antibiotics
Post on 06-Aug-2015
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SELECTIVE TOXICITYAction 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:
SELECTIVE TOXICITYInhibition 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
BACTERIAL RESISTANCEto 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)
BACTERIAL RESISTANCEto Antibiotics
SPREAD OF RESISTANCE*Generational
*Selection pressure
*Plasmid transfer
BACTERIAL RESISTANCEto Antibiotics
SPREAD OF RESISTANCE*Generational
*Selection pressure
*Plasmid transfer
BACTERIAL RESISTANCEto Antibiotics
SPREAD OF RESISTANCE*Generational
*Selection pressure
*Plasmid transfer
R
BACTERIAL RESISTANCEto 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
BACTERIAL RESISTANCEto 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?
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
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%
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
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’
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)
•Penicillins
*Benzyl penicillin
*Procaine penicillin &Benzathine penicillin
*Phenoxymethyl penicillin
*Broad – spectrum Ampicillin & Amoxycillin
*Penicillinase Resistant Methicillin & Flucloxacillin
* AntiPseudomonal Carbenicillin & Piperacillin
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
B lactam group•Penicillins
•Cephalosporins
B lactam ring is more protected less sensitive to B lactamases
Oral forms more palatable
B lactam group•Penicillins
•Cephalosporins+B.fragilis
H.influenza incl penicillinase producers (less with cephamandol)
++CSF penetr by Cefuroxime not Cefamandol
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
B lactam group•Penicillins
•Cephalosporins
•Monobactams
•Carbapenems
Imipenem/ Cilastatin*Now approved for neonates
*CNS irrit esp with meningitis
*Renal elim blocked by Cilastatin
Meropenem
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
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
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
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
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
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
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