Infectious Pulmonary Complications and Reinfection in Treated Cases of Pulmonary Tuberculosis: A Cohort Study from a Tertiary Care Centre in North India

Infectious Pulmonary Complications and Reinfection in Treated Cases of Pulmonary Tuberculosis: A Cohort Study from a Tertiary Care Centre in North India | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Infectious Pulmonary Complications and Reinfection in Treated Cases of Pulmonary Tuberculosis: A Cohort Study from a Tertiary Care Centre in North India Neha Saharan, Rajesh Gupta, Aparna Parmar, Anupama Gupta, Sakshi Bisht, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8808297/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background: Post-tuberculosis lung disease (PTLD) is an emerging global health concern, yet comprehensive data on the spectrum of infectious complications in treated pulmonary tuberculosis (TB) patients from India remains limited, as most existing studies evaluate bacterial, fungal, or reinfection outcomes in isolation. This study aimed to determine the prevalence of bacterial pathogens, fungal pathogens, and TB reinfection from respiratory samples in treated cases of pulmonary TB, and to identify associated clinical and laboratory predictors. Methods: This cohort study enrolled 100 patients who had completed pulmonary TB treatment at least six months prior, attending Pt. B.D. Sharma PGIMS, Rohtak. Respiratory samples were subjected to Gram stain, bacterial culture, acid-fast bacilli (AFB) smear, cartridge-based nucleic acid amplification test (CBNAAT), potassium hydroxide (KOH) mount, and fungal culture. Demographic, clinical, and laboratory parameters were analyzed for associations with infectious outcomes. Results: Bacterial infection was the most prevalent complication (36%), with Klebsiella pneumoniae (10%) and Pseudomonas aeruginosa (8%) being the commonest isolates. TB reinfection was confirmed in 26%, of which 7% demonstrated rifampicin resistance. Fungal infection was identified in 11%, including Candida (6%) and Aspergillus species (5%). Fever (p<0.001), hemoptysis (p<0.001), and leukocytosis (p=0.026) were significant predictors of bacterial infection. Anaemia was significantly associated with TB reinfection (p=0.028). A significant inverse association was observed between bacterial infection and TB reinfection (p=0.021). Conclusion: Treated pulmonary TB patients harbour a substantial infectious burden. Comprehensive microbiological evaluation and structured post-TB follow-up programs are essential for early detection and management of these complications. Post-tuberculosis lung disease bacterial superinfection pulmonary aspergillosis TB reinfection CBNAAT PTLD Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Tuberculosis (TB) remains the world's leading infectious disease killer, with an estimated 10.8 million new cases and 1.25 million deaths reported globally in 2023, of which India alone accounted for over 27% of the global burden [ 1 ]. Although standard anti-tubercular therapy achieves microbiological cure in the majority of drug-susceptible cases, it is now well-established that cure does not equate to the restoration of pulmonary health [ 2 ]. An estimated 155 million TB survivors are alive worldwide, and over half of pulmonary TB survivors demonstrate persistent respiratory morbidity following treatment completion [ 3 ]. Post-tuberculosis lung disease (PTLD), encompassing a spectrum of structural, functional, and infectious sequelae — including bronchiectasis, fibrosis, obstructive airways disease, and pulmonary vascular changes — has emerged as a major contributor to the global burden of chronic respiratory disease, accounting for nearly 47% of the 122 million disability-adjusted life-years (DALYs) attributed to incident TB in 2019 [ 4 ]. A systematic review and meta-analysis from low- and middle-income countries reported a pooled prevalence of abnormal lung function in 46.7%, persistent respiratory symptoms in 41.0%, and radiological abnormalities in 64.6% of post-TB patients, with the highest burden in the South-East Asian region [ 5 ]. The structurally damaged post-TB lung, characterised by residual cavitation, bronchiectasis, and impaired mucociliary clearance, serves as a fertile nidus for secondary infections [ 6 ]. Bacterial superinfections with gram-negative organisms such as Klebsiella pneumoniae and Pseudomonas aeruginosa are increasingly recognised in TB patients, further complicating clinical outcomes [ 7 ]. Chronic pulmonary aspergillosis (CPA) is another serious complication; a recent community-based study from North India reported that CPA complicates approximately 10% of patients with post-TB lung abnormalities, with an incidence of four new cases per 100 person-years following anti-tubercular therapy completion [ 8 ]. The revised estimate of CPA burden in India places the prevalence at approximately 1.5 million, with an estimated 100,000 deaths occurring annually [ 9 ]. Furthermore, TB recurrence poses a substantial challenge in high-incidence settings. A nationwide community-based prevalence survey from India (2019–2021) identified recurrent TB in 27.1% of prevalent TB cases, with drug-resistant TB being significantly more common among recurrent cases (11.3% versus 3.6%) [ 10 ]. Globally, a systematic review found a cumulative recurrence rate of 2.9% over five years, with reinfection being the predominant mechanism in high-burden settings [ 11 ]. Despite the growing recognition of PTLD as a global health priority, most existing studies have evaluated bacterial, fungal, or reinfection outcomes in isolation, and comprehensive data on the composite infectious burden in treated pulmonary TB patients from India remain limited [ 12 ]. This study was therefore undertaken to determine the prevalence of bacterial pathogens, fungal pathogens, and TB reinfection from respiratory samples in treated cases of pulmonary TB, and to identify associated clinical and laboratory predictors. MATERIALS AND METHODS Study Design and Setting This was a cohort study conducted in the Department of Respiratory Medicine in association with the Department of Microbiology at Pt. B.D. Sharma Post Graduate Institute of Medical Sciences (PGIMS), Rohtak, Haryana, India. The study was initiated after obtaining approval from the Institutional Ethics Committee. Written informed consent was obtained from all participants prior to enrolment. Study Population and Sample Size The sample size was calculated using the formula N = (Z₁₋α/₂)²PQ/L², where P = 56.7% (prevalence of chronic pulmonary aspergillosis in post-TB patients from a prior study), Q = 43.3%, L = 20% of P (allowable error = 11.3%), and Z₁₋α/₂ = 1.96 at 95% confidence interval, yielding a minimum required sample of 78 cases, rounded up to 100 for improved statistical power. Patients who had completed treatment for pulmonary tuberculosis at least six months prior and were attending the respiratory medicine outpatient or inpatient services were consecutively enrolled. Inclusion criteria comprised treated cases of pulmonary TB with a minimum post-treatment interval of six months and age greater than 18 years. Patients who did not provide consent and those who had completed TB treatment less than six months prior were excluded. Data Collection A structured proforma was used to record demographic details (age, gender, occupation), risk factors (smoking, alcoholism, diabetes mellitus, hypertension, hypothyroidism), viral co-infection status (HIV, HBsAg, HCV), and clinical symptoms (cough, sputum production, shortness of breath, fever, chest pain, hemoptysis). Laboratory investigations included complete haemogram, liver function tests (SGOT, SGPT, bilirubin, ALP, serum protein), and renal function tests (blood urea, serum creatinine). Microbiological Investigations Respiratory samples were collected as either expectorated sputum or induced sputum. Patients were instructed to gargle with plain water early morning, and sputum samples were collected after coughing into sterile, wide-mouthed, leak-proof containers. For non-expectorating patients, sputum induction was performed using 3% hypertonic saline nebulization for 15 minutes. In patients who failed to produce adequate sputum, bronchoalveolar lavage (BAL) was performed via fibreoptic bronchoscopy using standard technique with 30–40 mL normal saline. Sample adequacy was assessed using Bartlett's scoring method; specimens with a final score of zero or less were discarded and repeat samples collected. Each respiratory sample was subjected to the following investigations: (a) Gram stain for bacterial morphology classification; (b) bacterial culture on blood agar and MacConkey agar plates, incubated at room temperature and examined at 48-hour intervals, with isolation of more than 10,000 colony-forming units by semi-quantitative method considered pathogenic; (c) Ziehl-Neelsen staining for acid-fast bacilli (AFB); (d) cartridge-based nucleic acid amplification test (CBNAAT/GeneXpert MTB/RIF) for Mycobacterium tuberculosis detection and rifampicin resistance; (e) KOH mount for fungal elements; and (f) fungal culture on Sabouraud dextrose agar incubated at 28°C for seven days, with identification based on macroscopic and microscopic characteristics using standard mycological methods. Operational Definitions TB reinfection was defined as detection of Mycobacterium tuberculosis by CBNAAT in a patient who had previously completed a full course of anti-tubercular treatment. Bacterial infection was defined as isolation of a pathogenic organism at more than 10,000 CFU on semi-quantitative culture. Fungal infection was defined as detection of fungal elements on KOH mount and/or isolation of fungi on culture. Statistical Analysis Data were analyzed using appropriate statistical software. Continuous variables were expressed as mean ± standard deviation and compared using independent t-test (for normally distributed data) or Mann-Whitney U test (for non-normally distributed data). Categorical variables were expressed as frequencies and percentages, and compared using Chi-square test (when expected cell counts were ≥ 5) or Fisher's exact test (when expected cell counts were < 5). Pearson correlation coefficients were calculated between continuous laboratory variables. A p-value of less than 0.05 was considered statistically significant. RESULTS Baseline Profile The baseline demographic, clinical, and laboratory characteristics of the 100 enrolled patients are summarized in Table 1 . The cohort was predominantly middle-aged (mean age 49.6 ± 15.2 years) and male (67%), with housewives, labourers, and farmers together accounting for nearly two-thirds of participants. Smoking and alcoholism were the most prevalent risk factors, while diabetes mellitus and HIV co-infection were noteworthy comorbidities affecting one-fifth and one-eighth of patients respectively. Respiratory symptoms were near-universal, with cough and sputum production reported by approximately nine out of ten patients. Fever and hemoptysis, which later emerged as significant predictors of bacterial infection, were present in roughly two-thirds and one-third of the cohort respectively. Laboratory evaluation revealed a mean haemoglobin suggestive of widespread anaemia, alongside elevated mean leucocyte counts indicating ongoing inflammation or active infection in the majority. Liver transaminases were mildly elevated, while renal parameters remained largely within normal limits. Table 1 Baseline Demographic, Clinical, and Laboratory Characteristics (n = 100) A. Demographics Age (years), Mean ± SD (Range) 49.6 ± 15.2 (22–82) Age < 30 / 30–39 / 40–49 / 50–59 / 60–69 / ≥70 years, n 16 / 13 / 23 / 25 / 10 / 13 Male : Female, n (%) 67 (67.0) : 33 (33.0) Occupation — Housewife / Labourer / Farmer / Driver / Others, n 29 / 18 / 17 / 10 / 26 B. Risk Factors & Comorbidities, n (%) Smoking 65 (65.0) Alcoholism 47 (47.0) Diabetes Mellitus 20 (20.0) Hypertension 8 (8.0) Hypothyroidism 9 (9.0) HIV Positive 12 (12.0) HBsAg Positive 5 (5.0) HCV Positive 3 (3.0) Any Viral Co-infection 21 (21.0) C. Clinical Symptoms, n (%) Cough 90 (90.0) Sputum Production 88 (88.0) Shortness of Breath 74 (74.0) Fever 65 (65.0) Chest Pain 42 (42.0) Hemoptysis 36 (36.0) Previous TB Episodes — 1 / 2, n 90 / 10 D. Laboratory Parameters, Mean ± SD (Range) Haemoglobin (g/dL) 10.25 ± 1.63 (6.5–15.6) TLC (cells/cumm) 14,567.59 ± 6,151.19 (3,400–39,000) SGOT (U/L) 52.8 ± 24.88 (18–158) SGPT (U/L) 54.8 ± 47.16 (10–449) Bilirubin (mg/dL) 1.09 ± 0.42 (0.5–3.1) ALP (U/L) 110.39 ± 51.32 (39–320) Blood Urea (mg/dL) 42.34 ± 19.02 (8–97) Serum Creatinine (mg/dL) 0.94 ± 0.45 (0.1–3.1) Microbiological Outcomes The complete microbiological profile is detailed in Table 2 , and the overall prevalence of the three infectious complications is depicted in Fig. 1 . Bacterial superinfection was the most frequently identified complication, present in over one-third of patients, followed by TB reinfection in approximately one-quarter and fungal infection in about one-tenth of cases. Table 2 Microbiological Profile of Respiratory Samples (n = 100) A. Bacterial Culture, n (%) No growth (sterile) 64 (64.0) Klebsiella pneumoniae 10 (10.0) Pseudomonas aeruginosa 8 (8.0) Staphylococcus aureus 6 (6.0) Streptococcus pneumoniae 4 (4.0) Acinetobacter baumannii 3 (3.0) Escherichia coli 3 (3.0) Others (Citrobacter koseri, Proteus vulgaris) 2 (2.0) Total bacterial infection 36 (36.0) B. Gram Stain, n (%) No organism 74 (74.0) Gram-negative rods 17 (17.0) Gram-negative coccobacilli 3 (3.0) Gram-positive cocci 3 (3.0) Gram-positive diplococci 3 (3.0) C. CBNAAT Result, n (%) MTB Not Detected 74 (74.0) MTB Detected — Rifampicin Sensitive 19 (19.0) MTB Detected — Rifampicin Resistant 7 (7.0) Total TB reinfection 26 (26.0) D. AFB Smear, n (%) Negative 77 (77.0) 1+ 6 (6.0) 2+ 12 (12.0) 3+ 5 (5.0) AFB–CBNAAT concordance 97.0% E. KOH Mount, n (%) No fungal elements 83 (83.0) Septate hyphae 6 (6.0) Budding yeast cells 8 (8.0) Budding yeast + pseudohyphae 2 (2.0) Aseptate hyphae 1 (1.0) F. Fungal Culture, n (%) No growth (sterile) 89 (89.0) Candida species 6 (6.0) Aspergillus species 5 (5.0) Total fungal infection 11 (11.0) The spectrum of isolated organisms is illustrated in Fig. 2 . Among bacterial isolates, gram-negative organisms overwhelmingly predominated, with Klebsiella pneumoniae and Pseudomonas aeruginosa together accounting for half of all bacterial isolates. Staphylococcus aureus was the commonest gram-positive pathogen. Gram stain findings demonstrated good concordance with culture results, with gram-negative rods being the predominant morphological pattern. TB reinfection, confirmed by CBNAAT, was the second most common infectious outcome. Notably, more than a quarter of these reinfection cases demonstrated rifampicin resistance, raising concern for multidrug-resistant TB in this population. AFB smear positivity was detected at a marginally lower rate than CBNAAT, and the two tests showed excellent concordance of 97% (p < 0.001), with CBNAAT demonstrating superior sensitivity. Fungal elements were identified on KOH mount in nearly one-fifth of samples, though culture-confirmed fungal infection was lower. Candida species slightly outnumbered Aspergillus species among culture isolates (Fig. 2 ). The presence of septate hyphae on KOH mount correlated with Aspergillus isolation, while budding yeast cells corresponded to Candida detection. The majority of patients (90%) had a single prior TB episode, while 10% reported two previous episodes. Predictors of Infectious Outcomes The statistically significant associations identified in this study are presented in Table 3 , with key predictors summarized visually in Fig. 3 . Among clinical predictors, fever and hemoptysis emerged as the strongest indicators of bacterial superinfection, both reaching high levels of significance. Interestingly, chest pain showed an inverse association with bacterial infection, being significantly less common in infected patients. Sputum production demonstrated a borderline trend (p = 0.051) but did not achieve significance. Table 3 Statistically Significant Associations with Infectious Outcomes Association Outcome Present Outcome Absent Test p-value Predictors of Bacterial Infection (n = 36) Fever, n (%) 33/36 (91.7) 32/64 (50.0) Fisher's < 0.001 Hemoptysis, n (%) 22/36 (61.1) 14/64 (21.9) χ²=13.74 11,000), n (%) 33/78 (42.3) 3/22 (13.6) χ²=4.94 0.026 SGOT (U/L), Mean ± SD 57.5 ± 23.7 50.1 ± 25.3 Mann-Whitney 0.034 Predictors of TB Reinfection (n = 26) Haemoglobin (g/dL), Mean ± SD 9.36 ± 1.28 10.57 ± 1.64 t-test (t = − 3.84) < 0.001 Anaemia (Hb < 11 g/dL), n (%) 17/45 (37.8) 9/55 (16.4) χ²=4.84 0.028 Inter-pathogen Associations Bacterial Infection vs TB Reinfection † 4/36 (11.1) 22/64 (34.4) χ²=5.33 0.021 Diagnostic Concordance AFB Smear vs CBNAAT Concordant: 97% Discordant: 3% χ²=80.09 < 0.001 † Inverse association Among laboratory markers, total leucocyte count was significantly elevated in patients with bacterial infection, and categorical analysis confirmed leukocytosis as a reliable diagnostic marker. SGOT levels were also significantly higher in this group, potentially reflecting systemic inflammatory stress. Other liver and renal parameters did not differ significantly between groups. For TB reinfection, haemoglobin emerged as the most significant laboratory predictor. Patients with reinfection had markedly lower haemoglobin levels, and categorical analysis confirmed anaemia as a significant risk factor. A non-significant trend was observed toward younger patients having higher reinfection rates, though this did not reach statistical significance (p = 0.185). A notable finding was the significant inverse association between bacterial infection and TB reinfection — concurrent presence of both was uncommon, suggesting potentially distinct or competing pathophysiological mechanisms. Bacterial and fungal co-infection showed a similar inverse trend without reaching significance (p = 0.092). Gender, age group, smoking status, alcoholism, and diabetes mellitus were not significantly associated with any of the three infectious outcomes, though diabetic patients showed noteworthy trends toward higher fungal infection (20.0% vs 8.8%, p = 0.146) and TB reinfection rates (40.0% vs 22.5%, p = 0.185). Correlation analysis among continuous laboratory variables revealed strong positive correlations between blood urea and serum creatinine (r = 0.728, p < 0.001) and between SGOT and SGPT (r = 0.589, p < 0.001), consistent with their shared organ origins. TLC showed significant correlations with ALP (r = 0.316), serum creatinine (r = 0.307), and SGOT (r = 0.228), suggesting multi-organ inflammatory involvement in this cohort. DISCUSSION This study provides a comprehensive evaluation of the composite infectious burden in treated pulmonary TB patients, simultaneously assessing bacterial, fungal, and reinfection outcomes — an approach that distinguishes it from most prior investigations which have evaluated these complications in isolation [ 12 ]. The bacterial infection prevalence of 36% in our cohort is consistent with a retrospective cross-sectional study from Cambodia by Attia et al. [ 7 ], which reported bacterial co-infection rates of approximately 28–38% among TB patients, with gram-negative organisms predominating. However, our rate is notably higher than the 13–28% range reported in studies on respiratory bacterial superinfection in other chronic lung diseases [ 13 ]. The predominance of Klebsiella pneumoniae (10%) and Pseudomonas aeruginosa (8%) in our study aligns closely with findings from a nanopore sequencing-based case series by Shu et al. (2024) [ 13 ], which identified Klebsiella and Pseudomonas as the most frequent bacterial co-pathogens in patients with active and recurrent TB, particularly in the presence of cavitary lung disease. The 2024 WHO Bacterial Priority Pathogens List classifies both carbapenem-resistant K. pneumoniae and P. aeruginosa as critical-priority organisms [ 14 ], underscoring the clinical significance of their frequent isolation in our structurally damaged post-TB cohort. TB reinfection was detected by CBNAAT in 26% of cases, a figure that corroborates findings from the 2019–2021 nationwide community-based TB prevalence survey in India by Selvaraj et al. [ 10 ], which identified recurrent TB in 27.1% of prevalent cases. Globally, a systematic review by Mithunage and Denning (2024) [ 11 ] reported a cumulative five-year recurrence rate of 2.9%, though higher rates are well-recognised in high-burden settings such as India where ongoing community transmission facilitates exogenous reinfection. A systematic review and meta-analysis by Vega et al. (2024) [ 15 ] confirmed that HIV co-infection and multidrug resistance in the index episode are the strongest predictors of reinfection, while host nutritional status, including anaemia, was identified as a contributing factor in several included studies. Our finding that rifampicin resistance was present in 26.9% (7/26) of reinfection cases exceeds the national estimate of 16% among previously treated cases reported in the WHO Global TB Report 2024 [ 1 ], but is consistent with the high MDR-TB burden described by Husain and Kashyap (2023) [ 16 ], who highlighted that India accounts for 27% of global MDR/RR-TB cases, with acquired resistance being amplified by antimicrobial misuse and suboptimal treatment adherence. The excellent concordance of 97% between AFB smear and CBNAAT in our study supports the established utility of CBNAAT as a rapid and reliable tool for simultaneous TB detection and rifampicin resistance profiling, consistent with programmatic data from the India TB Report 2024 [ 17 ]. Fungal infection was identified in 11% of our cohort, with Candida (6%) slightly outnumbering Aspergillus species (5%). The Aspergillus prevalence is lower than the 14.5% CPA incidence reported by Jha et al. (2024) [ 18 ] at the end of anti-TB therapy in a prospective AIIMS study, and also lower than the pooled post-treatment CPA prevalence of 13% reported in a recent systematic review by Testa et al. (2025) [ 19 ]. This discrepancy likely reflects the absence of Aspergillus-specific IgG and galactomannan testing in our study, which are considered essential for accurate CPA diagnosis [ 8 , 9 ]. Lakhtakia et al. (2022) [ 20 ] similarly reported a wide spectrum of pulmonary aspergillus diseases in post-TB patients in India, emphasising that culture-based methods alone substantially underestimate the true burden of CPA. Anaemia emerged as a significant predictor of TB reinfection in our study (p = 0.028), a finding supported by a systematic review and meta-analysis by Getachew and Muluye (2021) [ 21 ], which demonstrated that anaemic individuals have significantly higher odds of developing active TB compared to non-anaemic counterparts. Araújo-Pereira et al. (2024) [ 22 ] further demonstrated that coexistent anaemia amplifies systemic inflammation and worsens TB disease severity, potentially facilitating reactivation or reinfection through impaired cell-mediated immunity. The significant association of fever, hemoptysis, and leukocytosis with bacterial infection in our study is clinically intuitive and mirrors findings from multiple studies on community-acquired pneumonia in structurally damaged lungs [ 6 , 7 ]. The inverse association between bacterial infection and TB reinfection (p = 0.021) is a novel observation not previously reported and may reflect competitive microbial interactions or divergent immunopathological pathways in the post-TB lung milieu, warranting further mechanistic investigation. In summary, these findings reinforce the concept that treated pulmonary TB patients require structured, comprehensive post-treatment surveillance programmes incorporating bacteriological, mycological, and molecular evaluations to enable early diagnosis and improve long-term respiratory outcomes. LIMITATIONS This study has several limitations that merit acknowledgement. Being a single-centre study, the findings may not be generalizable to all populations. The relatively small sample size of 100 patients may have resulted in type II errors, particularly for associations that showed trends without reaching statistical significance. Aspergillus-specific IgG and galactomannan assays were not performed, potentially underestimating the true prevalence of chronic pulmonary aspergillosis. High-resolution computed tomography correlation for structural lung disease classification was not included. Candida isolation from respiratory samples may represent colonization rather than true invasive infection. Additionally, drug sensitivity testing beyond rifampicin was not performed, limiting the full characterization of drug resistance patterns. CONCLUSION Treated pulmonary tuberculosis patients carry a substantial burden of secondary infectious complications, with bacterial superinfection, TB reinfection, and fungal infection being the principal findings in this cohort. Gram-negative organisms, particularly Klebsiella pneumoniae and Pseudomonas aeruginosa, dominated the bacterial spectrum. The detection of rifampicin resistance in over a quarter of reinfection cases raises concern for multidrug-resistant TB in this population. Fever, hemoptysis, and leukocytosis serve as practical clinical predictors of bacterial superinfection, while anaemia emerged as a significant risk marker for TB reinfection. These findings underscore the necessity of comprehensive microbiological evaluation and structured long-term follow-up programs for all patients completing pulmonary TB treatment, to enable early detection and targeted management of infectious complications. Declarations Ethics approval and consent to participate This study was approved by the Institutional Ethics Committee of Pt. B. D. Sharma Post Graduate Institute of Medical Sciences (PGIMS), Rohtak, Haryana, India. Written informed consent was obtained from all participants prior to enrolment. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors' contributions NS and SB conceptualized the study, collected data, and drafted the manuscript. RG supervised the study and critically revised the manuscript. AP performed microbiological investigations and interpreted results. AG contributed to data analysis and interpretation. RaG assisted in data collection and literature review. All authors read and approved the final manuscript. Acknowledgements Not applicable. Clinical trial registration Not applicable. References World Health Organization. Global Tuberculosis Report 2024. Geneva: World Health Organization; 2024. 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Coexistent anemia modulates systemic inflammation and exacerbates disease severity and adverse treatment outcomes in tuberculosis. Front Tuberc. 2024;2:1462654. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 17 Mar, 2026 Reviews received at journal 21 Feb, 2026 Reviewers agreed at journal 16 Feb, 2026 Reviews received at journal 14 Feb, 2026 Reviewers agreed at journal 14 Feb, 2026 Reviewers agreed at journal 11 Feb, 2026 Reviewers invited by journal 11 Feb, 2026 Editor invited by journal 10 Feb, 2026 Editor assigned by journal 07 Feb, 2026 Submission checks completed at journal 07 Feb, 2026 First submitted to journal 06 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8808297","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":591425028,"identity":"96dc879f-46cf-4971-9418-ff3058ad2153","order_by":0,"name":"Neha Saharan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIiWNgGAWjYFACHigtwcBw4AOQZmMnQQvjwRkgLcwkaGE+DGYT0iLffvbg54qaO3n80s0PDtv82ibPx8zA+OFjDm4tBmfykiXPHHtWLDnnmMHh3L7bhm3MDMySM7fh0cKQYyDZwHY4ccONBKCWntuMQC1szLx4tMj3vzH+2fDvcOL+G+kfDlv23LYnqIXhRo6ZZGMb0BaJHIPDDD9uJxLUYnDjjZllY9/hxBk3cgoO9jbcTm5jZmzG6xf5/hzjmw3fDif2z0jf/OHHn9u289ubD374iM9hKICxDUw2EKseBP6QongUjIJRMApGCgAAYMpYb7xVK0MAAAAASUVORK5CYII=","orcid":"","institution":"Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Neha","middleName":"","lastName":"Saharan","suffix":""},{"id":591425030,"identity":"569b92f7-ad03-4a49-986e-02ed77201c5a","order_by":1,"name":"Rajesh Gupta","email":"","orcid":"","institution":"Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Rajesh","middleName":"","lastName":"Gupta","suffix":""},{"id":591425031,"identity":"ae7ecb10-b8b8-4724-adc6-d7356f42b7c4","order_by":2,"name":"Aparna Parmar","email":"","orcid":"","institution":"Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Aparna","middleName":"","lastName":"Parmar","suffix":""},{"id":591425032,"identity":"77750981-d1c2-4d4b-b632-f31afb1c9942","order_by":3,"name":"Anupama Gupta","email":"","orcid":"","institution":"Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Anupama","middleName":"","lastName":"Gupta","suffix":""},{"id":591425033,"identity":"5e9c22f8-10d4-4c0e-8b91-646fd665254b","order_by":4,"name":"Sakshi Bisht","email":"","orcid":"","institution":"Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Sakshi","middleName":"","lastName":"Bisht","suffix":""},{"id":591425034,"identity":"3d2a55d3-e38f-483e-b850-f731b965c971","order_by":5,"name":"Raghav Gupta","email":"","orcid":"","institution":"Indraprastha University","correspondingAuthor":false,"prefix":"","firstName":"Raghav","middleName":"","lastName":"Gupta","suffix":""}],"badges":[],"createdAt":"2026-02-06 14:44:58","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8808297/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8808297/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102828904,"identity":"3277bed5-0720-4db4-8de5-dccf5b6379f9","added_by":"auto","created_at":"2026-02-17 09:26:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":37708,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePrevalence of Infectious Complications\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8808297/v1/ed1a11d290aa59e61fb9a5da.png"},{"id":102828848,"identity":"fb712d9d-42b1-4c9e-9308-540cf80408f5","added_by":"auto","created_at":"2026-02-17 09:26:32","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":55455,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDistribution of Bacterial and Fungal Species\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8808297/v1/0038c9eb21d35a3b9ffe0793.png"},{"id":102828925,"identity":"65c2bb51-5a90-442d-bf04-3938e5838636","added_by":"auto","created_at":"2026-02-17 09:26:47","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":99770,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSignificant Clinical and Laboratory Predictors\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8808297/v1/6e19692407ab47314fa19fb8.png"},{"id":102829053,"identity":"60317842-2fc3-4977-a493-aa0a6a74e3ed","added_by":"auto","created_at":"2026-02-17 09:27:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":976704,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8808297/v1/55a9abff-804f-48c0-93fa-da9292f75dec.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Infectious Pulmonary Complications and Reinfection in Treated Cases of Pulmonary Tuberculosis: A Cohort Study from a Tertiary Care Centre in North India","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eTuberculosis (TB) remains the world's leading infectious disease killer, with an estimated 10.8\u0026nbsp;million new cases and 1.25\u0026nbsp;million deaths reported globally in 2023, of which India alone accounted for over 27% of the global burden [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Although standard anti-tubercular therapy achieves microbiological cure in the majority of drug-susceptible cases, it is now well-established that cure does not equate to the restoration of pulmonary health [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. An estimated 155\u0026nbsp;million TB survivors are alive worldwide, and over half of pulmonary TB survivors demonstrate persistent respiratory morbidity following treatment completion [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Post-tuberculosis lung disease (PTLD), encompassing a spectrum of structural, functional, and infectious sequelae \u0026mdash; including bronchiectasis, fibrosis, obstructive airways disease, and pulmonary vascular changes \u0026mdash; has emerged as a major contributor to the global burden of chronic respiratory disease, accounting for nearly 47% of the 122\u0026nbsp;million disability-adjusted life-years (DALYs) attributed to incident TB in 2019 [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. A systematic review and meta-analysis from low- and middle-income countries reported a pooled prevalence of abnormal lung function in 46.7%, persistent respiratory symptoms in 41.0%, and radiological abnormalities in 64.6% of post-TB patients, with the highest burden in the South-East Asian region [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe structurally damaged post-TB lung, characterised by residual cavitation, bronchiectasis, and impaired mucociliary clearance, serves as a fertile nidus for secondary infections [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Bacterial superinfections with gram-negative organisms such as Klebsiella pneumoniae and Pseudomonas aeruginosa are increasingly recognised in TB patients, further complicating clinical outcomes [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Chronic pulmonary aspergillosis (CPA) is another serious complication; a recent community-based study from North India reported that CPA complicates approximately 10% of patients with post-TB lung abnormalities, with an incidence of four new cases per 100 person-years following anti-tubercular therapy completion [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The revised estimate of CPA burden in India places the prevalence at approximately 1.5\u0026nbsp;million, with an estimated 100,000 deaths occurring annually [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Furthermore, TB recurrence poses a substantial challenge in high-incidence settings. A nationwide community-based prevalence survey from India (2019\u0026ndash;2021) identified recurrent TB in 27.1% of prevalent TB cases, with drug-resistant TB being significantly more common among recurrent cases (11.3% versus 3.6%) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Globally, a systematic review found a cumulative recurrence rate of 2.9% over five years, with reinfection being the predominant mechanism in high-burden settings [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite the growing recognition of PTLD as a global health priority, most existing studies have evaluated bacterial, fungal, or reinfection outcomes in isolation, and comprehensive data on the composite infectious burden in treated pulmonary TB patients from India remain limited [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. This study was therefore undertaken to determine the prevalence of bacterial pathogens, fungal pathogens, and TB reinfection from respiratory samples in treated cases of pulmonary TB, and to identify associated clinical and laboratory predictors.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Setting\u003c/h2\u003e \u003cp\u003eThis was a cohort study conducted in the Department of Respiratory Medicine in association with the Department of Microbiology at Pt. B.D. Sharma Post Graduate Institute of Medical Sciences (PGIMS), Rohtak, Haryana, India. The study was initiated after obtaining approval from the Institutional Ethics Committee. Written informed consent was obtained from all participants prior to enrolment.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy Population and Sample Size\u003c/h3\u003e\n\u003cp\u003eThe sample size was calculated using the formula N = (Z₁₋α/₂)\u0026sup2;PQ/L\u0026sup2;, where P\u0026thinsp;=\u0026thinsp;56.7% (prevalence of chronic pulmonary aspergillosis in post-TB patients from a prior study), Q\u0026thinsp;=\u0026thinsp;43.3%, L\u0026thinsp;=\u0026thinsp;20% of P (allowable error\u0026thinsp;=\u0026thinsp;11.3%), and Z₁₋α/₂ = 1.96 at 95% confidence interval, yielding a minimum required sample of 78 cases, rounded up to 100 for improved statistical power.\u003c/p\u003e \u003cp\u003ePatients who had completed treatment for pulmonary tuberculosis at least six months prior and were attending the respiratory medicine outpatient or inpatient services were consecutively enrolled. Inclusion criteria comprised treated cases of pulmonary TB with a minimum post-treatment interval of six months and age greater than 18 years. Patients who did not provide consent and those who had completed TB treatment less than six months prior were excluded.\u003c/p\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cp\u003eA structured proforma was used to record demographic details (age, gender, occupation), risk factors (smoking, alcoholism, diabetes mellitus, hypertension, hypothyroidism), viral co-infection status (HIV, HBsAg, HCV), and clinical symptoms (cough, sputum production, shortness of breath, fever, chest pain, hemoptysis). Laboratory investigations included complete haemogram, liver function tests (SGOT, SGPT, bilirubin, ALP, serum protein), and renal function tests (blood urea, serum creatinine).\u003c/p\u003e\n\u003ch3\u003eMicrobiological Investigations\u003c/h3\u003e\n\u003cp\u003eRespiratory samples were collected as either expectorated sputum or induced sputum. Patients were instructed to gargle with plain water early morning, and sputum samples were collected after coughing into sterile, wide-mouthed, leak-proof containers. For non-expectorating patients, sputum induction was performed using 3% hypertonic saline nebulization for 15 minutes. In patients who failed to produce adequate sputum, bronchoalveolar lavage (BAL) was performed via fibreoptic bronchoscopy using standard technique with 30\u0026ndash;40 mL normal saline. Sample adequacy was assessed using Bartlett's scoring method; specimens with a final score of zero or less were discarded and repeat samples collected.\u003c/p\u003e \u003cp\u003eEach respiratory sample was subjected to the following investigations: (a) Gram stain for bacterial morphology classification; (b) bacterial culture on blood agar and MacConkey agar plates, incubated at room temperature and examined at 48-hour intervals, with isolation of more than 10,000 colony-forming units by semi-quantitative method considered pathogenic; (c) Ziehl-Neelsen staining for acid-fast bacilli (AFB); (d) cartridge-based nucleic acid amplification test (CBNAAT/GeneXpert MTB/RIF) for Mycobacterium tuberculosis detection and rifampicin resistance; (e) KOH mount for fungal elements; and (f) fungal culture on Sabouraud dextrose agar incubated at 28\u0026deg;C for seven days, with identification based on macroscopic and microscopic characteristics using standard mycological methods.\u003c/p\u003e\n\u003ch3\u003eOperational Definitions\u003c/h3\u003e\n\u003cp\u003eTB reinfection was defined as detection of Mycobacterium tuberculosis by CBNAAT in a patient who had previously completed a full course of anti-tubercular treatment. Bacterial infection was defined as isolation of a pathogenic organism at more than 10,000 CFU on semi-quantitative culture. Fungal infection was defined as detection of fungal elements on KOH mount and/or isolation of fungi on culture.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData were analyzed using appropriate statistical software. Continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and compared using independent t-test (for normally distributed data) or Mann-Whitney U test (for non-normally distributed data). Categorical variables were expressed as frequencies and percentages, and compared using Chi-square test (when expected cell counts were \u0026ge;\u0026thinsp;5) or Fisher's exact test (when expected cell counts were \u0026lt;\u0026thinsp;5). Pearson correlation coefficients were calculated between continuous laboratory variables. A p-value of less than 0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eBaseline Profile\u003c/h2\u003e \u003cp\u003eThe baseline demographic, clinical, and laboratory characteristics of the 100 enrolled patients are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The cohort was predominantly middle-aged (mean age 49.6\u0026thinsp;\u0026plusmn;\u0026thinsp;15.2 years) and male (67%), with housewives, labourers, and farmers together accounting for nearly two-thirds of participants. Smoking and alcoholism were the most prevalent risk factors, while diabetes mellitus and HIV co-infection were noteworthy comorbidities affecting one-fifth and one-eighth of patients respectively. Respiratory symptoms were near-universal, with cough and sputum production reported by approximately nine out of ten patients. Fever and hemoptysis, which later emerged as significant predictors of bacterial infection, were present in roughly two-thirds and one-third of the cohort respectively. Laboratory evaluation revealed a mean haemoglobin suggestive of widespread anaemia, alongside elevated mean leucocyte counts indicating ongoing inflammation or active infection in the majority. Liver transaminases were mildly elevated, while renal parameters remained largely within normal limits.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline Demographic, Clinical, and Laboratory Characteristics (n\u0026thinsp;=\u0026thinsp;100)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA. Demographics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years), Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (Range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49.6\u0026thinsp;\u0026plusmn;\u0026thinsp;15.2 (22\u0026ndash;82)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026thinsp;\u0026lt;\u0026thinsp;30 / 30\u0026ndash;39 / 40\u0026ndash;49 / 50\u0026ndash;59 / 60\u0026ndash;69 / \u0026ge;70 years, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 / 13 / 23 / 25 / 10 / 13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale : Female, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67 (67.0) : 33 (33.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOccupation \u0026mdash; Housewife / Labourer / Farmer / Driver / Others, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 / 18 / 17 / 10 / 26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB. Risk Factors \u0026amp; Comorbidities, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65 (65.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcoholism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47 (47.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes Mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (20.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (8.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypothyroidism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (9.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHIV Positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (12.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHBsAg Positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (5.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHCV Positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny Viral Co-infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (21.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC. Clinical Symptoms, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCough\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90 (90.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSputum Production\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88 (88.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShortness of Breath\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 (74.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65 (65.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChest Pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42 (42.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoptysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (36.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious TB Episodes \u0026mdash; 1 / 2, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90 / 10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD. Laboratory Parameters, Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (Range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemoglobin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.25\u0026thinsp;\u0026plusmn;\u0026thinsp;1.63 (6.5\u0026ndash;15.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTLC (cells/cumm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14,567.59\u0026thinsp;\u0026plusmn;\u0026thinsp;6,151.19 (3,400\u0026ndash;39,000)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSGOT (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.8\u0026thinsp;\u0026plusmn;\u0026thinsp;24.88 (18\u0026ndash;158)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSGPT (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.8\u0026thinsp;\u0026plusmn;\u0026thinsp;47.16 (10\u0026ndash;449)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilirubin (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.42 (0.5\u0026ndash;3.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALP (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e110.39\u0026thinsp;\u0026plusmn;\u0026thinsp;51.32 (39\u0026ndash;320)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood Urea (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.34\u0026thinsp;\u0026plusmn;\u0026thinsp;19.02 (8\u0026ndash;97)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum Creatinine (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45 (0.1\u0026ndash;3.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eMicrobiological Outcomes\u003c/h2\u003e \u003cp\u003eThe complete microbiological profile is detailed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, and the overall prevalence of the three infectious complications is depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Bacterial superinfection was the most frequently identified complication, present in over one-third of patients, followed by TB reinfection in approximately one-quarter and fungal infection in about one-tenth of cases.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMicrobiological Profile of Respiratory Samples (n\u0026thinsp;=\u0026thinsp;100)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA. Bacterial Culture, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo growth (sterile)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e64 (64.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKlebsiella pneumoniae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10 (10.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePseudomonas aeruginosa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (8.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStaphylococcus aureus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (6.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStreptococcus pneumoniae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (4.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcinetobacter baumannii\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (3.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEscherichia coli\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (3.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers (Citrobacter koseri, Proteus vulgaris)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (2.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal bacterial infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e36 (36.0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB. Gram Stain, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo organism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e74 (74.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGram-negative rods\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17 (17.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGram-negative coccobacilli\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (3.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGram-positive cocci\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (3.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGram-positive diplococci\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (3.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC. CBNAAT Result, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMTB Not Detected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e74 (74.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMTB Detected \u0026mdash; Rifampicin Sensitive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19 (19.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMTB Detected \u0026mdash; Rifampicin Resistant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (7.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal TB reinfection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e26 (26.0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD. AFB Smear, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e77 (77.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (6.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (12.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (5.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAFB\u0026ndash;CBNAAT concordance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e97.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE. KOH Mount, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo fungal elements\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e83 (83.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeptate hyphae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (6.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBudding yeast cells\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (8.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBudding yeast\u0026thinsp;+\u0026thinsp;pseudohyphae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (2.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAseptate hyphae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF. Fungal Culture, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo growth (sterile)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e89 (89.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCandida species\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (6.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspergillus species\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (5.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal fungal infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e11 (11.0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe spectrum of isolated organisms is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Among bacterial isolates, gram-negative organisms overwhelmingly predominated, with Klebsiella pneumoniae and Pseudomonas aeruginosa together accounting for half of all bacterial isolates. Staphylococcus aureus was the commonest gram-positive pathogen. Gram stain findings demonstrated good concordance with culture results, with gram-negative rods being the predominant morphological pattern.\u003c/p\u003e \u003cp\u003eTB reinfection, confirmed by CBNAAT, was the second most common infectious outcome. Notably, more than a quarter of these reinfection cases demonstrated rifampicin resistance, raising concern for multidrug-resistant TB in this population. AFB smear positivity was detected at a marginally lower rate than CBNAAT, and the two tests showed excellent concordance of 97% (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with CBNAAT demonstrating superior sensitivity.\u003c/p\u003e \u003cp\u003eFungal elements were identified on KOH mount in nearly one-fifth of samples, though culture-confirmed fungal infection was lower. Candida species slightly outnumbered Aspergillus species among culture isolates (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The presence of septate hyphae on KOH mount correlated with Aspergillus isolation, while budding yeast cells corresponded to Candida detection. The majority of patients (90%) had a single prior TB episode, while 10% reported two previous episodes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePredictors of Infectious Outcomes\u003c/h2\u003e \u003cp\u003eThe statistically significant associations identified in this study are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, with key predictors summarized visually in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Among clinical predictors, fever and hemoptysis emerged as the strongest indicators of bacterial superinfection, both reaching high levels of significance. Interestingly, chest pain showed an inverse association with bacterial infection, being significantly less common in infected patients. Sputum production demonstrated a borderline trend (p\u0026thinsp;=\u0026thinsp;0.051) but did not achieve significance.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStatistically Significant Associations with Infectious Outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAssociation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOutcome Present\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOutcome Absent\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTest\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePredictors of Bacterial Infection (n\u0026thinsp;=\u0026thinsp;36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33/36 (91.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32/64 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFisher's\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoptysis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22/36 (61.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14/64 (21.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u0026sup2;=13.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChest Pain, n (%) \u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8/36 (22.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34/64 (53.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u0026sup2;=7.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTLC (cells/cumm), Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16,715\u0026thinsp;\u0026plusmn;\u0026thinsp;6,283\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13,359\u0026thinsp;\u0026plusmn;\u0026thinsp;5,780\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMann-Whitney\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukocytosis (TLC\u0026thinsp;\u0026gt;\u0026thinsp;11,000), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33/78 (42.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3/22 (13.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u0026sup2;=4.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSGOT (U/L), Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57.5\u0026thinsp;\u0026plusmn;\u0026thinsp;23.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.1\u0026thinsp;\u0026plusmn;\u0026thinsp;25.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMann-Whitney\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.034\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePredictors of TB Reinfection (n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemoglobin (g/dL), Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.36\u0026thinsp;\u0026plusmn;\u0026thinsp;1.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.57\u0026thinsp;\u0026plusmn;\u0026thinsp;1.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003et-test (t\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;3.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnaemia (Hb\u0026thinsp;\u0026lt;\u0026thinsp;11 g/dL), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17/45 (37.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9/55 (16.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u0026sup2;=4.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.028\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInter-pathogen Associations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBacterial Infection vs TB Reinfection \u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/36 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22/64 (34.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u0026sup2;=5.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnostic Concordance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAFB Smear vs CBNAAT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eConcordant: 97%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDiscordant: 3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u0026sup2;=80.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u0026dagger; Inverse association\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong laboratory markers, total leucocyte count was significantly elevated in patients with bacterial infection, and categorical analysis confirmed leukocytosis as a reliable diagnostic marker. SGOT levels were also significantly higher in this group, potentially reflecting systemic inflammatory stress. Other liver and renal parameters did not differ significantly between groups.\u003c/p\u003e \u003cp\u003eFor TB reinfection, haemoglobin emerged as the most significant laboratory predictor. Patients with reinfection had markedly lower haemoglobin levels, and categorical analysis confirmed anaemia as a significant risk factor. A non-significant trend was observed toward younger patients having higher reinfection rates, though this did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.185).\u003c/p\u003e \u003cp\u003eA notable finding was the significant inverse association between bacterial infection and TB reinfection \u0026mdash; concurrent presence of both was uncommon, suggesting potentially distinct or competing pathophysiological mechanisms. Bacterial and fungal co-infection showed a similar inverse trend without reaching significance (p\u0026thinsp;=\u0026thinsp;0.092). Gender, age group, smoking status, alcoholism, and diabetes mellitus were not significantly associated with any of the three infectious outcomes, though diabetic patients showed noteworthy trends toward higher fungal infection (20.0% vs 8.8%, p\u0026thinsp;=\u0026thinsp;0.146) and TB reinfection rates (40.0% vs 22.5%, p\u0026thinsp;=\u0026thinsp;0.185).\u003c/p\u003e \u003cp\u003eCorrelation analysis among continuous laboratory variables revealed strong positive correlations between blood urea and serum creatinine (r\u0026thinsp;=\u0026thinsp;0.728, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and between SGOT and SGPT (r\u0026thinsp;=\u0026thinsp;0.589, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), consistent with their shared organ origins. TLC showed significant correlations with ALP (r\u0026thinsp;=\u0026thinsp;0.316), serum creatinine (r\u0026thinsp;=\u0026thinsp;0.307), and SGOT (r\u0026thinsp;=\u0026thinsp;0.228), suggesting multi-organ inflammatory involvement in this cohort.\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study provides a comprehensive evaluation of the composite infectious burden in treated pulmonary TB patients, simultaneously assessing bacterial, fungal, and reinfection outcomes \u0026mdash; an approach that distinguishes it from most prior investigations which have evaluated these complications in isolation [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The bacterial infection prevalence of 36% in our cohort is consistent with a retrospective cross-sectional study from Cambodia by Attia et al. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], which reported bacterial co-infection rates of approximately 28\u0026ndash;38% among TB patients, with gram-negative organisms predominating. However, our rate is notably higher than the 13\u0026ndash;28% range reported in studies on respiratory bacterial superinfection in other chronic lung diseases [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The predominance of Klebsiella pneumoniae (10%) and Pseudomonas aeruginosa (8%) in our study aligns closely with findings from a nanopore sequencing-based case series by Shu et al. (2024) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], which identified Klebsiella and Pseudomonas as the most frequent bacterial co-pathogens in patients with active and recurrent TB, particularly in the presence of cavitary lung disease. The 2024 WHO Bacterial Priority Pathogens List classifies both carbapenem-resistant K. pneumoniae and P. aeruginosa as critical-priority organisms [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], underscoring the clinical significance of their frequent isolation in our structurally damaged post-TB cohort.\u003c/p\u003e \u003cp\u003eTB reinfection was detected by CBNAAT in 26% of cases, a figure that corroborates findings from the 2019\u0026ndash;2021 nationwide community-based TB prevalence survey in India by Selvaraj et al. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], which identified recurrent TB in 27.1% of prevalent cases. Globally, a systematic review by Mithunage and Denning (2024) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] reported a cumulative five-year recurrence rate of 2.9%, though higher rates are well-recognised in high-burden settings such as India where ongoing community transmission facilitates exogenous reinfection. A systematic review and meta-analysis by Vega et al. (2024) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] confirmed that HIV co-infection and multidrug resistance in the index episode are the strongest predictors of reinfection, while host nutritional status, including anaemia, was identified as a contributing factor in several included studies. Our finding that rifampicin resistance was present in 26.9% (7/26) of reinfection cases exceeds the national estimate of 16% among previously treated cases reported in the WHO Global TB Report 2024 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], but is consistent with the high MDR-TB burden described by Husain and Kashyap (2023) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], who highlighted that India accounts for 27% of global MDR/RR-TB cases, with acquired resistance being amplified by antimicrobial misuse and suboptimal treatment adherence. The excellent concordance of 97% between AFB smear and CBNAAT in our study supports the established utility of CBNAAT as a rapid and reliable tool for simultaneous TB detection and rifampicin resistance profiling, consistent with programmatic data from the India TB Report 2024 [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFungal infection was identified in 11% of our cohort, with Candida (6%) slightly outnumbering Aspergillus species (5%). The Aspergillus prevalence is lower than the 14.5% CPA incidence reported by Jha et al. (2024) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] at the end of anti-TB therapy in a prospective AIIMS study, and also lower than the pooled post-treatment CPA prevalence of 13% reported in a recent systematic review by Testa et al. (2025) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. This discrepancy likely reflects the absence of Aspergillus-specific IgG and galactomannan testing in our study, which are considered essential for accurate CPA diagnosis [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Lakhtakia et al. (2022) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] similarly reported a wide spectrum of pulmonary aspergillus diseases in post-TB patients in India, emphasising that culture-based methods alone substantially underestimate the true burden of CPA.\u003c/p\u003e \u003cp\u003eAnaemia emerged as a significant predictor of TB reinfection in our study (p\u0026thinsp;=\u0026thinsp;0.028), a finding supported by a systematic review and meta-analysis by Getachew and Muluye (2021) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], which demonstrated that anaemic individuals have significantly higher odds of developing active TB compared to non-anaemic counterparts. Ara\u0026uacute;jo-Pereira et al. (2024) [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] further demonstrated that coexistent anaemia amplifies systemic inflammation and worsens TB disease severity, potentially facilitating reactivation or reinfection through impaired cell-mediated immunity. The significant association of fever, hemoptysis, and leukocytosis with bacterial infection in our study is clinically intuitive and mirrors findings from multiple studies on community-acquired pneumonia in structurally damaged lungs [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The inverse association between bacterial infection and TB reinfection (p\u0026thinsp;=\u0026thinsp;0.021) is a novel observation not previously reported and may reflect competitive microbial interactions or divergent immunopathological pathways in the post-TB lung milieu, warranting further mechanistic investigation.\u003c/p\u003e \u003cp\u003eIn summary, these findings reinforce the concept that treated pulmonary TB patients require structured, comprehensive post-treatment surveillance programmes incorporating bacteriological, mycological, and molecular evaluations to enable early diagnosis and improve long-term respiratory outcomes.\u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eLIMITATIONS\u003c/h2\u003e \u003cp\u003eThis study has several limitations that merit acknowledgement. Being a single-centre study, the findings may not be generalizable to all populations. The relatively small sample size of 100 patients may have resulted in type II errors, particularly for associations that showed trends without reaching statistical significance. Aspergillus-specific IgG and galactomannan assays were not performed, potentially underestimating the true prevalence of chronic pulmonary aspergillosis. High-resolution computed tomography correlation for structural lung disease classification was not included. Candida isolation from respiratory samples may represent colonization rather than true invasive infection. Additionally, drug sensitivity testing beyond rifampicin was not performed, limiting the full characterization of drug resistance patterns.\u003c/p\u003e \u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eTreated pulmonary tuberculosis patients carry a substantial burden of secondary infectious complications, with bacterial superinfection, TB reinfection, and fungal infection being the principal findings in this cohort. Gram-negative organisms, particularly Klebsiella pneumoniae and Pseudomonas aeruginosa, dominated the bacterial spectrum. The detection of rifampicin resistance in over a quarter of reinfection cases raises concern for multidrug-resistant TB in this population. Fever, hemoptysis, and leukocytosis serve as practical clinical predictors of bacterial superinfection, while anaemia emerged as a significant risk marker for TB reinfection. These findings underscore the necessity of comprehensive microbiological evaluation and structured long-term follow-up programs for all patients completing pulmonary TB treatment, to enable early detection and targeted management of infectious complications.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Ethics Committee of Pt. B. D. Sharma Post Graduate Institute of Medical Sciences (PGIMS), Rohtak, Haryana, India. Written informed consent was obtained from all participants prior to enrolment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNS and SB conceptualized the study, collected data, and drafted the manuscript. RG supervised the study and critically revised the manuscript. AP performed microbiological investigations and interpreted results. AG contributed to data analysis and interpretation. RaG assisted in data collection and literature review. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial registration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWorld Health Organization. Global Tuberculosis Report 2024. Geneva: World Health Organization; 2024. Licence: CC BY-NC-SA 3.0 IGO.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAllwood BW, Byrne A, Meghji J, Rachow A, van der Zalm MM, Schoch OD. Post-tuberculosis lung disease: clinical review of an under-recognised global challenge. Respiration. 2021;100(8):751\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDodd PJ, Yuen CM, Jayasooriya SM, van der Zalm MM, Seddon JA. Quantifying the global number of tuberculosis survivors: a modelling study. Lancet Infect Dis. 2021;21(7):984\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMenzies NA, Quaife M, Allwood BW, Byrne AL, Coussens AK, Harries AD, et al. Lifetime burden of disease due to incident tuberculosis: a global reappraisal including post-tuberculosis sequelae. Lancet Glob Health. 2021;9(12):e1679\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeghji J, Lesosky M, Joekes E, Banda P, Rylance J, Gordon S, et al. Patient outcomes associated with post-tuberculosis lung damage in Malawi: a prospective cohort study. Thorax. 2020;75(3):269\u0026ndash;78.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRavimohan S, Kornfeld H, Weissman D, Bisson GP. Tuberculosis and lung damage: from epidemiology to pathophysiology. Eur Respir Rev. 2018;27(147):170077.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAttia EF, Pho Y, Nhem S, Sok C, By B, Phann D, et al. Tuberculosis and other bacterial co-infection in Cambodia: a single center retrospective cross-sectional study. BMC Pulm Med. 2019;19(1):60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSoundappan K, Muthu V, Sehgal IS, Dhooria S, Prasad KT, Aggarwal AN, et al. Incidence and prevalence of chronic pulmonary aspergillosis in patients with post-tuberculosis lung abnormality: results from a community survey in North India. Mycoses. 2024;67(3):e13711.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDenning DW, Cole DC, Ray A. New estimation of the prevalence of chronic pulmonary aspergillosis (CPA) related to pulmonary TB \u0026mdash; a revised burden for India. IJID Reg. 2023;6:7\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSelvaraj S, Thiruvengadam K, Srinivasan R, Watson B, Thiruvalluvan E, Suresh V, et al. Recurrence of pulmonary tuberculosis in India: findings from the 2019\u0026ndash;2021 nationwide community-based TB prevalence survey. PLoS ONE. 2023;18(12):e0296009.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMithunage CT, Denning DW. Timing of recurrence after treatment of pulmonary TB. IJTLD Open. 2024;1(10):456\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNightingale R, Carlin F, Meghji J, McMullen K, Evans D, van der Zalm MM, et al. Post-TB health and wellbeing. Int J Tuberc Lung Dis. 2023;27(4):248\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShu W, Chen W, Yao L, Li R, Zhang L, Huang H, et al. A case series of co-infection in Mycobacterium tuberculosis and other pathogens: insights from nanopore sequencing. Egypt J Bronchol. 2024;18:19.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization. WHO bacterial priority pathogens list, 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. Geneva: WHO; 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVega V, Cabrera-Sanchez J, Rodr\u0026iacute;guez S, Verdonck K, Seas C, Otero L, et al. Risk factors for pulmonary tuberculosis recurrence, relapse and reinfection: a systematic review and meta-analysis. BMJ Open Respir Res. 2024;11(1):e002281.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHusain AA, Kashyap RS. Double trouble: compounding effects of COVID-19 pandemic and antimicrobial resistance on drug resistant TB epidemiology in India. Front Public Health. 2023;11:1305655.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCentral TB, Division. Ministry of Health and Family Welfare, Government of India. India TB Report 2024. New Delhi: Directorate General of Health Services; 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJha D, Kumar U, Meena VP, Sethi P, Singh A, Nischal N, et al. Chronic pulmonary aspergillosis incidence in newly detected pulmonary tuberculosis cases during follow-up. Mycoses. 2024;67(5):e13747.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTesta C, Menzies NA, Gao L, Denning DW, Bongomin F, Chakrabarti A, et al. Systematic review of chronic pulmonary aspergillosis among patients treated for pulmonary tuberculosis. Clin Infect Dis. 2025;81(4):e163.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLakhtakia L, Spalgais S, Kumar R. Spectrum of pulmonary aspergillus diseases in post TB lung diseases. Indian J Tuberc. 2022;69:523\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGetachew Y, Muluye M. Anemia as a risk factor for tuberculosis: a systematic review and meta-analysis. Environ Health Prev Med. 2021;26:13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAra\u0026uacute;jo-Pereira M, Kumar NP, Gangur C, Queiroz ATL, Rupert A, Babu S, et al. Coexistent anemia modulates systemic inflammation and exacerbates disease severity and adverse treatment outcomes in tuberculosis. Front Tuberc. 2024;2:1462654.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Post-tuberculosis lung disease, bacterial superinfection, pulmonary aspergillosis, TB reinfection, CBNAAT, PTLD","lastPublishedDoi":"10.21203/rs.3.rs-8808297/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8808297/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003ePost-tuberculosis lung disease (PTLD) is an emerging global health concern, yet comprehensive data on the spectrum of infectious complications in treated pulmonary tuberculosis (TB) patients from India remains limited, as most existing studies evaluate bacterial, fungal, or reinfection outcomes in isolation. This study aimed to determine the prevalence of bacterial pathogens, fungal pathogens, and TB reinfection from respiratory samples in treated cases of pulmonary TB, and to identify associated clinical and laboratory predictors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003eThis cohort study enrolled 100 patients who had completed pulmonary TB treatment at least six months prior, attending Pt. B.D. Sharma PGIMS, Rohtak. Respiratory samples were subjected to Gram stain, bacterial culture, acid-fast bacilli (AFB) smear, cartridge-based nucleic acid amplification test (CBNAAT), potassium hydroxide (KOH) mount, and fungal culture. Demographic, clinical, and laboratory parameters were analyzed for associations with infectious outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003eBacterial infection was the most prevalent complication (36%), with Klebsiella pneumoniae (10%) and Pseudomonas aeruginosa (8%) being the commonest isolates. TB reinfection was confirmed in 26%, of which 7% demonstrated rifampicin resistance. Fungal infection was identified in 11%, including Candida (6%) and Aspergillus species (5%). Fever (p\u0026lt;0.001), hemoptysis (p\u0026lt;0.001), and leukocytosis (p=0.026) were significant predictors of bacterial infection. Anaemia was significantly associated with TB reinfection (p=0.028). A significant inverse association was observed between bacterial infection and TB reinfection (p=0.021).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003eTreated pulmonary TB patients harbour a substantial infectious burden. Comprehensive microbiological evaluation and structured post-TB follow-up programs are essential for early detection and management of these complications.\u003c/p\u003e","manuscriptTitle":"Infectious Pulmonary Complications and Reinfection in Treated Cases of Pulmonary Tuberculosis: A Cohort Study from a Tertiary Care Centre in North India","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-17 09:24:14","doi":"10.21203/rs.3.rs-8808297/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-17T07:22:27+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-21T10:30:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"228914863890699186145491998712046117679","date":"2026-02-16T09:56:29+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-14T16:46:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"41195089882274115969770136859355305087","date":"2026-02-14T14:21:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"71171164799866281448852241445219440123","date":"2026-02-11T10:32:14+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-11T09:32:49+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-10T09:01:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-07T14:34:26+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-07T14:30:15+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pulmonary Medicine","date":"2026-02-06T14:22:15+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8c5d56dd-2282-48c2-a05a-fe8ab8b9bf49","owner":[],"postedDate":"February 17th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-07T07:41:32+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-17 09:24:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8808297","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8808297","identity":"rs-8808297","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}