Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal ß-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia: A Randomized Clinical Trial.

Importance: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with mortality of more than 20%. Combining standard therapy with a ß-lactam antibiotic has been associated with reduced mortality, although adequately powered randomized clinical trials of this intervention have not been conducted. Objective: To determine whether combining an antistaphylococcal ß-lactam with standard therapy is more effective than standard therapy alone in patients with MRSA bacteremia. Design, Setting, and Participants: Open-label, randomized clinical trial conducted at 27 hospital sites in 4 countries from August 2015 to July 2018 among 352 hospitalized adults with MRSA bacteremia. Follow-up was complete on October 23, 2018. Interventions: Participants were randomized to standard therapy (intravenous vancomycin or daptomycin) plus an antistaphylococcal ß-lactam (intravenous flucloxacillin, cloxacillin, or cefazolin) (n = 174) or standard therapy alone (n = 178). Total duration of therapy was determined by treating clinicians and the ß-lactam was administered for 7 days. Main Outcomes and Measures: The primary end point was a 90-day composite of mortality, persistent bacteremia at day 5, microbiological relapse, and microbiological treatment failure. Secondary outcomes included mortality at days 14, 42, and 90; persistent bacteremia at days 2 and 5; acute kidney injury (AKI); microbiological relapse; microbiological treatment failure; and duration of intravenous antibiotics. Results: The data and safety monitoring board recommended early termination of the study prior to enrollment of 440 patients because of safety. Among 352 patients randomized (mean age, 62.2 [SD, 17.7] years; 121 women [34.4%]), 345 (98%) completed the trial. The primary end point was met by 59 (35%) with combination therapy and 68 (39%) with standard therapy (absolute difference, -4.2%; 95% CI, -14.3% to 6.0%). Seven of 9 prespecified secondary end points showed no significant difference. For the combination therapy vs standard therapy groups, all-cause 90-day mortality occurred in 35 (21%) vs 28 (16%) (difference, 4.5%; 95% CI, -3.7% to 12.7%); persistent bacteremia at day 5 was observed in 19 of 166 (11%) vs 35 of 172 (20%) (difference, -8.9%; 95% CI, -16.6% to -1.2%); and, excluding patients receiving dialysis at baseline, AKI occurred in 34 of 145 (23%) vs 9 of 145 (6%) (difference, 17.2%; 95% CI, 9.3%-25.2%). Conclusions and Relevance: Among patients with MRSA bacteremia, addition of an antistaphylococcal ß-lactam to standard antibiotic therapy with vancomycin or daptomycin did not result in significant improvement in the primary composite end point of mortality, persistent bacteremia, relapse, or treatment failure. Early trial termination for safety concerns and the possibility that the study was underpowered to detect clinically important differences in favor of the intervention should be considered when interpreting the findings. Trial Registration: ClinicalTrials.gov Identifier: NCT02365493.

Delays in presentation and diagnosis of pulmonary tuberculosis: a retrospective study of a tertiary health service in Western Melbourne, 2011-2014.

BACKGROUND: Effective tuberculosis (TB) control relies on early diagnosis and prompt treatment commencement. AIM: To investigate delays in presentation and diagnosis of pulmonary TB (PTB) in a low incidence setting in Western Melbourne. METHODS: A single-centred retrospective observational cohort study of symptomatic patients ≥ 18 years newly diagnosed with PTB that were commenced on treatment between 1 December 2011 and 1 December 2014 at a tertiary teaching hospital in Western Melbourne. Main outcome measures included median duration of patient, health system and total delays to diagnosis of PTB and clinical factors associated with prolonged patient (>35 days) and health system (>21 days) delay. RESULTS: A total of 133 patients were included. The median (range) duration of patient, health system and total delay to diagnosis were 28 (0-610), 18 (0-357) and 89 (1-730) days respectively. Prolonged patient delay was associated with being from a country with an annual TB incidence of <50/100 000 (odds ratio (OR) 5.98, 95% confidence interval (CI) 1.19, 29.98) and diabetes mellitus (OR 3.02, 95% CI 1.04, 8.78) in multivariate analysis. Being Australian-born or a resident of Australia ≥6 years (OR 0.03, 95% CI 0.12, 0.74; OR 0.30, 95% CI 0.00, 0.033 respectively) was associated with reduced patient delay. CONCLUSIONS: In this low-incidence, high-resource setting, patient delays contribute most to total delay in PTB diagnosis. Strategies addressing this aspect of the TB diagnosis pathway, such as health literacy and promotion programmes for new migrants and raised primary healthcare awareness, could have the largest impact on reducing total PTB diagnosis delays.

Use of FDG PET/CT for investigation of febrile neutropenia: evaluation in high-risk cancer patients.

PURPOSE: Febrile neutropenia (FNP) is a frequent complication of cancer care and evaluation often fails to identify a cause. [(18) F]FDG PET/CT has the potential to identify inflammatory and infectious foci, but its potential role as an investigation for persistent FNP has not previously been explored. The aim of this study was to prospectively evaluate the clinical utility of FDG PET/CT in patients with cancer and severe neutropenia and five or more days of persistent fever despite antibiotic therapy. METHODS: Adult patients with a diagnosis of an underlying malignancy and persistent FNP (temperature ≥38°C and neutrophil count <500 cells/µl for 5 days) underwent FDG PET/CT as an adjunct to conventional evaluation and management. RESULTS: The study group comprised 20 patients with FNP who fulfilled the eligibility criteria and underwent FDG PET/CT in addition to conventional evaluation. The median neutrophil count on the day of the FDG PET/CT scan was 30 cells/µl (range 0-730 cells/µl). Conventional evaluation identified 14 distinct sites of infection, 13 (93 %) of which were also identified by FDG PET/CT, including all deep tissue infections. FDG PET/CT identified 9 additional likely infection sites, 8 of which were subsequently confirmed as "true positives" by further investigations. FDG PET/CT was deemed to be of 'high' clinical impact in 15 of the 20 patients (75 %). CONCLUSION: This study supports the utility of FDG PET/CT scanning in severely neutropenic patients with five or more days of fever. Further evaluation of the contribution of FDG PET/CT in the management of FNP across a range of underlying malignancies is required.

Derotation taping for metacarpal and phalangeal fractures.

Derotation taping for metacarpal and phalangeal fractures is a simple, noninvasive technique for management of acute fractures with malrotation. Ulnar nerve or ring block is performed followed by a closed reduction using a Jahss technique and then a rotatory manipulation. Plaster tape is applied, providing a supination torque on the finger. Those patients with a late presentation of a rotatory malunion are managed with a "K wire osteoclasis" which involves multiple percutaneous cortical K-wire perforations and then a manipulation.