Clinical Features and Treatment Outcomes of Bone and Joint Nontuberculous Mycobacterial Infections According to Immune Status: a 9-year Retrospective Observational Cohort.

OBJECTIVES: Nontuberculous mycobacteria (NTM) bone and joint infections (BJIs) are uncommon. We evaluated the characteristics of BJIs and identified differences according to immune status. METHODS: We performed a multicenter retrospective study in France involving patients with documented NTM BJI over a 9-year period. We collected the clinical and microbiological characteristics, management, and clinical outcomes of the patients. RESULTS: Ninety-five patients were included, of whom 50.5% (48/95) were immunosuppressed. Tenosynovitis was more frequent in the immunocompetent group, and native arthritis more common in the immunosuppressed group. M. marinum and M. abscessus complex were significantly more frequent in the immunocompetent group, and M. avium and M. xenopi were significantly more frequent in the immunosuppressed group. The combination of antibiotherapy with surgery tended to be more frequent in the immunocompetent than the immunosuppressed group (63.8% (30/47) vs 47.8% (22/46), respectively); of the latter, 45.7% (21/46) received antimicrobial therapy alone, a higher frequency than in the immunocompetent group (23.4%, 11/47). The median duration of antimicrobial treatment was similar in the two groups (11 months). Mortality was significantly higher in the immunosuppressed group. CONCLUSIONS: Although the clinical presentations and the NTM species involved in BJI differed according to immune status, most recovered completely after treatment.

One-stage revision for infected shoulder arthroplasty: prospective, observational study of 37 patients.

Background: Periprosthetic joint infection is a severe complication of joint replacement surgery. Thus two-stage exchange remains the gold standard, one-stage exchange is now widely recommended. We hypothesized that, for patients with chronic periprosthetic shoulder infection (PSI), treatment with a one-stage exchange would be an effective approach to eradicate infection, relieve pain, and restore function to the involved shoulder. Materials and methods: This monocenter cohort study in a Bone and Joint Infection Referral Center (11/2003-05/2020) included all patients with confirmed PSI treated by one-stage revision. Data were extracted from the prospective database, including demographics, infection characteristics, and functional evaluations (range of motion and Constant Score at admission and last follow-up). The primary outcome was the 2-year reinfection-free rate. Results: We included 37 patients. The refection-free rate was 5%. The most commonly isolated pathogen was Cutibacterium acnes (68%), isolated alone (15 patients, 41%) or as polymicrobial infections (10 patients, 27%). The Constant Score increased significantly from 24 to 53 (P = .001). Range of motion (forward elevation, abduction) was also significantly improved after surgery. Mean active forward elevation increased significantly by 45° from 60° to 105° postoperatively (P < .001), mean abduction increased by 42° from 55° to 97° (P < .001). Discussion: Results from our prospective cohort-extracted series suggest that one-stage revision is a reliable treatment with a low infection recurrence rate. Improved functional outcomes can be achieved with one-stage exchange. Our patients' overall functional results were similar to those previously reported for one-stage revision and better than those reported after two-stage exchange. Patients with multiple previous surgeries seem to have worse functional outcomes than the subgroup without surgery before the index arthroplasty. Conclusions: Our results and literature search findings suggest that one-stage revisions effectively eradicate PSIs, with good functional outcomes.

What clindamycin dose should be administered by continuous infusion during combination therapy with rifampicin? A prospective population pharmacokinetics study.

BACKGROUND: Despite its important drug-drug interaction, combined clindamycin/rifampicin therapy may achieve effective plasma clindamycin concentrations, provided clindamycin is administered by continuous infusion. However, the precise clindamycin dose remains unknown. OBJECTIVES: This study was undertaken to determine the daily clindamycin dose to be administered by continuous infusion in combination with rifampicin to achieve effective plasma clindamycin concentrations. PATIENTS AND METHODS: Two plasma clindamycin concentrations were determined prospectively for 124 patients with bone-and-joint infections treated with continuously infused clindamycin. Twenty patients received clindamycin monotherapy, 19 clindamycin combined with rifampicin and 85 received clindamycin successively without and with rifampicin. A population pharmacokinetic model was developed using NONMEM 7.5. Monte Carlo simulations were run to determine which regimens obtained clindamycin concentrations of at least 3 mg/L. RESULTS: A linear one-compartment model with first-order elimination accurately described the data. Clindamycin distribution volume was not estimated. Mean clindamycin clearances with rifampicin and without, respectively, were 33.6 and 10.9 L/h, with 12.8% interindividual variability. The lowest daily clindamycin dose achieving plasma concentrations of at least 3 mg/L in >90% of the patients, when combined with rifampicin, was 4200 mg/24 h. CONCLUSIONS: Our results support continuous infusion of 4200 mg of clindamycin/24 h, in combination with rifampicin. This high-dose regimen requires therapeutic drug monitoring-guided dose adaptation.

Invasive bone and joint infections from the French Scedosporiosis/lomentosporiosis Observational Study (SOS) cohort: no mortality with long-term antifungal treatment and surgery.

Little is known about localized osteoarticular Scedosporiosis (LOS). Most data come from case reports and small case series. Here we present an ancillary study of the nationwide French Scedosporiosis Observational Study (SOS), describing 15 consecutive cases of LOS diagnosed between January 2005 and March 2017. Adult patients diagnosed with LOS defined by osteoarticular involvement without distant foci reported in SOS were included. Fifteen LOS were analyzed. Seven patients had underlying disease. Fourteen patients had prior trauma as potential inoculation. Clinical presentation was arthritis (n = 8), osteitis (n = 5), and thoracic wall infection (n = 2). The most common clinical manifestation was pain (n = 9), followed by localized swelling (n = 7), cutaneous fistulization (n = 7), and fever (n = 5). The species involved were Scedosporium apiospermum (n = 8), S. boydii (n = 3), S. dehoogii (n = 1), and Lomentospora prolificans (n = 3). The species distribution was unremarkable except for S. boydii, which was associated with healthcare-related inoculations. Management was based on medical and surgical treatment for 13 patients. Fourteen patients received antifungal treatment for a median duration of 7 months. No patients died during follow-up. LOS exclusively occurred in the context of inoculation or systemic predisposing factors. It has a non-specific clinical presentation and is associated with an overall good clinical outcome, provided there is a prolonged course of antifungal therapy and adequate surgical management.

Localized osteoarticular scedosporiosis mostly occurs following direct inoculation. Management was most often based on voriconazole therapy and concomitant surgery. Unlike other invasive scedosporiosis, no patient died during follow-up.

Cutibacterium acnes Prosthetic Joint Infections: Is Rifampicin-Combination Therapy Beneficial?

No consensus has been reached on the optimal antibiotic regimen to treat Cutibacterium acnes PJIs (Ca-PJIs). In vitro studies showed excellent rifampicin efficacy against biofilm-associated C. acnes infections, but clinical studies did not confirm the superiority of rifampicin-combined therapy over monotherapy. This prospective cohort study was undertaken to analyze the outcomes of 70 patients who underwent exchange arthroplasty for chronic monomicrobial Ca-PJI and were treated with rifampicin or without between 2004 and 2019. The 37 patients treated from January 2004 to August 2014 were prescribed rifampicin-combination therapy and the 33 treated from September 2014 to December 2019 received monotherapy without rifampicin. The primary endpoint was the 2-year Kaplan-Meier-estimated reinfection-free probability, including relapses and new-pathogen PJIs. The 2-year reinfection-free rate was high and not different for patients who had received rifampicin or not (89.2% vs. 93.8%, respectively; p = 0.524). None of the patients relapsed and six developed new-pathogen PJIs. Our results do not support a benefit of rifampicin-combination therapy for patients who underwent exchange arthroplasty for chronic Ca-PJIs.

Pseudomonas aeruginosa prosthetic joint-infection outcomes: Prospective, observational study on 43 patients.

Objectives: Analysis the outcomes of Pseudomonas aeruginosa prosthetic joint infection (PJI), and of their clinical and microbiological characteristics, surgical strategies and antibiotic treatments. Methods: Monocenter cohort study in a Bone-and-Joint-Infection Referral Center (08/2004 to 10/2018) including all consecutive P. aeruginosa PJIs. Data were extracted from the prospective database, including the following events: relapses, new PJIs, related deaths. Results: Median [IQR]: among the 43 patients included (28 females; 72 [63-80] years old; 27 hip, 15 knee, and 1 shoulder PJIs), 29 (67%) had underlying comorbidities, 12 (28%) had previously been treated for another PJI and 9 (21%) had undergone previous surgeries for their P. aeruginosa PJI. Eleven (26%) PJIs were polymicrobial, 16 (37%) strains were wild type, 8 (19%) ciprofloxacin-resistant. PJIs were classified as late chronic (n = 33), early postoperative (n = 9) or acute hematogenous infection (n = 1). Forty patients underwent surgery: 27 one-stage and 5 two-stage exchanges, 3 debridement and implant retention, and 5 other surgical strategies. Antibiotic treatments were: 29 received 41 [37-43] days of combination therapy (IV anti-pseudomonal ß-lactam and 3-5 days of amikacin, then ß-lactam and oral ciprofloxacin), followed by oral ciprofloxacin for a total of 12 weeks; 10 received only IV antibiotics for 83 [77-86] days, including 37 [32-46] days of combination therapy; 49 days of ceftazidime alone for 1. During follow-up lasting 33 [24-64.5] months, 2 relapses, 3 new PJIs, and 2 related deaths occurred. Thirty-three (82%) patients and 93% of those managed with one-stage exchange experienced no event. Conclusion: Outcomes of our cohort's P. aeruginosa PJIs-predominantly monomicrobial, chronic, ciprofloxacin-susceptible, treated with one-stage exchange and prolonged IV antibiotics-were 82% favorable.

Osteoarticular Mycoses.

Osteoarticular mycoses are chronic debilitating infections that require extended courses of antifungal therapy and may warrant expert surgical intervention. As there has been no comprehensive review of these diseases, the International Consortium for Osteoarticular Mycoses prepared a definitive treatise for this important class of infections. Among the etiologies of osteoarticular mycoses are Candida spp., Aspergillus spp., Mucorales, dematiaceous fungi, non-Aspergillus hyaline molds, and endemic mycoses, including those caused by Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides species. This review analyzes the history, epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, inflammatory biomarkers, diagnostic imaging modalities, treatments, and outcomes of osteomyelitis and septic arthritis caused by these organisms. Candida osteomyelitis and Candida arthritis are associated with greater events of hematogenous dissemination than those of most other osteoarticular mycoses. Traumatic inoculation is more commonly associated with osteoarticular mycoses caused by Aspergillus and non-Aspergillus molds. Synovial fluid cultures are highly sensitive in the detection of Candida and Aspergillus arthritis. Relapsed infection, particularly in Candida arthritis, may develop in relation to an inadequate duration of therapy. Overall mortality reflects survival from disseminated infection and underlying host factors.

Population Pharmacokinetics of Orally Administered Clindamycin to Treat Prosthetic Joint Infections: A Prospective Study.

A population PK model of clindamycin orally administered to patients with prosthetic joint infections (PJIs) was developed using NONMEM 7.5. Monte-Carlo simulations were run to determine the probability of obtaining bone clindamycin concentrations equal to at least the MIC or four times the MIC for several MIC values and dosing regimens. One hundred and forty plasma concentrations prospectively obtained from 20 patients with PJIs were used. A one-compartment model with first-order absorption and elimination appropriately described the data. Mean PK-parameter estimates (F being the bioavailability) were: apparent clearance, CL/F = 23 L/h, apparent distribution volume, V/F = 103 l and absorption rate constant, Ka = 3.53/h, with respective interindividual variabilities (coefficients of variation) of 14.4%, 8.2% and 59.6%. Neither goodness-of-fit curves nor visual predictive checks indicated bias. The currently recommended 600 mg q8h regimen provided a high probability of obtaining concentrations equal to at least the MIC, except for MIC ≥ the clinical breakpoint for Staphylococcus spp. (0.25 mg/L). For such MIC values, higher daily doses and q6h regimens could be considered.

Clinical Features and Outcome of Multidrug-Resistant Osteoarticular Tuberculosis: A 12-Year Case Series from France.

The optimal treatment for osteoarticular infection due to multidrug-resistant tuberculosis strains (MDR-OATB) remains unclear. This study aims to evaluate the diagnosis, management and outcome of MDR-OATB in France. We present a case series of MDR-OATB patients reviewed at the French National Reference Center for Mycobacteria between 2007 and 2018. Medical history and clinical, microbiological, treatment and outcome data were collected. Twenty-three MDR-OATB cases were reported, representing 3% of all concurrent MDR-TB cases in France. Overall, 17 were male, and the median age was 32 years. Six patients were previously treated for TB, including four with first-line drugs. The most frequently affected site was the spine (n = 16). Bone and joint surgery were required in 12 patients. Twenty-one patients (91%) successfully completed the treatment with a regimen containing a mean of four drugs (range, 2-6) for a mean duration of 20 months (range, 13-27). Overall, high rates of treatment success were achieved following WHO MDR-TB treatment guidelines and individualized patient management recommendations by the French National TB Consilium. However, the optimal combination of drugs, duration of treatment and role of surgery in the management of MDR-OATB remains to be determined.

Streptococcal and Staphylococcus aureus prosthetic joint infections: are they really different?

BACKGROUND: Staphylococci and streptococci are the most frequent pathogens isolated from prosthetic joint infections (PJIs). The aim of this study was to analyze the outcome of streptococcal and methicillin-susceptible Staphylococcus aureus (MSSA) PJIs. METHODS: All monomicrobial streptococcal and MSSA PJIs managed in a French Referral Center (2010-2017) were sampled from the prospective PJIs cohort study. The primary outcome of interest was the cumulative reinfection-free survival at a 2-year follow-up. RESULTS: Two hundred and nine patients with 91 streptococcal and 132 staphylococcal infections were analyzed. Patients with streptococcal PJI were older, and infection was more frequently hematogenous. Reinfection-free survival rates at 2-years after all treatment strategies were higher for patients with streptococcal PJI (91% vs 81%; P = .012), but differed according to the strategy. After exchange arthroplasty, no outcome differences were observed (89% vs 93%; P = .878); after debridement, antibiotics and implant retention (DAIR), the reinfection-free survival rate was higher for patients with streptococcal PJI (87% vs 60%; P = .062). For patients managed with prolonged suppressive antibiotic therapy (SAT) alone, those with streptococcal PJIs had a 100% infection-free survival (100% vs 31%; P < .0001). CONCLUSIONS: Reinfection-free survival after DAIR and SAT was better for patients with streptococcal than those with MSSA PJIs. No difference was observed after prosthesis exchange.

Arthroplasty after septic arthritis of the native hip and knee: retrospective analysis of 49 joints.

Background: Arthroplasty after septic arthritis (SA) treatment raises diagnostic and therapeutic questions. The main objective was to evaluate infection-free survival of patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA) post-SA. Other objectives were to describe the population's characteristics, surgical strategies, results of preoperative examinations and cultures of intraoperative samples taken at implantation, and postoperative antibiotic therapy. Methods: This is a retrospective, observational, monocenter study, from January 2005 to May 2019, including all patients undergoing TKA or THA with prior or ongoing SA in the same joint. Infection-free survival was analyzed and reported. Results: Forty-seven patients, 29 men, 49 joints operated on (30 knees, 19 hips), were included. Median SA-to-arthroplasty interval was 32 [1-216] weeks. It was < 2  years for 43 joints and < 6  months for 19 joints. Six patients underwent arthroplasty while still on SA treatment. One-stage arthroplasty was done for 43 joints and two-stage arthroplasty for 6 joints. Eight (16 %) cultures of intraoperative specimens were positive. Median durations of postoperative antibiotic therapy were 10 d for sterile cultures and 82 d for those that were positive. At 2 years, infection-free survival rate was 95.9 % ( ± 0.02 ). After a median follow-up of 47 [18-142] months, no SA relapse was observed, but five patients developed new periprosthetic joint infections (PJIs) with a different microorganism. Conclusion: Arthroplasty may be a post-SA option, even within a short period of time. One-stage arthroplasty can be done if synovectomy is thorough, intraoperative samples are taken and antibiotics are administered until those culture results become available. We observed no SA relapse, but new PJIs occurred.

Antibiotic Therapy for Prosthetic Joint Infections: An Overview.

Prosthetic joint infection (PJI) is a severe complication after arthroplasty. Its management combines surgical intervention, whose type depends on the clinical situation, and prolonged high-dose antibiotics adapted to the responsible microorganism(s) and the patient. Antibiotics are only one part of the therapeutic regimen and are closely related to the surgical strategy. Their efficacy depends to a large extent on the choice and quality of the surgical procedure, and the quality of the microbiological diagnosis. Although guidelines have been published, many aspects of antibiotic therapy remain poorly established. Choosing the optimal agent(s) is one aspect, with others being optimization of drugs' pharmacokinetic/pharmacodynamic parameters, the choice of administration route, use of monotherapy or combination regimens, therapeutic drug-monitoring and patient education to improve compliance and tolerance. Herein, we address PJI management based on recent literature data, guidelines and the experience of our referral center for complex bone-and-joint infections.

Successive new-pathogen prosthetic joint reinfections: Observational cohort study on 61 patients.

OBJECTIVES: Prosthetic joint infection (PJI) treatment failure may be due to relapsing infection (same microorganism) or new-pathogen reinfection (npPJI). The aim was to describe npPJI epidemiological, clinical and microbiological characteristics, their treatments and outcomes, and identify their risk factors. METHODS: This observational, single-center, cohort study was conducted in a French Referral Center for Bone-and-Joint Infections between September 2004 and December 2015. Patients treated for at least two successive hip or knee PJIs in the same joint with a different pathogen were identified in the prospective database. We compared each patient's first PJI and subsequent npPJI(s) to analyze the type and microbiological characteristics of npPJIs. To search for npPJI risk factors, we compared those cases to a random selection of 122 "unique-episode" PJIs treated during the study period. RESULTS: Among 990 PJIs, 79 (8%) npPJIs occurring in 61 patients were included. New-pathogen prosthetic joint infections (npPJIs) developed more frequently in knee (14%) than hip prostheses (5%). Median interval from the first PJI to the npPJI was 26 months. New-pathogen prosthetic joint reinfections (npPJIs) more frequently spread hematogenously (60% vs 33%) and were predominantly caused by Staphylococcus (36%) or Streptococcus (33%) species. Multivariate analysis identified two risk factors: chronic dermatitis (odds ratio: 6.23; P<0.05) and cardiovascular diseases (odds ratio: 2.71; P<0.01). A curative strategy was applied to 70%: DAIR (29%), one-stage (28%), two-stage exchange arthroplasty (7%) or other strategies (7%). The others received prolonged suppressive antibiotic therapy (30%). CONCLUSIONS: New-pathogen prosthetic joint infections (npPJIs) are complex infections requiring management by multidisciplinary teams that should be adapted to each clinical situation.

Assessment of post-operative opioid prescribing practices in a community hospital ambulatory surgical center.

OBJECTIVE: To evaluate the prescribing practices and opioid consumption in an ambulatory setting to inform the development of evidence-based guidelines. DESIGN: A prospective study of adults undergoing outpatient open and laparoscopic surgeries over 3 months. One week after discharge, a telephonic interview quantified the number of opioids prescribed and consumed, degree of pain control and satisfaction, and whether additional pain medication was requested. SETTING: Community hospital ambulatory surgery center in Westchester County, New York. PARTICIPANTS: This study included 304 adults undergoing a variety of procedures by surgeons from multiple specialties. MAIN OUTCOME MEASURES: Quantify surgeons' postoperative opioid prescribing compared with patient opioid consumption. RESULTS: Eighty-one percent (N = 245) responded to the survey, of which 64 percent were prescribed opioids. Males and females were equally represented with the mean age of 59.4 years. Of those prescribed opioids, 92 percent filled the prescription. The most commonly prescribed opioids reported by the patients that filled their prescription (N = 145) were oxycodone (36.5 percent), oxycodone/acetaminophen (28.9 percent), and tramadol (22.7 percent). The mean number of opioid pills prescribed was 20 and the mean consumption was 6.7 pills, resulting in an average of 13 retained pills. Only 3.8 percent of the patients prescribed opioids at discharge called their provider for additional analgesia. Despite the low opioid consumption patients reported high satisfaction (4.5 on scale of 0-5) with pain control. Only 10.4 percent reported that the surgeon recommended an over the counter (OTC) analgesic option. There was variability in the amount of opioids prescribed within each surgical category. CONCLUSIONS: One week after outpatient surgery, patients consumed one-third of physician-prescribed opioids, yet they reported high pain management satisfaction. Our study will inform the development of a patient-centered interdisciplinary perioperative education program to more effectively tailor multimodal pain management in ambulatory surgical patients and collaterally reduce the number of retained opioids.

Coagulation disorders during treatment with cefazolin and rifampicin: rare but dangerous.

We describe a 79-year-old man with spondylodiscitis and unknown pathogen, treated with cefazolin and rifampicin. He developed a massive digestive hemorrhage. Prothrombin time was prolonged with severe vitamin-K-dependent clotting-factor deficiency. Severe bleeding can occur during cefazolin and rifampicin use. This deficiency should be assessed before prescribing cefazolin-rifampicin and prothrombin time monitored.

No evidence of tocilizumab treatment efficacy for severe to critical SARS-CoV2 infected patients: Results from a retrospective controlled multicenter study.

ABSTRACT: To assess tocilizumab (TCZ) efficacy associated to standard of care (SOC) compared to SOC alone in severe coronavirus associated disease 2019 (COVID-19) patients. In a matched case-control study from 3 French Hospital COVID-19 Departments, 27 patients with severe COVID-19 treated with TCZ and SOC were matched for baseline epidemiological and clinical features and compared to 27 severe COVID-19 patients treated with SOC alone. Baseline characteristics of the study population were comparable between groups. Eleven patients (20%) died. TCZ was not associated with clinical improvement as compared to SOC regarding oxygen-free status (44% vs 63%) and death (18.5% vs 22%), despite a higher decrease of the C-reactive protein at Day 7 (10.7 vs 52 mg/L; P < 10-3). Compared to the 43 patients alive at the end-of follow-up, patients who died were older (78 vs 64 years; P < 10-3), with 82% of them older than 72 years vs only 23% of live patients (P < 10-3). Age (OR = 1.15; 95%CI = 1.04-1.3; P = .008) and age over 72 years (OR) = 14.85; 95%CI = 2.7-80; P = .002) were independently associated with mortality. TCZ in addition to SOC for severe COVID-19 patients did not reduce mortality, subsequent need for invasive mechanical ventilation nor did it shorten the time of oxygen support, despite better control of the inflammatory response. More powerful and randomized controlled trials are warranted to determine if TCZ is effective in the management of COVID-19.

Influence of the clindamycin administration route on the magnitude of clindamycin-rifampicin interaction: a prospective pharmacokinetic study.

OBJECTIVES: An important clindamycin-rifampicin pharmacokinetic (PK) interaction has been reported, but the potential influence of the clindamycin administration route on that interaction is unknown. This prospective, observational, comparative PK study was undertaken to characterize and analyse the impact of the route, comparing the rifampicin enzyme-inductor effects on clindamycin clearance (CLclin) for oral versus intravenous (IV) administration. METHODS: Patients with bone-and-joint infections (BJIs) were treated with clindamycin monotherapy (n = 20) or clindamycin-rifampicin combination therapy (n = 19). Patients received continuous IV clindamycin infusion for 2-6 weeks, followed by an oral regimen. Liquid chromatography-mass spectrometry was used to measure plasma clindamycin concentrations at the end of IV and after 2 weeks of oral treatment. The ratios of the mean CLclin for the combination and monotherapy groups were calculated for IV (Riv) and oral (Rpo) routes, with the final ratio, Rf = Rpo/Riv, representing the fold change of the rifampicin-inducing effect from the IV to the oral route. RESULTS: Comparing monotherapy with combination-therapy groups, the former's median steady-state concentration was two-fold higher after IV administration (8.49 versus 3.82 mg/L, p < 0.001) and its median AUC0-8h was 12 times higher after oral intake (37.7 versus 3.1 mg.h/L, p < 0.001). Riv, Rpo and Rf were 2.68, 18.8 and 7.0 respectively. CONCLUSION: The magnitude of this interaction was markedly increased by oral intake, questioning the use of oral treatment for difficult-to-treat infections like BJIs. Nevertheless, the clindamycin-rifampicin combination seems possible provided that clindamycin is administered by continuous IV infusion.

Impact on the Gut Microbiota of Intensive and Prolonged Antimicrobial Therapy in Patients With Bone and Joint Infection.

There is a growing interest in the potentially deleterious impact of antibiotics on gut microbiota. Patients with bone and joint infection (BJI) require prolonged treatment that may impact significantly the gut microbiota. We collected samples from patients with BJI at baseline, end of antibiotics (EOT), and 2 weeks after antibiotic withdrawal (follow-up, FU) in a multicenter prospective cohort in France. Microbiota composition was determined by shotgun metagenomic sequencing. Fecal markers of gut permeability and inflammation as well as multi-drug-resistant bacteria (MDRB) and Clostridioides difficile carriage were assessed at each time point. Sixty-two patients were enrolled: 27 native BJI, 14 osteosynthesis-related BJI, and 21 prosthetic joint infections (PJI). At EOT, there was a significant loss of alpha-diversity that recovered at FU in patients with native BJI and PJI, but not in patients with osteosynthesis-related BJI. At EOT, we observed an increase of Proteobacteria and Bacteroidetes that partially recovered at FU. The principal component analysis (PCoA) of the Bray-Curtis distance showed a significant change of the gut microbiota at the end of treatment compared to baseline that only partially recover at FU. Microbiota composition at FU does not differ significantly at the genus level when comparing patients treated for 6 weeks vs. those treated for 12 weeks. The use of fluoroquinolones was not associated with a lower Shannon index at the end of treatment; however, the PCoA of the Bray-Curtis distance showed a significant change at EOT, compared to baseline, that fully recovered at FU. Levels of fecal neopterin were negatively correlated with the Shannon index along with the follow-up (r 2 = 0.17; p < 0.0001). The PCoA analysis of the Bray-Curtis distance shows that patients with an elevated plasma level of C-reactive protein (≥5 mg/L) at EOT had a distinct gut microbial composition compared to others. MDRB and C. difficile acquisition at EOT and FU represented 20% (7/35) and 37.1% (13/35) of all MDRB/C. difficile-free patients at the beginning of the study, respectively. In patients with BJI, antibiotics altered the gut microbiota diversity and composition with only partial recovery, mucosal inflammation, and permeability and acquisition of MDRB carriage. Microbiome interventions should be explored in patients with BJI to address these issues.