This study encompassed a total of 2663 MDR-TB patients confirmed through sputum culture, aiming to assess factors associated with both sputum culture conversion and body mass index. These patients received treatment across seven distinct PMDT sites in Punjab, Pakistan. Within this cohort, 50.4% of patients converted from a positive sputum culture to a negative one by the sixth month of treatment, with 22.1% of them being classified as underweight.
In contrast, a study conducted in Peshawar, Pakistan, reported a higher percentage (76.6%) of MDR-TB patients achieving a culture-negative status within an average of three months at various PMDT sites.
Within the current study, MDR-TB patients aged 40 years or older and those with a positive baseline sputum smear were notably less likely to undergo culture conversion compared to other patients. This finding aligns with existing literature that identifies older age as a risk factor for delayed culture conversion among individuals with MDR-TB. (16-19).
MDR-TB is a severe form of tuberculosis that is resistant to the most potent first-line drugs, making it challenging to treat among 46.6% enrolled in current study population. Recent studies also have suggested a significant relationship between the two variables, indicating that patients who have received either previous first-line anti-TB drug treatment may exhibit delayed sputum culture conversion if they do not have normal BMI like other studies in Bangladesh (20) Argentina (21) Armenia (22) Canada (23), France (24), India (25), Italy & Germany (26).
Multidrug-resistant tuberculosis (MDR-TB) becomes more concerning when there's significant resistance to fluoroquinolones and injectable drugs. MDR-TB strains resistant to these potent second-line drugs pose a major challenge for treatment outcomes. Among the 2663 cases studied, 812 (30.49%) had fluoroquinolone resistance, out of which only 255 (31%) of those with injectable drug resistance showed culture conversion, while 259 (31.9%) did not have culture conversion. This highlights the importance of optimizing therapy in such cases. Reasons contributing to drug resistance may include improper or inadequate treatment, which underscores the need for more effective strategies in managing drug-resistant tuberculosis. (27)
Incorrect prescribing practices (28) such as the inappropriate use of fluoroquinolones and injectable drugs in the absence of drug susceptibility testing, (29) without proper adherence can promote the selection of resistant strains, Mycobacterium tuberculosis can acquire genetic mutations that confer resistance to specific drugs (30). Resistance to fluoroquinolones and injectable drugs is often associated with specific genetic mutations in genes involved in drug targets or drug activation, such as gyrA and rrs. (30)
This study included a total of 2663 sputum culture confirmed MDR-TB patients, to evaluate the factors associated with sputum culture conversion and body mass index, treated at seven different PMDT sites of Punjab, Pakistan. In the current cohort, a total of 50.4% patients converted sputum positive culture to negative at the sixth month of treatment and 22.1% were underweight among them. In contrast, a study from Peshawar, Pakistan showed that 76.6% of the MDR-TB patients treated at different PMDT sites achieved culture negative status in an average of 03 months.
This study involved 2663 MDR-TB patients confirmed through sputum culture, aiming to assess factors related to sputum culture conversion and body mass index. These patients received treatment at seven PMDT sites in Punjab, Pakistan. Within this cohort, 50.4% of patients converted from a positive sputum culture to a negative one by the sixth month of treatment, with 22.1% of them being underweight.
Comparatively, a study conducted in Peshawar, Pakistan, reported a higher percentage (76.6%) of MDR-TB patients achieving a culture-negative status within an average of three months at various PMDT sites.
MDR-TB becomes more challenging when resistance to fluoroquinolones and injectable drugs is prominent. Strains of MDR-TB that are resistant to these potent second-line drugs pose significant difficulties in treatment outcomes. Among the 2663 cases, 812 (30.49%) exhibited fluoroquinolone resistance, and among these, only 255 (31%) of those resistant to injectable drugs showed culture conversion, while 259 (31.9%) did not. Optimizing therapy in such cases becomes crucial. Reasons for drug resistance may include improper or inadequate treatment. (27)
Incorrect prescribing practices (28) such as the inappropriate use of fluoroquinolones and injectable drugs in the absence of drug susceptibility testing, (29) without proper adherence can promote the selection of resistant strains, Mycobacterium tuberculosis can acquire genetic mutations that confer resistance to specific drugs (30). Resistance to fluoroquinolones and injectable drugs is often associated with specific genetic mutations in genes involved in drug targets or drug activation, such as gyrA and rrs. (30)
This study aimed to establish a clearer understanding of this relationship. It was a retrospective cohort study that encompassed a larger sample size of 2663 individuals. The study utilized standardized treatment protocols and employed rigorous data collection methods. Body Mass Index (BMI) was of particular interest due to its recognized potential in influencing treatment outcomes across various diseases.
Among the 670 individuals (48.98%) with low BMI, there was a observed culture conversion within six months, while 698 individuals had contrasting results. Some investigations have suggested a contrary association, unlike the findings observed in the current study, where lower BMI (underweight< 18.5 kg/m2) is linked to delayed sputum culture conversion like in Indonesia (11), India (31), Ethiopia (32). Longitudinal assessments throughout the treatment course, including regular sputum culture examinations and nutritional evaluations, helped elucidate the temporal relationship between BMI and sputum culture conversion. This perspective suggests that malnutrition or low body weight could compromise immune function, leading to slower bacterial clearance and poorer treatment outcomes. (33-35) Moreover, nutritional deficiencies commonly observed in patients with low BMI might affect drug absorption, distribution, and efficacy. (36)
In contrast, several studies have explored the relationship between sputum culture conversion and BMI in MDR-TB patients, yielding conflicting results. Some studies suggest that higher BMI is associated with delayed sputum culture conversion, (32, 37) indicating that individuals with increased body fat may experience prolonged bacterial clearance during treatment. These findings may be attributed to altered drug metabolism, impaired immune response, or pharmacokinetic factors influenced by adipose tissue. (38, 39)
When considering the association of MDR-TB patients, gender is an important factor to consider. Recent studies have indicated that the relationship between BMI and sputum culture conversion may vary based on gender as male gender has observed significant association as 631 (46.9%) males had no sputum conversion in a retrospective cohort of 6 months like another study conducted in Taiwan (40) unlike other studies (41) and (34). Therefore, the diversity in gender findings highlight the need for gender-specific considerations in the management and research with rather high sample size with prospective cohort emphasizing the importance of tailored interventions to optimize outcomes.
The association between sputum culture conversion and body mass index (BMI) among multidrug-resistant tuberculosis (MDR-TB) patients is a critical area of investigation due to the challenges posed by MDR-TB treatment. (9) The study conducted in Punjab, Pakistan, aimed to explore this relationship and its implications for treatment outcomes. The findings revealed that approximately 50.4% of the patients achieved sputum culture conversion within six months of treatment, with a notable proportion being underweight. (42)
Additionally, factors such as comorbidities, previous tuberculosis treatment, and resistance to injectable drugs and fluoroquinolones were prevalent among the patient population. The study's results provide valuable insights into the complex interplay between BMI and sputum culture conversion in MDR-TB patients. The association between BMI and treatment outcomes in MDR-TB has been a subject of interest in the literature, with conflicting results reported in various studies. (43-45)
The results underscore the necessity for thorough assessments that encompass various factors like comorbidities, smoking habits, socioeconomic status, and adherence to treatment. These comprehensive evaluations are crucial for better comprehension of the intricate treatment outcomes in MDR-TB patients. The study's conclusions align with prior research emphasizing the importance of Body Mass Index (BMI) in impacting treatment outcomes among individuals with MDR-TB. (46) For instance, (5) a study investigated the association between BMI and sputum culture conversion among South Korean patients with MDR-TB and found that BMI was a significant factor in predicting culture conversion within three months of treatment.
Similarly, (47) a study emphasized the importance of sputum bacteriology conversion and its impact on the treatment outcome of MDR-TB patients. Moreover, the study's focus on the prevalence of comorbidities, previous tuberculosis treatment, and resistance to injectable drugs and fluoroquinolones aligns with the broader literature on MDR-TB. Studies by (48) and (6) have highlighted the transmissibility and potential for disease progression of drug-resistant Mycobacterium tuberculosis, as well as the effect of metformin on culture conversion in tuberculosis patients with diabetes mellitus.(49)
However, it is essential to acknowledge the scarcity of studies specifically exploring the association between sputum culture conversion, BMI, and resistance to fluoroquinolones and injectable drugs in MDR-TB patients.
Novelty Statement
In this research on multidrug-resistant tuberculosis (MDR-TB) in Punjab, Pakistan, we embark on an exploration dynamic between body mass index (BMI) and sputum culture conversion among MDR-TB patients. Amid the global challenges posed by MDR-TB, our retrospective cohort analysis, spanning multiple Programmatic Management of Drug-Resistant Tuberculosis (PMDT) sites, provides the impact of BMI on treatment outcomes.
With the examination of 2663 confirmed MDR-TB patients, we unveil compelling correlations between distinct BMI categories (≥18.5 vs. <18.5 Kg/m^2) and the temporal dynamics of sputum culture conversion.
Through statistical analyses, our research not only sheds light on the average duration of sputum culture conversion but also unveils the proportion of patients achieving conversion within specific timeframes. The identification of key risk factors, such as prior first-line drug treatment and resistance to fluoroquinolone drugs, adds novel dimensions to our understanding of sputum culture conversion failure.
Our study provides valuable insights that can guide targeted interventions for an enhanced approach to MDR-TB patient care in the distinctive context of Punjab, Pakistan.