Simposium FK Baiturahmah, AB Pada Imunodefisiensi.. Dr Raveinal

ANTIBIOTIK PADA KEADAAN IMUNODEFISIENSI

RaveinalSub 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. Lymphocytes2. Monocytes/Macrophages3. Dendritic cells4. Granulocytes5. Mast cells

PhagocytosisIs 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-α 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 bakteriMekanisme pertahanan dipengaruhi oleh:

1.Struktur ddg sel2.Jenis bakteri (Gram + / Gram -)3.Mikrobakteria4.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 Ab2.Infasif tanpa toksisitas

Sebagian besar gabungan invasif dgn aktivitas toksin lokal dan produksi enzim merusak jaringan bakteri menyebar

Interaksi mikroba dgn imunitasMenghindari respon imun1.Produksi toksin menghambat khemota ksis 2.Membentuk kapsul fagosit tdk terjadi3. Memproduksi molekul yang menghambat fungsi

lisosom dgn fagosom atau menghambat makrofag berinteraksi dg IFN

4.Menurunkan sitokin proinflamatorik TNF-α,IL-1ß,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.

Inhibisi biosintesis protein

Makrolid, Tetrasiklin, Kloramfenikol.

As.folat antagonis

Sulfa-TrimethoprimInhibisi b-laktam

As.klavulanat, sulbaktam

Sitesis As nukleat

Rifampisin, quinolon.

Membran sitoplasma

Polimiksin B, Amfoterisin B

1. Cell wall synthesis

1. Cycloserine2. Glycopeptides (vancomycin, teicoplanin)3. Bacitracin4. Beta-lactams (penicillins, cephalosporins,

carbapenems, monobactams)

Inhibitors of bacterial cell wall synthesis

Cytoplasmic membranesynthesis of

new cell wall subunit

attached to lipid carrier

Glycopeptidesbind to terminal

D-ala-D-ala residues;prevent incorporation

of subunit into growing

peptidoglycan

NAG NAM P P C55 lipidBacitracin Prevents dephosphorylation of phospholipid carrier, which prevents regeneration of carrier necessary for synthesis to continue

L- lysine

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. Aminoglycosides2. Macrolides3. Tetracyclines 4. Chloramphenicol5. 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 contaminationFact: 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 WiselyAction: 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

Optimize Use

PreventTransmission

PreventInfection

EffectiveDiagnosis& Treatment

PathogenAntimicrobial-Resistant Pathogen

Antimicrobial Resistance

Antimicrobial Use

Infection

Susceptible Pathogen

TERIMA KASIH