抗生素英文课件精品- Antibiotics典型实例.pptVIP

AmpC ?-Lactamases Produced by almost all gram-negative bacteria Chrosomally encoded versions important in Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Morganella morganii, Pseudomonas aeruginosa and Serratia marcescens (not found in Salmonella and Klebsiella) AmpC ?-Lactamase genes have been found on transferable plasmids Class C ?-Lactamases All ?- lactams induce AmpC ?-lactamase production Only carbapenems are resistant to AmpC ?-lactamases If there is loss of porins as well, this will lead to carbapenem resistance Other ?- lactams will be hydrolysed Metallo-?-Lactamases Require Zinc or other heavy metal for activity Hydrolyse all ?-Lactams including carbapenems Most will be associated with resistance to many antibiotic classes Currently New Delhi Metallo-?-Lactamase (NDM-1) is a new flavour in the UK Associated with India Resistant to almost all antibiotics in use in the UK Aminoglycosides Highly positively charged compounds, concentration dependent activity Inhibit bacterial protein synthesis by irreversibly binding to 30S ribosomal unit Naturally occurring: Streptomycin Neomycin Kanamycin Tobramycin Gentamicin Semisynthetic derivatives: Amikacin (from Kanamycin) Netilmicin (from Sisomicin) 30S Ribosomal Unit Blockage by Aminoglycosides Causes mRNA decoding errors Block mRNA and transfer RNA translocation Inhibit ribosome recycling Ribosome recycling follows the termination of protein synthesis Spectrum of Activity Gram-Negative Aerobes Enterobacteriaceae; E. coli, K. pneumoniae, Proteus sp. Citrobacter, Enterobacter sp. Morganella, Providencia, Serratia Pseudomonas aeruginosa Acinetobacter Gram-Positive Aerobes (Usually in combination with ?-lactams) S. aureus and coagulase-negative staphylococci Viridans streptococci Enterococcus sp. (gentamicin) Mechanisms of Resistance Ribosome changes Prevents binding Loss of cell permeability Expulsion by efflux pumps Enzyme inactivation by Aminoglycoside modifying enzymes This