R. Anita Indriyanti
Pharmacological Department
Bandung Islamic University

1. Lippincott’s Illustrated Reviews :
Pharmacology, 2 nd ed
(Chapter 28)
2. Buku Pedoman Kuliah Farmakoklinik
Farmakologi III
Jilid 1 edisi 2
Prof. DR. Herri S. Sastramihardja, dr.,
SpFK

A medical doctor has to know the definite clinical pharmacology of antibiotics, how to select and use them rationally.
30% of inpatient individuals has been given antibiotics

Side effect
Definition AB
Resistance
Ideal antibiotics
In vitro
Classification
Spectra
Chemical structures
Mechanism of action

AB are chemical substances obtained from microbes/microorganisms (bacteria, fungi, actinomycetes) that able to inhibit or eradicate the growth of the other microorganisms.
Antimicrobial all antiinfections semisynthetic synthetic nature  antibiotics

1.
Most selective, most effective to infectied microorganisms
2.
More bactericidal effect in the site of action
3.
Antibacterial effect is not interfered by body fluid, exudate, plasma protein or enzymes and persist for a long duration in the blood
4.
Minimal toxicity
5.
Resistance develops slowly
6.
Given by any route
7.
Reachable cost

1. Primary bacteriostatic effect  inhibit the growth of m.o
Sulfonamide, tetrac, chloramph, erythromycin (low concentration), lincomycin, clindamycin and fusidic acid
2. Primary Bactericidal Effects 
Eradicate/kill
Pen, cef, aminoglic, erythromycin (high concentration), cotrimazol. Rifampisin and vankomycin.
Those classification is not absolute but relative

1. Narrow spectrum antibiotics (NSAB)
Main effect : sensitive for gram positive bacteria and bacil e.g. : Pen. G, Pen. Resistent penicillinase semisynthetics, bacitracin, macrolides, lincomycin, vancomycin
2. Broad Spectrum Antibiotics (BSAB)
Main effect : sensitive for gram positive and gram negative bacteriae e.g. : Pen. (ampicillin and amoxycillin), cefalosporins, tetracyclins, chloramphenicol, trimetroprim and sulfonamides

Widely used of BSAB  an umbrella in treating the unidentified bacterial infection
 resistance 
RESISTANCE and
MECHANISM OF ACTION recall in microbiology

SIDE EFFECTS
1.
ALLERGIC REACTION
2.
TOXIC REACTION
Direct effects in unproper dose e.g. : aminoglycosides
3.
SUPERINFECTION : new infection caused by pathogen microbes or fungi during AB therapy to primary infection.
SUPERINFECTION : frequent potentially harmed risk
Causa : Enterobacter, Pseudomonas,
Candida and other fungi. Those agents are difficult to be eradicated by today available antibiotics.

1.
Stop the giving antibiotics
2.
Treatment according to bacterial identification and sensitivity test
The specimen was taken from feces and secretion of upper respiratory tract, to be analyzed

RATIONAL THERAPY OF ANTIBIOTICS
ANTIBIOTICS
HOST
PHARMACOKINETICS
PHARMACODINAMICS

CHARACTERISTIC
OF ANTIBIOTICS
HOST ASPECTS
BIOCHEMICAL &
PHYSIOLOGICAL &
PATHOLOGICAL
CONDITIONS

PROPER INDICATION
PROPER DRUG
PROPER DOSAGE
SE MONITORING

RATIONAL USE OF AB
PROCEDURES
STEPS TO PROCEDURES
Define the patient problems specify the therapeutic objectives
Verify the suitable of your personal treatment
Start the treatment
Give information, instruction and warning
Monitoring and stop treatment
Clinical diagnosis
Identification, sensitivity test of bacteria
Pharmacodynamics
Pharmacokinetics
Host factors

PREVENTION IN HIGH
SUSCEPTIBILITY TO
GET INFECTION
PROPHYLAXIS
THERAPY
M.O
ERADICATING
DEFINITIVE THERAPY
EMPIRIC THERAPY
IN NON SURGICAL CONDITIONS
IN SURGICAL CONDITIONS

It is the most effective, least toxicity and the narrowest selection
Based on :
* identification of bacteria
* sensitivity test
* interpretation in the content of the overall clinical picture
* the AB of choice directed to M.O

Giving AB directly without identification and sensitivity test of bacteria, but…… obtaining specimen for lab. analysis before giving AB.
Empiric AB therapy based on local epidemiological data :
What is the pathogen M.O potentially infected
AB given based on susceptibility pattern
Initiated after obtaining specimen
Started with AM combination or single
BSAB

SELECTING AB IN EMPIRIC THERAPY
The site of infection
There are barriers inside the body : brain, prostate, bone
Other : foreign bodies local factors
Patient’s history :

Age  baby, child, adult, old age !
Immune system  immunocompromised!
Who?
Renal dysfunction  accumulation! How ?
Hepatic dysfunction  metabolism! How ?
Genetic factors  G6-PD. Attention, contraindication !
Pregnancy  teratogenic, embryogenic
Lactation  vulnerable AB for new born

INDICATION IN EMPIRIC THERAPY
Infection of unknown origin
Neutropenic patients
Characteristic symptoms of meningitis
MISUSE of AB :
Treatment of untreatable infection
Therapy of fever of unknown origin
Improper dosage
Inappropiate reliance on AB alone
Lack of adequate bacterial information

STRATEGIC FOR EMPIRIC THERAPY
Empiric therapy :
Coverage by a combination of antibiotics such as
Clindamycin plus gentamycin
Effective against gram positive, gram negatives and anaerobes
Or
A single broad spectrum AB
Such as imipenem/cilastatin
Receive culture report
With sensitivities
If gram positive only
↓
Continue gram pos.
Coverage, discontinue
Gram neg. and anaerobic
Coverage if mixed
↓ continue therapy as initiated
If gram negative only
↓
Continue gram neg.
coverage, discontinue
Gram pos. and anaerobic
Coverage
Chapter 28, Fig.28.1 Lippincott’s ed.2
nd
If anaerobic only
↓ continue anaerobic coverage, discontinue gram positive and gram negative coverage

PROPHYLAXIS
SURGICAL
1.
Contaminated op.
2.
Clean – contaminated op
3.
Selected op  may suffer post-op.infection
NON SURGICAL
PREVENT :
1. Streptococcal infection in patient with a history of
RHD
2. In pre-dental extraction who have implanted prosthetic devices
3. TB/meningitis in close contact individual
4. Protect fetus from infection in HIV-infected pregnant woman

Common Error in AB prophylaxis
1.
Selection of wrong AB
2.
The initial therapy too early or too late
3.
Excessive duration
4.
Inappropriate use of BSAB

DISADVANTAGES TO PROPHYLACTIC
AB
1.
Toxic/allergic reaction
2.
Superinfection with more resistant flora
3.
The infection may be temporarily masked
4.
Ecology of the hospital flora may be altered

COMMON CAUSES OF FAILURE OF AB
THERAPY
DRUGS : ө inappropriate drug ө inadequate dose ө improper route of administration ө accelerated inactivation ө poor penetration
HOST : ө poor host defence ө undrained pus ө retained infected foreign bodies ө crusta/necrotic tissues

Cont.
- Pathogen ө drug resistence ө superinfection ө dual infection initially
- Laboratory : ө erroneous report of susceptible pathogen

AB – COMBINATION
Synergisme (3) :
1) Blockade of sequential steps in a metabolit sequence
- Trimethoprim - sulfamethoxazol
2) Inhibition of enzymatic inactivation
- Amoxycillin - clavulanat
3) Enhancement - Aminoglycosides
- Penicillins - Aminoglycosides

Antagonism (2) :
1. Inhibition of cidal activity by static agent
- Tetracyclines – Betalactam AB
2. Induction of enzymatic inactivation
- Ampicillin - Piperacillin

CLINICAL INDICATION OF AB
COMBINATION :
► Mixed infection
► Synergism effect
► Risk of developing resistant organism <
► Increase AB coverage or
► Infection of unknown origin

DISADVANTAGES OF AB COMBINATION
- Increase risk of toxicity
- Increase MDR-pathogens
- Increase cost
- Increase antagonism (bacteriostatic
+ bactericide)