Infectious causes of fever of unknown origin in developing countries: An international ID-IRI study.

Background: Fever of unknown origin (FUO) in developing countries is an important dilemma and further research is needed to elucidate the infectious causes of FUO. Methods: A multi-center study for infectious causes of FUO in lower middle-income countries (LMIC) and low-income countries (LIC) was conducted between January 1, 2018 and January 1, 2023. In total, 15 participating centers from seven different countries provided the data, which were collected through the Infectious Diseases-International Research Initiative platform. Only adult patients with confirmed infection as the cause of FUO were included in the study. The severity parameters were quick Sequential Organ Failure Assessment (qSOFA) ≥2, intensive care unit (ICU) admission, vasopressor use, and invasive mechanical ventilation (IMV). Results: A total of 160 patients with infectious FUO were included in the study. Overall, 148 (92.5%) patients had community-acquired infections and 12 (7.5%) had hospital-acquired infections. The most common infectious syndromes were tuberculosis (TB) (n=27, 16.9%), infective endocarditis (n=25, 15.6%), malaria (n=21, 13.1%), brucellosis (n=15, 9.4%), and typhoid fever (n=9, 5.6%). Plasmodium falciparum, Mycobacterium tuberculosis, Brucellae, Staphylococcus aureus, Salmonella typhi, and Rickettsiae were the leading infectious agents in this study. A total of 56 (35.0%) cases had invasive procedures for diagnosis. The mean qSOFA score was 0.76±0.94 {median (interquartile range [IQR]): 0 (0-1)}. ICU admission (n=26, 16.2%), vasopressor use (n=14, 8.8%), and IMV (n=10, 6.3%) were not rare. Overall, 38 (23.8%) patients had at least one of the severity parameters. The mortality rate was 15 (9.4%), and the mortality was attributable to the infection causing FUO in 12 (7.5%) patients. Conclusions: In LMIC and LIC, tuberculosis and cardiac infections were the most severe and the leading infections causing FUO.

Prospective analysis of febrile neutropenia patients with bacteraemia: the results of an international ID-IRI study.

OBJECTIVES: Bacteraemia during the course of neutropenia is often fatal. We aimed to identify factors predicting mortality to have an insight into better clinical management. METHODS: The study has a prospective, observational design using pooled data from febrile neutropenia patients with bacteraemia in 41 centres in 16 countries. Polymicrobial bacteraemias were excluded. It was performed through the Infectious Diseases-International Research Initiative platform between 17 March 2021 and June 2021. Univariate analysis followed by a multivariate binary logistic regression model was used to determine independent predictors of 30-d in-hospital mortality (sensitivity, 81.2%; specificity, 65%). RESULTS: A total of 431 patients were enrolled, and 85 (19.7%) died. Haematological malignancies were detected in 361 (83.7%) patients. Escherichia coli (n = 117, 27.1%), Klebsiellae (n = 95, 22% %), Pseudomonadaceae (n = 63, 14.6%), Coagulase-negative Staphylococci (n = 57, 13.2%), Staphylococcus aureus (n = 30, 7%), and Enterococci (n = 21, 4.9%) were the common pathogens. Meropenem and piperacillin-tazobactam susceptibility, among the isolated pathogens, were only 66.1% and 53.6%, respectively. Pulse rate (odds ratio [OR], 1.018; 95% confidence interval [CI], 1.002-1.034), quick SOFA score (OR, 2.857; 95% CI, 2.120-3.851), inappropriate antimicrobial treatment (OR, 1.774; 95% CI, 1.011-3.851), Gram-negative bacteraemia (OR, 2.894; 95% CI, 1.437-5.825), bacteraemia of non-urinary origin (OR, 11.262; 95% CI, 1.368-92.720), and advancing age (OR, 1.017; 95% CI, 1.001-1.034) were independent predictors of mortality. Bacteraemia in our neutropenic patient population had distinctive characteristics. The severity of infection and the way to control it with appropriate antimicrobials, and local epidemiological data, came forward. CONCLUSIONS: Local antibiotic susceptibility profiles should be integrated into therapeutic recommendations, and infection control and prevention measures should be prioritised in this era of rapidly increasing antibiotic resistance.

Impact of Rapid Molecular Diagnostic Technique on Time to Optimal Antimicrobial Therapy and Hospital Outcomes in Pediatric Cancer Patients with Sepsis.

BACKGROUND: sepsis is a leading cause of morbidity and mortality in pediatric cancer patients. We sought to assess the impact of using rapid molecular diagnostic techniques on time to pathogen identification, early administration of targeted antimicrobial treatment, and hospital outcomes. PATIENTS AND METHODS: This prospective study was conducted at the Egyptian National Cancer Institute (1/2018-1/2019) on pediatric cancer patients with suspected sepsis. The cohort was divided into two groups. In one group, blood samples were sent for rapid molecular detection [multiplex-Polymerase Chain Reaction (PCR)] and blood cultures (PCR-group). While only blood cultures were collected for the second group (BC-group). RESULTS: In the entire cohort (n=120), the most common bacteria identified on blood cultures was Escherichia Coli (n=33,27.5%) followed by Klebsiella (n=31,25.8%). Multidrug-resistant bacteria were identified in 63 patients (52.5%). The median turnaround time to initial results was 5 hours in PCR-group (n=60), and 120 hours in BC-group (n=60)(P<0.001). For PCR-group, agreement in pathogen identification between the rapid molecular detection kit (PCR) and blood cultures was noted in 56 patients (93.3%). While the remaining four patients had no bacterial growth on blood cultures. The empirical antibiotic treatment for the PCR-group was modified based on the result of the PCR test. Antibiotic shift, based on blood culture sensitivity results, was done in 29 patients (48%) in PCR-group, compared to 45 patients (75%) in BC-group (P=0.003). Median sepsis episode duration [8-days vs. 10-days,P=0.361), and hospital mortality (42% vs. 50%, P=0.360) were slightly lower in PCR-group. However, this did not reach statistical significance. CONCLUSION: There was a substantial agreement in pathogen identification between the rapid molecular detection method (PCR) and blood culture results. PCR had a much shorter turnaround time, which allows for earlier start of optimal antimicrobial treatment, and might potentially improve hospital outcomes, which in turn will reduce associated health care costs.

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.

Classical fever of unknown origin in 21 countries with different economic development: an international ID-IRI study.

Fever of unknown origin (FUO) is a serious challenge for physicians. The aim of the present study was to consider epidemiology and dynamics of FUO in countries with different economic development. The data of FUO patients hospitalized/followed between 1st July 2016 and 1st July 2021 were collected retrospectively and submitted from referral centers in 21 countries through ID-IRI clinical research platform. The countries were categorized into developing (low-income (LI) and lower middle-income (LMI) economies) and developed countries (upper middle-income (UMI) and high-income (HI) economies). This research included 788 patients. FUO diagnoses were as follows: infections (51.6%; n = 407), neoplasms (11.4%, n = 90), collagen vascular disorders (9.3%, n = 73), undiagnosed (20.1%, n = 158), miscellaneous diseases (7.7%, n = 60). The most common infections were tuberculosis (n = 45, 5.7%), brucellosis (n = 39, 4.9%), rickettsiosis (n = 23, 2.9%), HIV infection (n = 20, 2.5%), and typhoid fever (n = 13, 1.6%). Cardiovascular infections (n = 56, 7.1%) were the most common infectious syndromes. Only collagen vascular disorders were reported significantly more from developed countries (RR = 2.00, 95% CI: 1.19-3.38). FUO had similar characteristics in LI/LMI and UMI/HI countries including the portion of undiagnosed cases (OR, 95% CI; 0.87 (0.65-1.15)), death attributed to FUO (RR = 0.87, 95% CI: 0.65-1.15, p-value = 0.3355), and the mean duration until diagnosis (p = 0.9663). Various aspects of FUO cannot be determined by the economic development solely. Other development indices can be considered in future analyses. Physicians in different countries should be equally prepared for FUO patients.

Outcome and safety of colistin usage in pediatric cancer patients with carbapenem-resistant enterobacteriaceae bacteremia at children cancer hospital Egypt.

Background: Carbapenem resistant Enterobacteriacae (CRE) bloodstream infection (BSI) causes complicated infections, especially in immunocompromised patients. This study aimed to assess the renal toxicity and the efficacy of therapy with colistin in a cohort of pediatric cancer patients with BSIs due to CRE and sensitivity to colistin. Patients and Methods: This was an observational, prospective cohort study from May 2017 to October 2017 in Children's Cancer Hospital Egypt 57,357. All patients who had blood stream infections due to CRE receiving intravenous colistin were prospectively enrolled. We used a standardized case form to record patient characteristics, including age, sex, weight, underlying comorbidities, type of infection, causative organism, and antibiotic susceptibility testing. Daily doses, duration of colistin therapy, and co-administered antibiotics (aminoglycosides, vancomycin) were collected. Furthermore, clinical and microbiological responses to treatment were reported. The dosing schedule was based on a loading dose of 5 MU and a 5-MU twice-daily divided maintenance dose, titrated on renal function. Clinical cure, bacteriological clearance, and daily serum creatinine were recorded. Results: One hundred and forty-one Blood Stream infectious episodes mainly due to Klebsiella Species (pneumoniae and Oxytoca) (27%) and Escherichia coli (68%) were analyzed. All strains were susceptible to colistin with Minimum inhibitory concentration (MICs) of 0.19-1.5 mg/L. Patients were predominantly females (69%), with a mean age of 7 years. It was used as a combination therapy with carbapenems (69.2%) or aminoglycosides (80%). The median duration of treatment was 9 days (Range 1-50 days). Clinical and microbiological cure was observed in 110 cases (80%). Acute kidney injury developed during five treatment courses (4%) in which colistin was used in combination with amikacin. No renal replacement therapy was required and subsided within 7 days from colistin discontinuation. Conclusions: Our study showed that colistin had a high efficacy without significant renal toxicity in severe infections due to CRE Gram-negative bacteria.

Résumé Carbapenem-resistant Gram-negative (CRE) bloodstream infection (BSI) causes complicated infections, especially in immunocompromised patients .This study aimed to assess the renal toxicity and the efficacy of therapy with colistin in a cohort of pediatric cancer patients with BSIs due to CRE and sensitivity to colistin. colistin proved to be effective and safe in managing CRE in children with cancer Mots-clés: Colistin, cancer, children, and Carbapenem-Resistant Enterobacteriaceae.

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.

Self-reported antibiotic stewardship and infection control measures from 57 intensive care units: An international ID-IRI survey.

We explored the self-reported antibiotic stewardship (AS), and infection prevention and control (IPC) activities in intensive care units (ICUs) of different income settings. A cross-sectional study was conducted using an online questionnaire to collect data about IPC and AS measures in participating ICUs. The study participants were Infectious Diseases-International Research Initiative (IDI-IR) members, committed as per their institutional agreement form. We analyzed responses from 57 ICUs in 24 countries (Lower-middle income (LMI), n = 13; Upper-middle income (UMI), n = 33; High-income (HI), n = 11). This represented (~5%) of centers represented in the ID-IRI. Surveillance programs were implemented in (76.9%-90.9%) of ICUs with fewer contact precaution measures in LMI ones (p = 0.02); (LMI:69.2%, UMI:97%, HI:100%). Participation in regional antimicrobial resistance programs was more significantly applied in HI (p = 0.02) (LMI:38.4%,UMI:81.8%,HI:72.2%). AS programs are implemented in 77.2% of institutions with AS champions in 66.7%. Infectious diseases physicians and microbiologists are members of many AS teams (59%&50%) respectively. Unqualified healthcare professionals(42.1%), and deficient incentives(28.1%) are the main barriers to implementing AS. We underscore the existing differences in IPC and AS programs' implementation, team composition, and faced barriers. Continuous collaboration and sharing best practices on APM is needed. The role of regional and international organizations should be encouraged. Global support for capacity building of healthcare practitioners is warranted.

Vaccine hesitancy and refusal among parents: An international ID-IRI survey.

INTRODUCTION: Although vaccines are the safest and most effective means to prevent and control infectious diseases, the increasing rate of vaccine hesitancy and refusal (VHR) has become a worldwide concern. We aimed to find opinions of parents on vaccinating their children and contribute to available literature in order to support the fight against vaccine refusal by investigating the reasons for VHR on a global scale. METHODOLOGY: In this international cross-sectional multicenter study conducted by the Infectious Diseases International Research Initiative (ID-IRI), a questionnaire consisting of 20 questions was used to determine parents' attitudes towards vaccination of their children. RESULTS: Four thousand and twenty-nine (4,029) parents were included in the study and 2,863 (78.1%) were females. The overall VHR rate of the parents was found to be 13.7%. Nineteen-point three percent (19.3%) of the parents did not fully comply with the vaccination programs. The VHR rate was higher in high-income (HI) countries. Our study has shown that parents with disabled children and immunocompromised children, with low education levels, and those who use social media networks as sources of information for childhood immunizations had higher VHR rates (p < 0.05 for all). CONCLUSIONS: Seemingly all factors leading to VHR are related to training of the community and the sources of training. Thus, it is necessary to develop strategies at a global level and provide reliable knowledge to combat VHR.

Characteristics, Treatment Complexity, and Outcome of Mixed-Phenotype Acute Leukemia in Children in a Low-Middle-Income Country.

Background: Mixed-phenotype acute leukemia (MPAL) in children is an uncommon subtype of acute leukemia that cannot be definitively assigned to a specific lineage. There is no consensus on the best approach to therapy. Management is more complex in low-middle-income countries (LMICs). Aim: To evaluate the clinicopathological characteristics and outcomes of patients with MPAL in a developing country. Patients and Methods: A retrospective descriptive study of 42 pediatric patients newly diagnosed with MPAL from July 2007 until December 2017. Results: The immunophenotyping was T/Myeloid in 24 patients (57.1%) and B/Myeloid in 16 (38.1%). Three subjects had MLL gene rearrangement, two had Philadelphia-positive chromosomes, and eight had FMS-like tyrosine kinase 3 (FLT3-ITD) internal tandem duplication (FLT3-ITD) with a ratio >0.4. Two subjects died before starting chemotherapy. Ten patients (25%) received acute lymphoblastic leukemia (ALL) induction, and all achieved complete remission (CR) with no induction deaths and no shift of therapy. Thirty patients (75%) started therapy with acute myeloid leukemia (AML) induction: five (16.6%) died during induction, 17 (56.7%) achieved CR, and 10 patients received maintenance ALL therapy after ending AML treatment. Four of the eight patients with induction failure were switched to ALL therapy. The 5-year event-free survival (EFS) and overall survival (OS) rates were 56.7% [standard error (SE): 8.1%] and 61% (SE: 8%), while the cumulative incidence of relapse was 21.7% (SE: 6.7%), with a median follow-up duration of 5.8 years. Patients treated with ALL-directed therapy had a 5-year EFS rate of 111 70% (SE: 14%) and OS rate of 78.8% (SE: 13%). Patients treated with ALL-directed therapy had a 5-year EFS rate of 70% (SE: 14.5%) and OS rate of 78.8% (SE: 13%). FLT3-ITD mutation showed a significantly lower 5-year EFS rate of 28.6% (SE: 17%) vs. 75% (SE: 9%) for the wild type, p = 0.032. Undernourished patients with a body mass index (BMI) z-score ≤-2 at presentation had a significantly lower 5-year EFS rate of 20% (SE: 17%) compared to 61.8% (SE: 8%) for patients with BMI z-score >-2, p = 0.015. Conclusion: This study supports ALL-directed therapy for pediatric MPAL in a setting of LMIC. Given the poor outcome of FLT3-ITD, the role of FLT3 inhibitor needs to be explored in this subset of cases.

Analyzing central-line associated bloodstream infection prevention bundles in 22 countries: The results of ID-IRI survey.

BACKGROUND: Because central line-associated bloodstream infections (CLABSIs) are a significant complication of central venous access, it is critical to prevent CLABSIs through the use of central line bundles. The purpose of this study was to take a snapshot of central venous access bundles in various countries. METHODS: The participants in intensive care units (ICUs) completed a questionnaire that included information about the health center, infection control procedures, and central line maintenance. The countries were divided into 2 groups: those with a low or low-middle income and those with an upper-middle or high income. RESULTS: Forty-three participants from 22 countries (46 hospitals, 85 ICUs) responded to the survey. Eight (17.4%) hospitals had no surveillance system for CLABSI. Approximately 7.1 % (n = 6) ICUs had no CLABSI bundle. Twenty ICUs (23.5%) had no dedicated checklist. The percentage of using ultrasonography during catheter insertion, transparent semi-permeable dressings, needleless connectors and single-use sterile pre-filled ready to use 0.9% NaCl were significantly higher in countries with higher and middle-higher income (P < .05). CONCLUSIONS: Our study demonstrated that there are significant differences in the central line bundles between low/low-middle income countries and upper-middle/high-income countries. Additional measures should be taken to address inequity in the management of vascular access in resource-limited countries.

Clinical characteristics and outcome of invasive fungal sinusitis in children with hematological malignancies.

Invasive fungal sinusitis (IFS) is a rare disease that requires careful attention and prompts management due to its high mortality among pediatric patients with hematological malignancies. This is a retrospective analysis of pediatric patients with hematological malignancies treated at Children's Cancer Hospital Egypt 57 357 (CCHE) through the period from 2008 till 2016 with proven IFS. Thirty-four patients were diagnosed with IFS. Five (15%) patients had an invasive rhino-cerebral fungal disease. Mucorales were isolated in 50% (n = 17) patients, Aspergillus in 38% (n = 13) patients, and mixed fungal in 12% (n = 4) patients. Sinuses were the only localized site in (45%). Extra-nasal spread was reported in 20 patients; Sino-pulmonary in 35% (n = 12), sino-cerebral in 15% (n = 5), and sino-orbital in 5% (n = 2) patients. Combined antifungal therapy with surgical debridement was done in 59% of patients with a better outcome when compared to those who received only medical antifungal treatment (P = .01). The overall mortality rate at week 12 was 35% (n = 12), and IFS attributable mortality was 20% (n = 7). IFS with cerebral extension carried the highest mortality rate for both 12-week all-cause (P = .04) and fungal-attributable (P = .01) mortality. Pediatric patients with hematologic malignancies are susceptible to invasive fungal sinusitis (IFS). Surgical debridement, combined with antifungal therapy, improves outcomes among those patients. IFS patients with cerebral extension had a higher risk of mortality. LAY SUMMARY: We studied the characteristics of invasive fungal sinusitis in children with hematological malignancies. Mucormycosis was the most common cause. Surgical debridement, combined with anti-fungal therapy, improves outcomes. Patients with rhino-cerebral fungal disease had a higher risk of mortality.

Profiles of multidrug-resistant organisms among patients with bacteremia in intensive care units: an international ID-IRI survey.

Evaluating trends in antibiotic resistance is a requisite. The study aimed to analyze the profile of multidrug-resistant organisms (MDROs) among hospitalized patients with bacteremia in intensive care units (ICUs) in a large geographical area. This is a 1-month cross-sectional survey for blood-borne pathogens in 57 ICUs from 24 countries with different income levels: lower-middle-income (LMI), upper-middle-income (UMI), and high-income (HI) countries. Multidrug-resistant (MDR), extensively drug-resistant (XDR), or pan-drug-resistant isolates were searched. Logistic regression analysis determined resistance predictors among MDROs. Community-acquired infections were comparable to hospital-acquired infections particularly in LMI (94/202; 46.5% vs 108/202; 53.5%). Although MDR (65.1%; 502/771) and XDR (4.9%; 38/771) were common, no pan-drug-resistant isolate was recovered. In total, 32.1% of MDR were Klebsiella pneumoniae, and 55.3% of XDR were Acinetobacter baumannii. The highest MDR and XDR rates were in UMI and LMI, respectively, with no XDR revealed from HI. Predictors of MDR acquisition were male gender (OR, 12.11; 95% CI, 3.025-15.585) and the hospital-acquired origin of bacteremia (OR, 2.643; 95%CI, 1.462-3.894), and XDR acquisition was due to bacteremia in UMI (OR, 3.344; 95%CI, 1.189-5.626) and admission to medical-surgical ICUs (OR, 1.481; 95% CI, 1.076-2.037). We confirm the urgent need to expand stewardship activities to community settings especially in LMI, with more paid attention to the drugs with a higher potential for resistance. Empowering microbiology laboratories and reports to direct prescribing decisions should be prioritized. Supporting stewardship in ICUs, the mixed medical-surgical ones in particular, is warranted.

Mucormycosis in the Middle East and North Africa: Analysis of the FungiScope® registry and cases from the literature.

BACKGROUND: Regional differences in the underlying causes, manifestations and treatment of mucormycosis have been noted in studies covering Europe, Asia and South America. OBJECTIVES: To review cases of mucormycosis across the Middle East and North Africa (MENA) region in order to identify epidemiological, treatment and outcome trends in this region. PATIENTS/METHODS: Cases of proven or probable invasive mucormycosis from the region were identified from the FungiScope® database and the medical literature. For each case, information on underlying condition, site of infection, pathogenic species, therapeutic intervention, type of antifungal therapy and outcome were analysed. RESULTS: We identified 310 cases of mucormycosis in the MENA region. The number of reported cases increased by decade from 23 before 1990 to 127 in the 2010s. In this region, the most common underlying conditions associated with mucormycosis were diabetes mellitus (49.7%) and conditions associated with immunosuppression (46.5%). The majority of patients received treatment with antifungals (93.5%), with a large proportion treated with both antifungals and surgery (70.6%). Overall mortality rates decreased from 47.8% before 1990 to 32.3% in the 2010s. CONCLUSIONS: The number of reported cases of mucormycosis in the MENA region has risen over the past few decades, in line with increases in the number of patients with underlying conditions associated with this infection. Although the majority of patients received treatment with antifungal therapies and/or surgery, the associated mortality rate remains high and there is a clear need for more effective prevention and treatment strategies in the MENA region.

Overview and outcome of mucormycosis among children with cancer: Report from the Children's Cancer Hospital Egypt.

Mucormycosis represents a real challenge in immunocompromised patients. This study aimed to describe the clinical characteristics, treatment outcome and infection-related mortality in our patients at the Children's Cancer Hospital 57357, Cairo, Egypt. This is a retrospective study during the period 2007-2017. Data analysis included demographic data, risk factors, diagnostic workup, treatment and outcome. During the study period, 45 patients developed proven mucormycosis according to EORTC/MSG criteria (2008). Ninety percentof cases were of haematological malignancies. Liposomal amphotericin B was the mainstay of treatment. Posaconazole was used as secondary prophylaxis in 35% of cases. Combination antifungal was used in three cases with progressive mucormycosis. Surgical intervention was achievable in 50% of cases. Therapy was successful in 35 patients (66%). Complications related to mucormycosis were seen in five cases with disfigurement and perforated hard palate. Chemotherapy delay with subsequent relapse of primary malignancy was reported in one case. Mucormycosis-related mortality was 33% (15 cases). Mucormycosis is a major cause of mortality among patients with haematological malignancies. Early diagnosis of Mucormycosis infection, with rapid initiation of appropriate antifungal therapy and surgical intervention, whenever feasible, is the backbone of mucormycosis treatment.

Outcome of Childhood Acute Megakaryoblastic Leukemia: Children's Cancer Hospital Egypt 57357 Experience.

INTRODUCTION: Acute megakaryoblastic leukemia is a rare subtype of pediatric acute myeloid leukemia (AML) with poor outcomes in patients with non-Down syndrome. The reported outcomes have been poor, and the prognostic factors have not been clearly determined. PATIENTS AND METHODS: To evaluate the prognostic significance of various cytogenetic abnormalities and minimal residual disease status determined by flow cytometry after induction I, we retrospectively analyzed the data of 80 patients with non-Down syndrome with a diagnosis of M7 AML treated at Children's Cancer Hospital Egypt (CCHE-57357) from July 2007 through December 2016. RESULTS: Of the 80 patients, 15 died during induction I and were excluded from the survival analysis. The overall survival, event-free survival, and cumulative incidence of relapse at 2 years was 52.6% ± 12.7%, 45.2% ± 12.3%, and 31.8% ± 11.5% respectively. Of the 90 patients, 61 had cytogenetic abnormalities, including trisomy 19,13q, trisomy 8, complex karyotype, t(1;22), KMT2A rearrangements, and trisomy 21. None of these had an effect on the outcomes. In addition, 34 patients had minimal residual disease < 0.1% after induction I, but the difference did not reach statistical significance. Patients with a delayed time to recovery (possibly due to myelofibrosis) had worse outcomes compared with those with early recovery (47% ± 19.2% vs. 63.2% ± 21.9%, respectively). CONCLUSION: Acute megakaryoblastic leukemia in patients with non-Down syndrome has a poor outcome with no clearly defined prognostic factors. However, future directions to risk stratify and tailor therapy should include assessment of the tumor biology according to the molecular pathways and study of the pathogenesis of myelofibrosis in this disease, which could affect the prognosis.

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.