Thesis (Ph.D)-Cairo University, 2025.

Bibliography: pages 85-102.

Background: The rapid worldwide spread of carbapenem-resistant Enterobacteriaceae (CRE)
constitutes a major challenge. CRE carrying additional resistance genes to multiple antibiotic
classes has created a generation of organisms nearly resistant to all available therapies. CRE
infections are associated with significant morbidity and mortality worldwide. This study aims
to define the clinical burden of CRE bloodstream infections (BSI), investigate predictors of
poor outcomes and risk factors for acquiring CRE BSI, and describe their phenotypic and
genotypic characteristics.
Methods: This prospective study included Children under 18 years of age with positive blood
culture for an Enterobacteriaceae (carbapenem-resistant phenotype [CRE] or carbapenem-
VHQVLWLYHSKHQRW\SH>&6(@DWDFKLOGUHQ¶VFDQFHUKRVSLWDOLQ(J\SW±2021) with adopting
antimicrobial stewardship program goals and introduction of PCR-based method (Cepheid
XpertCarba-R assay) which is developed for detecting carbapenemase genes with the
availability of results within one hour which can allow for rapid time to start active treatment
in less than 48h.
Results: The study focused on pediatric patients with positive blood cultures for
Enterobacteriaceae, specifically those with either carbapenem-resistant (CRE) or carbapenem-
sensitive (CSE) phenotypes. The participants were categorized into three groups: the first group
included 186 patients with CRE-positive blood cultures, the second group comprised 188
patients with CSE-positive blood cultures, and the final group served as a control with 383
participants. Among the CRE patients, 83% had hematological malignancies, while 17% had
solid tumors, with acute myeloid leukemia being the most prevalent hematological malignancy.
The primary risk factors for acquiring carbapenem-resistant Enterobacteriaceae (CRE), as
opposed to carbapenem-sensitive Enterobacteriaceae (CSE), include prolonged and severe
neutropenia (absolute neutrophil count (ANC) below 100), prior exposure to beta-lactam/beta-
lactamase inhibitors, recent hospitalizations, invasive procedures within the last 30 days,
admissions to intensive care units, and a history of colonization with CRE. Escherichia coli
was the most frequently isolated pathogen, accounting for 65% of cases, followed by Klebsiella
pneumoniae at 31%. The documented sites of infection included pneumonia (37%), typhlitis
(17%), skin and soft tissue infections (48%), and urinary tract infections (11%). Among the
CRE patients, 57 exhibited aminoglycoside resistance (30.6%), while quinolone resistance was
identified in 147 patients (79.0%). Additionally, colistin resistance was observed in 9 CRE
patients (4.8%). The Genotypic profile for CRE in our study reported that class B (71%) with
NDM reported in 126/186 (67%) and VIM 8/186 (4%) was the most common carbanamase
followed by Oxa-48 in 110/186 (59%) of patients while KPC enzyme reported only in
7/186(3.7%). Time to start active antibiotics were initiated within 48 hours for 89% of the
patients, with a clinical cure observed in 67% of cases. Microbiological clearance occurred in
less than 7 days for 62 % of patients. Sepsis related to CRE necessitated ICU admission for
(26%). The 30-day mortality rate was reported at 31 out of 186 patients (16%). In a multivariate
analysis of mortality predictors among patients with carbapenem-resistant Enterobacteriaceae
(CRE), several factors were identified to elevate the risk of death significantly. These included
a central venous catheter infection, extended hospital stays following infection, prolonged
neutropenia after bacteremia, isolation of Klebsiella pneumonia as the causative pathogen, and
the presence of the KPC and NDM genes as carbapenemase producers.
Conclusion: CRE-BSI is a major threat among pediatric cancer patients in limited-resource
countries and is considered a barrier against better outcomes. Antimicrobial stewardship
through routine screening for colonization detection and Rapid diagnosis by using gene expert
with rapid time to start adequate active antibiotics treatment is associated with improvement of
outcome and decreasing mortality.

الانتشار السريع فى جميع أنحاء العالم للبكتريا المعوية المقاومة للكاربابنيم يشكل تحديا كبيرا . تحمل هذه البكتريا جينات مقاومة اضافية لفئات المضادات الحيوية المتعددة تسببت فى وجود أجيال من الكائنات الحية مقاومة تقريبا لكافة المضادات الحيوية المتاحة. و من المعروف ان الاصابة بهذه البكتريا مرتبطة بأمراض و نسبة وفيات عالية . الهدف من هذه الدراسة هو التحقيق من عوامل الخطر المسببة للاصابة بالبكتريا المعوية المقاومة للكاربابنيم و تحديد تنبؤات الوفيات فى الاطفال نتيجة الاصابة بالبكتريا المعوية المقاومة للكاربابنيم و كذلك تحديد الانماط الجينية المهيمنة للبكتريا المعوية المقاومة للكاربابنيم. للاجابة على الاسئلة المذكورة أعلاه سوف نقوم بتنفيذ دراسة رصدية تحليلية فى مستشفى سرطان الاطفال 57357 على مدى عامين. تشمل الدراسة الاطفال اقل من 18سنة من كلا الجنسين و المصابين بالبكتريا المعوية المقاومة للكاربابنيم و تحديد عوامل الخطر و تحديد تنبؤات الوفيات عند األطفال المصابين بعدوى مجرى الدم و الناجمة عن الاصابة بالبكتريا المعوية المقاومة للكاربابنيم مما سيؤدى الى تدخلات من شأنها أن تقلل من ظهور مسببات المقاومة و سوف توجه الباحثين و العلماء الى وضع استراتيجيات وقائية فعالة والتى قد تحد من انتشار هذه المسببات

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