Antibiotic

Resistence
Kelompok 3
Yasmin Ghallyah Hasan N12221019
Zoraya Indah Permata N12221018
Mouren Christy N12221021
Adityawarman Suaib N12221020
Nurul Hikma Ashri N12221022
Anugrah N12221023
Antibiotic Mechanism Action
Fluorokuinolone
 Data resistensi Fluoroquinolone

Hayer, S. S., Casanova-Higes, A., Paladino, E., Elnekave, E., Nault, A., Johnson, T., Alvarez, J. (2022). Frontiers Media S.A.
 Farmakodinamik dan Farmakokinetik

• Swallow, S. (2015). Fluorine in medicinal chemistry. In Progress in Medicinal Chemistry (Vol. 54, pp. 65–133). Elsevier B.V.
• Mimouni, F. Z., Belboukhari, N., & Sekkoum, K. (2019). Mini Review: Is fluoroquinolone drug or poison? Journal of Complexity in Health Sciences, 2(2), 70–
Uddin, Tanvir Mahtab et al., 2021. Journal of Infection and Public Health 14 (2021) 1750–1766.
 MECHANISMS OF QUINOLONE RESISTANCE
Singkatan
QRDR : Quinolone Resistance Determining Regions
Qnr : Quinolone Resistence Gen
AAC(6’)- Ib-cr : aminoglycoside-modifying acetyltransferase
MFS, major facilitator superfamily
RND, resistance–nodulation–division
01 Target-site gene mutations in topoisomerases
Mutasi kromosom pada QRDR dari gen yang
mengkode subunit A dan B DNA girase dan
topoisomerase IV secara struktural mengubah protein
target, mengurangi afinitas pengikatan obatnya
0 Chromosomal mutations leading to reduced
2 drug accumulation
Mutasi kromosom yang menyebabkan penurunan
permeabilitas membran luar, baik dengan penurunan
ekspresi porin (b1) atau modifikasi membran luar (b2),
dan juga mutasi yang menyebabkan peningkatan
ekspresi pompa efflux
03 MDR efflux pump overexpression
Berkontribusi secara aditif terhadap resistensi dengan
mengurangi akumulasi kuinolon sitoplasma
04 Plasmid-mediated quinolone resistance (PMQR)
Gen resistensi kuinolon yang dikodekan oleh plasmid
Qnr dapat menghasilkan perlindungan protein target
(d1), varian AAC(6’)-Ib-cr yang mampu memodifikasi
pompa efflux kuinolon (d2) atau QepA dan OqxAB
tertentu yang secara aktif mengeluarkan kuinolon
Uluseker C, Kaster KM, Thorsen K, Basiry D, Shobana S, Jain M, Kumar G, Kommedal R and Pala-Ozkok I (2021). Front. Microbiol
Correia et al. 2017.Journal of Medical Microbiology 2017
Rifampisin
RIFAMPISIN
Prevalensi Resistensi Rifampisin

Wang, C, 2022, Global prevalence of resistance to rifampicin in Mycobacterium leprae: A meta-analysis, Journal of Global Antimicrobial
Resistance 31 (2022) 119–127
RIFAMPISIN
Struktur Kimia, Farmakokinetik - Farmakodinamik

Profil Farmakokinetik
• Cmax 0,94-27,7 µg/mL
• Ikatan Protein 70-80%

Farmakodinamik

Mekanisme Aksi : Menghambat DNA polymirase-

dependent dan RNA polymirase pada M. tuberkulosis.

1. Haride, KL, Fenn, SJ, 2022, JMM profile: rifampicin: a broad-spectrum antibiotic, Journal of Medical Microbiology, 71:001566

2. Abulfathi, A. A., Decloedt, E. H., Svensson, E. M., Diacon, A. H., Donald, P., & Reuter, H. (2019). Clinical Pharmacokinetics and
Pharmacodynamics of Rifampicin in Human Tuberculosis. Clinical Pharmacokinetics. doi:10.1007/s40262-019-00764-2 
RIFAMPISIN

Sprektum, Efek Samping dan Pemberian

Haride, KL, Fenn, SJ, 2022, JMM profile: rifampicin: a broad-spectrum antibiotic, Journal of Medical Microbiology, 71:001566
RIFAMPISIN
Mekanisme Kerja dan Resistensi

Setelah berada di bakteri, rifampisin berikatan dengan

β-subunit RNA polimerase (RPoB) untuk
menghambat sintesis RNA pada titik awal (antara
penambahan nukleotida kedua atau ketiga).

Resistensi terhadap rifampisin, terjadi melalui:

01. Ribosilasi ADP rifampisin sehingga tidak lagi
berinteraksi dengan RNA polimerase (karena dapat
ditularkan, pada tanda silang hitam di lingkaran
merah),

02. Efflux (pompa eflux kuning)

03. Mutasi RNA polimerase sehingga tidak dapat

berinteraksi dengan rifampisin (paling signifikan
secara klinis)

04. Mutasi promotor therpoB yang meningkatkan

tingkat produksi RNA polimerase sehingga melebihi
jumlah rifampisin dan membiarkan sebagian
polimerase bebas berfungsi.
Haride, KL, Fenn, SJ, 2022, JMM profile: rifampicin: a broad-spectrum antibiotic, Journal of Medical Microbiology, 71:001566
 Daftar Pustaka
1. Uluseker C, Kaster KM, Thorsen K, Basiry D, Shobana S, Jain M, Kumar G, Kommedal R and Pala-Ozkok I (2021) A Review on
Occurrence and Spread of Antibiotic Resistance in Wastewaters and in Wastewater Treatment Plants: Mechanisms and Perspectives.
Front. Microbiol. 12:717809. doi: 10.3389/fmicb.2021.717809

2. Swallow, S. (2015). Fluorine in medicinal chemistry. In Progress in Medicinal Chemistry (Vol. 54, pp. 65–133). Elsevier B.V.
https://doi.org/10.1016/bs.pmch.2014.11.001

3. Mimouni, F. Z., Belboukhari, N., & Sekkoum, K. (2019). Mini Review: Is fluoroquinolone drug or poison? Journal of Complexity in Health
Sciences, 2(2), 70–76. https://doi.org/10.21595/chs.2019.20952

4. Hayer, S. S., Casanova-Higes, A., Paladino, E., Elnekave, E., Nault, A., Johnson, T., … Alvarez, J. (2022, March 9). Global Distribution of
Fluoroquinolone and Colistin Resistance and Associated Resistance Markers in Escherichia coli of Swine Origin – A Systematic Review
and Meta-Analysis. Frontiers in Microbiology. Frontiers Media S.A. https://doi.org/10.3389/fmicb.2022.834793

5. Correia et al. 2017. Mechanisms of quinolone action and resistance: where do we stand? Journal of Medical Microbiology 2017;66:551–
559 DOI 10.1099/jmm.0.000475

6. Uddin, Tanvir Mahtab et al., 2021. Review Antibiotic resistance in microbes: History, mechanisms, therapeutic strategies and future
prospects. Journal of Infection and Public Health 14 (2021) 1750–1766.

7. Haride, KL, Fenn, SJ, 2022, JMM profile: rifampicin: a broad-spectrum antibiotic, Journal of Medical Microbiology, 71:001566

8. Wang, C, 2022, Global prevalence of resistance to rifampicin in Mycobacterium leprae: A meta-analysis, Journal of Global Antimicrobial
Resistance 31 (2022) 119–127

9. 2. Abulfathi, A. A., Decloedt, E. H., Svensson, E. M., Diacon, A. H., Donald, P., & Reuter, H. (2019). Clinical Pharmacokinetics and
Pharmacodynamics of Rifampicin in Human Tuberculosis. Clinical Pharmacokinetics. doi:10.1007/s40262-019-00764-2 
TERIMA
Kelompok 3

KASIH
 Antibiotics inhibiting nucleic acid synthesis
AB
01
Rifamycin
Rifamycin inhibit bacterial DNA-dependent RNA
polymerase, by attaching tightly to the polymerase sub
unit deep inside the DNA/RNA pathway, allowing direct
blocking of the elongating RNA. Bacterial RNA
polymerase enzymes vary structurally from eukaryotic
RNA polymerase enzymes, allowing for selective
toxicity against bacterial cells
02
Fluoroquinolone
s
Quinolones block DNA synthesis by inhibiting DNA gyrase and
topoisomerase IV, two basic type II topoisomerases. Both
targets cause one double stranded DNA molecule to move
through another, with the initial strand religated afterwardstrong
affinity for the A subunit of DNA gyrase, interfering with its
strand splitting and resealing role, preventing normal cell
division. Topoisomerase IV, which nicks and separates the
daughter DNA strand after DNA replication, is the main focus of
action in Grampositive bacteria. Drugs with higher affinity for
this enzyme can confer greater potency against Gram-positive
bacteria