PRINCIPLES OF ANTIMICROBIAL

THERAPY
By :
Herri S. Sastramihardja
Prof.,DR.,Dr.,SpFK

Depart. Of Pharmacology and Therapy

Medical Faculty Padjadjaran University

Introduction
AM drugs are effective in the treatment
of

infection, because oftheir selective toxicity

The selective toxicity is relative
Succesfull AM therapy
overprescribed
use without prescription
Clinician should first determine AM
necessitty

Selection of AM agent
Requires information about :

Identification & sensitivity of the organism

Site of infection
Safety the agent
Patient factors
Bactericidal vs bacteriostatik
Cost of therapy

THE TYPES OF AM
THERAPY
1. Directed (definitive) AM therapy
base on identification & susceptibility test
interpreted in the context of the overall
clinical picture
directed to specific organisms
most effective, least toxic, narrowest

THE TYPES OF AM THERAPY

(continued..)
2. Empirical (presumptive) AM therapy
base on local epidemiological data
- potential pathogen
- AM susceptibility patterns

3. Prophylactic AM therapy
restricted to certain situation

Indication of empiric therapy

Infection of unknown origin
Neutropenic patient
Symptoms characteristic of meningitis
Severe headache
Rigid of the neck
Sensitivity to bright lights

Infections are best treated early

Selecting a drugs in empiric therapy

Site of infection
Patient history
Hospital/community acquired
Immunocompromised ?
Medical record
Age
Started with AM combination
or
Single broad spectrum AM

Empiric therapy :
Coverage by a combination of
antibiotics such as, clindamycin plus
gentamicin, effective against gram
possitive, gram negative and
anaerobes, or a single broad
spectrum antibiotic, such as
imipenem cilastatin

Receive culture report

with sensitivities

If mixed
If Gram
positive only

Continue gram
positive coverage
discontinue gram
negative and
anaerobic coverage

If Gram
negative only

Continue therapy as
initiated
If anaerobic only

Continue gram
negative coverage
discontinue gram
positive and
anaerobic coverage

Continue anaerobic
coverage,
discontinue gram
positive and gram
negative coverage

Figure 1. Strategic for empiric therapy

Identification & sensitivity of the organism

Rapid assesment

gram stain, PCR,

educated guess

Conclusive diagnosis
culture (disk diffusion) methode
various concentration
(broth/dilution methode)

The effect of the site of infection (SI)

on therapy :
Adequate levels of AM in SI
Natural barrier (inadequate penetration)
Brain (blood-brain barrier)
Bactericidal effect
Prostate (prostatic epithelium)
Trimethoprim (a basic AM)
Bone
Foreign body, circulation Abnormality, obstruction

Safety of AM agent
Related to :
Inherent nature of AM
Patient factors that can predispose to toxicity

Penicillins
Choramphenicol

least toxic
potential for serious
toxicity

Side Effects of AM therapy

Hypersensitivity
Direct toxicity
Ototoxicity of aminoglycosides
Super infection
Upper respiratory tract
Intestinal tract
Genitourinary tract

Status of the patient

Immune system
Renal dysfunction
Hepatic dysfunction
Genetic factor
Pregnancy
Lactation
Age

 Immune system :
Immunocompromised host

Alcoholism
Diabetes
HIV
Malnutrition
Advanced age
Therapy with immunosuppresive drugs

Need high dose / long treatment of

bactericidal AM

 Renal dysfunction:
Accumulation of AM that are ordinary
eliminated by renal
Elderly

vulnerable to accumulation

Controlled by:
Adjusting the dose/dosage schedule
Monitoring serum levels
Used AM that undergo extensive
metabolism / billiary excretion

 Hepatic dysfunction
AM that are concentrated/eliminated by
the liver are contraindicated
Erythromycin, tetracycline, quinolone,
choramphenicol

Genetic factor
Enzym deficient
potential for
toxicity of certain agent
Sulfonamid, nitrofurantoin in G-6PD
deficient people
hemolysis

 Pregnancy
Most of AM cross the placenta to some
degrees
The problem are teratogenic/toxic effect
Metronidazol, rifampicin, trimetoprim
teratogenic
Tetracycline
tooth dysplasia + bone
growth inhibition
Aminoglycosides
ototoxic to the fetus

 Lactation
Many AM are excreted in breast milk
new borns microflora distorted
act as a sensitizer future allergy

 Age :
Most AM eliminated by the renal; renal
function changes with age
Renal/hepatic elimination in newborns <
Neonates particularly vulnerable to :
Chloramphenicol
Sulphonamides
Tetracyclines
Fluoroquinolones (>< cartilage growth)

Bacteriostatic vs bactericidal drugs

Bacteriostatic drugs
Arrest growth & replication of bacteria at
serum levels
Limiting the spread of infection
immune
system attacks, immobilizes & eliminated
the pathogens
Bactericidal drugs
Kills bacteria & total number of viable
organisms

 Bacteriostatic AM:
Choramphenicol, erythromycin,
clindamycin, lincomycin, sulfonamide,
trimetoprim

Bactericidal AM:
Penicillins, cephalosporins, carbapenem,
aminoglycosides, quinolones, vancomycin

Tetracycline
Metronidazole
Bismuth
subsalicylate
Amoxicillin
Clarithromycin

$5
$6
$11
$17
$120

Cost of therapy for peptic ulcers by H. pylori

Common causes of failure of AM therapy

Drug

inappropriate drug
inadequate dose
improper route of adm.
malabsorption
accelerated inactivation
poor penetrate

Host

poor host defenses

undrained pus
retained infected foreign bodies
dead tissues

 Pathogens

drug resistence
superinfection
dual infection initially

Laboratory

erroneous report of

susceptible pathogen

Misuses of AM
Treatment of untreatable infections
Therapy of fever of unknown arigin
Short duration
Persisting 2 weeks

Improper dosage
Inappropriate reliance an AM alone
Lack of adequate bacteriological information

Clinical indications of AM combination

Mixed infection
Synergism effect
Risk of developing resistant organisms
Antibiotics coverage
or
Infections of unknown origin

Three major mechanism of

AM synergism
1. Blokade of sequential steps in a metabolit
sequence
Trimetoprim-sulfomethoxazole
2. Inhibition of enzymatic inactivation
Amoxyline-clavulanat
3. Enhancement of AM agent uptake
Penicillins-aminoglycosides

Two major mechanism of

AM antagonism
1. Inhibition of cidal activity by static agent
Tetracyclines - .lactam AM
2. Induction of enzymatic inactivation
Ampicillin-piperacillin

Disadvantages of AM combinations

Risk of toxicity

The

selection of multiple-drug
resistant (=MDR) pathogens

Cost to the patient

Antagonism of AM effect
(bacteriostatic + bactericidal)

NRC WOUND
CLASSIFICATION
CRITERIA

1. Clean
- elective, primarily closed procedure
- expected infection rate 2%

2. Clean contaminated
- urgent or emergency case that is otherwise
clean
- expected infection rate 10 %

3. Contaminated

- acute nonpurulent inflammation present

- expected infection raye about 20 %

4. Dirty

- purulance or abscess present

- expected infection rate about 40 %

Surgical procedure for prophylactic AM

1. Contaminated operations
2. Clean-contaminated operations
3. Selected operations in which post operative
infections may be cathastropic:
Open heart surgery
Clean procedures that involved
placement of prosthetic materials
Immunocompromised host

General principles of AM surgical

prophylaxis
1. AM active >< common surgical wound
pathogen
2. AM-have proved efficacy in clinical trials
3. AM concentration > MIC of susp. Pathogens
4. Single dose, with most effective & least toxic
AM
5. Newer broad spectrum AM reserve
6. The least expensive AM

Common errors in AM prophylaxis

1.
2.
3.
4.

Selection of the wrong AM

First dose of AM too early or too late
Excessive duration of prophylaxis
Inappropriate use of broad spectrum AM

Some non-surgical clinical situation for

prophylactic AM
>< streptococcal Infections in patients with a
history of RHD
Pre-dental extractions who have implanted
prosthetic devices
>< TB / meningitis in close contact
individuals
Protect fetus in HIV-infection pregnant
woman

Disadvantages to prophylactic AM
1.
2.
3.
4.

Toxic/allergic reactions
Superinfection with more resintence flora
Infection temporarily masked
Ecology of the hospital flora may be altered

THANK YOU