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Abstrak :
Terapi kortikosteroid pada pasien COVID-19 dimediasi oleh efek supresifnya terhadap regulasi respons inflamasi. Namun, hasilnya seringkali tidak dapat diprediksi. Penelitian ini bertujuan untuk mengeksplorasi prediktor respons kortikosteroid pada pasien COVID-19 derajat sedang-berat. Penelitian ini dibagi dalam 2 tahap, tahap pertama merupakan studi kohort retrospektif yang melibatkan 244 pasien dan tahap kedua merupakan studi cross-sectional terhadap 34 pasien yang spesimen biologisnya tersimpan di RS pada awal dan hari kelima terapi kortikosteroid. Penelitian dilakukan pada bulan Oktober 2021 hingga Oktober 2022 di RSUP dr. M.Djamil, Laboratorium Pusat Diagnostik dan Riset Penyakit Infeksi FK UNAND, dan Laboratorium Kesehatan Daerah Provinsi Jawa Barat. Peneliti menganalisis berbagai variabel klinis (usia, derajat ARDS, riwayat penggunaan steroid, adanya diabetes, hipertensi, gangguan fungsi ginjal) dan laboratorium (rasio neutrofil-limfosit, kadar feritin dan D-dimer) dengan respons terhadap terapi kortikosteroid pada tahap pertama. Pada tahap kedua dilakukan penelusuran peran reseptor glukokortikoid (GR) berupa tingkat ekspresi, variasi isoform, dan mutasi ekson dengan respons klinis terhadap kortikosteroid. Ekspresi GR, isoform, dan mutasi dianalisis dengan RNA-sekuensing leukosit. Selain itu, hubungan ekspresi GR dan ekspresi IκBα dan glucocorticoid-induced leucine zipper protein (GILZ) sebagai jalur steroid juga dievaluasi. Pasien diklasifikasikan menjadi kelompok responsif dan tidak responsif berdasarkan perbaikan status klinis dan kebutuhan oksigen. Pada analisis multivariat terlihat bahwa kadar feritin dapat memprediksi respons terhadap terapi kortikosteroid (OR 2,95 [95% CI 1,33−6,53]). Kelompok responsif memiliki ekspresi GR, IκBα dan GILZ lebih tinggi pada awal dan hari kelima pemberian kortikosteroid dibandingkan pasien tidak responsif. Varian atau mutasi isoform GR tidak berkorelasi dengan respons klinis. Berdasarkan temuan tersebut disarankan bahwa kadar feritin dapat memprediksi respons steroid pada pasien COVID-19, namun perlu ditelusuri prediktor independen lainnya. Ekspresi GR, IκBα dan GILZ kemungkinan berkaitan dengan respons terapi terhadap kortikosteroid pada pasien COVID-19. ......The effect of corticosteroid therapy in COVID-19 patients is mediated by its suppressive effect on the regulations of inflammatory response. However, its clinical outcome is often unpredictable. This study aimed to explore the predictors of corticosteroid response in Moderate-Severe COVID-19 patients. This research was conducted in 2 stages, the first stage was a retrospective cohort study involving 244 moderate-severe COVID-19 patients and the second stage was a cross-sectional study of 34 COVID-19 patients whose biological specimens were stored in the hospital at the baseline and fifth days of corticosteroid therapy. The research was conducted from October 2021 to October 2022 at Dr. M.Djamil General Hospital, Laboratory of Diagnostic and Research Center for Infectious Diseases Faculty of Medicine, Universitas Andalas, and Regional Health Laboratory of West Java Province. In the first stage, a multivariate analysis was conducted between various clinical (age, degree of ARDS, history of steroid use, presence of diabetes, hypertension, impaired renal function) and laboratory variables (neutrophil-lymphocyte ratio, ferritin and D-dimer levels) with response to corticosteroid therapy. In the second stage, we attempted to explore the role of the glucocorticoid receptor (GR), such as the expression, the variation of GR isoform, and the mutations of GR exon with clinical response to corticosteroids. GR expression, isoform, and mutation were determined by RNA sequencing from white blood cells. In addition, the relationship between GR expression and the expression of IκBα and glucocorticoid-induced leucine zipper protein (GILZ) as steroid pathways was also evaluated. Based on the improvement of clinical and oxygen status, patients were classified into responder and non-responder groups. Our findings indicate that ferritin levels can predict response to corticosteroid therapy (OR 2.95 [95% CI 1.336.53]). The responder group had higher GR, IκBα dan GILZ expression at baseline and after five days of corticosteroid treatment than non-responsder group. The GR isoform variant or mutation did not correlate with clinical response. Based on this finding, we suggest that ferritin levels in covid-19 patients could predict steroid response. This study also shows that the expression of GR, IκBα and GILZ may be related to the therapeutic response to corticosteroids in COVID-19 patients.

Abstrak :
Terapi kortikosteroid pada pasien COVID-19 dimediasi oleh efek supresifnya terhadap regulasi respons inflamasi. Namun, hasilnya seringkali tidak dapat diprediksi. Penelitian ini bertujuan untuk mengeksplorasi prediktor respons kortikosteroid pada pasien COVID-19 derajat sedang-berat. Penelitian ini dibagi dalam 2 tahap, tahap pertama merupakan studi kohort retrospektif yang melibatkan 244 pasien dan tahap kedua merupakan studi cross-sectional terhadap 34 pasien yang spesimen biologisnya tersimpan di RS pada awal dan hari kelima terapi kortikosteroid. Penelitian dilakukan pada bulan Oktober 2021 hingga Oktober 2022 di RSUP dr. M.Djamil, Laboratorium Pusat Diagnostik dan Riset Penyakit Infeksi FK UNAND, dan Laboratorium Kesehatan Daerah Provinsi Jawa Barat. Peneliti menganalisis berbagai variabel klinis (usia, derajat ARDS, riwayat penggunaan steroid, adanya diabetes, hipertensi, gangguan fungsi ginjal) dan laboratorium (rasio neutrofil-limfosit, kadar feritin dan D-dimer) dengan respons terhadap terapi kortikosteroid pada tahap pertama. Pada tahap kedua dilakukan penelusuran peran reseptor glukokortikoid (GR) berupa tingkat ekspresi, variasi isoform, dan mutasi ekson dengan respons klinis terhadap kortikosteroid. Ekspresi GR, isoform, dan mutasi dianalisis dengan RNA-sekuensing leukosit. Selain itu, hubungan ekspresi GR dan ekspresi I?B? dan glucocorticoid-induced leucine zipper protein (GILZ) sebagai jalur steroid juga dievaluasi. Pasien diklasifikasikan menjadi kelompok responsif dan tidak responsif berdasarkan perbaikan status klinis dan kebutuhan oksigen. Pada analisis multivariat terlihat bahwa kadar feritin dapat memprediksi respons terhadap terapi kortikosteroid (OR 2,95 [95% CI 1,33−6,53]). Kelompok responsif memiliki ekspresi GR, I?B? dan GILZ lebih tinggi pada awal dan hari kelima pemberian kortikosteroid dibandingkan pasien tidak responsif. Varian atau mutasi isoform GR tidak berkorelasi dengan respons klinis. Berdasarkan temuan tersebut disarankan bahwa kadar feritin dapat memprediksi respons steroid pada pasien COVID-19, namun perlu ditelusuri prediktor independen lainnya. Ekspresi GR, I?B? dan GILZ kemungkinan berkaitan dengan respons terapi terhadap kortikosteroid pada pasien COVID-19.Terapi kortikosteroid pada pasien COVID-19 dimediasi oleh efek supresifnya terhadap regulasi respons inflamasi. Namun, hasilnya seringkali tidak dapat diprediksi. Penelitian ini bertujuan untuk mengeksplorasi prediktor respons kortikosteroid pada pasien COVID-19 derajat sedang-berat. Penelitian ini dibagi dalam 2 tahap, tahap pertama merupakan studi kohort retrospektif yang melibatkan 244 pasien dan tahap kedua merupakan studi cross-sectional terhadap 34 pasien yang spesimen biologisnya tersimpan di RS pada awal dan hari kelima terapi kortikosteroid. Penelitian dilakukan pada bulan Oktober 2021 hingga Oktober 2022 di RSUP dr. M.Djamil, Laboratorium Pusat Diagnostik dan Riset Penyakit Infeksi FK UNAND, dan Laboratorium Kesehatan Daerah Provinsi Jawa Barat. Peneliti menganalisis berbagai variabel klinis (usia, derajat ARDS, riwayat penggunaan steroid, adanya diabetes, hipertensi, gangguan fungsi ginjal) dan laboratorium (rasio neutrofil-limfosit, kadar feritin dan D-dimer) dengan respons terhadap terapi kortikosteroid pada tahap pertama. Pada tahap kedua dilakukan penelusuran peran reseptor glukokortikoid (GR) berupa tingkat ekspresi, variasi isoform, dan mutasi ekson dengan respons klinis terhadap kortikosteroid. Ekspresi GR, isoform, dan mutasi dianalisis dengan RNA-sekuensing leukosit. Selain itu, hubungan ekspresi GR dan ekspresi I?B? dan glucocorticoid-induced leucine zipper protein (GILZ) sebagai jalur steroid juga dievaluasi. Pasien diklasifikasikan menjadi kelompok responsif dan tidak responsif berdasarkan perbaikan status klinis dan kebutuhan oksigen. Pada analisis multivariat terlihat bahwa kadar feritin dapat memprediksi respons terhadap terapi kortikosteroid (OR 2,95 [95% CI 1,33−6,53]). Kelompok responsif memiliki ekspresi GR, I?B? dan GILZ lebih tinggi pada awal dan hari kelima pemberian kortikosteroid dibandingkan pasien tidak responsif. Varian atau mutasi isoform GR tidak berkorelasi dengan respons klinis. Berdasarkan temuan tersebut disarankan bahwa kadar feritin dapat memprediksi respons steroid pada pasien COVID-19, namun perlu ditelusuri prediktor independen lainnya. Ekspresi GR, I?B? dan GILZ kemungkinan berkaitan dengan respons terapi terhadap kortikosteroid pada pasien COVID-19.Terapi kortikosteroid pada pasien COVID-19 dimediasi oleh efek supresifnya terhadap regulasi respons inflamasi. Namun, hasilnya seringkali tidak dapat diprediksi. Penelitian ini bertujuan untuk mengeksplorasi prediktor respons kortikosteroid pada pasien COVID-19 derajat sedang-berat. Penelitian ini dibagi dalam 2 tahap, tahap pertama merupakan studi kohort retrospektif yang melibatkan 244 pasien dan tahap kedua merupakan studi cross-sectional terhadap 34 pasien yang spesimen biologisnya tersimpan di RS pada awal dan hari kelima terapi kortikosteroid. Penelitian dilakukan pada bulan Oktober 2021 hingga Oktober 2022 di RSUP dr. M.Djamil, Laboratorium Pusat Diagnostik dan Riset Penyakit Infeksi FK UNAND, dan Laboratorium Kesehatan Daerah Provinsi Jawa Barat. Peneliti menganalisis berbagai variabel klinis (usia, derajat ARDS, riwayat penggunaan steroid, adanya diabetes, hipertensi, gangguan fungsi ginjal) dan laboratorium (rasio neutrofil-limfosit, kadar feritin dan D-dimer) dengan respons terhadap terapi kortikosteroid pada tahap pertama. Pada tahap kedua dilakukan penelusuran peran reseptor glukokortikoid (GR) berupa tingkat ekspresi, variasi isoform, dan mutasi ekson dengan respons klinis terhadap kortikosteroid. Ekspresi GR, isoform, dan mutasi dianalisis dengan RNA-sekuensing leukosit. Selain itu, hubungan ekspresi GR dan ekspresi I?B? dan glucocorticoid-induced leucine zipper protein (GILZ) sebagai jalur steroid juga dievaluasi. Pasien diklasifikasikan menjadi kelompok responsif dan tidak responsif berdasarkan perbaikan status klinis dan kebutuhan oksigen. Pada analisis multivariat terlihat bahwa kadar feritin dapat memprediksi respons terhadap terapi kortikosteroid (OR 2,95 [95% CI 1,33−6,53]). Kelompok responsif memiliki ekspresi GR, I?B? dan GILZ lebih tinggi pada awal dan hari kelima pemberian kortikosteroid dibandingkan pasien tidak responsif. Varian atau mutasi isoform GR tidak berkorelasi dengan respons klinis. Berdasarkan temuan tersebut disarankan bahwa kadar feritin dapat memprediksi respons steroid pada pasien COVID-19, namun perlu ditelusuri prediktor independen lainnya. Ekspresi GR, I?B? dan GILZ kemungkinan berkaitan dengan respons terapi terhadap kortikosteroid pada pasien COVID-19. ......The effect of corticosteroid therapy in COVID-19 patients is mediated by its suppressive effect on the regulations of inflammatory response. However, its clinical outcome is often unpredictable. This study aimed to explore the predictors of corticosteroid response in Moderate-Severe COVID-19 patients. This research was conducted in 2 stages, the first stage was a retrospective cohort study involving 244 moderate-severe COVID-19 patients and the second stage was a cross-sectional study of 34 COVID-19 patients whose biological specimens were stored in the hospital at the baseline and fifth days of corticosteroid therapy. The research was conducted from October 2021 to October 2022 at Dr. M.Djamil General Hospital, Laboratory of Diagnostic and Research Center for Infectious Diseases Faculty of Medicine, Universitas Andalas, and Regional Health Laboratory of West Java Province. In the first stage, a multivariate analysis was conducted between various clinical (age, degree of ARDS, history of steroid use, presence of diabetes, hypertension, impaired renal function) and laboratory variables (neutrophil-lymphocyte ratio, ferritin and D-dimer levels) with response to corticosteroid therapy. In the second stage, we attempted to explore the role of the glucocorticoid receptor (GR), such as the expression, the variation of GR isoform, and the mutations of GR exon with clinical response to corticosteroids. GR expression, isoform, and mutation were determined by RNA sequencing from white blood cells. In addition, the relationship between GR expression and the expression of I?B? and glucocorticoid-induced leucine zipper protein (GILZ) as steroid pathways was also evaluated. Based on the improvement of clinical and oxygen status, patients were classified into responder and non-responder groups. Our findings indicate that ferritin levels can predict response to corticosteroid therapy (OR 2.95 [95% CI 1.336.53]). The responder group had higher GR, I?B? dan GILZ expression at baseline and after five days of corticosteroid treatment than non-responsder group. The GR isoform variant or mutation did not correlate with clinical response. Based on this finding, we suggest that ferritin levels in covid-19 patients could predict steroid response. This study also shows that the expression of GR, I?B? and GILZ may be related to the therapeutic response to corticosteroids in COVID-19 patients.

Abstrak :
ABSTRAK
Latar belakang Kematian akibat sepsis dan syok septik pada pasien rawatan Intensive Care Unit (ICU) yaitu 20-30%. Pemberian antibiotik empirik yang tepat merupakan salah satu langkah awal yang sangat penting. Amikasin merupakan salah satu antibiotik terpilih untuk tata laksana sepsis di ICU RSUPN dr. Cipto Mangunkusumo (RSCM). Saat ini belum pernah dilakukan penelitian mengenai ketercapaian kadar terapi amikasin dengan menggunakan dosis standar amikasin pada pasien sepsis dewasa di ICU RSCM, sehingga studi ini menjadi penelitian pertama di Indonesia. Penelitian ini bertujuan untuk mengetahui ketercapaian kadar amikasin optimal pada pasien ICU RSCM. Metode Data dikumpulkan secara potong lintang melalui observasi terhadap hasil pemeriksaan kadar plasma amikasin, pengukuran minimum inhibitory concentration (MIC) dan perhitungan rasio Cmax/MIC pada pasien sepsis di ICU RSCM periode Mei-September tahun 2015. Hasil penelitian Proporsi pasien sepsis dengan kadar amikasin optimal ialah sebesar 57% (4/7). Kadar puncak amikasin yang dapat dicapai dengan dosis 1000 mg sekali sehari tanpa menghiraukan berat badan ialah median 86,4 (43,5-238) µg/mL. Pada penelitian ini ditemukan 87% pasien dengan kadar puncak amikasin di atas 64 µg/mL, meskipun amikasin 1000 mg tersebut lebih rendah dari dosis yang dianjurkan untuk sepsis (25 mg/kgBB). Sebagian besar (78,3 %) subyek pada kenyataannya menerima dosis 15-25 mg/kgBB, dengan pemberian 1000 mg amikasin tanpa memperhatikan berat badan. Bakteri yang banyak ditemukan dari hasil kultur pasien sepsis di ICU RSCM, yaitu K. pneumoniae, A. baumanii, P. aeruginosa dan E. coli. Rentang nilai MIC untuk patogen tersebut berturut-turut yaitu 0,75 - >256 µg/mL, 0,75 - >256 µg/mL, 1,5 - >256 µg/mL dan 0,75 - 16) µg/mL. Sebanyak 84% isolat K. pneumoniae masih sensitif terhadap amikasin, diikuti oleh 63% untuk A. baumanii, 47% P. aeruginosa dan 100% untuk E. coli. Kesimpulan Optimalitas amikasin terhadap bakteri Gram negatif penyebab sepsis bergantung kadar puncak dan MIC bakteri. Kadar puncak plasma amikasin yang dicapai dengan dosis 1000 mg sekali sehari sangat bervariasi. Pemberian amikasin dengan dosis per kgBB dapat dipertimbangkan. Kepekaan beberapa bakteri Gram negatif terhadap amikasin mulai menurun dengan rentang MIC yang cukup lebar. Pengukuran ketercapaian kadar optimal dalam terapi definitif dapat dilakukan untuk meningkatkan keberhasilan terapi.ABSTRACT
Background The mortality caused by sepsis and septic shock in the Intensive Care Unit (ICU) is 20-50%. The important first step to reduce this conditions is to give the right empirical antibiotics. Amikacin is one of the antibiotics of choice for the sepsis and septic shock in ICU of Cipto Mangunkusumo (CM) Hospital. Studies on the amikacin plasma level in adult patients being given amikacin in ICU RSCM has never been done. The objective of this study is to explore the plasma level of amikacin in septic patients in CM Hospital. Methods This was a cross sectional study. Data on plasma amikacin level, microbiological culture, measurement of minimum inhibitory concentration (MIC), and amikacin optimal level in septic patients admitted to ICU of RSCM during May-September 2015. Results The proportion of septic patients that achieve amikacin optimal level was 57% (4/7). Peak amikacin level that can be reached with 1 gram per day dose was 86,4 (43,5-238) g/mL. Although amikacin was given less than recommended dose for sepsis (25 mg/body weight), 87% patients was found to have peak amikacin level > 64 µg/mL. Most (78.3%) of the patients received amikacin with dose range 15-25 mg/kgBW, in which patients was given 1000 mg of amikacin regardless of the body weight. The organisms commonly identified from the microbiological culture septic in patients in ICU of RSCM were K. pneumoniae, A. baumanii, P. aeruginosa, and E. coli. The MIC for these pathogen were 0.75 - >256 µg/mL, 0.75 - >256 µg/mL, 1.5 - >256 µg/mL and 0.75 ? 16 µg/mL, respectively. Most (84%) of K. pneumoniae isolates was still sensitive to amikacin, while 63% A. baumanii isolate, 47% of P. aeruginosa, and 100% of E. coli were sensitive to amikacin. Conclusions Amikacin?s efficacy to eradicate Gram negative microorganism causing sepsis depend on peak level and MIC of the microorganism. By giving 1000 mg dose per day of amikacin, highly variable peak plasma concentration of the drug was observed. Therefore, amikacin dosing based on weight might be useful to reduce the wide variation. In this study, we found that sensitivity of some Gram negative pathogen are decreasing, with wide range of MIC. Evaluation of optimal level for definitive therapy might be useful to reach more successful treatment.;Background The mortality caused by sepsis and septic shock in the Intensive Care Unit (ICU) is 20-50%. The important first step to reduce this conditions is to give the right empirical antibiotics. Amikacin is one of the antibiotics of choice for the sepsis and septic shock in ICU of Cipto Mangunkusumo (CM) Hospital. Studies on the amikacin plasma level in adult patients being given amikacin in ICU RSCM has never been done. The objective of this study is to explore the plasma level of amikacin in septic patients in CM Hospital. Methods This was a cross sectional study. Data on plasma amikacin level, microbiological culture, measurement of minimum inhibitory concentration (MIC), and amikacin optimal level in septic patients admitted to ICU of RSCM during May-September 2015. Results The proportion of septic patients that achieve amikacin optimal level was 57% (4/7). Peak amikacin level that can be reached with 1 gram per day dose was 86,4 (43,5-238) g/mL. Although amikacin was given less than recommended dose for sepsis (25 mg/body weight), 87% patients was found to have peak amikacin level > 64 µg/mL. Most (78.3%) of the patients received amikacin with dose range 15-25 mg/kgBW, in which patients was given 1000 mg of amikacin regardless of the body weight. The organisms commonly identified from the microbiological culture septic in patients in ICU of RSCM were K. pneumoniae, A. baumanii, P. aeruginosa, and E. coli. The MIC for these pathogen were 0.75 - >256 µg/mL, 0.75 - >256 µg/mL, 1.5 - >256 µg/mL and 0.75 ? 16 µg/mL, respectively. Most (84%) of K. pneumoniae isolates was still sensitive to amikacin, while 63% A. baumanii isolate, 47% of P. aeruginosa, and 100% of E. coli were sensitive to amikacin. Conclusions Amikacin?s efficacy to eradicate Gram negative microorganism causing sepsis depend on peak level and MIC of the microorganism. By giving 1000 mg dose per day of amikacin, highly variable peak plasma concentration of the drug was observed. Therefore, amikacin dosing based on weight might be useful to reduce the wide variation. In this study, we found that sensitivity of some Gram negative pathogen are decreasing, with wide range of MIC. Evaluation of optimal level for definitive therapy might be useful to reach more successful treatment.;Background The mortality caused by sepsis and septic shock in the Intensive Care Unit (ICU) is 20-50%. The important first step to reduce this conditions is to give the right empirical antibiotics. Amikacin is one of the antibiotics of choice for the sepsis and septic shock in ICU of Cipto Mangunkusumo (CM) Hospital. Studies on the amikacin plasma level in adult patients being given amikacin in ICU RSCM has never been done. The objective of this study is to explore the plasma level of amikacin in septic patients in CM Hospital. Methods This was a cross sectional study. Data on plasma amikacin level, microbiological culture, measurement of minimum inhibitory concentration (MIC), and amikacin optimal level in septic patients admitted to ICU of RSCM during May-September 2015. Results The proportion of septic patients that achieve amikacin optimal level was 57% (4/7). Peak amikacin level that can be reached with 1 gram per day dose was 86,4 (43,5-238) g/mL. Although amikacin was given less than recommended dose for sepsis (25 mg/body weight), 87% patients was found to have peak amikacin level > 64 µg/mL. Most (78.3%) of the patients received amikacin with dose range 15-25 mg/kgBW, in which patients was given 1000 mg of amikacin regardless of the body weight. The organisms commonly identified from the microbiological culture septic in patients in ICU of RSCM were K. pneumoniae, A. baumanii, P. aeruginosa, and E. coli. The MIC for these pathogen were 0.75 - >256 µg/mL, 0.75 - >256 µg/mL, 1.5 - >256 µg/mL and 0.75 ? 16 µg/mL, respectively. Most (84%) of K. pneumoniae isolates was still sensitive to amikacin, while 63% A. baumanii isolate, 47% of P. aeruginosa, and 100% of E. coli were sensitive to amikacin. Conclusions Amikacin?s efficacy to eradicate Gram negative microorganism causing sepsis depend on peak level and MIC of the microorganism. By giving 1000 mg dose per day of amikacin, highly variable peak plasma concentration of the drug was observed. Therefore, amikacin dosing based on weight might be useful to reduce the wide variation. In this study, we found that sensitivity of some Gram negative pathogen are decreasing, with wide range of MIC. Evaluation of optimal level for definitive therapy might be useful to reach more successful treatment.

Abstrak :
Background: Amikacin is one of the antibiotics of choice for sepsis and septic shock. Pharmacokinetic of amikacin can be influenced by septic condition with subsequent effect on its pharmacodynamic. At Cipto Mangunkusumo Hospital (RSCM), Jakarta, adult patients in the ICU were given standard amikacin dose of 1 g/day, however the achievement of optimal plasma level had never been evaluated. This study aimed to evaluate whether the optimal plasma level of amikacin was achieved with the use of standard dose in septic conditions. Methods: all septic patients admitted to the intensive care unit of a national tertiary hospital receiving standard dose of 1g/day IV amikacin during May-September 2015 were included in this study. Information of minimum inhibitory concentration MIC was obtained from microbial culture. Cmax of amikacin was measured 30 minutes after administration and optimal level was calculated. Optimal amikacin level was considered achieved when Cmax/MIC ratio >8. Results: average Cmax achieved for all patients was 86.4 (43.5-238) µg/mL with 87% patients had Cmax of >64 µg/mL.MIC data were available for 7 of 23 patients. MICs for identified pathogens were 0.75 - >256 µg/mL (K. pneumonia), 0.75 - >256 µg/mL(A. baumanii), 1.5 - >256 µg/mL (P. aeruginosa)and 0.75 - 16 µg/mL(E. coli). Four out of seven patients achieved optimal amikacin level. Conclusion: despite high Cmax, only half of the patients achieved optimal amikacin level with highly variable Cmax. This study suggests that measurement of Cmax and MIC are important to optimize septic patients management.