Background: Observational studies have suggested that accelerated surgery is associated with improved outcomes in patients with a hip fracture. The HIP ATTACK trial assessed whether accelerated surgery could reduce mortality and major complications. Methods:We randomised 2970 patients from 69 hospitals in 17 countries. Patients with a hip fracture that required surgery and were ≥45 years of age were eligible. Patients were randomly assigned to accelerated surgery (goal of surgery within 6 hours of diagnosis; 1487 patients) or standard care (1483 patients). The co-primary outcomes were 1.) mortality, and 2.) a composite of major complications (i.e., mortality and non-fatal myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia, life-threatening bleeding, and major bleeding) at 90 days after randomisation. Outcome adjudicators were masked to treatment allocation, and patients were analysed according to the intention-to-treat principle; ClinicalTrials.gov, NCT02027896. Findings:The median time from hip fracture diagnosis to surgery was 6 hours (interquartile range [IQR] 4-9) in the accelerated-surgery group and 24 hours (IQR 10-42) in the standard-care group, p<0.0001. Death occurred in 140 patients (9%) assigned to accelerated surgery and 154 patients (10%) assigned to standard care; hazard ratio (HR) 0.91, 95% CI 0.72-1.14; absolute risk reduction (ARR) 1%, 95% CI -1-3%; p=0.40. The primary composite outcome occurred in 321 patients (22%) randomised to accelerated surgery and 331 patients (22%) randomised to standard care; HR 0.97, 95% CI 0.83-1.13; ARR 1%, 95% CI -2-3%; p=0.71.Interpretation: Among patients with a hip fracture, accelerated surgery did not significantly lower the risk of mortality or a composite of major complications compared to standard care.

Level IV (retrospective study).

Background Optimal treatment of prosthetic joint infection and chronic osteomyelitis consists of surgical removal of biofilm-embedded bacteria, followed by a 6–12 week course of antimicrobial therapy. However, when optimal surgery is not feasible, oral prolonged suppressive antibiotic therapy (PSAT) is recommended to prevent prosthesis loosening and/or relapse of infection. Since 2010, we have used infection salvage therapy using off-label subcutaneous (sc) injection of a β-lactam as PSAT for patients in whom oral PSAT is not possible. Methods A single-centre prospective cohort study (2010–18) reporting treatment modalities, efficacy and safety in all patients receiving sc PSAT. NCT03403608. Results The 10 included patients (median age 79 years) had polymicrobial (n = 5) or MDR bacterial (n = 4) prosthetic joint infection (knee, n = 4; hip, n = 3) or chronic osteomyelitis (n = 3). After initial intensive therapy, seven patients received ertapenem, three patients received ceftriaxone and one patient received ceftazidime by sc injection (one patient received 8 days of ceftriaxone before receiving ertapenem). In one patient, sc PSAT failed with recurrent signs of infection under treatment. In three patients, sc PSAT had to be discontinued due to side effects; in only one of these was the sc route implicated (skin necrosis following direct sc injection and not gravity infusion). Median treatment duration was 433 days. In six patients, sc PSAT was successful with favourable outcome at the time of writing. Interestingly, three patients with MDR bacterial carriage at baseline lost this under PSAT during follow-up. Conclusions As salvage therapy, sc PSAT delivered by gravity infusion is a safe and interesting alternative when an optimal surgical strategy is not feasible and no oral treatment is available.

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IV.

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Objectives Long-acting lipoglycopeptides are promising therapeutic options in Staphylococcus aureus bone and joint infections (BJIs). This study evaluated the ability of dalbavancin to eradicate the intraosteoblastic reservoir of S. aureus, associated with BJI chronicity. Methods Osteoblastic cells were infected with a standardized inoculum of the S. aureus reference strain HG001 and incubated for 24 h with dalbavancin, vancomycin or rifampicin using the MIC, 10×MIC, 100×MIC and/or the intraosseous concentrations reached using standard therapeutic doses (i.e. vancomycin, 10 mg/L; rifampicin, 2 mg/L; and dalbavancin, 6 mg/L). The remaining intracellular bacteria were quantified by plating cell lysates. Results MICs of dalbavancin, vancomycin and rifampicin were 0.125, 1 and 0.004 mg/L, respectively. Dalbavancin significantly reduced the intracellular inoculum of S. aureus starting at a concentration equal to the MIC, with a significant dose effect, ranging from a reduction of 31.4% (95% CI = 17.6%–45.2%) at MIC to 51.6% (95% CI = 39.8%–63.4%) at 100×MIC compared with untreated cells. Of note, dalbavancin was the only molecule to significantly reduce the intraosteoblastic inoculum at low concentration (MIC). At intraosseous concentrations, dalbavancin reduced the intracellular inoculum by 49.6% (95% CI = 45.1%–54.1%) compared with untreated cells (P &lt; 0.001), with no significant difference compared with vancomycin (38.1%; 95% CI = 19.2%–57.0%; P = 0.646), and was less efficient than rifampicin (69.0%; 95% CI = 63.2-74.8; P &lt; 0.001). Conclusions Dalbavancin was able to decrease the intraosteoblastic S. aureus inoculum by 50% at intraosseous concentrations reached during standard human therapeutic dosing, with no difference compared with vancomycin, and remained less efficient than rifampicin. However, it was the only molecule significantly active at low concentration.