الفهرس 
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Abstract
Chemotherapy-related febrile neutropenia (FN) is a frequent complication in children with cancer. Neutropenia is a major risk factor for infection in these patients. Among children with FN, the main symptom of infection upon initial presentation may be fever only.
The criteria for sepsis definition are still considered too sensitive and insufficiently specific despite several consensus conferences. This can result in erroneous or delayed diagnosis, particularly in children. Furthermore, the clinical signs or most typical laboratory findings of sepsis occur later, when multiple organ system failure has already occurred and mortality considerably increased. This diagnostic uncertainty (to treat as sepsis or noninfectious SIRS) may delay the initiation of lifesaving standard therapies. Over treatment of many cancer patients without a confirmed bacterial infection increase the risk of bacterial resistance development in these children. Diagnosis at early stage for BSI could not only provide a basis for accurate medications and precise therapies but also reduce the economic burdens of patients in clinical practice.
A biomarker can be very helpful in the appropriate management of these patients and may help to avoid unnecessary diagnostic tests, hospitalization, and unwarranted antimicrobial therapy.
This prospective study was carried out in the Pediatric Oncology Department, at South Egypt Cancer Institute (SECI) and the Medical research center, Faculty of Medicine Assuit University during the period from October 2016 to March 2017.
The study included 68 pediatric cancer patients in South Egypt Cancer Institute, with a total of 85 febrile episodes. The data collected included age, diagnosis, type of chemotherapy, absolute neutropenic count (ANC), grade of fever. We excluded patients under empirical antibiotic therapy.
Two blood culture bottles were drawn from each patient and transported to the Microbiology Laboratory. One set was diagnosed by the conventional methods of microbiology and the other by Vitek2 automated system. Antibiotic sensitivity tests were performed by both methods. Another blood sample was drawn on day 1 fever,centrifuged and the serum was stored at -80 until analyzed by ELISA to measure the levels of IL-6, IL-10 and procalcitonin in the blood.
It was found that the majority of patients had hematological malignancies (76.5%). Blood stream bacterial infection was detected in 29.4% of the blood samples collected during the febrile episodes. Most were Gram positive cocci (48%) with predominance of Coagulase negative staphylococci (32.1%). E-coli were the most common Gram negative organisms (21.4%).
In Gram positive bacteria, high percentages of resistance were found for oxacillin (100) %, for trimethoprim- sulfamethoxazole and (93.3%) and for erythromycin (86.7%). No resistance was detected against linezolid or vancomycin. The Gram negative bacteria were highly resistant to both trimethoprim-sulfamethoxazole and ampicillin (92.3% each) followed by ampicillin/sulbactam, and cefazolin (84.6% each). The least resistance was reported for amikacin (15.4%) and meropenem (23.1%). The percentage of multidrug resistance in gram positive bacteria is high (73.3%) and it is very high in Gram negative bacteria (92.3%).
Verification of Vitek2 automated system at SECI was performed and it was found that there was 100% agreement between the type of bacteria identified by Vitek2 system and the conventional methods regarding enterococci, non-heamolytic streptococci, klebsiella, E-coli and enterobacter aerogenes. There were discrepancies regarding the remaining isolate (CoNS,staph aureus ,pseudomonas,and acinetobacter)
Generally there was 92.3% agreement between the results of sensitivity tests of Vitek2 and Kirby Bauer disc diffusion method in Gram positive bacteria. The errors included: minor error 1%, major error 2%, and very major error 4.6%.
There was 95.7% agreement between the results of sensitivity tests of Vitek2 and Kirby Bauer disc diffusion method in Gram negative bacteria. The errors included: minor error 1.9%, major error 1.4%, and very major error 1%.
The levels of Interleukin-6, Interleukin-10 and procalcitonin were significantly higher in sepsis group compared to non-sepsis group. There was no significant relationship between biomarker level and type of infection or with mortality. The IL-6 at a cut off= 0.925 ng/L (AUC 0.975) had the best sensitivity 96% and considerable specificity 88.3%. Combining two biomarkers (PCT+IL-6, IL-10+PCT and IL-6+IL-10) increased both the sensitivity and specificity more than each biomarker alone at the same cut off point significantly. The best combination was PCT+IL-6 as it had the highest sensitivity (99.5) %.