Biofilm Formation is not Necessary for Development of Quinolone-Resistant “Persister” cells in an Attached Staphylococcus Epidermidis Population

Abstract

Staphylococcus epidermidis is a common pathogen in device-associated infections which is able to attach onto polymeric surfaces and develop multilayered biofilms. Attached S. epidermidis displays reduced susceptibility to antimicrobial agents. In this study we investigated the influence of ciprofloxacin and the group IV quinolones gatifloxacin, gemifloxacin, and moxifloxacin with the minimal attachment killing (MAK) assay. MAK concentrations were determined for three biofilm-positive wild-type strains and their isogenic biofilm-negative mutants Depending on strain and investigated quinolone, it was possible to distinguish between a heterogeneous MAK (MAKhetero), and a homogeneous resistance (MAKhomo) which corresponds to the model of a few persisting cells under antibiotic treatment. A lower MAKhomo was detected for the biofilm-negative mutants as well as for the corresponding wild-types for some of the tested quinolones, which seems to be a result of higher bacterial inocula, whereas the MAKhetero concentrations were comparable for mutants and wild-types for nearly all of the tested antibiotics and strains. These data indicate that biofilm formation is not necessary for persistence of attached S. epidermidis cells under treatment with quinolones and could explain therapeutic failure in foreign body-associated infections due to biofilm-negative S. epidermidis isolates. The individual resistance phenotypes of investigated strains indicate that the determination of MAK concentrations might help to predict the therapy outcome of foreign body-associated infections with both biofilm-positive and biofilm-negative S. epidermidis. Thus, the relatively high activity displayed by group IV quinolones against individual attached staphylococcal isolates indicates a possible treatment option with the respective quinolones for foreign body-associated infections due to these isolates. (Int J Artif Organs 2008; 31: 752–60)