In-hospital mortality of HIV-associated cryptococcal disease in patients treated with amphotericin B versus fluconazole
Date
2014-02-18
Authors
Poswa, Xoliswa Pennley
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Abstract
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.
Description
Thesis (M.Sc. (Med.) (Epidemiology and Biostatistics))--University of the Witwatersrand, Faculty of Health Sciences, 2012.