is no official guidance regarding provision of a minimum standard of rest facilities for doctors in the National Health Service, and the way in which rest is achieved by trainee anaesthetists during their on-call shift depends on rota staffing and workload. We conducted a national survey to assess the incidence and effects of fatigue among the 3772 anaesthetists in training within the UK. We achieved a response rate of 59% (2231/3772 responses), with data from 100% of NHS trusts. Fatigue remains prevalent among junior anaesthetists, with reports that it has effects on physical health (73.6% [95%CI 71.8-75.5]), psychological wellbeing (71.2% [69.2-73.1]) and personal relationships (67.9% [65.9-70.0]). The most problematic factor remains night shift work, with many respondents commenting on the absence of breaks, inadequate rest facilities and 57.0% (55.0-59.1) stating they had experienced an accident or near-miss when travelling home from night shifts. We discuss potential explanations for the results, and present a plan to address the issues raised by this survey, aiming to change the culture around fatigue for the better.

Maghemite nanoparticles coated with human serum albumin: combining targeting by the iron-acquisition pathway and potential in photothermal therapies.

Human serum albumin (HSA), the most abundant plasma protein in human blood, is a natural transport vehicle with multiple ligand binding sites. It, therefore, constitutes an attractive candidate for drug delivery. Targeting may occur via the most known interaction of the protein with the neonatal Fc receptor (FcRn). Here, we investigate another HSA delivery path, involving the transferrin receptor, and we elaborate a maghemite-HSA nanohybrid, opening up new opportunities for medical applications. Fluorescence spectrophotometric titration and size-exclusion chromatography were used to substantiate, in cell-free assays, an interaction between HSA and the transferrin receptor R1. This occurs with a dissociation constant, KD of 6.7 nM. This interaction was confirmed in HeLa cell culture where, by confocal microscopy, rhodamine-labeled HSA is shown to be internalized. HSA was then covalently conjugated onto maghemite nanoparticles (NPs) to give a NP-HSA nanohybrid. The therapeutic potential of this hybrid was demonstrated through its heating capacity in magnetic hyperthermia (MH) and near-infrared (NIR) photothermia (PT). In particular, the Specific Absorption Rate (SAR) in the PT Therapy (PTT) mode, using a 808 nm NIR-LASER (1 W cm-2) and at iron concentration as low as 2.5 mM, was found to be very high, equal to 1870 W g-1 with a temperature increment of 9.2 °C. The nanohybrids incubated with HeLa cells were mainly localized at the cell surface. When the PTT mode was applied under the same conditions as in vitro, mortality was higher in HeLa cells than in fibroblasts (non-malignant cells). Cytotoxicity was checked in both cell lines without the PTT mode; the nanohybrids do not seem to affect cell viability. These results make the nanohybrids very promising agents for NIR-PT and for targeting in cancer therapy, since non-malignant cells were not damaged.

Are hip hemiarthroplasty and total hip arthroplasty infections different entities? The importance of hip fractures.

Hip hemiarthroplasty (HHA) and total hip arthroplasty (THA) infections are usually considered as one entity; however, they may show important differences. We analyze these differences, as well as predictors of treatment failure (TF) and poor functional status among patients with prosthetic hip infections (PHIs). A multicenter cohort study of consecutive patients with PHIs was performed. The main outcome variable was TF after the first surgical treatment performed to treat the infection. Multivariate analysis was used to identify predictors of TF. A total of 127 patients with PHI were included (43 HHA, 84 THA). Patients with HHA infections were more frequently women (88% vs. 54%; p < 0.001), had comorbidities (86% vs. 67%, p = 0.02), and were older (median age 79 vs. 65 years, p < 0.001), and the reason for arthroplasty was more frequently a fracture (100% vs. 18%, p < 0.001). Failure of initial treatment and crude mortality were more frequent among HHA patients (44% vs. 23%, p = 0.01 and 28% vs. 7%, p = 0.001, respectively). However, HHA was not associated with TF in the multivariate analysis when hip fracture was considered; thus, variables independently associated with TF were hip fracture, inadequate surgical management, prosthesis retention, and higher C-reactive protein level. Failure of the first surgical treatment was associated with poorer functional status. HHA and THA infections showed significant differences in epidemiology, clinical features, and outcome. Although patients with HHA infections had a higher risk of TF, this was related to the reason for hip implant: a hip fracture. Success of the initial management of infection is a predictor of better clinical and functional outcome.

Surgical treatment for infective endocarditis in elderly patients.

OBJECTIVES: We evaluate the clinical, echographic and prognostic characteristics of infective endocarditis (IE) in a large population of elderly patients, and the results of surgical approach. METHODS: Multicentric, prospective, observational cohort study with 961 consecutive left-sided IE: 356 patients aged ≥65 years were compared with 605 younger. Indications for cardiac surgery, potential surgical risk, time and outcome, were compared. RESULTS: Hospital-acquired endocarditis, comorbidity, renal failure and septic shock were more frequent in elderly, but embolisms were less. Intracardiac destruction and ventricular failure were similar in both groups, but significantly fewer elderly patients underwent cardiac surgery (36% vs 51%; p < 0.01), and this group showed a worse outcome (43.2% of mortality vs 27% in younger; p < 0.01), resulting age as an independent predictor of mortality (OR: 1.02 CI95%: 1.01-1.03). Compared with medical treatment, surgery showed lower percentages of mortality compared with medical treatment (23.3% vs 31.3%; p = 0.03) in younger group, but a high mortality was observed with both procedures (47.6% vs 40.3%; p = 0.1) in the elderly. CONCLUSIONS: Although similar percentages of heart failure and intracardiac complications, increasing age is associated with higher mortality in IE. Lower rates of surgical treatment and a worse outcome after operation are common features in elderly patients.

Streptococcus agalactiae left-sided infective endocarditis. Analysis of 27 cases from a multicentric cohort.

SUMMARY OBJECTIVE: To evaluate the current trends in the clinical characteristics and the prognosis of Streptococcus agalactiae infective endocarditis (IE), uncommon disease associated with high mortality. METHODS: Descriptive analysis of 27 cases of a large cohort (961 episodes) of infective endocarditis collected in seven hospitals of Andalusia (Spain) between 1984 and 2008. RESULTS: Native valves were affected in most cases (85. 2%), multiple valves were frequently involved (22.2%). The median age of the patients was 65 (51-76) years (59.3% men), with a comorbidity, according to the Charlson index, of 2.6+/-2.3. The most frequent underlying diseases were diabetes mellitus (25.9%), chronic obstructive pulmonary disease (14.8%), neoplasms (14.8%), urological disorders (11%) and chronic liver disease (11%). Clinical presentation was characterized by rapid worsening (median of 9 (5.7-15) days from onset of symptoms until diagnosis), a high rate of embolisms (37%) and cardiac complications (abscesses, fistulas or valve rupture) - 37% of cases. Surgery was performed in 12 patients (44.4%) and a high mortality (40.7%) was observed. CONCLUSION: S. agalactiae IE is a serious disease with aggressive course and high mortality rate and affects patients with debilitating diseases. We must be alert of the development of complications and consider early valve surgery when it is necessary.

Healthcare-associated infective endocarditis: an undesirable effect of healthcare universalization.

Invasive medical technology has led to an increase in the incidence of healthcare-associated infective endocarditis (HAIE). A prospective multicentre cohort study was conducted at seven hospitals in Andalusia, Spain, to establish the characteristics of HAIE and to compare them with those of community-acquired infective endocarditis (CAIE). HAIE was defined as either infective endocarditis (IE) manifesting >48 h after admission to hospital, or IE associated with a significant invasive procedure performed in the 6 months before diagnosis. Seven hundred and ninety-three cases of IE were investigated, and HAIE accounted for 127 (16%). As compared with patients with CAIE, patients with HAIE were older (60.1 ± 14.4 years vs. 53.6 ± 17.5 years) and had more comorbidities (Charlson index 3.3 ± 2.3 vs. 1.8 ± 2.3) and staphylococcal infections (58.3% vs. 24.8%). Vascular manipulation was the main cause of bacteraemia responsible for HAIE (63%). Peripheral vein catheter-associated bacteraemia accounted for 32.8% of the catheter-related bacteraemias. In-hospital mortality (44.9% vs. 24.2%) was higher in the HAIE group. Septic shock (OR 2.2, 95% CI 2.9-30.2) and surgery not performed because of high surgical risk (OR 1.6, 95% CI 1.2-20) were independent predictors of mortality in HAIE. The present study demonstrates that HAIE is a growing health problem associated with high mortality. Careful management of vascular devices is essential to minimize the risk of bacteraemias leading to HAIE.

beta-lactam susceptibility of Escherichia coli isolates from urinary tract infections exhibiting different resistance phenotypes.

Susceptibility to beta-lactams was determined in 203 recent Spanish E. coli isolates from urinary tract infections exhibiting different resistance phenotypes: a) susceptible (n = 60); b) quinolone-resistant (n = 45); c) penicillinase (n=64); d) hyperproduction of penicillinase (n=8); e) inhibitor resistant TEM (IRT) (n=18), and f) extended spectrum betalactamase (ESBL) (n=8).Minimum inhibitory concentration (MIC) determination by agar dilution and susceptibility tests for ESBL detection by macrodilution were performed following CLSI recommendations. All the beta-lactams tested showed high activity against susceptible and penicillinase phenotypes, with close to 100 % susceptibility. Hyperproduction of penicillinase increased MIC90 values for all antibiotics except for meropenem, with 100% resistance to cefuroxime and amoxicillin/clavulanic acid, and 100% susceptibility to cefotaxime, piperacillin/tazobactam and meropenem. All the antibiotics, except for amoxicillin/clavulanic acid, exhibited high activity against IRT. Meropenem, cefminox and piperacillin/tazobactam exhibited the highest activity against ESBL, followed by amoxicillin/clavulanic acid. The most active compound among the parenteral antibiotics was meropenem, regardless of the resistance phenotype. Among the oral antibiotics, the most active compound was cefditoren with the exception of ESBL where amoxicillin/clavulanic acid where the MIC90 value was one dilution lower.

â - lactam susceptibility of Escherichia coli isolates from urinary tract infections exhibiting different resistance phenotypes

Susceptibility to â-lactams was determined in 203 recentSpanish E. coli isolates from urinary tract infectionsexhibiting different resistance phenotypes: a) susceptible(n = 60); b) quinolone-resistant (n = 45); c) penicillinase(n=64); d) hyperproduction of penicillinase (n=8); e) inhibitorresistant TEM (IRT) (n=18), and f) extended spectrumbetalactamase (ESBL) (n=8). Minimum inhibitory concentration(MIC) determination by agar dilution and susceptibilitytests for ESBL detection by macrodilution were performedfollowing CLSI recommendations. All the â-lactamstested showed high activity against susceptible and penicillinasephenotypes, with close to 100 % susceptibility.Hyperproduction of penicillinase increased MIC90 values forall antibiotics except for meropenem, with 100% resistanceto cefuroxime and amoxicillin/clavulanic acid, and 100%susceptibility to cefotaxime, piperacillin/tazobactam andmeropenem. All the antibiotics, except for amoxicillin/clavulanicacid, exhibited high activity against IRT. Meropenem,cefminox and piperacillin/tazobactam exhibited thehighest activity against ESBL, followed by amoxicillin/clavulanicacid. The most active compound among the parenteralantibiotics was meropenem, regardless of the resistancephenotype. Among the oral antibiotics, the most activecompound was cefditoren with the exception of ESBL whereamoxicillin/clavulanic acid where the MIC90 value wasone dilution lower (AU)

Se determinó la susceptibilidad a betalactámicos de203 aislados recientes de E. coli procedentes de infeccionesdel tracto urinario en España y que presentaban distintosfenotipos de resistencia: a) susceptible (n = 60);b) resistente a quinolonas (n=45); c) productor de penicilinasa(n=64); d) hiperproductor de penicilinasa (n=8);e) resistente a inhibidores de TEM (IRT) (n=18), y f) productorde betalactamasas de espectro extendido (BLEE)(n=8). La determinación de la concentración mínima inhibitoria(CMI) por dilución en agar y los tests de susceptibilidadpara la detección de BLEE se realizaron siguiendolas recomendaciones del Clinical and Laboratory StandardsInstitute (CLSI). Frente a los fenotipos susceptible yproductor de penicilinasa, todos los betalactámicos ensayadosexhibieron gran actividad, con una sensibilidadcercana al 100% de los aislados. La hiperproducción depenicilinasa incrementó los valores de CMI90 de todos losantibióticos, excepto de meropenem, con un 100% de resistenciaa cefuroxima y amoxicilina/clavulánico y un 100% desensibilidad a cefotaxime, piperacilina/tazobactam y meropenem.Todos los antibióticos, excepto amoxicilina/clavulánico,presentaron gran actividad frente a las cepas IRT.Meropenem, cefminox y piperacilina/tazobactam presentaronla mayor actividad frente a BLEE, seguidas de amoxicilina/clavulánico. Entre los antibióticos parenterales, elcompuesto más activo fue meropenem, con independenciadel fenotipo de resistencia. Entre los antibióticos oralesel compuesto más activo fue cefditoren, excepto frentea las cepas BLEE, donde amoxicilina/clavulánico presentóen un valor de CMI90 una dilución menor (AU)

Evaluation of the in-vitro cidal activity and toxicity of a novel peroxygen biocide: 2-butanone peroxide.

The monomer of 2-butanone peroxide is a novel peroxygen derivative with potential use as biocide in the hospital environment. The aim of this study was to test the biocidal activity of different concentrations of the compound against American Tissue Culture Collection strains from 11 different micro-organisms, including bacteria, mycobacteria, spores, fungi and virus, following the European Standard guidelines. Toxicity tests were also carried out following United States Environmental Protection Agency Standards. 2-Butanone peroxide exhibited biocidal activity at 0.12% against Legionella pneumophila, at 0.5% against Escherichia coli, Pseudomonas aeruginosa and Enterococcus hirae, and at 1% against Staphylococcus aureus after 5 min contact at room temperature. Mycobactericidal activity was obtained at 0.5% after 60 min contact at 20 degrees C, and sporicidal activity was obtained at 4% after 60 min at 40 degrees C. Good fungicidal (against yeasts and moulds) and virucidal (adenovirus and poliovirus) activities were obtained at 0.5% after 60 min contact. Toxicity assessment showed negative results in the acute dermal irritation test, acute eye irritation test and acute oral toxicity test. The skin sensitisation test was negative. The safety profile in the toxicity tests and the basic cidal activity against the strains tested suggest that 2-butanone peroxide in the control of hospital infections.