超级细菌的发现、演变、结构、发病机理及预防(英文教学)案例实例.pptVIP

Clinical Utility ABx Route In vivo Efficacy Cross-Resistance AEs DAL IV Animal model of PCN-resistant NBPP Partial with vancomycin; clinical significance unclear Redman syndrome with TEL; Rare ? in platelets ORI IV High AUC:MIC ratios in ELF and plasma in murine NBPP TEL IV Good penetration into ELF and AMs in human volunteers; Phase III trial pending Gotfried M et al. ICAAC. 2005. Lehoux D et al. ICAAC. 2007. Novel Fluoroquinolone Garenoxacin (PO/IV) Bactericidal MIC90 = 0.06 ?g/mL for penicillin-, macrolide-, and ? 6 drug- resistant S. pneumoniae MIC90 = 1 ?g/mL for CIP- and LEV- resistant S. pneumoniae More potent than MOX Wu P et al. Antimicrob Agents Chemother. 2001. Jones RN et al. Diag Micro Infect Dis. 2007. * Polymyxins a group of polypeptide antibiotics that consists of 5 chemically different compounds (polymyxins A-E), were discovered in 1947 Only polymyxin B and polymyxin E (colistin) have been used in clinical practice the primary route of excretion is renal * Colistin The target of antimicrobial activity of colistin is the bacterial cell membrane Colistin has also potent anti-endotoxin activity The endotoxin of G-N bacteria is the lipid A portion of LPS molecules, and colistin binds and neutralizes LPS * Colistin Active: Acinetobacter species, Pseudomonas aeruginosa, Enterobacteriaciae * Colistin 160 mg (2 million IU) ever 8 h 240 mg (3 million IU) every 8 h for life-threatening infections AmpC and Extended-Spectrum ?-lactamase (ESBL) production are the most important mechanisms of ?-lactam resistance in nosocomial infections The antimicrobial and clinical features of these resistance mechanisms are highlighted in the following slides ?-Lactam Antibiotic Resistance ?-Lactam Resistance: AmpC Production Worldwide problem: Incidence increased from 17% to 23% between 1991 and 2001 in UK Very common in Gram-negative bacilli AmpC gene is usually sited on chromosomes, but can be present on plasmids Enzyme production is eithe