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THE BASICS OF CLINICAL RELEVANCE Feb 2007 Dr W Lowman Objectives • 1. Correlate the physicochemical properties of the gram-negative cell wall, with the clinically relevant pathogenetic and virulence factors of gram-negative bacteria. 1. 2. List the key differences between the gram-positive and gram-negative cell wall. 3a. Understand the complexity of the interaction between the cell wall and antimicrobials. 3b. Relate this interaction to the clinical phenomenon of antibiotic resistance. Feb 2007 Dr W Lowman G- cell wall Cytoplasmic membrane Periplasmic space Peptidoglycan Outer membrane -LPS Feb 2007 Dr W Lowman Feb 2007 Dr W Lowman Nomenclature • Family- Enterobacteriaceae • Genus- Escherichia; Escherichia • Species- coli; coli Pseudomonas aeruginosa Klebsiella pneumoniae Feb 2007 Dr W Lowman ID principles • Based on phenotypic criteria in routine clinical laboratory. - growth characteristics; cell morphology & staining; biochemical reactions; serological reactions • Molecular methods more precise but primarily used for taxonomic purposes. - G+C% content; DNA-DNA hybridization; 16S rRna Feb 2007 Dr W Lowman Bacteria & oxygen (O2) SPECTRUM Obligate AnO2 Strict Aerotolerant Microaerophile Moderate Faculatative Anaerobe ABILITY TO TOLERATE & GROW IN PRESENCE OF OXYGEN (ENERGY- OXYGEN USED AS TERMINAL ELECTRON ACCEPTOR) Feb 2007 Dr W Lowman Obligate Aerobe Feb 2007 Dr W Lowman Clinical spectrum Infections • Community-acquired • Nosocomial-acquired Not always clear-cut. Term ONSET may be more appropriate “Healthcare-associated infection” Feb 2007 Dr W Lowman Community-acquired • GIT infections- diarrhoeal illness - Salmonella, Shigella, E.coli, Yersinia - Outbreaks NB! Feb 2007 Dr W Lowman Community-acquired • • • Urinary tract infections E.coli Proteus spp. Lower respiratory tract infections Wound/ SSTI Feb 2007 Dr W Lowman Nosocomial infections • ANYTHING • NB! in terms of antibiotic resistance. • Most resistant organisms typically found in this group. • Empiric treatment becomes an important challenge and requires informed guesswork. Antibiotic susceptibilities Pathogen(s) Feb 2007 Dr W Lowman Antibiotic resistance Penetration Enzymes Binding Feb 2007 Dr W Lowman ANTIBIOTICS ARE NOT THE ANSWER! Feb 2007 Dr W Lowman Feb 2007 Dr W Lowman