Homozygous BclI G allele carriers are at risk for traumatic memories, posttraumatic stress disorder symptoms, and lower health-related quality of life after cardiac surgery and intensive care unit therapy. The BclI single-nucleotide polymorphism may help to identify individuals at need for tailored medical care.

ObjectivesTo describe the patient populations and infections being treated with daptomycin, as well as the efficacy and safety outcomes.Patients and methodsData from the European Cubicin Outcomes Registry and Experience (EU-CORESM), retrospectively collected at 118 institutions between January 2006 and August 2008, were analysed.ResultsDaptomycin treatment was documented in 1127 patients with diverse infections, including complicated skin and soft tissue infections (33%), bacteraemia (22%), endocarditis (12%) and osteomyelitis (6%). It was used empirically, before microbiological results became available, in 53% of patients. Staphylococcus aureus was the most common pathogen (34%), with 52% of isolates resistant to methicillin; coagulase-negative staphylococci and enterococci were also frequent, with 22% of Enterococcus faecium isolates resistant to vancomycin. Daptomycin was used as first-line therapy in 302 (27%) patients. When used second line, the most common reasons for discontinuation of previous antibiotic were treatment failure and toxicity or intolerance. The use of concomitant antibiotics was reported in 65% of patients. Most frequent doses were 6 mg/kg (47%) and 4 mg/kg (32%). The median duration of daptomycin therapy was 10 days (range 1–246 days) in the inpatient setting and 13 days (range 2–189 days) in the outpatient setting. The overall clinical success rate was 79%, with a clinical failure rate of <10% for all infection types. Low failure rates were observed in first- and second-line therapy (6% and 8%, respectively). Daptomycin demonstrated a favourable safety and tolerability profile regardless of treatment duration.ConclusionsDaptomycin has a relevant role in the treatment of Gram-positive infections.

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IntroductionDaptomycin, a rapid concentration-dependent bactericidal antibiotic, is approved at a dose of 4 mg/kg/day for the treatment of complicated skin and soft tissue infections (cSSTI) and at a dose of 6 mg/kg/day for the treatment of Staphylococcus aureus right-sided infective endocarditis (RIE) and bacteremia associated with cSSTI and RIE. Studies have reported the successful use of high-dose daptomycin (>6 mg/kg/day) in patients with difficult-to-treat infections. The present analysis evaluated the effectiveness and safety of high doses (>6 mg/kg/day) of daptomycin for the treatment of different Gram-positive infections.MethodsEuropean Cubicin® Outcomes Registry and Experience (EU-CORE) is a non-interventional, multicenter, retrospective, patient registry designed to collect real-world data from patients treated with daptomycin between 2006 and 2012. Clinical outcomes were assessed at the end of daptomycin treatment for three dose groups: ≤6, >6 to <8, and ≥8 mg/kg/day. Safety was assessed for up to 30 days post-daptomycin treatment.ResultsOf the 6075 patients enrolled in EU-CORE, 4892 patients received daptomycin doses ≤6 mg/kg/day, while 1097 patients received high doses (>6 mg/kg/day). The primary infections with the largest proportion of patients treated with a high dose (>6 mg/kg/day) were osteomyelitis (37.1%), foreign body/prosthetic infection (31.6%), and endocarditis (27.6%). S. aureus was identified in 42.9% of patients with positive cultures treated with either ≤6 or >6 mg/kg/day. The overall clinical success rate was 82.0% (899/1097) with high doses (>6 mg/kg/day) and 80.3% (3928/4890) with doses ≤6 mg/kg/day. Numerically higher clinical success rate was observed for endocarditis and foreign body/prosthetic infection, as well as for coagulase-negative staphylococcal and enterococcal infections, with high-dose daptomycin treatment. There were no new or unexpected safety findings at doses >6 mg/kg/day.ConclusionThese results suggested that daptomycin at doses >6 mg/kg/day was effective and well tolerated. High-dose daptomycin is a potential therapeutic option in patients with difficult-to-treat Gram-positive infections.FundingThis study was funded by Novartis Pharma AG.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-015-0267-4) contains supplementary material, which is available to authorized users.

The mammalian-target-of-rapamycin/mTOR-inhibitor sirolimus as a component of the immunosuppressive strategy after solid organ transplantation is effective at preventing allograft rejection. However, recent reports indicate that sirolimus is associated with altered sex hormone levels and impaired sperm quality parameters.Herein, we report on a case of sirolimus-associated infertility in a young male heart-lung transplant recipient and provide a detailed synopsis of potential mechanisms by which sirolimus may negatively influence spermatogenesis. Testicular immunohistochemistry, the course of sex hormone and sperm quality parameters of our patient support the hypothesis that mTOR might act as an important key regulator in the reproductive system. Fortunately, due to withdrawal of sirolimus as part of the maintenance, immunosuppression improved sperm quality and sex hormone parameters could be observed. Recently, these improvements even resulted in a spontaneous pregnancy of the patient's wife more than 1 year after the drug was withdrawn. In our view, oligospermia as a possible and at least partly reversible side-effect of mTOR inhibitors has to be taken into consideration, particularly, when administrated to young male patients.

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