Tesis

Perbandingan Seftazidim dan Sefepim sebagai Terapi Empiris Demam Neutropenia pada Leukemia Akut Anak: Tinjauan penurunan Suhu dan Kenaikan Jumlah Neutrofil Absolut = Comparison of Seftazidime and Sefepime as Empirical Therapy in Febrile Neutropenic Children with Acute Leukemia: Review of Time to Fever Defervescence and Absolute Neutrophil Count.

Latarbelakang: Demam neutropenia merupakan komplikasi tersering pada terapi anak dengan keganasan. Pemberian antibiotik empiris dapat menurunkan angka morbiditas dan mortalitas. Sefepim, antibiotik sefalosporin generasi IV, dilaporkan lebih sensitif terhadap bakteri Gram negatif serta menunjukkan penurunan demam lebih cepat dan mempersingkat lama perawatan dibandingkan seftazidim sehingga dipikirkan sebagai antibiotik monoterapi lini pertama dengan pemberian menggunakan cara de-eskalasi sesuai pedoman antibiotic stewardship. Metode: Randomized controlled trial dengan single blinding dilakukan pada 72 pasien leukemia anak dengan demam neutropenia, 36 subyek mendapatkan Seftazidim dan 36 subyek lainnya mendapatkan Sefepim. Setelah 72 jam, dilakukan penilaian terhadap penurunan suhu dan kenaikan jumlah neutrofil absolut pada setiap sunyek. Hasil: Kelompok sefepim mengalami penurunan suhu lebih cepat dan kenaikan jumlah neutrofil absolut lebih tinggi dibandingkan kelompok seftazidim, dengan kenaikan jumlah neutrofil absolut (≥ 1000/mm3) saat 72 jam menunjukkan perbedaan bermakna antara kedua kelompok (p=0.003). Tidak terdapat perbedaan bermakna antara kedua kelompok terhadap jumlah penurunan suhu (p=0,101), median penurunan suhu (p=0,167), dan median jumlah neutrofil absolut (p=0,235). Sebagian besar biakan darah dan urin steril. Bakteri Gram negatif merupakan 72% dari biakan darah yang tumbuh. Hasil uji sensitivitas antibiotik biakan darah menunjukkan bahwa bakreri Gram negatif paling sensitif terhadap Sefepim, ditemukan pada 75% isolat dibandingkan dengan 38% isolat yang sensitif terhadap seftazidim. Kesimpulan: Sefepim memberikan penurunan suhu dan kenaikan jumlah neutrofil absolut lebih baik pada 72 jam dibandingkan seftazidim walaupun secara statistika tidak berbeda bermakna. Sefepim lebih sensitif untuk kuman Gram negatif dan positif.
Kata kunci: demam, neutropenia, suhu, jumlah neutrofil absolut, antibiotik.


Introduction: Febrile neutropenia is the most common complication in children undergoing cancer therapy. Administration of empirical antibiotic decreases morbidity and mortality. Cefepime, a fourth generation cephalosporin, has been reported to be more sensitive against Gram-negative bacteria and effective in reducing febril episodes and length of hospital stay compared to Ceftazidime. Thus being thought as first-line monotherapy agent administered using antimicrobial stewardship de-escalation strategy. Methods: A single blind randomized controlled trial was conducted in seventy-two acute leukemic patients with episodes of febrile neutropenia, 36 episodes were given Ceftazidime and another 36 episodes were given Cefepime. After 72 hours of antibiotic course, time to defervescence of fever and absolute nutrophil count in each episode were evaluated. Results: Cefepime group shows a better outcome in duration of fever defervescence and increase of absolute neutrophil count compared to ceftazidime group with absolute nutrophil count (≥ 1000/mm3) at 72 hours showed a significant difference between groups (p=0.003). There were no significant differences in frequency of fever defervescence (p=0,101), median time of defervescence (p=0,167) and median absolute neutrophil count at 72 hours (p=0,235) between groups. Most blood and urine cultures evaluated were sterile. Gram-negative bacteria were isolated in 72% of blood culture positive. Antibiotic susceptibility analysed from blood culture showed that Gramnegative bacteria were most susceptible to cefepime, found in 75% of isolates compared to 38% of isolates susceptible to ceftazidime. Conclusion: Cefepime group has a better outcome in duration of fever defervescence and increase of absolute neutrophil count at 72 hours compared to ceftazidime group although statistically there were no significant difference. Cefepime is more susceptible to Gram negative and positive bacteria.
Keywords: Fever, neutropenia, temperature, absolute neutrophil count, antibiotic.