Clinical Characteristics and Impact of Clostridium difficile Infection during Treatment of Rifampicin-Susceptible Pulmonary Tuberculosis
Article information
Abstract
Background
Anti-tuberculosis (TB) treatment, although infrequently associated with Clostridium difficile infection (CDI), necessitates updated research on the incidence and clinical features of CDI among TB patients, especially as the demographic of older TB patients in South Korea is growing.
Methods
A total of 168 patients with rifampin-susceptible pulmonary TB were enrolled in this study. Initial clinical features of the CDI-suspected group, risk factors for CDI, the primary outcome of all-cause mortality, and secondary outcomes, including delayed conversion of acid-fast bacillus (AFB) smear and culture, were analyzed.
Results
The incidence rate of CDI among TB patients was 15.0 cases per 10,000 patient- days. Among initial features associated with TB-related CDI, patients exhibiting diarrhea of Bristol stool scale type 7 for more than 2 days were more likely to receive a CDI diagnosis. Old age and hypoalbuminemia were significant risk factors for CDI occurrence. In the primary outcome analysis, CDI was associated with a 4.63-fold increase in all-cause mortality according to the unadjusted analysis. However, this association dissipated in the adjusted analysis. Older age, underlying respiratory disease, and pneumonia at baseline were strong predictors of all-cause mortality. No significant factors were detected in the analysis of delayed AFB smear and culture conversion.
Conclusion
Despite the lack of an independent association between CDI and all-cause mortality among TB patients, monitoring older adults with undernutrition and persistent diarrhea for CDI is crucial.
Introduction
Clostridium difficile infection (CDI) is one of the most common hospital-acquired infections that can lead to prolonged hospital stays and poorer outcomes. CDI can be caused by various factors including the use of antibiotics, bowel operations, or intensive care for critical conditions, and it is typically characterized by loose stool or diarrhea [1]. It is generally treated with oral vancomycin for at least 10 days, although cases involving septic conditions, fulminant colitis, and severe forms of ileus with toxic megacolon require longer treatment durations and the addition of intravenous metronidazole [2,3]. Particularly in immunocompromised patients or those surgically treated for inflammatory bowel diseases or cancer, early clinical diagnosis and prompt initiation of empirical treatment for CDI are crucial due to the high risk of developing life-threatening complications [4].
Anti-tuberculosis (TB) treatment is recognized as a rare cause of CDI. There have been only a few documented cases of rifampicin-associated pseudomembranous colitis, and limited research has been conducted concerning the clinical characteristics of CDI following anti-TB treatment, attributable to its low incidence [5-8]. In South Korea, the most recent reported incidence of CDI among TB patients was 2.83 cases per 1,000 TB patients from 2008 to 2013, with no further data available subsequently [8]. According to the latest report on TB, based on the national TB survey in South Korea, the proportion of TB patients aged 65 years or older increased to 51.3% in 2021, even as the total number of TB patients declined [9]. New research on CDI in older TB patients is critically needed to assess the current incidence and develop management protocols to enhance clinical outcomes for these at-risk patients, given that CDI is predominantly a geriatric disease linked with antibiotic use and extensive healthcare engagement [10-12].
The aim of this study is to elucidate the clinical characteristics of TB patients with CDI. Initially, we examined the initial symptoms and signs in patients suspected of having CDI to gauge the diverse clinical manifestations of TB-associated CDI, beyond merely diarrhea. Subsequently, we analyzed the risk factors associated with the development of CDI during TB treatment. Finally, we investigated the impact of CDI on two clinical outcomes: all-cause mortality and delayed conversion of acid-fast bacillus (AFB) smear and culture.
Materials and Methods
1. Patient groups
Between April 2022 and April 2023, 185 patients diagnosed with rifampin-susceptible pulmonary TB through microbiological tests, including gene amplification techniques or both molecular and phenotypic drug susceptibility tests, were admitted to Masan National Tuberculosis Hospital (MNTH) in Changwon, South Korea. None of these patients had been diagnosed with CDI at the time of admission. Considering that the average duration from antibiotic exposure to CDI onset is approximately 13 days, 168 patients who stayed more than 2 weeks were ultimately enrolled in our study (Figure 1) [13]. These patients received standard treatment with first-line drugs, including isoniazid (INH) (300 to 400 mg once daily), rifampin (600 to 750 mg once daily), ethambutol (1,000 to 1,400 mg once daily), and pyrazinamide (1,250 to 1,750 mg once daily). Where rifampin administration was contraindicated due to adverse drug reactions, rifabutin (300 mg once daily) was used as an alternative. Drug doses were determined based on the patient’s body weight and therapeutic drug monitoring (TDM) results. Those displaying adverse drug reactions or having contraindications to standard therapy received additional treatment with quinolones and cycloserine. Newly diagnosed patients underwent a 6-month treatment regimen, while those with extensive lesions, as assessed by attending physicians, and those diagnosed with relapsed TB received treatment for 9 months. Patients with both relapsed TB and extensive lesions were treated for 12 months.
Patient selection flow. TB: tuberculosis; AFB: acid-fast bacillus.
2. Definition
In our study, we employed the classification of diagnosis based on the history of previous TB treatment as described by the World Health Organization (WHO) in 2013 [14]. ‘New patients’ were defined as those never treated for TB or who have taken anti-TB drugs for less than 1 month. ‘Relapsed TB’ was considered as those with a recurrent episode of TB after being declared ‘cured’ or ‘treatment completed’ at the end of their most recent TB treatment. Patients who were lost during follow-up or who experienced treatment failure during their latest TB treatment were defined as ‘lost to follow-up’ and ‘treatment failure,’ respectively. Patients with a history of TB treatment whose outcome after their most recent course was unknown or undocumented were classified as ‘others.’
The definition of treatment outcomes introduced by WHO in 2021 was utilized in describing treatment outcomes [15]. Treatment success was defined as the sum of ‘cured’ and ‘treatment completed’ categories. Patients who died were classified as those who expired during TB treatment. Those who discontinued TB treatment due to adverse drug reactions were categorized as ‘lost to follow-up’ group. Patients transferred out for other medical reasons or whose outcomes were not reported in any hospital were categorized as ‘not evaluated.’
3. Diagnosis and management of CDI patients
All attending physicians for each patient at our center systematically monitored stool patterns from the initiation of TB treatment. Diarrhea was defined as stool corresponding to Bristol stool scale type 7, and loose stools were defined as those corresponding to Bristol stool scale types 5 and 6 [16,17]. The VIDAS C. difficile Toxin A & B Assay (bioMérieux, Marcy-l'Étoile, France) was conducted in the patients clinically suspected of CDI with stool patterns characterized by Bristol stool scale types 5 to 7. The onset of CDI was recognized at the time when the toxin assay was performed. Isolation was promptly enforced for confirmed cases. TB treatment continued unchanged, regardless of CDI occurrence. An initial episode of CDI was treated with four daily doses of oral vancomycin 125 mg for 10 to 14 days. For recurrent episodes, treatment included tapered and pulsed dosing of vancomycin, beginning with four daily doses for the first 2 weeks, followed by bi-daily doses for the next week, daily doses for the subsequent week, doses every other day for the next week, and doses every 3 days during the final week.
4. Data collection
Baseline characteristics of the enrolled patients were examined, including age, sex, body mass index (BMI) at the baseline visit, history of smoking and alcohol use, underlying diseases, the classification of diagnosis when initiating TB treatment, presence of miliary TB, TB pleurisy, extrapulmonary TB, or paradoxical responses, length of hospital stay, follow-up periods, types of anti-TB drugs, and treatment outcomes. The number of patients with INH-resistant TB was separately calculated. The length of hospital stay was defined as the duration from admission to discharge, and the follow-up period was defined as the interval from the initiation of TB treatment to the date of the last clinical visit, whether at discharge or during an outpatient visit. Additionally, other characteristics such as the use of other antibiotics for any combined infections during TB treatment and the presence of combined bacterial pneumonia at the baseline visit were also documented.
We specifically targeted patients suspected of CDI, surveying the detailed abdominal symptoms and signs they initially reported. Patients were asked five types of questions about whether they experienced only diarrhea, only nausea and vomiting, only abdominal pain, nausea with loose stool, or only fever. All these symptoms and signs were considered present if they persisted for at least 48 hours, regardless of frequency, due to inaccuracy in assessing the changes in bowel habits. Fever was defined as a tympanic temperature over 37.5°C. Several dichotomous variables were established for the analyses of risk factors and clinical outcomes. The old-aged group was defined as patients aged over 70.
BMI under 16 kg/m2, hypoalbuminemia, and vitamin D deficiency were assessed at the baseline visit and included as nutritional factors indicating undernutrition. Body weight loss over 5% of usual body weight (UBW) was evaluated 1 month after admission and also considered a marker of undernutrition [18,19]. Hypoalbuminemia was defined as a serum albumin level less than 2.5 g/dL, and similarly, vitamin D deficiency was defined as less than 10.0 ng/mL [20-22].
5. Clinical outcomes
The primary outcome was all-cause mortality during TB treatment, analyzed in all enrolled patients. The secondary outcomes included delayed conversion of AFB smear and AFB culture, defined as taking more than 8 weeks (56 days). Sputum assays were performed biweekly following admission. Successful conversion was regarded as consistent culture or smear negativity following the initial conversion until the end of follow-up or TB treatment. Negative conversion of AFB culture was defined as the initial simultaneous negative conversion of both solid and liquid media.
6. Subgroup analyses
Three types of subgroup analyses were conducted. Subgroup A’s analysis involved 86 patients suspected of CDI undergoing C. difficile toxin assay to identify initially manifested clinical features of CDI among TB patients. Subgroup B’s analysis was on 114 AFB culture positive patients, and subgroup C’s on 100 AFB smear positive patients, to examine predictive factors for delayed conversion. Smear and culture positivity were initially evaluated at treatment initiation; culture positivity was defined as a positive result in either liquid or solid culture.
7. Statistical analysis
Descriptive data for baseline characteristics were calculated for all variables. Data normality was assessed by visually inspecting the distribution. Categorical variables were presented as numbers and proportion with analysis using either a chi-square test or Fisher’s exact test. Continuous data were reported as mean±standard deviation, depending on the data distribution, and were assessed using an independent t-test. Variance equality was evaluated with Levene’s test.
A chi-square test or Fisher’s exact test was performed for subgroup A analysis. Logistic regression analysis was used to evaluate risk factors for CDI occurrence across the entire patient cohort, estimating odds ratio (OR) and 95% confidence interval (CI) using both univariable and multivariable effects.
The analysis of the primary outcome was conducted using the Fine-Gray model, where CDI occurrence was treated as a time-varying covariate. Cumulative incidence functions were presented to illustrate the impact of CDI on all-cause mortality, as determined through Fine-Gray model analysis. Subgroup analyses B and C utilized the time dependent Cox-regression analysis, with CDI occurrence as a time-varying covariate, aligning with the primary outcome analysis. Hazard ratio (HR) and corresponding 95% CI were assessed using both the univariable and multivariable effects, and multivariable analyses were performed solely with factors that showed statistical significance in the univariable analysis.
All analyses were conducted utilizing R Studio 2024.04.0 (R Foundation for Statistical Computing, Vienna, Austria) and SAS version 9.4 (SAS Institute Inc., Cary, NC, USA). Statistical significance was assessed based on a p-value less than 0.05. The Institutional Review Board of MNTH (IRB-398837-2023-E03) approved this study. Written informed consent was obtained from each patient and guardian for the use of their data in statistical analyses, with no refusals reported.
Results
1. Baseline characteristics
The baseline characteristics of the 168 patients finally enrolled, categorized into CDI and non-CDI groups, are presented in Table 1. Likewise, the administered anti-TB drugs and treatment outcomes are outlined in Table 2. The mean age was 74.4±14.1 in the CDI group and 67.9±17.1 in the non-CDI group, highlighting a significant age difference between the groups (p=0.023). Comparisons of BMI, stratified at 16.0, 18.5, and 23.0 kg/m2, showed no significant differences between the two groups (p=0.757). There were no significant differences observed for any anti-TB drugs, including quinolones, or other antimicrobial agents such as intravenous piperacillin/tazobactam, vancomycin, and meropenem.
Baseline characteristics
Antituberculosis drugs and treatment outcomes
In the CDI group, 52.2% of patients were successfully treated and 30.4% were classified as ‘not evaluated.’ Among the six deaths, five were due to worsening pneumonia and one was due to septic shock associated with CDI-related acute respiratory distress syndrome (ARDS). In the non-CDI group, 73.0% were successfully treated and 23.0% were classified as ‘not evaluated.’ Among the four deaths, three were due to worsening pneumonia and one was due to coronavirus disease 2019 (COVID-19) pneumonia. No deaths were attributed to pulmonary TB. A total of three patients discontinued TB treatment due to adverse reactions such as anorexia and cognitive impairment. There were no observed treatment failures in either group.
2. Incidence of CDI among TB patients
The cumulative incidence of CDI among TB patients was 46 (27.3%) out of 168 patients, with an incidence rate of 15.0 cases per 10,000 patient-days. The median time from the initiation of TB treatment to the occurrence of CDI was 57 days (interquartile range, 32.0 to 98.3). Twelve patients (26.0%) were identified as having recurrent CDI. Among them, one patient experienced a second recurrence, totaling two recurrences for that individual. There were no cases of fulminant colitis, and all CDI patients, except for one who died from CDI-related ARDS, were successfully treated according to the treatment protocol.
3. Clinical features of the patients screened for CDI
Among the 86 patients screened, 46 (53.4%) were diagnosed with CDI (toxin-positive group). In the toxin-positive group, the most common initial symptom was diarrhea only, reported in 69.6% of patients, which was more frequent than in the toxin-negative group. Nausea with loose stool and nausea and vomiting only were observed in 19.6% and 6.5% each. Isolated abdominal pain was reported only in this group, with a proportion of 4.3%. In the toxin-negative group, 42.5% of patients reported diarrhea only. Nausea with loose stool was observed in 20.0%, while 25.0% experienced nausea and vomiting only. Isolated fever was only reported in this group, with a proportion of 12.5%. The overall symptom distribution between the two groups was statistically significant (p=0.005), as shown in Table 3.
Subgroup A analysis: initial clinical manifestation of the CDI-suspected group undergoing Clostridium difficile toxin assay
4. Risk factors for CDI occurrence
Risk factors for CDI occurrence are outlined in Table 4. In the univariable analysis, being over the age of 70 was identified as a significant factor, with an OR of 2.21 (95% CI, 1.08 to 4.49; p=0.029). Nutritional factors such as a BMI under 16 kg/m2 and hypoalbuminemia also emerged as significant, demonstrating ORs of 2.23 (95% CI, 1.01 to 4.92; p=0.046) and 8.35 (95% CI, 2.11 to 33.07; p=0.002) respectively. Weight loss exceeding 5% of UBW a month after admission, vitamin D deficiency, underlying renal diseases, and the administration of quinolones including levofloxacin and moxifloxacin, as well as other antibiotics, were not significant. In the multivariable analysis, age over 70 and hypoalbuminemia were noted as significant factors, with ORs of 2.94 (95% CI, 1.27 to 6.78; p=0.011) and 8.35 (95% CI, 1.90 to 36.60; p=0.004), respectively.
Risk factors for CDI occurrence
5. The primary outcome (all-cause mortality)
The results of the analyses on the primary outcome are presented in Table 5 and Figure 2. In the unadjusted analysis, CDI emerged as a predictive factor with a HR of 4.63 (95% CI, 1.33 to 16.08; p=0.020). The age group over 70 also proved significant, exhibiting an HR of 8.37 (95% CI, 1.13 to 64.81; p=0.042). The presence of underlying respiratory diseases such as asthma, chronic obstructive pulmonary disease, or interstitial lung disease, as well as TB pleurisy and combined pneumonia at baseline, demonstrated HRs of 4.84 (95% CI, 1.25 to 18.71; p=0.022), 4.12 (95% CI, 1.16 to 14.60; p=0.028), and 4.63 (95% CI, 1.33 to 16.08; p=0.016), respectively. Nutritional factors such as a BMI under 16 kg/m2, hypoalbuminemia, and vitamin D deficiency were not identified as predictive factors. In the adjusted analysis, CDI did not emerge as significant, while old age, underlying respiratory diseases, and combined pneumonia exhibited HRs of 10.43 (95% CI, 2.05 to 53.21; p=0.001), 4.33 (95% CI, 1.11 to 16.89; p=0.038), and 3.57 (95% CI, 1.00 to 12.73; p=0.053), respectively.
Predictive factors for the primary outcome (all-cause mortality) suggested by the Fine-Gray model
Cumulative incidence function based on the influence of Clostridium difficile infection (CDI) on the all-cause mortality.
6. The secondary outcomes (delayed conversion of AFB smear and culture)
The results of the analyses on the secondary outcomes are detailed in Table 6. All factors evaluated using unadjusted time dependent Cox-regression analysis, including CDI, were determined to be non-significant; these factors include the older age group, undernutrition, underlying respiratory diseases, TB pleurisy, or combined pneumonia at the baseline visit, and paradoxical response.
Subgroup B and C analyses: predictive factors for the secondary outcome (delayed conversion of AFB smear and AFB culture) suggested by the unadjusted time dependent Cox-regression analysis
Discussion
Several key findings from our study indicated that, among TB patients with CDI, diarrhea was the predominant symptom compared to other gastrointestinal manifestations. Additionally, the risk of CDI occurrence was higher in individuals with advanced age and undernutrition. Furthermore, while our adjusted analysis did not prove it definitively, CDI appeared to influence all-cause mortality. Other notable findings included a higher incidence of CDI and a later onset of CDI compared to cases following the use of other types of antibiotics. While the global incidence of CDI has been reported to range from five to eight cases per 10,000 patient-days, our study observed an incidence of 15 cases per 10,000 patient-days [23,24]. This increased incidence is likely due to the advanced age of our study population and the incomplete isolation measures despite the efforts of healthcare staff to ensure proper infection control. Our findings indicate that CDI typically occurred at least 1 month after the initiation of TB treatment, with an average onset around 2 months. In contrast, cephalosporins, a key group of antibiotics known to induce CDI, have been reported to cause CDI within a median time of 8 days [13,25].
Our study highlights several unique aspects compared to previous research. First, all analyses were carried out exclusively on inpatients diagnosed with rifampin-susceptible pulmonary TB, who were closely monitored throughout the follow-up periods. Second, due to the characteristics of MNTH, where patients were transferred from local hospitals nationwide at the initial phase of TB treatment and later transferred back to those centers for outpatient care, the formation of a sizable ‘not evaluated’ group was inevitable. This group accounted for 25% of the total enrolled patients. We aimed to address the potential bias associated with our specific population and applied the Fine-Gray model to mitigate the competing risk posed by the ‘not evaluated’ group in the primary outcome analysis. Third, CDI was considered a time-varying covariate in the analysis of clinical outcomes. Fourth, our study reflected the demographic trends in South Korea, particularly the increasing number of elderly individuals, within the patient population with an average age of 69.7.
Several studies have emphasized the importance of monitoring for symptoms and signs other than diarrhea prior to diagnosing CDI. Chung et al. [26] argued that CDI should be considered in the differential diagnosis when treating hospitalized patients with unexplained abdominal discomfort and leukocytosis due to the risk of progression to fulminant colitis or ileus. Jaber et al. [27] suggested that the severity of CDI should be gauged not only by diarrhea but by other clinical features such as hemodynamic status and laboratory parameters. Our subgroup A analysis focused on detailed categorization of initial clinical characteristics, leveraging our clinical experience with TB treatment. Our results showed that stool corresponding to Bristol stool scale type 7 is the dominant symptom in TB patients with CDI, and patients with nausea and loose stools defined as those corresponding to Bristol stool scale type 5 or 6 can be reassured of a physiological bowel habit change commonly observed during TB treatment. Patients with high fever, lacking colitis-associated symptoms, should initially be considered for other types of infections such as pneumonia or urinary tract infections, especially in older patients.
The most recently identified risk factors for CDI occurrence, suggested by Japanese and European researchers in 2021, include the use of medications such as antibiotics, proton pump inhibitors, histamine H2-receptor blockers, nonsteroidal anti-inflammatory drugs, previous hospital admissions or bowel surgery, comorbid conditions like inflammatory bowel disease, cardiac disease, chronic kidney disease, advanced age, and nasogastric tube feeding [1,2]. Due to its low overall incidence, studies of TB-related CDI have been limited. Legenza et al. [5] suggested that TB is highly associated with CDI in South Africa compared to high-resource countries. Additionally, Lee et al. [8] argued that rifampin is the causative agent of CDI, noting the absence of recurrence after discontinuation or substitution of anti-TB drugs excluding rifampin. This suggests that rifampin may have played a key role in triggering CDI, as no recurrence was observed when other anti-TB drugs were discontinued or reintroduced in the absence of rifampin.
Unlike previous studies that only explored the relationship between TB and CDI, our focus was to assess the impacts of advanced age, undernutrition, and severity of TB on CDI development. In unadjusted analyses, advanced age, a BMI below 16 kg/m2 and severe albumin deficiency at baseline were identified as significant influences on CDI occurrence, although BMI did not show a relationship with CDI in adjusted analyses. The use of quinolones for TB treatment and other types of antibiotics, previously reported as strong triggers for CDI, was not found to be significant among TB patients [28,29]. Based on these findings, it is highly recommended that clinicians prioritize developing appropriate nutritional plans for malnourished elderly patients with TB. However, the administration of albumin should be approached with caution due to the lack of evidence regarding its impact on infection-associated outcomes, despite the increased risk of CDI occurrence associated with hypoalbuminemia [30-32]. Though the small sample size contributed to wide CIs, posing a statistical limitation, the analysis of the primary outcome (all-cause mortality) in our study revealed a novel finding that has not been previously reported. In the unadjusted analysis, TB patients with CDI exhibited a 4.63-fold increase in mortality; however, adjustments for confounding variables showed no significant influence of CDI on all-cause mortality.
The impact of CDI might be underestimated, as advanced age is already a significant factor in both the occurrence of CDI and in all-cause mortality. Contrary to previous studies, undernutrition and the severity of TB were not associated with increased mortality. Singla et al. [33] asserted that severe malnutrition and advanced disease evident in chest radiography were significantly independent predictors of early mortality in TB patients in the emergency department. According to a systematic review by Nicholson et al. [34], lower body weight at the time of TB diagnosis was identified as a principal risk factor for mortality associated with TB. To enhance the survival rate among older adults, rigorous monitoring for CDI as well as treatment for other respiratory conditions or infections is crucial, and clinicians should prioritize initial nutritional support.
Previous studies have noted that certain predictive factors are associated with our secondary outcome, delayed sputum conversion. Velayutham et al. [35] found that a BMI under 18 kg/m2 correlates with poor sputum conversion in multidrug resistant TB. Similarly, Wagnew et al. [36] documented the relationship between undernutrition and unsuccessful treatment outcomes in their systematic review. Nakamura et al. [37] posited that the presence of lung cavities in patients is likely to prolong the time needed for successful sputum conversion. However, our study discovered that factors including advanced age, undernutrition, and CDI did not significantly impact the negative conversion of AFB smear and culture extending beyond 8 weeks. These results indicate that initial conditions and complications related to treatment have a less critical relationship with delayed sputum conversion. Instead, appropriate administration of anti-TB drugs based on drug susceptibility tests, TDM, and directly observed therapy are crucial for achieving successful sputum conversion.
This study faced several limitations. Firstly, selection bias may have arisen, as about 15% of the patients who were transferred from long-term care facilities consisted of up to half being asymptomatically colonized with C. difficile [38]. Secondly, inadequate isolation protocols for CDI patients could have led to an overestimation of CDI incidences, affecting the timing of CDI occurrences. Thirdly, the study did not identify which anti-TB drugs facilitate CDI development nor describe the pharmacological mechanisms by which these drugs may delay the onset of CDI in comparison to other antibiotics. Fourthly, failure to account for the timing of other antimicrobial use, such as meropenem, compromised the statistical reliability of the CDI risk factor analysis. Lastly, biweekly sputum assays may not be adequate for employing survival analysis in secondary outcome assessments. Data derived from more frequent sputum collections are essential for obtaining statistically significant results in future studies.
In this retrospective study, we analyzed the clinical characteristics of CDI among TB patients within an older adult population. TB patients presenting with diarrhea classified as Bristol Stool type 5 or higher should be screened for CDI, particularly those with type 7 stools, who require rigorous monitoring for CDI. Reassurance and conservative treatment are crucial for patients exhibiting other abdominal signs and symptoms. Notably, older age, low BMI, and severe hypoalbuminemia at baseline were significant risk factors for CDI. Though displaying a 4.63-fold increase in mortality in the unadjusted analysis, CDI was not independently associated with all-cause mortality among TB patients. Old age and combined respiratory conditions were identified as independent significant factors in the adjusted analysis. No factors significantly predicted the delayed conversion of AFB smear and culture. Further research involving a larger population of older adults is imperative to better understand the outcomes related to CDI in pulmonary TB patients.
Notes
Authors’ Contributions
Conceptualization: Ha SW. Methodology: all authors. Formal analysis: Ha SW. Data curation: all authors. Software: Ha SW. Validation: all authors. Investigation: all authors. Writing - original draft preparation: Ha SW. Writing - review and editing: all authors. Approval of final manuscript: all authors.
Conflicts of Interest
No potential conflict of interest relevant to this article was reported.
Funding
No funding to declare.