Population Dynamics of S. aureus Under Short Term Serial Antibiotic Treatment

Abstract

Population Dynamics of S. aureus Under Short Term Serial Antibiotic Treatment

During bactericidal antibiotic treatment of growing populations, a certain proportion of the total population survive. These surviving cells are often only phenotypically refractory to treatment rather than genetically resistant. In accordance with this phenomena, antibiotic treatments employing two drugs in parallel on growing populations have been investigated. The results of these two drug parallel treatments mirror the results found with single drugs in that, a fraction of the initial growing population surviving treatment in the vast majority of cases. While the trend of parallel drug usage during treatment of bacterial infections is becoming more prevalent, multidrug therapy is often currently used in a serial manner upon lack of empirical improvement among patients during the course of a bacterial infection. To investigate the implications of serial drug treatment upon bacterial population dynamics, we pose the question; would schedule rather than ad hoc serial drug treatment of growing S. aureus populations generate a larger reduction in the number of viable cells among an initially growing population? Through the use of antibiotic time-kill experiments, and four classes of bactericidal antibiotics, we were able to evaluate the in vitro efficacy of single-step serial treatments after initial population declines began. The results of these experiments indicate that serial drug treatments are no more effective than the single most effective drug(s) used at similar multiplicities of cidal units (cu). As such, over short time courses, initial susceptibility to, and efficacy of, a single drug is the predominate feature(s) in limiting initially growing populations and scheduled addition of a second drug provides little tangible benefit in a generally susceptible population.