A time-to-event modelling of sputum conversion within two months after antituberculosis initiation among drug-susceptible smear positive pulmonary tuberculosis patients: Implementation of internal and external validation.

Delayed sputum conversion has been associated with a higher risk of treatment failure or relapse among drug susceptible smear-positive pulmonary tuberculosis patients. Several contributing factors have been identified in many studies, but the results varied across regions and countries. Therefore, the current study aimed to develop a predictive model that explained the factors affecting time to sputum conversion within two months after initiating antituberculosis agents among Malaysian with drug-susceptible smear-positive pulmonary tuberculosis patients. Retrospective data of pulmonary tuberculosis patients followed up at a tertiary hospital in the Northern region of Malaysia from 2013 until 2018 were collected and analysed. Nonlinear mixed-effect modelling software (NONMEM 7.3.0) was used to develop parametric survival models. The final model was further validated using Kaplan-Meier-visual predictive check (KM-VPC) approach, kernel-based hazard rate estimation method and sampling-importance resampling (SIR) method. A total of 224 patients were included in the study, with 34.4 % (77/224) of the patients remained positive at the end of 2 months of the intensive phase. Gompertz hazard function best described the data. The hazard of sputum conversion decreased by 39 % and 33 % for moderate and advanced lesions as compared to minimal baseline of chest X-ray severity, respectively (adjusted hazard ratio (aHR), 0.61; 95 % confidence intervals (95 % CI), (0.44-0.84) and 0.67, 95 % CI (0.53-0.84)). Meanwhile, the hazard also decreased by 59 % (aHR, 0.41; 95 % CI, (0.23-0.73)) and 48 % (aHR, 0.52; 95 % CI, (0.35-0.79)) between active and former drug abusers as compared to non-drug abuser, respectively. The successful development of the internally and externally validated final model allows a better estimation of the time to sputum conversion and provides a better understanding of the relationship with its predictors.

Population pharmacokinetics analyses of rifampicin in adult and children populations: A systematic review.

AIMS: Rifampicin has become an essential component as the first-line therapy for pulmonary tuberculosis (PTB). Several population pharmacokinetic (PK) studies on rifampicin in adult and child populations have been studied previously, therefore the aims of the systematic review were (i) to summarize the relevant published studies and significant covariates that influence the PK of rifampicin across different populations, and (ii) to identify any knowledge gap that requires additional research in the future. METHODS: A total of 121 relevant population PK articles were systematically identified using PubMed and Scopus from inception to October 2021. Review articles, in-vitro and physiological methods, animal studies and noncompartmental analysis were excluded. RESULTS: Nineteen studies, of which 16 involved adults, two involved children, and one involved both adults and children, were included in the review. The structural model of rifampicin can be described as one compartment with a transient compartment absorption model and first-order elimination in most of the studies. Pharmaceutical formulation, body weight, gender, pregnancy status, diabetes and nutritional supplementation were found to be the significant covariates that affect the PK parameters. External validation of the developed PK model was only conducted in two studies. CONCLUSIONS: The source of variability for PK parameters of rifampicin remains inconsistent and poorly understood even though there were many potential covariates investigated in the selected studies. Exploring other possible factors and implementing a strict sampling strategy by considering the induction effects might uncover precise and reliable information. Furthermore, external validation should be frequently conducted to produce better predictability of model performance.

Perception and practices of public hospital pharmacists towards the antimicrobial stewardship programme in the State of Selangor, Malaysia.

Objective: The increase in antimicrobial resistance and the lack of new antimicrobial agents in drug discovery pipelines have called for global attention to mitigate the problem of antimicrobial misuse. While an antimicrobial stewardship (AMS) programme has been implemented in Malaysia, the perception and practices of public hospital pharmacists remain unknown. The aim of this study was to determine the perception and practices of Malaysian public hospital pharmacists towards the AMS programme in the state of Selangor, Malaysia. Methods: A cross-sectional study, using a validated 23-item self-administered questionnaire, was conducted among pharmacists from 11 public hospitals in the State of Selangor, Malaysia, from December 2016 to January 2017. All public hospital pharmacists (n=432) were invited to participate in the survey. A 5-point Likert scale was employed in the questionnaire; the perception section was scored from 1 (strongly disagree) to 5 (strongly agree) while the practice section was scored from 1 (never) to 5 (always). Both descriptive and inferential statistical analyses were used to analyse data. Results: Of the 432 pharmacists surveyed, 199 responded, giving a response rate of 46.0%. The majority of the respondents agreed (n=190, 95.5%) that the AMS programme improves patient care at their hospitals (median=5; IQR=1). Slightly less than half of the respondents indicated that a local antibiotic guideline was established in their hospitals (median=3, IQR=2.5), and had taken part in antimicrobial awareness campaigns to promote optimal use of antimicrobials in hospitals (median=3, IQR=1). Conclusions: Overall, the perception and practices of the surveyed hospital pharmacists towards AMS programme were positive. National antibiotic guidelines, which take into consideration local antimicrobial resistance patterns, should be used fully to improve antimicrobial usage and to reduce practice variation. Collaboration among healthcare professionals should be strengthened to minimise the unfavourable consequences of unintended use of antimicrobial agents while optimising clinical outcomes.