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 foreign body infections, bacteria may multiply less optimally. We examined the effects of several classes of lipophilic antistaphylococcal agents to determine their antimicrobial activity towards coagulase-positive and coagulase-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 bacteria in the log phase, in which a variety of antibiotics produced relevant killing. Concerning the staphylococci examined, antibiotic killing was greatly dependent on the growth rate. Most of the two-fold combinations containing 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 chemotherapeutic agents for established bacterial infections and infections involving foreign bodies are discussed. Antimicrobial combinations including rifampicin and a second lipophilic antistaphylococcal drug may be most promising and appropriate as coating substances for intravascular devices or for clinical application in cases of implant infections.