Mustapha, Faizah
(2018)
Clinical and molecular characterization of burkholderia pseudomallei isolated from patients in Hospital Sultanah Nurzahirah (HSNZ) and treatment outcome.
Masters thesis, Universiti Sains Malaysia.
Abstract
Introduction
Melioidosis is a potentially fatal disease caused by environmental saprophyte,
Burkholderia pseudomallei. It is commonly found in soil and surface water in endemic
regions of Southeast Asia and a common cause of community acquired sepsis and
pneumonia in the east coast of Peninsular Malaysia.
Methodology
This is a prospective cohort study conducted to evaluate the demographic data, clinical
features and treatment outcome of culture-proven melioidosis at Hospital Sultanah
Nurzahirah, Terengganu from October 2016 till June 2017. Molecular confirmation of
B. pseudomallei was performed using a PCR-based assay targeting sctQ gene of the
TTS1 cluster. Twenty isolates were then subsequently genotyped using DNA
sequencing of multiple gene loci to determine the genetic relatedness of the strains and
to correlate the identified genotypes with clinical presentations and outcomes. The
mortality rates of patients who receive early and appropriate empirical anti-melioidosis
therapy was compared to those who did not receive appropriate empirical therapy. A
total of 52 cases were included in the study. Patients’ clinical data were obtained from
electronic clinical notes.Results
Ninety six percent of melioidosis patients in this study had at least one underlying
illness with the most common being diabetes mellitus. Bacteremic melioidosis was seen
in most patients (n=48, 92.3%). Majority of them had bacteremic localized infection
(57.7%), followed by disseminated bacteremia (26.9 %) and bacteremia with no focal
lesion (7.7%). The remaining four patients (7.7%) had non bacteremic localized
infection. Community acquired pneumonia and fever of unknown origin were the
common presentation on admission. Lung was the most common organ involved
(61.5%), followed by liver (15.4%), spleen, central nervous system and soft tissue
(9.6%), joint and urinary tract (3.8%). All the culture-proven isolates were successfully
confirmed with PCR. Constructed phylogenetic tree from sequencing of multiple gene
loci revealed genetic diversity among B. pseudomallei strains, and there is no clustering
seen with the clinical presentation or outcome. The overall mortality rate was 53.9%
(n=28/52) and all patients who died had bacteremic melioidosis. Only 15 out of 52
patients (28.9%) were prescribed appropriate empirical antibiotics, with corresponding
mortality of 26.7%. The mortality was significantly higher (64.9%) in those who did not
receive appropriate empirical antibiotic therapy.
Conclusion
The clinical manifestations of melioidosis in Terengganu state were diverse and
comparable to other countries worldwide. B. pseudomallei genotypes showed genetic
diversity indicating distribution of different strains in the environment. The overall
mortality rate is high, particularly in those who did not receive early and appropriate
empirical antibiotics. Thus, a high index of suspicion in endemic country and the early
use of appropriate empirical antibiotic therapy is crucial to prevent death.
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