[HIV, antiretroviral therapy and suicidal behaviour: a multidisciplinary case report and underlying neuroimmunological pathways]. / Hiv, antiretrovirale therapie en suïcidaliteit; een multidisciplinaire gevalsbeschrijving en bijbehorend neuro-immunologisch model.

The relationship between hiv, major depressive disorder and suicidal ideation is well established. For example, hiv-positive patients are seven times more likely to develop depression, and suicidal behaviour is also more prevalent. Antiretroviral therapy is known to further enhance these risks. We saw a 53-year-old patient with a depressive episode and suicidal ideation, possibly related to the use of dolutegravir/abacavir/lamivudine. We provide an overview of the literature and we present a neuro-immunological hypothesis for this psychiatric adverse event, which may occur even after months of treatment.

Management of S. aureus bacteraemia in the Netherlands; infectious diseases consultation improves outcome.

BACKGROUND: Staphylococcus aureus bacteraemia is associated with a high mortality rate. Previously it has been shown that consultation by an internist-infectious diseases specialist (IDS) improves the outcome of patients. In this study, we evaluated the differences in management and outcome between patients with, and those without IDS consultation. METHODS: All adult patients with a positive blood culture for S. aureus from January 2010 to December 2013 were retrospectively identified with the electronic registration system of our Laboratory for Medical Microbiology. Clinical and microbiological characteristics were retrieved from the electronic patient files, as well as information on bedside consultation by an IDS. RESULTS: A total of 234 patients with S. aureus bacteraemia were included in the study, of whom 77.8% were consulted by an IDS. Management of patients with IDS consultation was more often according to guidelines than was the case without consultation by an IDS; follow up blood cultures were taken more often (97.8% vs. 80.8%, p < 0.001), patients received echocardiography more often (70.9% vs. 50.0%, p = 0.007), and they were more often treated adequately (86.6% vs. 59.2%, p < 0.001). The detection rate of complications in the IDS group was higher (59.3% vs. 32.7%, p = 0.001) and 30-day mortality rate was lower (12.1% vs. 23.1%, p = 0.04). This was confirmed by multivariate analysis. CONCLUSION: In patients with a S. aureus bacteraemia, bedside consultation by an IDS results in better adherence to diagnostic and treatment guidelines, with higher detection of complications and a higher survival rate.

Safety and immunogenicity of HBAI20 Hepatitis B vaccine in healthy naïve and nonresponding adults.

Approximately 5% of the healthy adult population respond inadequately to the commercial recombinant hepatitis B vaccines. As the recombinant vaccines all have an aluminium-based adjuvant, we tried to enhance the immune response by adding a cytokine-based adjuvant. This new adjuvant AI20, containing 20 µg recombinant human IL-2 attached to 20 µg aluminium hydroxide, was added to HBVaxPro©-10 µg (HBAI20). In a double-blind randomized controlled trial (RCT), 24 naïve subjects were randomized to receive either HBAI20 or commercial HBVaxPro©-10 µg vaccine. In an open-label study, 10 nonresponders received HBAI20 vaccine. All participants received 3 vaccinations (0, 1 and 6 months). In the RCT, the occurrence of any adverse events or severe events was similar between the trial arms. At month 7, all naïve participants were seroprotected; moreover, 92% in the HBAI20 group had protective antibodies 10 days after the second vaccination vs 58% in the HBVaxPro©-10 µg group, P = .16. In the open-label study, no serious adverse events were noted. The HBAI20 vaccine was able to elicit protective anti-HBs titres in 90% of nonresponders, 1 month after the third vaccination. According to these results, the new HBAI20 vaccine seems safe, well-tolerated and may promote more rapid protection against hepatitis B infection.

Safety and tolerability of voriconazole in patients with baseline renal insufficiency and candidemia.

Acutely ill patients with candidemia frequently suffer from renal insufficiency. Voriconazole's intravenous formulation with sulfobutylether beta-cyclodextrin (SBECD) is restricted in patients with renal insufficiency. We evaluated the use of intravenous voriconazole formulated with SBECD in candidemic patients with renal insufficiency and compared treatment outcome and safety to those who received a short course of amphotericin B deoxycholate followed by fluconazole. We reviewed data on treatment outcome, survival, safety, and tolerability from the subset of patients with moderate (creatinine clearance [CrCl], 30 to 50 ml/min) or severe (CrCl, <30 ml/min) renal insufficiency enrolled in a trial of voriconazole compared to amphotericin B deoxycholate followed by fluconazole for treatment of candidemia in 370 patients. Fifty-eight patients with renal impairment were identified: 41 patients on voriconazole and 17 on amphotericin B/fluconazole. The median duration of treatment was 14 days for voriconazole (median, 7 days intravenous) and 11 days for amphotericin B/fluconazole, 3 days of which were for amphotericin B. Despite the short duration of exposure, worsening of renal function or newly emerged renal adverse events were reported in 53% of amphotericin B-treated patients compared to 39% of voriconazole-treated patients. During treatment, median serum creatinine decreased in the voriconazole arm, whereas creatinine increased in the amphotericin B/fluconazole arm, before return to baseline at week 3. All-cause mortality at 14 weeks was 49% in the voriconazole arm compared to 65% in the amphotericin B/fluconazole arm. Intravenous voriconazole formulated with SBECD was effective in patients with moderate or severe renal insufficiency and candidemia and was associated with less acute renal toxicity than amphotericin B/fluconazole.

[Amphotericin B: the end of an era]. / Amfotericine B: het einde van een tijdperk.

For 45 years, amphotericin B has been the drug of choice for the treatment of invasive mycoses. Because of its severe toxicity, lipid-associated formulations of amphotericin B have been developed. Although comparative trials are scarce, there appears to be no convincing advantage of these new formulations in terms of efficacy. The lipid-associated amphotericins are significantly less nephrotoxic than conventional amphotericin B, although there are major differences in the infusion-related toxicity of the various lipid-associated preparations. The current armamentarium of azoles and echinocandins for the treatment of invasive mycoses has only left a very minor role for both conventional and lipid-associated amphotericin B in the treatment of a few specific, rare mycoses.

An open multicentre comparative study of the efficacy, safety and tolerance of fluconazole and itraconazole in the treatment of cancer patients with oropharyngeal candidiasis.

Oropharyngeal candidiasis is a frequent infection in cancer patients who receive cytotoxic drugs. In this study, the efficacy, safety and tolerance of fluconazole and itraconazole were compared in non-neutropenic cancer patients with oropharyngeal candidiasis. Of 279 patients who were randomised between the two treatment groups, 252 patients were considered to be eligible (126 in each group). The clinical cure rate was 74% for fluconazole and 62% for itraconazole (P=0.04, 95% Confidence Interval (CI): 0.5-23.3%). The mycological cure rate was 80% for fluconazole and 68% for itraconazole (P=0.03, 95% CI: 1.2-22.6%). The safety and tolerance profile of both drugs were comparable. This study has shown that in patients with cancer and oropharyngeal candidiasis, fluconazole has a significantly better clinical and mycological cure rate compared with itraconazole.

Voriconazole salvage treatment of invasive candidiasis.

Data on the salvage treatment of invasive candidiasis with voriconazole in 52 patients intolerant of other antifungal agents or with infection refractory to other antifungal agents were analyzed. Patients had received a mean of two previous antifungal agents (range, 1-4 agents), and 83% had received an azole. Manifestations of invasive candidiasis included candidemia (37%), disseminated disease (25%), and infection of other sites (38%). The median duration of voriconazole therapy was 60 days (range, 1-314 days). The overall rate of response was 56% (95%CI, 41-70), with the following response rates observed for individual Candida species: Candida albicans, 44% (20-70); Candida glabrata, 38% (14-68); Candida krusei, 70% (35-93); Candida tropicalis, 67% (30-93); and other Candida spp., 100% (40-100). The response rate in patients who had failed previous azole therapy was 58% (42-73). Common adverse events (~20%) included nausea and emesis, abnormal liver enzymes, and visual disturbances. Serious adverse events occurred in four patients, and nine patients died. Voriconazole has promise as a salvage agent for the treatment of invasive candidiasis, even in the settings of previous azole therapy and infection due to Candida krusei.

Duration of antifungal treatment and development of delayed complications in patients with candidaemia.

The optimal duration of antifungal treatment of candidaemia is unknown. Prolonged treatment has been advocated to prevent late-onset complications caused by metastatic infectious foci. To evaluate the relationship between duration of antifungal therapy and the development of delayed complications in patients with candidaemia, a retrospective descriptive study was performed in a tertiary care centre. The study included 180 consecutive patients with candidaemia identified by at least one positive blood culture. Development of late-onset complications of candidaemia during long-term follow-up was monitored. Of the patients treated with antifungal agents, 55% completed treatment without apparent complications, 33% died during therapy, 12% developed disseminated disease and one patient continues to receive ongoing treatment. Of the 81 patients who completed treatment as scheduled, 25% received treatment for less than 2 weeks, 31% for 2-4 weeks and 38% for more than 4 weeks; duration of therapy was unknown in 6%. Only three (2%) patients developed delayed complications; in these patients, the duration of antifungal treatment had been 3 weeks, 5 weeks and 22 weeks, respectively. In conclusion, despite theoretical concerns, there seems to be no correlation between the duration of antifungal treatment and the development of late complications in patients with candidaemia. This suggests that treatment of 2 weeks or less may be sufficient, provided the initial response to therapy is favourable.

Epidemiology of opportunistic invasive mycoses.

Invasive aspergillosis and disseminated candidiasis are the two major manifestations of opportunistic invasive mycoses. Their incidence has risen considerably during the past decades, due to more intensive anticancer chemotherapy, organ transplantations, intensive care, and aggressive surgical interventions. Especially bone marrow transplant recipients are at risk for developing invasive aspergillosis. Whether the infection is acquired through contaminated water or through airborne spores is a matter of much debate. Candidemia and disseminated candidiasis commonly originate from the gastrointestinal tract. Abdominal surgery and mucosal damage due to anticancer chemotherapy are the majors factor through which gut colonization may lead to invasive disease. A shift in the epidemiology of disseminated candidiasis has been noted, with an increasing incidence of Candida glabrata, C. tropicalis and C. krusei strains.