ANTIBIOTIK PADA KEADAAN IMUNODEFISIENSI

Raveinal Sub Bagian Alergi Imunologi Klinik FK UNAND / RS M Jamil Padang

SISTEM IMUN

Sistem Imun
mekanisme utama yang melindungi tubuh terhadap invasi dari organisma terhadap ketahanan sel atau tubuh dari benda asing seperti mikroorganisme, toksin, bahan kimia, obat obatan atau sel kanker.

Imunitas nonspesifik dan spesifik

Makrofag yang teraktifasi akan memicu sel T spesifik dari sistem imun spesifik / di dapat untuk memproduksi berbagai antibodi

Cellular components of the immune system

The cellular component develops from the pluripotent hematopoietic stem cell.
The cellular components of the immune system are : 1. Lymphocytes 2. Monocytes/Macrophages 3. Dendritic cells 4. Granulocytes 5. Mast cells

Phagocytosis
Is the uptake of particulate material by engulfment. Three steps in the process of phagocytosis : - Recognition and attachment - Engulfment - Killing and degradation

GAMBARAN DEFISIENSI IMUN

Ditemukan tanda peningkatan kerentanan thdp infeksi rekuren, kronis, oportunistik & respon buruk thdp antibiotik Primer relatif jarang Sekunder timbul oleh berbagai faktor sesudah lahir Defisiensi imun sering mengenai limfosit, komplemen dan fagositosis

Defisiensi sistem imun

Defisiensi sel B limfosit : Infeksi berulang spt otitis media, pnemonia Defisiensi sel T limfosit : rentan terhadap virus, jamur dan protozoa Defisiensi fagositosis : infeksi sistemk kuman dgn virulensi rendah, infeksi piogenik Defisiensi komplemen : infeksi bakteri, autoimunitas

Cellular targets of pathogenic bacteria

Figure 2-45

Tumor necrosis factor- has important local protective effects but can have severely detrimental effects systemically.

Opportunistic Infections in HIV

Bacterial/ Mycobacterial Mycobacterium Avium Complex (MAC) Salmonellosis Syphilis Tuberculosis Bacterial pneumonia Fungal Candidiasis Coccidioidomycosis Cryptococcal meningitis Histoplasmosis Protozoal Cryptosporidium Pneumocystis carinii Pneumonia (PCP) Toxoplasmosis Viral Cytomegalovirus Hepatitis Herpes simplex Herpes zoster Human papiloma virus Oral hairy leukoplakia Progressive Multifocal Leukoencephalopathy (PML)

Bentuk imunitas thd bakteri

1.Imunitas thd toksin bakteri Exotoxin dan endotoksin dari bakteri akan dimusnahkan oleh respons imun penjamu penyakit dpt dicegah. 2.Imunitas thd kapsul bakteri Bakteri menghindari fagositosis melapisi dirinya dgn polisakarida menghambat fagositosis.

3.Imunitas bakteri yg hidup intraseluler Bakteri menghindari respons imun

penjamu, utk berkembang biak di dlm sel khusus sel fagosit

Respon imun tertadap infeksi :

1.Jumlah & fungsi Th, Ts dan Tc yg teraktivasi. 2.Jumlah & fungsi sel B 3.Jumlah sel memori Pola reaksi imunologik bergantung pada jenis dan sifat mikroorganisme

Infeksi bakteri
Mekanisme pertahanan dipengaruhi oleh: 1.Struktur ddg sel 2.Jenis bakteri (Gram + / Gram -) 3.Mikrobakteria 4.Spiroketa Lapisan luar bakteri Gram () terdiri lipid peka thd lisis C dan sel sitotoksik tertentu. Untuk yang lain fagositosis.

 Sel NK lisis membran sel Gram (- ) Sel Tc infeksi bakteri intraseluler merusak membran sel bakteri bakteri keluar dan dihancurkan dengan cara lain.

Sifat patogenitas bakteri

1.Toksik tanpa infansif C.difteria & V.cholerae diikat oleh Ab 2.Infasif tanpa toksisitas Sebagian besar gabungan invasif dgn aktivitas toksin lokal dan produksi enzim merusak jaringan bakteri menyebar

Interaksi mikroba dgn imunitas

Menghindari respon imun 1.Produksi toksin menghambat khemota ksis 2.Membentuk kapsul fagosit tdk terjadi 3. Memproduksi molekul yang menghambat fungsi lisosom dgn fagosom atau menghambat makrofag berinteraksi dg IFN 4.Menurunkan sitokin proinflamatorik TNF-,IL-1,IL-6

Three basic principles of antimicrobial therapy:

1. Selective toxicity - kill organisms not a man! 2. Reach the site of infection at adequate
concentrations

3. Penetrate and bind to target microbe

Klasifikasi & Mekanisme Kerja AB

Dinding kuman
Penisilin, sefalosporin, glukopeptida, fosfomisin.

Membran sitoplasma
Polimiksin B, Amfoterisin B

Inhibisi biosintesis protein

Makrolid, Tetrasiklin, Kloramfenikol.

Sitesis As nukleat
Rifampisin, quinolon.

As.folat antagonis
Sulfa-Trimethoprim

Inhibisi b-laktam
As.klavulanat, sulbaktam

1. Cell wall synthesis

1. 2. 3. 4. Cycloserine Glycopeptides (vancomycin, teicoplanin) Bacitracin Beta-lactams (penicillins, cephalosporins, carbapenems, monobactams)

Inhibitors of bacterial cell wall synthesis

Cytoplasmic membrane NAG synthesis of new cell wall subunit attached to lipid carrier Glycopeptides bind to terminal D-ala-D-ala residues; prevent incorporation of subunit into growing peptidoglycan
NAM P P C55 lipid

L- lysine

Bacitracin Prevents dephosphorylati on of phospholipid carrier, which prevents regeneration of carrier necessary for synthesis to continue

2. Inhibitors of protein synthesis

Ribosomal subunits involved in mRNA translation in bacterial systems are smaller (30S & 50S) than in eukaryotic (mammalian) translation (40S & 60S) Most antibiotics acting upon the ribosome are bacteriostatic, but aminoglycosides are bactericidal

Inhibitors of protein synthesis

1. 2. 3. 4. 5. Aminoglycosides Macrolides Tetracyclines Chloramphenicol Fusidic acid

3. Nucleic acid synthesis:

Inhibition of synthesis of precursors : Sulphonamides, Trimethoprim Inhibitors of DNA replication : Quinolones Inhibitors of RNA polymerase : Rifampicin

Use Antimicrobials Wisely

Action: Treat infection, not contamination

Fact: A major cause of antimicrobial overuse is treatment of contaminated
cultures.

Actions:
use

proper antisepsis for blood & other cultures culture the blood, not the skin or catheter hub use proper methods to obtain & process all cultures

Use Antimicrobials Wisely Action: Treat infection, not colonization

Fact:
A major cause of antimicrobial overuse is treatment of colonization.

Actions:
treat pneumonia, not the tracheal aspirate treat bacteremia, not the catheter tip or hub treat urinary tract infection, not the indwelling catheter

Antimicrobial

Key Prevention Strategies

Susceptible Pathogen Pathogen Antimicrobial-Resistant Pathogen
Prevent Transmission Prevent Infection

Antimicrobial Resistance
Optimize Use

Infection
Effective Diagnosis & Treatment

Antimicrobial Use

TERIMA KASIH