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An IV infusion started when the plasma concentration of the drug is zero will reach 94% of its plasma steady state after 4 half-lives or in this situation, 24 hours after the beginning of the infusion. With the vast majority of IV infusions, the rate of drug entry into the body is constant and most display first order elimination, which means that a constant fraction of the agent is cleared per unit time. In this situation, the half-life is constant and determines the rate at which a drug approaches steady state. Therefore, regardless of the rate of infusion, after one, two, and three half lives, a drug reaches 50%, 75%, and 87.5% of its final steady state concentration, respectively. Volume of distribution and rate of infusion are necessary for determining the final steady concentration but are not needed for solving how quickly a drug will reach that concentration. For convenience, in practice it is often assumed that after four half lives a drug reaches steady state even though in actuality it is only 94% of its final concentration. Bamberger et al. report that The National Nosocomial Infections Surveillance System found that 60 percent of hospital-acquired S. aureus isolates in 2003 were methicillin-resistant S. aureus (MRSA). They suggest that vancomycin should only be used for the treatment of methicillin-sensitive S. aureus (MSSA) in patients allergic to penicillins. Schilling et al. report that vancomycin is bactericidal against most gram-positive species, including streptococci and staphylococci, with the exception of the Enterococcus species, for which it is bacteriostatic. They state that although it is bactericidal, it appears to kill bacteria more slowly than beta-lactam antibiotics, and therefore it may take longer to clear bacteremia. Illustration A shows a graph reviewing number of half lives to reach steady state. Incorrect Answers: Answer 1: After one half life the concentration is 50% of the steady state. Answer 2: After two half-lives the concentration is 75% of the steady state. Answer 3: After three half-lives the concentration is 88% of the steady state. Answer 5: After five half lives the concentration is 97% of the steady state.
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