Prognostic significance of survivin expression in pediatric ewing sarcoma.

Survivin is an inhibitor of apoptosis protein that inhibits caspases and blocks cell death. It is undetectable in most normal adult tissues. High survivin expression has been detected in various tumors and has been correlated with therapy resistance and poor outcome. We conducted this study to examine survivin expression in pediatric Ewing sarcoma (ES) and evaluate its role in predicting clinical outcome. Formalin-fixed paraffin-embedded tumor tissues from 108 pediatric ES patients were examined by immunostaining with survivin rabbit monoclonal antibodies. Survivin was detected in tumor tissues of 72 (66.7%) patients. High expression (≥50%) was detected in 18 (16.7%) patients. High survivin expression was shown to be a significant univariate parameter for poorer overall (OS) and event free survival (EFS) with p value 0.033, and 0.037 respectively. It was confirmed as an independent factor in multivariate analysis for OS (p: 0.041; HR: 1.97 with 95% CI of 1.03-3.79) and EFS (p: 0.049; HR: 1.86 with 95% CI of 1.00-3.46). These results suggest that high survivin expression identifies a group of patients with poor prognosis and this may help to refine risk adapted treatment; however, this needs to be confirmed in prospective studies.

Temporal trends in childhood cancer survival in Egypt, 2007 to 2017: A large retrospective study of 14 808 children with cancer from the Children's Cancer Hospital Egypt.

Childhood cancer is a priority in Egypt due to large numbers of children with cancer, suboptimal care and insufficient resources. It is difficult to evaluate progress in survival because of paucity of data in National Cancer Registry. In this study, we studied survival rates and trends in survival of the largest available cohort of children with cancer (n = 15 779, aged 0-18 years) from Egypt between 2007 and 2017, treated at Children's Cancer Hospital Egypt-(CCHE), representing 40% to 50% of all childhood cancers across Egypt. We estimated 5-year overall survival (OS) for 14 808 eligible patients using Kaplan-Meier method, and determined survival trends using Cox regression by single year of diagnosis and by diagnosis periods. We compared age-standardized rates to international benchmarks in England and the United States, identified cancers with inferior survival and provided recommendations for improvement. Five-year OS was 72.1% (95% CI 71.3-72.9) for all cancers combined, and survival trends increased significantly by single year of diagnosis (P < .001) and by calendar periods from 69.6% to 74.2% (P < .0001) between 2007-2012 and 2013-2017. Survival trends improved significantly for leukemias, lymphomas, CNS tumors, neuroblastoma, hepatoblastoma and Ewing Sarcoma. Survival was significantly lower by 9% and 11.2% (P < .001) than England and the United States, respectively. Significantly inferior survival was observed for the majority of cancers. Although survival trends are improving for childhood cancers in Egypt/CCHE, survival is still inferior in high-income countries. We provide evidence-based recommendations to improve survival in Egypt by reflecting on current obstacles in care, with further implications on practice and policy.

Clinical features and outcome of hepatosplenic fungal infections in children with haematological malignancies.

Hepatosplenic fungal infection (HSFI) is a severe invasive fungal infection observed during neutrophil recovery in patients with acute leukaemia treated with intensive chemotherapy. Retrospective analysis including all paediatric haematological malignancies patients with HSC treated in Children Cancer Hospital Egypt (2013-2018). Twenty-five patients with acute leukaemia developed HSFI (19 patients diagnosed as hepatosplenic candidiasis). Most of the cases (92%) occurred during the induction phase. Organs affected were as follows: liver in 18 patients, renal in 13 patients, spleen in 12 patients, skin in four patients and retina in one patient. Five (20%) patients had proven HSC, 14 (56%) probable and six (24%) possible HSFI. Ten patients had a PET-CT for response assessment. Candida tropicalis was the most common isolated spp. from blood/tissue culture. Six (24%) patients developed HSFI on top of antifungal prophylaxis. Steroids were given in 12 (52%) patients with HSFI as immune reconstitution syndrome (IRS). Caspofungin was the first line of treatment in 14 (56%) patients, liposomal amphotericin B in six (24%) patients and azoles in five (20%) patients. HSFI was associated with delayed of intensification phase of chemotherapy (median 42 days). The success rate was reported in 24 patients with complete response (68%) and partial response in (28%) patients, while failure (death) seen in 1(4%) patient. HSC is still a major challenge in paediatric leukaemias patients with impact on treatment delay and survival outcome. PET scan, non-culture diagnostics and steroid role evidence in IRS are growing. Antifungal stewardship for screening, early detection for high-risk patients and better response assessment is challenging.

Early Deaths in Pediatric Acute Leukemia: A Major Challenge in Developing Countries.

Children with acute leukemia may experience high treatment-related mortality, which often occurs early in the induction phase. The aim of the study was to assess the incidence and risk factors related to increased mortality during induction therapy of pediatric patients with acute leukemia. This is a retrospective study that included pediatric acute leukemia patients who presented to the National Cancer Institute, Cairo University, between January 2011 and December 2013. The study included 370 patients, 253 with acute lymphoblastic leukemia, 100 with acute myeloid leukemia, and 17 with mixed phenotype acute leukemia. The total and induction death rates were 40.5% and 19.2%, respectively. Most of the early deaths were attributed to infections (64.7%) and cerebrovascular accidents (18.3%). Using enhanced supportive care measures during 2013 had significantly reduced the overall and induction mortality rates (29% and 13.6%, respectively, in 2013 vs. 46% and 20.3% in 2011). Induction deaths in pediatric acute leukemia remain a major challenge in developing countries, and using enhanced supportive care measures is effective to improve the survival outcome in this group of patients.

Investigation and Management of a Rhizomucor Outbreak in a Pediatric Cancer Hospital in Egypt.

We describe an outbreak of mucormycosis in a pediatric oncology hospital during December 2010 and the measures taken to stop it. The outbreak began with two consecutive cases of laboratory-documented mucormycosis infections within 1 week. Investigations to track the source were conducted immediately. Air plate cultures from machines and ducts supplying patients' rooms revealed the growth of Rhizomucor. Of five affected patients, all had acute leukemia and three were histopathologically proven. All patients were treated with liposomal amphotericin B after mucormycosis was diagnosed. Posaconazole was used as a secondary prophylaxis in one case. Three patients died.

Early Ventricular Dysfunction After Anthracycline Chemotherapy in Children.

The aim of this study was to determine the effect of induction dose of anthracycline chemotherapy on the biventricular function among children with acute hematological malignancies (AHM) using tissue Doppler imaging (TDI) and 2D speckle tracking echocardiography (2D-STE). Thirty pediatric patients with AHM and a mean age of 9.24 ± 4.14 years performed conventional echocardiography, TDI and 2D-STE. After induction chemotherapy, the RV showed mainly a diastolic alteration in its function manifested in significant reduction in the tricuspid TDI-derived E' and E'/A' ratio compared with the baseline (20.40 ± 3.81 vs. 17.47 ± 3.87 cm/s, p = 0.001, 1.29 ± 0.27 vs. 1.03 ± 0.37, p < 0.01, respectively), while the TDI-derived RV MPI and isovolumetric relaxation time of RV were significantly increased (0.32 ± 0.06 vs. 0.36 ± 0.08, p < 0.01, 24.73 ± 8.62 vs. 28.47 ± 11.51 ms, p < 0.05, respectively). The LV showed post-chemotherapy mainly an alteration in its longitudinal systolic function in the form of a reduction in MAPSE (13.61 ± 2.00 vs. 11.95 ± 1.75 mm; p < 0.001), TDI-derived systolic velocity of lateral mitral annulus (10.98 ± 2.34 vs. 10.03 ± 1.83 cm/s, p < 0.05), 2D-STE-derived global longitudinal strain (-21.58 ± 2.54 vs. -19.18 ± 3.59 %, p = 0.001) and 2D-STE-derived global longitudinal strain rate (-1.76 ± 0.22 vs. 1.55 ± 0.29 1/s, p < 0.05), with preservation of LV diastolic function when compared to baseline. TDI and 2D-STE could be used for early detection of anthracycline-induced cardiotoxicity in the pediatric age group. Early after induction chemotherapy, the RV develops mainly diastolic dysfunction, while the LV showed a relative longitudinal systolic impairment.

Optimizing vancomycin therapeutic drug monitoring compliance in pediatric oncology: towards personalized medication management.

Aim: Vancomycin, a crucial treatment for Gram-positive bacteria, necessitates therapeutic drug monitoring (TDM) to prevent treatment failures. We investigated the healthcare professional's compliance toward TDM of vancomycin recommendations and follow-up levels. Materials & methods: We collected data from 485 patients who received vancomycin in the Children's Cancer Hospital Egypt 57357 medical records system (Cerner) over 4 months, from January to April 2020. Results: Our data shows that only 54% of patients had TDM requests from healthcare professionals for the total patients who received vancomycin treatment. The healthcare professionals' compliance with the recommendations was 91.7%, while the follow-up levels were 66.7%. Conclusion: While overall adherence to recommendations is strong, enhancing compliance with follow-up levels remains a priority for improvement.

[Box: see text].

Carbapenem-Resistant Enterobacteriaceae (CRE) among Children with Cancer: Predictors of Mortality and Treatment Outcome.

Carbapenem-resistant Enterobacteriaceae (CRE) is an important emerging threat among pediatric cancer patients, with a high mortality rate. This retrospective study included all pediatric cancer patients with (CRE) bloodstream infections (BSIs) at a children's cancer hospital in Egypt (2013-2017). Two hundred and fifty-four pediatric cancer patients with CRE BSI were identified; 74% had hematological malignancies, and 26% had solid tumors. Acute myeloid leukemia was the most common hematological malignancy (50%). The main clinical features for acquiring CRE-BSI were previous antibiotics exposure (90%), profound neutropenia (84%), prolonged steroid use (45%), previous colonization with a resistant pathogen (35%), ICU admission within 90 days (28%), and central venous catheter use (24%). E. coli was the most common isolated pathogen (56%), followed by Klebsiella pneumoniae (37%). All isolates were resistant to carbapenem with an MIC < 4-8 µg/mL in 100 (45%) and >8 µg/mL in 153 (55%). The overall mortality rate was 57%, and 30 day mortality was reported in 30%. Upon multivariate analysis, for the patients with Klebsiella pneumoniae BSI, carbapenem resistance with an MIC > 8 µg/mL and associated typhlitis or pneumonia were predictors of poor outcome. In conclusion, CRE-BSI is a major threat among pediatric cancer patients in limited resource countries with limited options for treatment. Antimicrobial stewardship for early detection through routine screening, adequate empirical treatment, and timely adequate therapy may impact the outcome for such high-risk patient groups.

Cost-effectiveness of childhood cancer treatment in Egypt: Lessons to promote high-value care in a resource-limited setting based on real-world evidence.

Background: Childhood cancer in low-and middle-income countries is a global health priority, however, the perception that treatment is unaffordable has potentially led to scarce investment in resources, contributing to inferior survival. In this study, we analysed real-world data about the cost-effectiveness of treating 8886 children with cancer at a large resource-limited paediatric oncology setting in Egypt, between 2013 and 2017, stratified by cancer type, stage/risk, and disease status. Methods: Childhood cancer costs (USD 2019) were calculated from a health-system perspective, and 5-year overall survival was used to represent clinical effectiveness. We estimated cost-effectiveness as the cost per disability-adjusted life-year (cost/DALY) averted, adjusted for utility decrement for late-effect morbidity and mortality. Findings: For all cancers combined, cost/DALY averted was $1384 (0.5 × GDP/capita), which is very cost-effective according to WHO-CHOICE thresholds. Ratio of cost/DALY averted to GDP/capita varied by cancer type/sub-type and disease severity (range: 0.1-1.6), where it was lowest for Hodgkin lymphoma, and retinoblastoma, and highest for high-risk acute leukaemia, and high-risk neuroblastoma. Treatment was cost-effective (ratio <3 × GDP/capita) for all cancer types/subtypes and risk/stage groups, except for relapsed/refractory acute leukaemia, and relapsed/progressive patients with brain tumours, hepatoblastoma, Ewing sarcoma, and neuroblastoma. Treatment cost-effectiveness was affected by the high costs and inferior survival of advanced-stage/high-risk and relapsed/progressive cancers. Interpretation: Childhood cancer treatment is cost-effective in a resource-limited setting in Egypt, except for some relapsed/progressive cancer groups. We present evidence-based recommendations and lessons to promote high-value in care delivery, with implications on practice and policy. Funding: Egypt Cancer Network; NIHR School for Primary Care Research; ALSAC.

Knowledge, attitudes and practice regarding pharmacovigilance and adverse drug reaction reporting among physicians and pharmacists in Egypt: a step toward personalized medicine implementation.

Aim: To assess the knowledge, attitudes, and practices of the healthcare professionals working at Children's Cancer Hospital Egypt regarding pharmacovigilance (PV) and adverse drug reaction (ADR) reporting, in addition to the ADR reporting barriers. Materials & methods: A cross-sectional study was conducted at Children's Cancer Hospital Egypt from July to September 2021 using a validated questionnaire. Results: About 37 physicians (20.3%) and 145 pharmacists (79.7%) responded to the survey. Overall, the knowledge (median: 40%) and practice (median: 50%) of PV and the reporting of ADRs were low; however, attitudes were mostly positive. The main barrier to reporting ADRs was The difficulty of determining whether or not ADRs occurred (42.3%). Conclusion: Understanding of PV and ADR reporting could improve the huge gap between ADRs experienced and ADRs reported. In order to be able to assess the impact of personalized medicine implementation, adequate ADR reporting should be well established.

Since no medication is completely safe, many of them are associated with multiple adverse reactions that may affect patients' health in terms of morbidity and, even worse, mortality. These concerns greatly increase the importance of reporting adverse drug reactions (ADRs), which highlights the essential role of pharmacovigilance (PV) centers. This study was performed at Children's Cancer Hospital using a validated questionnaire; to collect information on healthcare professionals' demographics and their knowledge of, attitudes toward and practices in PV; analyze reasons for the the under-reporting of ADRs; and recommend possible ways to improve reporting. The majority of the healthcare professionals had poor knowledge and practice of PV and ADR reporting, which clearly explains the huge gap between ADRs experienced and ADRs reported. However, they have a positive attitude toward PV and ADR reporting.

Knowledge, attitudes and practices of Egyptian healthcare professionals toward therapeutic drug monitoring service as a principal component of personalized medicine.

Aim: To assess pharmacists' and physicians' knowledge, attitudes and practices toward therapeutic drug monitoring (TDM) service at the Children's Cancer Hospital Egypt 57357. Materials & methods: This was a single-site cross-sectional study where all practicing pharmacists and physicians were eligible to participate. Results: A statistically significant difference in the knowledge scores between pharmacists and physicians (p = 0.022) was found. In general, attitudes toward TDM among pharmacists and physicians were positive. Regarding practices, pharmacists were more likely than physicians to agree or strongly agree that they have studied some scientific references on TDM (p = 0.034), but more physicians recommend the TDM service (p = 0.046). Conclusion: A multidisciplinary educational program in Egypt for TDM for both medicine and pharmacy staff will improve interprofessional collaboration in the clinical setting, leading to better personalized medication management.

The objective of the present survey was to evaluate the knowledge, attitudes and practices of pharmacists and physicians toward therapeutic drug monitoring (TDM) services at the Children's Cancer Hospital Egypt 57357. TDM is defined as 'measuring the amount of specific drugs in patients' blood to ensure that the concentrations of administered drugs are both effective and safe'. A single-centered study was conducted at the CCHE where all pharmacists and physicians participated. There was a remarkable difference in the knowledge scores between pharmacists and physicians. Generally, both pharmacists and physicians demonstrated positive attitudes toward TDM. In real-life practice, pharmacists were more likely than physicians to agree that they had scientific evidence about TDM. Multidisciplinary educational programs for TDM among physicians and pharmacists would improve interprofessional collaboration for the benefit of patients in Egypt.

COVID-19-Associated Pulmonary Fungal Infection among Pediatric Cancer Patients, a Single Center Experience.

Patients with COVID-19 are at risk of developing secondary complications such as invasive pulmonary aspergillosis and mucormycosis. This is a retrospective study including all cancer children diagnosed with COVID-19-associated pulmonary fungal infection (CAPFI) during the period 2020-2021. A total of 200 patients were diagnosed with COVID-19, out of which 21 (10%) patients were diagnosed with CAPFI, 19 patients (90%) with COVID-aspergillosis (CAPA), and 2 (10%) patients with COVID-mucormycosis (CAM). Patients with CAPFI were classified using the "2020 ECMM/ISHAM consensus criteria"; proven in 2 (10%) patients, probable in 12 (57%), and possible in 7 (33%) patients. Although the hematological malignancy patients were already on antifungal prophylaxis, breakthrough fungal infection was reported in 16/21 (75%), 14 (65%) patients had CAPA while on echinocandin prophylaxis, while 2 (10%) patients had CAM while on voriconazole prophylaxis. Overall mortality was reported in 8 patients (38%) while CAPFI-attributable mortality was reported in 4 patients (20%). In conclusion, clinicians caring for pediatric cancer patients with COVID-19 should consider invasive pulmonary fungal infection, even if they are on antifungal prophylaxis, especially with worsening of the clinical chest condition. A better understanding of risk factors for adverse outcomes may improve clinical management in these patients.

SARS-CoV-2 genome variations and evolution patterns in Egypt: a multi-center study.

A serious global public health emergency emerged late November 2019 in Wuhan City, China, by a new highly pathogenic virus, SARS-CoV-2. The virus evolution spread has been tracked by three developing databases: GISAID, Nextstrain and PANGO to understand its circulating variants. In this study, 110 diagnosed positive COVID-19 patient's samples, were collected from Kasr Al-Aini Hospital and the Children Cancer Hospital Egypt 57357 between May 2020 and January 2021, with clinical severity ranging from mild to severe. The viral genomes were sequenced by next generation sequencing, and phylogenetic analysis was performed to understand viral transmission dynamics. According to Nextstrain clades, most of our sequenced samples belonged to clades 20A and 20D, which in addition to clade 20B were present from the beginning of sample collection in May 2020. Clades 19A and 19B, on the other hand, appeared in the mid and late 2020 respectively, followed by the disappearance of clade 20B at the end of 2020. We identified a relatively high prevalence of the D614G spike protein variant and novel patterns of mutations associated together and with different clades. We also identified four mutations, spike H49Y, ORF3a H78Y, ORF8 E64stop and nucleocapsid E378V, associated with higher disease severity. Altogether, our study contributes genetic, phylogenetic, and clinical correlation data about the spread of the SARS-CoV-2 pandemic in Egypt.

Antibiotic resistance is associated with longer bacteremic episodes and worse outcome in febrile neutropenic children with cancer.

PURPOSE: With the increasing emergence of multiresistant pathogens, better understanding of these infections is necessary. The aim of the present study was to evaluate the risk factors associated with isolating a multiresistant organism (MRO) from a positive blood culture in pediatric cancer patients with febrile neutropenia (F&N), and to study its impact on clinical course and outcome of febrile episodes. PATIENTS AND METHODS: The association between MRO with underlying malignancy, age, disease status, hospitalization during episode, absolute neutrophil count, absolute monocyte count, clinical foci of infection, and pathogens isolated was assessed in bacteremic pediatric cancer patients. The MRO phenotype was defined as diminished susceptibility to ≥3 of the broad spectrum antibody classes. RESULTS: Among 239 episodes of blood stream infections (BSI), Gram-positive, and Gram-negative organisms were detected in 180 (75%), and 59(25%) episodes, respectively; with 38% of isolates showing multiresistance (n = 92). Significant risk factors (P < 0.05) for MRO were hospitalization, Gram-negative organisms, presence of clinical focus of infection, reduced ANC, prolonged duration of neutropenia, and previous intake of antibiotics. Of the episodes with prolonged duration of fever extending for more than 7 days 62% (64|93) were associated with a multiresistant phenotype, while it accompanied 72% (18|25) of the cases with an unfavorable outcome; P-value <0.001. CONCLUSION: Isolation of MRO is more likely to be associated with a prolonged course and an unfavorable outcome. Continuous multidisciplinary surveillance of BSI is warranted to develop strategies for antimicrobial resistance control.

Deciphering Multidrug-Resistant Acinetobacter baumannii from a Pediatric Cancer Hospital in Egypt.

Infection by multidrug-resistant (MDR) Acinetobacter baumannii is one of the major causes of hospital-acquired infections worldwide. The ability of A. baumannii to survive in adverse conditions as well as its extensive antimicrobial resistance make it one of the most difficult to treat pathogens associated with high mortality rates. The aim of this study was to investigate MDR A. baumannii that has spread among pediatric cancer patients in the Children's Cancer Hospital Egypt 57357. Whole-genome sequencing was used to characterize 31 MDR A. baumannii clinical isolates. Phenotypically, the isolates were MDR, with four isolates showing resistance to the last-resort antibiotic colistin. Multilocus sequence typing showed the presence of eight clonal groups, two of which were previously reported to cause outbreaks in Egypt, and one novel sequence type (ST), Oxf-ST2246. Identification of the circulating plasmids showed the presence of two plasmid lineages in the isolates, strongly governed by sequence type. A large number of antimicrobial genes with a range of resistance mechanisms were detected in the isolates, including ß-lactamases and antibiotic efflux pumps. Analysis of insertion sequences (ISs) revealed the presence of ISAba1 and ISAba125 in all the samples, which amplify ß-lactamase expression, causing extensive carbapenem resistance. Mutation analysis was used to decipher underlying mutations responsible for colistin resistance and revealed novel mutations in several outer membrane proteins, in addition to previously reported mutations in pmrB. Altogether, understanding the transmissibility of A. baumannii as well as its resistance and virulence mechanisms will help develop novel treatment options for better management of hospital-acquired infections. IMPORTANCE Acinetobacter baumannii represents a major health threat, in particular among immunocompromised cancer patients. The rise in carbapenem-resistant A. baumannii, and the development of resistance to the last-resort antimicrobial agent colistin, complicates the management of A. baumannii outbreaks and increases mortality rates. Here, we investigate 31 multidrug resistant A. baumannii isolates from pediatric cancer patients in Children's Cancer Hospital Egypt (CCHE) 57357 via whole-genome sequencing. Multilocus sequence typing (MLST) showed the presence of eight clonal groups including a novel sequence type. In silico detection of antimicrobial-resistant genes and virulence factors revealed a strong correlation between certain virulence genes and mortality as well as several point mutations in outer membrane proteins contributing to colistin resistance. Detection of CRISPR/Cas sequences in the majority of the samples was strongly correlated with the presence of prophage sequences and associated with failure of bacteriophage therapy. Altogether, understanding the genetic makeup of circulating A. baumannii is essential for better management of outbreaks.

Management and Outcome of Coronavirus Disease 2019 (COVID-19) in Pediatric Cancer Patients: A Single Centre Experience from a Developing Country.

INTRODUCTION: Sufficient data pertaining to the impact of the Coronavirus disease 2019 (COVID-19) on pediatric cancer patients is still lacking. The aim of this prospective study was to describe clinical management and outcomes of COVID-19 in pediatric oncology patients. PATIENTS AND METHODS: Conducted between May 1, 2020 and November 30, 2020, this study included 76 pediatric oncology patients with confirmed COVID-19. Remdesivir (RDV) was the antiviral therapy used. RESULTS: The median age of patients was 9 years. Sixty patients were on first line treatment. Hematological malignancies constituted 86.8% of patients. Severe to critical infections were 35.4% of patients. The commonest symptom was fever (93.4%). Chemotherapy was delayed in 59.2% of patients and doses were modified in 30.2%. The 60-day overall survival (OS) stood at 86.8%, with mortalities occurring only among critical patients. Of sixteen acute leukemia patients in the first induction therapy, 13 survived and 10 achieved complete remission. A negative RT-PCR within 2 weeks and improvement of radiological findings were statistically related to disease severity (P = .008 and .002, respectively). Better OS was associated with regression of radiological findings after 30 days from infection (P = .002). Forty-five patients received RDV, 42.1% had severe and critical forms of infection compared to 25.7% in the No-RDV group and yet OS was comparable in both groups. CONCLUSION: Most pediatric cancer patients with COVID-19 should have good clinical outcomes except for patients with critical infections. Cancer patients can tolerate chemotherapy including induction phase, alongside COVID-19 treatment. In severe and critical COVID-19, RDV might have a potential benefit.

Author Correction: Genotypic characterization of multiple drug resistant Escherichia coli isolates from a pediatric cancer hospital in Egypt.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genotypic characterization of multiple drug resistant Escherichia coli isolates from a pediatric cancer hospital in Egypt.

Infection with multiple drug resistant (MDR) Escherichia coli poses a life threat to immunocompromised pediatric cancer patients. Our aim is to genotypically characterize the plasmids harbored in MDR E. coli isolates recovered from bacteremic patients of Children's Cancer Hospital in Egypt 57357 (CCHE 57357). In this study, 21 carbapenem-resistant E. coli (CRE) isolates were selected that exhibit Quinolones and Aminoglycosides resistance. Plasmid shot-gun sequencing was performed using Illumina next- generation sequencing platform. Isolates demonstrated resistant to all beta-lactams, carbapenems, aminoglycosides and quinolones. Of the 32 antimicrobial resistant genes identified that exceeded the analysis cutoff coverage, the highest represented genes were aph(6)-Id, sul2, aph(3″)-Ib, aph(3')-Ia, sul1, dfrA12, TEM-220, NDM-11. Isolates employed a wide array of resistance mechanisms including antibiotic efflux, antibiotic inactivation, antibiotic target replacements and antibiotic target alteration. Sequenced isolates displayed diverse insertion sequences, including IS26, suggesting dynamic reshuffling of the harbored plasmids. Most isolates carried plasmids originating from other bacterial species suggesting a possible horizontal gene transfer. Only two isolates showed virulence factors with iroA gene cluster which was found in only one of them. Outside the realms of nosocomial infections among patients in hospitals, our results indicate a transfer of resistant genes and plasmids across different organisms.

Treatment of immunocompromised patients with suspected invasive fungal infections: economic analysis of diagnostic-driven versus empirical strategies in Algeria and Egypt.

Background: Invasive fungal infections (IFIs) in immunocompromised patients are associated with high mortality and treatment costs. Identifying appropriate, cost-effective treatment strategies is crucial to reduce the burden of IFIs. This economic assessment compared strategies for treating immunocompromised patients in Algeria and Egypt.Methods: We developed a decision analytic model incorporating clinical and cost inputs associated with a diagnostic-driven (DD) and standard empirical (SE) strategy. Costs and clinical outcomes were used to calculate incremental cost-effectiveness ratios (ICERs) per death avoided.Results: In both countries, 73.8 (DD) and 125.3 (SE) hypothetical patients per 1,000 received antifungal therapy; 73.8 (DD) and 32.7 (SE) had diagnosed IFIs. Survival at 180 days was similar between DD and SE strategies in Algeria (92.0% vs 91.6%) and Egypt (90.2% vs 90.0%). Total costs per patient were lower with the DD than SE strategy (Algeria: $839 vs $1,591; Egypt: $4,077 vs $4,717). ICERs indicated that the DD compared with SE strategy was associated with better clinical outcomes at a lower overall cost in both countries.Conclusion: Diagnostic-driven compared to empirical therapy may be cost-saving in Algeria and Egypt for the management of immunocompromised patients with persistent neutropenic fever, with no increase in mortality.

Increasing Antimicrobial Resistance Monitored in Surveillance Analysis of Blood Stream Infections in Febrile Neutropenic Pediatric Oncology Patients.

BACKGROUND: Continuous surveillance of pattern of blood stream infection is necessary in febrile neutropenia (FN)especially with the recent escalating trend in the management of pediatric cancer patients towards intensified regimens and with the increase in infections caused by resistant organisms limiting the choice of antibiotics. AIM: To monitor change in pattern of blood stream infections (BSI) in FN pediatric cancer patients. MATERIALS AND METHODS: Surveillance of FN episodes with positive BSI was prospectively monitored and compared to a previous surveillance in the same pediatric oncology unit. RESULTS: A total of 232 BSI positive episodes were documented in 192 patients during a 6 months period. The results of recent surveillance analysis showed an increase in intensified regimens of chemotherapy, antimicrobial resistance, fungal infections, and prolonged duration of episodes when compared to previous surveillance, with p value sof <0.001, 0.005, 0.021, and <0.001, respectively. There was an apparent decrease in the crude mortality but this was not statistically significant, to 6% in 2011 from 10 % in 2006. CONCLUSIONS: The pattern of BSI at our institution is still inclining towards gram positive organisms but is showing a shift towards more antibiotic resistance and fungal infections.