TAILIEUCHUNG - Chapter 128. Pneumococcal Infections (Part 6)

Pneumococcal Infections: Treatment Antibiotic Susceptibility β-Lactam antibiotics, the cornerstone of therapy for serious pneumococcal infection, bind covalently to the active site and thereby block the action of enzymes (endo-, trans-, and carboxypeptidases) needed for cell-wall synthesis. Because these enzymes were identified by their reaction with radiolabeled penicillin, they are called penicillin-binding proteins. Until the late 1970s, virtually all clinical isolates of S. pneumoniae were susceptible to penicillin (., were inhibited in vitro by concentrations of . | Chapter 128. Pneumococcal Infections Part 6 Pneumococcal Infections Treatment Antibiotic Susceptibility 0-Lactam antibiotics the cornerstone of therapy for serious pneumococcal infection bind covalently to the active site and thereby block the action of enzymes endo- trans- and carboxypeptidases needed for cell-wall synthesis. Because these enzymes were identified by their reaction with radiolabeled penicillin they are called penicillin-binding proteins. Until the late 1970s virtually all clinical isolates of S. pneumoniae were susceptible to penicillin . were inhibited in vitro by concentrations of pg mL . Since then an increasing number of isolates have shown some degree of resistance to penicillin. Resistance results when spontaneous mutation or acquisition of new genetic material alters penicillin-binding proteins in a manner that reduces their affinity for penicillin thereby necessitating a higher concentration of penicillin for their saturation. The genetic information that renders pneumococci resistant to penicillin is acquired from oral streptococci and is transmitted along with genes that convey resistance to other antibiotics as well. Selection of antibiotic-resistant strains worldwide especially in countries where antibiotics are available without prescription and in loci of high antibiotic use such as day-care centers greatly contributes to the prevalence of multidrug resistance. At present 20 of pneumococcal isolates in the United States exhibit intermediate resistance to penicillin minimal inhibitory concentration MIC pg mL and 15 are resistant MIC pg mL Fig. 128-3 . The rate of resistance is lower in countries that by tradition are conservative in their antibiotic use . Holland and Germany and higher in countries where usage is more liberal . France . In Hong Kong and Korea resistance rates approach 80 . These definitions of resistance however were based on drug levels achievable in CSF during treatment of meningitis whereas

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