RATIONAL USE OF ANTIBIOTICS

1
RATIONAL USE OF ANTIBIOTICS

• R. Anita Indriyanti
• Pharmacological Department
• Bandung Islamic University

2
References

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

3

• 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

4
Resistance

• Side effect

Definition
Ideal antibiotics
AB
Spectra
In vitro
Classification
Chemical structures
Mechanism of action
5
DEFINITION

• 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

6
IDEAL ANTIBIOTICS CRITERIA

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

7
In vitro

• 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

8
SPECTRUM OF AB EFFECTS

• 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

9

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

10
SIDE EFFECTS

• ALLERGIC REACTION
• TOXIC REACTION
• Direct effects in unproper dose e.g.
  aminoglycosides
• 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.

11
AVOIDING SUPERINFECTION

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

12
RATIONAL THERAPY OF ANTIBIOTICS
HOST
ANTIBIOTICS

• PHARMACOKINETICS
• PHARMACODINAMICS

13
HOST ASPECTS BIOCHEMICAL PHYSIOLOGICAL
PATHOLOGICAL CONDITIONS

• CHARACTERISTIC
• OF ANTIBIOTICS

14
DEFINITION OF RATIONAL USE OF ANTIBIOTICS (WHO)

• PROPER INDICATION
• PROPER DRUG
• PROPER DOSAGE
• SE MONITORING

15

• 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
16
RATIONAL USE OF ANTIBIOTICS
PREVENTION IN HIGH SUSCEPTIBILITY TO GET INFECTION

• THERAPY ERADICATING
• M.O
• DEFINITIVE THERAPY
• EMPIRIC THERAPY

PROPHYLAXIS IN NON SURGICAL CONDITIONS IN
SURGICAL CONDITIONS
17
DEFINITIVE THERAPY

• 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

18
EMPIRIC AB THERAPY

• 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

19
SELECTING AB IN EMPIRIC THERAPY

• The site of infection
• There are barriers inside the body
• brain, prostate, bone
• Other foreign bodies
• local factors
• Patients history

20
PATIENT 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

21
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

22
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 if mixed
• ? ?
• Continue gram pos. continue therapy
• Coverage, discontinue as initiated
• Gram neg. and anaerobic
• Coverage

Chapter 28, Fig.28.1 Lippincotts ed.2nd
23

• PROPHYLAXIS
• SURGICAL
• Contaminated op.
• Clean contaminated op
• Selected op ? may suffer
• post-op.infection

• NON SURGICAL
• PREVENT
• Streptococcal infection in patient with a history
  of RHD
• In pre-dental extraction who have implanted
  prosthetic devices
• TB/meningitis in close contact individual
• Protect fetus from infection in HIV-infected
  pregnant woman

24

• Common Error in AB prophylaxis
• Selection of wrong AB
• The initial therapy too early or too late
• Excessive duration
• Inappropriate use of BSAB

25

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

26

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

27

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

28

• 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

29

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

30

• CLINICAL INDICATION OF AB COMBINATION
• ? Mixed infection
• ? Synergism effect
• ? Risk of developing resistant
• organism lt
• ? Increase AB coverage or
• ? Infection of unknown origin

31

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

32
Thank You