A prospective multicentre evaluation of BioFire® Joint Infection Panel for the rapid microbiological documentation of acute arthritis.

OBJECTIVES: To assess the performance of the rapid syndromic BioFire® Joint Infection Panel (BF-JIP) to detect bacterial and fungal pathogens, as well as antibiotic resistance genes, directly in synovial fluid specimens collected from patients with acute arthritis. METHODS: The study was conducted in six French bacteriological laboratories. To assess the performances of BF-JIP, results were compared with those of synovial fluid 14-day culture and, in case of discrepancy, with those of complementary molecular methods and intraoperative samples. A total of 308 synovial fluid specimens were tested after collection from 308 adults and children presenting with clinical and biological suspicion of acute arthritis; patients presenting with acute periprosthetic joint infection were included according to the European Bone and Joint Infection Society 2021 criteria. RESULTS: Only one specimen failed (no result). On the basis of the consolidated data, the BF-JIP was concordant with the 14-day culture in 280 (91.2%) of the 307 specimens finally included in the study. The positive percentage agreement was 84.9% (95% CI, 78.8-89.8%) and the negative percentage agreement was 100% (95% CI, 97.2-100%). The positive predictive value was extremely high (100%; 95% CI, 97.6-100%), whereas the negative predictive value was lower (82.6%; 95% CI, 75.7-88.2%), partially explained by the missing target species in the panel. DISCUSSION: The BF-JIP showed high performances to detect pathogens involved in acute arthritis.

Staphylococcus lugdunensis prosthetic joint infection: A multicentric cohort study.

OBJECTIVES: To describe Staphylococcus lugdunensis prosthetic joint infection (PJI) management and outcome. METHODS: Adults with proven S. lugdunensis PJI were included in a multicentric retrospective cohort. Determinants for failure were assessed by logistic regression and treatment failure-free survival curve analysis (Kaplan-Meier). RESULTS: One hundred and eleven patients were included (median age 72.4 [IQR, 62.7-79.4] years), with a knee (n = 71, 64.0%) or hip (n = 39, 35.1%) PJI considered as chronic in 77 (69.4%) cases. Surgical management consisted in debridement, antibiotic with implant retention (DAIR; n = 60, 54.1%), two-stage (n = 28, 25.2%) or one-stage (n = 15, 13.5%) exchange. Total duration of antimicrobial therapy was 13.1 (IQR, 11.8-16.9) weeks. After a median follow-up of 99.9 (IQR, 53.9-178.1) weeks, 22 (19.8%) S. lugdunensis-related treatment failures were observed. Independent determinants for outcome were diabetes (OR, 3.741; p = 0.036), sinus tract (OR, 3.846; p = 0.032), DAIR (OR, 3.749; p = 0.039) and rifampin-based regimen (OR, 0.319; p = 0.043). Twenty-four (40.0%) of the 60 DAIR-treated patients experienced treatment failure, with hip location (OR, 3.273; p = 0.048), delay from prosthesis implantation (OR, 1.012 per month; p = 0.019), pre-surgical CRP level >115 mg/L (OR, 4.800; p = 0.039) and mobile component exchange (OR, 0.302; p = 0.069) constituting additional determinants of outcome. CONCLUSIONS: Staphylococcus lugdunensis PJI are difficult-to-treat infections, with pivotal roles of an optimal surgical management.

Pharmacokinetics, efficacy and tolerance of cefoxitin in the treatment of cefoxitin-susceptible extended-spectrum beta-lactamase producing Enterobacterales infections in critically ill patients: a retrospective single-center study.

BACKGROUND: Cefoxitin is active against some extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE), but has not been evaluated so far in the intensive care unit (ICU) settings. Data upon its pharmacokinetics (PK), tolerance and efficacy in critical conditions are scanty. We performed a retrospective single-center study in a university hospital medical ICU, in subjects presenting with cefoxitin-susceptible ESBL-PE infection and treated with cefoxitin. The primary aim was to determine cefoxitin PK. Secondary endpoints were efficacy, tolerance, and emergence of cephamycin-resistance. RESULTS: Forty-one patients were included in this study, mainly with ESBL-PE pneumonia (35 patients, 85%). Cefoxitin was administered during a median [interquartile range (IQR)] duration of 5 [4-7] days. Cefoxitin serum concentrations strongly depended on renal function. Target serum concentration (> 5 × minimum inhibitory concentration (MIC) 24 h after cefoxitin onset was obtained in 34 patients (83%), using a median [IQR] daily dose of 6 [6-6] g with continuous administration. The standard dosage of 6 g/24 h was not sufficient to achieve the PK/PD target serum concentration for MIC up to 4-8 mg/L, except in patients with severe renal impairment and those treated with renal replacement therapy. Treatment failure occurred in 26 cases (63%), among whom 12 patients (29%) died, 13 patients (32%) were switched to alternative antibiotic therapy and 11 patients (27%) presented with relapse of infection with the same ESBL-PE. Serious adverse events attributed to cefoxitin occurred in 7 patients (17%). Acquisition of cephamycin-resistance with the same Enterobacterales was identified in 13 patients (32%), and was associated with underdosage. CONCLUSION: Continuous administration of large doses of cefoxitin appears necessary to achieve the PK/PD target in patients with normal renal function. Renal status, MIC determination and therapeutic drug monitoring may be useful for treatment individualization in this setting. The treatment failure rate was 63%. The cefoxitin safety profile was favorable, but we observed a high rate of cephamycin-resistance emergence.

Osteocutaneous-flap-related osteomyelitis following mandibular reconstruction: a cohort study of an emerging and complex bone infection.

Osteocutaneous flap (OCF) mandible reconstruction is at high risk for surgical site infection. This study aimed to describe diagnosis, management, and outcome of OCF-related osteomyelitis. All patients managed at our institution for an OCF-related osteomyelitis following mandible reconstruction were included in a retrospective cohort study (2012-2019). Microbiology was described according to gold-standard surgical samples, considering all virulent pathogens, and potential contaminants if present on at least two samples. Determinants of treatment failure were assessed by logistic regression and Kaplan-Meier curve analysis. The 48 included patients (median age 60.5 (IQR, 52.4-66.6) years) benefited from OCF mandible reconstruction mostly for carcinoma ( n = 27 / 48 ; 56.3 %) or osteoradionecrosis ( n = 12 / 48 ; 25.0 %). OCF-related osteomyelitis was mostly early ( ≤ 3 months post-surgery; n = 43 / 48 ; 89.6 %), presenting with local inflammation ( n = 28 / 47 ; 59.6 %), nonunion (wound dehiscence) or sinus tract ( n = 28 / 47 ; 59.6 %), and/or bone or device exposure ( n = 21 / 47 ; 44.7 %). Main implicated pathogens were Enterobacteriaceae ( n = 25 / 41 ; 61.0 %), streptococci ( n = 22 / 41 ; 53.7 %), Staphylococcus aureus ( n = 10 / 41 ; 24.4 %), enterococci ( n = 9 / 41 ; 22.0 %), non-fermenting Gram-negative bacilli ( n = 8 / 41 ; 19.5 %), and anaerobes ( n = 8 / 41 ; 19.5 %). Thirty-nine patients (81.3 %) benefited from surgery, consisting of debridement with implant retention (DAIR) in 25 / 39 (64.1 %) cases, associated with 93 (IQR, 64-128) days of antimicrobial therapy. After a follow-up of 18 (IQR, 11-31) months, 24 / 48 (50.0 %) treatment failures were observed. Determinants of treatment outcomes were DAIR (OR, 3.333; 95 % CI, 1.020-10.898) and an early infectious disease specialist referral (OR, 0.236 if ≤ 2  weeks; 95 % CI, 0.062-0.933). OCF-related osteomyelitis following mandibular reconstruction represents difficult-to-treat infections. Our results advocate for a multidisciplinary management, including an early infectious-disease-specialist referral to manage the antimicrobial therapy driven by complex microbiological documentation.

Heterogeneous vancomycin resistance in Staphylococcus aureus does not predict development of vancomycin resistance upon vancomycin pressure.

BACKGROUND: It is unclear whether Staphylococcus aureus with heterogeneous intermediate vancomycin resistance (hVISA) can develop vancomycin resistance faster than vancomycin-susceptible S. aureus (VSSA) strains. METHODS: We compared the kinetics of vancomycin MIC increase for 15 days of sustained in vitro vancomycin exposure for clinical hVISA (n = 12) and VSSA (n = 24) isolates, as well as for reference strains Mu3 (hVISA) and ATCC 29213 (VSSA). Clinical isolates were categorized as hVISA using the population analysis profile method. MICs were monitored for 15 days and the rate of MIC increase under exposure, for each strain, was evaluated in a linear regression model relative to time. RESULTS: All isolates acquired vancomycin resistance upon exposure. Vancomycin MICs increased faster for VSSA compared with hVISA isolates (P < 0.01). CONCLUSIONS: The hVISA phenotype does not correspond to an enhanced adaptation potential to in vitro vancomycin pressure.

Safety of Tedizolid as Suppressive Antimicrobial Therapy for Patients With Complex Implant-Associated Bone and Joint Infection due to Multidrug-Resistant Gram-Positive Pathogens: Results From the TediSAT Cohort Study.

A prospective cohort study was conducted to evaluate long-term safety of tedizolid as suppressive antimicrobial treatment in patients with implant-associated bone and joint infection caused by multidrug-resistant gram-positive pathogens. Seventeen patients received tedizolid with a median duration of treatment of 6 months. No patients developed a serious adverse event.

Evaluation of intraosteoblastic activity of dalbavancin against Staphylococcus aureus in an ex vivo model of bone cell infection.

OBJECTIVES: Long-acting lipoglycopeptides are promising therapeutic options in Staphylococcus aureus bone and joint infections (BJIs). This study evaluated the ability of dalbavancin to eradicate the intraosteoblastic reservoir of S. aureus, associated with BJI chronicity. METHODS: Osteoblastic cells were infected with a standardized inoculum of the S. aureus reference strain HG001 and incubated for 24 h with dalbavancin, vancomycin or rifampicin using the MIC, 10×MIC, 100×MIC and/or the intraosseous concentrations reached using standard therapeutic doses (i.e. vancomycin, 10 mg/L; rifampicin, 2 mg/L; and dalbavancin, 6 mg/L). The remaining intracellular bacteria were quantified by plating cell lysates. RESULTS: MICs of dalbavancin, vancomycin and rifampicin were 0.125, 1 and 0.004 mg/L, respectively. Dalbavancin significantly reduced the intracellular inoculum of S. aureus starting at a concentration equal to the MIC, with a significant dose effect, ranging from a reduction of 31.4% (95% CI = 17.6%-45.2%) at MIC to 51.6% (95% CI = 39.8%-63.4%) at 100×MIC compared with untreated cells. Of note, dalbavancin was the only molecule to significantly reduce the intraosteoblastic inoculum at low concentration (MIC). At intraosseous concentrations, dalbavancin reduced the intracellular inoculum by 49.6% (95% CI = 45.1%-54.1%) compared with untreated cells (P < 0.001), with no significant difference compared with vancomycin (38.1%; 95% CI = 19.2%-57.0%; P = 0.646), and was less efficient than rifampicin (69.0%; 95% CI = 63.2-74.8; P < 0.001). CONCLUSIONS: Dalbavancin was able to decrease the intraosteoblastic S. aureus inoculum by 50% at intraosseous concentrations reached during standard human therapeutic dosing, with no difference compared with vancomycin, and remained less efficient than rifampicin. However, it was the only molecule significantly active at low concentration.

Performance of the Hologic Panther Fusion® MRSA Assay for the nasal screening of methicillin-sensitive and methicillin-resistant Staphylococcus aureus carriage.

Staphylococcus aureus (SA) nasal carriage screening is usually based on either culture or molecular biology. The aim of the study was to evaluate the performance of the Panther Fusion® MRSA Assay (PF) that proposes a complete automation of the molecular screening for MSSA and MRSA carriage. Four hundred thirty-four nasal samples collected on ESwab™ were screened using PF. Results were compared with standard culture on BBL™ CHROMagar™ Staph aureus and chromID® MRSA agar. Discordant results were analyzed with additional techniques: Xpert SA Nasal Complete on GeneXpert (GX), culture on selective agar after 24 h in broth enrichment, and, if necessary, characterization of mec gene and SCCmec cassette using DNA microarray. The PF presented an overall agreement of 97.5% for SA detection and 97.9% for MRSA detection. Furthermore, 7.1% (31/434) of the samples were SA-negative in primary culture but SA-positive using PF and GX, confirming the greater sensitivity of molecular tests compared with culture. Of note, 4 out of 30 MRSA-positive samples were not detected due to an atypical SCCmec cassette, while 2 samples were falsely detected as MRSA due to co-colonization with a MSSA drop-out strain and a methicillin-resistant coagulase-negative staphylococcal strain. Considering all results, the PF instrument appears as a reliable and rapid (< 3 h) package for MSSA/MRSA nasal screening. This technology using random access capability and direct sampling of the primary container is innovative and corresponds therefore to a new step in complete molecular biology automation in bacteriology.

Plasma Cell Infiltration on Histopathological Samples of Chronic Bone and Joint Infections due to Cutibacterium acnes: A series of 21 Cases.

Introduction: Histopathological definition of bone and joint infection (BJI) is based on Mirra's criterion (≥ 5 polymorphonuclears (PMNs) per field in 5 high power fields (HPFs)). However, this definition does not seem appropriate for chronic BJIs caused by slow-growing germs such as Cutibacterium acnes (C. acnes). The aim of this study was to confirm that Mirra's criterion is not adequate for diagnosis of BJIs due to C. acnes. The second objective was to determine if plasma cell infiltration could be useful for the diagnosis of chronic BJIs due to C. acnes. Methods: We retrospectively selected 25 consecutive patients from 2009 to 2013 with chronic BJIs due to C. acnes. Histological analysis was performed on the 21 cases with at least two C. acnes positive cultures. In addition of Mirra's criterion, the number of plasma cells (≥5 plasma cells/5 HPFs, defined as "CRIOAc Lyon's criterion") was implemented in the histopathological analysis. Patients were defined as infected, if at least one of the two criteria were present. Results: According to Mirra's and CRIOAc Lyon's criteria, positive histopathology was observed in 12 (57.1%) and 15 (71.4%) cases respectively. Considering the 9 cases with negative Mirra's criterion, high plasma cell infiltration (≥5 plasma cells per field/5 HPFs) was observed in 5 cases (55.6%), and low plasma cells infiltration (2-5 plasma cells per field/5 HPFs) was observed in 4 other cases (44.4%). Conclusions: Adding CRIOAc Lyon's criterion to Mirra's criterion might restore some histopathological diagnosis of chronic BJIs due to C. acnes when a chronic BJI is clinically suspected.

Novel staphylococcal cassette chromosome composite island (SCC-CI) with a new subtype of SCCmecVI cassette found in ST5 methicillin-resistant Staphylococcus aureus in France.

An emergent kanamycin-susceptible ST5 methicillin-resistant Staphylococcus aureus (MRSA) lineage has been identified in France. Whole-genome sequencing revealed a 40-kb staphylococcal cassette chromosome (SCC) composite island with a mosaic structure including three SCC elements: a ΨSCCcop/ars, a SCCLim88A with a ccrC recombinase, and a novel subtype of SCCmec type VI (VIb). This mosaic structure suggests a high recombination rate of SCC elements from distinct staphylococci species.

Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus in Horses, Cats, and Dogs Over a 5-Year Period in France.

Methicillin-resistant Staphylococcus aureus (MRSA) has been reported as a worldwide pathogen in humans and animals including companion animals, i.e., cats, dogs, and horses. France lacked a comprehensive nationwide study describing the molecular features of MRSA circulating among companion animals over a large period of time. Here is reported the characterization of 130 non-duplicate clinical MRSA isolates collected from those three animal species from 2010 to 2015 through the French national Resapath network. Characterization of isolates was performed using phenotypic (antimicrobial susceptibility tests) and molecular (DNA arrays, spa-typing) methods. A horse-specific epidemiology was observed in France with the large dissemination of a unique clone, the CC398 clone harboring a Staphylococcal chromosomal cassette mec (SCCmec) type IV and spa-type t011. It was even the unique clone collected in 2015 whereas the clone CC8 USA500 (SCCmec type IV), classically described in horses, was present until 2014. Contrarily, cats and dogs were mainly infected by human-related MRSA isolates, i.e., clones usually reported in human infections, thus mirroring the human epidemiology in hospitals in France. Isolates belonging to the CC398 clone (SCCmec type IV or V) were also identified in 21.4% of dogs' and 26.5% of cats' MRSA isolates. In order to differentiate human-related from CC398 MRSA, tetracycline-resistance [or tet(M) detection] could be useful since this resistance is scarce in human-related strains but constant in CC398 MRSA isolates. In all, our data give a nationwide epidemiological picture of MRSA in companion animals over a 5-year period in France, adding further epidemiological information on the contribution of those animal species to a major public health issue. Considering the wide dissemination of CC398 MRSA isolates and the fact that 11/64 (17.2%) of them presented the Immune Evasion Cluster which enhances CC398 capacities to colonize humans, a specific attention should be paid in the coming years to determine the risk associated to the transmission in people in frequent contacts with companion animals. Our data also show that the prevalence of MRSA has likely decreased in cats, dogs, and horses between 2012 and 2015 in France. This trend should be monitored in the years to come.