Killing effects of antibiotics and two-fold antimicrobial combinations on proliferating and non growing staphylococci

Antimicrobial agents are generally tested against bacteria in the log phase of multiplication to produce the maximal bactericidal effect. In case of f oreign body infections, bacteria may multiply less optimally. We examined t he effects of several classes of lipophilic antistaphylococcal agents to de termine their antimicrobial activity towards coagulase-positive and coagula se-negative staphylococci during the non-growing and slowly growing phases. Only two-fold combinations containing rifampicin were bactericidal (3-log kill) against Staphylococcus aureus. This was in contrast to growing bacter ia in the log phase, in which a variety of antibiotics produced relevant ki lling. Concerning the staphylococci examined, antibiotic killing was greatl y dependent on the growth rate. Most of the two-fold combinations containin g rifampicin showed additive and synergistic antibacterial activity both in growth and stationary states as measured by the killing kinetics. The theoretical and clinical implications of delayed killing by chemotherap eutic agents for established bacterial infections and infections involving foreign bodies are discussed. Antimicrobial combinations including rifampic in and a second lipophilic antistaphylococcal drug may be most promising an d appropriate as coating substances for intravascular devices or for clinic al application in cases of implant infections.