Baseline glycated hemoglobin and potassium level correlated with pretreatment QT-corrected interval among patients with diabetic drug-resistant tuberculosis.

Background: Bedaquiline is a core drug with an optimized background regimen for treating drug-resistant tuberculosis (DR-TB) patients. One of the adverse effects of bedaquiline is QT-corrected (QTc) interval prolongation. TB patients with diabetes mellitus (DM) are more likely to develop QTc interval prolongation during TB treatment than those without DM. This study aimed to correlate baseline electrolyte levels (potassium, calcium, and magnesium), thyroid-stimulating hormone (TSH), body mass index (BMI), blood glucose, glycated hemoglobin (HbA1c), and pretreatment QTc interval among patients with diabetic DR TB who received regimens containing bedaquiline. Methods: It was a prospective study with a cross-sectional design. Blood samples, BMI, and electrocardiogram were collected at baseline before starting the regimen for DR-TB. Pearson correlation was used to correlate between baseline electrolyte level, TSH, BMI, complete blood count, blood glucose, HbA1c, and pretreatment QTc interval. Results: Seventy-two DR-TB patients met the inclusion criteria, half with DM. The blood glucose and HbA1c were significantly higher in patients with DM. Pretreatment QTc interval was similar between the two groups. Levels of calcium, magnesium, TSH, blood glucose, and BMI were not correlated with pretreatment QTc interval. There was a correlation between baseline potassium and HbA1c levels with pretreatment QTc interval (P < 0.05; r = 0.357 and r = -0.376, respectively). Baseline potassium level correlates with the pretreatment QTc interval in those without DM. Conclusion: Baseline HbA1c and potassium levels correlate with pretreatment QTc interval among DR-TB patients with DM. Our study indicates the importance of monitoring HbA1c and potassium levels during DR-TB therapy containing bedaquiline for early detection of QTc prolongation.

Identification of Drug-Related Problems (DRPS) of drugs with special dosage forms in geriatric patients (study at the outpatient pharmacy unit, Airlangga University Hospital, Surabaya)

Background: Geriatric syndrome is a condition of decreased organ function that causes DRPs, especially drugs with special dosage forms, such as an inhaler, insulin pens, and modified release drugs. Objective: To identify DRPs of drugs with special dosage forms in geriatric patients at the Outpatient Pharmacy Unit of RSUA Surabaya. Methods: It was an observational and prospective study with the interview method. Each problem identified was given a score to be analyzed descriptively and statistically. Data collection was carried out from April to June 2022. Results: The sample is 82 special dosage forms, there are drug delivery devices including inhaler (26%) and insulin pen (29%), and drug delivery systems including OROS (33%), retard (6%), and sustained-release (6%). DRPs were found in 40% of them. In inhaler form, the DRPs of DPI are failure to load the dose, shaking after the dose was loaded, and not checking the remaining dose after using the device. While in MDI, no DRPs were found. The DRPs of insulin pens are errors in device storage (25%), injection position (8%), and repeated use of blunt/broken needles (38%). While in modified release drugs is an error in drug storage (5%). The percentages of nonadherence are Turbuhaler 33%, Breezhaler 60%, Diskus 25%, MDI 0%, insulin pen 29%, and modified release drugs 24%. The solution is given by using verbal education such as leaflets. Statistical analysis showed a significant difference in the insulin pen and the modified release drug, while there was no significant difference in the inhaler. Conclusion: Each type of drug with a special dosage form has its problems and problem-solving in the form of interventions has not given maximum results. (AU)

Favorable outcome of individual regimens containing bedaquiline and delamanid in drug-resistant tuberculosis: A systematic review.

Background: Drug-resistant tuberculosis (DR-TB) is a public health concern that is difficult to treat, requiring long and complex treatment with highly effective drugs. Bedaquiline and/or delamanid have already shown promising outcomes in patients with DR-TB, increasing the rate of culture conversion and lowering TB-related mortality. Methods: We comprehensively searched and evaluated the effectiveness of individual regimens containing bedaquiline and delamanid on culture conversion and treatment success. We assessed for quality either observational or experimental studies. Results: We identified 14 studies that met the inclusion criteria using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart with 12 observational and 2 experimental studies. Of 1691 DR-TB patients enrolled in the included studies, 1407 of them concomitantly received regimens containing bedaquiline and delamanid. Overall multidrug resistant (MDR), preextensively drug resistant (XDR), and XDR-TB were seen in 21.4%, 44.1%, and 34.5%, respectively. Of 14 studies, 8 of them reported favorable outcomes including sputum culture conversion and cure rate at the end of treatment, meanwhile 6 studies only reported sputum culture conversion. Sputum culture conversion at the end of the 6th month was 63.6%-94.7% for observational studies, and 87.6%-95.0% for experimental studies. The favorable outcome at the end of treatment was 67.5%-91.4%. With high pre-XDR and XDR cases among DR-TB patients with limited treatment options, regimens containing bedaquiline and delamanid provide successful treatment. Conclusion: In DR-TB patients receiving regimens containing bedaquiline and delamanid, favorable outcomes were high including sputum conversion and cure rate.

Scoping review: QT interval prolongation in regimen containing bedaquiline and delamanid in patients with drug-resistant tuberculosis.

Background: A regimen containing bedaquiline-delamanid is recommended in management of drug-resistant tuberculosis (DR TB) to increase a success rate. However, this regimen was rare in a clinical setting due to a potential risk of QT prolongation. Several studies have reported the incidence of QT prolongation after administration of this regimen, but the results are inconsistent due to different sample size, study design, and covariate. The aim of this review is to summarize and analyze the published articles related to QT prolongation of bedaquiline and delamanid in PubMed and ScienceDirect databases using a scoping review. Methods: This scoping review was conducted under PRISMA for scoping review. The outcomes of this review were incidence of QT prolongation and death. We found 8 articles to be included in this review. Results: The incidence of QT prolongation was higher for DR TB patients who received a regimen containing bedaquiline and delamanid. However, this review found no clinical symptoms, such as cardiac arrhythmias, torsade de pointes, or even death. DR TB patients, especially the elderly, were at risk for QT prolongation. Special consideration in patients with HIV and low level of potassium should be closely monitored for QT interval. Conclusion: The regular measurement of electrocardiography was highly recommended to evaluate QT interval. Generally, the use of individualized regimen containing bedaquiline and delamanid is relatively safe in DR TB patients.