Safety and Efficacy of Prolonged Use of Dalbavancin in Bone and Joint Infections.

Dalbavancin is a lipoglycopeptide with potent activity against Gram-positive microorganisms, a long half-life, a favorable safety profile, and a high concentration in bone, which makes it an interesting alternative for treatment of osteoarticular infections. We performed a multicentric retrospective study of all patients with an osteoarticular infection (septic arthritis, spondylodiscitis, osteomyelitis, or orthopedic implant-related infection) treated with at least one dose of dalbavancin between 2016 and 2017 in 30 institutions in Spain. In order to evaluate the response, patients with or without an orthopedic implant were separated. A total of 64 patients were included. Staphylococcus epidermidis and Staphylococcus aureus were the most frequent microorganisms. The reasons for switching to dalbavancin were simplification (53.1%), adverse events (25%), or failure (21.9%). There were 7 adverse events, and no patient had to discontinue dalbavancin. In 45 cases, infection was related to an orthopedic implant. The implant material was retained in 23 cases, including that in 15 (65.2%) patients that were classified as cured and 8 (34.8%) that presented improvement. In 21 cases, the implants were removed, including those in 16 (76.2%) cases that were considered successes, 4 (19%) cases were considered improved, and 1 (4.8%) case that was considered a failure. Among the 19 cases without implants, 14 (73.7%) were considered cured, 3 (15.8%) were considered improved, and 2 (10.5%) were considered failures. The results show that dalbavancin is a well-tolerated antibiotic, even when >2 doses are administered, and is associated with a high cure rate. These are preliminary data with a short follow-up; therefore, it is necessary to gain more experience and, in the future, to establish the most appropriate dose and frequency.

Asthma Exacerbations in the Pediatric Emergency Department at a Tertiary Hospital: Association With Environmental Factors.

INTRODUCTION: Children with asthma experience recurrent respiratory symptoms and exacerbations due to multiple environmental factors. The aim of this study was to describe the prevalence and triggers of asthma exacerbations and their management in a cohort of pediatric patients attended in an emergency department (ED). METHODS: We performed an observational, retrospective, single-center study in the pediatric ED of Hospital Universitario La Paz, Madrid, Spain in 2015. Children with asthma exacerbations attending the ED were included after a thorough search using our institutional computer database. Pollen and atmospheric mold spore counts and pollution data were collected for that period from official websites. Multiple logistic regression was used to assess the association between daily pollution (NO2, PM10, ozone, pollen, and molds) and admissions to the ED because of asthma. RESULTS: During 2015, a total of 50 619 patients were attended in the ED of our hospital. Of these, 2609 (5%) were diagnosed with asthma exacerbation/bronchospasm. The patient had to be admitted to hospital in 21.7% of cases. The main triggers of asthma exacerbations were respiratory infection in 1841 cases (70.6%). A significant correlation was found between grass pollen counts and ED admissions (P<.0001). A positive correlation was also found between ED admissions and NO2 0.58 (95%CI, 0.02-0.87) and PM10 0.75 (95%CI, 0.31-0.93) (P<.05). CONCLUSION: Environmental factors such as grass pollen counts and pollution (NO2 and PM10) are associated with a higher frequency of admission to the ED.

Evaluation of an Online Educational Program for Parents and Caregivers of Children With Food Allergies.

BACKGROUND AND OBJECTIVE: The increasing prevalence of food allergy affects both patients and their families. Objective: The aim of this study was to evaluate the impact of an online educational program designed for parents and caregivers of children with food allergies. The program was developed by a multidisciplinary group comprising health care professionals, researchers, and expert patients under the participatory medicine model. MATERIAL AND METHODS: Participants took a 2-week online educational program covering major topics in food allergy management. General knowledge about the disease, symptoms, treatment, and topics relevant to families' daily lives were evaluated. The contents included educational videos, online forums, and live video chats. A pretest/posttest questionnaire survey was used to evaluate the impact of the program. RESULTS: A total of 207 participants enrolled in the educational program, which was completed by 130 (62.8%). Knowledge acquisition improved significantly following participation in the program in 15 out of 30 items (50%), reaching P<.001 for 8 items (26.7%). Of the 207 participants who started the program, 139 (67.1%) visited online forums, and 27.5% attended video chats. Average overall satisfaction with the educational program was 8.78 (on a scale of 0 to 10). CONCLUSIONS: The results obtained show that parents improved their knowledge in all areas of food allergy. The high level of satisfaction among participants suggests that digital learning tools are effective and motivational, enabling patients to acquire appropriate knowledge and thus increasing their quality of life.

Environmental assessment of potential toxic trace element contents in the inundated floodplain area of Tablas de Daimiel wetland (Spain).

Contamination of aquatic systems with potentially toxic trace elements (PTEs) is a major problem throughout the world. The National Park Tablas de Daimiel (NPTD) is considered to make up one of the two most important wetlands in the Biosphere Reserve called "Wet Spot." Since PTEs are good indicator of the prevailing environmental conditions and possible contamination, soil samples collected from 43 sites were analyzed in order to investigate the levels and its distribution of these elements, in the inundated floodplain area of the NPTD wetland. In addition, some physicochemical parameters such as pH, electrical conductivity and organic matter were measured. The total concentrations of 32 trace elements were determined by X-ray fluorescence. The results show that there was accumulation of lead (Pb), tin (Sn), selenium (Se), antimony (Sb), copper (Cu), vanadium (V), nickel (Ni), zinc (Zn), arsenic (As), strontium (Sr) and zirconium (Zr)-in some cases at high concentrations. The interpolated maps showed that the distributions of some of these elements and in some cases the trend in spatial variability are pronounced and decrease from the inlet to the outlet. The values for some elements are higher than the reference values, which is consistent with contamination (some values are higher by a factor of more than 10 compared to the reference). In the case of iodine (I), the levels at some sample points are significantly more than ten times the reference; Se appears in the range from 1.0 to 9.8 mg/kg, with an average value of 3.1 mg/kg, and these can be considered as seleniferous soils. The concentrations found are consistent with the introduction in the wetland of pollution by human activities, such as agricultural non-point sources, uncontrolled fertilization over many years, treatment with urban wastewater and other possible sources.

Efficacy of Lysophosphatidylcholine in Combination with Antimicrobial Agents against Acinetobacter baumannii in Experimental Murine Peritoneal Sepsis and Pneumonia Models.

Immune response stimulation to prevent infection progression may be an adjuvant to antimicrobial treatment. Lysophosphatidylcholine (LPC) is an immunomodulator involved in immune cell recruitment and activation. In this study, we aimed to evaluate the efficacy of LPC in combination with colistin, tigecycline, or imipenem in experimental murine models of peritoneal sepsis and pneumonia. We used Acinetobacter baumannii strain Ab9, which is susceptible to colistin, tigecycline, and imipenem, and multidrug-resistant strain Ab186, which is susceptible to colistin and resistant to tigecycline and imipenem. Pharmacokinetic and pharmacodynamic parameters for colistin, tigecycline, and imipenem and the 100% minimal lethal dose (MLD100) were determined for both strains. The therapeutic efficacies of LPC, colistin (60 mg/kg of body weight/day), tigecycline (10 mg/kg/day), and imipenem (180 mg/kg/day), alone or in combination, were assessed against Ab9 and Ab186 at the MLD100 in murine peritoneal sepsis and pneumonia models. The levels of pro- and anti-inflammatory cytokines, i.e., tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10), were determined by enzyme-linked immunosorbent assay (ELISA) for the same experimental models after inoculating mice with the MLD of both strains. LPC in combination with colistin, tigecycline, or imipenem markedly enhanced the bacterial clearance of Ab9 and Ab186 from the spleen and lungs and reduced bacteremia and mouse mortality rates (P < 0.05) compared with those for colistin, tigecycline, and imipenem monotherapies. Moreover, at 4 h post-bacterial infection, Ab9 induced higher TNF-α and lower IL-10 levels than those with Ab186 (4 µg/ml versus 3 µg/ml [P < 0.05] and 2 µg/ml versus 3.4 µg/ml [P < 0.05], respectively). LPC treatment combined with colistin, tigecycline, or imipenem modestly reduced the severity of infection by A. baumannii strains with different resistance phenotypes compared to LPC monotherapy in both experimental models.

Sequential antimicrobial treatment with linezolid for neurosurgical infections: efficacy, safety and cost study.

BACKGROUND: Evidence for the effectiveness of linezolid in neurosurgical infections (NSIs) is growing. The comfortable oral dosage and tolerance of linezolid opens the possibility for sequential antimicrobial treatment (SAT) in stable patients after a period of intravenous treatment. METHODS: To evaluate the efficacy and safety of SAT with oral linezolid in patients with NSI and to analyse the cost implications, an observational, non-comparative, prospective cohort study was conducted on clinically stable consecutive adult patients at the Neurosurgical Service. Following intravenous treatment, patients were discharged with SAT with oral linezolid. RESULTS: A total of 77 patients were included. The most common NSIs were: 41 surgical wound infections, 20 subdural empyemas, 18 epidural abscesses, and 16 brain abscesses. Forty-four percent of patients presented two or more concomitant NSIs. Aetiological agents commonly isolated were: Propionibacterium acnes (36 %), Staphylococcus aureus (23 %), Staphylococcus epidermidis (21 %) and Streptococcus spp. (13 %). The median duration of the SAT was 15 days (range, 3-42). The SAT was interrupted in five cases due to adverse events. The remainder of the patients were cured at the end of the SAT. A total of 1,163 days of hospitalisation were saved. An overall cost reduction of €516,188 was attributed to the SAT. Eight patients with device infections did not require removal of the device, with an additional cost reduction of €190,595. The mean cost saving per patient was €9,179. CONCLUSIONS: SAT with linezolid was safe and effective for the treatment of NSI. SAT reduces hospitalisation times, which means significant savings of health and economic resources.

A Strategic Study about Quality Characteristics in e-Health Systems Based on a Systematic Literature Review.

e-Health Systems quality management is an expensive and hard process that entails performing several tasks such as analysis, evaluation, and quality control. Furthermore, the development of an e-Health System involves great responsibility since people's health and quality of life depend on the system and services offered. The focus of the following study is to identify the gap in Quality Characteristics for e-Health Systems, by detecting not only which are the most studied, but also which are the most used Quality Characteristics these Systems include. A strategic study is driven in this paper by a Systematic Literature Review so as to identify Quality Characteristics in e-Health. Such study makes information and communication technology organizations reflect and act strategically to manage quality in e-Health Systems efficiently and effectively. As a result, this paper proposes the bases of a Quality Model and focuses on a set of Quality Characteristics to enable e-Health Systems quality management. Thus, we can conclude that this paper contributes to implementing knowledge with regard to the mission and view of e-Health (Systems) quality management and helps understand how current researches evaluate quality in e-Health Systems.

The oxidative stress induced in vivo by Shiga toxin-2 contributes to the pathogenicity of haemolytic uraemic syndrome.

Typical haemolytic uraemic syndrome (HUS) is caused by Shiga toxin (Stx)-producing Escherichia coli infections and is characterized by thrombotic microangiopathy that leads to haemolytic anaemia, thrombocytopenia and acute renal failure. Renal or neurological sequelae are consequences of irreversible tissue damage during the acute phase. Stx toxicity and the acute inflammatory response raised by the host determine the development of HUS. At present there is no specific therapy to control Stx damage. The pathogenic role of reactive oxygen species (ROS) on endothelial injury has been largely documented. In this study, we investigated the in-vivo effects of Stx on the oxidative balance and its contribution to the development of HUS in mice. In addition, we analysed the effect of anti-oxidant agents as therapeutic tools to counteract Stx toxicity. We demonstrated that Stx induced an oxidative imbalance, evidenced by renal glutathione depletion and increased lipid membrane peroxidation. The increased ROS production by neutrophils may be one of the major sources of oxidative stress during Stx intoxication. All these parameters were ameliorated by anti-oxidants reducing platelet activation, renal damage and increasing survival. To conclude, Stx generates a pro-oxidative state that contributes to kidney failure, and exogenous anti-oxidants could be beneficial to counteract this pathogenic pathway.

Effects of the combined administration of propranolol plus sorafenib on portal hypertension in cirrhotic rats.

Low doses of sorafenib have been shown to decrease portal pressure (PP), portal-systemic shunts, and liver fibrosis in cirrhotic rats. Nonselective beta blockers (NSBB) are the only drugs recommended for the treatment of portal hypertension. The aim of our study was to explore whether the combination of propranolol and sorafenib might show an additive effect reducing PP in cirrhotic rats. Groups of common bile duct-ligated cirrhotic rats (CBDL) and sham-operated control rats were treated by gavage with vehicle, propranolol (30 mg·kg(-1)·day(-1)), sorafenib (1 mg·kg(-1)·day(-1)), or propranolol+sorafenib. Treatment began 2 wk after the CBDL or sham operation. Hemodynamic evaluation was performed after 2 wk of treatment. In cirrhotic rats, propranolol and sorafenib produced a significant (P < 0.001) and similar reduction in PP (-19 and -15%, respectively). This was achieved through different mechanisms: whereas propranolol decreased PP by reducing portal blood flow (-35%; P = 0.03), sorafenib decreased PP without decreasing portal flow indicating decreased hepatic resistance. After propranolol+sorafenib, the fall in PP was significantly greater (-30%; P < 0.001) than with either drug alone, demonstrating an additive effect. However, the reduction in portal flow (-39%) under combined therapy was not significantly greater than after propranolol alone. Sorafenib, alone or in combination with propranolol, produced significant reduction in portal-systemic shunting (-25 and -33%, respectively), splanchnic vascularization (-37 and -41%, respectively), liver fibrosis (38%), and hepatic neovascularization (-42 and -51%, respectively). These effects were not observed after propranolol alone. In conclusion, the combination of propranolol+sorafenib causes a greater reduction in PP than either drug alone and decreases markedly the extent of portal-systemic shunting, splanchnic and hepatic neovascularization, and liver fibrosis, suggesting that this drug combination is a potentially useful strategy in the treatment of portal hypertension.

Efficacy of rifampin, in monotherapy and in combinations, in an experimental murine pneumonia model caused by panresistant Acinetobacter baumannii strains.

The objective of this work was to evaluate the efficacy of rifampin, and its combinations with imipenem or sulbactam, in an experimental pneumonia model caused by two panresistant Acinetobacter baumannii strains (HUVR99 and HUVR113). Minimum inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) (µg/ml) of the strains were rifampin 128/>128 for both strains, imipenem 128/>256 and 256/>256 for HUVR99 and HUVR113, respectively, and sulbactam >256/>256 for both strains. In time-kill studies, at MICs, rifampin was bactericidal for both strains and sulbactam against the HUVR99 strain. Rifampin plus imipenem or sulbactam, at the MIC or mice C (max), were synergistic. In vivo, against HUVR99 and HUVR113, rifampin (73% and 40%) and its combinations improved the survival with respect to the control group (20% and 0%, p < 0.05), respectively. Rifampin (87% and 46%) and its combinations improved the sterilization of blood cultures with respect to the control groups (0%, p < 0.05). In regard to the bacterial clearance from lungs, rifampin (2.57 ± 2.47 and 5.35 ± 3.03 log(10) cfu/g) and its combinations with imipenem or sulbactam diminished the bacterial lung concentration with respect to the control group (10.89 ± 3.00 and 11.86 ± 0.49, p < 0.05) with both strains. In conclusion, rifampin alone or associated to imipenem or sulbactam were effective for the treatment of murine pneumonia caused by selected panresistant A. baumannii strains.

Efficacy of tigecycline vs. imipenem in the treatment of experimental Acinetobacter baumannii murine pneumonia.

The in vivo activity of tigecycline was evaluated in an experimental pneumonia model (C57BL/6 mice) by Acinetobacter baumannii. Two clinical strains were used: minimum inhibitory concentrations (MICs) of imipenem and tigecycline 1 and 2 microg/mL (imipenem-susceptible, IPM-S), and 8 and 2 microg/mL (imipenem-intermediate, IPM-I), respectively. For imipenem (30 mg/Kg), T/CMI (h) were 1.04 and 0.51 for IPM-S and IPM-I, respectively. For tigecycline (5 mg/Kg), the area under the concentration-time curve (AUC)/MIC(0-24 h) (serum and lung) were 9.24 and 4.37 (for the two strains), respectively. In the efficacy experiments with the IPM-S, imipenem (log CFU/g 3.59 +/- 0.78, p = 0.006) and tigecycline (2.82 +/- 1.2, p = 0.054) decreased the bacterial counts in lungs with respect to its controls; with the IPM-I, both imipenem (1.21 +/- 0.52, p = 0.002) and tigecycline (3.21 +/- 0.28, p = 0.035) decreased the bacterial counts with respect to the controls. In the survival experiments, with the IPM-S, the mortality was the same in the control (67%) and in the tigecycline (77%) groups, and imipenem reduced it (21%, p = 0.025); with the IPM-I, the mortality was the same in the control (87%) and in the tigecycline (85%) groups, and imipenem (0%) reduced it (p < 0.001). In summary, the present study shows that tigecycline is less efficacious than imipenem in the treatment of experimental A. baumannii pneumonia caused by IPM-S and IPM-I strains.

Superinfection during treatment of nosocomial infections with tigecycline.

We performed a retrospective and observational study of 51 patients treated with tigecycline, as the treatment for nosocomial infections due to multidrug-resistant microorganisms, to evaluate the superinfection rate and their etiologies. Superinfections were diagnosed in 12 (23.5%) patients (seven due to Pseudomonas aeruginosa, 13.7%) and one patient had P. aeruginosa colonization. Five patients with superinfection died (41.6%), three due to superinfections and two to underlying diseases. The superinfection rate observed during tigecycline treatment is higher than that previously reported. Pseudomonas aeruginosa is the most frequent agent, being the cause of 58.5% of all superinfections.

Macular oedema associated with taxanes: A case report and literature review. / Edema macular asociado a taxanos: presentación de un caso y revisión de la literatura.

BACKGROUND AND PURPOSE: Although taxanes are a frequently used group of chemotherapy agents, they can, rarely, lead to macular oedema. The purpose of this article is to review and communicate, in an integrated way, the data of the cases previously reported in the literature, as well as to present a new case. MATERIAL AND METHODS: Narrative review of reports of cases of macular oedema associated with taxanes, and communication of the clinical case of a 73-year-old woman who, after treatment with paclitaxel for metastatic breast cancer, developed macular oedema that disappeared after discontinuing the drug. RESULTS: The review included 57 cases with data from 109 eyes collected in 52 articles. The large majority (76.79%) of the cases were women, and the mean age was 58.75 years. The cancer that most frequently motivated the treatment was breast cancer (60.72%), and 92.5% of cases had metastases. The most frequently associated drug was paclitaxel (52.63%). The median time to symptom development was 4.25 months. At the initial examination, 92.86% of the cases had bilateral oedema and the mean visual acuity was 0.4 (decimal scale). The mean macular thickness was 509.63 microns, and 97.83% of the eyes had no or minimal angiographic findings. In 90.57% of the cases, the treatment with taxanes was interrupted, and some other treatment was used in 43.86% of the cases, with the most widely used being acetazolamide. The outcome was favourable, to a greater or lesser extent, in 96.23% of cases. CONCLUSIONS: Despite being a rare entity, macular oedema associated with the use of taxanes is a disorder that every oncologist and ophthalmologist should be aware of, taking into account the good outcome of the condition that usually occurs when treatment is suspended.

Lymphocyte Transformation Test (LTT) in Allergy to Benznidazole: A Promising Approach.

Benznidazole (Bzn) from the nitroimidazole family and nifurtimox from nitrofurans family, are drugs used as first and second line treatment for acute and chronic phases of Chagas disease (CD). Even though skin reactions are frequent, confirmed allergy to Bzn is rare, and there are few cases reported in the literature. Since CD treatment is very restrained, the possibility of cross-reactivity between members of the same and other pharmacological families highlights the importance of an adequate diagnosis that allows alternative treatments in CD and other diseases. We report a series of 31 patients (69% women) referred to our Allergy unit with suspected hypersensitivity to Bzn, twenty three of them with mild reactions and eight of them with severe reactions. LTT with Bzn was performed in 31 patients and in 8 negative controls. LTT was also performed in 25 and 20 of these patients with nifurtimox and Mtn, respectively. Twenty-one out of thirty-one patients were Bzn prick tested, and all were negative. We obtained 2/19 positive results on patch tests to Bzn. LTT with Bzn was positive in 22/31 patients (Sensitivity 75.9% and specificity 100%). The test was considered positive with a stimulation index ≥2. There was a positive result in 7/25 patients for nifurtimox and in 7/20 patients with Mtn. After negative LTT and skin tests, oral provocation was performed in 4/9 patients, all negative. LTT is a safe test that seems to be more useful than skin tests (prick and patch test), particularly in severe reactions, in confirming delayed hypersensitivity to Bzn and detecting cross reactivity with other imidazoles such as Mtn and reactivity to other drugs like nifurtimox. Tests for these drugs need to be included in the workup of patients with hypersensitivity to Bzn in case they are needed as an alternative treatment for CD or to treat other frequent infectious diseases.