CASE HISTORY
Harrison was a 73-year-old man with kidney failure.He was admitted to the hospital with fever and hypotension,both of which are symptoms of bacteremia.When bacteria from Harrison's blood were grown on horse blood agar,it showed colonies typical of methicillin-resistant Staphylococcus aureus (MRSA)and confirmed the diagnosis of bacteremia.Further investigation uncovered his home dialysis line as the source of MRSA.He was treated with intravenous vancomycin (an antibiotic that targets cell wall synthesis),but the bacteremia persisted.The bacteria were tested and found to be partly resistant to vancomycin,though sensitive to rifampin (which targets RNA polymerase),ciprofloxacin (which targets DNA gyrase),and linezolid (which targets protein synthesis).The vancomycin was discontinued,and therapy was begun with rifampin,ciprofloxacin,and linezolid.Harrison's symptoms improved,but within three weeks the bacteremia returned.Bacteria cultured from his blood now showed resistance to rifampin and ciprofloxacin.Linezolid was administered alone for six weeks,but five days after linezolid treatment ended,the bacteremia recurred.Linezolid was administered again,for another six weeks.Then a new blood culture revealed a form of MRSA with small colonies.The small-colony variant was partly resistant to linezolid while fully resistant to all the other antibiotics.Harrison was now treated with trimethoprim-sulfamethoxazole.These final antibiotics had to be administered indefinitely,as they could not fully eliminate MRSA from Harrison's system.
A laboratory technician cultures the small-colony form of MRSA for 100 generations on agar media without antibiotics,selecting the largest colony for passage at each generation.Would you predict the 100th generation would be more or less resistant to linezolid than the isolate from Harrison's highly resistant infection?

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The Answer of CASE HISTORY
Harrison was a 73-year-old man with kidney failure.He was admitted to the hospital with fever and hypotension,both of which are symptoms of bacteremia.When bacteria from Harrison's blood were grown on horse blood agar,it showed colonies typical of methicillin-resistant Staphylococcus aureus (MRSA)and confirmed the diagnosis of bacteremia.Further investigation uncovered his home dialysis line as the source of MRSA.He was treated with intravenous vancomycin (an antibiotic that targets cell wall synthesis),but the bacteremia persisted.The bacteria were tested and found to be partly resistant to vancomycin,though sensitive to rifampin (which targets RNA polymerase),ciprofloxacin (which targets DNA gyrase),and linezolid (which targets protein synthesis).The vancomycin was discontinued,and therapy was begun with rifampin,ciprofloxacin,and linezolid.Harrison's symptoms improved,but within three weeks the bacteremia returned.Bacteria cultured from his blood now showed resistance to rifampin and ciprofloxacin.Linezolid was administered alone for six weeks,but five days after linezolid treatment ended,the bacteremia recurred.Linezolid was administered again,for another six weeks.Then a new blood culture revealed a form of MRSA with small colonies.The small-colony variant was partly resistant to linezolid while fully resistant to all the other antibiotics.Harrison was now treated with trimethoprim-sulfamethoxazole.These final antibiotics had to be administered indefinitely,as they could not fully eliminate MRSA from Harrison's system.
A laboratory technician cultures the small-colony form of MRSA for 100 generations on agar media without antibiotics,selecting the largest colony for passage at each generation.Would you predict the 100th generation would be more or less resistant to linezolid than the isolate from Harrison's highly resistant infection?