Strain-to-strain variability among Staphylococcus aureus causing prosthetic joint infection drives heterogeneity in response to levofloxacin and rifampicin

Abstract

Introduction Levofloxacin and rifampicin are the preferred treatment for prosthetic joint infection (PJI) caused by Staphylococcus aureus, especially when managed with implant retention (DAIR). However, a significant variability of success has been reported, which could be related to intrinsic characteristics of the microorganism. Our aim was to evaluate the variability in the anti-biofilm response to levofloxacin and rifampicin in a clinical collection of S. aureus. Material and methods Eleven levofloxacin- and rifampicin-susceptible S. aureus isolates causing PJI managed with DAIR were included. Levofloxacin, rifampicin and levofloxacin + rifampicin were tested in an in vitro static biofilm model in microtitre plates, where 48 h biofilms were challenged with antimicrobials during 24 h. Additionally, two genetically similar strains were tested in the CDC Biofilm Reactor, where 48 h biofilms were treated during 56 h. Antimicrobial activity was assessed by viable biofilm-embedded cells recount, and by crystal violet staining. Results All antimicrobial regimens showed significant anti-biofilm activity, but a notable scattering in the response was observed across all strains (inter-strain coefficient of variation for levofloxacin, rifampicin and levofloxacin + rifampicin of 22.8%, 35.8% and 34.5%, respectively). This variability was tempered with the combination regimen when tested in the biofilm reactor. No correlation was observed between the minimal biofilm eradicative concentration and the antimicrobial activity. Recurrent S. aureus isolates exhibited higher biofilm-forming ability compared with strains from resolved infections (7.6 log10 cfu/cm2±0.50 versus 9.0 log10 cfu±0.07). Conclusions Significant variability may be expected in response to levofloxacin and rifampicin among biofilm-embedded S. aureus. A response in the lower range, together with other factors of bad prognosis, could be responsible of treatment failure.

The In Vitro Antibacterial Activity of Phytogenic and Acid-Based Eubiotics against Major Foodborne Zoonotic Poultry Pathogens

“…In addition, it has been suggested that the type of strain, the origin and the environmental conditions may impact the level of biofilm production by L. monocytogenes independently of the planktonic growth rate [ 80 ]. On the other hand, the genotypic and phenotypic characteristics of S. aureus strains may be responsible for the variability in biofilm formation [ 81 ]. Furthermore, a wide range of virulence pathways related to infectivity, toxin generation and antimicrobial resistance are associated with the strain variation of the bacteria [ 82 ].…”

Comparison of Staphylococcus aureus tolerance between antimicrobial blue light, levofloxacin, and rifampin

“…Literature support for this is minimal. While levofloxacin and rifampin are commonly combined for orthopedic infections, such as prosthetic joint infections (PJI), no studies compare their efficacy against planktonic bacteria vs. biofilms (Meléndez-Carmona et al, 2022 ). Nevertheless, a review of other studies indicates that biofilms are still typically more tolerant to combination antibiotic treatments than planktonic bacteria.…”

“…Therefore, when combined with another antibiotic effective against biofilms, such as levofloxacin, significant antimicrobial efficacy is probable. Additionally, Meléndez-Carmona et al ( 2022 ) performed biofilm studies specifically on a levofloxacin + rifampin combination. They demonstrated that the combination had high efficacy with CDC reactor-grown biofilms (48 h).…”

“…It presented a benchmark of how Staphylococcal strains may act. Nevertheless, Meléndez-Carmona et al ( 2022 ) indicated heterogeneity is present in antimicrobial response among different S. aureus strains. It would therefore be highly beneficial to extend the results of this study to different S. aureus strains and other bacteria common to orthopedic infections.…”

Rifampicin in periprosthetic joint infections: where do we stand and where are we headed?

“…More insight is needed regarding patients who do not seem to benefit of rifampicin combination therapy. Apart from the question which Gram positive microorganisms should be treated with rifampicin combination therapy, factors like differences in strain variability [53], joint differences [22], and achieving adequate serum levels should be taken into account. In addition, the duration of infection should be considered when evaluating the efficacy of rifampin.…”