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.

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.

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.

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.

Antibiotic sensitivity/resistance pattern of hospital acquired blood stream infection in children cancer patients: A retrospective study.

BACKGROUND: The literature shows a growing emphasis on understanding the local patterns of antimicrobial resistance (AMR). We aimed to evaluate the spectrum of local microorganisms that cause bloodstream infections (BSI) and their AMR patterns in an Egyptian institution treating children with cancer. METHODS: We conducted a single-centre, retrospective, study on children with confirmed primary, hospital-acquired, BSIs over one year. The microbiological examination of blood samples was done according to the Clinical and Laboratory Standards Institute. The antibiotic sensitivity test was done using VITEK® 2 system. RESULTS: We retrieved the data of 607 children with a median age of 5 (0.25-18) years old. The most encountered diagnosis was acute lymphoblastic leukaemia (40%). Most identified microorganisms were gram-negative bacilli, mainly Escherichia coli (27.8%), followed by Klebsiella pneumoniae (12.2%). Gram-negative bacilli showed high resistance to piperacillin/tazobactam, levofloxacin, and meropenem. The lowest resistance rates for Gram-negative bacilli isolates were noted for colistin and tigecycline. Similarly, the gram-positive cocci showed high resistance to ampicillin/sulbactam, cefoxitin, and clindamycin; and low resistance regarding vancomycin and linezolid. CONCLUSION: Resistance proportions (pattern) were similar to those reported in other countries with a higher distribution of E coli and a growing resistance to levofloxacin. Further investigation of the predisposing factors and the development of more effective strategies for the prevention of BSI should be a significant public health priority.

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.

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.

Incidence, risk factors, and outcome of blood stream infections during the first 100 days post-pediatric allogeneic and autologous hematopoietic stem cell transplantations.

Bloodstream infections (BSI) are a frequently observed complication after hematopoietic stem cell transplant (HSCT). Retrospective analysis of clinical and microbiological data during the first 100 days from 302 consecutive pediatric patients who underwent HSCT for a malignant disease at our institute between January 2013 and June 2017. A total of 164 patients underwent autologous and 138 allogeneic HSCT. The overall incidence of BSI was 37% with 92% of infectious episodes occurring during the pre-engraftment phase. Gram-positive bacteria (GPB) accounted for 54.6% of the isolated pathogens, gram-negative bacteria (GNB) for 43.9%, and fungi for 1.4%. Coagulase-negative staphylococci and Escherichia coli were the most commonly isolated GPB and GNB, respectively. Forty-five percent of GNB were extended-spectrum beta-lactamase producers and 21% were multidrug-resistant organisms. Fluoroquinolone resistance was 92% and 68%, among GPB and GNB, respectively. Risk factors for BSI in univariate analysis were allogeneic HSCT, delayed time to engraftment more than 12 days, previous BSI before HSCT, and alternative donor. In multivariate analysis, only HSCT type (allogeneic vs autologous P = .03) and previous BSI within 6 months before HSCT (P = .016) were significant. Overall survival at day 100 was 98% and did not differ significantly between patients with and without BSI (P = .76). BSI is common in children undergoing HSCT for malignant diseases. Allogeneic HSCT recipients and previous BSI within 6 months before HSCT are associated with increased risk of post-transplant BSI. With current supportive measures, BSI does not seem to confer an increased risk for 100-day mortality.

High Prevalence of VIM, KPC, and NDM Expression among Surgical Site Infection Pathogens in Patients Having Emergency Surgery.

BACKGROUND: The rate of surgical site infection (SSI) in patients who undergo emergency operations is higher than in other patients. Previous studies showed an increasing role of gram- negative pathogens (GNP) in SSI. We aimed to identify GNP causing SSIs after emergency surgery, to characterize the carbapenemase-resistance genes in carbapenem-resistant pathogens (CRPs), and to identify the risk factors for SSI caused by CRP. METHOD: We conducted a one-year prospective study from September 2014 in the Emergency Hospital of Cairo University Hospitals. Surveillance for SSIs was conducted according to the case definitions of the U.S. Centers for Disease Control and Prevention. Clinical specimens from patients suspected of having SSI were collected; pathogens were identified by Bruker matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectometry. Antimicrobial susceptibility was tested by the VITEK-2 and E-test. Carbapenem-resistant GNPs were characterized by multiplex polymerase chain reaction for IMP, VIM, SPM, OXA-48, NDM, KPC, BIC, AIM, GIM, SIM, and DIM. Clinical data for patients with SSI infected with CRP were compared with the non-infected patients for detection of risk factors. RESULTS: Surgical site infection affected 6.7% of patients who had emergency operations, and GNP represented 85% of these pathogens. Carbapenem-resistant pathogens caused 61% of the SSI, including all those caused by Acinetobacter baumannii, 70% of those caused by Pseudomonas aeruginosa, and 67% of those caused by Klebsiella pneumoniae. The PCR revealed that VIM, KPC, and NDM were the most common resistance genes. Risk factors for SSI were previous hospitalization, longer hospital stay, type of surgical incision, and abundant drainage; whereas previous hospitalization and infection by non-enteric environmental GNP were the risk factors for SSI caused by CRP. CONCLUSION: The rate of SSIs caused by CRP was high after emergency surgery. VIM, KPC, and NDM were the most commonly found genes. Prior hospitalization and infection by non-enteric GNP were risk factors, which can be mitigated by eradication of bacterial populations in environmental reservoirs and control of transmission.

The prevalence of chlamydia trachomatis among patients with acute conjunctivitis in Kasr Alainy ophthalmology clinic.

INTRODUCTION: Trachoma is a leading cause of avoidable blindness and endemic conjunctivitis in 57 countries. It infects approximately 84 million people globally, and continues to threaten over 10% of the world's population with the risk of blindness. METHODS: This is a cross sectional descriptive study assessing patients presenting with acute conjunctivitis. A full history was taken from patients followed by examination of both eyes. A conjunctival swab was taken and a sample of tears was collected and handled at the central laboratory unit at Kasr AlAiny hospital for culture and sensitivity of the swab and ELISA for tears searching for Immunoglobulin G and Immunoglobulin M of chlamydia trachomatis. RESULTS: The prevalence of bacterial conjunctivitis encounted for 45.7% and non-bacterial 54.3% of the studied group. The anti-chlamydial antibodies were positive in the tears of 31.1% of patients. While the other bacterial organisms responsible for 14.6%. CONCLUSION: The study concluded that trachoma accounts for one third of the cases of acute conjunctivitis while the other bacterial organisms responsible for about 14.6%. More than half of the cases have other causes as viral, allergic, mechanical or chemical induced conjunctivitis.