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Predictors of early and interim culture un-conversion in multidrug-resistant/rifampicin-resistant tuberculosis: a retrospective multi-center cohort study in China

Antimicrobial Resistance & Infection Control volume 13, Article number: 126 (2024) Cite this article

Abstract

Background

We aimed to evaluate the predictors for early and interim culture conversion within 2 months and 6 months of treatment in multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) patients in China.

Methods

This study included adult MDR/RR-TB patients with a positive baseline sputum culture from 8 institutions located in different cities in China from May 2018 to January 2022. We mainly used logistic regression model to derive possible predictors of early and interim culture conversion.

Results

A total of 813 patients were enrolled and 28.5% of them received multidrug-resistant treatment regimens containing bedaquiline. Of these, 362 (44.5%) patients experienced culture conversion within 2 months of treatment, and 649 (79.8%) within 6 months. The results of the multivariable logistic regression analysis revealed that acid-fast bacilli smear positive (adjusted odds ratio [aOR] = 1.637, 95% confidence interval [CI] = 1.197–2.238), cavities (aOR = 1.539, 95% CI = 1.132–2.092), bilateral disease (aOR = 1.638, 95% CI = 1.183–2.269), and viral hepatitis (aOR = 2.585, 95% CI = 1.189–5.622) were identified as risk factors for early culture un-conversion within 2 months of treatment. Additionally, smoking history (aOR = 2.197, 95% CI = 1.475–3.273), previous treatment for tuberculosis (aOR = 1.909, 95% CI = 1.282–2.844), bilateral disease (aOR = 2.201, 95% CI = 1.369–3.537), viral hepatitis (aOR = 2.329, 95% CI = 1.094–4.962) were identified as risk factors for interim culture un-conversion within 6 months of treatment, while patients with regimen containing bedaquiline (aOR = 0.310, 95% CI = 0.191–0.502) was a protective factor.

Conclusions

A history of smoking, a baseline sputum AFB smear positive, lung cavities, bilateral disease, previous anti-tuberculosis treatment, or a comorbidity of viral hepatitis can be used as the predictors for early and interim culture un-conversion in MDR/RR-TB patients, while bedaquiline was a protective factor .

Introduction

In 2022, tuberculosis (TB) was the world’s second leading cause of death from a single infectious agent, after coronavirus disease (COVID-19). In 2022, there were approximately 10.6 million cases developed TB worldwide, leading to an estimated 1.3 million deaths [1]. Globally, about 410 thousand individuals were diagnosed with multidrug-resistant/ rifampin-resistant tuberculosis (MDR/RR-TB) [1]. The treatment success rate for MDR/RR-TB cases was only 63% [1]. China specifically accounted for 7.1% of the global TB burden with 12.4 thousand confirmed cases of MDR/RR-TB and a treatment success rate of 51% [1]. MDR/RR-TB continues to be a significant public health concern in China. Notably, due to the impact of COVID-19, China was among the ten countries responsible for approximately 70% of the global gap between the estimated number of MDR/RR-TB cases and the number of individuals receiving treatment in 2022 [1]. Therefore, MDR/RR-TB remains a catastrophic issue for patients, society, and the health system, particularly in high TB burden countries like China. It is crucial to increase treatment success rate for MDR/RR-TB in order to optimize TB prevention and control in China.

Previous studies showed that achieving culture conversion within the initial 2 or 6 months of treatment were associated with treatment success in MDR-TB patients [2,3,4,5,6,7], and the overall association was substantially greater at 6 months [2, 7]. Despite the importance of sputum culture conversion in the management of MDR/RR-TB, no sufficient studies of MDR/RR-TB have reported on predictors of early and interim sputum culture un-conversion in China.

Several studies have investigated possible independent risk factors associated with culture conversion or treatment outcomes. However, there is limited research on predictors of early and interim culture conversion in MDR-TB patients. In a multicountry study, it was found that MDR/RR-TB patients with HIV, cavitary disease, and highly positive sputum smear had a lower probability of conversion within 6 months of treatment [8]. Male, cavitary disease, uncontrolled diabetes mellitus (DM), resistance to ofloxacin were found to be significant risk factors for 2-month sputum culture un-conversion [9,10,11,12] (Only 3.8 ~ 5.9% [10,11,12] of the patients were MDR-TB). The majority of studies have focused on identifying risk factors that influence the conversion time or rates of the entire treatment, as well as poor outcomes in patients with MDR-TB. Previous TB treatment, a baseline positive smear, bilateral disease, cavitation, resistance to ofloxacin or fluoroquinolones (FQs), XDR-TB, low body mass index (BMI), smoking, alcoholism or alcohol use, and surgical resection, were found to be associated with a longer sputum culture conversion time, lower conversion rate, or poor treatment outcome in patients with MDR/RR/XDR-TB [3, 7, 13,14,15,16,17,18,19,20,21]. On the contrary, a treatment regimen containing bedaquiline (BDQ) could achieve early culture conversion [22] or increase conversion rate [23,24,25], and a systematic review suggested that the BDQ-containing regimen reduced the rate of culture-positive compared to the no-BDQ-containing regimens [26]. These risk factors could also potentially influence early and interim culture conversion in MDR/RR-TB patients.

The ability to achieve culture conversion in a short term is crucial for reducing transmission of MDR/RR-TB and increasing treatment success. It is also beneficial to explore the factors that are effective in shortening the treatment duration of MDR/RR-TB patients. Therefore, the objective of this study was to evaluate the predictors linked to early and interim culture un-conversion among multicenters of MDR/RR-TB patients in China.

Methods

Study design and participants

This study was a multi-center retrospective cohort study. The participants for this study were recruited from 8 institutions located in different cities in China, namely Chengdu, Beijing, Wuhan, Suzhou, Anqing, Nanning, Chongqing and Harbin. The study included adults (≥ 18 years old) who were diagnosed with multidrug-resistant/rifampicin-resistant/pre-extensively-drug resistant tuberculosis (MDR/RR/pre-XDR-TB) based on the guidelines of the World Health Organization (WHO) and China [27, 28]. The patients enrolled received the initial treatment regimen for MDR/RR/pre-XDR-TB between May 2018 and January 2022. Patients with a negative baseline sputum culture and unknown culture status were excluded from the study.

Ethical approval and consent to participate

This was an observational analysis of de-identified medical records. Individual informed consent was not obtained. Given that the medical information of inpatients was recorded anonymously by case history and would not bring any risk to the participants, the ethics committee of the Chengdu Public Health Clinical Center approved this study (YJ-K2022-81-01). The anonymity and confidentiality of the participants were guaranteed.

Early and interim culture conversion outcome

The main outcome of this study was sputum culture conversion within the initial 6 months of treatment, which was a commonly used interim endpoint in studies investigating MDR-TB treatment [22, 29,30,31]. It was also closely related to the final treatment outcomes [2, 7]. We also observed the secondary outcome of sputum culture conversion within the first 2 months of treatment, which was important for early prevention and control measures of tuberculosis, and it was also correlated with final treatment outcomes [2,3,4,5,6,7].

Definitions of culture conversion

Culture conversion was defined as two or more consecutive negative cultures at least 30 days apart in a patient with a positive initial culture.

Definition of drug resistance

According to WHO [27], MDR/RR-TB referred to multidrug-resistant tuberculosis (resistant to both rifampicin and isoniazid) or rifampicin-resistant tuberculosis. Pre-XDR-TB referred to tuberculosis resistant to rifampicin (and possibly isoniazid) and at least one fluoroquinolone. Resistance categories were determined based on the results of drug susceptibility testing, using either molecular or genotypic techniques to identify mutations that confer resistance, or using phenotypic methods to assess susceptibility to anti-tuberculosis drugs.

Data collection

Epidemiological and clinical data, laboratory tests, baseline anti-tuberculosis treatment regimens, adverse effects, and sputum culture conversion status (culture conversion was described in the Definitions of culture conversion) at 2, 6, and 24 months of treatment, were collected from the medical records of eight institutions. Two physicians, QC and XZT, reviewed all the data, and any discrepancies in interpretation between the two primary reviewers were assessed by a third researcher, LPZ.

Laboratory examination

Baseline HIV infection, diabetes mellitus (DM), viral hepatitis (including hepatitis B and C), and anemia (defined as hemoglobin levels below 130 g/L in adult males and 120 g/L in adult females) were assessed through laboratory testing. Sputa samples were collected and analyzed for GeneXpert MTB/rifampin (RIF) (Xpert) as well as examined under smear microscopy for AFB. The BACTEC MGIT960 system (Becton Dickinson & Co., Franklin Lakes, NJ, USA) was used for MTB culture. All patients enrolled were tested for drug susceptibility. Molecular (Xpert) or genotypic techniques (targeted next-generation sequencing) were used to identify mutations with drug resistance, or phenotypic methods were used to assess susceptibility to anti-tuberculosis drugs.

Anti-tuberculosis treatment

The anti-tuberculosis treatment regimens in this study were primarily individualized and managed by qualified physicians, in accordance with the guidelines of WHO [32,33,34] and China [28]. The treatment regimens were classified into two categories for this study: regimen containing BDQ and regimen without BDQ. Patients who received anti-tuberculosis regimen containing BDQ in this study were administered 400 mg of BDQ once daily for the initial 2 weeks, followed by 200 mg three times a week for the subsequent 22 weeks. The duration of BDQ use should be at least 24 weeks.

Statistical analysis

Normally distributed continuous variables were expressed as mean ± standard deviation, and other variables were expressed as medians (Q1, Q3). Categorical variables were expressed as n (%). Predictors of early and interim culture conversion were selected based on the baseline epidemiological data, clinical characteristics, laboratory testing, and treatment regimen. We compared characteristics using Chi-square test, T/T’ test and Mann-Whitney U test. An initial univariate logistic regression was performed. Multivariable logistic regression was performed by including variables that were significant at P<0.05 in univariable logistic regression. Each multivariate model included relevant variables from the univariable logistic regressions pertaining to culture un-conversion within 2 months and 6 months of treatment in MDR/RR-TB patients. Collinearity analysis estimated the correlation between predictor variables.

In the secondary analyses, patients were categorized into subgroups based on gender, age, BMI, smoking, alcohol use, treatment history for TB, comorbidity of DM, anemia, viral hepatitis, sputum smear, the presence of cavities on chest radiograph, pulmonary lesion area (bilateral or unilateral), drug-resistant pattern, and baseline treatment regimen (regimen with or without BDQ). The Kaplan-Meier curve was used to represent the time of culture conversion within 24 months for each subgroup. Differences in each subgroup was analyzed using the log-rank test.

Statistically significant results were considered for two-sided p values less than 0.05. All statistical analyzes were performed using SPSS version 24.0 (SPSS Inc, Chicago, IL, USA).

Results

Overview

A total of 1416 patients with RR/MDR/Pre-XDR-TB were screened and 813 patients were enrolled in this study (Fig. 1). The 813 included patients were treated at 8 different institutions in various regions of China: the East (Suzhou and Anqing: 106 patients, 13.0%), West (Chengdu and Chongqing: 332 patients, 40.8%), South (Nanning: 33 patients, 4.1%), North (Beijing and Harbin: 144 patients, 17.7%), and Central region (Wuhan: 198 patients, 24.4%). The 813 patients received individual multidrug regimens including BDQ-containing regimens (28.5%) and regimens without BDQ(71.5%). Among the patients, 455 (55.9%) had MDR-TB, 125 (15.3%) had RR-TB, and 233 (28.7%) had Pre-XDR TB. The median age of the patients was 37.00 (27.00, 52.00) years, with 67.5% of them being male. The median BMI was 20.31 (18.17, 22.28) kg/m2, and 28.4% of the patients were underweight. Only one patient had acquired immune deficiency syndrome (AIDS) with a normal CD4+ T cell count. The most common comorbidity was anemia (29.2%), followed by DM (15.1%). Approximately 33.5% of the patients had history of alcohol use, and 21.3% had a history of smoking. More than half of the patients (59.7%) had been previously treated for TB. Out of the total patients, 524 (64.5%) had a positive AFB of sputum smears. Chest images showed that 514 patients (63.2%) had cavities and 589 patients (71.0%) had bilateral disease. The most common clinical symptoms reported were cough (86.7%) and sputum (76.8%) (Table 1). Besides, only three patients received surgical therapy before 6 months of treatment.

Fig. 1
figure 1

Overview of the analysis cohort

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Table 1 Predictors for early and interim sputum culture conversion in MDR/RR-TB patients
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Early and interim sputum culture conversion

Among the 813 patients, 362 patients (44.5%) achieved sputum culture conversion within 2 months of treatment, while 649 patients (79.8%) achieved conversion within 6 months. Median time to culture conversion among those who converted within 6 months was 2.00 (1.50, 3.00) month. In the group of patients who had a positive sputum culture within 2 months of treatment, we observed significantly higher proportions of certain factors compared to the culture conversion group. These factors included BMI<18.5 kg/m2, smoking, alcohol use, previous treatment for TB, AFB smear positive, presence of cavities, bilateral disease, anemia, viral hepatitis, cough, sputum, night sweat, weight loss, chest pain, and dyspnea (all P<0.05). Furthermore, in the group of patients who had sputum culture un-conversion within 6 months of treatment, we also observed significant differences in the proportions of certain factors compared to the culture conversion group. Factors that had higher proportions in the un-conversion group included male, age, BMI<18.5 kg/m2, smoking, alcohol use, previous treatment for TB, presence of cavities, bilateral disease, viral hepatitis, night sweats, weight loss, chest pain, and dyspnea. On the other hand, the culture conversion group had a higher proportion of patients with a baseline regimen including BDQ compared to the un-conversion group (all P<0.05) (Table 1).

Predictors of early and interim culture un-conversion

The results of the multivariable logistic regression analysis revealed several predictors for early and interim culture un-conversion during tuberculosis treatment. AFB smear positive (adjusted odds ratio [aOR] = 1.637, 95% confidence interval [CI] = 1.197–2.238), cavities (aOR = 1.539, 95% CI = 1.132–2.092), bilateral disease (aOR = 1.638, 95% CI = 1.183–2.269), and viral hepatitis (aOR = 2.585, 95% CI = 1.189–5.622) were identified as independent risk factors for early culture un-conversion within 2 months of treatment (Table 2). Additionally, smoking (aOR = 2.197, 95% CI = 1.475–3.273), previous treatment for TB (aOR = 1.909, 95% CI = 1.282–2.844), bilateral disease (aOR = 2.201, 95% CI = 1.369–3.537), and viral hepatitis (aOR = 2.329, 95% CI = 1.094–4.962) were identified as independent risk factors for interim culture un-conversion within 6 months of treatment, while patients with regimen containing BDQ (aOR = 0.310, 95% CI = 0.191–0.502) was protective factor (Table 3).

Table 2 Factors associated with risk of culture un-conversion within 2 months of treatment in MDR/RR-TB patients
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Table 3 Factors associated with risk of culture un-conversion within 6 months of treatment in all patients
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Kaplan-Meier estimates of culture conversion within 24 months among subgroups

In this study, 737 out of 813 patients (90.6%) had culture conversion within 24 months of treatment. The Kaplan-Meier survival curve demonstrated that several factors were associated with culture conversion time within 24 months of treatment among subgroups. These factors included gender, age, BMI, smoking, alcohol use, previous treatment for TB, DM, anemia, baseline AFB smear, cavities, bilateral disease, and regimen with BDQ (all P<0.05) (Fig. 2).

Fig. 2
figure 2

Kaplan-Meier estimates of culture conversion within 24 months of treatment among subgroups in patients with MDR/RR-TB

Abbreviations: BDQ, bedaquiline; BMI, body mass index; DM, diabetes mellitus; RR-TB, rifampicin-resistant tuberculosis; LZD, linezolid; MDR-TB, multidrug-resistant tuberculosis; pre-XDR-TB, pre-extensive drug-resistant tuberculosis

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Discussion

Faster sputum cultures could simplify patient care and increase cost-effectiveness. Shortening the processing time of sputum cultures is important from a public health perspective, as MDR/RR-TB patients with positive sputum cultures are contagious and may spread the disease to contacts. It is crucial to investigate the factors that predict early and interim sputum culture un-conversion in a high TB burden country like China.

This study was conducted in eight institutions located in various regions of China, including the East, West, South, North, and Central region. This geographical diversity was beneficial in minimizing any imbalances in demographic characteristics. The study conducted a multivariable analysis to collect common risk factors associated with culture conversion and treatment outcomes which covering various aspects including socio-demographic characteristics, epidemiology, clinical features, comorbidities, DST patterns, and treatment regimens from previous studies [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26] to reduce the impact of confounding factors. Additionally, the study collected retrospective clinical data from 2018 to 2022, coinciding with the introduction of BDQ to China under the New Drug Introduction & Protection project. The findings from this study can help identify possible predictors for early and interim culture un-conversion and contribute to the future implementation of BDQ-containing regimens and related short-course regimens (such as the 6-month BPaLM regimen or the 9-month all-oral regimen [27]) in China.

In this study, 44.5% of the overall MDR/RR-TB patients achieved culture conversion within 2 months, in line with the previous studies of MDR-TB (ranging from 30%~57.4% [3, 5, 9, 35]). About 79.8% (649/813) patients achieved culture conversion within 6 months of treatment, consistent with previous studies (ranging from 70%~90%) [8, 22, 29, 35,36,37]. The median time for conversion was 2.00 (1.50, 3.00) months within 6 months of treatment, which falls within the duration reported in previous studies (31 days to 91.5 days [3, 6–7, 13, 15–16, 39,40,−41]).

Through a multivariate analysis, we discovered various factors that independently predicted early and interim culture un-conversion. Patients who had a positive AFB smear, cavities, bilateral disease, and viral hepatitis were found to have a higher probability of experiencing culture un-conversion within 2 months of treatment. Additionally, male patients with a history of smoking, previous treatment for TB, bilateral disease, viral hepatitis, and those who received a regimen without BDQ were more likely to experience culture un-conversion within 6 months of treatment. Part of the predictors of early and interim culture un-conversion were overlapped. Notably, the relationship between sputum culture conversion and a successful outcome was found to be significantly stronger at 6 months compared to 2 months [2]. As a result, it is important to give more consideration to the independent risk factors that influence the interim sputum culture conversion.

The presence of an initial positive or a high grade AFB smear, which indicated a relatively high bacillary burden, was a known predictor of a longer time for sputum conversion in patients with pulmonary tuberculosis [8, 13, 15, 38, 39], and a single center study in Korea found that an initial positive AFB smear was associated with culture un-conversion within 3 months of treatment [40]. These findings are consistent with our study. Notably, a positive AFB smear might had a greater influence on early culture conversion compared to interim in our study.

Historically, patients with MDR-TB [9] and drug-susceptible tuberculosis (DS-TB) [10] who had cavities have been found to have a higher risk of culture un-conversion within 2 months of treatment compared to patients without cavities, which was consistent with the findings of our study. Cavities have long been recognized as a risk factor for delayed culture conversion and treatment failure in TB [4, 6,7,8, 16, 38, 39, 41,42,43]. The presence of cavities might hinder the penetration of drugs and consequently reduce the effectiveness of antimicrobial agents [21].

In a prospective cohort study on MDR-TB in America, it was found that bilateral disease (OR 1.90, 95% CI 1.20–3.01) was identified as an independent risk factor for a poor treatment outcome [17]. Our study also found a similar association between bilateral disease and early /interim culture un-conversion. Patients with more extensive lung lesions may experience a longer duration for culture conversion. It is important to note that while bilateral cavitations have often been considered as a potential risk factor for poor treatment outcomes or culture conversion [4, 6], our study separated the lesion scope and cavity, reducing the mutual influence of objective predictors.

Viral hepatitis was identified as an independent predictor for culture un-conversion within early and interim treatment in patients with MDR/RR-TB. This finding was consistent with a study in Armenia and Georgia, which showed that co-infection with hepatitis C virus (aOR 4.45, 95%CI 1.23–16.13) was associated with unsuccessful outcomes in MDR-TB patients who received BDQ through compassionate use [44]. However, the endTB observational study found no association between hepatitis C infection and conversion [8]. This lack of association could be attributed to differences in sample size, race, treatment regimen, and other factors. Notably, HCV co-infection was found to be linked with higher levels of drug-induced liver injury (DILI) in MDR-TB patients [45, 46]. Although we assessed the proportion of adverse effects in our study, we were unable to analyze the relationship between viral hepatitis and DILI due to the retrospective nature of the study and the lack of information on the timing of adverse effects occurrence, the specific type of viral hepatitis, and the antiviral treatment status. Additionally, there is currently no published data available on the effects of new treatments for HCV infection with direct-acting antivirals on mortality and hepatotoxicity in co-infected MDR-TB patients [44].

Substantial evidence exists suggesting that smoking delays culture conversion or associated with culture un-conversion in MDR-TB patients [15, 16, 47], consistent with our finding that smoking was an independent risk factor for interim culture un-conversion. Smoking has been linked to compromised immune mechanisms, such as a reduction in the phagocytic function of alveolar macrophages [48]. Therefore, in a country with a high burden of MDR-TB like China, it is suggested that a new approach to TB control should include a smoking cessation program to potentially reduce the time for culture conversion. The history of previous tuberculosis treatment has been identified as an independent predictor for delayed culture conversion [14] and poor treatment outcome [6, 17] in patients with MDR-TB. This finding aligns with our findings, which showed that previous treatment for tuberculosis was independently associated with interim culture un-conversion.

According to the guideline of WHO [32] and the consensus of China [28] in 2018 and 2019 respectively, BDQ has been designated as a Group A drug for the treatment of MDR/RR/XDR-TB. Regimens containing BDQ have shown potential in achieving early culture conversion [22] or increasing the conversion rate [23,24,25,26]. Since the use of BDQ is still limited in China, part of this study objective to determine whether a regimen containing BDQ can facilitate early and interim culture conversion. Our study found that regimens containing BDQ were an independent predictor for interim culture conversion, similar to previous studies [22,23,24,25,26]. In a study conducted in China, MDR-TB patients who received a BDQ-containing regimen achieved a culture conversion rate of 80.6% (108/134) at the 8th week and 96.8% (120/124) at the 24th week [49]. The culture conversion rate at the 24th week in this study was similar to our study (88.8% for patients who received BDQ-containing regimen within 6 months), suggesting that BDQ has the potential to achieve early culture conversion. In this study, only 5.6% (13/232) of patients who received a BDQ-containing regimen experienced a QTcF prolongation exceeding 500 ms. This suggested that BDQ-containing regimens have an acceptable level of cardiotoxicity. However, short-course regimens such as the 6-month BPaLM/BPaL regimen have not been utilized in China due to the unavailability of pretomanid. Additionally, the 9-month all-oral regimen containing BDQ has not been widely adopted. Therefore, it is crucial to promote the use of BDQ-containing regimens and encourage the adoption of shorter treatment regimens in China.

In addition to the independent predictors mentioned above, our study also identified several factors that were significantly associated with early or interim culture un-conversion. These factors included male, age, BMI<18.5 kg/m2, alcohol use, and anemia. These associations were observed in the univariate analysis. Two previous studies have shown that being male is an independent risk factor for 2-month sputum culture un-conversion [10, 12]. However, our study differs from these previous ones as they mainly focused on DS-TB, with only 3.8%~5.9% of the patients being MDR-TB [10, 12], and elderly patients with a mean age of 64.7 ± 19.2 years [12]. Additionally, age was found to be significantly associated with sputum smear conversion time in patients with new DS-TB [42]. Alcoholism [13] or drinking [15] were independent predictors of less likely conversion in MDR-TB patients. Baseline anemia was reported to be associated with an unfavorable treatment outcome [50, 51]. However, gender, age, alcohol use, and baseline anemia alone were not sufficient to be considered independent risk factors for early and interim culture conversion in MDR/RR-TB patients.

Notably, a single-center study conducted in Korea revealed that failure to achieve sputum culture conversion within 3 months was independently associated with a low BMI(< 18.5 kg/m2) [42] in MDR-TB patients, which contrasts with our finding. Additionally, we found that the comorbidity of DM was not a risk factor for culture un-conversion within 2 and 6 months of treatment in multivariate analysis, consistent with another cohort study conducted in China [49]. However, a study conducted in Korea reported that uncontrolled diabetes was identified as an independent risk factor for a positive sputum culture after 2 months of treatment (aOR, 2.11; P = 0.042) in multivariable analysis [6], which differs from our study. These discrepancies above may be attributed to the fact that we did not collect information on the management of DM in our study, as well as differences in race, age, and sample size between the studies.

In our study, pre-XDR-TB was not a predictor of culture un-conversion at 2 and 6 months of treatment. A total of 233 patients had pre-XDR-TB in this study, all of whom exhibited resistance to FQs. However, according to previous studies, resistance to FQs or ofloxacin has been identified as an independent predictor of less likely conversion [13] or an extended time to conversion [7, 15] in patients with MDR-TB. Additionally, one study conducted in Pakistan [9] found that resistance to ofloxacin had a statistically significant negative association with culture conversion at two months. The inconsistency in results may be attributed to the fact that those studies did not include anti-TB treatment regimens in their analyses, and patients received treatment prior to 2014, which did not include Group A drugs other than FQs (such as BDQ or linezolid). Consequently, MDR-TB patients resistant to FQs had fewer treatment options, making it more challenging to achieve sputum culture conversion. In contrast, approximately 42.5% (99/233) of patients with pre-XDR-TB in our study received BDQ-containing regimens, which was higher than the proportion of patients with MDR/RR-TB (22.9%, 133/580). The selection of more effective drugs (such as bedaquiline, linezolid, delamanid, and pretomanid) may mitigate the impact of drug resistance types, such as pre-XDR-TB, on early and interim culture conversion.

Furthermore, we utilized the Kaplan-Meier survival curve to analyze the relationship between culture conversion time within 24 months of treatment and possible high-risk factors. Our findings revealed that virus hepatitis may have a more significant impact on early and interim culture un-conversion, rather than in subsequent treatment (Fig. 2). On the other hand, factors such as gender, age, BMI, alcohol use, and anemia may have a greater impact on culture un-conversion during the later stages of treatment. However, due to the limited data available on the occurrence time and frequency of adverse effects during treatment, as well as the specific timing of drug interruption and regimen change, only a brief discussion was provided in this study. Therefore, these hypotheses require further investigation.

These findings suggested that the aforementioned objective independent predictors can often be identified before the diagnosis or early treatment of MDR/RR-TB, offering clinicians an opportunity to identify patients who may benefit from targeted management. This may involve the use of improved initial regimens that include BDQ, and increased medical attention to high risk populations. In low-resource settings where sputum cultures are not regularly conducted, more frequent monitoring of sputum cultures in high-risk patients can enable earlier detection of those who do not experience conversion.

This study has several limitations. Firstly, it should be noted that MDR/RR-TB patients in China are recommended to undergo monthly sputum culture tests. However, not all patients were able to complete these tests monthly after 6 months of treatment. As a result, we have utilized the available data to develop a logistic multivariable model instead of Cox regression. This model helped identify certain predictors for early and interim un-conversion. We were only able to present the conversion time within 24 months in different subgroups based on the available data, but it is not possible to compare predictors associated with culture conversion in the early, interim and whole course. Additionally, this study did not collect the occurrence time of adverse effects and changes in treatment regimen throughout the entire duration of the treatment. Therefore, only the initial regimens were considered in the multivariate analysis, and the adverse effects were not taken into consideration. Furthermore, the study did not differentiate between viral hepatitis caused by hepatitis B and hepatitis C, and it did not collect data on the glycemic control status of patients with diabetes mellitus. Moreover, based on the medical records, patients generally reported regular medication usage; therefore, treatment adherence was not included in this study. However, it is important to note that some patients may exhibit poor treatment adherence outside the outpatient clinic, which is not captured in the records. Lastly, the study did not assess the cost-effectiveness of MDR-TB treatment in terms of catastrophic health expenditures.

Conclusions

This study identified specific predictors for early and interim sputum culture conversion for MDR/RR-TB in China. A history of smoking, a baseline sputum AFB smear positive, lung cavities, bilateral disease, previous anti-tuberculosis treatment, or a comorbidity of viral hepatitis requires increased medical attention to achieve faster culture conversion can be used as the predictors for early and interim culture un-conversion in MDR/RR-TB patients, while BDQ was a protective factor. Optimizing the management of MDR/RR-TB patients should be prioritized by considering these predictors and vulnerable subgroups. Furthermore, treatment regimens for MDR/RR-TB should incorporate new anti-tuberculosis drugs like BDQ, whenever feasible.

Adverse effects

The study found that the most common adverse effect was liver injury (47.1%), followed by anemia (36.5%), peripheral neuritis (24.5%), leukopenia (19.4%), optic neuritis (12.8%), thrombopenia (12.7%), acute renal injury (defined according to the Kidney Disease: Improving Global Outcomes clinical practice guidelines [52]) (5.8%), and prolonged Fridericia-corrected QT (QTcF) interval (≥ 500ms) (2.2%).

Data availability

No datasets were generated or analysed during the current study.

References

  1. World Health Organization. Global Tuberculosis Report. 2023. Geneva: World Health Organization. 2023.

  2. Kurbatova EV, Cegielski JP, Lienhardt C, Akksilp R, Bayona J, Becerra MC, et al. M. Sputum culture conversion as a prognostic marker for end-of-treatment outcome in patients with multidrug-resistant tuberculosis: a secondary analysis of data from two observational cohort studies. Lancet Respir Med. 2015;3(3):201–9. https://doi.org/10.1016/S2213-2600(15)00036-3.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Holtz TH, Sternberg M, Kammerer S, Laserson KF, Riekstina V, Zarovska E, et al. Time to sputum culture conversion in multidrug-resistant tuberculosis: predictors and relationship to treatment outcome. Ann Intern Med. 2006;144(9):650–9. https://doi.org/10.7326/0003-4819-144-9-200605020-00008.

    Article  PubMed  Google Scholar 

  4. Ahmad Khan F, Salim MAH, du Cros P, Casas EC, Khamraev A, Sikhondze W et al. Effectiveness and safety of standardised shorter regimens for multidrug-resistant tuberculosis: individual patient data and aggregate data meta-analyses. Eur Respir J;50(1):1700061. https://doi.org/10.1183/13993003.00061-2017

  5. Rodriguez M, Monedero I, Caminero JA, Encarnación M, Dominguez Y, Acosta I, et al. Successful management of multidrug-resistant tuberculosis under programme conditions in the Dominican Republic. Int J Tuberc Lung Dis. 2013;17(4):520–5. https://doi.org/10.5588/ijtld.12.0481.

    Article  CAS  PubMed  Google Scholar 

  6. Soeroto AY, Pratiwi C, Santoso P, Lestari BW. Factors affecting outcome of longer regimen multidrug-resistant tuberculosis treatment in West Java Indonesia: a retrospective cohort study. PLoS ONE. 2021;16(2):e0246284. https://doi.org/10.1371/journal.pone.0246284.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Javaid A, Ahmad N, Afridi AK, Basit A, Khan AH, Ahmad I, et al. Validity of time to Sputum Culture Conversion to predict cure in patients with multidrug-resistant tuberculosis: a retrospective single-center study. Am J Trop Med Hyg. 2018;98(6):1629–36. https://doi.org/10.4269/ajtmh.17-0936.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Franke MF, Khan P, Hewison C, Khan U, Huerga H, Seung KJ, et al. Culture Conversion in patients treated with bedaquiline and/or Delamanid. A prospective Multicountry Study. Am J Respir Crit Care Med. 2021;203(1):111–9. https://doi.org/10.1164/rccm.202001-0135OC.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Basit A, Ahmad N, Khan AH, Javaid A, Syed Sulaiman SA, Afridi AK, et al. Predictors of two months culture conversion in multidrug-resistant tuberculosis: findings from a retrospective cohort study. PLoS ONE. 2014;9(4):e93206. https://doi.org/10.1371/journal.pone.0093206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lee EH, Lee JM, Kang YA, Leem AY, Kim EY, Jung JY, et al. Prevalence and impact of diabetes Mellitus among patients with active pulmonary tuberculosis in South Korea. Lung. 2017;195(2):209–15. https://doi.org/10.1007/s00408-017-9978-4.

    Article  PubMed  Google Scholar 

  11. Yoon YS, Jung JW, Jeon EJ, Seo H, Ryu YJ, Yim JJ, et al. The effect of diabetes control status on treatment response in pulmonary tuberculosis: a prospective study. Thorax. 2017;72(3):263–70. https://doi.org/10.1136/thoraxjnl-2015-207686.

    Article  PubMed  Google Scholar 

  12. Feng JY, Huang SF, Ting WY, Chen YC, Lin YY, Huang RM, Lin CH, Hwang JJ, Lee JJ, Yu MC, Yu KW, Lee YC, Su WJ. Gender differences in treatment outcomes of tuberculosis patients in Taiwan: a prospective observational study. Clin Microbiol Infect. 2012;18(9):E331–7. https://doi.org/10.1111/j.1469-0691.2012.03931.x.

    Article  PubMed  Google Scholar 

  13. Kurbatova EV, Gammino VM, Bayona J, Becerra MC, Danilovitz M, Falzon D, et al. Predictors of sputum culture conversion among patients treated for multidrug-resistant tuberculosis. Int J Tuberc Lung Dis. 2012;16(10):1335–43. https://doi.org/10.5588/ijtld.11.0811.

    Article  CAS  PubMed  Google Scholar 

  14. Bade AB, Mega TA, Negera GZ. Malnutrition is Associated with delayed Sputum Culture Conversion among patients treated for MDR-TB. Infect Drug Resist. 2021;14:1659–67. https://doi.org/10.2147/IDR.S293461.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Liu Q, Lu P, Martinez L, Yang H, Lu W, Ding X, et al. Factors affecting time to sputum culture conversion and treatment outcome of patients with multidrug-resistant tuberculosis in China. BMC Infect Dis. 2018;18(1):114. https://doi.org/10.1186/s12879-018-3021-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Magee MJ, Kempker RR, Kipiani M, Tukvadze N, Howards PP, Narayan KM, et al. Diabetes mellitus, smoking status, and rate of sputum culture conversion in patients with multidrug-resistant tuberculosis: a cohort study from the country of Georgia. PLoS ONE. 2014;9(4):e94890. https://doi.org/10.1371/journal.pone.0094890.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Gegia M, Kalandadze I, Kempker RR, Magee MJ, Blumberg HM. Adjunctive surgery improves treatment outcomes among patients with multidrug-resistant and extensively drug-resistant tuberculosis. Int J Infect Dis. 2012;16(5):e391–6. https://doi.org/10.1016/j.ijid.2011.12.018.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Leimane V, Riekstina V, Holtz TH, Zarovska E, Skripconoka V, Thorpe LE, et al. Clinical outcome of individualised treatment of multidrug-resistant tuberculosis in Latvia: a retrospective cohort study. Lancet. 2005;365(9456):318–26. https://doi.org/10.1016/S0140-6736(05)17786-1.

    Article  PubMed  Google Scholar 

  19. Kwon YS, Kim YH, Suh GY, Chung MP, Kim H, Kwon OJ, et al. Treatment outcomes for HIV-uninfected patients with multidrug-resistant and extensively drug-resistant tuberculosis. Clin Infect Dis. 2008;47(4):496–502. https://doi.org/10.1086/590005.

    Article  PubMed  Google Scholar 

  20. Jeon DS, Kim DH, Kang HS, Hwang SH, Min JH, Kim JH, et al. Survival and predictors of outcomes in non-HIV-infected patients with extensively drug-resistant tuberculosis. Int J Tuberc Lung Dis. 2009;13(5):594–600.

    CAS  PubMed  Google Scholar 

  21. Yew WW, Chan CK, Chau CH, Tam CM, Leung CC, Wong PC, et al. Outcomes of patients with multidrug-resistant pulmonary tuberculosis treated with ofloxacin/levofloxacin-containing regimens. Chest. 2000;117(3):744–51. https://doi.org/10.1378/chest.117.3.744.

    Article  CAS  PubMed  Google Scholar 

  22. Diacon AH, Pym A, Grobusch MP, de los Rios JM, Gotuzzo E, Vasilyeva I, et al. Multidrug-resistant tuberculosis and culture conversion with bedaquiline. N Engl J Med. 2014;371(8):723–32. https://doi.org/10.1056/NEJMoa1313865.

    Article  CAS  PubMed  Google Scholar 

  23. Chesov D, Heyckendorf J, Alexandru S, Donica A, Chesov E, Reimann M, et al. Impact of bedaquiline on treatment outcomes of multidrug-resistant tuberculosis in a high-burden country. Eur Respir J. 2021;57(6):2002544. https://doi.org/10.1183/13993003.02544-2020.

    Article  CAS  PubMed  Google Scholar 

  24. Esmail A, Oelofse S, Lombard C, Perumal R, Mbuthini L, Goolam Mahomed A, et al. An all-oral 6-Month Regimen for Multidrug-resistant tuberculosis: a Multicenter, Randomized Controlled Clinical Trial (the NExT Study). Am J Respir Crit Care Med. 2022;205(10):1214–27. https://doi.org/10.1164/rccm.202107-1779OC.

    Article  CAS  PubMed  Google Scholar 

  25. Zhang SJ, Yang Y, Sun WW, Zhang ZS, Xiao HP, Li YP, et al. Effectiveness and safety of bedaquiline-containing regimens for treatment on patients with refractory RR/MDR/XDR-tuberculosis: a retrospective cohort study in East China. BMC Infect Dis. 2022;22(1):715. https://doi.org/10.1186/s12879-022-07693-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tong E, Wu Q, Chen Y, Liu Z, Zhang M, Zhu Y, et al. The efficacy and safety of Bedaquiline in the treatment of pulmonary tuberculosis patients: a systematic review and Meta-analysis. Antibiot (Basel). 2023;12(9):1389. https://doi.org/10.3390/antibiotics12091389.

    Article  CAS  Google Scholar 

  27. World Health Organization. WHO consolidated guidelines on tuberculosis. Module 4: treatment-drug-resistant tuberculosis treatment, 2022 update[M]. Geneva: World Health Organization; 2022.

    Google Scholar 

  28. Chinese Society of Tuberculosis of Chinese Medical Association. [Chinese expert consensus on multidrug-resistant tuberculosis and rifampicin-resistant tuberculosis treatment]. Zhonghua Jie He He Hu Xi Za Zhi. 2019;42(10):733–49.

    Google Scholar 

  29. von Groote-Bidlingmaier F, Patientia R, Sanchez E, Balanag V Jr, Ticona E, Segura P, et al. Efficacy and safety of delamanid in combination with an optimised background regimen for treatment of multidrug-resistant tuberculosis: a multicentre, randomised, double-blind, placebo-controlled, parallel group phase 3 trial. Lancet Respir Med. 2019;7(3):249–59. https://doi.org/10.1016/S2213-2600(18)30426-0.

    Article  Google Scholar 

  30. Maretbayeva SM, Rakisheva AS, Adenov MM, Yeraliyeva LT, Algozhin YZ, Stambekova AT, et al. Culture conversion at six months in patients receiving bedaquiline- and delamanid-containing regimens for the treatment of multidrug-resistant tuberculosis. Int J Infect Dis. 2021;113(Suppl 1):S91–5. https://doi.org/10.1016/j.ijid.2021.03.075.

    Article  CAS  PubMed  Google Scholar 

  31. Ghosh S, Breitscheidel L, Lazarevic N, Martin A, Hafkin J, Hittel N. Compassionate use of delamanid in adults and children for drug-resistant tuberculosis: 5-year update. Eur Respir J. 2021;57(5):2002483. https://doi.org/10.1183/13993003.02483-2020.

    Article  CAS  PubMed  Google Scholar 

  32. World Health Organization. WHO treatment guidelines for multidrug- and rifampicin-resistant tuberculosis, 2018 update[M]. Geneva: World Health Organization; 2018.

    Google Scholar 

  33. World Health Organization. WHO consolidated guidelines on drug-resistant tuberculosis treatment[M]. Geneva: World Health Organization; 2019.

    Google Scholar 

  34. World Health Organization. WHO consolidated guidelines on tuberculosis. Module 4: treatment - drug-resistant tuberculosis treatment[M]. Geneva: World Health Organization; 2020.

    Google Scholar 

  35. Kang H, Jo KW, Jeon D, Yim JJ, Shim TS. Interim treatment outcomes in multidrug-resistant tuberculosis using bedaquiline and/or delamanid in South Korea. Respir Med. 2020;167:105956. https://doi.org/10.1016/j.rmed.2020.105956.

    Article  PubMed  Google Scholar 

  36. Mbuagbaw L, Guglielmetti L, Hewison C, Bakare N, Bastard M, Caumes E, et al. Outcomes of Bedaquiline Treatment in patients with multidrug-resistant tuberculosis. Emerg Infect Dis. 2019;25(5):936–43. https://doi.org/10.3201/eid2505.181823.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kim CT, Kim TO, Shin HJ, Ko YC, Hun Choe Y, Kim HR, et al. Bedaquiline and delamanid for the treatment of multidrug-resistant tuberculosis: a multicentre cohort study in Korea. Eur Respir J. 2018;51(3):1702467. https://doi.org/10.1183/13993003.02467-2017.

    Article  CAS  PubMed  Google Scholar 

  38. Telzak EE, Fazal BA, Pollard CL, Turett GS, Justman JE, Blum S. Factors influencing time to sputum conversion among patients with smear-positive pulmonary tuberculosis. Clin Infect Dis. 1997;25(3):666–70. https://doi.org/10.1086/513772.

    Article  CAS  PubMed  Google Scholar 

  39. Wang JY, Lee LN, Yu CJ, Chien YJ, Yang PC, Tami Group. Factors influencing time to smear conversion in patients with smear-positive pulmonary tuberculosis. Respirology. 2009;14(7):1012–9. https://doi.org/10.1111/j.1440-1843.2009.01598.x.

    Article  PubMed  Google Scholar 

  40. Park HO, Kim SH, Moon SH, Byun JH, Kim JW, Lee CE, et al. Association between Body Mass Index and Sputum Culture Conversion among South Korean patients with Multidrug resistant tuberculosis in a tuberculosis Referral Hospital. Infect Chemother. 2016;48(4):317–23. https://doi.org/10.3947/ic.2016.48.4.317.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kurbatova EV, Taylor A, Gammino VM, Bayona J, Becerra M, Danilovitz M, et al. Predictors of poor outcomes among patients treated for multidrug-resistant tuberculosis at DOTS-plus projects. Tuberculosis (Edinb). 2012;92(5):397–403. https://doi.org/10.1016/j.tube.2012.06.003.

    Article  PubMed  Google Scholar 

  42. Güler M, Unsal E, Dursun B, Aydln O, Capan N. Factors influencing sputum smear and culture conversion time among patients with new case pulmonary tuberculosis. Int J Clin Pract. 2007;61(2):231–5. https://doi.org/10.1111/j.1742-1241.2006.01131.x.

    Article  PubMed  Google Scholar 

  43. Mahishale V, Patil B, Lolly M, Eti A, Khan S. Prevalence of smoking and its impact on treatment outcomes in newly diagnosed pulmonary tuberculosis patients: a hospital-based prospective study. Chonnam Med J. 2015;51(2):86–90. https://doi.org/10.4068/cmj.2015.51.2.86.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Hewison C, Bastard M, Khachatryan N, Kotrikadze T, Hayrapetyan A, Avaliani Z, et al. Is 6 months of bedaquiline enough? Results from the compassionate use of bedaquiline in Armenia and Georgia. Int J Tuberc Lung Dis. 2018;22(7):766–72. https://doi.org/10.5588/ijtld.17.0840.

    Article  CAS  PubMed  Google Scholar 

  45. Lee SS, Lee CM, Kim TH, Kim JJ, Lee JM, Kim HJ, et al. Frequency and risk factors of drug-induced liver injury during treatment of multidrug-resistant tuberculosis. Int J Tuberc Lung Dis. 2016;20(6):800–5. https://doi.org/10.5588/ijtld.15.0668.

    Article  CAS  PubMed  Google Scholar 

  46. Chien JY, Huang RM, Wang JY, Ruan SY, Chien YJ, Yu CJ, et al. Hepatitis C virus infection increases hepatitis risk during anti-tuberculosis treatment. Int J Tuberc Lung Dis. 2010;14(5):616–21.

    PubMed  Google Scholar 

  47. Salindri AD, Kipiani M, Kempker RR, Gandhi NR, Darchia L, Tukvadze N, et al. Diabetes reduces the rate of Sputum Culture Conversion in patients with newly diagnosed Multidrug-resistant tuberculosis. Open Forum Infect Dis. 2016;3(3):ofw126. https://doi.org/10.1093/ofid/ofw126.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Lin HH, Ezzati M, Chang HY, et al. Association between tobacco smoking and active tuberculosis in Taiwan: prospective cohort study. Am J Respir Crit Care Med. 2009;180(5):475–80. https://doi.org/10.1164/rccm.200904-0549OC.

    Article  PubMed  Google Scholar 

  49. Shi L, Gao J, Gao M, Deng P, Chen S, He M, et al. Interim effectiveness and safety comparison of Bedaquiline-containing regimens for treatment of Diabetic Versus non-diabetic MDR/XDR-TB patients in China: a Multicenter Retrospective Cohort Study. Infect Dis Ther. 2021;10(1):457–70. https://doi.org/10.1007/s40121-021-00396-9.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Kuaban A, Balkissou AD, Ekongolo MCE, Nsounfon AW, Pefura-Yone EW, Kuaban C. Incidence and factors associated with unfavourable treatment outcome among patients with rifampicin-resistant pulmonary tuberculosis in Yaoundé, Cameroon. Pan Afr Med J. 2021;38:229. https://doi.org/10.11604/pamj.2021.38.229.28317.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Anley DT, Akalu TY, Merid MW, Tsegaye T. Development and validation of a Nomogram for the prediction of unfavorable treatment outcome among Multi-drug resistant tuberculosis patients in North West Ethiopia: an application of Prediction Modelling. Infect Drug Resist. 2022;15:3887–904. https://doi.org/10.2147/IDR.S372351.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120(4):c179–84. https://doi.org/10.1159/000339789.

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors are grateful to the participants in this study and also the generous support of Chengdu Health Commission, Chengdu Science and Technology Bureau, and Sichuan Medical Association.

Funding

This work was supported by the Medical Research Project of Chengdu Health Commission [grant number 2023038, 2023560, 2022262], and the Technology Innovation Research and Development project of Chengdu Science and Technology Bureau [grant number 2022-YF05-02148-SN, 2022-YF05-02139-SN], and Key Research and Development Project of Science and Technology Department of Sichuan Province [grant number 2023YFS0220], and Sichuan Medical Association [grant number S22042].

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Author notes

  1. Qing Chen, Wei He, Juan Du and Wanli Kang contributed equally to this work.

Authors and Affiliations

  1. Department of Tuberculosis, Public Health Clinical Center of Chengdu, Jingjusi 18 Street, Jingjiang District, Chengdu, 610061, Sichuan, China

    Qing Chen, Wei He, Liping Zou, Xianzhen Tang, Zhouli Guo & Guihui Wu

  2. Department of Tuberculosis, Wuhan Pulmonary Hotel, Hubei, China

    Juan Du

  3. Beijing Chest Hospital, Beijing Tuberculosis and Thoracic Tumor Research Institute, Capital Medical University, Beijing, China

    Wanli Kang & Shenjie Tang

  4. Department of Tuberculosis, the Fifth People’s Hospital of Suzhou, Jiangsu, China

    Peijun Tang

  5. Department of Tuberculosis, Harbin Chest Hospital, Heilongjiang, China

    Chunhui Guo

  6. Department of Respiratory and Critical Care Medicine, Anqing Municipal Hospital, Anhui, China

    Qing Pan

  7. Department of Tuberculosis, The Fourth People’s Hospital of Nanning, Guangxi, China

    Qingdong Zhu

  8. Department of General Internal Medicine, Chongqing Public Health Medical Center, Chongqing, China

    Song Yang

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Contributions

QC, WH, GHW, and SJT had the idea for and designed the study and had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. QC and SJT drafted the paper. QC, WH, LPZ, XZT, GHW, and SJT did the analysis. QC, WH, JD, WLK, LPZ, XZT, PJT, CHG, QP, QDZ, SY and ZLG collected the data and did the follow up. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Guihui Wu or Shenjie Tang.

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Chen, Q., He, W., Du, J. et al. Predictors of early and interim culture un-conversion in multidrug-resistant/rifampicin-resistant tuberculosis: a retrospective multi-center cohort study in China. Antimicrob Resist Infect Control 13, 126 (2024). https://doi.org/10.1186/s13756-024-01480-8

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Keywords

Antimicrobial Resistance & Infection Control

ISSN: 2047-2994

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