View
427
Download
7
Category
Preview:
DESCRIPTION
Citation preview
Antibiotics : Use and overuse
KM MuraliMD (Med), DM (Neph), DNB (Neph), F Neph (Canada)
Consultant NephrologistMIMS, Kozhikode
First world war
Second world war
Cold war
Man
vs
Microbe
Timeless war
Spread of “jewish poison”
Anton V Leeuwenhock : “animalcules”
1674 AD
Louis Pasteur: “germ theory of disease”
1857
1822 - 1895
Gram Staining
Gram Positive
Staphylococci Coagulase + ve
Coagulase - ve
Streptococci
Enterococci
Gram +ve bacilli
Gram +ve anaerobes
Gram Positive Gram Negative
EnterobacteriaceaeEschericiae
Klebsiellae Proteaceae
Pseudomonas
Vibrio
Hemophilus
Others
Gram Staining
Staphylococci Coagulase + ve
Coagulase - ve
Streptococci
Enterococci
Gram +ve bacilli
Gram +ve anaerobes
The “antibiotic surge”
• Penicillin 1941
• Streptomycin 1944
• Tetracycline 1948
• Erythromycin 1952
• Vancomycin 1958
• Methicillin 1959
• Gentamicin 1962
“...... It’s time to close the book on infectious
diseases, the war against pestilence is over”
William Stewart, Surgeon General
Message to US Congress, 1969
Antibacterial weaponry
Penicillins Fluoroquinolones
Cephalosporins Macrolides
Monobactams Sulfonamides
Carbopenams Streptogramins
Aminoglycosides Oxazolidinediones
Glycopeptides Others
+
DNA
DNA-RNA polymerase
Cell wall
Cell membrane
Protein synthesis
Folate synthesis
PABA
DHFA
THFA
Penicillin and beta-lactam ring
• The prototype Penicillin G
• Acid resistant Penicillin V
• Penicillinase resistant Methicillin, Oxacillin
• “Broad Spectrum” Amoxicillin, Ampicillin
• “Antipseudomonas” Azlocillin, piperacillin• Combinations Augmentin, Timentin• (+ -lactamase inhibitor)
The big penicillin family
Penicillin vs Cephalosporin
Penicillin vs Cephalosporin vs Carbapenams
Penicillin vs Aztreonam
Penicillin vs Vancomycin
“Excessive use of penicillin can lead to its resistance”
- Sir Alexander Fleming (1941)
Preliminary reports of resistance
• Penicillin 1941 1942
• Streptomycin 1944 1946
• Tetracycline 1948 1952
• Erythromycin 1952 1955
• Vancomycin 1958 1990
• Methicillin 1959 1968
• Gentamicin 1962 1975
• Ciprofloxacin 1988 1989
Staphylococcus aureus PCN resistance
0
5
10
15
20
25
30
1990 1992 1994 1996 1998 2000
Year
Non ICU
ICU
Enterococcus Vancomycin resistance
0
5
10
15
20
25
30
35
40
Ove
rall
Per
cent
Res
ista
nce
PCN ERY CLINDA TET TMP-SMX
1994-19951997-19981999-2000
Streptococcus antibiotic resistance
RESISTANCE : Survival of the fittest
Revertant
ResistantCompensatory mutations
Passages
Categories of resistance
Acquired
Staphylococci
Streptococci
Gram –ve cocci
Enterobacteriaceae
Intrinsic
Pseudomonas
Enterococci
Categories of acquired resistance
• Mutational
• Single drug
• Low level resistance
• Surpassable
Transferable
Often multiple drugs
High level resistance
Unsurpassable
• Enzymatic inactivation of drug
Biochemical basis of drug resistance
Beta – lactamase opens penicillin ring
Beta - lactamase
Penicillinase
Oxacilinase
Cephalosporinase
Carbenicilinase
Carbapenamase
ESBL
Beta – lactamase inhibitors
• Flucloxacillin
• Clavulanate
• Sulbactam
• Tazobactam
• Enzymatic inactivation of drug
• Alteration of drug target
Biochemical basis of drug resistance
• Penicillin binding proteins (PBPs)– Streptococcus pneumoniae (penicillin)– Staphylococcus aureus (MRSA, nafcillin; mecA gene)
• Ribosomal binding site (23S rRNA)– Streptococcus pneumoniae, Helicobacter pylori (macrolides)
• DNA gyrase– Gram negative bacteria (quinolones)
• Cell wall precursor targets– Vancomycin resistant enterococci (VRE)
Alteration of Drug Target
Vancomycin resistance in enterococcus
• Enzymatic inactivation of drug
• Alteration of drug target
• Changes in drug uptake or efflux
Biochemical basis of drug resistance
The toughest enemy: Pseudomonas
Pseudomonas: Efflux pump
Conspiracy: Sharing of intelligence
Pseudomonas
Enterobacteriacea
Campylobacter
Staphylococci
Enterococci
Streptococci
Man vs Microbe : Are we lost ??
• We are not winning
• But let us not lose
• Let us not overuse antibiotics
Physician practices in antibiotic use
• 2/3 of outpatient antibiotic use is avoidable
• 40% inpatient antibiotic selection incorrect
• Costly antibiotics being overused
Ground realities in Indian scenario
• Poor awareness about sample collection
• Poor microbiological infrastructure
• Low yield of blood culture
• Low yield of anaerobic bacteriae
• Lack of faith in laboratory reports
EMPIRICAL ANTIBIOTIC THERAPY
IS DIRECTED AGAINST THE MOST PROBABLE PATHOGEN……………..
NOT AGAINST ALL PATHOGENS !!!
BUT THEN CULTURES SHOULD FOLLOW
Empirical initiation of therapyEmpirical completion of therapy
ICU Antibiotic cocktail
• One for gram positive
• One for gram negative
• One for anaerobe
• One for ‘atypical’
• One for the master and one for the dame !!
Practical solutions
• Prevention of infection
• Give only essential treatment
• Monitoring policies
Preventing infections
• Universal precautions
• Hand washing
• Avoid non-essential lines and tubes
• Isolation of patients infected with muti-drug resistant pathogens
Essential treatment
• Use the right antibiotic
• Avoid broad spectrum antibiotic
• Use the right dose
• Use for the right time
Monitoring policies
• Infection control surveillance
• Bacteriological surveillance
• Prescription surveillance
Thank you Thank you
Recommended