Correction to: AMBIsome Therapy Induction OptimisatioN (AMBITION): High Dose AmBisome for Cryptococcal Meningitis Induction Therapy in sub-Saharan Africa: Study Protocol for a Phase 3 Randomised Controlled Non-Inferiority Trial.

Following publication of the original article [1], we have been notified that one of the author names was listed incorrectly. Both incorrect and correct author names are presented below. The original publication has been corrected.

AMBIsome Therapy Induction OptimisatioN (AMBITION): High Dose AmBisome for Cryptococcal Meningitis Induction Therapy in sub-Saharan Africa: Study Protocol for a Phase 3 Randomised Controlled Non-Inferiority Trial.

BACKGROUND: Cryptococcal meningitis (CM) is a major cause of mortality in HIV programmes in Africa despite increasing access to antiretroviral therapy (ART). Mortality is driven in part by limited availability of amphotericin-based treatment, drug-induced toxicities of amphotericin B deoxycholate and prolonged hospital admissions. A single, high-dose of liposomal amphotericin (L-AmB, Ambisome) on a fluconazole backbone has been reported as non-inferior to 14 days of standard dose L-AmB in reducing fungal burden. This trial examines whether single, high-dose L-AmB given with high-dose fluconazole and flucytosine is non-inferior to a seven-day course of amphotericin B deoxycholate plus flucytosine (the current World Health Organization [WHO] recommended treatment regimen). METHODS: An open-label phase III randomised controlled non-inferiority trial conducted in five countries in sub-Saharan Africa: Botswana, Malawi, South Africa, Uganda and Zimbabwe. The trial will compare CM induction therapy with (1) a single dose (10 mg/kg) of L-AmB given with 14 days of fluconazole (1200 mg/day) and flucytosine (100 mg/kg/day) to (2) seven days amphotericin B deoxycholate (1 mg/kg/day) given alongside seven days of flucytosine (100 mg/kg/day) followed by seven days of fluconazole (1200 mg/day). The primary endpoint is all-cause mortality at ten weeks with a non-inferiority margin of 10% and 90% power. Secondary endpoints are early fungicidal activity, proportion of grade III/IV adverse events, pharmacokinetic parameters and pharmacokinetic/pharmacodynamic associations, health service costs, all-cause mortality within the first two and four weeks, all-cause mortality within the first ten weeks (superiority analysis) and rates of CM relapse, immune reconstitution inflammatory syndrome and disability at ten weeks. A total of 850 patients aged ≥ 18 years with a first episode of HIV-associated CM will be enrolled (425 randomised to each arm). All patients will be followed for 16 weeks. All patients will receive consolidation therapy with fluconazole 800 mg/day to complete ten weeks of treatment, followed by fluconazole maintenance and ART as per local guidance. DISCUSSION: A safe, sustainable and easy to administer regimen of L-AmB that is non-inferior to seven days of daily amphotericin B deoxycholate therapy may reduce the number of adverse events seen in patients treated with amphotericin B deoxycholate and shorten hospital admissions, providing a highly favourable and implementable alternative to the current WHO recommended first-line treatment. TRIAL REGISTRATION: ISRCTN, ISRCTN72509687 . Registered on 13 July 2017.

ESBL-producing enterobacteriaceae-related urinary tract infections in kidney transplant recipients: incidence and risk factors for recurrence.

BACKGROUND: Urinary tract infections (UTIs) represent the first cause of bacterial infections in renal transplant recipients. In a period of increasing resistance to antimicrobial agents, the factors leading to the development of UTI in previously urinary colonized renal transplant recipients as well as the factors associated with recurrence of UTIs have to be determined. The aims of this retrospective study were (1) to assess the incidence of extended-spectrum beta-lactamase-producing enterobacteriaceae (ESBL-PE)-related UTI in kidney transplant recipients, (2) to identify factors associated with ESBL-PE infection and (3) to determine the risk factors for recurrence. METHODS: We included all kidney transplant recipients admitted in our hospital between January 2009 and January 2012 who had a monobacterial ESBL-PE UTI or bacteriuria. RESULTS: During the study period, 659 patients underwent kidney transplantation; 72 patients had ESBL-PE bacteriuria, representing a 10.9% prevalence, and among the latter 34 (47.2%) presented an ESBL-PE-related UTI. Fourteen patients (41.2%) experienced a UTI relapse associated with two factors: advanced age (p = 0.032) and persistent bacteriuria 48 h after appropriate antibiotic therapy (p = 0.04). No other risk factor for recurrence was found, including the presence and management of a ureteral stent during the first UTI, causative microorganisms, or diabetes mellitus. CONCLUSIONS: In this specific population, regarding the risk of relapse there is an urgent need for prospective studies to test the best treatment strategy.

Future directions in mucormycosis research.

Mucormycosis has emerged as an important opportunistic infection, especially in severely immunosuppressed hosts. The evolving epidemiology, immunopathogenesis, molecular virulence studies, early diagnosis, and pitfalls in designing clinical studies of mucormycosis are discussed in this article.