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Abstrak :
Latar belakang. Berbagai studi sebelumnya menunjukkan bahwa insidens kolonisasi dan infeksi C.difficile semakin meningkat, terutama pada pasien rawat inap yang mendapat terapi antibiotika. Namun belum ada penelitian yang mendapatkan data kedua insidens tersebut di Indonesia, terutama di RSCM. Tujuan. Untuk mengetahui insidens kolonisasi dan infeksi C.difficile pasien rawat inap yang mendapat terapi antibiotika di RSCM. Metode. Dilakukan studi kohort prospektif berbasis surveilans pada 96 pasien rawat inap yang mendapat terapi antibiotika di RSCM pada periode penelitian. Dilakukan pemeriksaan feses dengan uji kromatografi cepat C.DIFF QUIK CHEK COMPLETETM pada awal dan akhir penelitian. Dilakukan follow-up selama 5-7 hari perawatan pada semua pasien. Insidens kolonisasi strain non-toksigenik adalah pasien yang memiliki hasil pemeriksaan fesesnya konversi GDH/Toksin -/- saat awal perawatan menjadi GDH/Toksin +/-. Insidens kolonisasi strain toksigenik adalah pasien yang memiliki konversi GDH/Toksin -/- saat awal perawatan menjadi GDH/Toksin +/+. Insidens infeksi adalah pasien yang memiliki konversi GDH/Toksin -/- saat awal perawatan menjadi GDH/Toksin +/+ yang disertai satu atau lebih gejala yang berhubungan dengan infeksi C.difficile. Hasil. Dari 96 subjek penelitian, 13 subjek mengalami kolonisasi non-toksigenik; 8 subjek mengalami kolonisasi toksigenik; 9 subjek mengalami infeksi. Terdapat 11 subjek yang mengalami gejala klinis, namun hasil pemeriksaan fesesnya tidak ditemukan toksin yang positif (2 subjek hanya mengalami kolinisasi non-toksigenik dan 9 subjek tidak mengalami kolonisasi atau infeksi) sehingga dianggap bukan merupakan infeksi C.difficile. Kesimpulan. Insidens kolonisasi C.difficile adalah 22%, dimana kolonisasi strain non-toksigenik adalah 14% (IK95% 13-16) dan strain toksi. ...... Background. Previous studies showed that there have been a significant increasing of the incidence of C.difficile colonization and infection, particularly among hospital inpatients prescribed antibiotics. However, there is no such data available in Indonesia, mainly at Cipto Mangunkusumo Hospital. Objective. To determine the incidence of Clostridium difficile colonization and infection among hospital inpatients prescribed antibiotics at Cipto Mangunkusumo Hospital. Methods. A surveillance-based prospective cohort study was conducted on 96 inpatients prescribed antibiotics at Cipto Mangunkusumo Hospital during the study period. All patient was followed-up for 5-7 days hospitalization. We obtained rectal swabs or stool samples on admission and day 5-7 of hospitalization and performed a rapid chromatography test C.DIFF QUIK CHEK COMPLETETM to determine colonization or infection. Incidence of non-toxigenic colonization was defined as a conversion of baseline result GDH/toxin -/- into GDH/toxin +/- as the second result. Incidence of toxigenic colonization was defined as as a conversion of baseline result GDH/toxin -/- into GDH/toxin +/+ as the second result. Incidence of infection was defined as a conversion of baseline result GDH/toxin -/- into GDH/toxin +/+ as the second result, accompanied by one or more C.difficile infection-associated clinical symptoms. Results. A total of 96 subjects were included in the study; 13, 8 and 9 had a non-toxigenic colonization, toxigenic colonization, and infection, respectively. 11 subjects with clinical symptoms could not be determined whether they had a C.difficile infection because of the “toxin-negative” findings from their stool examination (2 subjects had non-toxigenic colonization and 9 subjects had neither colonization nor infection). Conclusion. The incidence of C.difficile colonization was 22%, which 14% (95% CI 13-16) was the incidence of non-toxigenic colonization and 8% (95% CI 7-10) was the incidence of toxigenic colonization. The incidence of C.difficile infection was 9% (95% CI 8-11).

Abstrak :
Latar belakang : Peresepan antibiotik (AB) yang tidak tepat umum terjadi di seluruh dunia dan berkontribusi pada meningkatnya organisme yang resisten. Diperlukan sistem surveilans untuk memantau penggunaan AB dan resistensi untuk pengambilan keputusan yang tepat. Indonesia belum pernah menerapkan Point prevalence survey (PPS) dalam evaluasi AB dan resistensi. Tujuan: untuk mengetahui profil penggunaan antibiotik dan resistensi mikroorganisme di rumah sakit menggunakan metode PPS Metode : penelitian potong lintang. Dilakukan pengumpulan data demografi, penggunaan antibiotik dan kultur resistensi mikroorganisme menggunakan formulir PPS. Hasil : Pada hari penelitian dilakukan survei terhadap 451 pasien, ditemukan 244 (54,1%) pasien mendapatkan AB dengan diagnosis paling banyak adalah pneumonia (25%). Alasan penggunaan antibiotik adalah untuk tatalaksana infeksi dari komunitas sebanyak 50,8%, infeksi dari fasilitas kesehatan sebanyak 15,5%, penggunaan AB sebagai profilaksis sebanyak 30,7% dan 3% tidak ditemukan alasan indikasi penggunaan AB. Diresepkan 368 AB, di mana hanya 46 (12,5%) AB yang digunakan sebagai terapi definitif. Tiga AB yang paling sering digunakan adalah ceftriaxone (15,5%), levofloxacin 9,2% and ampicillin sulbactam 7,9%. Tanggal evaluasi penggunaan AB hanya tertulis pada 88 (22,3%) AB. Tidak tersedia pedoman tatalaksana lokal sebanyak 83 (22,6%) penggunaan AB dan hanya 214 (58,2%) AB yang diresepkan sesuai dengan pedoman tata laksana lokal. Kami melakukan evaluasi terhadap 244 pasien yang menggunakan AB dan hanya 91 (38%) pasien yang dilakukan pemeriksaan kultur dan tes resistensi. Didapatkan 222 sampel, dimana 81 (36,5%) adalah steril. Tiga mikroorganisme terbanyak adalah Klebsiella pneumoniae 47 (20,7%), Pseudomonas aeruginosa 22 (9,9%) dan Escherichia coli 20 (9%). Jumlah mikroorganisme extended-spectrum β-lactamase (ESBL) didapatkan sebesar 21,4%, resisten terhadap karbapenem 12,5% dan Multiple drug resistance (MDR) sebesar 17,7%. Kesimpulan : lebih dari setengah pasien yang disurvei menggunakan AB dan angka kepatuhan penggunaan antibiotik masih belum baik, evaluasi resistensi kuman terbatas karena jumlah sampel yang diperiksa kurang. Pelaksanaan PPS terbukti efektif dan efisien. ......Background: Inappropriate antibiotic prescribing appears to be common worldwide and is contributing to the selection of resistant organisms. Surveillance systems to monitor antimicrobial use and resistance are needed to improve decision making and assess the effect of interventions. Point prevalence surveys (PPSs) in Indonesian hospitals have not yet been applied. Aim : to evaluate the antibiotic prescribing trends and microorganism resistance using PPS methods Methods: A one day, cross-sectional PPS was performed whereas total of 10 days were taken. Data on demographics, antimicrobial use and culture/resistance test of all adult inpatients were collected using a data collection form. Results: On the day of the study 451 adults patients were surveyed, 244 (54.1%) were received 368 antibiotics and the most common diagnosis was pneumonia (25%). Reasons of using the antibiotics were to treat community acquired infection (CAI) 50.8%, hospital acquired infection (HAI) 15.5%, prophylaxis 30.7% and 3% was unknown. 368 antibiotics prescriptions were issued, of which 46 (12.5%) were used for definitive therapy. The top three antibiotics prescribed were ceftriaxone (15.5%), levofloxacin 9.2% and ampicillin sulbactam 7.9%. Review date of using antibiotics were performed in 88 (22.3%). Local guidelines was not available for 83 (22.6%) of prescribed antibiotics and among prescribed antibiotics with local guidelines available compliance was 214 (58.2%). We evaluate the culture test among those received antibiotics (244), 91 (38%) patients were performed culture and resistance test. From these 222 samples of culture, 81 (36.5%) was sterile. The most three growth microorganisms were Klebsiella pneumoniae 47 (20.7%), Pseudomonas aeruginosa 22 (9.9%) and Escherichia coli 20 (9%). The number of extendedspectrum β-lactamase (ESBL) recorded at 21.4%, Carbapenem Resistanculture ce was 12.5% and Multiple drug resistance was 17.7%. Conclusions: more than half-of-patients surveyed by PPS in an hospital in Indonesia were on antibiotics, has a limitation due to availability of result and sample. Conducting PPS in teaching hospital proved to be effective and efficient.

Abstrak :
ABSTRAK Latar Belakang: Kandidemia merupakan infeksi aliran darah dengan morbiditas dan mortalitas yang tinggi. Gambaran klinis kandidemia sulit dibedakan dengan pasien sepsis sehingga sering terlambat didiagnosis. Kultur darah sebagai baku emas diagnostik kandidemia memiliki beberapa keterbatasan, sedangkan prediktor yang ada saat ini sulit diaplikasikan dalam praktik klinis sehari-hari. Telah ada penelitian tentang faktor risiko kandidemia di luar negeri dan Indonesia, tetapi belum ada yang membahas khusus pada pasien sepsis dewasa non neutropenia. Tujuan: Mengetahui faktor risiko kandidemia pada pasien sepsis non neutropenia. Metode: Desain kasus kontrol dengan mengambil data rekam medik pasien sepsis sejak Januari 2011 sampai Juli 2015 di Rumah Sakit Cipto Mangunkusumo. Penilaian faktor risiko dilakukan dengan metode Chi-square dan dilanjutkan dengan analisis regresi logistik multivariat dengan mengikutsertakan variabel perancu. Hasil: Dari 51 kasus dan 153 kontrol didapatkan faktor risiko yang berhubungan dengan kejadian kandidemia adalah kateter urin [adjusted OR=5,239 (IK 95% 2,141 ? 12,819), p<0,001], nutrisi parenteral [adjusted OR=2,583 (IK 95% 1,297 ? 5,144), p=0,007], kortikosteroid [adjusted OR=2,183 (IK 95% 1,002 ? 4,755), p=0,049], dan antibiotik spektrum luas [adjusted OR=4,047 (IK 95% 1,178 ? 13,904), p=0,026]. Kesimpulan: Kateter urin, nutrisi parenteral, kortikosteroid, dan antibiotik spektrum luas merupakan faktor risiko penting karena dapat meningkatkan risiko kejadian kandidemia pada pasien sepsis non neutropenia.

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ABSTRACT Background: Candidemia is a bloodstream infection with high morbidity and mortality. Clinical manifestations of candidemia resemble with sepsis patients so that diagnosis was delayed. Blood culture as a diagnostic gold standard had some limitations, while the current predictors difficult to apply in daily clinical practice. There were studies about risk factors of candidemia in other countries and Indonesia, but no one had studied specifically in adult non-neutropenic sepsis patients. Objective: To identify the risk factors for candidemia in non-neutropenic sepsis patients. Method: A case-control study from medical records of septic patients was conducted during the period January 2011 ? July 2015 in Cipto Mangunkusumo Hospital. We analyzed risk factors using Chi-square method followed by multivariate logistic regression adjusted with confounding factors. Results: A total 51 cases and 153 controls were analyzed to identify the risk factors of candidemia. After adjustment, candidemia was associated with urinary catheter [adjusted OR=5,239 (95% CI 2,141 ? 12,819), p<0,001], parenteral nutrition [adjusted OR=2,583 (95% CI 1,297 ? 5,144), p=0,007], corticosteroids [adjusted OR=2,183 (95% CI 1,002 ? 4,755), p=0,049], and broad spectrum antibiotics [adjusted OR=4,047 (95% CI 1,178 ? 13,904), p=0,026]. Conclusion: Urinary catheter, parenteral nutrition, corticosteroids, and broad spectrum antibiotics are important risk factors that can increase the risk of candidemia in non-neutropenic sepsis patients.

Abstrak :
Pada sepsis terjadi inflamasi sistemik yang menyebabkan ketidakseimbangan mekanisme hemostasis, yaitu, peningkatan aktivasi koagulasi, penurunan antikoagulan alamiah, dan penurunan aktivitas fibrinolisis. Ketidakseimbangan ini bermanifestasi pada pembentukan trombus mikrovaskular yang menyebabkan perfusi jaringan menurun, terjadi disfungsi organ dan kematian. Tujuan penelitian ini mengetahui peranan kadar D-dimer, kadar FDP dan rasio FDP/D-dimer dalam memprediksi mortalitas 14 hari pada pasien sepsis. Penilaian skor Acute physiology and Chronic Health Evaluation II (APACHE II) digunakan untuk memprediksi morbiditas dan mortalitas. Desain penelitian potong lintang, penyajian data secara deskriptif. Subjek penelitian berjumlah 55 orang yang terdiri dari 32 laki-laki dan 23 perempuan dengan rerata usia 51,62 tahun. Pada subjek penelitian, dinilai korelasi kadar FDP, kadar D-dimer, dan rasio FDP/D-dimer dengan skor APACHE II. Pada hasil penelitian, didapatkan 20 pasien hidup dan 35 pasien meninggal. Median kadar FDP (12,9μg/mL) dan kadar D-dimer (7μg/mL) subjek meninggal lebih tinggi dibandingkan median kadar FDP (10,9μg/mL) dan kadar D-dimer (5,2 μg/mL) subjek hidup. Median rasio FDP/D-dimer subjek meninggal (1,9) lebih rendah dibandingkan subjek hidup (2,1). Koefisien korelasi Spearman antara kadar FDP, kadar D-dimer, dan rasio FDP/D-dimer dengan skor APACHE II berturut-turut 0,176, 0,187, dan -0,182. Ketiga korelasi itu secara statistik tidak bermakna (p ≥ 0,05). Pada penelitian ini disimpulkan bahwa kadar FDP, kadar D-dimer, dan rasio FDP/D-dimer tidak dapat digunakan sebagai prognosis keluaran sepsis pada mortalitas 14 hari. ......Systemic inflamation in sepsis could leads to an imbalance homeostatic mechanisms including elevated coagulation activity, decreasing level of natural anticoagulant, and decreased fibrinolysis activity. This could leads to formation of microvascular thrombus which eventually will cause tissue hypoperfusion, organ dysfunction and death. The aim of this research is to understand the role of d-dimer and fibrin degradation products (FDP) and FDP/d-dimer ratio in predicting 14-days mortality rate on sepsis patient. The morbidity and mortality rate on this research were based on APACHE II scoring system. This is a cross sectional research and all data are presented in a descriptive report. Participant of this research was 55 people (32 male and 23 female), average age was 51,62 years old. This research evaluate the correlation between FDP level, d-dimer level and FDP/d-dimer ratio with APACHE II scoring system. From all the participant we had 20 subject alive and 35 died during this research. The median level of FDP (12,9μg/mL) and d-dimer (7μg/mL) in those who die were higher than those who live (10,9μg/mL and 5,2 μg/mL). The median FDP/d-dimer ratio in those who die (1,9) was lower comparing to those who live (2,1). Spearman coefficient of correlation between FDP level, d-dimer level and FDP/d-dimer ratio with APACHE II scoring system were 0.176; 0.187; and – 0.182 repectively. This was not significant statistically (p ≥ 0,05). This research has come to a conclusion that FDP and d-dimer level, and FDP/d-dimer ratio cant be used as a prognostic outcome in sepsis on 14 days mortality.

Abstrak :
Latar Belakang: Sepsis merupakan masalah kesehatan global dan memiliki morbiditas dan mortalitas yang tinggi. Rasio neutrofil-limfosit merupakan pemeriksaan sederhana yang dapat dilakukan di fasilitas terbatas dan tidak memerlukan biaya besar, tetapi belum ada studi yang meneliti perannya dalam memprediksi mortalitas 28 hari pada pasien sepsis, menggunakan kriteria sepsis-3 yang lebih spesifik. Tujuan: Mengetahui peran rasio neutrofil-limfosit dalam memprediksi mortalitas 28 hari pada pasien sepsis. Metode: Penelitian ini menggunakan desain kohort retrospektif terhadap pasien sepsis yang dirawat di RSCM pada tahun 2017. Data diambil dari rekam medis pada bulan Maret-Mei 2018. Nilai rasio neutrofil-limfosit yang optimal didapatkan menggunakan kurva ROC. Subjek kemudian dibagi menjadi dua kelompok yang di bawah dan di atas titik potong. Kedua kelompok kemudian dianalisis menggunakan analisis kesintasan dengan program SPSS. Hasil: Dari 326 subjek, terdapat 12 subjek loss to follow-up. Rerata usia sampel 56,4 + 14,9 tahun, dengan fokus infeksi terbanyak di saluran napas (59,8%), dan penyakit komorbid terbanyak adalah keganasan padat (29,1%). Nilai titik potong rasio neutrofil-limfosit yang optimal adalah 13,3 (AUC 0,650, p < 0,05, sensitivitas 63%, spesifisitas 63%). Pada analisis bivariat menggunakan cox regression didapatkan kelompok dengan nilai rasio neutrofil-limfosit> 13,3 memiliki crude HR sebesar 1,84 (IK 95% 1,39-2,43) dibandingkan dengan kelompok yang nilai rasio neutrofil-limfosit < 13,3. Setelah menyingkirkan kemungkinan faktor perancu, didapatkan adjusted HR untuk kelompok dengan nilai rasio neutrofil-limfosit tinggi adalah 1,60 (IK 95% 1,21-2,12). Simpulan: Nilai rasio neutrofil-limfosit memiliki akurasi lemah dalam memprediksi mortalitas 28 hari pasien sepsis dengan nilai titik potong optimal 13,33. Kelompok dengan nilai rasio neutrofil-limfosit > 13,3 memiliki risiko mortalitas 28 hari yang lebih tinggi dibandingkan dengan kelompok nilai rasio neutrofil-limfosit < 13,3. ......Background: Sepsis is a global health problem with high morbidity and mortality. Neutrophil to lymphocyte ratio is a simple test which can be done in limited facility, but there is no study conducted to know its potential in predicting 28-day-mortality in septic patients, using the more specific sepsis-3 criteria. Objectives: To investigate neutrophil to lymphocyte ratio as a predictor of 28-day-mortality in septic patients. Methods: A retrospective cohort study was conducted using medical records in Cipto Mangunkusumo Hospital for septic patients who were admitted in 2017. Neutrophil to lymphocyte ratio cut off was determined using ROC curve, then subjects were divided into two groups according to its neutrophil to lymphocyte ratio value. The groups were analyzed using survival analysis with SPSS. Result: From 326 subjects, 12 subjects were loss to follow-up. Age mean was 56.4 + 14.9 years. Lung infection (59.8%) was the most frequent source of infections and solid tumor (29.1%) was the most frequent comorbidities. The optimal cut off value for neutrophil to lymphocyte ratio was 13.3 (AUC 0.650, p < 0.05, sensitivity 63%, specificity 63%). Bivariate analysis using cox regression showed that group with neutrophil to lymphocyte ratio > 13.3 had greater risk for 28-day-mortality than group with neutrophil to lymphocyte ratio < 13.3 with crude HR 1.84 (95% CI 1.39-2.43). After adjustment for possible confounding, adjusted HR for group with higher neutrophil to lymphocyte ratio was 1.60 (95% CI 1.21-2.12). Conclusion: Neutrophil to lymphocyte ratio had poor accuracy in predicting 28-day-mortality in septic patients with 13.3 as the optimal cut off value. Group with neutrophil to lymphocyte ratio > 13.3 had greater significant risk for mortality in 28 days than group with neutrophil to lymphocyte ratio < 13.3.

Abstrak :
ABSTRAK
Berbagai studi terkini menunjukkan hubungan antara vitamin D dan sepsis. Vitamin D berperan sebagai stimulator produksi peptida antimikroba dan mencegah inflamasi yang berlebihan. Insufisiensi dan defisiensi vitamin D berhubungan dengan risiko terjadinya sepsis. Saat ini belum terdapat data mengenai hubungan status vitamin D dengan pasien infeksi tanpa sepsis, sepsis, dan sepsis berat. Tujuan penelitian ini dilakukan untuk mendapatkan hubungan antara proporsi status vitamin D dengan pasien infeksi tanpa sepsis, sepsis, dan sepsis berat. Desain penelitian potong lintang, terdiri dari 60 pasien infeksi terbagi menjadi kelompok infeksi tanpa sepsis, sepsis, dan sepsis berat masing-masing 20 pasien. Diagnosis sepsis berdasarkan modifikasi SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference 2001. Status vitamin D ditetapkan menurut rekomendasi Holick. Pada ketiga kelompok tersebut dicatat data karakteristik subjek dan dilakukan pemeriksaan 25(OH)D. Status vitamin D pada subjek penelitian ini didapatkan sebanyak 5 (8,33%) orang insufisiensi dan 55 (91,67%) orang defisiensi vitamin D Proporsi insufisiensi pada kelompok infeksi tanpa sepsis adalah 5%, sepsis 10%, dan sepsis berat 10%. Proporsi defisiensi pada kelompok infeksi tanpa sepsis adalah 95%, sepsis 90%, dan sepsis berat 90%. Didapatkan perbedaan tidak bermakna proporsi insufisiensi dan defisiensi vitamin D pada kelompok infeksi tanpa sepsis, sepsis, dan sepsis berat. Kami menyimpulkan status vitamin D tidak berhubungan dengan beratnya sepsis. Proporsi insufisiensi dan defisiensi pada pasien infeksi tanpa sepsis, sepsis, dan sepsis berat masing-masing didapatkan 5% dan 95%; 10% dan 90%; 10% dan 90%.

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ABSTRACT
Recent studies have shown that there is a relationship between vitamin D and sepsis. Vitamin D has a a role as a potent stimulator of antimicrobial peptides and prevent an over reaction of the inflammatory response. Insufficiency and deficiency of vitamin D have been associated with sepsis event. Nevertheless, there is no data about the relationship between vitamin D status with infection without sepsis, sepsis, and severe sepsis patient. The aim of this study was to obtain the relationship between proportions of vitamin D with infection without sepsis, sepsis, and severe sepsis patient. This was a cross-sectional study, 60 patients with infection were divided into groups of infection without sepsis, sepsis, and severe sepsis, each consisted of 20 patients. Diagnosis of sepsis was based on modified SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference 2001. Vitamin D status was defined according to Holick recommendations. Baseline characteristics of subjects were recorded and 25(OH)D concentrations were measured in subjects of each groups. According to status of Vitamin D, 5 (8,33%) subjects were insufficiency and 55 (91,67%) were deficiency. The proportions of vitamin D insufficiency at infection without sepsis group were 5%, sepsis 10%, and severe sepsis 10%. The proportions of vitamin D deficiency at infection without sepsis group were 95%, sepsis 90%, and severe sepsis 90%. The proportions of insufficiency and deficiency at infection without sepsis, sepsis, and severe sepsis patient were not significantly different (p > 0.05). It is concluded that vitamin D status were not related to infection severity. The proportions of vitamin D insufficiency and deficiency at infection without sepsis, sepsis, and severe sepsis, i.e. 5% and 95%; 10% and 90%; 10% and 90%, respectively.

Abstrak :
Sepsis merupakan respons inflamasi sistemik pejamu terhadap infeksi. Respons inflamasi dimediasi oleh sitokin yang akan dilepaskan ke sirkulasi. Pelepasan sitokin akan menyebabkan terjadinya aktivasi koagulasi melalui peningkatan ekspresi tissue factor (TF) dan penurunan inhibitor alamiah, serta penurunan fibrinolisis. Tissue factor (TF) merupakan inisiator penting pada proses koagulasi, yang diekspresikan di sirkulasi darah oleh monosit aktif. Aktivasi TF selain menyebabkan aktivasi koagulasi juga dapat memodulasi inflamasi pada pasien sepsis berat. Heparin selain sebagai antikoagulan, berperan sebagai antiinflamasi. Berdasarkan fungsi heparin sebagai antiinflamasi dan peranan TF dalam inflamasi, ingin diteliti apakah pemberian heparin dapat menurunkan aktivitas TF yang diekspresikan monosit pada keadaan inflamasi. Penelitian ini bertujuan untuk mengetahui perbedaan aktivitas TF monosit pada orang sehat dan pasien sepsis berat dan perbedaan aktivitas TF monosit pada pasien sepsis berat dengan pemberian heparin in vitro dibandingkan dengan kelompok tanpa heparin. Penelitian ini merupakan penelitian eksperimental dengan menggunakan sampel 10 orang pasien sepsis berat dan 5 orang sehat. Darah sitrat dipisahkan sel mononuklear darah tepi (peripheral blood mononuclear cell/ PBMC) dengan teknik Ficoll-Paque, dan isolat monosit diperoleh dari PBMC menggunakan Monoclonal Antibody Cell Sorter (MACS) microbeads. Isolat monosit dipisahkan menjadi tiga kelompok, yaitu kelompok pertama langsung diperiksa aktivitas TF, kelompok kedua diinkubasi 6 jam dengan heparin 0.1 IU, dan kelompok ketiga diinkubasi 6 jam tanpa heparin. Isolat monosit kemudian dibuat lisat sel dan supernatan diukur aktivitas TF (Actichrome TF). Hasil penelitian menunjukkan terdapat perbedaan bermakna aktivitas TF monosit pada pasien sepsis berat dibandingkan orang sehat (p=0.002). Aktivitas TF monosit pada pasien sepsis berat yang mendapat heparin 0.1 IU berbeda bermakna setelah jam ke-6 dibandingkan tanpa heparin (p=0.003). ......Sepsis is a host systemic inflammatory response to infection. Inflammatory response is mediated by cytokines released into circulation. Cytokine leads to coagulation activation by elevating tissue factor (TF) expression, reducing natural inhibitors, and impeding fibrinolysis. TF is an important initiator in coagulation process, expressed in blood circulation by active monocytes. TF activates coagulation and modulates inflammation in severe septic patients. Heparin acts as anticoagulant and antiinflammatory agent. Based on heparin as antiinflammatory agent and role of TF in inflammation, heparin can decrease TF activity expressed on monocyte in inflammation. This study aims to find the difference between monocyte TF activities in healthy people and severe septic patients, and also between monocyte TF activities in severe septic patients receiving heparin in vitro and without heparin group. This study is a laboratory experiment using 10 samples from severe septic patients and 5 healthy samples. Peripheral blood mononuclear cells (PBMCs) are separated from citrate blood using Ficoll-Paque technique. Monocyte isolation is performed using Monoclonal Antibody Cell Sorter (MACS) microbeads. Monocyte isolate is divided into three groups, first group is measured for TF activity directly, second group is incubated 6 hours with heparin 0.1 IU, and third group is incubated without heparin. Cell lysate is processed from monocyte isolate and supernatant is measured for activity TF (Actichrome TF). The result shows a significant difference between monocyte TF activity in severe septic patients compared to healthy people (p = 0.002). Monocyte TF activity in severe septic patients with heparin 0.1 IU/mL in the 6th hour is also significantly different than without heparin group (p = 0.003).

Abstrak :
ABSTRAK Latar belakang Restricted antibiotics adalah golongan antibiotik spektrum luas yang termasuk dalam kategori lini 3 kebijakan dan pedoman penggunaan antibiotik PPRA. Restricted antibiotics digunakan secara global terkait dengan banyaknya kejadian resistensi bakteri. Penggunaan restricted antibiotic yang tidak tepat dapat menimbulkan masalah resistensi hingga superinfeksi yang lebih besar, peningkatan mortalitas dan biaya pengobatan. Restriksi pemberian antibiotik ini didasarkan pada risiko resistensi yang lebih besar yang dapat ditimbulkannya, toksisitas dan pertimbangan farmakoekonomik. Tujuan Untuk mengevaluasi penggunaan restricted antibiotic di IGD RSCM. Metode Penelitian dilakukan secara kohort prospektif, deskriptif dengan mengambil data pasien usia > 18 tahun yang mendapatkan restricted antibiotic di IGD RSCM selama periode 29 Juli-31 September 2015. Kuantitas penggunaan restricted antibiotic dievaluasi dengan metode ATC/DDD WHO (DDD/100 bed-days) dan kualitas penggunaan restricted antibiotic dievaluasi dengan metode Gyssen. Biaya penggunaan restricted antibiotic dihitung berdasarkan ketetapan biaya oleh RSCM. Penelitian ini juga melihat gambaran dan kesesuaian hasil kultur kuman dengan terapi yang diberikan serta menilai outcome klinik pasien yang mendapatkan restricted antibiotic di IGD RSCM. Hasil penelitian Hasil penelitian menunjukkan kuantitas penggunaan restricted antibiotic mencapai 78,3 DDD/100 bed-days dengan penggunaan terbanyak adalah meropenem dan sefepim. Sebanyak 86,7% restricted antibiotic diberikan secara empirik. Hasil pemeriksaan kultur kuman dan uji kepekaan kuman menunjukkan Acinetobacter baumannii dan Pseudomonas aeruginosa merupakan isolat kuman yang menunjukkan resistensi terhadap beberapa restricted antibiotic. Berdasarkan kriteria Gyssen, penggunaan restricted antibiotic termasuk kategori tepat sebesar 45,7%. Biaya terbesar penggunaan restricted antibiotic terdapat pada meropenem dan sefepim. Sebanyak 34 pasien meninggal selama perawatan dengan hasil kultur yang tidak sesuai dengan restricted antibiotic yang digunakan. Kesimpulan Kuantitas penggunaan dan prevalensi ketidaktepatan penggunaan restricted antibiotic secara umum cukup tinggi di IGD RSCM. Beberapa bakteri menunjukkan resistensi terhadap beberapa restricted antibiotic.

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ABSTRACT Background Restricted antibiotics have been used globally due to high prevalence of bacterial resistance. The inappropriate use of restricted antibiotic contributes significantly to the increase of antimicrobial resistance with many consequence such as risk of toxicity, increase of mortality and cost of treatment. Restriction of these antibiotics based on risk of resistance, toxicity and pharmacoeconomics considerations. Objective To evaluate the use of restricted antibiotic in adult patients in emergency unit of Cipto Mangunkusumo hospital. Methods We performed descriptive, cohort prospective study of adult patients those admitted to the emergency unit of Cipto Mangunkusumo hospital. We reviewed the medical record and electronic health record every day. Subject were patients aged more than 18 years old who received restricted antibiotic from July 29 to September 31, 2015 and all patients were followed up every day until they discharged from hospital. The use of restricted antibiotics were quantitavely evaluated using the ATC/DDD system (DDD/100 bed-days) and qualitatively analyzed using the Gyssen method. All the cost of restricted antibiotic use were calculated using standard price in Cipto Mangunkusumo hospital. This study also assess the clinical outcome and the pattern of sensitivity test of patient those received restricted antibiotic in emergency unit of Cipto Mangunkusumo hospital. Results The study results showed that the quantity of restricted antibiotic were 78,3 DDD/100 bed-days during July 29 to September 31, 2015 in the emergency unit of Cipto Mangunkusumo hospital. The most frequently used restricted antibiotic were meropenem dan sefepim. Restricted antibiotic used as empiric therapy was 86.7%. The culture and sensitivity test results showed that Acinetobacter baumannii and Pseudomonas aeruginosa were isolate that have resistance to several restricted antibiotics. Only 45.7% restricted antibiotic use were considered to be definitely appropriate based on Gyssen method. Meropenem and cefepim contribute to the higher cost during hospitalization and 34 patients used restricted antibiotic died during treatment have non concurrent of sensitivity to restricted antibiotic used. Conclusion The quantity of restricted antibiotic and prevalence of inappropriate restricted antibiotic use in this emergency department of Cipto Mangunkusumo hospital was generally high. Some bacterias have been resistance to several restricted antibiotic.

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ABSTRAK
Sepsis merupakan penyakit umum di perawatan intensif dan hampir 1/3 pasien yang dirawat di ICU adalah pasien sepsis. Banyak penelitian dilakukan untuk mencari penanda sepsis yang handal dan jumlah apoptosis limfosit mulai banyak diteliti sebagai penanda sepsis. Apoptosis limfosit terjadi mulai 24 jam pertama setelah onset sepsis. Saat ini belum terdapat data yang menunjukkan dapat digunakannya jumlah apoptosis limfosit sebagai penanda prognostik sepsis. Tujuan penelitian ini adalah mengetahui dapat tidaknya jumlah apoptosis limfosit digunakan sebagai penanda prognostik pada pasien sepsis berat

Desain penelitian adalah uji prognosis secara prospektif, terdiri dari 30 pasien sepsis berat dibagi berdasarkan mortalitas 14 hari, yaitu 15 pasien hidup dan 15 pasien meninggal. Diagnosis sepsis berdasarkan modifikasi definisi sepsis oleh International Sepsis Definitions Conference 2001. Jumlah apoptosis limfosit dihitung menggunakan metode flowcytometry dengan reagen antibodi monoklonal CD45 berlabel PerCP, Annexin V berlabel FITC, dan Propidium Iodide. Pada kedua kelompok tersebut dicatat data karakteristik subyek dan dilakukan penghitungan jumlah apoptosis limfosit

Rerata jumlah apoptosis limfosit pada kelompok pasien hidup adalah 0,992% dengan simpang baku 0,44% dan rerata jumlah apoptosis limfosit pada kelompok pasien meninggal adalah 1,5853% dengan simpang baku 0,57%. Jumlah apoptosis limfosit pada kedua kelompok berbeda bermakna dengan nilai p 0,004. Ditentukan nilai cut-off jumlah apoptosis limfosit 0,97%untuk menentukan prognosis pasien sepsis, dengan AUC 0,791 (IK 95% 0,631 ? 0,951), sensitivitas 86,7%, dan spesifisitas 60%. Kurva Kapplan Meier berdasarkan nilai cut-off 0,97% menunjukkan gambar yang memenuhi asumsi proporsional hazard dengan rasio hazard 0,182 (IK 95% 0,041 - 0,814), p = 0,026. Kami menyimpulkan jumlah apoptosis limfosit pasien sepsis berat dapat digunakan untuk memprediksi pasien yang meninggal dilihat dari mortalitas 14 hari, dengan nilai AUC sedang. Cut-off jumlah apoptosis limfosit 0,97% dapat digunakan sebagai cut-off dalam tatalaksana pasien sepsis berat

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ABSTRACT
Sepsis is a common illness in intensive care, almost 1/3 of patients admitted to the ICU were sepsis patients. There are plenty of researches to find a reliable marker of sepsis and the number of apoptotic lymphocytes began widely studied as a marker of sepsis. Apoptosis of lymphocytes occurred from the first 24 hours after the onset sepsis. There are currently no data on whether the number of apoptotic lymphocytes can be used as a prognostic marker of sepsis. The purpose of this study was to determine whether the number of apoptotic lymphocytes can be used as a prognostic marker in patients with severe sepsis

This was a prospective prognosis study, consisting of 30 severe sepsis patients grouped based on 14-day mortality, 15 patients are survivors and 15 patients are nonsurvivors. The diagnosis of sepsis is based on a modified definition of sepsis by the International Sepsis Definitions Conference 2001. The number of apoptotic lymphocytes was calculated using flowcytometry with PerCP-labeled anti-CD45 monoclonal antibody, FITC-labeled Annexin V, and Propidium Iodide. In both groups, characteristics of subjects were recorded and the number of apoptotic lymphocytes was calculated.

The mean of apoptotic lymphocytes in the survivor group is 0.992% with a standard deviation of 0.44%, and the mean of apoptotic lymphocytes in the nonsurvivor group is 1.5853% with a standard deviation of 0.57%. The difference between the two groups is significant with p = 0.004. This study yields an apoptotic lymphocytes cut-off value of 0.97% to determine prognosis of severe sepsis patients, with AUC of 0.791 (CI 95% from 0.631 to 0.951), 86.7% sensitivity and 60% specificity. Kapplan Meier curve based on the 0.97% cut-off demonstrates that hazard proportion is fulfilled with hazard ratio of 0.182 (95% CI 0.041 to 0.814) and p= 0.026. It is concluded that the number of apoptotic lymphocytes in severe sepsis patients can be used to predict nonsurvivors based on 14-day mortality, with moderate AUC. The apoptotic lymphocytes cut-off value of 0.97% can be used as a cut-off for severe sepsis patient management

Abstrak :
Sepsis dikenal secara luas sebagai sindrom klinis yang merupakan hasil dari respon sistemik yang hebat terhadap infeksi dan melibatkan gangguan pada berbagai organ penderitanya Sepsis merupakan penyebab kematian tersering pada pasien yang dirawat di unit perawatan intensif Proses inflamasi dengan respon maladaptif terhadap proses tersebut merupakan mekanisme terjadinya disfungsi organ multipel dan kematian pada sepsis. Heparin juga diketahui dapat memodulasi proses inflamasi, namun belum banyak penelitian yang menjelaskan dosis heparin sebagai antiinflamasi. Penelitian ini ingin mengkaji lebih jauh pengaruh dosis heparin terhadap aktivasi faktor transkripsi Nuclear Factor Kappa Beta (NFkB) melalui pengukuran terhadap kadar NFkB sub unit p65 dan produksi sitokin proinflamasi Tumor Necrosis Factor Alpha (TNF-?) untuk memberikan dasar ilmiah mengenai penggunaan dosis heparin sebagai antiinflamasi pada pasien dengan sepsis berat. Penelitian ini merupakan eksperimental laboratorik dengan menggunakan sampel dari 5 orang sukarelawan sehat dan 10 orang pasien sepsis berat. Sel mononuklear darah tepi (peripheral blood mononuclear cells/PBMC) dari darah vena diperoleh dengan teknik Ficoll-hypaque. Fraksi non-monosit dari PBMC menggunakan Monoclonal Antibody Cell Sorter (MACS) microbeads. Isolasi monosit diresuspensi pada medium Roswell Park Memorial Institute (RPMI) yang disuplementasi dengan 10% fetal bovine serum (FBS). Sel kemudian dipaparkan dengan heparin 0.1 IU/ml (1?g/ml), 1 IU/ml (10 ?g/ml), dan 10 IU/ml (100 ?g/ml), sedangkan kontrol tidak diberi perlakuan. Setelah diinkubasi pada 37°C dan 5% CO2 selama 6 jam dan 24 jam, pelet sel diukur NFkB sedangkan supernatan diukur TNF-? dengan metode ELISA. Hasil penelitian menunjukkan kadar NFkB sub unit 65 dan produksi TNF-? pada kultur monosit pasien sepsis berat yang mendapat heparin ditemukan secara signifikan lebih rendah daripada kontrol. Heparin dosis rendah 0.1 IU/ml (1?g/ml), secara signifikan menurunkan aktivasi NF?B dan produksi TNF-? lebih besar. Penelitian ini menunjukkan bahwa heparin menghambat aktivasi NFkB sehingga menurunkan produksi sitokin TNF-?. Heparin dengan dosis rendah menunjukkan pengaruh sebagai antiinflamasi lebih besar. Hasil yang diperoleh diharapkan memberikan pemahaman baru mengenai pengaruh dosis heparin sebagai anti-inflamasi pada pasien sepsis berat. ......Sepsis is a severe systemic response to infection, based on the Systemic Inflammatory Response Syndrome (SIRS) plus infection proven or clinically suspected infection, with evidence of organ failure due to hypo-perfusion. Anti-inflammatory therapy is one of the important therapeutic modality and applied potential as sepsis therapy. Inflammatory process with a maladaptive response to this process is the mechanism for the occurrence of multiple organ dysfunction and mortality in sepsis. Bacterial lipopolysaccharide binds to CD14 receptors and toll-like receptor (TLR) on the surface of monocytes and activates intracellular signal transduction involving beta-Kinase Inhibitor Kappa/IKKB that activates Nuclear Factor Kappa-Beta (NFkB) enter the nucleus and initiate transcription of RNA that encodes the production of cytokines TNF-?. Heparin has long been known as an anticoagulant, but also known to modulate the inflammatory process. This study want to examine further role of heparin as an anti-inflammatory to provide a scientific basis for the use of heparin in sepsis. Peripheral blood mononuclear cells (peripheral blood mononuclear cells/PBMC) of patients with severe sepsis obtained by Ficoll-Hypaque technique. Non-monocyte fraction of PBMC were removed using a Monoclonal Antibody Cell Sorter (MACS) microbeads. Isolation of monocytes resuspended in Roswell Park Memorial Institute medium (RPMI) supplemented with 10% fetal bovine serum (FBS). Cells then exposed to 0.1 IU heparin (1 ?g/ml), 1 IU (10 ug/ml), and 10 IU (100 ?g/ml), whereas controls did not. After incubation at 37°C and 5% CO2 for 6 hours and 24 hours, each sample is aspirated into micro centrifuge tube and rotated at a speed of 400 g for 5 min. Cell pellet was measured for NFkB and supernatant measured for TNF-?. Both were measured by ELISA. The results showed NFkB activation and TNF-? production in cultured monocytes severe sepsis patients who received heparin found to be significantly lower than controls. Low-dose heparin 0.1 IU (1?g/ml), significantly decreased the activation of NFkB and TNF-? production a lot more. This study demonstrates how heparin interfere an inflammatory response in severe sepsis patients monocytes through interrupt NFkB activation that decrease the production of cytokines TNF-?. The results are expected to provide new insights into the role of heparin as an anti-inflammatory in patients with severe sepsis.