Tesis

Efektivitas Algoritme Demam Neutropenia Kiara pada Pasien Anak dengan Demam Neutropenia Risiko Tinggi: Tinjauan Terhadap Luaran Terapi = Effectiveness of the Kiara Algorithm in Pediatric Patients with High-Risk Neutropenic Fever: A Review of Therapy Outcomes.

Latar belakang: Demam neutropenia dan komplikasinya adalah salah satu penyebab utama tingginya morbiditas dan mortalitas pasien anak dengan kanker, termasuk di RSCM. Selain antibiotik empiris, tata laksana lain seperti stratifikasi risiko, eskalasi dan modifikasi antibiotik, inisiasi antijamur dan penggunaan GCSF belum disusun menjadi suatu algoritme khusus sehingga praktiknya masih bervariasi. Salah satu antibiotik empiris yang banyak direkomendasikan adalah piperasilin tazobaktam. Tata laksana yang seragam direkomendasikan untuk menjaga kualitas layanan dan memperbaiki luaran. Tujuan: Mengetahui efektivitas algoritme Kiara dibandingkan tanpa algoritme dalam tata laksana demam neutropenia risiko tinggi pada anak dengan luaran bebas demam, kenaikan absolute neutrophil count (ANC) >500/µL dalam 7 hari, dan pertumbuhan mikroorganisme serta resistensi antibiotik. Metode: Uji klinis terbuka, terandomisasi dengan kontrol pada anak 0-18 tahun dengan demam neutropenia risiko tinggi, sejak Januari-Mei 2024. Kelompok uji mendapat antibiotik empiris piperasilin-tazobaktam. Eskalasi, modifikasi antibiotik, antijamur, dan G-CSF diberikan sesuai algoritme. Kelompok kontrol mendapat seftazidim serta tata laksana tanpa menggunakan algoritme. Pasien dipantau selama 7 hari. Hasil: Terkumpul 58 subjek, terbanyak adalah pasien tumor padat dengan gejala infeksi saluran pencernaan. Komplikasi dialami oleh 8 subjek, setengahnya merupakan kasus pneumonia, dengan 75% merupakan pasien malnutrisi, 37,5% menggunakan akses sentral dan 87,5% memiliki hasil kultur yang positif. Hasil kultur positif terbanyak adalah pada urin (14,5%), feses (10,2%), dan darah (6%). Kuman gram negatif terbanyak adalah Klebsiella pneumoniae (37%), Acinetobacter sp (20%), dan Escherichia coli (14,2%), sedangkan kuman gram positif terbanyak adalah Staphylococcus aureus (40%), Enterococcus faecalis (30%), dan Staphylococcus epidermidis (20%). Resistensi seftazidim didapatkan lebih tinggi (50% vs 31,1%) dan eskalasi-modifikasi antibiotik lebih banyak di kelompok kontrol. Simpulan: Algoritme Kiara tidak lebih baik dalam hal lama demam dan capaian kondisi bebas demam dalam 7 hari pemantauan. Pemberian GCSF di kelompok uji yang lebih selektif terbukti dapat meningkatkan kadar ANC >500/µL, sama baik dengan kelompok kontrol yang menggunakan GCSF dua kali lebih banyak.
Kata Kunci: algoritme, demam neutropenia, piperasilin-tazobaktam, seftazidim


Background: Neutropenic fever and its complications are one of the main causes of high morbidity and mortality in pediatric cancer patients, including in Cipto Mangunkusumo Hospital. Apart from empiric antibiotics, other management such as risk stratification, antibiotic escalation and modification, antifungal initiation, and use of GCSF have not been compiled into a specific algorithm so practice still varies. Piperacillin-tazobactam is one of treatment choice in children with neutropenic fever. Local guidelines are recommended to maintain quality of care and improve outcomes. Objective: To determine the effectiveness of the Kiara algorithm versus without algorithm in the management of high-risk febrile neutropenia in children with outcomes of fever-free, increase in absolute neutrophil count (ANC) >500/µL in 7 days, as well as the growth of bacteria and antibiotic resistance. Methods: Open, randomized clinical trial with controls in children aged 0-18 years with high-risk febrile neutropenia, from January-May 2024. Experimental groups received piperacillin-tazobactam empirically. Escalation and modification of antibiotics, antifungals, and G-CSF were administered according to the algorithm. The control group received ceftazidime and treatment without an algorithm. Patients were followed up to 7 days of monitoring. Results: A total of 58 subjects were included, most of whom were solid tumor patients with symptoms of digestive tract infections. Complications were experienced by 8 subjects, half of them were pneumonia and 75% were malnourished, 37,5% with central venous catheter and 87,5% had positive culture. Highest bacteria growth is in urine (14,5%), feces (10,2%), and blood (6%). The majority of gram-negative bacteria are Klebsiella pneumoniae (37%), Acinetobacter sp (20%), and Escherichia coli (14,2%) while the gram-positive bacteria are Staphylococcus aureus (40%), Enterococcus faecalis (30%), and Staphylococcus epidermidis (20%). Antibiotic resistance was higher in the control group (50% vs 31,1%) as well as the antibiotic escalation and modification rate. Conclusion: The Kiara algorithm was not proven to be better in achieving fever-free conditions within 7 days of monitoring. The more selective administration of GCSF in the algorithm was proven to increase ANC levels to >500/µL, comparable to the control group with twice GCSF use.
Keywords: Algorithm, ceftazidime, febrile neutropenia, piperacillin-tazobactam