Analysis of the Results of Tuberculosis Drug Resistance Surveillance in Yuexiu District, Guangzhou City, 2013–2022
ABSTRACT
Introduction
The objectives of the study are to understand the drug-resistant situation and trend of tuberculosis patients in Yuexiu District, Guangzhou City, from 2013 to 2022, and to provide a scientific basis for the development of rational drug-resistant tuberculosis prevention and control strategies in Guangzhou City.
Methods
All patients who were diagnosed with active tuberculosis in Guangzhou Chest Hospital from January 1, 2013 to December 31, 2022 were collected as study subjects, and a total of 5191 patients were enrolled in the study. Comprehensive data on the basic characteristics, diagnostic, and therapeutic information of the study subjects were collected. Sputum specimens were subjected to smear, isolation, and culture. Culture-positive strains of bacteria were identified by bacterial groups. A total of 1659 strains of Mycobacterium tuberculosis (MTB) isolates were obtained. The drug susceptibility test was carried out using the proportionality method on the MTB isolates for nine types of antituberculosis medicines: isoniazid (INH), rifampicin (RFP), ethambutol (EMB), streptomycin (Sm), kanamycin (Km), ofloxacin (Ofx), capreomycin (Cm), propylthioisonicotinamide (Pto), and p-aminosalicylic acid (PAS). A comparative analysis of the resistance patterns among the strains was conducted.
Results
A total of 1659 patients with MTB were cultured, revealing 438 drug-resistant cases. Among these, 255 were monoresistant, 121 were polyresistant, and 62 were multidrug resistant. The overall resistance rate was 26.40% (438/1659), with mono-resistance rate at 15.37% (255/1659), polyresistance rate at 7.29% (121/1659), and multidrug resistance rate at 3.74% (62/1659). In descending order, the resistance rates of MTB isolates to any of the nine antituberculosis drugs were Sm (12.24%, 203/1659), INH (9.22%, 153/1659), EMB (7.35%, 122/1659), RFP (6.99%, 116/1659), PAS (3.25%, 54/1659), Pto (3.13%, 52/1659), Ofx (2.71%, 45/1659), Cm (2.17%, 36/1659), and Km (2.17%, 36/1659). The differences in resistance rates were statistically significant (p < 0.01), with Sm exhibiting the highest resistance rate and Km the lowest.
In the primary treatment group, 388 patients (25.55%) were drug resistant, while 50 patients (35.46%) in the retreatment group were drug resistant. Thirty-nine patients (2.57%) in the primary treatment group were multidrug resistant, compared to 23 patients (16.31%) in the retreatment group. The resistance rate and multidrug resistance rate of isolates from retreatment patients were significantly higher than primary treatment patients (p < 0.05).
Conclusions
The problem of drug-resistant tuberculosis transmission in Guangzhou requires attention, and drug-resistant screening should be further increased to effectively control the source of infection.
1 Introduction
Tuberculosis (TB) is a major infectious disease worldwide, with high morbidity and mortality rate. The global burden of multidrug-resistant tuberculosis (MDR-TB) continues to increase without any signs of decreasing and poses a serious threat to global TB control efforts.
In 2023, the World Health Organization (WHO) released its Global Tuberculosis Report, estimating that 10.6 million people worldwide had TB in 2022, up from 10.3 million in 2021. An estimated 410,000 people had multidrug- or rifampicin-resistant TB in 2022, among whom only about two-fifths were receiving treatment [1].
MDR-TB has become a significant public health problem worldwide [2]. We collected demographic data and diagnostic information of active TB patients enrolled in Guangzhou Chest Hospital and the results of drug susceptibility testing (DST) of isolated strains from 2013 to 2022. We analyzed these results to understand the level of MDR-TB and changes in Yuexiu District of Guangzhou, providing a reference for the development of TB prevention, control, and treatment policies.
2 Methods
2.1 Source of Information
All newly diagnosed patients with active TB in Guangzhou Chest Hospital from January 1, 2013 to December 31, 2022 were enrolled in the study. All enrolled participants signed the patient informed consent form, and 5191 cases were finally included. The basic conditions, diagnosis, and treatment information of the study subjects were collected, and the sputum specimens were smeared and isolated for culture. Drug susceptibility and mycobacterial group identification tests were conducted on culture-positive strains for nine anti-TB drugs using the proportional method, and a total of 1659 isolates of Mycobacterium tuberculosis (MTB) were obtained. The cohort comprised 1221 male and 438 female cases, with age distributions as follows: 72 cases aged 0–19 years, 601 cases aged 20–39 years, 576 cases aged 40–59 years, and 410 cases aged 60 years and above. Furthermore, the cohort included 1518 primary treated cases and 141 re-treated cases.
2.2 Laboratory Quality Control
The laboratory staff participates in proficiency testing and inter-room quality control activities organized by the National Tuberculosis Reference Laboratory (NTRL) for drug sensitivity testing of anti-TB drugs each year. For each batch of samples, drug sensitivity testing the sensitive strain of MTB (H37Rv) provided by the NTRL is used as a quality control.
2.3 Definition of Drug-Resistant TB
Definitions of drug-, multidrug-, mono-, and polo-resistant TB refer to the Drug-resistant Tuberculosis Chemotherapy Guidelines (2019 short version) [3]. Definitions of primary and re-treatment refer to Technical Guidelines for Tuberculosis Control and Prevention in China [4].
2.3.1 Mono-Resistant TB
TB patients infected with MTB have been shown to be resistant to only one first-line anti-TB drug by in vitro drug susceptibility testing.
2.3.2 Polyresistant TB
TB patients infected with MTB confirmed by in vitro DST to be resistant to more than one first-line anti-TB drug (but not both isoniazid and rifampicin).
2.3.3 Multidrug-Resistant TB
TB patients infected with MTB have been shown by in vitro DST to be resistant to at least both isoniazid and rifampicin.
2.3.4 Primarily Treated Patients
Patients who have not received anti-TB treatment or have been on anti-TB treatment for less than 1 month.
2.3.5 Re-treatment Patients
Patients on anti-TB treatment for at least 1 month, and patients who have failed initial treatment and relapsed [4].
2.4 Statistical Processing
Excel 2019 software was used to organize and summarize the data, and SPSS 22.0 (IBM, Armonk, NY, USA) software was applied to analyze the data. The counting data were described by percentage (%), and the difference of drug resistance among groups was compared by chi-square test. The trend of drug resistance over time was analyzed by the chi-square trend test, with significance defined as p < 0.05.
3 Results
3.1 Drug Resistance Situation of Strains
From January 1, 2013 to December 31, 2022, MTB isolates from 5191 patients in Yuexiu District, Guangzhou City, were analyzed, identifying 438 cases of drug resistance, with a resistance rate of 26.40% (438/1659). There were 255 cases of mono-resistance, with a mono-resistance rate of 15.37% (255/1659); 121 cases of polyresistance, with a polyresistance rate of 7.29% (121/1659); 62 cases of multidrug resistance, with a multidrug resistance rate of 3.74% (62/1659). No statistically significant changes were observed in the drug resistance, mono-resistance, polyresistance, or multidrug resistance rate (p > 0.05). Trends in resistance rates were observed, with an increase in mono-drug and poly-drug resistance rates and a decrease in multidrug resistance rate, although these changes did not show statistical significance (p > 0.05), as shown in Table 1.
| Drug-resistance | Multidrug resistance | Mono resistance | Poly resistance | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Year | Strain number | Strain number | Drug resistance rate (%) | Strain number | Multidrug resistance rate (%) | Strain number | Mono resistance rate (%) | Strain number | Multi-resistance rate (%) |
| 2013 | 39 | 9 | 23.08 | 2 | 5.13 | 5 | 12.82 | 2 | 5.13 |
| 2014 | 117 | 28 | 23.93 | 4 | 3.42 | 17 | 14.53 | 7 | 5.98 |
| 2015 | 105 | 27 | 25.71 | 3 | 2.86 | 16 | 15.24 | 8 | 7.62 |
| 2016 | 182 | 49 | 26.92 | 6 | 3.30 | 29 | 15.93 | 14 | 7.69 |
| 2017 | 217 | 59 | 27.19 | 7 | 3.23 | 35 | 16.13 | 17 | 7.83 |
| 2018 | 200 | 57 | 28.50 | 6 | 3.00 | 33 | 16.50 | 18 | 9.00 |
| 2019 | 230 | 58 | 25.22 | 10 | 4.35 | 34 | 14.78 | 14 | 6.09 |
| 2020 | 197 | 54 | 27.41 | 8 | 4.06 | 31 | 15.74 | 15 | 7.61 |
| 2021 | 208 | 54 | 25.96 | 9 | 4.33 | 30 | 14.42 | 15 | 7.21 |
| 2022 | 164 | 43 | 26.22 | 7 | 4.27 | 25 | 15.24 | 11 | 6.71 |
| Total | 1659 | 438 | 26.40 | 62 | 3.74 | 255 | 15.37 | 121 | 7.29 |
| Chi-square value | 0.016 | 0.209 | 0.134 | 0.388 | |||||
| p value | 0.992 | 0.769 | 0.935 | 0.824 | |||||
3.2 Distribution of Different Characteristics of Strains
In all, 1659 MTB isolates included 1221 males and 438 females. Three hundred and twenty-four males and 115 females were found to be drug resistant, but the difference was not statistically significant (p > 0.05). Forty-six males and 16 females were identified as multidrug resistant. The overall resistance rate among the 1659 MTB isolates was 26.40% (438/1659), whereas the multidrug resistance rate was 3.74% (62/1659), and the difference between the resistance rate and multidrug resistance rate of different genders was not statistically significant (p > 0.05). The number of drug-resistant patients undergoing primary treatment was 388, contributing to a resistance rate of 25.55% (388/1518). In contrast, among re-treated patients, the number was 50, yielding a resistance rate of 35.46% (50/141). Thirty-nine patients were classified as multidrug resistant among primary treatment, equating to a rate of 2.57% (39/1518). In re-treated patients, 23 cases exhibited multidrug resistance, constituting a higher rate of 16.31% (23/141). Both the resistance rate and multidrug resistance rate of isolates from re-treated patients were significantly higher than those from primary-treatment patients (p < 0.05), as shown in Table 2.
| Characteri zation | Strain number | Drug resistance | Multidrug resistance | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Strain number | Drug resistance rate (%) | Chi-square value | p value | Strain number | Multidrug resistance rate (%) | Chi-square value | p value | ||
| Gender | 0.013 | 0.909 | 0.011 | 0.916 | |||||
| Male | 1221 | 323 | 26.45 | 46 | 3.77 | ||||
| Female | 438 | 115 | 26.26 | 16 | 3.65 | ||||
| Age group (years) | 0.253 | 0.881 | 0.0506 | 0.975 | |||||
| 0–19 | 72 | 19 | 26.39 | 3 | 4.17 | ||||
| 20–39 | 601 | 154 | 25.62 | 22 | 3.66 | ||||
| 40–59 | 576 | 156 | 27.08 | 21 | 3.65 | ||||
| ≥ 60 | 410 | 109 | 26.59 | 16 | 3.90 | ||||
| Patient category | 6.413 | 0.011 | 67.732 | < 0.001 | |||||
| Primary treatment | 1518 | 388 | 25.55 | 39 | 2.57 | ||||
| Re-treatment | 141 | 50 | 35.46 | 23 | 16.31 | ||||
3.3 Resistance of Strains to Anti-TB Drugs
The resistance rates of MTB isolates to the nine anti-TB drugs, in descending order, were as follows: Sm > INH > EMB > RFP > PAS > Pto > Ofx > Cm > Km, with statistically significant differences (chi-square value = 72.569, p < 0.01). Trend analysis showed statistically significant differences in the resistance rates of isolates to the three first-line anti-TB drugs (RFP, Sm, and EMB) across each years. The differences in the resistance rates were statistically significant, and the changes in the resistance rates of the strains to RFP, EMB, and Sm showed an increasing trend. The resistance rates to INH, Km, and PAS showed a decreasing trend, while the resistance rates to other drugs remained basically stable, as shown in Table 3.
| INH resistance | RFP resistance | Sm resistant | EMB resistance | Km resistance | OFx resistance | Cm resistance | PAS resistance | Pto resistance | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Certain year | Number of strains | Number of strain | Drug resistance rate (%) | Number of strain | Drug resistance rate (%) | Number of strain | Drug resistance rate (%) | Number of strain | Drug resistance rate (%) | Number of strain | Drug resistance rate (%) | Number of strain | Drug resistance rate (%) | Number of strain | Drug resistance rate (%) | Number of strain | Drug resistance rate (%) | Number of strain | Drug resistance rate (%) |
| 2013 | 39 | 4 | 10.26 | 2 | 5.13 | 2 | 5.13 | 2 | 5.13 | 1 | 2.56 | 1 | 2.56 | 1 | 2.56 | 2 | 5.13 | 1 | 2.56 |
| 2014 | 117 | 11 | 9.40 | 3 | 2.56 | 18 | 15.38 | 15 | 12.82 | 2 | 1.71 | 4 | 3.42 | 3 | 2.56 | 3 | 2.56 | 4 | 3.42 |
| 2015 | 105 | 9 | 8.57 | 15 | 14.29 | 4 | 3.81 | 3 | 2.86 | 2 | 1.90 | 3 | 2.86 | 2 | 1.90 | 4 | 3.81 | 3 | 2.86 |
| 2016 | 182 | 17 | 9.34 | 9 | 4.95 | 25 | 13.74 | 11 | 6.04 | 4 | 2.20 | 5 | 2.75 | 4 | 2.20 | 3 | 1.65 | 5 | 2.75 |
| 2017 | 217 | 21 | 9.68 | 17 | 7.83 | 25 | 11.52 | 18 | 8.29 | 4 | 1.84 | 6 | 2.76 | 4 | 1.84 | 7 | 3.23 | 7 | 3.23 |
| 2018 | 200 | 19 | 9.50 | 13 | 6.50 | 27 | 13.50 | 15 | 7.50 | 3 | 1.50 | 6 | 3.00 | 4 | 2.00 | 4 | 2.00 | 6 | 3.00 |
| 2019 | 230 | 21 | 9.13 | 19 | 8.26 | 31 | 13.48 | 14 | 6.09 | 5 | 2.17 | 6 | 2.61 | 5 | 2.17 | 9 | 3.91 | 8 | 3.48 |
| 2020 | 197 | 18 | 9.14 | 13 | 6.60 | 21 | 10.66 | 16 | 8.12 | 6 | 3.05 | 4 | 2.03 | 4 | 2.03 | 7 | 3.55 | 7 | 3.55 |
| 2021 | 208 | 19 | 9.13 | 14 | 6.73 | 28 | 13.46 | 15 | 7.21 | 6 | 2.88 | 6 | 2.88 | 5 | 2.40 | 8 | 3.85 | 6 | 2.88 |
| 2022 | 164 | 14 | 8.54 | 11 | 6.71 | 22 | 13.41 | 13 | 7.93 | 3 | 1.83 | 4 | 2.44 | 4 | 2.44 | 7 | 4.27 | 5 | 3.05 |
| Total | 1659 | 153 | 9.22 | 116 | 6.99 | 203 | 12.24 | 122 | 7.35 | 36 | 2.17 | 45 | 2.71 | 36 | 2.17 | 54 | 3.25 | 52 | 3.13 |
| Chi-square trend value | 0.012 | 9.823 | 9.788 | 9.974 | 0.595 | 0.098 | 0.493 | 1.327 | 0.715 | ||||||||||
| p value | 0.999 | < 0.01 | < 0.01 | < 0.01 | 0.743 | 0.952 | 0.781 | 0.515 | 0.916 | ||||||||||
3.4 Drug Resistance of Strains From Different Types of Patients
The drug resistance rate, multidrug resistance rate, and poly-drug resistance rate of isolates from patients with re-treatment were all higher than those from patients undergoing primary treatment, as shown in Table 4.
| Certain year | Primary patient culture strain | Re-treatment patient culture strain | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Total bacteria number of strains | Number of resistant strains | Drug resistance rate of strain (%) | Number of multidrug-resistant strains | Multidrug resistance rate of strain (%) | Number of single drug-resistant strains | Single drug resistance rate of strain (%) | Number of multidrug-resistant strain | Multidrug resistance rate of strain (%) | Total bacteria number of strains | Number of resistant strains | Drug resistance rate of strain (%) | Number of multidrug-resistant strains | Multidrug resistance rate of strain (%） | Number of single drug- resistant strains | Single drug resistance rate of strain (%) | Number of multidrug- resistant strain | Multidrug resistance rate of strain (%) | |
| 2013 | 33 | 8 | 24.24 | 1 | 3.03 | 4 | 12.12 | 1 | 3.03 | 6 | 2 | 33.33 | 1 | 16.67 | 1 | 16.67 | 1 | 16.67 |
| 2014 | 107 | 27 | 25.23 | 2 | 1.87 | 16 | 14.95 | 5 | 4.67 | 10 | 4 | 40.00 | 2 | 20.00 | 1 | 10.00 | 2 | 20.00 |
| 2015 | 96 | 25 | 26.04 | 2 | 2.08 | 14 | 14.58 | 6 | 6.25 | 9 | 3 | 33.33 | 1 | 11.11 | 2 | 22.22 | 2 | 22.22 |
| 2016 | 168 | 41 | 24.40 | 4 | 2.38 | 27 | 16.07 | 10 | 5.95 | 14 | 5 | 35.71 | 2 | 14.29 | 2 | 14.29 | 4 | 28.57 |
| 2017 | 199 | 53 | 26.63 | 4 | 2.01 | 32 | 16.08 | 12 | 6.03 | 18 | 6 | 33.33 | 3 | 16.67 | 3 | 16.67 | 5 | 27.78 |
| 2018 | 181 | 51 | 28.18 | 3 | 1.66 | 30 | 16.57 | 13 | 7.18 | 19 | 6 | 31.58 | 3 | 15.79 | 3 | 15.79 | 5 | 26.32 |
| 2019 | 213 | 51 | 23.94 | 7 | 3.29 | 31 | 14.55 | 11 | 5.16 | 17 | 7 | 41.18 | 3 | 17.65 | 3 | 17.65 | 3 | 17.65 |
| 2020 | 180 | 47 | 26.11 | 5 | 2.78 | 27 | 15.00 | 12 | 6.67 | 17 | 6 | 35.29 | 3 | 17.65 | 4 | 23.53 | 3 | 17.65 |
| 2021 | 193 | 49 | 25.39 | 6 | 3.36 | 28 | 14.51 | 12 | 6.22 | 15 | 5 | 33.33 | 3 | 20.00 | 2 | 13.33 | 3 | 20.00 |
| 2022 | 148 | 37 | 25.00 | 5 | 3.57 | 22 | 14.86 | 8 | 5.41 | 16 | 6 | 37.50 | 2 | 12.50 | 3 | 18.75 | 3 | 18.75 |
| Chi square trend value | 1518 | 0.0117 | 0.131 | 0.224 | 0.809 | 141 | 0.369 | 0.565 | 0.129 | 0.088 | ||||||||
| p value | 0.943 | 0.963 | 0.494 | 0.641 | 0.832 | 0.754 | 0.938 | 0.957 | ||||||||||
4 Conclusion and Comment
The resistance rate of 1659 MTB isolates from patients with primary treatment was 25.55%, and 35.46% for those with re-treatment. These rates were lower than those reported in Hebei Province, specifically 33.07% for primary treatment and 44.19% for re-treatment [5]. The rate of multi-drug resistance from patients with primary treatment was 2.57%, which was lower than the rate in Hebei Province (5.52%). The rate of multi-drug resistance from patients with re-treatment was 16.31%, which was higher than the rate in Hebei Province (6.98%).
The total resistance rate of MTB isolates was 26.40%, which was lower than the national resistance baseline survey (39.12%) and Hebei Province (34.20%), but higher than Beijing City (24.83%) [6], Shanghai Municipality (21.00%), and Fujian Province (19.04%) [7], and comparable to Gansu Province (26.26%) [8].
The multidrug resistance rate of 3.74% was lower than those reported in Beijing (5.28%), Shanghai (4.98%), Fujian (3.84%), and Gansu provinces (8.44%), as well as the national average level (4.50%) and the baseline survey on drug resistance of TB in China (8.32%) [9, 10]. It was also lower than the rate of multi-drug resistance (4.90%) [11]. The 2007 province-wide multi-drug resistance baseline survey in Guangdong Province indicated that Guangzhou has made progress in monitoring MDR-TB epidemic surveillance, preventive control, and treatment follow-up. More patients with drug-resistant re-treatment may be not included in the surveillance due to seeking medical attention at higher-level or out-of-province hospitals.
The rates of drug resistance and multi-drug resistance in primary treatment patients were lower than those in re-treatment patients, but the absolute number of drug-resistant patients and multi-drug resistance in primary treatment patients was much higher. Primary-treatment patients were individuals who had never used drugs or had been using drugs for less than a month, potentially resulting in a high prevalence of primary drug resistance. A study by Meijian showed that primary drug resistance was an important reason for the emergence of drug-resistant TB at present.
Therefore, it is particularly important to actively carry out screening for drug resistance to anti-TB drugs, expediting the development and implementation of TB testing methods with high sensitivity and good specificity, aiming to increase the positive detection rate of pathogens. This endeavor facilitates the early identification of patients with drug-resistant TB, thereby reinforcing the treatment of primary patients and ensuring rigorous tracking and follow-up management of TB patients. Such measures are instrumental in bolstering treatment adherence among primary patients and increasing the cure rate.
The rates of multi-drug resistance and drug resistance in re-treatment patients were higher than those in primary-treatment patients, and a history of anti-TB treatment may serve as a risk factor for the development of drug resistance and multi-drug resistance. It may also be related to the high medical cost, poor treatment compliance, and irregular or inappropriate medication use among re-treatment patients. Consequently, prompt drug sensitivity testing is imperative for re-treatment-resistant patients, and a reasonable and effective chemotherapy regimen should be formulated based on the results of drug sensitivity testing to improve the cure rate and further mitigating the progression of drug resistance.
The rates of drug resistance and multidrug resistance were higher in men compared to women. This may be attributed to the higher prevalence of smoking and alcohol consumption among male patients. Additionally, it may be related to the greater variability in men's workplaces, which may lead to irregular treatment. Thus, it is important to enhance the frequency and rigor of tracking and follow-up treatments for male patients.
The age group of 40–59 years old exhibited the highest drug resistance rate, which may be related to the high pressure of study, work, life, and mental stress, similar to the results from Gansu Province [8].
In addition, drug resistance posed a significant hindrance to the effective prevention and treatment of TB [12]. TB, an infectious disease that is both curable and preventable, becomes difficult to treat when resistance develops against the most effective and tolerable first-line anti-TB drugs [13].
The annual resistance rates of MTB strains isolated from Yuexiu District in Guangzhou City showed an overall increasing trend for RFP, EMB, and Sm, while showing an overall decreasing trend for INH, Km, and PAS. The resistance rate to Ofx (2.71%) was lower than the national level (3.49%), as well as those reported in Hunan Province (5.02%) [14] and Fujian Province (5.02%) [4]. This discrepancy may be related to the adjustment of the clinical treatment program for TB in Guangdong Province in the last 10 years, which has discontinued the use Ofx.
In summary, the problem of drug-resistant TB in Yuexiu District, Guangzhou City, still requires great attention. The implementation of drug-resistant screening among TB patients should be further strengthened. Timely conduct of drug sensitivity tests is essential, and reasonable and effective treatment programs should be formulated to improve the cure rates and thus mitigate the spread of drug-resistant TB.
Author Contributions
Conception and design: Xueqiu Li. Analyze and process data: Xueqiu Li. Drafted the manuscript: Xueqiu Li. Review and editing: Xueqiu Li and Jianxiong Liu.
Acknowledgments
This study was supported by the Guangzhou Municipal Health Science and Technology Project (20241A011048) and Guangzhou Science and Technology Program (2023A03J0539).
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
The authors have nothing to report.
