Assessment of the impact of telehealth intervention in patients with bone and joint infection.

OBJECTIVES: Patients with bone and joint infections (BJI) are involved in a complex care pathway and require prolonged antimicrobial treatment. Some studies have suggested that a pharmacist-led telehealth intervention (TI) could help to ensure better follow-up of chronic diseases. To our knowledge, there are no data on the effects of pharmacist-led TI on patients with BJI. The aim of this study is to assess the impact of a TI on patients treated for BJIs at three weeks after hospital discharge. PATIENTS AND METHODS: Patients encountered during hospitalization and receiving standardized care including TI were included in the study. All adverse events (AE) reported by patients during TI were evaluated. Impact of pharmaceutical interventions (PIs) provided by a clinical pharmacist following TI was evaluated by CLEO© (CLinical, Economic and Organizational) scale. Patient satisfaction concerning TI was assessed by an anonymous questionnaire following medical consultation at the end of antimicrobial treatment. RESULTS: Over a 4-month period, 36 patients received TI. Fifty-two AEs were identified in 21 patients (58%). Two patients were hospitalized due to an AE. Clinical pharmacists provided 34 pharmaceutical interventions (PIs) for 23 patients (64%). According to CLEO scale, 11 PIs had a major clinical impact (32%), 6 PIs (18%) had a favorable impact on the direct cost of treatment and 27 PIs (79%) had positive organizational impact. Concerning TI process, patients were satisfied or very satisfied, with an average score of 9.6/10. CONCLUSION: TI led to a high number of pharmaceutical interventions (PIs), with a meaningful clinical, organizational, and economic impact. Patients were also highly satisfied with this intervention.

Disability-adjusted life years from bone and joint infections associated with antimicrobial resistance: an insight from the 2019 Global Burden of Disease Study.

PURPOSE: Bone and joint infections, complicated by the burgeoning challenge of antimicrobial resistance (AMR), pose significant public health threats by amplifying the disease burden globally. We leveraged results from the 2019 Global Burden of Disease Study (GBD) to explore the impact of AMR attributed to bone and joint infections in terms of disability-adjusted life years (DALYs), elucidating the contemporary status and temporal trends. METHODS: Utilizing GBD 2019 data, we summarized the burden of bone and joint infections attributed to AMR across 195 countries and territories in the 30 years from 1990 to 2019. We review the epidemiology of AMR in terms of age-standardized rates, the estimated DALYs, comprising years of life lost (YLLs) and years lived with disability (YLDs), as well as associations between DALYs and socio-demographic indices. RESULTS: The GBD revealed that DALYs attributed to bone and joint infections associated with AMR have risen discernibly between 1990 and 2019 globally. Significant geographical disparities and a positive correlation with socio-demographic indicators were observed. Staphylococcus aureus infections, Group A Streptococcus, Group B Streptococcus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter-related bone and joint infections were associated with the highest DALYs because of a high proportion of antimicrobial resistance. Countries with limited access to healthcare, suboptimal sanitary conditions, and inconsistent antibiotic stewardship were markedly impacted. CONCLUSIONS: The GBD underscores the escalating burden of bone and joint infections exacerbated by AMR, necessitating urgent, multi-faceted interventions. Strategies to mitigate the progression and impact of AMR should emphasize prudent antimicrobial usage and robust infection prevention and control measures, coupled with advancements in diagnostic and therapeutic modalities.

Pan-genome mediated therapeutic target mining in Kingella kingae and inhibition assessment using traditional Chinese medicinal compounds: an informatics approach.

Kingella kingae causes bacteremia, endocarditis, osteomyelitis, septic arthritis, meningitis, spondylodiscitis, and lower respiratory tract infections in pediatric patients. Usually it demonstrates disease after inflammation of mouth, lips or infections of the upper respiratory tract. To date, therapeutic targets in this bacterium remain unexplored. We have utilized a battery of bioinformatics tools to mine these targets in this study. Core genes were initially inferred from 55 genomes of K. kingae and 39 therapeutic targets were mined using an in-house pipeline. We selected aroG product (KDPG aldolase) involved in chorismate pathway, for inhibition analysis of this bacterium using lead-like metabolites from traditional Chinese medicinal plants. Pharmacophore generation was done using control ZINC36444158 (1,16-bis[(dihydroxyphosphinyl)oxy]hexadecane), followed by molecular docking of top hits from a library of 36,000 compounds. Top prioritized compounds were ZINC95914016, ZINC33833283 and ZINC95914219. ADME profiling and simulation of compound dosing (100 mg tablet) was done to infer compartmental pharmacokinetics in a population of 300 individuals in fasting state. PkCSM based toxicity analysis revealed the compounds ZINC95914016 and ZINC95914219 as safe and with almost similar bioavailability. However, ZINC95914016 takes less time to reach maximum concentration in the plasma and shows several optimal parameters compared to other leads. In light of obtained data, we recommend this compound for further testing and induction in experimental drug design pipeline.Communicated by Ramaswamy H. Sarma.

Epidemiology, Management, and Outcomes of Large and Small Native Joint Septic Arthritis in Adults.

BACKGROUND: Native joint septic arthritis (NJSA) is poorly studied. We describe the epidemiology, treatment, and outcomes of large joint NJSA (LNJSA) and small joint NJSA (SNJSA) in adults at Middlemore Hospital, Auckland, New Zealand. METHODS: This was a coding-based retrospective study of patients ≥16 years old admitted between 2009 and 2014. Prosthetic joint infections were excluded. RESULTS: Five hundred forty-three NJSA episodes were included (302 LNJSA, 250 SNJSA). Only 40% had positive synovial fluid culture. Compared to SNJSA, LNJSA has higher incidence (13 vs 8/100 000 person-years [PY]), occurs in older, more comorbid patients, and is associated with greater rates of treatment failure (23% vs 12%) and mortality, despite longer antibiotic treatment. Total incidence is higher than previously reported (21/100 000 PY), with marked interethnic variation. Incidence rises with age (LNJSA only) and socioeconomic deprivation (LNJSA and SNJSA). Tobacco smokers and males are overrepresented. The most commonly involved joints were knee (21%) and hand interphalangeal (20%). Staphylococcus aureus was the most common pathogen (53%). Mean antibiotic duration was 25 days for SNJSA and 40 days for LNJSA, and the mean number of surgical procedures was 1.5 and 1.6, respectively. Treatment failure was independently associated with LNJSA, age, intra-articular nonarthroplasty prosthesis, and number of surgical procedures. CONCLUSIONS: This is the largest contemporary series of adult NJSA. SNJSA has better outcomes than LNJSA and may be able to be safely treated with shorter antimicrobial courses. Incidence is high, with significant ethnic and socioeconomic variation. Microbiological NJSA case ascertainment underestimates case numbers as it frequently excludes SNJSA.

Clinical and Economic Impact of Implementing OVIVA Criteria on Patients With Bone and Joint Infections in Outpatient Parenteral Antimicrobial Therapy.

The OVIVA study demonstrated noninferiority for managing bone and joint infections (BJIs) with oral antibiotics. We report that 79.7% of OPAT patients being treated for BJIs at our center would be eligible for oral antibiotics, saving a median (IQR) 19.5 IV-antibiotic days (8.5-37) and GBP 1234 (569-2594) per patient.

Successful outpatient parenteral antibiotic therapy delivery via telemedicine.

Objectives: Most outpatient parenteral antimicrobial therapy (OPAT) services use a hospital-based model of care in which patients remain in proximity to large hospitals facilitating clinical review. We aimed to evaluate clinical outcomes and complication rates for patients living in geographically isolated locations managed by telemedicine-supported OPAT. Methods: This was a retrospective cohort study. Results: Between 2011 and 2015, we delivered 88 episodes of care involving 83 adult patients resulting in 2261 days of OPAT. The median age was 56 years, 8 of 83 (10%) were indigenous Australian and the median Charlson comorbidity index score was 2 (IQR 1-4). The median distance of patients' residence from our hospital was 288 km (IQR 201-715) and the median duration on the programme was 26 days (IQR 14-34). Bone and joint infections accounted for 75% of infections treated. Favourable clinical outcomes (improvement or cure) were achieved in 87% of patients and the unplanned, OPAT-related readmission rate was 8%. Nineteen percent and 10% of patients had drug-related and line-related adverse effects, respectively. Conclusions: Despite a complex case mix, our adverse event and readmission rates are similar to the published literature describing a non-telemedicine model to deliver OPAT. High rates of favourable clinical outcomes and likely cost benefits suggest that telemedicine-supported OPAT is an efficacious and safe substitute for inpatient care in our setting.

Duration of intravenous antibiotic therapy for children with acute osteomyelitis or septic arthritis: a feasibility study.

BACKGROUND: There is little current consensus regarding the route or duration of antibiotic treatment for acute osteomyelitis (OM) and septic arthritis (SA) in children. OBJECTIVE: To assess the overall feasibility and inform the design of a future randomised controlled trial (RCT) to reduce the duration of intravenous (i.v.) antibiotic use in paediatric OM and SA. DESIGN: (1) A prospective service evaluation (cohort study) to determine the current disease spectrum and UK clinical practice in paediatric OM/SA; (2) a prospective cohort substudy to assess the use of targeted polymerase chain reaction (PCR) in diagnosing paediatric OM/SA; (3) a qualitative study to explore families' views and experiences of OM/SA; and (4) the development of a core outcome set via a systematic review of literature, Delphi clinician survey and stakeholder consensus meeting. SETTING: Forty-four UK secondary and tertiary UK centres (service evaluation). PARTICIPANTS: Children with OM/SA. INTERVENTIONS: PCR diagnostics were compared with culture as standard of care. Semistructured interviews were used in the qualitative study. RESULTS: Data were obtained on 313 cases of OM/SA, of which 218 (61.2%) were defined as simple disease and 95 (26.7%) were defined as complex disease. The epidemiology of paediatric OM/SA in this study was consistent with existing European data. Children who met oral switch criteria less than 7 days from starting i.v. antibiotics were less likely to experience treatment failure (9.6%) than children who met oral switch criteria after 7 days of i.v. therapy (16.1% when switch was between 1 and 2 weeks; 18.2% when switch was > 2 weeks). In 24 out of 32 simple cases (75%) and 8 out of 12 complex cases (67%) in which the targeted PCR was used, a pathogen was detected. The qualitative study demonstrated the importance to parents and children of consideration of short- and long-term outcomes meaningful to families themselves. The consensus meeting agreed on the following outcomes: rehospitalisation or recurrence of symptoms while on oral antibiotics, recurrence of infection, disability at follow-up, symptom free at 1 year, limb shortening or deformity, chronic OM or arthritis, amputation or fasciotomy, death, need for paediatric intensive care, and line infection. Oral switch criteria were identified, including resolution of fever for ≥ 48 hours, tolerating oral food and medicines, and pain improvement. LIMITATIONS: Data were collected in a 6-month period, which might not have been representative, and follow-up data for long-term complications are limited. CONCLUSIONS: A future RCT would need to recruit from all tertiary and most secondary UK hospitals. Clinicians have implemented early oral switch for selected patients with simple disease without formal clinical trial evidence of safety. However, the current criteria by which decisions to make the oral switch are made are not clearly established or evidence based. FUTURE WORK: A RCT in simple OM and SA comparing shorter- or longer-course i.v. therapy is feasible in children randomised after oral switch criteria are met after 7 days of i.v. therapy, excluding children meeting oral switch criteria in the first week of i.v. therapy. This study design meets clinician preferences and addresses parental concerns not to randomise prior to oral switch criteria being met. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

The impact of PCR in the management of prosthetic joint infections.

An accurate diagnosis of prosthetic joint infection (PJI) remains a challenging clinical problem and is essential for the success of treatment regardless of the treatment option chosen by patients and surgeons. In recent years, PCR for the diagnosis of PJI has received much attention. Here, we review the impact of common PCR-based techniques on identifying causative organisms, antibiotic management and economics of PJI.

[Septic arthritis of undetermined origin in children: a proposal for the assessment and its therapy]. / Une arthrite septique d'origine indéterminée chez l'enfant.

Septic arthritis is not a frequent, but quite classical pathology in children. It can be followed by a severe outcome in case of delayed and/or inadequate treatment. The drainage of the infected joint associated with a prompt and adapted antibiotherapy are together the cornerstones of this treatment. The isolation and identification of the causative microorganism is also of the highest importance. Up to now, unfortunately, a large proportion of septic arthritis are treated by antibiotics although all culture remain negative. This paper has two objectives: one is to present the different steps to optimize the assessment and diagnosis; the second, to increase the sensitivity of the pathogen identification. At last, we present our proposal for empirical antibiotherapy.

Knee joint infection after ACL reconstruction: prevalence, management and functional outcomes.

PURPOSE: Septic arthritis after an ACL reconstruction is a rare but serious complication. Functional outcomes of these patients have not been studied in depth in large series. The aim of this study was to determine the prevalence and management of knee joint infection following ACL reconstruction and to assess the functional outcomes. METHODS: A retrospective assessment of knee joint infections occurring after arthroscopically assisted ACL reconstructions done from 2006 to 2009 in two hospitals by the same surgical team is presented. Patients with signs and symptoms of joint infection along with blood and synovial effusion laboratory parameters suggestive of infection were considered as septic arthritis. All the patients were treated with antibiotic therapy according to antibiotic sensitivity and had at least one arthroscopic lavage. Final outcomes were assessed and compared with a control group using the KT-1000 arthrometer, functional testing and radiological examination. RESULTS: Fifteen (1.8 %) out of 810 patients included in the study were considered as a joint infection. Microbiology showed that coagulase-negative Staphylococcus was present in 10 patients, Staphylococcus Aureus in three patients (2 MSSA and 1 MRSA) and Propinebacterium sp. in one patient. In one patient, the micro-organism was unknown. At a mean follow-up of 39.3 ± 13 months, the Lysholm score was 77.7 ± 15.3, the IKDC score was 70.4 ± 19.5, and the KT-1000 compared to the non-injured contralateral knee showed a mean difference of 1.3 ± 2 mm. Functional outcomes in the control group were slightly better than those obtained in the infected group (Lysholm score; 90.7 ± 9.4, p = 0.007. IKDC score; 86.6 ± 6.8, p = 0.004). All but one patient retained their reconstructed ACL. CONCLUSIONS: The prevalence of septic arthritis after an ACL reconstruction in this series was 1.8 %. Arthroscopic lavages along with antibiotic treatment led us to preserve all but one graft. Functional outcomes in the infected patients were not as good as those obtained in patients without infection.

[Outpatient parenteral antimicrobial therapy (OPAT) in bone and joint infections]. / Antibiothérapie parentérale ambulatoire (APA), par voie intraveineuse dans les infections ostéoarticulaires.

The medical treatment of many bone and joint infections (including chronic osteomyelitis, prosthetic joint infection, and septic arthritis) requires prolonged intravenous antimicrobial therapy. For some patients, this treatment could be administered outside the hospital in a program that offers outpatient parenteral antimicrobial therapy (OPAT). In France, we have no registry of patients receiving OPAT. Initiation of this program requires specific criteria based on a patient evaluation and selection, and an interdisciplinary team of professionals committed to high-quality patient care. Various vascular access devices and infusion pump therapy are used to administer OPAT. The most common parenteral agents for OPAT are beta-lactams and glycopeptids (specifically vancomycin). Antimicrobial courses are stopped prematurely in 3 to 10% of the cases because of an adverse reaction or vascular access complications. Several published studies demonstrate the effectiveness of OPAT and higher patient satisfaction than hospital care. In addition, OPAT is clearly more cost-effective than intravenous therapy provided in the hospital setting. Some diagnoses, such as cellulites, community-acquired pneumonia, and endocarditis may be managed with OPAT.

Role of linezolid in the treatment of orthopedic infections.

Gram-positive organisms, particularly staphylococci and streptococci, are responsible for the majority of bone and joint infections. The rising incidence of antimicrobial resistance among Staphylococcus aureus, coagulase-negative staphylococci and enterococci means that novel antibiotics with unique mechanisms of antimicrobial activity are needed, especially in orthopedic infections. Linezolid is the first of the oxazolidinones, a new class of antibacterial agents particularly effective against Gram-positive infections including methicillin- and vancomycin-resistant strains. With an excellent oral bioavailability and acceptable safety profile, linezolid offers a valuable alternative to more traditional therapies, such as glycopeptides. No large randomized trials have been published on its use in patients with orthopedic infections, but early results are encouraging. Reported adverse events, especially bone marrow suppression and optic neuropathy seen with prolonged administration, mean that treatment of such patients must be undertaken with careful follow-up of laboratory tests. Until now, little resistance has been reported.

The safety and efficacy of linezolid in orthopaedic practice for the treatment of infection due to antibiotic-resistant organisms.

Linezolid is the first of a new class of antibacterial agents, the oxazolidinones. It is particularly effective against Gram-positive infections and little resistance has been reported, even amongst methicillin- and vancomycin-resistant bacteria. The compound's excellent oral bioavailability and reasonable safety profile, along with the increasing incidence of resistant infections, means that linezolid offers a valuable alternative to more traditional therapies such as vancomycin. Although no large randomised trials have been carried out in patients with orthopaedic infections such as osteomyelitis and septic arthritis, early results are encouraging. However, the apparent increase in observed adverse events, particularly bone marrow suppression, seen with prolonged administration, means that treatment of such patients must be undertaken with careful surveillance, at least until these complications are better understood.

[Teicoplanin in the treatment of bone and joint infections due to methicillin resistant staphylococci. Experience in adult patients]. / Teicoplanina en el tratamiento de las infecciones osteoarticulares por Staphylococcus meticilino-resistente. Experiencia en adultos.

We retrospectively evaluated 89 episodes of bone and joint infections due to methicillin-resistant staphylococci: 56 chronic osteomyelitis (CO), 10 septic arthritis (SA) and 23 infections associated to arthroplasties (IAA). We analyzed the efficacy of Teicoplanin (T) in three times a week or daily administration schemes and adequate surgery (AS). Also, we determined cost savings derived from outpatient parenteral antibiotic therapy (OPAT). The overall efficacy of T in CO and both in cases with and without implants, was higher when antibiotic therapy was associated to AS (86 vs. 46%, p = 0.001; 100 vs. 33%, p = 0.0049 and 76 vs. 50%, p = 0.09). All SA were cured. The overall efficacy of T was higher in IAA with implant removal vs. surgical debridement (100 vs. 54%, p = 0.045). In all cases, T was similarly effective when administered three times a week vs. daily administration, when associated to AS. The savings derived from OPAT were 897 days/bed and USS 179,400. Adverse effects were few and light (8 episodes, 9%). The results obtained are similar to those published in the literature and show that T administered daily or in a three times a week scheme and associated to AS, is effective and safe for the treatment of bone and joint infections. The savings derived from OPAT, mainly related to reduced hospitalization, are significant in these pathologies, which usually require long treatment periods.

Cost-effectiveness of antibiotic prophylaxis for bacterial arthritis.

The outcome of bacterial arthritis is generally poor: the mortality is 10 - 15% and there is loss of joint function in 25 - 50% of the survivors. The incidence of bacterial arthritis is low: 2 - 6 cases per 100,000 people per year. Risk factors are age, joint disease (especially rheumatoid arthritis [RA]), diabetes mellitus and the presence of a prosthetic joint. The predominant situations that can lead to bacterial arthritis are skin infections of the feet and rarely invasive medical or dental procedures. Due to the severity of the disease, antibiotic prophylaxis of haematogenous bacterial arthritis in patients with prosthetic joints is advocated. However, due to the rarity of the disease it is unclear whether the advantages of prophylaxis outweigh the disadvantages of the large-scale use of antibiotics, such as side effects, costs and bacterial resistance. In a decision-analysis of a large group of patients with joint diseases, antibiotic treatment of skin infections appeared to be cost-effective in the prevention of haematogenous bacterial arthritis, mainly in high-risk patients. On the other hand, prophylaxis around medical or dental procedures was not cost-effective, except possibly in a small group of patients with increased risk.

[The comparative costs of vancomycin treatment versus teicoplanin in osteoarticular infection caused by methicillin-resistant staphylococci]. / Le coût comparatif du traitement par vancomycine versus teicoplanine dans l'infection ostéoarticulaire à staphylocoques résistants à la méticilline.

This clinical and economical study compared two glycopeptides regimen i.e., vancomycin and teicoplanin in the treatment of osteoarticular infection involving methicillin-resistant staphylococcus. After randomization, 15 patients (group 1) received vancomycin (23 F per gram) in continuous infusion through a central venous catheter and 15 others (group 2) intramuscular teicoplanin (311-357 F a 400 mg vial). The clinical study focused on treatment tolerance in an in-patient setting as well as in a non in-patient one. The cost analysis focused on total expenses including those of antibiotics, those of medical devices for antibiotic administration and those of the complications caused by the antibiotics use. Total expenses per patient averaged 8744 F with vancomycin and 8555 F with teicoplanin (NS). The apparent money saving by using a cheap antibiotic (i.e. vancomycin) was illusionary as one took in account the expenses for medical devices e.g., central venous catheters required to administer vancomycin and the complications due to the use of these devices.

Antibiotic prophylaxis for haematogenous bacterial arthritis in patients with joint disease: a cost effectiveness analysis.

OBJECTIVE: To assess the cost effectiveness of antibiotic prophylaxis for haematogenous bacterial arthritis in patients with joint disease. METHODS: In a decision analysis, data from a prospective study on bacterial arthritis in 4907 patients with joint disease were combined with literature data to assess risks and benefits of antibiotic prophylaxis. Effectiveness and cost effectiveness calculations were performed on antibiotic prophylaxis for various patient groups. Grouping was based on (a) type of event leading to transient bacteraemia-that is, infections (dermal, respiratory/urinary tract) and invasive medical procedures-and (b) the patient's susceptibility to bacterial arthritis which was increased in the presence of rheumatoid arthritis, large joint prostheses, comorbidity, and old age. RESULTS: Of the patients with joint disease, 59% had no characteristics that increased susceptibility to bacterial arthritis, and 31% had one. For dermal infections, the effectiveness of antibiotic prophylaxis was maximally 35 quality adjusted life days (QALDs) and the cost effectiveness maximally $52 000 per quality adjusted life year (QALY). For other infections, the effectiveness of prophylaxis was lower and the cost effectiveness higher. Prophylaxis for invasive medical procedures seemed to be acceptable only in patients with high susceptibility: 1 QALD at a cost of $1300/QALY; however, the results were influenced substantially when the level of efficacy of the prophylaxis or cost of prophylactic antibiotics was changed. CONCLUSION: Prophylaxis seems to be indicated only for dermal infections, and for infections of the urinary and respiratory tract in patients with increased susceptibility to bacterial arthritis. Prophylaxis for invasive medical procedures, such as dental treatment, may only be indicated for patients with joint disease who are highly susceptible.