Treatment failures secondary to in vivo development of drug resistance by microorganisms

In two patients development of resistance to antibiotics by initially sensitive infecting organisms was associated with relapse or persistence of active infection. The first patient developed Staphylococcus epidermidis resistant to chloramphenicol during therapy with this agent for an infection that followed a cerebrospinal fluid shunt, and the second patient developed bacteremia due to ampicillin-resistant Salmonella during therapy with ampicillin. Treatment failure resulting from in vivo development of resistance to antimicrobial agents has been described for most of the major classes of antiinfective drugs and for numerous microorganisms. Although in many of these instances reinfection with a resistant organism cannot be excluded, there are many examples of apparent mutation or initial infection with both sensitive and resistant bacterial populations that is followed by selective multiplication of the resistant population or acquisition of resistance by an initially sensitive infecting organism. This phenomenon can be a cause of treatment failure and has appeared in patients in whom, by available tests, drug levels were found adequate. Isolation days after the institution of antimicrobial therapy of what appears to be the same organism as was initially recovered should prompt repeated sensitivity tests, at least to the agents being administered, if the patient's clinical course has not been one of satisfactory improvement.