Implementation and Evaluation of Antimicrobial Stewardship Program in Medical ICU in Cairo University Specialized Pediatric Hospital

BACKGROUND: High antibiotics use in pediatric intensive care units (PICUs) results in antibiotic resistance, the unfavorable clinical outcome of patients, increase the length of hospital stay, and drug expenditure. AIM: This study aimed at setting clinical guidelines customized according to local diseases epidemiology and local cumulative antimicrobial susceptibility, implementing, and evaluating the Antimicrobial Stewardship Program (ASP) effect in; optimizing antibiotics use, decreasing antibiotics expenditure, decreasing the length of therapy and stay in hospitals, and improving patients’ clinical outcomes. METHODS: A prospective study was conducted at a PICU of the Specialized Pediatric Hospital, Cairo University. Facility-specific guidelines were set, and the ASP was implemented and evaluated through the following indicators; adherence of physicians to the guidelines, ASP recommendations and acceptance of them, the rate of mortality, length of stay, drug costs, antibiotics days of therapy, and length of therapy. RESULTS: The adherence to the ASP guidelines was positively correlated to the patient’s clinical outcome (p = 0.018). In post ASP period, the average length of stay and the length of therapy significantly decreased (p = 0.047, p = 0.001, respectively), the rate of adherence to the ASP guidelines was (91.9%), the days of therapy of ceftazidime, ceftriaxone, and amikacin decreased significantly (p = 0.041, p = 0.026, p = 0.004, respectively). The most common ASP recommendation was drug schedule/frequency change (26.1%) followed by drug discontinuation (17.8%) and the most common antibiotic required intervention was ampicillin-sulbactam (21.6%). CONCLUSION: The antimicrobial stewardship is very effective in optimizing antibiotics use and leads to favorable outcomes in terms of decreased length of therapy, hospital stay, and mortality rate of the patients

Risk Factors of Hypocalcemic Patients at Surgical Intensive Care Unit of Zagazig University Hospitals

Background: Hypocalcemia may be present as an asymptomatic laboratory finding or as a severe life-threatening condition. Objective: The study aimed to estimate incidence rate of hypocalcemia and to identify risk factors associated with hypocalcemia in patients of Surgical Intensive Care Unit of Zagazig University Hospitals. Patients and methods: This study involved 310 patients who enrolled to Surgical Intensive Care Unit, Zagazig University Hospitals over a period of six months. Total serum calcium concentration and ionized calcium concentration were measured. Results: The distribution of the studied cases according to admission diagnosis, 40% of the studied cases were admitted to ICU due to sepsis and septic shock, 16% polytrauma, 10% respiratory failure, 10% post-operative monitoring, 6% with ICH, 6% with uncontrolled HTN, 4% with ischemic stroke, 2% pancreatitis, 2% dehydration and electrolyte imbalance, 2% DKA and one case due to organophosphorus poisoning and 1% rhabdomyolysis. There was statistically significant negative correlation between GCS score and Ca total and ionized at 3rd day. However, a statistically significant positive correlation was detected between Ph and Ca total at 3rd day. Only sepsis, septic shock, hypertensive crisis, aminoglycosides, respiratory failure and APACHE score were significant risk factors for hypocalcemia. Conclusion: Hypocalcemia is more common in cases with sepsis and septic shock, hypertensive crisis, respiratory failure and cases with electrolyte disturbance

Crude Coal Tar and Ultraviolet (UV) A radiation (Modified Goeckerman Technique) in Treatment of Psoriasis

Background: Psoriasis is a chronic inflammatory dermatosis that has a substantial impact on the quality of life. Goeckerman\u27s technique (GT) has been recruited for the treatment of psoriasis with high clearance rates and long periods of remission.Psoriasis is a chronic inflammatory dermatosis that has a substantial impact on the quality of life. Goeckerman’s technique (GT) has been implemented for the treatment of psoriasis with high clearance rates and long periods of remission. The objective of this article was to evaluate the efficacy and safety of modified GT (crude coal tar 2.5% plus UVA) as an alternative therapeutic modality for psoriatic patients with skin types III-V. Twenty two patients with moderate, severe, and erythrodermic psoriasis were included in this study. All patients received modified GT (crude coal tar 2.5% plus UVA) six days per week for a period of 3 months. Assessment of the rate of reduction of psoriasis area severity index (PASI) was performed, as well as photographic documentation of each patient at baseline and after completion of therapy. There was a significant reduction in PASI scores after therapy in all patients (P=0.001). The rate of PASI reduction after therapy was &gt;50% in 63.6% of patients; 27.3% of patients achieved &gt;75% reduction and 9.1% of patients achieved 26-50% reduction. No serious side effects were reported in any of the patients. Modified GT is a safe and effective therapeutic option for patients with moderate and severe psoriasis.</p

Evolution of Resistance to Aurora Kinase B Inhibitors in Leukaemia Cells

Aurora kinase inhibitors are new mitosis-targeting drugs currently in clinical trials for the treatment of haematological and solid malignancies. However, knowledge of the molecular factors that influence sensitivity and resistance remains limited. Herein, we developed and characterised an in vitro leukaemia model of resistance to the Aurora B inhibitor ZM447439. Human T-cell acute lymphoblastic leukaemia cells, CCRF-CEM, were selected for resistance in 4 µM ZM447439. CEM/AKB4 cells showed no cross-resistance to tubulin-targeted and DNA-damaging agents, but were hypersensitive to an Aurora kinase A inhibitor. Sequencing revealed a mutation in the Aurora B kinase domain corresponding to a G160E amino acid substitution. Molecular modelling of drug binding in Aurora B containing this mutation suggested that resistance is mediated by the glutamate substitution preventing formation of an active drug-binding motif. Progression of resistance in the more highly selected CEM/AKB8 and CEM/AKB16 cells, derived sequentially from CEM/AKB4 in 8 and 16 µM ZM447439 respectively, was mediated by additional defects. These defects were independent of Aurora B and multi-drug resistance pathways and are associated with reduced apoptosis mostly likely due to reduced inhibition of the catalytic activity of aurora kinase B in the presence of drug. Our findings are important in the context of the use of these new targeted agents in treatment regimes against leukaemia and suggest resistance to therapy may arise through multiple independent mechanisms

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Phytochemical analysis and antidiabetic potential of Elaeagnus umbellata (Thunb.) in streptozotocin-induced diabetic rats: pharmacological and computational approach

Abstract Background The fruit of Elaeagnus umbellata has high medicinal values and is an excellent source of phytochemicals. This study was aimed to evaluate the antioxidant, enzyme inhibitory and antidiabetic potential of Elaeagnus umbellata. Methods The antioxidant potential of the crude extract and subfractions of E. umbellata fruit were determined using DPPH (2, 20-diphenyl-1-picrylhydrazyl) and ABTS (2, 2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) assays. The enzyme inhibitory potentials of extracts against α-amylase and α-glucosidase enzymes were also determined. The in vivo anti-hyperglycemic effects of the extract in STZ-induced type 2 diabetes were determined using Sprague Dawley adult rats. HPLC system (Agilent 1260) was used for the identification of bioactive compounds present in extracts. Molecular docking was used to identify and compare the interaction between the compounds (active constituents) and standard inhibitor acarbose with the α-amylase and α-glucosidase active sites. Results The chloroform, ethyl acetate, and butanol fractions showed significant antioxidant potential with IC50 values of 40, 45 and 60 μg/mL against DPPH and 57, 70 and 120 μg/mL against ABTS free radicals respectively. The chloroform and ethyl acetate were highly active against α-amylase and α-glucosidase (IC50 values 58 and 200 μg/ml against α-amylase 60 and 140 μg/ml against α-glucosidase. The crude extract, chloroform, and ethyl acetate fractions were more potent in controlling the hyperglycemia in STZ-induced type 2 diabetes in rats and considerable reduction of glucose level was observed compared to the non-treated group. Furthermore, the extracts were also found useful in controlling the secondary complications associated with type 2 diabetes mellitus which was evident from the observed substantial reduction in the blood level of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, total cholesterol, low-density lipoproteins, and triglycerides. The molecular docking approach indicated the favorable inhibitory interaction between the docked compounds and the active sites of the α-amylase and α-glucosidase. All docked compounds occupied the same binding site as occupied by acarbose. Conclusion It was concluded that E. umbellata can be used in the treatment of type 2 diabetes and oxidative stress. The extracts were also found to be effective in relieving the secondary complications associated with type 2 diabetes. Graphical abstrac

A phase 2 study of the combination of gemcitabine and cisplatin in patients with locally advanced or metastatic breast cancer previously treated with anthracyclines with/without taxanes

BACKGROUND AND OBJECTIVES: Many patients with relapsed metastatic breast cancer are pre-treated with taxanes and anthracyclines, which are usually given in the neoadjuvant/adjuvant setting or as first-line treatment for metastatic disease. The primary objective of this study was to determine the overall response rate for combination treatment with gemcitabine and cisplatin in patients with locally advanced or metastatic breast cancer who had relapsed after receiving one adjuvant/neoadjuvant or first-line metastatic chemotherapy regimen containing an anthracycline with/without a taxane. Secondary endpoints included duration of response, time to progression, one-year survival probability, and toxicity. DESIGN AND SETTING: A single-arm, open-label, phase 2 study conducted at 17 investigative sites in Egypt. PATIENTS AND METHODS: Treatment consisted of gemcitabine (1250 mg/m2) on Days 1 and 8 and cisplatin (70 mg/m2) on Day 1 of each 21-day cycle. Treatment continued until disease progression or a maximum of 6 cycles. RESULTS: Of 144 patients all were evaluable for safety and 132 patients were evaluable for efficacy. The overall response rate was 33.3% and 45.5% of the patients with stable disease as their best response. The median time to progression was 5.1 months and the one-year survival probability was 73%. The most common grade 3/4 adverse events were nausea/vomiting (20.1%), neutropenia (19.4%), anemia (13.9%), asthenia (11.1%), diarrhea (9.7%), stomatitis (7.6%), leucopenia (7.6%), and thrombocytopenia (6.2%). Twelve (8.3%) patients had serious adverse events. CONCLUSIONS: The results of this study indicate that gemcitabine and cisplatin were active and generally well tolerated in pretreated patients with locally advanced or metastatic breast cancer

Mitotic index of CEM and CEM/AKB4 cells in the presence and absence of 4 µM ZM447439.

<p>*Percentages of mitotic cells were calculated after counting at least 1000 cells in three independent experiments.</p