INTRODUCTION
Cephalosporin
Agents
generation
cefazolin, cephalexin, cefadroxil,
1st generation
cephalothin, cephapirin,cephradine
cefuroxime, cefoxitin, cefotetan,
2nd generation cefprozil, loracarbef, cefmetazole,
cefonicid, cefamandole, cefaclor
ceftriaxone, cefotaxime,
ceftazidime, cefdinir, cefpodoxime,
3rd generation
cefixime, ceftibuten, cepoperazone,
ceftizoxime, cefditoren
4th generation cefepime
5th generation ceftaroline, ceftofibrole
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INTRODUCTION
2010: Ceftaroline
2011: Ceftaroline-R
Staphylococcus
CEFTAROLINE
Informasi mengenai perijinan
FDA EMA TGA
Approval year 2010 2012 2013
Brand name Teflaro® Zinforo®
600 mg atau 400 mg serbuk 600 mg serbuk steril untuk larutan
Bentuk sediaan
steril dalam 20 ml vial (IV) injeksi (IV)
acute bacterial skin and skin structure infections (ABSSSI) dan
Indikasi
community-acquired bacterial pneumonia (CABP)‡
Informasi dari European Medicine Agency (EMA)
600 mg setiap 12 jam melalui infus selama 1 jam baik untuk ABSSSI (5-
Dosis
14 hari) dan CABP (5-7 hari) untuk pasien dewasa ≥ 18 tahun
FDA: food and drug administration (USA) | EMA: european medicine agency | TGA: therapeutics goods
administration (AUS)
‡FDA, TGA: untuk dewasa ≥ 18 tahun
EMA: neonate, infants, children, adolescent, adult
CEFTAROLINE
Struktur dan aktivitas
MITT
• Seluruh pasien yang memenuhi protokol penelitian dan
terdiagnosis penyakit (CAP/SSTI) dengan/tanpa gejala klinis
yang memperoleh terapi antibiotik
cMITT
• Seluruh pasien pada MITT yang memiliki tanda dan gejala
klinis penyakit (CAP/SSTI) yang memperoleh terapi
antibiotik dengan/tanpa confounding factor dan test of
cure (TOC)
CE
• Pasien dalam cMITT tanpa confounding factor, dengan/
tanpa test mikrobiologi
Modified intention to treat (MITT)
Clinical modified intention to treat (cMITT) ME
Clinically evaluable (CE) • Pasien dalam CE dengan test mikrobiologi
Microbiologically evaluable (ME)
EVIDENCE - PNEUMONIA (1)
EVIDENCE - PNEUMONIA (1)
Primary outcome:
• Overall clinical cure – tanda dan gejala klinis pneumonia atau perbaikan kondisi pada saat
berhenti menggunakan antibiotik. Dinilai pada saat end of test (EOT) dan test of cure
(TOC)
Secondary outcome:
• Risiko kejadian adverse effect (ringan, sedang, dan berat), discontinuation karena AE,
relapse rate, mortalitas
EVIDENCE - PNEUMONIA (1)
OUTCOME 1:
overall clinical cure
rates
based on patient population
EVIDENCE - PNEUMONIA (1)
OUTCOME 1:
overall clinical cure
rates
based on patient group
EVIDENCE - PNEUMONIA (1)
OUTCOME 1:
overall clinical cure
rates
based on patient group
EVIDENCE - PNEUMONIA (1)
OUTCOME 1:
overall clinical cure
rates
based on patogens
EVIDENCE - PNEUMONIA (1)
OUTCOME 1:
overall clinical cure
rates
based on patogens
EVIDENCE - PNEUMONIA (1)
OUTCOME 1:
overall clinical cure
rates
based on patogens
OUTCOME 2:
Risk of adverse effect
OUTCOME 2:
Risk of adverse effect
EVIDENCE - PNEUMONIA (1)
OUTCOME 2:
Risk of adverse effect
14 studies
14 studies
CEFTAROLINE VS CEFTRIAXONE / VANCO/LINZ / OTHERS
Primary outcome:
• Overall clinical cure – tanda dan gejala klinis cSSSI atau perbaikan kondisi pada saat
berhenti menggunakan antibiotik. Dinilai pada saat test of cure (TOC) → 8-15 hari setelah
dosis terakhir
Secondary outcome:
• Tingkat kegagalan terapi dari segi klinis
• Risiko kejadian adverse effect → treatment-emergent AEs (TEAEs), AE serius, dan
penghentian terapi karena AE
EVIDENCE – SSTI (1)
OUTCOME 1:
overall clinical cure
rates
EVIDENCE – SSTI (1)
OUTCOME 2:
overall clinical
failure rates
Based on different pathogen
EVIDENCE – SSTI (1)
OUTCOME 2:
overall clinical
failure rates
Based on different pathogen
EVIDENCE – SSTI (1)
OUTCOME 3:
Risiko adverse
effects
EVIDENCE – PNEUMONIA/SSTI (1)
OUTCOME 2: mortalitas
EVIDENCE – PNEUMONIA/SSTI (1)
OUTCOME 3: adverse effect
EVIDENCE – PNEUMONIA/SSTI in PEDIATRIC (1)
EVIDENCE – PNEUMONIA/SSTI in PEDIATRIC (1)
EVIDENCE – PNEUMONIA/SSTI in PEDIATRIC (1)
EVIDENCE – PNEUMONIA/SSTI in PEDIATRIC (1)
OUTCOME: adverse effect
GUIDELINE CAP – ATS/IDSA 2019
GUIDELINE VAP – IDSA 2016
Ceftaroline?
GUIDELINE HAP – IDSA 2016
Ceftaroline?
GUIDELINE CAP - TAIWAN 2019
GUIDELINE CAP – NICE 2019
Ceftaroline?
GUIDELINE HAP – NICE 2019
Ceftaroline?
GUIDELINE SSTI – IDSA 2014
GUIDELINE ABSSi – IDSA 2019
GUIDELINE SUMMARY
IDSA
Indication
2014 2019
Ceftaroline for ABSSSi Recommended for MRSA SSTI
RESTRICTION – WHO AWaRe CLASSIFICATION
A Wa Re
access watch reserve
Amikacin Cloxacillin Azithromycin Gatifloxacin
Cefaclor Gemifloxacin
Amoxicillin Dicloxacillin Cefamandole Imipenem/Cil
Amoxicillin/Clav Doxycycline Cefepime Kanamycin
Cefixime Levofloxacin
Ampicillin Flucloxacillin Cefoperazone Lincomycin
Aztreonam Fosfomycin (IV)
Ampicillin/Sulbac Gentamicin Cefotaxime Meropenem Ceftaroline fosamil Linezolid
Benzathine benzylP Metronidazole (IV/O) Cefoxitin Moxifloxacin Ceftazidime/avibac Meropenem/Vabor
Cefpodoxime Neomycin
Cefadroxile Nitrofurantoin Ceftibuten Norfloxacin Ceftobiprole med Minocycline (IV)
Cefalexin Oxacillin Ceftriaxone Oxytetracycline Ceftolozane Polymixin B
Cefalotin SMX/TMP Cefuroxime Piperacillin Colistin Televacin
Ciprofloxacin Piperacillin/tazo
Cefazoline Tetracycline Clarithromycin Rifampicin Daptomycin Tigecycline
Cefradine Thiamphenicol Doripenem Spiramycin
Ertapenem Streptomycin
Chloramphenicol TMP Erythromycin Tobramycin
Clindamycin Fosfomycin (oral) Vancomycin (IV/Oral)
OFF LABEL USE OF CEFTAROLINE
OFF LABEL USE OF CEFTAROLINE
AVAILABILITY
INDONESIA: belum tersedia
Harga:
Merk Harga Total perkiraan biaya bila Total perkiraan biaya bila digunakan
digunakan untuk CAP untuk SSTi
Pneumonia pengobatan 5-7 hari 2 SSTi pengobatan 5-14 hari 2 x 600
£ 375.00 ~ Rp. 6.778.415 untuk x 600 mg mg
Zinforo® 10 vial @600 mg (BNF; 2018)
(Pfizer Ltd) 1 hari = Rp. 1.354.000,- 1 hari = Rp. 1.354.000,-
Maka 1 vial = ± Rp. 677.000,- Total biaya= ± Rp. 6.770.000 – Rp. Total biaya= ± Rp. 6.770.000 – Rp.
9.478.000 18.956.000
Pneumonia pengobatan 5-7 hari 2 SSTi pengobatan 5-14 hari 2 x 600
$2,015.24 ~ Rp. 28.318.354
x 600 mg mg
untuk 10 vial @400 mg atau 600
Teflaro®
mg (drug.com)
(Allergan plc) 1 hari = Rp. 5.662.000,- 1 hari = Rp. 1.354.000,-
Total biaya= ± Rp. 28.310.000 – Rp. Total biaya= ± Rp. 6.770.000 – Rp.
Maka 1 vial = ± Rp.2.831.000,-
39.634.000 18.956.000
The Scottish Medicines Consortium, has advised (Dec 2012) that ceftaroline fosamil (Zinforo ®) is accepted for RESTRICTED
use within NHS Scotland when meticillin– resistant S. aureus is suspected in complicated skin and soft-tissue infection and
vancomycin cannot be used. (BNF; 2018)
AVAILABILITY
Harga:
Zinforo (Ceftaroline) Viccilin Sx (Ampicillin/ Broadced (Ceftriaxone) Lancef (Cefotaxime)
Sulbactam)
1 gram/vial = Rp. 164.500 1 gram/vial = Rp. 126.000,-
1,5 gram x 10 vial = Rp. 82.000
1 vial 8.200
Dosis guideline: 1-2 Dosis guideline: 1-2 gram setiap 8
1 hari 2 vial = Rp.
gram/hari jam (3x sehari)
1.354.000,- Sehari 1,5-3 gram setiap 6 jam
4 vial 1,5 gram= Rp. 32.800
Sehari= Rp. 164.500 – Rp. 3x1 gram = Rp. 378.000
8 vial 1,5 gram= 65.600
329.000 3x2 gram = Rp. Rp. 756.000
The Scottish Medicines Consortium, has advised (Dec 2012) that ceftaroline fosamil (Zinforo ®) is accepted for RESTRICTED
use within NHS Scotland when meticillin– resistant S. aureus is suspected in complicated skin and soft-tissue infection and
vancomycin cannot be used. (BNF; 2018)
CONCLUSION
1. Berdasarkan beberapa penelitian Ceftaroline terbukti efektif dan aman bila digunakan
untuk mengatasi CAP dan SSTi. Beberapa panduan terapi, salah satunya IDSA
merekomendasikan penggunaan Ceftaroline untuk indikasi CAP dan SSTi. Hal tersebut
dapat disebabkan oleh tingkat kejadian infeksi akibat community acquired MRSA (Ca-
MRSA) relatif tinggi.
Chen, C. et al. (2019) ‘The efficacy and safety of ceftaroline in the treatment of acute bacterial infection in pediatric patients – a
systemic review and meta-analysis of randomized controlled trials’, Infection and Drug Resistance, 12, pp. 1303–1310.
Duplessis, C. and Crum-Cianflone, N. (2011) ‘Ceftaroline: a new Cephalosporins with Acitivity Against Methicilin-Resistant
Staphylococcus aureus (MRSA)’, Clin Med Rev Ther, 3.
Gallagher, J. and MacDougall, C. (2018) Antibiotics Simplified. 4th ed. Philadelphia: Jones & Bartlett Learning.
Golan, Y. (2019) ‘Current Treatment Options for Acute Skin and Skin- structure Infections’, Clinical Infectious Diseases, 68.
Hajj, M., Turgeon, R. and Wilby, K. (2017) ‘Ceftaroline fosamil for community-acquired pneumonia and skin and skin structure
infections : a systematic review’, International Journal of Clinical Pharmacy. Springer International Publishing.
Kalil, A. C. et al. (2016) ‘Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia : 2016 Clinical
Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society’, Clinical Infectious Diseases,
63(5), pp. 61–111.
Lan, S., Chang, S., Lai, C. and Lu, L. (2019) ‘Ceftaroline Efficacy and Safety in Treatment of Complicated Skin and Soft Tissue
Infection : A Systemic Review and Meta-Analysis of Randomized Controlled Trials’, Journal of Clinical Medicine, 8(776), pp. 1–10.
Lan, S., Chang, S., Lai, C., Lu, L., et al. (2019) ‘Efficacy and Safety of Ceftaroline for the Treatment of Community-Acquired
Pneumonia : A Systemic Review and Meta-Analysis of Randomized Controlled Trials’, Journal of Clinical Medicine, 8(824).
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