Cryptococcal infection in HIV-infected patients with CD4+ T-cell counts under 100/μL diagnosed in a high-income country: a multicentre cohort study

Abstract

Background: Nephrotoxicity and neurotoxicity are commonly associated with polymyxin treatment; however, the emergence of multidrug-resistant Gram-negative bacteria with limited therapeutic options has resulted in increased use of polymyxins. Objectives: To determine the rates of nephrotoxicity and neurotoxicity during polymyxin treatment and whether any factors influence these. Data sources: Medline, Embase and Cochrane Library databases were searched on 2 January 2020. Study eligibility criteria: Studies reporting nephrotoxicity and/or neurotoxicity rates in patients with infections treated with polymyxins were included. Reviews, meta-analyses and reports not in English were excluded. Participants: Patients hospitalized with infections treated with systemic or inhaled polymyxins were included. For comparative analyses, patients treated with nonepolymyxin-based regimens were also included. Methods: Meta-analyses were performed using a random-effects model; subgroup meta-analyses were conducted where data permitted using a mixed-effects model. Results: In total, 237 reports of randomized controlled trials, cohort and caseecontrol studies were eligible for inclusion; most were single-arm observational studies. Nephrotoxic events in 35,569 patients receiving polymyxins were analysed. Overall nephrotoxicity rate was 0.282 (95% confidence interval (CI) 0.259e0.307). When excluding studies where >50% of patients received inhaled-only polymyxin treatment or nephrotoxicity assessment was by methods other than internationally recognized criteria (RIFLE, KDIGO or AKIN), the nephrotoxicity rate was 0.391 (95% CI 0.364e0.419). The odds of nephrotoxicity were greater with polymyxin therapies compared to nonepolymyxin-based regimens (odds ratio 2.23 (95% CI 1.58e3.15); p < 0.001). Meta-analyses showed a significant effect of polymyxin type, dose, patient age, number of concomitant nephrotoxins and use of diuretics, glycopeptides or vasopressors on the rate of nephrotoxicity. Polymyxin therapies were not associated with a significantly different rate of neurotoxicity than nonepolymyxin-based regimens (p 0.051). The overall rate of neurotoxicity during polymyxin therapy was 0.030 (95% CI 0.020e0.043).

Adaptive immunology of Cryptococcus neoformans infections—an update

“…Cryptococcus can also appear in association with idiopathic CD4 + T-cell cytopenia without HIV infection, and the chance of disseminated cryptococcosis is high in patients with a CD4 + Tcell count lower than 400 cells/ml (13). Recent studies have suggested that routine screening of HIV-infected patients with a CD4 + T-cell count <100 cells/ml for cryptococcal infection can prevent CM in both resource-limited and high-income countries (14).…”

Neglected mycobiome in HIV infection: Alterations, common fungal diseases and antifungal immunity

“…Evidence suggests that host immune responses to cryptococcosis play a critical role in disease progression ( 95 – 97 ). CM can occur following primary lung infection or by reactivation and dissemination of latent pulmonary infection in the setting of cell-mediated immunodeficiency when CD4 + T-cell counts are <100 cells/μl in the late-stages of HIV-infection ( 98 ). Previous studies have shown that CD4 + T cells possibly mediate protective host immunity against cryptococcal via production of Th1-type cytokine responses, including IL-2, IL-12, tumor necrosis factor alpha (TNF-α), and IFN-γ, which play an essential role in recruitment of lymphocytes and phagocytes to clear the infection ( 99 , 100 ).…”