A murine femoral ostectomy model with hardware exchange to assess antibiotic-impregnated spacers for implant-associated osteomyelitis.

Implant-associated osteomyelitis is a chronic infection that complicates orthopaedic surgeries. Once infected, 50 % of patients suffer treatment failure, resulting in high healthcare costs. While various small animal models have been developed to investigate the efficacy of prophylactic and therapeutic treatments, the minute scale of murine-model bone and hardware has been prohibitive for evaluating interventions with a complete implant exchange in the setting of an infected critical defect. To address this, the aim of the present study was to develop a murine femur model in which an initial mid-diaphyseal infection was established by surgical implantation of a titanium screw contaminated with bioluminescent Staphylococcus aureus (Xen36). 7 d after the infection was established, an ostectomy was performed to remove the middle segment (3 mm flanking the infected screw hole) and a bone-cement spacer, with or without impregnated gentamicin, was secured with a plate and screws to fix the septic segmental defect. Longitudinal bioluminescent imaging revealed a significant decrease in Xen36 growth following one-stage revision, with the antibiotic-impregnated spacer treated systemically with vancomycin (p < 0.05). This result was corroborated by a significant decrease in colony forming units (CFU) recovered from spacer, bone, soft tissue and hardware 12 d post-operative (p < 0.05). However, ~ 105 CFU/g Xen36 still persisted within the bone despite a clinical therapeutic regimen. Therefore, the model enables the investigation of new therapeutic strategies to improve upon the current standard of care in a mouse model of implant-associated osteomyelitis that employs reconstruction of a critical defect.

3D printed bioceramics for dual antibiotic delivery to treat implant-associated bone infection.

Surgical implant-associated bone infections (osteomyelitis) have severe clinical and socioeconomic consequences. Treatment of chronic bone infections often involves antibiotics given systemically and locally to the affected site in poly (methyl methacrylate) (PMMA) bone cement. Given the high antibiotic concentrations required to affect bacteria in biofilm, local delivery is important to achieve high doses at the infection site. PMMA is not suitable to locally-deliver some biofilm-specific antibiotics, including rifampin, due to interference with PMMA polymerisation. To examine the efficacy of localised, combinational antibiotic delivery compared to PMMA standards, we fabricated rifampin- and vancomycin-laden calcium phosphate scaffolds (CPS) by three-dimensional (3D) printing to treat an implant-associated Staphylococcus aureus bone infection in a murine model. All vancomycin- and rifampin-laden CPS treatments significantly reduced the bacterial burden compared with vancomycin-laden PMMA. The bones were bacteria culture negative in 50 % of the mice that received sustained release vancomycin- and rifampin-laden CPS. In contrast, 100 % of the bones treated with vancomycin monotherapy using PMMA or CPS were culture positive. Yet, the monotherapy CPS significantly reduced the bacterial metabolic load following revision compared to PMMA. Biofilm persisted on the fixation hardware, but the infection-induced bone destruction was significantly reduced by local rifampin delivery. These data demonstrate that, despite the challenging implant-retaining infection model, co-delivery of rifampin and vancomycin from 3D printed CPS, which is not possible with PMMA, significantly improved the outcomes of implant-associated osteomyelitis. However, biofilm persistence on the fixation hardware reaffirms the importance of implant exchange or other biofilm eradication strategies to complement local antibiotics.

Use of pooled residual laboratory sera to assess human immunodeficiency virus prevalence among patients in Italy. The Italian Study Group on Occupational Risk of HIV infection.

An anonymous unlinked seroprevalence study of human immunodeficiency virus (HIV) infection was performed by testing pools of ten sera remaining from specimens submitted consecutively to clinical pathology laboratories at 18 Italian public hospitals during four consecutive days in April 1991. Sera from positive pools were retested individually by three different enzyme immunoassays (EIAs) and considered positive if reactive by all three assays. Only the sera with discordant EIA results were retested by Western blot. Of a total of 22,590 sera, 278 were HIV positive (1.2%). The highest rates were seen in hospitals located in metropolitan areas (1.5%), in infectious disease departments (28%) and in drug addiction treatment units (28%); among men aged 21-30 (4.6%) and 31-40 years (4%); and among women aged 21-30 years (1.6%). The distribution of seropositive patients by gender and age group suggests an increasing role of heterosexual transmissions of the infection. The presence of anti-HIV antibodies in sera from patients of both sexes, in all age groups, and from all clinical settings reinforces the need for health care workers to adhere to universal precautions issued to prevent occupational bloodborne infections.