Long-Term Pharmacokinetics of Dalbavancin in ABSSSI and Osteoarticular Settings: A Real-Life Outpatient Context

Dalbavancin is a lipoglycopeptide approved for treatment of Gram-positive infections of skin and skin-associated structures (ABSSSI). Currently, off-label use at high dosages for osteoarticular infections deserves attention. This work aimed to study the long-term plasma pharmacokinetics of dalbavancin in outpatients with ABSSSI or osteoarticular infections, treated either with one or two 1500 mg doses of dalbavancin. A liquid chromatography-tandem mass spectrometry method was used to measure total dalbavancin concentrations in plasma samples. The results were analyzed through a non-compartmental analysis (NCA). Breakpoint minimum inhibitory concentration (MIC) was used to calculate AUC/MIC and T>MIC parameters, adjusted by 93% protein binding. A total of 14 patients were enrolled, 11 with osteoarticular infection and 3 with ABSSSI. Long-term pharmacokinetics showed median T>MIC (0.125 mg/L) of 11.9 and 13.7 weeks for single and dual dose, respectively. Similarly, median AUC0-2w/MIC ratios of 20,590 and 31,366 were observed for single and dual dose regimens, respectively. No adverse events were observed, and treatment success was achieved in 12/14 patients. Failure was associated with the worst clinical conditions, bone infections, and single dose. The results of this study show that dalbavancin exposure exceeds previously suggested pharmacodynamic targets. Optimization of these targets is needed for the osteoarticular setting.

TO STUDY CORRELATION OF SERUM VITAMIN D LEVEL WITH OSTEOARTICULAR INFECTION

Background: To study correlation of serum vitamin D level with osteoarticular infection Methods: All patients (5 to 65 years of age) were presented with pain and raised local temperature of osteoarticular joint or prosthetic joint in the Orthopaedic department of S.M.S. Medical college and attached hospitals, were included in the study. Results: The mean (SD) of S. Vitamin D (ng/mL) in the Osteoarticular Infection: Present group was 19.08 (8.41). The mean (SD) of S. Vitamin D (ng/mL) in the Osteoarticular Infection: Absent group was 18.53 (9.26). The median (IQR) of S. Vitamin D (ng/mL) in the Osteoarticular Infection: Present group was 17.7 (14.15-23.3). The median (IQR) of S. Vitamin D (ng/mL) in the Osteoarticular Infection: Absent group was 14.85 (11.6-23.3). The S. Vitamin D (ng/mL) in the Osteoarticular Infection: Present ranged from 8.2 -38. The S. Vitamin D (ng/mL) in the Osteoarticular Infection: Absent ranged from 9.2 - 46. Conclusion: Our study result were similar in respect to other authors but statistically not significant, therefore requires reopening of the debate on correlation of serum vitamin D with osteoarticular infections. Keywords: Osteoarticular Infection, Vitamin D, Joint

Fulminant Infective Endocarditis Due to Kingella Kingae and Several Complications in a 6-Year-Old Girl: A Case Report

Kingella kingae is a gram-negative coccobacillus belonging to the HACEK group (Haemophilus species, Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) and is a common oropharyngeal colonizer of healthy young children. Osteoarticular infection is the most commonly reported invasive Kingella kingae infection in children, usually presenting a mild clinical picture. However, it can also cause severe invasive infections, especially infective endocarditis, with a high complication rate. We report the case of a 6-year-old girl, with no past medical history, who presented with fulminant infective endocarditis due to Kingella kingae. She received emergency venoarterial extracorporeal membrane oxygenation support, rapidly underwent cardiac surgery, and was then treated using ceftriaxone for 4 weeks as recommended by the American Heart Association. The patient's postoperative course was marked by a cerebral ischemic stroke consistent with septic embolism. She also presented with a para-aortic pseudoaneurysm that required a secondary surgical procedure, with a good postoperative result. This report illustrates a case of fulminant infective endocarditis due to Kingella kingae and responsible for two major complications. We also describe the preventive valve surgery performed to ensure the preservation of valve function and its capacity for growth.

Osteoarticular Infection of the Shoulder Joint Due to Trichophyton Spp. in a Dog

A 10-year-old Labrador Retriever was referred for persistent lameness due to chronic right shoulder pain, unresponsive to various pain management therapies. Radiographs indicated signs of severe degenerative changes in the joint. Synovial fluid analysis was not diagnostic. Septic arthritis was suspected based on computed tomography and clinical signs. Arthroscopy allowed joint exploration, tissue biopsies, and copious joint lavage. Trichophyton spp. proliferation was identified on antimicrobial culture and histological analysis on samples obtained during arthroscopy. Oral griseofulvin therapy was initiated. Two months later, the referring veterinarian decided to interrupt the treatment after a negative synovial culture despite persistent lameness. Euthanasia was elected upon after pain also appeared on the tarsus; a post-mortem exam was not authorized by the owner. The origin of the infection remains unclear as this patient had no skin lesions and its immunological status was unknown. However, dermatophytosis has been reported in healthy dogs without skin lesions. To the author's knowledge, this is the first report of an osteoarticular infection with a dermatophyte in a dog.

Optimal microbiological sampling for the diagnosis of osteoarticular infection

Infection is a dire complication afflicting every field of orthopaedics and traumatology. If specific clinical, laboratory and imaging parameters are present, infection is often assumed even in the absence of microbiological confirmation. However, apart from confirming infection, knowing the exact infecting pathogen(s) and their antimicrobial susceptibility patterns is paramount to help guide treatment. Every effort should therefore be undertaken with that goal in mind. Not all microbiological findings carry the same relevance, and knowing exactly how and where a sample was collected is key. Several different sampling techniques are available, and one must be aware of both advantages and limitations. Microbiological sampling alternatives in some of the most common clinical scenarios such as native and prosthetic joint infections, osteomyelitis and fracture-related infections, spinal and diabetic foot infections will be discussed. Orthopaedic surgeons should also be aware of basic laboratory sample processing techniques as they have a direct impact on the way specimens should be dealt with and transported to the laboratory. Only by knowing these basic principles will surgeons be able to participate in the multidisciplinary discussion and decision making around how to interpret microbiological findings in each specific patient. Cite this article: EFORT Open Rev 2021;6:390-398. DOI: 10.1302/2058-5241.6.210011

Risk Factors of Daptomycin-Induced Eosinophilic Pneumonia in a Population with Osteoarticular Infection

Background: Daptomycin-induced eosinophilic pneumonia (DEP) is a rare but severe adverse effect and the risk factors are unknown. The aim of this study was to determine risk factors for DEP. Methods: A retrospective cohort study was performed at the Bone and Joint Infection Unit of the Hospital Universitari Bellvitge (January 2014–December 2018). To identify risk factors for DEP, cases were divided into two groups: those who developed DEP and those without DEP. Results: Among the whole cohort (n = 229) we identified 11 DEP cases (4.8%) and this percentage almost doubled in the subgroup of patients ≥70 years (8.1%). The risk factors for DEP were age ≥70 years (HR 10.19, 95%CI 1.28–80.93), therapy >14 days (7.71, 1.98–30.09) and total cumulative dose of daptomycin ≥10 g (5.30, 1.14–24.66). Conclusions: Clinicians should monitor cumulative daptomycin dosage to minimize DEP risk, and be cautious particularly in older patients when the total dose of daptomycin exceeds 10 g.

Clinical, biological and bacteriological characteristics of osteoarticular infections in infants less than 12 months of age

Aim: This retrospective study’s objective was to evaluate osteoarticular infection in infants less than 12 months of age, with a particular focus on biological features and bacteriological etiology. Material & methods: We retrospectively reviewed the medical records of every infant younger than 12 months old admitted in our institution for a suspected osteoarticular infection between January 1980 and December 2016. Results: Sixty-nine patients records were reviewed, including eight neonates, 16 infants from 1 to 5 months old, and 45 from 6 to 12 months old. Conclusion: Neonates and infants aged from 6 to 12 months old were more exposed to infections. Staphylococcus aureus remained the main pathogen in children <6 months, whereas Kingella kingae has become the most frequently isolated microorganism in infants aged from 6 to 12 months old.

Osteoarticular infection in children

Aims We aimed to describe the epidemiological, biological, and bacteriological characteristics of osteoarticular infections (OAIs) caused by Kingella kingae. Methods The medical charts of all children presenting with OAIs to our institution over a 13-year period (January 2007 to December 2019) were reviewed. Among these patients, we extracted those which presented an OAI caused by K. kingae and their epidemiological data, biological results, and bacteriological aetiologies were assessed. Results K. kingae was the main reported microorganism in our paediatric population, being responsible for 48.7% of OAIs confirmed bacteriologically. K. kingae affects primarily children aged between six months and 48 months. The highest prevalence of OAI caused by K. kingae was between seven months and 24 months old. After the patients were 27 months old, its incidence decreased significantly. The incidence though of infection throughout the year showed no significant differences. Three-quarters of patients with an OAI caused by K. kingae were afebrile at hospital admission, 11% had elevated WBCs, and 61.2% had abnormal CRPs, whereas the ESR was increased in 75%, constituting the most significant predictor of an OAI. On MRI, we noted 53% of arthritis affecting mostly the knee and 31% of osteomyelitis located primarily in the foot. Conclusion K. kingae should be recognized currently as the primary pathogen causing OAI in children younger than 48 months old. Diagnosis of an OAI caused by K. kingae is not always obvious, since this infection may occur with a mild-to-moderate clinical and biological inflammatory response. Extensive use of nucleic acid amplification assays improved the detection of fastidious pathogens and has increased the observed incidence of OAI, especially in children aged between six months and 48 months. We propose the incorporation of polymerase chain reaction assays into modern diagnostic algorithms for OAIs to better identify the bacteriological aetiology of OAIs. Cite this article: Bone Joint J 2021;103-B(3):578–583.