Intraosteoblastic activity of levofloxacin and rifampin alone and in combination against clinical isolates of meticillin-susceptible Staphylococcus aureus causing prosthetic joint infection

Meléndez-Carmona, María Ángeles; Muñoz‐Gallego, Irene; Viedma, Esther; Lora‐Tamayo, Jaime; Cháves, Fernando

doi:10.1016/j.ijantimicag.2019.06.018

Cited by 14 publications

(24 citation statements)

References 20 publications

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“…Both antibiotics showed a significant CFU decrease (a log10 of CFU) compared to bacterial CFUs within untreated cells, whereas the combination did not show higher activity compared to levofloxacin monotherapy. Rifampin, alone and in combination with levofloxacin, showed a significant increase in the percentage of SCVs and a significant reduction in the number of intracellular CFUs in comparison with untreated osteoblast cells [111]. Dupieux et al (2017) demonstrated that, when using S. aureus strains to infect osteoblasts, daptomycin did not reduce MSSA number and was poorly active against MRSA.…”

Section: Antimicrobial Activity Against Intraosteoblastic Pathogensmentioning

confidence: 97%

Staphylococcus aureus Internalization in Osteoblast Cells: Mechanisms, Interactions and Biochemical Processes. What Did We Learn from Experimental Models?

et al. 2021

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Bacterial internalization is a strategy that non-intracellular microorganisms use to escape the host immune system and survive inside the human body. Among bacterial species, Staphylococcus aureus showed the ability to interact with and infect osteoblasts, causing osteomyelitis as well as bone and joint infection, while also becoming increasingly resistant to antibiotic therapy and a reservoir of bacteria that can make the infection difficult to cure. Despite being a serious issue in orthopedic surgery, little is known about the mechanisms that allow bacteria to enter and survive inside the osteoblasts, due to the lack of consistent experimental models. In this review, we describe the current knowledge about S. aureus internalization mechanisms and various aspects of the interaction between bacteria and osteoblasts (e.g., best experimental conditions, bacteria-induced damages and immune system response), focusing on studies performed using the MG-63 osteoblastic cell line, the best traditional (2D) model for the study of this phenomenon to date. At the same time, as it has been widely demonstrated that 2D culture systems are not completely indicative of the dynamic environment in vivo, and more recent 3D models—representative of bone infection—have also been investigated.

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Section: Antimicrobial Activity Against Intraosteoblastic Pathogensmentioning

confidence: 97%

Staphylococcus aureus Internalization in Osteoblast Cells: Mechanisms, Interactions and Biochemical Processes. What Did We Learn from Experimental Models?

et al. 2021

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“…Rifampicin has been evaluated in combination with levofloxacin, tigecycline and vancomycin, with no clear advantages of combinations. 27 , 28 , 54 This observation might be due to the already optimal activity of rifampicin alone in this model.…”

Section: Pharmacokinetics and Intraosteoblastic Activity Of Antistaphylococcal Antibioticsmentioning

confidence: 81%

“…62 , 72 , 73 In the acute infection model, rifampicin killed more than 99.9% of intraosteoblastic bacteria in a time-dependent manner after 20–48 h, 21 , 26 , 54 , 74 even though less-impressive results have been reported in another study. 27 In the study by Ellington et al ., 21 efficacy of rifampicin rapidly decreased as the bacterial intracellular persistence time increased. However, maintained rifampicin efficacy in the chronic infection model has been reported.…”

Section: Pharmacokinetics and Intraosteoblastic Activity Of Antistaphylococcal Antibioticsmentioning

confidence: 97%

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

Marro

Abad

Blocker

et al. 2021

Journal of Antimicrobial Chemotherapy

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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.

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“…Both antibiotics showed a significant CFU decrease (a Log10 of CFU) compared to bacterial CFUs within untreated cells, whereas the association did not show higher activity compared to levofloxacin monotherapy. Rifampin, alone and in combination with levofloxacin, showed a significant increase in the percentage of SCVs and a significant reduction in the number of intracellular CFUs in comparison with untreated osteoblast cells (Meléndez-Carmona et al, 2019). Dupieux et al (2017) demonstrated that using S. aureus strains to infect osteoblast, daptomycin did not reduce MSSA number and was poorly active against MRSA.…”

Section: Figurementioning

confidence: 99%

<em>Staphylococcus aureus</em> Internalization in Osteoblast Cells: Mechanisms, Interactions and Biochemical Processes. What did We Learn from Experimental Models?

Musso¹,

Stracquadanio²,

Costantino³

et al. 2020

Preprint

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Bacterial internalization is a strategy that non-intracellular microorganisms use to escape the host immune system and survive inside the human body. Among bacteria species, Staphylococcus aureus showed ability to interact and infect osteoblasts causing osteomyelitis as well as bone and joint infection, while also becoming increasingly resistant to antibiotic therapy and a reservoir of bacteria that can make the infection difficult to cure. Despite being a serious issue in orthopedic surgery, little is known about the mechanisms that allow bacteria to enter and survive inside the osteoblasts, also due to the lack of consistent experimental models. In this review, we describe the current knowledge about S. aureus internalization mechanisms and various aspects of the interaction between bacteria and osteoblasts (e.g. best experimental conditions, bacteria-induced damages and immune system response), focusing on studies performed using the MG-63 osteoblastic cell line, so far the best model for the study of this phenomenon.

show abstract

Intraosteoblastic activity of levofloxacin and rifampin alone and in combination against clinical isolates of meticillin-susceptible Staphylococcus aureus causing prosthetic joint infection

Cited by 14 publications

References 20 publications

Staphylococcus aureus Internalization in Osteoblast Cells: Mechanisms, Interactions and Biochemical Processes. What Did We Learn from Experimental Models?

Staphylococcus aureus Internalization in Osteoblast Cells: Mechanisms, Interactions and Biochemical Processes. What Did We Learn from Experimental Models?

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

<em>Staphylococcus aureus</em> Internalization in Osteoblast Cells: Mechanisms, Interactions and Biochemical Processes. What did We Learn from Experimental Models?

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