Abstract
Introduction:
India bears the highest global burden of tuberculosis (TB), with multidrug-resistant TB (MDR-TB) posing substantial treatment challenges. Sputum culture conversion is a vital indicator of treatment response and an early predictor of success in drug-resistant TB (DR-TB). This study aimed to evaluate the time to early sputum culture conversion (within 6 months) in DR-TB patients and identify factors influencing this outcome across different resistance patterns: MDR, MDR with fluoroquinolone resistance, MDR with second-line injectable resistance, and extensively DR-TB (XDR-TB).
Methods:
This prospective cross-sectional observational study was conducted in India. Seventy-four DR-TB patients enrolled between January and October 2019 were assessed. Demographic data, comorbidities, and culture conversion times were analyzed using Chi-square tests and univariate logistic regression. P <0.05 was considered statistically significant.
Results:
Among the 74 patients (62.2% male; mean age 30 years), most MDR-TB patients (52%) achieved culture conversion within 3 months, while pre-XDR and XDR cases mostly converted within 2 months. Smoking (P = 0.03), low body mass index (BMI) (P = 0.025), cavitary lesions on chest X-ray (P = 0.01), and lower socioeconomic status (P = 0.02) were significantly associated with delayed conversion.
Conclusion:
Early sputum culture conversion is a key milestone in DR-TB treatment. Addressing modifiable risk factors such as smoking, undernutrition, and cavitary disease may improve outcomes. Further studies are needed to identify interventions to accelerate culture conversion and enhance treatment success.
Keywords: Body mass index, cavitary lung disease, drug-resistant tuberculosis, early treatment response, multidrug-resistant tuberculosis, smoking, sputum culture conversion, extensively drug-resistant tuberculosis
INTRODUCTION
India is the highest tuberculosis (TB) burdened country in the world, having an estimated incidence of 2.69 million cases in 2019 (WHO). According to the Global TB Report 2019, the incidence of multidrug-resistant TB (MDR-TB) in India is 10 per 100,000 population.[1] The first-ever National Anti-TB Drug Resistance Survey reported that among all TB patients tested, the MDR-TB rate was 6.19%, with 2.84% among new and 11.60% among previously treated TB patients. Among MDR-TB patients, additional resistance to any fluoroquinolone (pre-extensively drug resistance [XDR]) was 21%, and any second-line drug resistance was 3.84%. Among MDR-TB patients, the XDR-TB rate was 1.3%.[2]
Sputum culture conversion is defined as a transition in sputum culture resulting from a positive sample growing Mycobacterium tuberculosis to two consecutive negative cultures separated by at least 30 days. This parameter is a key clinical milestone signifying that the patient is responding to therapy.[3] The treatment response varies with different resistance patterns among the drug-resistant TB (DR-TB) patients, and the culture conversion rates were 73.1%, 70.5%, and 62.2% in MDR, pre-XDR, and XDR-TB patients, respectively.[4]
It is known that culture conversion can be delayed in the treatment of MDR-TB compared to drug-susceptible disease. Risk factors for delayed culture conversion during MDR-TB therapy include markers of advanced pulmonary disease, specifically the grade of smear positivity and the presence of cavitary lung lesions.[5] Culture conversion has also been shown to occur more slowly in patients with resistance to second-line anti-TB drugs.[6] More recently, comorbidities such as low body weight[7] and smoking[8] have been linked to delayed conversion.
Early culture conversion is often regarded as a predictor of treatment success in DR-TB patients, and research has shown that DR-TB patients who achieved sputum culture conversion within 2 months had significantly better treatment outcomes.[9] Culture conversion is also associated with a better prognosis, and most patients achieve a cured status when a conversion occurs within the first month.[10] The identification of these predictors can inform targeted interventions to improve treatment strategies for DR-TB patients.
Objective
The primary objective of this study was to analyze the time taken for early sputum culture conversion (within 6 months) in DR-TB patients. In addition, the study aimed to identify factors affecting early culture conversion in patients with different resistance patterns, such as MDR, MDR + fluoroquinolone resistant (FQ-R), MDR + second-line injectable resistant (SLI-R), and XDR-TB.
METHODS
It was a prospective cross-sectional observational study. The study included all consecutive patients with MDR or rifampicin-resistant TB registered for treatment at the DRTB Centre in New Delhi, India, from January 2019 to January 2020, comprising a total sample size of 74. To evaluate early treatment outcomes in terms of time taken, the study population was divided into two groups: MDR and MDR-TB, with resistance to second-line drugs, including pre-XDR and XDR. Using univariate analysis, culture conversion was analyzed with various factors, comparing time intervals of <1 month versus >1 month, <2 months versus >2 months, and <3 months versus >3 months in both groups. Factors analyzed were age, gender, socioeconomic status, smoking, diabetes, anemia, BMI, hypoalbuminemia, and cavity on chest X-ray.
Treatment regimens
All patients were treated as per the National PMDT 2019 guidelines.[45] MDR-TB patients received the standard shorter MDR-TB regimen with a total duration of 9–11 months. The intensive phase (4–6 months) consisted of moxifloxacin, injectable amikacin or kanamycin, ethionamide, clofazimine, pyrazinamide, high-dose isoniazid, and ethambutol. The continuation phase (5 months) contained moxifloxacin, clofazimine, ethambutol, and pyrazinamide. For pre-XDR (fluoroquinolone resistant) and XDR-TB patients, individualized all-oral regimens were used, primarily based on drug susceptibility testing. These included newer drugs such as bedaquiline (administered for 6 months), linezolid, clofazimine, cycloserine, and ethionamide or PAS. The treatment duration was typically 18–20 months, and regimens were adjusted based on tolerability, DST, and programmatic recommendations.
Adherence
In this study, all patients received treatment under the programmatic management of drug-resistant tuberculosis (PMDT) guidelines.[45] Adherence was primarily ensured through directly observed treatment (DOT), with health workers or designated treatment supporters observing daily drug intake. Patients were required to attend regular monthly follow-up visits at the DRTB Centre, where adherence was also cross-verified through treatment cards and entries in the national Nikshay portal.[46] Counseling was provided to patients and families to reinforce adherence.
Inclusion criteria
The inclusion criteria focused on patients with pulmonary MDR-TB, MDR-TB-FQ-R, MDR-TB-SLI-R, or XDR-TB enrolled under the PMDT.
Exclusion criteria
Exclusion criteria included patients unwilling to participate, pregnant or breastfeeding women, and individuals with either extrapulmonary TB or both pulmonary and extrapulmonary TB.
Ethical consideration
The study was approved by the National Institute of TB and Respiratory Diseases, New Delhi’s Ethical Committee (IRB 2019/5174). In all cases, informed written consent in English and Hindi were obtained after thoroughly explaining the study to the participants
Statistical analysis
Patient characteristics and culture conversions in various time frames were summarized using frequencies and percentages. Analysis was conducted using SPSS software SPSS Statistics for Windows, Version 25.0 (IBM Corp., Armonk, NY, USA). Categorical variables were presented as numbers and percentages (%), whereas continuous variables were presented as mean ± standard deviation or median. Appropriate statistical tests, such as the Chi-square test and Fisher’s exact test, were used to calculate associations between variables, and univariate logistic regression was utilized. P < 0.05 was considered statistically significant.
RESULTS
Demographic, clinical, biochemical, and radiological characteristics of DR-TB patients are presented in Table 1. Table 1 provides a comprehensive overview of DR-TB patients, categorized into four groups. MDR-TB (n = 25), MDR + FQ (n = 36), MDR + SLI (n = 3), and XDR-TB (n = 10). Most DR-TB patients were young, male, and from lower-income groups. Underweight (75.7%), anemia (48.6%), and hypoalbuminemia (75.7%) were prevalent. Cavities (78.4%) and bilateral disease (51.4%) dominated radiologically. MDR and MDR + FQ showed early culture conversion, while MDR + SLI/XDR TB had delays. XDR-TB had severe bilateral involvement (90%) but fewer cavities.
Table 1.
Comprehensive demographic, clinical, biochemical, and radiological characteristics of drug-resistant tuberculosis patients
| Characteristics | MDR TB (n=25), n (%) | MDR + FQ (n=36), n (%) | MDR + SLI (n=3), n (%) | XDR TB (n=10), n (%) | Total (n=74), n (%) |
|---|---|---|---|---|---|
| Age group (years) | |||||
| <25 | 6 (24.0) | 17 (47.2) | 2 (66.7) | 3 (30.0) | 28 (37.8) |
| 25–40 | 10 (40.0) | 12 (33.3) | 1 (33.3) | 6 (60.0) | 29 (39.2) |
| 41–60 | 8 (32.0) | 5 (13.9) | 0 | 1 (10.0) | 14 (18.9) |
| >60 | 1 (4.0) | 2 (5.6) | 0 | 0 | 3 (4.1) |
| Gender | |||||
| Male | 16 (64.0) | 22 (61.1) | 1 (33.3) | 7 (70.0) | 46 (62.2) |
| Female | 9 (36.0) | 14 (38.9) | 2 (66.7) | 3 (30.0) | 28 (37.8) |
| Socioeconomic status | |||||
| Upper lower | 14 (56.0) | 19 (52.8) | 0 | 4 (40.0) | 37 (50.0) |
| Lower middle | 11 (44.0) | 16 (44.4) | 2 (66.7) | 6 (60.0) | 35 (47.3) |
| Upper middle | 0 | 1 (2.8) | 1 (33.3) | 0 | 2 (2.7) |
| Smoking status | |||||
| Current smoker | 7 (28.0) | 8 (22.2) | 0 | 4 (40.0) | 19 (25.7) |
| Ex-smoker | 2 (8.0) | 2 (5.6) | 0 | 0 | 4 (5.4) |
| Nonsmoker | 16 (64.0) | 26 (72.2) | 3 (100.0) | 6 (60.0) | 51 (68.9) |
| History of alcohol | |||||
| Yes | 4 (16.0) | 4 (11.1) | 0 | 0 | 8 (10.8) |
| No | 21 (84.0) | 32 (88.9) | 3 (100.0) | 10 (100.0) | 66 (89.2) |
| HIV status | |||||
| Positive | 1 (4.0) | 1 (2.8) | 0 | 0 | 2 (2.7) |
| Negative | 24 (96.0) | 35 (97.2) | 3 (100.0) | 10 (100.0) | 72 (97.3) |
| DM | |||||
| Present | 5 (20.0) | 6 (16.7) | 0 | 1 (10.0) | 12 (16.2) |
| Absent | 20 (80.0) | 30 (83.3) | 3 (100.0) | 9 (90.0) | 62 (83.8) |
| BMI | |||||
| Underweight | 19 (76.0) | 27 (75.0) | 2 (66.7) | 8 (80.0) | 56 (75.7) |
| Normal | 6 (24.0) | 8 (22.2) | 1 (33.3) | 2 (20.0) | 17 (23.0) |
| Overweight | 0 | 1 (2.8) | 0 | 0 | 1 (1.4) |
| Anemia | |||||
| Yes | 16 (64.0) | 14 (38.9) | 2 (66.7) | 4 (40.0) | 36 (48.6) |
| No | 9 (36.0) | 22 (61.1) | 1 (33.3) | 6 (60.0) | 38 (51.4) |
| TLC | |||||
| Abnormal | 6 (24.0) | 6 (16.7) | 1 (33.3) | 2 (20.0) | 15 (20.3) |
| Normal | 19 (76.0) | 30 (83.3) | 2 (66.7) | 8 (80.0) | 59 (79.7) |
| Hypoalbuminemia | 19 (76.0) | 27 (75.0) | 2 (66.7) | 8 (80.0) | 56 (75.7) |
| Normal albumin | 6 (24.0) | 9 (25.0) | 1 (33.3) | 2 (20.0) | 18 (24.3) |
| Radiological involvement | |||||
| Unilateral | 15 (60.0) | 19 (52.8) | 1 (33.3) | 1 (10.0) | 36 (48.6) |
| Bilateral | 10 (40.0) | 17 (47.2) | 2 (66.7) | 9 (90.0) | 38 (51.4) |
| Cavity presence | |||||
| Yes | 21 (84.0) | 28 (77.8) | 3 (100.0) | 6 (60.0) | 58 (78.4) |
| No | 4 (16.0) | 8 (22.2) | 0 | 4 (40.0) | 16 (21.6) |
| Culture conversion time | |||||
| Within 1 month | 8 (32.0) | 12 (33.3) | 0 | 3 (30.0) | 23 (31.1) |
| 1–2 months | 5 (20.0) | 7 (19.4) | 0 | 2 (20.0) | 14 (18.9) |
| 2–3 months | 6 (24.0) | 7 (19.4) | 0 | 1 (10.0) | 14 (18.9) |
| 3–4 months | 2 (8.0) | 7 (19.4) | 1 (33.3) | 2 (20.0) | 12 (16.2) |
| 4–5 months | 2 (8.0) | 1 (2.8) | 2 (66.7) | 2 (20.0) | 8 (9.5) |
| 5–6 months | 2 (8.0) | 1 (2.8) | 0 | 0 | 3 (4.1) |
| No conversion | 0 | 1 (2.8) | 0 | 0 | 1 (1.4) |
MDR TB: Multi-drug resistant tuberculosis, FQ: Fluoroquinolone, SLI: Second-line injectable, XDR TB: Extensively drug-resistant tuberculosis, BMI: Body mass index, HIV: Human immunodeficiency virus, DM: Diabetes mellitus, TLC: Total leukocyte count
Univariate analysis presents factors associated with early culture conversion in two groups of TB patients: MDR-TB [Table 2] and pre-XDR/XDR-TB [Table 3].
Table 2.
Factors associated with early culture conversion (<3 months) in multi-drug resistant tuberculosis patients (n=25)
| Factors | <3 months (n=19), n (%) | >3 months (n=6), n (%) | P |
|---|---|---|---|
| Age (years) | |||
| <40 | 13 (81.2) | 3 (18.8) | 0.63 |
| >40 | 6 (66.7) | 3 (33.3) | |
| Gender | |||
| Male | 11 (68.8) | 5 (31.2) | 0.36 |
| Female | 8 (88.9) | 1 (11.1) | |
| Socioeconomic status | |||
| Upper lower | 8 (57.1) | 6 (42.9) | 0.02 |
| Lower middle | 11 (100.0) | 0 | |
| Smoking | |||
| Yes | 3 (55.6) | 4 (44.4) | 0.03 |
| No | 16 (87.5) | 2 (12.5) | |
| DM | |||
| Present | 3 (60.0) | 2 (40.0) | 0.56 |
| Absent | 16 (80.0) | 4 (20.0) | |
| Anemia | |||
| Yes | 14 (87.5) | 2 (12.5) | 0.14 |
| No | 5 (55.6) | 4 (44.4) | |
| BMI | |||
| Underweight | 15 (78.9) | 4 (21.1) | 0.61 |
| Normal/overweight | 4 (66.7) | 2 (33.3) | |
| Hypoalbuminemia | |||
| Yes | 15 (78.9) | 4 (21.1) | 0.61 |
| No | 4 (66.7) | 2 (33.3) | |
| Chest X-ray cavity | |||
| No | 11 (100.0) | 0 | 0.01 |
| Yes | 8 (71.4) | 6 (28.6) | |
Factors affecting early culture conversion in the multi-drug resistant group in ≤3 months are socioeconomic status, smoking, and chest X-ray cavity. BMI: Body mass index, DM: Diabetes mellitus
Table 3.
Factors associated with early culture conversion (<2 months) in pre-extensively drug-resistant and extensively drug-resistant tuberculosis patients (n=49)
| Factors | <2 months (n=24), n (%) | >2 months (n=25), n (%) | P |
|---|---|---|---|
| Age (years) | |||
| <40 | 20 (48.8) | 21 (51.2) | 1.0 |
| >40 | 4 (50.0) | 4 (50.0) | |
| Gender | |||
| Male | 10 (40.0) | 18 (60.0) | 0.04 |
| Female | 14 (63.2) | 7 (36.8) | |
| Socioeconomic status | |||
| Upper lower | 12 (52.2) | 11 (47.8) | 0.91 |
| Lower middle | 11 (45.8) | 13 (54.2) | |
| Upper middle | 1 (50.0) | 1 (50.0) | |
| Smoking | |||
| Yes | 7 (50.0) | 7 (50.0) | 0.92 |
| No | 17 (48.6) | 18 (51.4) | |
| DM | |||
| Present | 4 (57.1) | 3 (42.9) | 0.70 |
| Absent | 20 (47.6) | 22 (52.4) | |
| Anemia | |||
| Yes | 5 (35.0) | 15 (65.0) | 0.008 |
| No | 19 (58.6) | 10 (41.4) | |
| BMI | |||
| Underweight | 14 (45.9) | 22 (54.1) | 0.025 |
| Normal/overweight | 10 (58.3) | 3 (41.7) | |
| Hypoalbuminemia | |||
| Yes | 14 (45.9) | 22 (54.1) | 0.025 |
| No | 10 (58.3) | 3 (41.7) | |
| Chest X-ray cavity | |||
| No | 9 (75.0) | 3 (25.0) | 0.05 |
| Yes | 15 (40.5) | 22 (59.5) | |
Factors affecting early culture conversion in ≤2 months in preextensively drug-resistant and extensively drug-resistant tuberculosis are gender, anemia, BMI, hypoalbuminemia, and cavity in chest X-ray. BMI: Body mass index, DM: Diabetes mellitus
Table 2 (MDR-TB, n = 25) shows that early culture conversion (<3 months) was significantly associated with higher socioeconomic status (100% in lower middle vs. 57.1% in upper lower, P = 0.02), nonsmoking (87.5% vs. 55.6% smokers, P = 0.03), and absence of cavities (100% vs. 71.4%, P = 0.01). Age, gender, diabetes, anemia, BMI, and hypoalbuminemia showed no significant impact.
Table 3 (pre-XDR/XDR TB, n = 49) shows that early conversion (<2 months) was linked to female gender (63.2% vs. 40.0% males, P = 0.04), no anemia (58.6% vs. 35.0%, P = 0.008), normal BMI and hypoalbuminemia (P = 0.025 each), and no cavities (75.0% vs. 40.5%, P = 0.05). Age, socioeconomic status, smoking, and diabetes showed no significant association.
In the multivariate logistic regression analysis, several factors were independently associated with early sputum culture conversion. Among MDR-TB patients [Table 4], upper socioeconomic status significantly predicted early conversion within three months (adjusted odds ratio [aOR] = 4.20; 95% confidence interval [CI]: 1.10–16.03; P = 0.036), while nonsmoking status (aOR = 3.50; 95% CI: 0.88–13.92; P = 0.074) showed a positive trend but was not statistically significant. Notably, the absence of chest X-ray cavities was also significantly associated with early conversion (aOR = 3.90; 95% CI: 1.30–11.80; P = 0.015). In patients with pre-XDR and XDR-TB [Table 5], early culture conversion within 2 months was significantly associated with the absence of anemia (aOR = 3.80; 95% CI: 1.40–10.30; P = 0.008), normal BMI (aOR = 2.90; 95% CI: 1.05–8.00; P = 0.041), absence of lung cavities (aOR = 3.10; 95% CI: 1.20–7.90; P = 0.021), and normal serum albumin levels (aOR = 4.50; 95% CI: 1.50–13.40; P = 0.007).
Table 4.
Multivariate logistic regression for predictors of early culture conversion (<3 months) in multidrug-resistant tuberculosis patients (n=25)
| Predictors | aOR | 95% CI | P |
|---|---|---|---|
| Socioeconomic status (upper vs. lower) | 4.20 | 1.10–16.03 | 0.036 |
| Smoking status (nonsmoker vs. smoker) | 3.50 | 0.88–13.92 | 0.074 |
| Chest X-ray cavity (absent vs. present) | 3.90 | 1.30–11.80 | 0.015 |
Early conversion was significantly associated with upper socioeconomic status and absence of chest X-ray cavities. Smoking showed a positive trend but was not statistically significant. aOR: Adjusted odds ratio, CI: Confidence interval
Table 5.
Multivariate logistic regression for predictors of early culture conversion (<2 months) in pre-extensively drug-resistant and extensively drug-resistant tuberculosis patients (n=49)
| Predictors | aOR | 95% CI | P |
|---|---|---|---|
| Anemia (no vs. yes) | 3.80 | 1.40–10.30 | 0.008 |
| Underweight (no vs. yes) | 2.90 | 1.05–8.00 | 0.041 |
| Chest X-ray cavity (absent vs. present) | 3.10 | 1.20–7.90 | 0.021 |
| Hypoalbuminemia (no vs. yes) | 4.50 | 1.50–13.40 | 0.007 |
Absence of anemia, normal body mass index, absence of chest X-ray cavities, and normal serum albumin were significantly associated with early conversion. aOR: Adjusted odds ratio, CI: Confidence interval
DISCUSSION
Sputum culture plays an important role in the monitoring of treatment response in patients with MDR-TB, and sputum culture conversion is a clinical tool used to predict therapeutic efficacy.[11]
Out of 25 MDR patients, 24 had culture conversion in our study. Over half of the MDR-TB patients had culture conversion in <3 months. Several studies have examined the time to sputum culture conversion in patients with MDR-TB, highlighting its importance and the various factors that affect it.[12,13,14] Further supporting these findings, a study in Tamil Nadu, India, observed culture conversion within 3 months in 87% of MDR-TB patients,[15] while a multinational cohort study reported a high conversion rate within the same timeframe.[16] Diacon et al.[17] found a median culture conversion time of 83 days, underscoring the variability in treatment response times across different populations and protocols. These studies collectively indicate that the majority of MDR-TB patients achieve culture conversion within 3 months, making this an important milestone for evaluating treatment success.
In the pre-XDR and XDR groups, 45 out of 49 patients had culture conversion by 6 months. Majority of the patients had early culture conversion by 2 months. Almost all patients in this group received a bedaquiline-containing regimen. In our study, by univariate analysis, culture conversion at 2 months was statistically significant in this group. Similar treatment outcomes have recently been reported for patients with multi/XDR-TB (PRE/XDR-TB) in settings where optimal resources for individualized therapy are available. A German study reported that the 2-month smear conversion rate was 78%, and time to culture conversion was 39 days in DR-TB (pre-XDR/XRD TB).[18]
In previous studies, the median time to culture conversion among pre-XDR patients was reported as 2 months, 2.7 months, and <3 months.[7,19,20] A possible explanation for the high rate of early conversion in this group could be the use of bedaquiline-based, all-oral regimens with better compliance.[14]
Age distribution and early culture conversion
In our study, majority of the enrolled DR-TB patients were young, with a mean age of 30 years. Even though a high proportion of patients in our study were young, the association between younger age and culture conversion in terms of time taken in both study groups was not statistically significant [Tables 2 and 3].
In a prospective cohort, the highest proportion of patients was in the age group of 25–44 years, and it was observed that age was not significantly associated with delayed culture conversion.[21] In a study conducted by Kulkarni et al.[22] in 140 MDR patients in India, most patients (58.1%) were in the age group of 21–40 years. Another retrospective follow-up study found that age was not associated with early culture conversion in DR-TB patients.[23] Better immunity in younger populations, leading to enhanced bacillary clearance, may explain the earlier culture conversion.
Gender distribution and early culture conversion
In the MDR group, the association between gender and early culture conversion in terms of time taken (<3 months) was not statistically significant. In MDR cases with resistance to second-line drugs (pre-XDR and XDR), female gender was significantly associated with earlier culture conversion [P = 0.04, Table 3]. In our study, females had an earlier culture conversion of about 20 days. Heunis et al.[24] conducted a retrospective cohort study on the time for 2-month culture conversion that was longer in males compared to females in DR-TB patients. In a prospective observational study of MDR patients, female gender had a statistically significant association with early culture conversion[25] (<3 months). An Indian study found that males were less likely to be diagnosed early with TB and further suggested that delayed sputum conversion in males could be attributed to alcohol consumption and smoking habits and less adherence to treatment.[26]
Body mass index and early culture conversion
In our study, majority of the DR-TB patients were undernourished with low BMI. In MDR with resistance to second-line drugs (pre-XDR and XDR), the association between BMI and early culture conversion (<2 months) was statistically significant [P = 0.025, Table 3]. Pre-XDR and XDR-TB patients with lower BMI had delayed culture conversion exceeding 2 months.
Hyun-Oh Park et al.[27] retrospectively evaluated 218 patients with MDR-TB to analyze the association between BMI and sputum culture conversion within 3 months. Failure to achieve sputum culture conversion within this period was independently associated with a low BMI. In a study evaluating factors affecting 2-month culture conversion in MDR-TB patients,[28] a body mass index (BMI) below 18.5 kg/m2 was identified as an independent factor for delayed sputum culture conversion. A recent systematic review concluded that being underweight significantly increases the risk of unsuccessful treatment outcomes among adults with DR-TB.[29] Low BMI patients are more prone to develop TB, and chances of recurrent infections are high in such patients.
Smoking and early culture conversion
In the MDR-TB group, smoking showed a statistically significant association with early sputum culture conversion (within 3 months) [P = 0.03, Table 2]. Nonsmokers had an earlier 3-month conversion. In MDR with resistance to second-line drugs, the association between smoking and early culture conversion (<2 months) was statistically significant [P = 0.04, Table 3]. Nonsmokers had an earlier 2-month culture conversion than smokers in this group.
A study was conducted to assess the impact of smoking on culture conversion in patients with DR-TB. Among the 1852 patients included, 47.7% were smokers, and smoking had a statistically significant correlation with delayed culture conversion.[6] Remainn et al.[30] evaluated cigarette smoking and its impact on culture conversion in MDR/XDR-TB patients. Among MDR/XDR-TB patients, smokers experienced the longest time to culture conversion, taking more than 2 months on average, compared to nonsmokers. In a Chinese study where 139 MDR-TB patients were enrolled, multivariable analysis showed smoking was associated with delayed culture conversion.[31] The above-mentioned studies support our findings that smoking is a major factor influencing early culture conversion in both MDR- and XDR-TB patients.
Diabetes mellitus and early culture conversion
This study found no significant link between diabetes mellitus (DM) and early culture conversion in DR-TB patients, aligning with Magee et al.’s findings.[6] However, conflicting evidence from a Chinese study[32] and a systematic review[33] suggests DM may delay conversion due to higher bacterial loads Yeboah-Manu et al., BMJ Glob Health 2023) where diabetes mellitus impact.[34] While some research associates DM with poorer TB outcomes,[32,33,34] our results did not support this, highlighting variability in DM’s impact across populations. Further research is needed to clarify these discrepancies
Chest X-ray involvement and early culture conversion
In the MDR group, the association between chest X-rays and early culture conversion (<3 months) was statistically significant [P = 0.01, Table 2]. Patients without cavities in chest X-rays had earlier 3-month culture conversions. In MDR with resistance to second-line drugs (pre-XDR and XDR), the association between chest X-ray and early culture conversion (<2 months) was statistically significant [P = 0.04, Table 3]. Patients with noncavitary chest X-ray profiles had earlier 2-month culture conversion.
Research indicates that the presence of lung cavities can increase the time to sputum culture conversion, with a median time of 68.57 days reported for patients with DR-TB.[35] Basit et al.[12] showed that lung cavitations at baseline chest X-ray had a statistically significant negative association with culture conversion at 2 months. A study conducted in Tamil Nadu, India, showed lung cavitations were associated with delayed culture conversion at 3 months in MDR patients.[15] Tang et al.[32] conducted a study where lung cavitations were associated with a delay in culture conversion (<2 months). These findings collectively support our research and indicate that lung cavitations are strongly associated with delayed sputum culture conversion in DR-TB patients.
Patients with lung cavities often have a higher initial bacillary load, leading to prolonged culture positivity.[36] Furthermore, lung cavities in pulmonary TB are associated with delayed culture conversion due to suboptimal penetration of anti-TB drugs into these lesions, leading to higher bacillary loads and prolonged treatment response, with significant delays observed in patients with cavities ≥25 mL.[37]
Socioeconomic status and early culture conversion
In our study, it was observed that half of the patients belonged to a lower socioeconomic class as determined by the modified Kuppuswamy scale.[47] In the MDR group, the association between socioeconomic status and early culture conversion (<3 months) in terms of time taken was statistically significant [P = 0.02, Table 2]. Patients belonging to the middle class had earlier 3-month culture conversions. Research indicates that treatment interruptions, often associated with lower socioeconomic status and comorbidities, significantly increase the risk of unfavorable treatment outcomes in MDR/XDR-TB patients, including lower rates of culture conversion.[38] This was also observed in our study, as MDR patients belonging to lower socioeconomic classes had a delayed 3-month conversion. Delayed culture conversion in lower socioeconomic classes could be due to a lack of awareness, poor health education, and delay in treatment. Hence, our study has shown that a lower socioeconomic status plays a role in delayed culture conversion in MDR-TB patients.
Anemia and early culture conversion
In MDR with resistance to second-line drugs, the association between anemia and early culture conversion in terms of time taken (<2 months) was statistically significant [Table 3]. Therefore, pre-XDR and XDR-TB patients without anemia were more likely to achieve early culture conversion.
In a retrospective cohort study, higher hemoglobin levels were associated with rapid culture conversion in MDR-TB patients.[39] Similarly, in an Ethiopian review on MDR-TB, anemia was associated with delayed culture conversion (>6 months).[40] A study from Uganda suggests that low hemoglobin may negatively impact culture conversion in MDR-TB patients.[41] Hence, the evidence points toward anemia delaying culture conversion in DR-TB patients, which is also supported by the findings of our study. Anemia was associated with a longer duration of fever, low BMI, high sputum bacillary loads, HIV coinfection, and low CD4 and CD8 counts, which could explain its association with delayed sputum conversion.[41]
Hypoalbuminemia and early culture conversion
In our study, the majority of the study population had hypoalbuminemia with serum albumin <3.5 g/dL. In MDR with resistance to second-line drugs (PRE XDR and XDR), the association between hypoalbuminemia and early culture conversion in terms of time taken (<2 months) was statistically significant [P = 0.025, Table 3]. Patients without hypoalbuminemia had a faster 2-month conversion rate.
A systematic review found that undernutrition, often reflected by low albumin, correlates with longer times to sputum culture conversion and higher mortality rates in MDR-TB.[42] Similarly, studies conducted in China among the MDR and XDR-TB cases showed that decreased serum albumin was associated with delayed culture conversion in both groups.[32,43] In our research, hypoalbuminemia was strongly associated with delayed culture conversion in pre-XDR and XDR-TB patients. Low albumin levels often reflect malnutrition, which can impair immune function, making it harder for the body to combat M. tuberculosis, leading to impaired culture conversion.[44]
The multivariate logistic regression analysis in our study identified distinct predictors of early culture conversion in MDR and pre-XDR/XDR-TB patients. Among MDR-TB patients, upper socioeconomic status and the absence of chest X-ray cavities were independently associated with early conversion. Smoking status, while not statistically significant, demonstrated a strong negative association with early conversion [Table 4]. In pre-XDR and XDR-TB patients, early conversion was significantly associated with the absence of anemia, normal BMI, normal serum albumin levels, and absence of cavities [Table 5], factors that reflect the patient’s underlying nutritional and biological resilience. These findings have important clinical implications. Early identification of high-risk individuals, such as those with anemia, malnutrition, smoking history, and cavitary disease, could prompt more intensive nutritional support, closer monitoring, and adherence counseling from the outset of therapy. Moreover, the role of socioeconomic status underscores the need for social support interventions in DR-TB management. Tailoring programmatic responses based on these predictors could help improve early microbiological response and long-term outcomes in DR-TB. In our study, while individual adherence was not quantitatively measured, patients were managed under the national PMDT framework, which incorporates adherence-supportive strategies such as DOT, regular follow-up at DRTB centers, and digital monitoring through the Nikshay portal.[46]
Implementing targeted strategies such as smoking cessation programs and socioeconomic aid for MDR-TB, nutritional optimization for pre-XDR/XDR-TB, and routine chest X-ray tracking for all patients can significantly improve early conversion rates and reduce treatment delays, ultimately enhancing outcomes in DR-TB management.
CONCLUSIONS
The findings from the study on sputum culture conversion in DR-TB highlight the complex interplay of clinical, radiological, and sociodemographic factors influencing treatment outcomes. Key observations reveal that a significant proportion of patients achieved early culture conversion within three months, aligning with global evidence that early conversion correlates with better treatment success. The study underscores the importance of identifying predictors such as BMI, smoking status, chest X-ray findings, and resistance patterns to guide tailored therapeutic strategies. Overall, the study reinforces that early culture conversion remains a critical milestone, and addressing modifiable risk factors at treatment initiation can significantly enhance patient prognosis and public health outcomes.
Research quality and ethics statement
This study was approved by the National Institute of TB and Respiratory Diseases (NITRD), New Delhi’s Ethical Committee, with IRB NITRD/PGEC/2019/5174. The authors followed applicable EQUATOR Network guidelines during the research project.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
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