Bacteriology
Kinetics of biofilm formation by Staphylococcus lugdunensis strains in bone and joint infections

https://doi.org/10.1016/j.diagmicrobio.2017.05.002Get rights and content

Abstract

Objective

To describe the clinical presentation and 1-year follow-up of patients with bone and joint infections (BJIs) caused by Staphylococcus lugdunensis and evaluate its biofilm-forming capacities.

Patients and methods

Overall, 28 patients with BJIs from VISLISI clinical trials were included. We evaluated 1-year clinical follow-up and analyzed biofilm production kinetics of the 28 strains using the BioFilm Ring Test®.

Results

Of all patients, 12 had osteoarticular infections without material and 16 had prosthetic joint infections, of which 9 underwent a 1-stage revision procedure. At the 1-year follow-up, all patients were cured but needed a surgical intervention. Diabetes affected 46.4% of all patients. Of all, 20 strains (71.4%) started biofilm formation within 2 h, but all strains started the formation after 4 h experiment, and 25 strains (89.3%) reached a maximum after 6 h.

Conclusions

This study describes the clinical and surgical management of BJIs caused by S. lugdunensis and shows that 1-stage prosthesis exchange procedures may be efficient. Further, It shows that biofilm production by this strain was not marginal and directly impacted clinical and surgical management.

Introduction

Staphylococcus lugdunensis is a coagulase negative staphylococcus species (CNS) that may cause various infections with unusual severity (Babu and Oropello, 2011). This commensal skin bacteria was originally described mainly in the skin and soft tissue infections, but recent retrospective studies have emphasized its role in bone and joint infections (BJIs), particularly prosthetic and joint infections (PJIs) (Douiri et al., 2016, Lourtet-Hascoët et al., 2016, Seng et al., 2017, Shah et al., 2010). These clinical observations are supported by some microbiological properties of this atypical CNS. Indeed, it produces a bound coagulase via a clumping factor, but this is only one of multiple adhesion factors described in this species. It exhibits a high binding percentage to purified collagen I and IV and immunoglobulin G, but it also binds fibrinogen, laminin, fibronectin, and plasminogen (Paulsson et al., 1993). Two adhesins, the fibrinogen binding protein (locus Fbl) and the von Willebrand factor binding protein (locus vwbl), have been reported (Mitchell, 2004, Nilsson et al., 2004). But additional surface components that recognize adhesive matrix molecules may exist, as suggested by genome sequence analysis of S. lugdunensis strains, N920143 and HKU09–01, which indicates several putative proteins covalently anchored to the cell wall surface (Heilbronner et al., 2011). Besides its ability to bind extracellular matrix components, S. lugdunensis produces a biofilm that is mainly proteinaceous and contains iron-regulated surface determinants (Hussain et al., 2015, Zapotoczna et al., 2012). We recently conducted a prospective clinical trial that confirmed the pathogenicity of S. lugdunensis and facilitated the identification of a novel metalloprotease named lugdulysin, which is statistically linked to deep BJIs (Argemi et al., 2016). It represented approximately 35% of all infections, and this rate was in accordance with a previous published study (Douiri et al., 2016). In this secondary analysis of VISLISI clinical trial, we focused on the clinical characteristics, treatment, and evaluated the outcome at the 1-year follow-up of all patients who presented with BJIs. We performed a biofilm production analysis at the microbiological level using a recently available technology called the BioFilm Ring Test® (BRT; BioFilm Control, Saint-Beauzire, France), based on superparamagnetic bead mobility in bacterial suspensions (Chavant et al., 2007, Olivares et al., 2016). This device was used previously to evaluate biofilm production by Staphylococcus aureus and other CNS, and some S. aureus strains were shown to produce biofilm within 4–5 h, a result of high importance from a clinical perspective as biofilm-associated infection has emerged as a therapeutic challenge (Chavant et al., 2007, Di Domenico et al., 2016, Tasse et al., 2016). Biofilm-embedded bacteria represent a physical and biochemical barrier to antibiotic diffusion, and mechanical debridement of material-associated infections sometimes remains as the univocal solution to eliminate bacteria and biofilm (Flemming et al., 2016, Lebeaux et al., 2014).

Section snippets

Study population

VISLISI clinical trial was previously reported (NCT: 02026895) (Argemi et al., 2016). Overall, 81 patients with S. lugdunensis infection in the Strasbourg University Hospital from November 2013 to March 2016 were included in the study. All procedures performed were in accordance with the ethical standards of the National Research Committee and with the 1964 Helsinki declaration and its later amendments. The study was approved by the French Ethical Committee under registration number

Study population

Of the 28 patients included in the analysis, 12 had material-free infections and 16 had PJIs. Age, sex, background, and infection characteristics are reported in Table 1, Table 2. Regarding material-free infections, metatarsophalangeal localizations were the most frequent (n = 7, 58.3%) followed by concomitant diabetes (n = 8, 66.7%). Only 1 patient (8.3%) had fever but 3 (25%) had sepsis. Two (16.6%) had postoperative infections, both of which occurred after a sternotomy caused by cardiac

Discussion

We described the first prospective study regarding BJIs caused by S. lugdunensis as a secondary analysis of the VISLISI clinical trial (Argemi et al., 2016). The high rate of osteoarticular infections, particularly total knee arthroplasty infections, was previously reported in 2 retrospective cohorts (Lourtet-Hascoët et al., 2016, Shah et al., 2010) and our data strengthened these observations. Our study did not identify a high proportion of urogenital abnormalities in patient backgrounds as

Conclusion

This study confirmed that S. lugdunensis samples and infections should be managed similarly to S. aureus ones. IDSA guidelines for the management of vertebral osteomyelitis in adults recommend that clinicians should consider this pathogen as a virulent pathogen, as they do for S. aureus, and not perform an image-guided aspiration biopsy in case of positive blood cultures.

Conflict of interests

All authors report no conflicts of interest relevant to this article.

Funding

VISLISI clinical trial was funded by a grant from the Collège des Universitaires des Maladies Infectieuses et Tropicales and by public funding from EA7290 Virulence Bactérienne Précoce, Faculté de Médecine, Strasbourg and supported by the University Hospital of Strasbourg.

Acknowledgments

We thank all the patients who participated in the study as well as doctors and nurses from Hôpitaux Universitaires de Strasbourg. We gratefully thank BioFilm Control for providing all necessary materials to perform the biofilm experiments. The authors would like to thank Enago (www.enago.com) for the English language review, Nicolas Lefebvre and Cécile Ronde-Oustau for their precious help during manuscript revision.

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