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"ABSTRAKPneumonia komunitas merupakan salah satu penyakit infeksi yang umum terjadi danmerupakan salah satu penyebab kematian dan kesakitan terbanyak. Penyakit ini memilikidampak terhadap sosioekonomi dimana tingginya biaya kesehatan terutama disebabkanoleh biaya rawat inap. Evaluasi farmakoekonomi dilaksanakan untuk menilai efektivitasbiaya antibiotik untuk mengetahui apakah pengobatan antibiotik memberikan outcometerapi yang baik dengan biaya yang minimal. Penelitian dilakukan terhadap kombinasiseftriakson-azitromisin dan levofloksasin tunggal sebagai antibiotik empiris untuk pasienpneumonia rawat inap. Analisis efektivitas biaya dilakukan dengan membandingkan totalbiaya medis langsung dan efektivitas yang dilihat dari lama rawat masing-masingkelompok pengobatan. Penelitian dilakukan di RSUP Persahabatan, Jakarta, dengandesain penelitian studi kohort retrospektif, dimana pengambilan data dilakukan secararetrospektif terhadap data sekunder, berupa rekam medis pasien dari tahun 2014-2016.Jumlah pasien yang dilibatkan dalam analisis 100 pasien, yaitu 64 pasien menggunakanantibiotik seftriakson iv dan azitromisin oral, dan 36 pasien menggunakan levofloksasiniv tunggal. Median biaya antibiotik berbeda signifikan antara kelompok seftriaksonazitromisindan kelompok levofloksasin, yaitu Rp.130.756,- dan Rp.286.952,-. Medianbiaya medis langsung kelompok seftriakson-azitromisin lebih tinggi dibandingkankelompok levofloksasin tunggal, yaitu Rp. 6.494.998,- dan Rp. 5.444.242,-. Keberhasilanterapi kelompok seftriakson-azitromisin yaitu 95,3 , sementara keberhasilan terapikelompok levofloksasin sebesar 97,2 namun tidak terdapat perbedaaan signifikan.Median lama rawat LOS dan lama rawat terkait antibiotik LOSAR kelompoklevofloksasin berturut-turut sebesar 6 hari dan 5 hari, lebih singkat dibandingkan LOSdan LOSAR kelompok seftriakson-azitromisin, yaitu 7 hari dan 6 hari. Nilai ACERkelompok levofloksasin sebesar Rp.56.011,-/persen efektivitas lebih rendahdibandingkan kelompok seftriakson-azitromisin sebesar Rp. 68.153,-/persen efektivitas.Berdasarkan hasil penelitian disimpulkan bahwa levofloksasin lebih cost-effectivedibanding kombinasi seftriakson-azitromisin.

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ABSTRACTCommunity Acquired Pneumonia CAP is one of the most common infectious diseasesand is one of the leading causes of death and morbidity. This disease has an impact onsocioeconomic where the high cost of health is mainly caused by the cost ofhospitalization. A pharmacoeconomic evaluation was conducted to assess the costeffectivenessof antibiotics to find out whether antibiotic treatment results in a goodtherapeutic outcome with a minimal cost. The study was conducted on a combination ofceftriaxone azithromycin and single levofloxacin as an empirical antibiotic for inpatientCAP patients. Cost effectiveness analysis is conducted by comparing the total directmedical costs and the effectiveness measured from length of stay of each treatmentgroup. The study was conducted in RSUP Persahabatan, Jakarta, with a cohortretrospective design study, where retrospective data retrieval was conducted onsecondary data, in the form of patient medical records from 2014 2016. The number ofpatients involved in the analysis of 100 patients, ie 64 patients using combination of ivceftriaxone and oral azithromycin, and 36 patients using single iv levofloxacin. Medianantibiotic costs differed significantly between the ceftriaxone azithromycin group andthe levofloxacin group, which were Rp.130,756, and Rp.286,952, . Median directmedical costs of the ceftriaxone azithromycin group were higher than the singlelevofloxacin group, which was Rp. 6,494,998, and Rp. 5,444,242, . Success rate ofgroup of ceftriaxone azithromycin group was 95.3 , while the success rate oflevofloxacin group was 97.2 but there was no significant difference. Median length ofstay LOS and length of stay antibiotic related LOSAR of levofloxacin group wererespectively 6 days and 5 days, shorter than LOS and LOSAR of ceftriaxoneazithromycingroup, which were 7 days and 6 days. The value of the ACER levofloxacingroup was Rp.56.011, percent effectiveness, lower than the ceftriaxone azithromycingroup of Rp. 68.153, percent effectiveness. Based on the results of the study, it isconcluded that levofloxacin is more cost effective than a combination of ceftriaxoneazithromycin."

"Pneumonia komunitas merupakan peradangan akut pada parenkim paru yang bersumber dari masyarakat dengan tingkat mortalitas, morbiditas, dan beban biaya yang tinggi terutama pada pasien rawat inap. Rata-rata biaya yang dibutuhkan bagi pasien pneumonia komunitas di Indonesia dalam satu periode rawat inap kurang-lebih mencapai Rp11.877.120. Pemilihan antibiotik empiris yang tepat penting dalam mengendalikan infeksi dan mengurangi beban total biaya pengobatan. Studi farmakoekonomi digunakan untuk mengetahui intervensi antibiotik yang paling unggul dari aspek efektivitas-biaya. Penelitian ini bertujuan untuk menganalisis efektivitas-biaya levofloksasin monoterapi dibandingkan dengan kombinasi seftriakson-azitromisin pada pasien pneumonia komunitas rawat inap non-ICU di RSUD Tangerang Selatan. Desain studi yang digunakan merupakan cross-sectional dengan metode pengumpulan data secara retrospektif terhadap data rekam medis, data penggunaan obat, dan data billing. Efektivitas terapi dinilai sebagai proporsi pasien yang mencapai kestabilan klinis setelah 72 jam penggunaan antibiotik. Data biaya yang digunakan berupa data biaya medis langsung berdasarkan perspektif rumah sakit. Sampel pada penelitian ini berjumlah 86 pasien yang merupakan 43 pasien dari masing-masing kelompok terapi. Hasil penelitian menunjukkan adanya perbedaan bermakna antara efektivitas kelompok levofloksasin dan kombinasi seftriakson-azitromisin (p < 0,05). Berdasarkan perhitungan REB (rasio efektivitas-biaya), kelompok levofloksasin memiliki nilai sebesar Rp78.028,22/% efektivitas dan kelompok kombinasi seftriakson-azitromisin Rp107.666,91/% efektivitas.

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Community-acquired pneumonia (CAP) is an acute inflammation of the lung parenchyma that originates from the community and carries a high mortality, morbidity, and cost burden, particularly in hospitalized patients. The average cost of treating CAP patients in Indonesia during a single hospitalization period is Rp11,877,120. Selecting the appropriate empiric antibiotic is crucial in controlling the infection and reducing the overall treatment costs. Pharmacoeconomic studies are conducted to determine the most effective and cost-efficient antibiotic intervention. This study aims to analyze the cost-effectiveness of levofloxacin monotherapy compared to the combination of ceftriaxone-azithromycin in non-ICU inpatient CAP cases at RSUD Tangerang Selatan. The study design was cross-sectional, utilizing a retrospective data collection method that involved medical records, drug usage data, and billing information. The therapy's effectiveness was assessed by the proportion of patients who achieved clinical stability after 72 hours of antibiotic use. The cost data utilized represents direct medical costs from the hospital's perspective. The study sample consisted of 86 patients, with 43 patients in each treatment group. The results indicated a significant difference in the effectiveness of the levofloxacin group compared to the ceftriaxone-azithromycin combination (p < 0.05). Calculation of the Average Cost-Effectiveness Ratio (ACER) revealed that the levofloxacin group had a value of Rp78,028.22 per % effectiveness, while the ceftriaxone-azithromycin combination group had a value of Rp107,666.91 per % effectiveness. "

"Rumah Sakit Karya Bhakti Pratiwi menggunakan seftriakson dan levofloksasin sebagai pilihan terapi utama berdasarkan pengalaman klinis pada pasien pneumonia komunitas dewasa rawat inap. Perbedaan biaya antara kedua obat ini menjadi alasan berlangsungnya penelitian ini. Tujuan penelitian ini adalah melakukan analisis efektivitas-biaya AEB dari seftriakson dan levofloksasin sehingga diperoleh pengobatan yang lebih efektif-biaya. Penelitian ini menggunakan desain cross-sectional dengan data sekunder berupa data peresepan dan data administrasi biaya pasien pneumonia rawat inap tahun 2017 yang berasal dari Sistem Informasi Rumah Sakit. Pengambilan sampel menggunakan teknik total sampling. Sampel yang dilibatkan pada penelitian ini sebanyak 33 pasien, yaitu 23 pasien menggunakan seftriakson dan 10 pasien menggunakan levofloksasin. Efektivitas pengobatan diukur berdasarkan lama hari rawat. Biaya diperoleh dari median total biaya pengbatan yang berasal dari biaya obat utama, biaya obat lain, biaya obat penyakit penyerta, biaya alat kesehatan, biaya laboratorium, biaya radiologi, biaya fisioterapi, biaya pelayanan, biaya administrasi, dan biaya rawat inap. Berdasarkan hasil penelitian, rata-rata lama hari rawat pasien yang menggunakan seftriakson adalah 3,43 hari dan levofloksasin 3,50 hari dan tidak terdapat perbedaan signifikan pada analisis Mann-Whitney p=0,440. Median total baya pengobatan seftriakson sebesar Rp2.183.356,54 lebih murah dibandingkan levofloksasin Rp2.819.895,56. Seftriakson secara umum memiliki nilai REB sebesar Rp636.547,10/hari lebih efektif-biaya dibandingkan levofloksasin dengan nilai REB: Rp805.684,40/hari.

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Karya Bhakti Pratiwi Hospital has been using ceftriaxone and levofloxacin as the empirical therapy option in community acquired pneumonia in adult patients. The difference in the cost between these two drugs encouraged researcher to perform Cost effectiveness analysis CEA to obtain more cost effective treatment. The study design was a cross sectional, data were collected retrospectively with total sampling method using data from the prescribing data and administrative financial data of inpatient pneumonia in 2017 from Hospital Information System. The number of samples were 33 patients, consisted of 23 patients using ceftriaxone and 10 patients using levofloxacin.

The effectiveness of treatment has measured by the length of stay. The total costs therapy were obtained from the median total cost from major drug costs, other drug costs, medical equipment costs, laboratory costs, radiology costs, physiotherapy costs, service fees cost, administrative costs, and hospitalization costs. Based on the results of the study, the efficacy of ceftriaxone with an average length of stay was 3.43 days and levofloxacin 3.50 days. The median total costs therapy of ceftriaxone was cheaper Rp2,183,356.54 than levofloxacin Rp2,819,895.56. The result shows that ceftriaxone generally REB Rp 636.547,10 day more cost effective than levofloxacin REB Rp805,684.40 day."

"ABSTRAKLatar belakang: Pneumonia komunitas merupakan penyakit yang sering terjadi dan berhubungan dengan angka kesakitan dan kematian yang tinggi. Perhimpunan Dokter Paru Indonesia (PDPI) mengeluarkan pedoman pemberian antibiotik penanganan pasien pneumonia komunitas di Indonesia untuk mengurangi angka kematian pasien pneumonia komunitas.Tujuan: untuk mengetahui angka kepatuhan penggunaan panduan antibiotik untuk pasien pneumonia komunitas yang di rawat inap berdasarkan panduan PDPI di RSUP Persahabatan serta pengaruhnya terhadap lama perawatan dan angka mortalitas pasien.Metode: Penelitian observasional kohort retrospektif di Rumah Sakit Umum Pusat Persahabatan. Data diambil dari data rekam medis pasien yang didiagnosis pneumonia komunitas, yang dirawat di ruang rawat inap Departemen Pulmonologi dan Ilmu Kedokteran Respirasi RSUP Persahabatan, periode Juli 2014 sampai dengan Juli 2016.Hasil: Sampel penelitian 107 subjek, dengan karateristik pasien laki-laki 70,1% dan perempuan 29,9%. Median usia 56 tahun dengan usia minimum 18 tahun dan usia maksimum 96 tahun. Angka kepatuhan dokter terhadap penggunaan antibiotik berdasarkan pedoman penatalaksanaan pneumonia PDPI pada pasien pneumonia komunitas yang dirawat inap di RSUP Persahabatan sebesar 70,1%. Angka mortalitas pasien pneumonia komunitas berhubungan secara bermakna dengan kesesuaian pemberian antibiotik dengan pedoman PDPI dan derajat risiko PSI dengan nilai OR berturut-turut 2,93 (95%IK1,23-6,94) dan OR 3.02 (95%IK 1.25-7.29). Kesimpulan: Angka kepatuhan penggunaan antibiotik angka kepatuhan penggunaan panduan antibiotik untuk pasien pneumonia komunitas berdasarkan panduan PDPI berhubungan dengan angka mortalitas pasien.

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ABSTRACT<>br>Background: Community acquired pneumonia (CAP) is a common disease and is associated with high morbidity and mortality. Indonesian Society of Respirology has been recommended empiric antibiotic guidelines for patients with community-acquired pneumonia in 2014. These guidelines are designed to reduce the mortality rate of CAP patients. Objective: to determine the compliance rate of antibiotic guidance for inpatient community pneumonia patients based on PDPI antibiotic guidelines in Persahabatan Hospital and its effect on the length of stay and mortality rate CAP patients. Method: This is a retrospective cohort observational study inPersahabatan Hospital. Data were collected from medical records of patients diagnosed with CAP, who were admitted to the Department of Pulmonology and Respiratory Medicine during July 2014 to July 2016. Results: The sample was 107 subjects. Proportion male and female were 70.1% and 29.9%. The median age was 56 years old with a minimum age was 18 years and a maximum age was 96 years. Doctors' compliance rates on PDPI's guidelines for the management CAP patients was 70.1%. The mortality rate of CAP patients was significantly associated with the national guidelines-concordant empiric antibiotic therapy and the class risk of PSI with OR 2.93 (95% IK1,23-6,94) and OR 3.02 (95% IK 1.25-7.29) reversely. "

"Latar belakang dan tujuan: Dari berbagai literatur, salah satu penyebab kegagalan respons klinis pasien pneumonia komunitas adalah akibat pemberian terapi antibiotik yang tidak tepat. Pemberian terapi antibiotik yang tidak tepat dapat meningkatkan risiko kematian dan resistensi antibiotik di kemudian hari. Tujuan penelitian ini adalah untuk mengevaluasi ketepatan penggunaan antibiotik dengan menggunakan metode Gyssens yang merupakan alat penilaian kualitatif yang dipakai oleh PPRA di Indonesia serta membandingkannya dengan luaran pasien pneumonia komunitas.Metode: Penelitian ini merupakan penelitian kohort retrospektif di Rumah Sakit Umum Pusat Persahabatan. Data diambil dari rekam medis pasien berusia di atas 18 tahun yang didiagnosis pneumonia komunitas dan dirawat inap selama periode Januari- Desember 2019. Penelitian ini menganalisis pemberian antibiotik empiris pada saat pasien pertama kali didiagnosis pneumonia komunitas.Hasil: Jumlah sampel pada penelitian ini adalah 108 subjek. Proporsi pasien yang diberikan antibiotik empiris tidak tepat berdasarkan metode Gyssens adalah 58,3% dan yang diberikan antibiotik empiris telah tepat adalah 41,7%. Pasien yang mendapatkan terapi antibiotik empiris tidak sesuai dengan pedoman PDPI memiliki risiko meninggal sebesar 2,875 kali lipat (IK 95% 1,440 – 5,739, p=0,004). Pasien yang diberikan antibiotik empiris dalam waktu setelah 8 jam didiagnosis pnemunia komunitas memiliki risiko meninggal sebesar 3,018 kali lipat (IK 95% 1,612 – 5,650, p=0,002). Dari analisis multivariat, faktor prediktor independen yang berhubungan dengan kejadian mortalitas pasien pneumonia komunitas dalam 30 hari adalah kejadian pneumonia berat dengan risiko sebesar 7,3 kali lipat (IK 95% 2,24-23,88, p=0,001), penyakit CVD dengan risiko sebesar 5,8 kali lipat (IK 95% 1,28-26,46, p=0,023), dan ketidaktepatan pemberian antibiotik empiris dengan risiko sebesar 4,2 kali lipat (IK 95% 1,02-17,74, p=0,048).Kesimpulan: Pada penelitian ini terdapat hubungan yang bermakna antara penggunaan antibiotik empiris tidak tepat berdasarkan metode Gyssens dengan luaran pasien yaitu kejadian mortalitas 30 hari (p=0,001).

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Background and Purpose: From many literatures, one of the causes of clinical response failure in community-acquired pneumonia patients is due to the inappropriate empirical antibiotics use. Improper administration of empirical antibiotics can increase the risk of death and antibiotic resistance later in life. The purpose of this study is to evaluate the appropriateness of the empirical antibiotics use using the Gyssens method which is a qualitative assessment tool used by the antibiotic stewardship program in Indonesia and to compare it with the outcome of community-acquired pneumonia patients.

Method: This study is a retrospective cohort study at the Persahabatan General Hospital. Data is taken from the medical records of patients over the age of 18 who are diagnosed with community-acquired pneumonia and hospitalized during the January- December 2019 period. This study analyzes the administration of empirical antibiotics when the patient is first diagnosed with community-acquired pneumonia.

Results: The number of samples in this study were 108 subjects. The proportion of patients who were given empirical antibiotics incorrectly based on the Gyssens method was 58.3% and those given empirical antibiotics were appropriate was 41.7%. Patients who received empirical antibiotic therapy not in accordance with PDPI guidelines had a 2.875-fold risk of death (95% CI 1.440 - 5.739, p = 0.004). Patients who were given empirical antibiotics after 8 hours of being diagnosed by the community-acquired pneumonia had a risk of death of 3,018-fold (95% CI 1.612 – 5.650, p = 0,002). From a multivariate analysis, independent predictors related to the mortality of community- acquired pneumonia patients within 30 days were the incidence of severe pneumonia with a risk of 7.3-fold (95% CI 2.24-23.88, p = 0.001), CVD with a risk of 5.8-fold (95% CI 1.28-26.46, p = 0.023), and inappropriate empirical antibiotics use with a risk of 4.2 fold (95% CI 1.02-17.74, p = 0.048).

Conclusion: In this study there was a significant relationship between the use of inappropriate empirical antibiotics use based on the Gyssens method and the outcome of community-acquired patients, which was the 30-days mortality (p = 0.001)."

"[ABSTRAK Latar belakang: Penggunaan antibiotik empirik pada tata laksana penyakit infeksi, misalnya pneumoniakomunitas, sebaiknya mempertimbangkan bukti kemanfaatan klinis dan hasilsensitivitas antibiotik pada suatu institusi pelayanan kesehatan. Penggunaan antibiotikyang tidak tepat dapat menyebabkan kegagalan terapi, resistensi kuman, komplikasidan kematian. Biaya yang tinggi juga merupakan keluaran langsung dari penggunaanantibiotik namun biasanya tidak dilaporkan. Oleh sebab itu, analisis terhadap biaya,keluaran klinis, dan pola sensitivitas kuman menjadi sangat penting untuk menentukanantibiotik empirik pada terapi pneumonia komunitas.Tujuan:Tujuan penelitian ini adalah menentukan antibiotik yang paling efektif dari aspek biayadan keluaran klinis pada tata laksana pneumonia komunitas.Metode:Penelitian ini dilakukan secara retrospektif pada pasien pneumonia komunitas di RSUDr. Soetomo Surabaya sejak 1 Januari sampai 31 Desember 2013. Analisis costeffectiveness digunakan untuk evaluasi farmakoekonomi berdasarkan perbaikan klinishari ke-5, mortalitas, dan biaya total.Hasil:Sebanyak 434 pasien dirawat di RSU Dr. Soetomo dan menerima antibiotik empirik.Sebanyak 200 pasien dikelompokkan menjadi 4 grup: seftriakson(35%), seftazidim(26%), levofloksasin (14,5%), dan kombinasi seftazidim dan levofloksasin (24,5%).Perbaikan klinis hari ke-5 tertinggi adalah kelompok yang diberi seftazidim sekitar67,3%. Seftriakson merupakan antibiotik empirik yang paling efektif dengan ACER505.585,3 untuk perbaikan klinis hari ke-5 namun hasil sensitivitas kumanmenunjukkan bahwa seftazidim masih lebih sensitif dari pada seftriakson (61,1% vs38,5%) dengan nilai ACER seftazidim sebesar 763.322. Kombinasi seftazidim danlevofloksasin digunakan untuk pasien dengan klinis yang buruk (PSI: 84,1+28,6) danberdampak pada tingginya biaya pengobatan (ACER 23685450.5).Kesimpulan:Seftazidim dapat dipertimbangkan sebagai antibiotik empirik yang efektif dan efisiendalam tata laksana pneumonia komunitas yang dirawat di rumah sakit. Kombinasi seftazidim dan levofloksasin juga dapat dipertimbangkan untuk pasien pneumonia komunitas yang berat.ABSTRACT Introduction:

Empirical antibiotic use in the management of infectious disease such as community

pneumonia should be considered based on evidence of clinical effectiveness and

institutional antibiotic sensitivity results. Inappropriate antibiotic leads to failure in

treatment, microbial resistance, complications and mortality. In addition, high cost is

one of the direct impact of this condition that is usually under-reported. Thus, analysis

of cost and clinical outcome, besides antibiotic sensitivity pattern, should be performed

to find effective empirical antibiotic in the treatment in community acquired

pneumonia (CAP).

Aim:

The objective of the study was to determine the most effective antibiotic in cost and

clinical outcome in CAP.

Methodology:

This study has been conducted retrospectively in patient with CAP in Dr. Soetomo

Hospital Surabaya from 1 January to 31 December 2013. Cost effectiveness analysis

was used to evaluate pharmacoeconomic outcomes based on clinical improvement in

day 5, mortality, and total cost.

Results:

There were 434 hospitalized patients with pneumonia that received empirical

antibiotic. Two hundred patients were selected based on inclusion and exclusion

criteria of this study. Subjects were categorized into 4 groups: ceftriaxone (35%),

ceftazidim (26%), levofloxacin (14.5%), and combination ceftazidim and levofloxacin

(24.5%). Clinical improvement in day 5 and clinical remission was assessed with

highest number in ceftazidim group, roughly 67.3% and 76,9% respectively.

Furthermore, ceftriaxone was the most effective one with ACER 505585.3 for day 5

outcome. However, the ceftazidim sensitivity was higher than ceftriaxone (61,1% vs

38,5%), while ceftazidime was in the one second position with ACER 763322. The

combination ceftazidim and levofloxacin particularly used in worse clinical symptom

(PSI: 84,1+28,6) and lead to the highest cost with ACER 23685450.5.

Conclusion:

Ceftazidim should be considered as effective and efficient empirical antibiotic in the

management of hospitalized CAP. However, combination ceftazidim and levofloxacin is also could be effective to improve clinical sign for particular patient even with severe CAP. , Introduction:

Empirical antibiotic use in the management of infectious disease such as community

pneumonia should be considered based on evidence of clinical effectiveness and

institutional antibiotic sensitivity results. Inappropriate antibiotic leads to failure in

treatment, microbial resistance, complications and mortality. In addition, high cost is

one of the direct impact of this condition that is usually under-reported. Thus, analysis

of cost and clinical outcome, besides antibiotic sensitivity pattern, should be performed

to find effective empirical antibiotic in the treatment in community acquired

pneumonia (CAP).

Aim:

The objective of the study was to determine the most effective antibiotic in cost and

clinical outcome in CAP.

Methodology:

This study has been conducted retrospectively in patient with CAP in Dr. Soetomo

Hospital Surabaya from 1 January to 31 December 2013. Cost effectiveness analysis

was used to evaluate pharmacoeconomic outcomes based on clinical improvement in

day 5, mortality, and total cost.

Results:

There were 434 hospitalized patients with pneumonia that received empirical

antibiotic. Two hundred patients were selected based on inclusion and exclusion

criteria of this study. Subjects were categorized into 4 groups: ceftriaxone (35%),

ceftazidim (26%), levofloxacin (14.5%), and combination ceftazidim and levofloxacin

(24.5%). Clinical improvement in day 5 and clinical remission was assessed with

highest number in ceftazidim group, roughly 67.3% and 76,9% respectively.

Furthermore, ceftriaxone was the most effective one with ACER 505585.3 for day 5

outcome. However, the ceftazidim sensitivity was higher than ceftriaxone (61,1% vs

38,5%), while ceftazidime was in the one second position with ACER 763322. The

combination ceftazidim and levofloxacin particularly used in worse clinical symptom

(PSI: 84,1+28,6) and lead to the highest cost with ACER 23685450.5.

Conclusion:

Ceftazidim should be considered as effective and efficient empirical antibiotic in the

management of hospitalized CAP. However, combination ceftazidim and levofloxacin is also could be effective to improve clinical sign for particular patient even with severe CAP. ]"