Lysosomal alkalization to potentiate eradication of intra-osteoblastic Staphylococcus aureus in the bone and joint infection setting

Abstract

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Can intracellular Staphylococcus aureus in osteomyelitis be treated using current antibiotics? A systematic review and narrative synthesis

“…In vitro, clindamycin treatments against S. aureus showed a high variation in intracellular activity between <1-log to 5-log reduction if cells were treated immediately after the infection. 43 , 53 – 58 No measurable reductions were reported with delayed treatment after 12 h 54 or 7 days. 55 Clindamycin showed limited effects against S. aureus SCVs, reducing the number of intracellular bacteria by 1-log after 72 h and extracellular bacteria by 2-log after 24 h in THP-1 macrophages.…”

“… 17 Furthermore, clindamycin was also reported to induce SCV formation. 55 The concentration of clindamycin used in the studies varied between 1.3–20 μg·mL −1 , but most commonly 4 μg·mL −1 was used, 17 , 43 , 53 – 58 which is a concentration that might realistically be reached in the bone. The MICs for various S. aureus strains were between 0.004–8 μg·mL −1 at pH 7.…”

“…However, acidic pH can increase the MIC fourfold or more to >38 μg·mL −1 compared to 4–8 μg·mL −1 in the same strain at pH 7. 43 This indicates that the treatment efficacy in patients depends on the pH of the compartment where the antibiotic and bacteria interact. Therefore, increasing the intracellular pH could be a strategy to improve treatment efficacy.…”

“…To better predict treatment efficacy, data from multiple sources have been combined, for example, pharmacokinetic data to determine the concentration of the antibiotic in bone, 40 , 41 the uptake and clearance of drugs inside specific cells 42 and the effect of drugs on host cell metabolism or antibiotic activity at various pH levels. 43 However, it is still uncertain whether specific treatments actually reduce intracellular bacterial numbers. Osteomyelitis is best modeled in infected cells using antibiotic concentrations that are known to be achieved in the bone.…”

Key Role of Staphylococcal Fibronectin-Binding Proteins During the Initial Stage of Staphylococcus aureus Keratitis in Humans

“…Further studies are needed to assess if eye drops containing molecules able to mask fibronectin motifs targeted by bacteria could be used to prevent BK. In addition, it is important that effective treatments for intracellular bacteria be researched and improved ( Abad et al., 2021 ). Finally, whether S. aureus carriage can increase the risk of endogenous S. aureus keratitis remains unknown probably because of a relatively low incidence as compared to other kinds of S. aureus infections ( Verhoeven et al., 2014 ).…”