Prosthetic joint infections: 6 weeks of oral antibiotics results in a low failure rate.

BACKGROUND: Need for parenteral administration and total duration of antibiotic therapy for prosthetic joint infection (PJI) are debated. We report our PJI management, in which outpatient care is privileged. METHODS: This was a retrospective multicentre cohort study of PJI managed from January 2017 to Jun 2021. Microbial diagnosis was based on surgical samples. Surgical procedures and antibiotic treatments were reported. Chronic PJI was defined by a course >1 month. Oral antibiotic therapy (OAT) was defined by exclusive use of oral antibiotics or by ≤3 days of parenteral treatments. Management failure was defined by clinical and/or microbial relapse of PJI over 24 months after surgical treatment. RESULTS: One hundred and seventy-two patients from 13 institutions were included: 103 were male (60%) and mean age was (±SD): 73 ±â€Š12 years. Sites for PJI were mainly hip (50%) and knee (35%), being chronic infections in 70 cases (41%). The main bacterial genus in monomicrobial infections was Staphylococcus spp. (60%). We recorded 41 (24%) implant exchanges. An OAT was prescribed in 76 cases (44%), and the median (range) course for parenteral route was 6 days (4-180) for 96 cases. Median (range) duration of antimicrobials was 42 days (21-180). Management failure was observed in 7/76 (9.2%) cases treated with OAT and 15/96 (15.6%) treated with prolonged parenteral therapy. In multivariate analysis, risk factors for failure were a knee PJI [adjusted OR (95% CI) = 3.27 (1.27-8.40)] and a polymicrobial infection [4.09 (1.46-11.49)]. CONCLUSIONS: OAT for 6 weeks for PJI was associated with a low rate of management failure.

Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial.

BACKGROUND: Duration of treatment for patients with vertebral osteomyelitis is mainly based on expert recommendation rather than evidence. We aimed to establish whether 6 weeks of antibiotic treatment is non-inferior to 12 weeks in patients with pyogenic vertebral osteomyelitis. METHODS: In this open-label, non-inferiority, randomised controlled trial, we enrolled patients aged 18 years or older with microbiologically confirmed pyogenic vertebral osteomyelitis and typical radiological features from 71 medical care centres across France. Patients were randomly assigned to either 6 weeks or 12 weeks of antibiotic treatment (physician's choice in accordance with French guidelines) by a computer-generated randomisation list of permuted blocks, stratified by centre. The primary endpoint was the proportion of patients who were classified as cured at 1 year by a masked independent validation committee, analysed by intention to treat. Non-inferiority would be declared if the proportion of cured patients assigned to 6 weeks of treatment was not less than the proportion of cured patients assigned to 12 weeks of treatment, within statistical variability, by an absolute margin of 10%. This trial is registered with EudraCT, number 2006-000951-18, and Clinical Trials.gov, number NCT00764114. FINDINGS: Between Nov 15, 2006, and March 15, 2011, 359 patients were randomly assigned, of whom six in the 6-week group and two in the 12-week group were excluded after randomisation. 176 patients assigned to the 6-week treatment regimen and 175 to the 12-week treatment regimen were analysed by intention to treat. 160 (90·9%) of 176 patients in the 6-week group and 159 (90·9%) of 175 of those in the 12-week group met the criteria for clinical cure. The difference between the groups (0·05%, 95% CI -6·2 to 6·3) showed the non-inferiority of the 6-week regimen when compared with the 12-week regimen. 50 patients in the 6-week group and 51 in the 12-week group had adverse events, the most common being death (14 [8%] in the 6-week group vs 12 [7%] in the 12-week group), antibiotic intolerance (12 [7%] vs 9 [5%]), cardiorespiratory failure (7 [4%] vs 12 [7%]), and neurological complications (7 [4%] vs 3 [2%]). INTERPRETATION: 6 weeks of antibiotic treatment is not inferior to 12 weeks of antibiotic treatment with respect to the proportion of patients with pyogenic vertebral osteomyelitis cured at 1 year, which suggests that the standard antibiotic treatment duration for patients with this disease could be reduced to 6 weeks. FUNDING: French Ministry of Health.

Antibiotic Consumption 2017-2022 in 30 Private Hospitals in France: Impact of Antimicrobial Stewardship Tools and COVID-19 Pandemic.

Our aim was to determine the impact of antimicrobial stewardship tools (ASTs) and the COVID-19 pandemic on antibiotic consumption (AC). We used the national software Consores® to determine AC in DDD/1000 days of hospitalization from 2017 to 2022 in voluntary private hospitals in France. The ASTs considered were: 1. internal guidelines; 2. the list of antibiotics with restricted access; 3. the presence of an antibiotic referent or 4. an ID specialist; and 5. proof of an annual meeting on antimicrobial resistance. Institutions with dedicated units for COVID-19 patients were specified. In 30 institutions, the total AC varied from (means) 390 to 405 DDD/1000 DH from 2017 to 2022. Fluoroquinolones and amoxicillin/clavulanate consumption decreased from 50 to 36 (p = 0.003) and from 112 to 77 (p = 0.025), respectively, but consumption of piperacillin/tazobactam increased from 9 to 21 (p < 0.001). Over the study period, 10 institutions with ≤2 AST had lower AC compared to 20 institutions with ≥3 AST (p < 0.01). COVID-19 units opened in 10 institutions were associated with a trend toward higher macrolide consumption from 15 to 25 from 2017 to 2020 (p = 0.065) and with an acceleration of piperacillin/tazobactam consumption from 2020 to 2022 (p ≤ 0.003). Antibiotic consumption in 30 private hospitals in France was inversely related to the number of AST. The COVID-19 pandemic was associated with limited impact on AC, but special attention should be paid to piperacillin/tazobactam consumption.

Use of a Porous Alumina Antibiotic-Loaded Ceramic to Treat Bone Defect and Bone Infection After Road Trauma.

To describe the use of a porous alumina ceramic loaded with antibiotics for the reconstruction of bilateral tibial fractures in a patient who presented with bone loss and infection after a motorcycle road injury. A 70-year-old man presented open fractures of his both tibiae (proximal involvement on the right side and diaphyseal on the left side). After initial treatment with multiple débridements and the placement of bilateral external fixators, he had bone loss to both tibiae and had developed infections of both legs with multiple organisms identified (Stenotrophomonas maltophilia, Enterobacter cloacae, and Pseudomonas aeruginosa). We used a porous alumina ceramic, designed according to the defects to fill. This ceramic was loaded with antibiotics (gentamicin and vancomycin). The goal was to obtain locally high concentrations of antibiotics to eradicate bacteria that could have remain in the surgical wound. Ceramic parts were placed 4 months after the trauma. Local antibiotic concentrations largely exceeded the pharmacological parameters for antibiotics efficacy. External fixators were removed 3 months after implantation. After a follow-up of more than 1 year, there is no relapse of infection, and the patient resumed walking while ceramic parts were left in place and that bone started colonizing ceramic parts. This ceramic that combines strength and the possibility of antibiotic loading allows thinking of new ways to treat infected fractures with bone loss. Indeed, its mechanical strength provides primary stability, and antibiotics make it possible to secure implantation in an infected area.

Long-term Prognosis Following Vascular Graft Infection: A 10-Year Cohort Study.

Background: Vascular graft infection (VGI) remains a severe disease with high mortality and relapse rates. We performed a retrospective single-center cohort study to highlight factors associated with long-term all-cause mortality in patients with vascular graft infection. Methods: All patients hospitalized in our facility over 10 years for VGI were included. VGI was defined by the presence of a vascular graft or an aortic stent graft (stent or fabric), associated with 2 criteria among clinical, biological, imaging, or microbiological elements in favor of VGI. The primary outcome was all-cause mortality. Empirical antibiotic therapy was considered as appropriate when all involved pathogens were susceptible in vitro to the antibiotics used. The surgical strategy was defined as nonoptimal when the graft was not removed in a late-onset surgery (>3 months) or no surgery was performed. Results: One hundred forty-six patients were included. Empirical antibiotic therapy was administered in 98 (67%) patients and considered appropriate in 55 (56%) patients. Surgery was performed in 136 patients (96%) and considered as optimal in 106 (73%) patients. In multivariable analysis, appropriate empirical antibiotic therapy was associated with a lower probability of mortality (hazard ratio, 0.47 [95% confidence interval, .30-.79]; P = .002). Long-term survival did not differ according to whether the surgical strategy was considered optimal or not (log-rank = 0.66). Conclusions: Appropriate empirical antibiotic therapy is a cornerstone of the management of VGI. Whenever possible, antibiotics must be associated with optimal surgical management. However, surgery could potentially be avoided in comorbid patients who are treated with appropriate antibiotics.

Diagnostic Value of 18F-FDG PET/CT vs. Chest-Abdomen-Pelvis CT Scan in Management of Patients with Fever of Unknown Origin, Inflammation of Unknown Origin or Episodic Fever of Unknown Origin: A Comparative Multicentre Prospective Study.

Fluorodesoxyglucose Positron Emission Tomography (PET/CT) has never been compared to Chest-Abdomen-Pelvis CT (CAPCT) in patients with a fever of unknown origin (FUO), inflammation of unknown origin (IUO) and episodic fever of unknown origin (EFUO) through a prospective and multicentre study. In this study, we investigated the diagnostic value of PET/CT compared to CAPCT in these patients. The trial was performed between 1 May 2008 through 28 February 2013 with 7 French University Hospital centres. Patients who fulfilled the FUO, IUO or EFUO criteria were included. Diagnostic orientation (DO), diagnostic contribution (DC) and time for diagnosis of both imaging resources were evaluated. One hundred and three patients were included with 35 FUO, 35 IUO and 33 EFUO patients. PET/CT showed both a higher DO (28.2% vs. 7.8%, p < 0.001) and DC (19.4% vs. 5.8%, p < 0.001) than CAPCT and reduced the time for diagnosis in patients (3.8 vs. 17.6 months, p = 0.02). Arthralgia (OR 4.90, p = 0.0012), DO of PET/CT (OR 4.09, p = 0.016), CRP > 30 mg/L (OR 3.70, p = 0.033), and chills (OR 3.06, p = 0.0248) were associated with the achievement of a diagnosis (Se: 89.1%, Sp: 56.8%). PET/CT both orients and contributes to diagnoses at a higher rate than CAPCT, especially in patients with FUO and IUO, and reduces the time for diagnosis.

Prolonged course of Fosfomycin-Trometamol for chronic prostatitis: an unknown good option.

BACKGROUND: Bacterial prostatitis can be difficult to treat as more and more bacteria are resistant to fluoroquinolone and/or Sulfamethoxazole-Trimethoprim which are the antibiotics of choice. Fosfomycin-Trometamol which is registered for uncomplicated urinary tract infections can be an option when other treatments can't be used. OBJECTIVE: To describe a case of prostatitis cured using a prolonged course of Fosfomycin-Trometamol. Patient: A 67 years-old man with a chronic bacterial prostatitis, with recurrences for more than 3 years, due to E. coli was treated with Fosfomycin-Trometamol 3g once a day for a week followed by 3 months of the same dose every two days. Prostatitis was clinically and bacteriologically cured and no relapse occurred after 6 months of follow-up. CONCLUSION: Fosfomycin-Trometamol can be a good option for the treatment of bacterial prostatitis when other antibiotics can't be used either for resistance or allergy.

Case Report: CD8+ T-Lymphocyte Deficit: A Prerequisite for Pasteurella spp. Infection?

Background: Immunity against Pasteurella spp. is not well-known for humans. Methods: We've tested T CD8+ lymphocytes in a patient with a chronic prosthetic joint infection due to Pasteurella spp. to search for a deficit which could have favored her infection. As this deficit was found, we've searched for such a deficit in other patients with Pasteurella spp. Infections, either acute or subacute. Results: Eight patients were tested and all had a persistent T CD8+ lymphocytes deficit. This is striking as these cells are involved in the response to this type of infection in animal models. Conclusion: The authors suggest that a deficit in CD8+ T lymphocytes can be one of the causes for the onset of infections with P. multocida.

Nonhealing wound due to Rhodococcus equi in an apparently immunocompetent patient, revealing CD8+ T-lymphocyte deficiency.

We describe a case of a nonhealing wound due to Rhodococcus equi. Failure of the wound to heal led to immunological investigations and the discovery of a previously unknown CD8+ T-lymphocyte deficit responsible for the chronic infection. The infection was cured after a 3-month course of a combination of antibiotics.

An antibiotic loaded ceramic sternum to treat destroyed infected sternum: 4 cases.

BACKGROUND: After its destruction during refractory deep sternal wound infection (DSWI), current sternum reconstructions mainly rely on muscle flaps technique, but such technique have pitfalls and limits. To tackle the limited possibilities to use device implantation because of the risk of infection, we developed a self-protected device allowing its implantation in an infected area. METHODS: We used gentamicin alone or in combination with vancomycin loaded in a porous ceramic sternum to replace sternums destroyed during DSWI. The aim was to mechanically replace the sternum and to secure the implantation by killing the remaining bacteria in the wound thanks to the loaded antibiotic. RESULTS: This device was implanted in four infected patients during DWSI with sternal dehiscence. No complication occurred during surgeries, and wound healing was obtained quickly. Local antibiotic concentrations largely exceeded the ones needed for their efficacy while no antibiotic was found in the blood. All patients are well-being. However previously unknown gentamicin resistant bacteria, present in the surgical wound at the time of positioning, required sternal implant removal for one patient after 19 months. For all patients, pulmonary function tests (PFT) improved after implantation. CONCLUSIONS: The ceramic sternum played its role consolidating the thoracic cage without stiffening. The antibiotic loaded in the sternum allowed a secure implantation, killing bacteria before the colonization of the implant even in this infected area. These four implantations are promising for patients with sternal destruction after DSWI.

Antibiotic-loaded ceramic sternum for sternal replacement in a patient with deep sternal wound infection.

A 68-year-old man presented with destruction of his sternum after cardiac surgery. Classical management with multiple debridements, vacuum dressings and antibiotics failed. A replacement of his sternum was performed using an antibiotic-loaded porous alumina ceramic sternum. Despite the infected wound, the ceramic sternum did not get infected due to the high antibiotic concentration obtained locally. Two years after the surgery, no relapse occurred and the pulmonary function tests improved.

Does low hydroxyl group surface density explain less bacterial adhesion on porous alumina?

BACKGROUND: Bacterial adhesion depends on surface materials. Recently it was suggested that ceramic-on-ceramic bearings could be less prone to infection than other bearings. We examined the possibility that porous alumina ceramic could be less susceptible to bacterial adhesion. HYPOTHESIS: As hydroxyl groups (OH) on material surface are a major factor governing the surface properties (for example: adsorption, first non-specific step of bacterial adhesion), we hypothesized that alumina had lower OH group density than other material. Thus, we asked (i) if bacterial adhesion was lower on alumina than on titanium alloy, stainless steel and polyethylene and (ii) if OH group density was also lower on alumina. MATERIAL AND METHODS: We performed (i) in vitro bacterial cultures on porous alumina, titanium, stainless steel and polyethylene using Staphylococcus aureus and Pseudomonas aeruginosa, known to adhere to surfaces. Bacterial cultures were done 3 times in duplicate for each material and each strain. Colony Forming Units (CFU) per cm2 were measured; (ii) Neutral red reagent helped obtaining OH density estimates using spacer arms. UV-visible spectrophotometry method with Neutral red test, reproduced twice for each surface, provided µg/cm2 measurements of OH density. RESULTS: There was significantly less P. aeruginosa adherent on porous alumina (2.25×104 CFU/cm2) than on titanium (4.27×105 CFU/cm2, p=0.01), on stainless steel (2.44×105 CFU/cm2, p=0.02) and on polyethylene (7.29×105 CFU/cm2, p<0.001). S. aureus was significantly less adherent on porous alumina (3.22×105 CFU/cm2) than on polyethylene (5.23×106 CFU/cm2, p=0.01), but there was no difference with titanium (1.64×106 CFU/cm2, p=0.08) and stainless steel (1.79×106 CFU/cm2, p=0.1). There was significantly lower Neutral red grafted on porous alumina (0.09µg/cm2) than on titanium (8.88µg/cm2, p<0.0001), on stainless steel (39.8µg/cm2, p=0.002) and on polyethylene (4.5µg/cm2, p<0.01). However, no correlation was found between bacterial adherence and OH group density. DISCUSSION: Bacterial adherence on porous alumina was lower than on other bearings. Although there were less surface OH groups on porous alumina, we failed establishing a statistical correlation between bacterial adherence and OH group density. LEVEL OF EVIDENCE: IV, in vitro study.

Antibiotic-loaded Porous Alumina Ceramic for One-stage Surgery for Chronic Osteomyelitis.

The classic treatment of chronic osteomyelitis is usually a two-stage surgery combined with systemic antibiotic therapy for several months. We report the case of a patient presenting a chronic osteomyelitis caused by methicillin-resistant Staphylococcus aureus who was treated with a one-stage surgery using an antibiotic-loaded ceramic. We used a porous alumina ceramic loaded with gentamicin to reconstruct the bone removed during débridement and to avoid its colonization. All bacteriological samples performed before and during the surgery revealed the presence of a methicillin-resistant S aureus. Because of the local release of the antibiotic, very high concentrations (more than 50 times the concentration needed) were administered in the surgical wound, thus helping to cure the infection. Owing to the strength of the ceramic, the patient was allowed to walk 10 days after the surgery. After a follow-up at 14 months, the patient is well-being, without any relapse of the infection. The CT-scan follow-up shows an osseointegration of the ceramic. Even, if it is too early to tell that infection is completely cured, these first results are encouraging for the use, in the future, of this antibiotic-loaded ceramic for complex bone infection.

Alumina Biocompatibility.

Alumina (Al2O3) ceramic is widely used for medical devices and its biocompatibility is well known and is reported in articles and textbooks. However, finding proof of this assertion gathered over more than 40 years can be challenging. We performed a literature review about alumina biocompatibility to compile data from the literature. We searched for articles on the biocompatibility of alumina in relation to the ISO 10993-1 International Standard, which defines the biocompatibility of biomaterials. For every biological effect listed in the norm, such as cytotoxicity, sensitization, implantation, and genotoxicity, in vitro and in vivo tests in animals and humans did not reveal any abnormal biological response. Proof for the the well-known biocompatibility of alumina is summarized in this review.

Porous alumina ceramic sternum: A reliable option for sternal replacement.

CONTEXT: To date, there is no gold standard technique for sternum replacement. Current techniques rely on metallic prosthesis, meshes and bars, or bone grafts. However, they have several pitfalls. AIMS: The aim of this article is to report the results of sternal replacement with a porous alumina ceramic sternum. SETTINGS AND DESIGN: Surgeries were performed in two teaching hospitals in France. METHODS: We designed a porous alumina ceramic prosthesis which possesses interesting characteristics for this surgery such as great biocompatibility, a certain level of bacterial resistance, radiolucency, and compatibility with radiotherapy. The implant is stitched to the ribs with suture thread and does not require osteosynthesis material. RESULTS: Six patients with a mean age of 60.6 years received this prosthesis. Indication was tumor in five cases and mediastinitis in one case. The mean follow-up is 20 months (3-37 months). No major complication occurred and healing was fine for all patients. Patients did not complain of breathing discomfort or pain related to the prosthesis. CONCLUSIONS: This new technique is promising even if there are only six patients in this study.

Characteristics of and risk factors for severe neurological deficit in patients with pyogenic vertebral osteomyelitis: A case-control study.

Severe neurological deficit (SND) is a rare but major complication of pyogenic vertebral osteomyelitis (PVO). We aimed to determine the risk factors and the variables associated with clinical improvement for SND during PVO.This case-control study included patients without PVO-associated SND enrolled in a prospective randomized antibiotic duration study, and patients with PVO-associated SND managed in 8 French referral centers. Risk factors for SND were determined by logistic regression.Ninety-seven patients with PVO-associated SND cases, and 297 controls were included. Risk factors for SND were epidural abscess [adjusted odds ratio, aOR 8.9 (3.8-21)], cervical [aOR 8.2 (2.8-24)], and/or thoracic involvement [aOR 14.8 (5.6-39)], Staphylococcus aureus PVO [aOR 2.5 (1.1-5.3)], and C-reactive protein (CRP) >150 mg/L [aOR 4.1 (1.9-9)]. Among the 81 patients with PVO-associated SND who were evaluated at 3 months, 62% had a favorable outcome, defined as a modified Rankin score ≤ 3. No factor was found significantly associated with good outcome, whereas high Charlson index [adjusted Hazard Ratio (aHR) 0.3 (0.1-0.9)], low American Spinal Injury Association (ASIA) impairment scale at diagnosis [aHR 0.4 (0.2-0.9)], and thoracic spinal cord compression [aHR 0.2 (0.08-0.5)] were associated with poor outcome. Duration of antibiotic treatment was not associated with functional outcome.SND is more common in cervical, thoracic, and S. aureus PVO, in the presence of epidural abscess, and when CRP >150 mg/L. Although neurological deterioration occurs in 30% of patients in early follow-up, the functional outcome is quite favorable in most cases after 3 months. The precise impact of optimal surgery and/or corticosteroids therapy must be specified by further studies.