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

Abstract

Staphylococcus aureus – a major aetiological agent of bone and joint infection (BJI) – is associated with a high risk of relapse and chronicity, in part due to its ability to invade and persist in non-professional phagocytic bone cells such as osteoblasts. This intracellular reservoir protects S. aureus from the action of the immune system and most antibiotics. To date, the choice of antimicrobial strategies for BJI treatment mostly relies on standard susceptibility testing, bone penetration of antibiotics and their ‘antibiofilm’ activity. Despite the role of intracellular persistent S. aureus in the development of chronic infection, the ability of antibiotics to target the S. aureus intraosteoblastic reservoir is not considered in therapeutic choices but might represent a key determinant of treatment outcome. This review provides an overview of the intracellular pharmacokinetics of antistaphylococcal drugs used in the treatment of BJI and of their ability to target intraosteoblastic S. aureus. Thirteen studies focusing on the intraosteoblastic activity of antibiotics against S. aureus were reviewed, all relying on in vitro models of osteoblast infection. Despite varying incubation times, multiplicities of infection, bacterial strains, and the types of infected cell lines, rifamycins and fluoroquinolones remain the two most potent antimicrobial classes for intraosteoblastic S. aureus eradication, consistent with clinical data showing a superiority of this combination therapy in S. aureus orthopaedic device-related infections.

Neisseria gonorrhoeae Limits Chlamydia trachomatis Inclusion Development and Infectivity in a Novel In Vitro Co-Infection Model

“…However, gentamycin alone reduced CtE infectivity by 50%, potentially explaining the observed discrepancy. Gentamycin, though generally regarded as largely unable to penetrate host cells ( Tabrizi and Robins-Browne, 1993 ; Marro et al., 2021 ), has been shown to enter host cells and affect the growth/development of intracellular bacteria ( VanCleave et al., 2017 ). We suspect that the effect of gentamycin on CtE infectivity may have been ameliorated by Ng inoculum irreversibly binding gentamycin.…”

Microscopy-based phenotypic profiling of infection by Staphylococcus aureus clinical isolates reveals intracellular lifestyle as a prevalent feature

“…Overall, the phenotypic and genomic datasets from this comprehensive large-scale study constitute a valuable and unique resource to further delve into the complexity of S. aureus-host crosstalk. Moreover, this systematic understanding of S. aureus intracellularity has relevant implications for the management and treatment of staphylococcal infections, since many of the most commonly used antibiotics are ineffective against intracellular pathogens 64,65 . As such, even in cases of bacterial culture tests that show a broad antibiotic susceptibility, the lack of intracellular effect of the drugs might lead to treatment failure, relapse, or chronic infections.…”

LipoParticles: a lipid membrane coating onto polymer particles to enhance the internalization in osteoblast cells

“…In the context of BJIs, Staphylococcus aureus can survive intracellularly inside osteoblasts (the bone forming cells) and is thus protected from the activity of most antibiotics and from the immune system. 2,3 New antibiotics are regularly discovered and developed to fight staphylococcal infections. 4 However, in the specific context of intracellular Staphylococcus aureus, the ability of antibiotics to cross through the host cell membrane to attain intracellular localization is still an important issue that could explain the high rate of relapse in staphylococcal BJIs.…”

“…In the context of BJIs, Staphylococcus aureus can survive intracellularly inside osteoblasts (the bone forming cells) and is thus protected from the activity of most antibiotics and from the immune system. 2,3…”