Achieving vancomycin serum trough concentrations of 15 to 20 mg/L did not result in an increased attainment of the AUC/MIC target relative to troughs of 10 to 14.9 mg/L but may increase nephrotoxicity risk.

SummaryWhat is known and objective: Limited evidence describes dalbavancin use in infective endocarditis (IE). Case description:A 27-year-old pregnant female received 4 weeks of dalbavancin for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia and tricuspid valve IE after conventional therapy was no longer an option due to non-compliance. Despite having a smaller cardiac vegetation following dalbavancin, she was bacteraemic <2 weeks later with vancomycin-intermediate (VISA) and telavancin-non-susceptible S. aureus.What is new and conclusion: This is the first report of unsuccessful IE treatment with dalbavancin. Blood cultures grew VISA and lipoglycopeptide-non-susceptible S. aureus <2 weeks following dalbavancin. Both outcomes raise concerns about using dalbavancin for IE. K E Y W O R D Sbacteremia, dalbavancin, endocarditis, MRSA, pregnancy, Staphylococcus aureus | WHAT IS KNOWN AND OBJECTIVEStaphylococcus aureus is the leading cause of infectious endocarditis and is known to cause right-sided endocarditis, particularly in injection drug users.1,2 The management of infective endocarditis (IE) in this population poses significant compliance concerns and often warrants intravenous treatment in the inpatient setting. 3The novel semi-synthetic lipoglycopeptide dalbavancin is pharmacokinetically unique due to its long terminal half-life. It is approved for the single-dose treatment of acute bacterial skin and skin structure infections in adult patients and has activity against most gram-positive organisms including methicillin-resistant S. aureus (MRSA). 4 Clinicians may be tempted to use dalbavancin for off-label indications such as IE given its antibacterial activity and extensive half-life. Unfortunately, the effectiveness of dalbavancin for these off-label indications is largely uncertain. We report a case of failed treatment for MRSA tricuspid valve endocarditis with dalbavancin after conventional therapies were not viable due to patient non-compliance.

IntroductionThe use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals.Materials and MethodsA set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed.ResultsNone of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count.DiscussionNo associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.

DRPs with the potential to cause patient harm or impair treatment efficacy often occur with OPAT, most commonly ADRs and DIs. Enhanced monitoring and transitions of care management may reduce the incidence of these DRPs.

The AUC-based monitoring resulted in fewer patients with dose adjustments when trough levels were 10 to 14.9 mg/L. The AUC-based monitoring has the potential to reduce unnecessary vancomycin exposure and warrants further investigation.