Antibiotic therapy - Antibiotic Therapy and Resistance...

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Antibiotic Therapy and Resistance Patterns in ICU Ajay Handa Dept of Pulmonary Medicine PGIMER
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Aspects • Antibiotic resistance •E S B L • Genetic basis • Infection control policies • Antibiotic control policies • Antibiotic therapy • Future directions
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Antibiotic resistance • Past six decades more than 15 classes of systemic antimicrobials have been introduced into clinical practice • Greatest strides have been made with improvement of hygiene and social conditions !! • Antibiotic armamentarium is being lost rapidly due to bacterial resistance ,which can be disastrous (pre-antibiotic era )
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Historical Aspects • 1941 Albert Alexander first recepient of penicillin • 1942 first resistant isolates of Staph aureus reported • 1960 Methicillin introduced • 1964 first MRSA reported • 1980s MRSA became major nosocomial infection
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Historical aspects • 1980s –ESBL producing GN bacteria • 1990 Vancomycin resistant Enterococci emerged • 2000 VISA (intermediate level resistance) • 2002-VRSA (high level resistance) • 2002- Linezolid resistant enterococci and Staphylococci reported
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Antibiotic resistance • Bacterial response to antimicrobial may be rapid or slow onset of resistance • Once resistance develops in one part of world others should anticipate it. • Antibiotic resistance is greatest in ICU large teaching hosp and medical centers and spreads to general wards and smaller hosp
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ICU: the" hotspots” • Greater severity of illness • Increased use of invasive devices • Colonization /infection by multiresistant bacteria • Empirical use of antibiotics • Relative overcrowding • Health care staff busy • Promotes spread from patient to patient
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Antibiotic resistance • Resistant strains are as virulent as their susceptible relatives and cause higher morbidity/mortality. • For every new drug introduced there are resistance mechanism in the bacteria waiting to emerge “Depressing evolutionary progress”
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Resistance equation • Risk of emergence antibiotic resistance genetic selection Antibiotic pressure Risk of cross infection
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Genetic basis Genetic selection underlies all resistance Some single amino acid substitution by mutation (ESBL) are rapid and some need multiple genes to cause resistance (VRE) • Mutations • Plasmids • Transposons • Integrons
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Beta Lactamases • Major defence of GNB against B lactams • Hundreds have co-evolved with newer drugs • Spread from Staphylococci to H Influenzae and N gonorrhoeae • With over-use of new B lactams in last 2 decades “new” Extended spectrum beta lactamases(ESBLs), carbapenemases
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Beta Lactamases • Classified based on Prim structure – Class A (Serine residue) – Class B (metallo-enzyme) – Class C (Serine residue) – Class D (Serine residue) • Class B&C - encoded by chromosomal genes
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New Beta lactamases • TEM type ESBL • SHV type ESBL • CTX type ESBL • OXA type ESBL • Plasmid mediated Amp C enzymes • Carbapenemases
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Antibiotic therapy - Antibiotic Therapy and Resistance...

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