An in Vitro Test for Chemotherapeutic Agents used in Subacute Bacterial Endocarditis

Abstract

A number of methods have been used in attempting to evaluate the efficiency of drugs used in the treatment of subacute bacterial endocarditis. These may be grouped generally into two categories: in vivo and in vitro experiments. The in vivo method of evaluating drug action would be ideal if the characteristic valvular lesions of subacute bacterial endocarditis could be established unequivocally with the animal surviving. Further, the period of survival would have to be sufficiently long so that the efficacy of the therapeutic procedure instituted could be ascertained later at necropsy. Although several workers have reported the successful production of subacute bacterial endocarditic lesions in dogs,' and in rabbits,2 there is no certain way of determining the presence of valvular damage in the living animal. Accordingly experience with therapeutic procedures in the experimental animals has been limited. The testing of drug efficacy by determining the protective level following intraperitoneal injection of the offending organisms, may not accurately reflect the value of the drug, since intraperitoneal implants are readily accessible to both the drug and cellular factors of the body defense mechanism. In contradistinction, an endocarditic lesion is characterized in part by the presence of an outer zone of fibrin which may interfere with the penetration of a therapeutic agent, or prevent mobilization of cellular defense elements at the bacterial locus in the valve. Nevertheless, this small animal method affords a means of assaying the potential bactericidal or bacteriostatic action of drugs in the living organism especially as developed ecently.3 In vitro test methods offer an index of the degree of bactericidal or bacteriostatic power of a drug by its influence upon the bacterial growth curve characteristics. Perhaps the most reliable work employing this technic is that reported by Osgood,4 in which growth curves of bacteria inoculated into human marrow cultures are observed following the introduction of antibacterial agents. Yet, even this, as well as all other in vitro methods, is of limited value in studies of the action of agents upon the infective organism in subacute bacterial endocarditis, because of the unassayed r le of the fibrin barrier. This factor was