title: Bioluminescence and 19F magnetic resonance imaging visualize the efficacy of lysostaphin alone and in combination with oxacillin against Staphylococcus aureus in murine thigh and catheter-associated infection models.
abstract: Staphylococci are the leading cause of hospital-acquired infections worldwide. Increasingly, they resist antibiotic treatment owing to the development of multiple antibiotic resistance mechanisms in most strains. Therefore, the activity and efficacy of recombinant lysostaphin as a drug against this pathogen have been evaluated. Lysostaphin exerts high levels of activity against antibiotic-resistant strains of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). The therapeutic value of lysostaphin has been analyzed in two different clinically relevant in vivo models, a catheter-associated infection model and a thigh infection model. We infected mice with luciferase-expressing S. aureus Xen 29, and the efficacies of lysostaphin, vancomycin, oxacillin, and combined lysostaphin-oxacillin were investigated by determining numbers of CFU, detecting bioluminescent signals, and measuring the accumulation of perfluorocarbon emulsion at the site of infection by (19)F magnetic resonance imaging. Lysostaphin treatment significantly reduced the bacterial burden in infected thigh muscles and, after systemic spreading from the catheter, in inner organs. The efficiency of lysostaphin treatment was even more pronounced in combinatorial therapy with oxacillin. These results suggest that recombinant lysostaphin may have potential as an anti-S. aureus drug worthy of further clinical development. In addition, both imaging technologies demonstrated efficacy patterns similar to that of CFU determination, although they proved to be less sensitive. Nonetheless, they served as powerful tools to provide additional information about the course and gravity of infection in a noninvasive manner, possibly allowing a reduction in the number of animals needed for research evaluation of new antibiotics in future studies.
authors.affiliation: Institute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hertlein
authors.forename: Volker
authors.initials: V
authors.lastname: Sturm
authors.forename: Udo
authors.initials: U
authors.lastname: Lorenz
authors.forename: K
authors.initials: K
authors.lastname: Sumathy
authors.forename: Peter
authors.initials: P
authors.lastname: Jakob
authors.forename: Knut
authors.initials: K
authors.lastname: Ohlsen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D055499:Catheter-Related Infections / Q000188:drug therapy*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D005462:Fluorine Radioisotopes; D008163:Luminescent Measurements / Q000379:methods; D008248:Lysostaphin / Q000008:administration & dosage / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D010068:Oxacillin / Q000008:administration & dosage / Q000627:therapeutic use*; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013848:Thigh / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D005462:Fluorine Radioisotopes; D008248:Lysostaphin; D010068:Oxacillin