Therapy of intracellular Staphylococcus aureus by tigecyclin

Abstract

BackgroundIn the fields of traumatology and orthopaedics staphylococci are the most frequently isolated pathogens. Staphylococcus aureus and Staphylococcus epidermidis are known to be the major causative agents of osteomyelitis. The increasing number of multiresistant Staphylococcus aureus and resistant coagulase-negative staphylococci as a trigger of complicated osteomyelitis and implant-associated infections is a major problem. Antibiotic therapy fails in 20% of cases. Therefore the development of novel antibiotics becomes necessary.MethodsThis study analyses tigecyclin, the first antibiotic of the glycylines, as a potential therapy for osteomyelitis caused by multiresistant Staphylococcus aureus. Therefore its intracellular activity and the potential use in polymethylmetacrylate-bone cement are examined. The intracellular activity of tigecyclin is determined by a human osteoblast infection model. The investigation of the biomechanical characteristics is conducted concerning the ISO 5833-guidelines.ResultsTigecyclin shows in vitro an intracellular activity that ranges between the antimicrobial activity of gentamicin and rifampicin. A significant negative effect on the biomechanical characteristics with an impaired stability is detected after adding tigecyclin to polymethylmetacrylate-bone cement with a percentage of 1.225% per weight.ConclusionsThis study shows that tigecyclin might be a potent alternative for the systemic therapy of osteomyelitis and implant-associated infections whereas the local application has to be reconsidered individually.

Rifamycin Derivatives Are Effective Against Staphylococcal Biofilms In Vitro and Elutable From PMMA

“…Assays were performed in triplicate. Intracellular invasion assays were performed to evaluate the effectiveness of rifamycins against internalized S. aureus, as previously described [33]. Briefly, osteoblasts were seeded in 24-well plates at 2 9 10 4 cells/mL and infected with S. aureus at a concentration corresponding to a multiplicity of infection of 50.…”

Staphylococcus aureus vs. Osteoblast: Relationship and Consequences in Osteomyelitis

“…Recent studies investigated the effect of tigecyclin, teicoplanin, ofloxacin, and linezolid. These antibiotics—which are recommended in the treatment of osteomyelitis—have an intermediate intracellular antimicrobial effectiveness, higher than gentamicin or vancomycin and lower or equivalent to rifampicin (Kreis et al, 2013 ; Valour et al, 2015a ). Ofloxacin, daptomycin, and vancomycin were also deemed to limit intracellular SCVs emergence (Valour et al, 2015a ).…”

In vitroantibiotic activity against intraosteoblasticStaphylococcus aureus: a narrative review of the literature

“… 34 , 51 , 52 However, studies on macrophages and fibroblasts have shown that prolonged cell exposure allowed an increase in the aminoglycosides’ C/E ratio up to 2 to 4. 53 A time-dependent activity of gentamicin at 10 mg/L on S. aureus intracellular load was consequently highlighted, 54 sustained in the chronic model. 25 Because gentamicin is not able to diffuse into cells, its ability to target intracellular S. aureus could be due to infection-related pinocytosis allowing gentamicin to penetrate concomitantly in the same subcellular compartment as the bacteria.…”