2. SELECTIVE TOXICITY
Action on a structure or pathway not present
in human cells
•Inhibition of Cell wall synthesis:
B lactams , Vancomycin
•Inhibition of Protein synthesis:
* 30S ribosomal subunit: Aminoglycosides & Tetracyclines
* 50S ribosomal
subunit: Macrolides &Chloramphenicol
•Inhibition of Nucleic acid synthesis:
3. SELECTIVE TOXICITY
Inhibition of Nucleic acid synthesis:
• Quinolones (Topoisomerase inhibitors) –DNA
synthesis; DNA coiling
• Rifampicin (– DNA dependent RNA polymerase)
inhibits transcription
• Sulphonamides (PABA analogues block folic acid
synthesis) block C transfer needed for Thymidine
& purine synthesis
• TMP & pyrimethamine (folate antagonists) block
reduction of FH2
4. BACTERIAL RESISTANCE
to Antibiotics
Chromosomal:
Mutation (1:10^-7 –1:10^-12) alteration of structural
receptor
Plasmid- mediated: (extra chr. DNA)
R factors usually code for enzymes eg
B-lactamases (esp of G-ve bacteria) &
acetyl-transferase (chloramphenicol)
5. BACTERIAL RESISTANCE
to Antibiotics
SPREAD OF RESISTANCE
*Generational
*Selection pressure
*Plasmid transfer
6. BACTERIAL RESISTANCE
to Antibiotics
SPREAD OF RESISTANCE
*Generational
*Selection pressure
*Plasmid transfer
7. BACTERIAL RESISTANCE
to Antibiotics
SPREAD OF RESISTANCE
*Generational
*Selection pressure
*Plasmid transfer
R
8. BACTERIAL RESISTANCE
to Antibiotics
Staphylococci & penicillin then methicillin
PNEUMOCOCCI:
•The most common bacterial pathogens in children (acute OM,
sinusitis, pneumonia, sepsis& meningitis)
•Till 1980 >90% of isolates were highly sensitive to penicillin
•Currently, 25-50% of isolates have intermediate or high penicillin
resistance due to altered PBP
9. BACTERIAL RESISTANCE
to Antibiotics
*Other B lactams &/or increased dose can be effective esp in
non-CNS infections
*10% of isolates are multiresistant
Increased tendency to Vancomycin use has resulted in the
increasing problem of Vancomycin-Resistant enterococci
Is a post-antibiotic era the anticipated future?
10. Factors favouring the development
of antibiotic resistance
•Prolonged / repeated antibiotic courses
•Incomplete eradication of the organism
•Prolonged sub-therapeutic antibiotic levels
•Induction of resistance by drugs
•Hospital-based spread of resistant organisms
13. When?
Which?
How much?
How long?
•Proven bacterial infection
•Suspected bacterial infection
•Prevention of bacterial infection
Barden et al.(1998) have found
the self-reported rate of antibiotic
prescriptions which could have
been omitted without impairing
patient care was
10-50%
14. Suggested targets for economising
antibiotic use:
•Non-specific URTI (essentially viral)
•Non-streptococcal pharyngitis (GABHS are the only
common bacterial cause representing <15% of cases)
•Acute ‘cough illness’
•Asthma (antibiotics rarely alter the course of acute
episodes)
•Secretory otitis media
•Diarrhoeal diseases
15. Possible reasons for antibiotic overuse:
DIAGNOSTIC DIFFICULTY:
*Clinical
*Lack of rapid reliable tests
*Reluctance to use diagnostic tests (parent stress, cost,
time,etc)
AVOID DELAY IN STARTING THERAPY:
*Awaiting test results
*2ry bacterial infection in known viral illnesses
PARENT REQUESTS
‘IT WON’T HARM’
17. B lactam group
•Penicillins
•Cephalosporins
•Monobactams
•Carbapenems
*Contain B-lactam ring
*Inhibit cell wall synthesis
osmotic lysis
*Low toxicity (?CNS
stimulation?)
*Allergy is rare but may be
serious
*Elimination primarily renal
(exceptions)
19. B lactam group
•Penicillins PENICILLINASE INHIBITORS
•Sulbactam / Ampicillin
•Clavulinate / Amoxycillin.
•Used to overcome resistance due
to Penicillinase production:
Staph, some Gm-ve(H.influenza, Moraxella,
E.coli, Kleb. ) and anaerobes(B.fragilis)
•Tazobactam / Piperacillin
20. B lactam group
•Penicillins
•Cephalosporins
B lactam ring is
more protected
less sensitive to B
lactamases
Oral forms more
palatable
21. B lactam group
•Penicillins
•Cephalosporins
+B.fragilis
H.influenza incl
penicillinase
producers (less
with cephamandol)
++CSF penetr by
Cefuroxime not
Cefamandol
22. B lactam group
•Penicillins
•Cephalosporins
*less G+ esp Staph
*NOT for enterococci
&Listeria
*++G- bacilli
including some
aminoglycoside R
*Variable: Pseudomon
&Bacteroides
Dual
Excr
CNS
ACQUIRED RESISTANCE TO ONE
INVOLVES THE WHOLE GROUP
23. B lactam group
•Penicillins
•Cephalosporins
•Monobactams
•Carbapenems
24. B lactam group
•Penicillins
•Cephalosporins
•Monobactams
•Carbapenems
Aztreonam
25. B lactam group
•Penicillins
•Cephalosporins
•Monobactams
•Carbapenems
Imipenem/ Cilastatin
*Now approved for neonates
*CNS irrit esp with
meningitis
*Renal elim blocked by
Cilastatin
Meropenem
26. AMINOGLYCOSIDES
*Irreversible binding to 30S -- ptn synthesis
*Active against Gm –ve bacilli
*Anaerobes, streptococci & pneumococci are
RESISTANT
*Synergism with B-lactams if given 1-2h after them
*Gram –ve resistance due to inactivating enz varies
within the group
*Ototoxicity nephrotoxicity
*Cleared exclusively by Glomerular filtration
27. MACROLIDES
*Prevent peptide bond formation by blocking the
action of peptidyl-transferase at 50S
*Concentrated in tissues esp. Azithromycin &
Clarithromycin
*Azithromycin has good GIT tolerance & no
hepatic interactions
*Broad spectrum includes most G+ve , atypical
pathogens: ( intracellular , no cell wall)
Chlamydia ,
Mycoplasma & Legionella
28. CHLORAMPHENICOL
*Irreversible binding to 30S -- ptn synthesis
*Active against Anaerobes
Atypicals
Gm +ve
. Gm –ve but not Pseudomonas
*Excellent CSF penetration
*Toxicity limits its use esp in neonates
*Thiamphenicol may be less toxic
29. VANCOMYCIN
*Glycopeptide which blocks formation of the
peptide portion of peptidoglycan
*Most Gm +ve including:
MRSA
Pneumococci including multiresistant
Clostridia including Cl difficile
Enterococci ( resistance escalating)
*Ototoxic , Nephrotoxic , Red Man Syndrome
30. SULPHONAMIDE + TMP
Co-Trimexazole
*Combination is bactericidal
*Effective in Gm –ve
QUINOLONES
*Concern about joint damage not confirmed in
humans
*Covers most Gm –ve & some Staph & Strept
*CNS: dizziness , confusion
31. IDENTIFY ORGANISM
•Culture & sensitivity
•Common pathogens by
disease & age
•Common pathogen by
Procedure & place
DRAWBACKS OF C/S
*Delay in results
*Financial factors
*Inaccuracy
-Contamination (pt or lab)
-Antibiotic ttt
-Incomplete testing for all AB
-Anaerobes & fungi
*Don’t change a
clinically effective ttt
*Don’t step-up
unless sensitivity is
higher
