Basic Principles

of Antimicrobial
Therapy

Dwi Indria Anggraini1, Rovina Ruslami2

1
Dept. Pharmacology Faculty of Medicine,
Lampung University
2
Dept. Pharmacology Faculty of Medicine,
Overview
 Overview

Selective toxicity of antimicrobial (AM)

ability to kill invading m.o without harming

hosts cells

Effective treatment in infectious disease

BUT it requires an appropriate concentration

to attack the m.o while tolerabled by the
host
Terms
Chemotheraphy
 Molecular basis of
chemotherapy
Chemotherapeutic drugs should be toxic
for invading m.o in the host
Selective toxicity depends on biochemical
differences between parasite host
Biochemical reaction as potential targets :
Class I: glucose & other carbon source
Class II: energy and class I compound to make
amino acid, nucleotides, etc
Class III: small molecules are built into larger
molecules, e.g. proteins, nucleic acid,
peptidoglycan
 Biochemical reactions as
potential targets
Class I: poor targets
 Formed structure of the
cell
Plasma membrane affected by:
How to select AM?

We need information about:

However
Critically ill patient (C.I.P) need
immediate AM
Empiric therapy

cover infections by both gr (+), (-), &/

anaerob

To prevent worsening the condition

To prevent the death

 I. Empiric therapy..
When?
 Empiric therapy
Empiric therapy Receive culture
Coverage by a combination of
Coverage by a such
antibiotics combination
as, of report with
antibiotics such
clindamycin
clindamycin
plusas,
plus
sensitivities
gentamicin, effective
gentamicin,
against gr (), greffective
(-) and
against gr (), gr
anaerobes, or a single (-)broad
and
anaerobes,
spectrum or a single
antibiotic, such broad
as If mixed
spectrum
imipenem antibiotic, such as
cilastatin
If mixed
If Gram
imipenem cilastatin If Gram
positive
positive
only
only If Gram Continue
Cont. gr (+) coverage. If Gram
negative therapy as
negative
only initiated
discontinue gram (-) & only
anaerobic coverage If anaerobic
If anaerobic
only
only
Cont. gr (-) coverage
Cont. anaerobic
Discontinue gr (+) and coverage
anaerobic coverage
Discontinue gr (+) &
(-) coverage

Strategic for empiric

II. Pay attention to specific cond related to
PK
Liver dysfunction
Renal dysfunction
Pay attention to specific cond related to PK

Poor perfusion
Pay attention to specific cond related to PK
Pay attention to specific cond related to PK
III. Safety and Cost-benefit

Safety
IV. Bacteriostatic vs.
Bactericidal AM
V. Spectrum of AM
 VI. Combination of AM
Select if possible only single AM
It prevents:
Superinfections
emerge of drug resistance
Minimize toxicity
the cost

BUT sometimes wee need drug

combination
Synergism more effective (B-lactam + AMG)
Wider coverage
 VII. Complication of AM
Therapy
1. Hypersensitivity
 VIII. Classification of AM
a. Chemical structure
Virus multiplication and modes of
action of antiviral agents
 Stages of Virus Replication and Possible Targets
of Action of Antiviral Agents
Stage of replication Classes of selective inhibitor

Cell entry
Attachment Soluble receptor decoy, antireceptor
Penetration antibodies
Uncoating Ion chanel blockers, capsid stabilzer
Release of viral genome
Transcription of viral genome Inhibitor of polimerase, reverse
trans
Transcription of viral messenger RNA criptase, helicase, primase,
integrase
Replication of viral genome
Translation of viral proteins Interferon, antisense oligonucleoti-
Regulatory proteins (early) Inhibitors of regolatory proteins
Structural proteins (late)
Posttranslational modifications
Proteolytic cleavage Protease inhibitor
Myristoylation, glycosylation
Assembly of virion components Interferon
Release Neuraminidase inhibitor, antiviral
Budding, cell lysis antibody, cytotoxic lymphocytes
ANTIFUNGAL DRUGS

27
Anti
fungal
Endo- and
ectoparas
ites:
therapeut
ic agents
 Resistance to AM
If with max dose of AM (tolerated by the host)
 Resistance to AM
Can be spread
Resistance to AB:
mechanism?
 Multidrug Resistance
(MDR)
Resistance to commonly used AB
MDR- TB (resistant to >2 anti-TB drugs)
Some strains of Staph. &enterococc. (resistant to
most all AB)

Lead to serious untreatable infection

THANK
YOU