We extensively studied the epidemiology and time course of endemic methicillin-resistant Staphylococcus aureus (MRSA) in the Millard Fillmore Hospital, a 600-bed teaching hospital in Buffalo. The changeover from methicillin-susceptible S. aureus to MRSA begins on the first hospital day, when patients are given cefazolin as presurgical prophylaxis. Under selective antibiotic pressure, colonizing flora change within 24 to 48 hours. For patients remaining hospitalized, subsequent courses of third-generation cephalosporins further select and amplify the colonizing MRSA population. Therefore, managing antibiotic selective pressure might be essential. Other strategies include attention to dosing, so that serum concentrations of drug exceed the minimum inhibitory concentration, and antibiotic cycling. Although there are some promising new antibiotics on the horizon, it is necessary to deal with many resistance patterns by using the combined strategies of infection control and antibiotic management.
In 64 adults treated with gentamicin sulfate, peak and trough serum concentrations rose gradually and declined in two phases after the final dose. Seventeen patients experienced renal damage. The 17 patients had greater amounts of gentamicin in tissues even after the first dose and before any renal effects were noted. This pharmacokinetics analysis provided evidence that patients who experience gentamicin-related nephrotoxic effects while receiving recommended doses of gentamicin could be distinguished from patients with no toxic effects because they experienced abnormal tissue accumulation before detectable changes in renal function occurred.
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