Polymorphisms of SLCO1B1 Gene in Sundanese Ethnic Population of Tuberculosis Patients in Indonesia.

BACKGROUND: The blood level of rifampicin, one of the tuberculosis (TB) drugs, depends on the organic anion transporting polypeptide 1B1 (OATP1B1) in hepatocytes. This protein is encoded by the solute carrier organic anion 1B1 (SLCO1B1) gene. Its genetic variation has been reported to have an impact on clinical outcomes and drug efficacy. However, the polymorphism in the SLCO1B1 gene has not been examined in Indonesia yet. We aimed to identify the frequency of polymorphism in SLCO1B1 gene among pulmonary TB patients in Bandung, Indonesia. METHODS: Cross-sectional study was conducted in West Java. 145 pulmonary TB patients who were treated with first-line drugs treatment (including rifampicin 450 mg daily) were analyzed for polymorphism in SLCO1B1 gene. Patients aged between 18-64 years old and mainly came from Sundanese ethnic group (92.4%). Genetic variants were detected using Polymerase Chain Reaction (PCR) and Sanger sequencing. RESULTS: Polymorphism of c.463C>A(rs11045819) was not identified, while heterozygous and homozygous polymorphism of c.85-7793C>T(rs4149032) were identified in 74 (51.0%) and 56 (38.6%) patients, respectively. The minor allele frequency (MAF) of T (mutant) allele of c.85-7793C>T(rs4149032) was 64.13% (186/209), higher than in the general population, which the MAF of rs4149032 is 53.6% based on 1000 genome database. CONCLUSION: This study highlights the presence of different allele frequencies of polymorphisms within the population, which might affect treatment outcomes.

Chromobacterium violaceum: A Review of an Unexpected Scourge.

Chromobacterium violaceum is a common environmental bacterium that rarely causes disease in humans but has a high fatality rate if it does. Due to the rarity of the cases, clinicians are often unaware of the rapid progression of C. violaceum infection and its unexpected antibiotic resistance pattern, which contribute to the failure of patient management. Our review provides the clinical characteristics, possible sources of exposure, and comorbidities and determines factors associated with survival. We gathered information on 132 cases of C. violaceum causing disease in humans published between 1953 and 2020. Patients were predominantly male with a median age of 17.5, interquartile range (IQR) of 5.0-40.0 years, and a third of them were known to have immune deficiencies or comorbidities. Portals of entry were mainly through a wound in the leg and feet (28.0%), the torso (8.5%), or hands and arms (6.8%). It is not uncommon to acquire infection through unintended contact with contaminated water or dust through the mouth or inhalation. The median incubation period is 4.0 days (IQR 2.0-8.0 days) with a duration of clinical course of 17.5 days (IQR 8.0-30.8 days). The high rate of positive blood cultures (56.1%) and abscesses in internal organs (36.4%) shows the significant severity of this disease. Sepsis and Bacteremia were related to mortality with a risk ratio (RR) of 5.20 (95% CI, 0.831-32.58) and 2.14 (95% CI, 1.05-4.36), respectively. Appropriate antibiotic use prevented death at a RR 0.33 (95% CI, 0.21-0.52). Most patients who recovered and survived were treated with aminoglycosides, fluoroquinolones and carbapenems. This review shows the malignant nature of C. violaceum infection and the need for clinicians to be aware and provide prompt source management for patients. Appropriate empiric and targeted antibiotic regiment guided by susceptibility test results is of vital importance.