ETD Collection

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Subject: search.filters.subject.Amphotericin B

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    Amphotericin B nephrotoxicity in patients with crytopococcal meningitis
    (2017) Gerald, Maroka Kafofora
    Cryptococcal infections, which occur mainly as opportunistic infection in immunosuppressed patients, contributes 20% to HIV-related mortality especially in resource-limited regions like Sub-Saharan Africa with the number of infected people at 6,100,000 in 2012 in South Africa according to UNAIDS.7 Currently, Amphotericin B deoxycholate forms the cornerstone of all treatment protocols for cryptococcal meningitis, especially in these regions. Amphotericin B deoxycholate, the original formulation, is associated with significant risk of nephrotoxicity with up to 80% of those receiving the drug showing an increase in serum creatinine level, a marker of renal function.10 The availability of the safer lipid formulations of amphotericin B are limited by their costs, more so in resource-limited regions.8 However, in South Africa data on Amphotericin B associated nephrotoxicity is sparse. Aims The aim of this study is, therefore, to describe nephrotoxicity regarding incidence and outcome in patients with cryptococcal meningitis at Klerksdorp/Tshepong Hospital Complex on Amphotericin B administered per local protocol. Objectives  To define the frequency of acute kidney injury (AKI) on amphotericin B in this cohort of patients who had enough data for analysis.  To assess whether electrolyte abnormalities predict AKI by multivariable analysis in the cohort in this study  To describe overall outcome based on:  Mortality.  Progression to chronic kidney disease, as evidenced by un-resolving of renal dysfunction for three months or more.3  Need for acute dialysis.  Morbidity related to known sequela of cryptococcal meningitis. Methods This is a retrospective observational review of amphotericin B nephrotoxicity in patients with cryptococcal meningitis at Klerksdorp/Tshepong Hospital Complex from July 2013 to June 2014 to describe amphotericin B deoxycholate associated nephrotoxicity. Name and file numbers for patients who tested positive for cryptococcal meningitis, by either cryptococcal latex antigen or India ink on cerebrospinal fluid, were obtained from national health laboratory service (NHLS). 165 names and file number where retrieved but only 53 had sufficient data for the study. Results The files reviewed showed that 83% developed acute kidney injury with 5.66% progressing to chronic kidney disease. However, only 28 participants had a record of follow-up attendance. Mortality was 18.87% with no statistically significant association with acute kidney injury. However, mortality was higher in the acute kidney injury group (9:1). None of the study participants received dialysis. There was also a statistically significant association between being on antiretroviral treatment (Tenofovircontaining regimen) and acute kidney injury. The dose of amphotericin B was positively associated with the development of acute kidney injury. 90.56% of the participants received fluid supplementation per protocol recommendations during amphotericin B therapy. Conclusion Amphotericin B is a nephrotoxic drug with the risk of AKI significantly increased in patients on Tenofovir, necessitating ART regimen review before initiating therapy. The treatment protocol should be applied more strictly including correct dose, electrolyte and fluid supplementation to minimize nephrotoxic effects. Cryptococcal meningitis in HIVinfected patients on treatment has a mortality of 18.87% in this cohort which was lower compared to available literature, which estimates mortality at 30 to 40% on amphotericin B based protocols. 12, 16, 21 This cohort did not reveal any other statistically significant occurrence of long-term complications of cryptococcal meningitis.
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    In-hospital mortality of HIV-associated cryptococcal disease in patients treated with amphotericin B versus fluconazole
    (2014-02-18) Poswa, Xoliswa Pennley
    Introduction Cryptococcal disease (CD) is the most common cause of morbidity and mortality among patients living with HIV I AIDS in many parts of sub-Saharan Africa. Globally the highest number of HIV -associated CD cases occur in sub-Saharan Africa (720 000/957 900) and mortality rates among patients on antifungal treatment remain unacceptably high. This study aimed to estimate and compare in-hospital mortality of HIV-associated CD among patients who were treated with amphotericin B versus fluconazole versus mixed treatment with amphotericin B and fluconazole. Materials and Methods We performed an analytical, cross-sectional analysis of data from a national laboratory-based surveillance programme through a network of public sector laboratories in South Africa. The study period was 1 January 2005 to 31 December 2006. The analysis used a subset of data from laboratory confirmed cases with completed case report forms and available data on outcome. The exposure was measured in 3 levels defined as treatment during the induction phase of therapy for at least 7 days with either amphotericin B or fluconazole or mixed treatment (initiation of treatment with one regimen and switching on to the other within 7 days of treatment). Outcome was defined as: patients who died between 7 and 30 days in hospital. Chi-squared test was used to compare characteristics among the treatment groups and multiple logistic regression models were constructed to identify risk factors for in-hospital death. Results Sixty two percent of the patients (1,363/2,211) were treated for ?:.7 days and 38% (848/2,211) for <7 days. In the group treated for ?:.7 days, mortality was 359/1,363 (26%) and the median time to death was 12 days (IQR 9-18). There was no significant difference in case fatality among patients treated with: amphotericin B (29%), fluconazole (27%) or mixed treatment (24%), (p-value = 0.28). On multivariate analysis, factors significantly associated with in-hospital mortality were: patients between the age group of 40-59 years, province in which the patients resided and altered mental status. In the group treated for <7 days patients treated with fluconazole were 82% less likely to die than patients treated with amphotericin B. Discusslon and Conclusion In-hospital mortality was high and similar among all treatment regimens in the ?:.7 days group. However a significant reduction in mortality was noted in the <7 days group treated with fluconazole. The reason for the later findings is unclear. It may be that amphotericin B alone is not superior but equivalent to fluconazole in the first 7 days of treatment and 5-flucytocine may be the intervention required to improve outcome in the first 7 days. Or it may be that patients are reaching care too late for a significant impact in disease outcome to be observed and prevention of CD is required in the form of ART and primary prophylaxis. Selection bias in that patients in the fluconazole group are less sick than in the amphotericin B-group is the most likely reason for lower mortality. The study findings call for more standardization of optimum treatment as well as advocacy for the availability of 5-flucytocine. Factors associated with high mortality require further investigations for interventions to improve patient outcomes.