This study included 154 patients with MDR/pre-XDR/XDR-TB, all of whom were on treatment with a Linezolid-containing regimen. The demographic distribution of these patients is crucial to understanding the population at risk for ADRs and how these reactions may differ across various groups. The demographic insights are crucial for developing targeted interventions to manage ADRs in this population. Younger patients and those in economically productive age groups may benefit from close monitoring for early signs of ADRs, coupled with interventions aimed at maintaining their economic and social roles. Gender-specific approaches may also be warranted, considering the potential for differential ADR profiles between males and females. Moreover, the socioeconomic distribution highlights the need for financial and social support mechanisms to assist patients in managing the dual burden of DR-TB and its treatment. This could include government or NGO-led initiatives to provide financial aid, access to nutritional supplements, and free or subsidized healthcare services, particularly for those in the lower-middle and upper-lower socioeconomic classes. The age distribution in this study showed that the majority of patients (51.95%) were in the 21-40 years age group, with a mean age of 33.80 ± 14.26 years. This finding is significant because the age group of 21-40 years typically represents the most economically productive segment of the population. Moreover, our study's findings of a significant proportion of ADRs in young adults’ contrast with a study by Zhang et al., (7)which found that older patients, particularly those above 60 years, were more susceptible to severe ADRs from Linezolid. This contradiction could be due to variations in patient characteristics, such as comorbidities and baseline nutritional status, which are known to influence drug toxicity. The gender distribution revealed a higher prevalence of males (58.44%) compared to females (41.56%) in the study population that is 90 males and 64 females participated in our study. This male predominance is consistent with the global epidemiology of TB, where men are generally more affected than women. The reasons for this gender disparity could be multi-factorial, including biological, behavioral, and social factors. Men may be more exposed to TB due to their work environments, lifestyle choices, or health-seeking behaviors, which could also influence their susceptibility to drug resistance and subsequent treatment regimens. The majority of patients presented with a cough with expectoration (91.56%), followed by breathlessness (41.56%) and chest pain (40.26%). These findings align with the typical clinical presentation of pulmonary TB, where a persistent cough, often productive, is the most common symptom. In previous studies, as conducted by Dheda et al. (8), similar symptom profiles were observed among DR-TB patients, particularly the predominance of cough with expectoration. These studies also noted that symptoms like breathlessness and chest pain were common among patients with extensive lung involvement, which correlates with the findings of our study. The treatment history of the patients aligns with findings from other studies, study conducted by Yang et al. and Ghimire et al. (10), reported high rates of previous treatment among DR-TB patients. This study found a statistically significant increase in RBS levels post-treatment (p < 0.001). This aligns with previous studies, such as that by Tang et al. (11), which reported hyperglycemia as a potential side effect of Linezolid, especially in patients with pre-existing diabetes or glucose intolerance. A significant decrease in Hb levels was observed post-treatment (p < 0.001), which is consistent with the known myelosuppressive effects of Linezolid. This side effect, particularly anemia, has been well-documented in studies like those by Bressler et al. (12), where long-term Linezolid use was associated with bone marrow suppression. The drop in Hb levels necessitates regular hematological monitoring during treatment to mitigate severe anemia and consider alternative therapies if necessary. The increase in Total Bilirubin levels post-treatment (p = 0.013) suggests hepatic involvement, which is a recognized adverse effect of Linezolid. This observation is supported by studies such as that by Taegtmeyer et al. (13), which highlighted hepatotoxicity as a concern in patients receiving prolonged Linezolid therapy. The liver’s role in drug metabolism means that Linezolid’s impact on liver function tests, including bilirubin levels, warrants careful monitoring to prevent serious liver injury. Both total protein (p = 0.047) and albumin levels (p = 0.049) decreased significantly post-treatment. This could be indicative of nutritional deficits or an adverse impact on protein synthesis, possibly due to Linezolid’s side effects on the gastrointestinal system or its potential interference with liver function. Studies by Li et al. (14) support this finding, showing that patients on Linezolid may experience hypoalbuminemia and reduced protein levels, which can complicate the treatment process by exacerbating other drug-related toxicities. Peripheral neuropathy is a well-documented side effect of Linezolid, particularly in long-term use, as observed in this study. The findings align with previous research by Senneville et al. (15) and Youssef et al. (16), which reported that peripheral neuropathy is one of the most common adverse effects of Linezolid, particularly when used in prolonged courses necessary for treating DR-TB. The prevalence of mild to moderate neuropathy in nearly 70% of patients underscores the importance of regular neurological assessments during treatment. However, the current study’s findings contrast with a recent study by Alffenaar et al. (17), which reported lower rates of neuropathy in a cohort treated with a lower dose of Linezolid (600 mg daily) compared to the standard 1200 mg dose. This difference could be attributed to the dose-dependent nature of Linezolid’s neurotoxicity, suggesting that lower doses might reduce the risk of neuropathy without compromising efficacy. The discrepancy in neuropathy rates also highlights the need for individualized dosing strategies to balance efficacy and safety in DR-TB treatment. This study reveals that only 0.65% of the patients developed optic neuritis during the follow-up period. This low incidence aligns with the findings of earlier studies by Rodríguez et al. (18), which documented optic neuritis as a rare but serious side effect of Linezolid, particularly with prolonged use. The rarity of this adverse effect in the current study may reflect the close monitoring and early detection protocols in place, which help mitigate the severity of this complication. Contradictorily, a study by Narita et al. (19) reported a higher incidence of optic neuritis, particularly in older patients or those with pre-existing visual impairments. The difference could be due to variations in patient demographics, including age and baseline ocular health, which were not extensively detailed in the current study but could significantly influence the incidence of optic neuritis. The prevalence of anemia observed in this study aligns with the results of Bressler et al. (12), who also documented a high incidence of anemia in patients receiving long-term Linezolid therapy. The study by Li et al. (14) further supports this finding, emphasizing that anemia is a dose-limiting toxicity of Linezolid, often necessitating dose reductions or discontinuation of therapy. However, the current study’s anemia rates are higher than those reported in a recent study by Zhang et al. (7), which found that concomitant use of erythropoiesis-stimulating agents (ESAs) significantly reduced the incidence of anemia in patients on Linezolid. This difference suggests that the proactive management of anemia through supportive therapies like ESAs could mitigate this common side effect, an approach that may not have been uniformly applied in the present study. 30.52% of patients had their dose reduced to half within the first six months of treatment, and in 29.22% of the cases, the drug was stopped and replaced due to the severity of ADRs. The need for dose adjustments or discontinuation of Linezolid in a significant proportion of patients highlights the drug’s dose-dependent toxicity. This finding is consistent with studies such as that by Alffenaar et al. (17), which demonstrated that lower doses of Linezolid (600 mg daily) were associated with fewer severe ADRs compared to the standard 1200 mg dose, without compromising the drug's efficacy. The high rate of dose reductions and discontinuations in the current study underscores the importance of balancing efficacy with safety, particularly in long-term treatments like those required for DR-TB. All 115 patients who developed ADRs due to Linezolid were classified as "Possible" according to the WHO-UMC Causality Assessment Scale. This universal classification suggests a strong likelihood that the ADRs observed were related to Linezolid, albeit without absolute certainty, which is typical in clinical settings where multiple factors could contribute to adverse outcomes. The uniformity of the "Possible" classification across all cases is consistent with other studies that have examined the causality of ADRs in TB treatments. A study by Thawani et al. (20) used the WHO-UMC scale to assess ADRs in a similar cohort and found that Linezolid was frequently implicated, particularly in hematological toxicities such as anemia and thrombocytopenia.

In conclusion, the study provides valuable insights into the management of Linezolid in the treatment of drug-resistant TB. It highlights the importance of individualized treatment plans, regular monitoring for ADRs, and the need for dose adjustments to optimize patient outcomes while minimizing toxicity. These findings contribute to the ongoing efforts to improve the management of MDR/XDR-TB, particularly in high-burden settings like India, where the challenge of drug-resistant TB remains a significant public health concern.

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