Current osteomyelitis mouse models, a systematic review

Osteomyelitis is an inflammatory bone disease caused by an infecting microorganism leading to a gradual bone loss. Due to the difficulty in studying osteomyelitis directly in patients, animal models allow researchers to investigate the pathogenesis of the infection and the development of novel prophylactic, anti-inflammatory and antimicrobial treatment strategies. This review is specifically focused on the in vivo mouse osteomyelitis studies available in literature. Thus, a systematic search on Web of Science and PubMed was conducted using the query “(infection) AND (mice OR mouse OR murine) AND (model OR models) AND (arthroplasty OR fracture OR (internal fixator) OR (internal fixation OR prosthesis OR implant OR osteomyelitis)”. After critical assessment of the studies according to the inclusion and exclusion criteria, 135 studies were included in the detailed analysis. Based on the model characteristics, the studies were classified into five subject groups: haematogenous osteomyelitis, post-traumatic osteomyelitis, bone-implant-related infection, peri-prosthetic joint infection, fracture-related infection. In addition, the characteristics of the mice used, such as inbred strain, age or gender, the characteristics of the pathogens used, the inoculation methods, the type of anaesthesia and analgesia used during surgery and the procedures for evaluating the pathogenicity of the infecting micro-organism were described. Overall, the mouse is an excellent first step in vivo model to study the pathogenesis, inflammation and healing process of osteomyelitis and to evaluate novel prophylaxis and treatment strategies.

Late Neonatal Sepsis with Acute Haematogenous Osteomyelitis Foci: Clinical Case

Background. The incidence of sepsis among newborns ranges from 1–12 to 38 per 1,000 live births in the world according to scientific literature [1, 2]. The clinical case demonstrates the features of the newborn organism sensitivity and the therapeutic and diagnostic process difficulties.Clinical case description. The boy was born on the 37th week of gestation, 1st of twins, with body weight 3330 g, height 51 cm, APGAR score 8/9 points. He was on breastfeeding. His condition has deteriorated rapidly on the 9th day of life. The condition was severe due to intoxication syndrome, necrotising enterocolitis (NEC) manifestation, further development of systemic inflammatory response syndrome and multiple organ dysfunction syndrome. Severe pain syndrome and movement restraint in limbs have appeared on the 20th day of life. X-ray imaging: NEC signs, multiple osteomyelitis foci in the limbs.Conclusion. Modern adequate diagnosis and justified treatment tactics have led to positive outcome: child’s condition has improved, body weight has increased, pain syndrome has been managed, the volume of movements in the limbs has increased, inflammatory markers have stabilised. The child was discharged from hospital in satisfactory condition at the age of 2 months.

Amoxicillin-Clavulanic Acid Empirical Oral Therapy for the Management of Children with Acute Haematogenous Osteomyelitis

According to the Guidelines of the European Society of Pediatric Infectious Diseases (ESPID), in low methicillin-resistant Staphylococcus aureus (MRSA) prevalence settings, short intravenous therapy is recommended in uncomplicated cases of acute haematogenous osteomyelitis (AHOM), followed by empirical oral therapy, preferentially with first/second-generation cephalosporin or dicloxacillin or flucloxacillin. However, several practical issues may arise using some of the first-line antibiotics such as poor palatability or adherence problems. Clinical, laboratory and therapeutic data from children with AHOM hospitalized in one Italian Paediatric Hospital between 2010 and 2019 were retrospectively collected and analyzed. The aim of the study was to highlight the extent of the use and the possible role of amoxicillin-clavulanic acid in the oral treatment of children with AHOM. Two hundred and ten children were included. S.aureus was identified in 42/58 children (72.4% of identified bacteria); 2/42 S.aureus isolates were MRSA (4.8%). No Kingella kingae was identified. Amoxicillin-clavulanic acid was the most commonly used oral drug (60.1%; n = 107/178) and it was associated with clinical cure in all treated children. Overall, four children developed sequelae. One (0.9%) sequela occurred among the 107 children treated with amoxicillin-clavulanic acid. Our results suggest that amoxicillin-clavulanic acid might be an option for oral antibiotic therapy in children with AHOM.

Criteria for Differentiation of Non-Bacterial and Haematogenous Osteomyelitis: A Case-Control Study With Prospective Verification of the Outcomes

Background. Patients with haematogenous and non-bacterial osteomyelitis have similar clinical symptoms (pain in the nidus area, soft tissue swelling, fever) and laboratory signs (increased erythrocyte sedimentation rate, leukocyte count, C-reactive protein concentration). The criteria for distinguishing these two states are not determined.Objective. Our aim was to determine diagnostic criteria to differentiate haematogenous and non-bacterial osteomyelitis.Methods. The study included data of patients under the age of 18 years with non-bacterial or haematogenous osteomyelitis hospitalised to two clinical centres from 2009 to 2016. The diagnosis was established and re-verified according to archival data (medical history) and after two years of observation (at least once a year). Clinical, anamnestic and laboratory data (haemoglobin, leukocytes, leukocyte formula, platelets, ESR and C-reactive protein, CRP) as well as the results of radiation diagnostics (X-ray, CT scan, MRI or osteosyntigraphy) obtained at the disease onset were taken into account as potential diagnostic criteria.Results. Out of 145 patients with non-bacterial or haematogenous osteomyelitis, the diagnosis was re-verified in 138, of them non-bacterial osteomyelitis — in 91, haematogenous osteomyelitis — in 47. The following criteria had the highest diagnostic value for establishing cases of non-bacterial osteomyelitis: detection of bone destruction foci surrounded by osteosclerosis area [sensitivity (Se) 1.0; specificity (Sp) 0.79]; absence of fever (Se 0.66; Sp 0.92); the number of bone destruction foci > 1 (Se 0.73; Sp 1.0); CRP 55 mg/L (Se 0.94; Sp 0.73); negative results of bacteriological examination of the material from the bone destruction focus (Se 1.0; Sp 0.67).Conclusion. Diagnostic criteria for differentiation of non-bacterial and haematogenous osteomyelitis have been described. Further research on the efficacy of using these criteria to reduce the risk of diagnostic errors, decrease the diagnostic pause, reduce the risk of non-bacterial osteomyelitis complications is needed.