Bimonthly, Established in 2001
Responsible Institution: Ministry of the Education People's Republic of China
Sponsor: Huashan Hospital, Fudan University
Eitor in-Chief: ZHANG Yingyuan
Objective To screen out the independent risk factors for cefoperazone and sulbactam - related coagulation disorder and construct a nomogram prediction model. Methods The data of 694 patients who received cefoperazone and sulbactam (2:1) treatment in the Fifth Affiliated Hospital of Guangzhou Medical University from July 2017 to December 2023 were retrospectively collected. The patients were divided into a normal coagulation group and an abnormal coagulation group. Univariate analysis and multivariate Logistic regression analysis were performed to screen the independent risk factors. A nomogram model was constructed based on the independent risk factors. The predictive efficacy of the model was evaluated by the receiver operating characteristic (ROC) curve, calibration curve, and Hosmer-Lemeshow goodness-of-fit test. Results Among the 694 patients, 156 had abnormal coagulation, with an incidence of 22.48%. Univariate analysis showed that age, age groups, hypertension, diabetes mellitus, cerebrovascular diseases, renal function, liver function, diet type, nutrition score, serum albumin, and serum creatinine were significantly different between the two groups (P < 0.05). Multivariate logistic regression analysis indicated that renal function, liver function, nutritional score, and fasting were independent risk factors for cefoperazone and sulbactam-related coagulation disorder. A nomogram model was constructed based on these independent risk factors. Internal validation: The area under ROC curve (AUC) was 0.728 (95% CI: 0.685 - 0.771), and the χ2 value of the Hosmer-Lemeshow goodness-of-fit test was 11.987 (P = 0.101), suggesting that the model had good discrimination and calibration. Conclusions Renal function, liver function, nutritional score, and fasting are independent risk factors for cefoperazone and sulbactam-related coagulation disorder. The nomogram model can directly predict the risk of medication, reminding clinicians of the risk.
Objective Analyze the plasma concentration of rifampicin in tuberculosis patients and explore the factors influencing the concentration for rational use of antimicrobial agents in clinical practice. Methods A retrospective study was conducted to collect clinical and laboratory data from patient and investigate the relevant factors affecting the plasma concentration of rifampicin. Results Overall, 40.8% of the 206 patients had rifampicin plasma concentrations below the lower limit of the reference range. Multiple linear regression analysis indicated that age and direct bilirubin (DBIL) levels were positively correlated with rifampicin plasma concentration (P < 0.05). Dosage of rifampicin, combined with human immunodeficiency virus (HIV) infection, and combined with kidney disease were significantly associated with rifampicin plasma concentrations (P < 0.05). Conclusions Low rifampicin plasma concentration was found in a high proportion of patients, underscoring the need to optimize dosing regimen based on therapeutic drug monitoring. The effects of age, dosage of rifampicin, DBIL levels, combined with HIV infection, and combined with kidney disease on rifampicin plasma concentration should be considered.
Objective To analyze the clinical characteristics of Rhodococcus equi infection in AIDS patients. Methods Clinical data were collected from the patients with AIDS and R. equi infection during the period from July 2013 to July 2023 in the Fourth People’s Hospital of Nanning. The data were analyzed retrospectively to explore the clinical characteristics, treatment, and prognosis of patients co-infected with HIV and R. equi. Results The patients infected with HIV and R. equi were clinically characterized by fever (87.0%), cough (87.0%), expectoration (82.6%) and emaciation (69.6%). Chest CT often showed opacities of large consolidation, cavity, spot, cord-like, and masses. Most of the patients had CD4+ T cell count < 50 cells /μL (87.0%). Definitive diagnosis was based on the detection of etiological pathogens. Bronchoalveolar lavage fluid, blood samples, pleural effusion, and aspirated tissue samples showed high positive rates for detection of the pathogen. Systemic antibiotic was required for the treatment. The mortality rate was 8.7%. Conclusions R. equi infection is a rare disease, which often occurs in immunocompromised subjects. The clinical manifestations are not specific. Diagnosis of R. equi infection is mainly based on detection of the pathogen. Long time is required for culture of the pathogen. It is often misdiagnosed in clinical practice. Timely diagnosis and combination therapy can improve the prognosis. The treatment of R. equi infection usually lasts 3-6 weeks in patients with normal immune function. The treatment should be extended to 3-6 months for immunocompromised patients. The primary disease should be actively treated simultaneously to improve immune function.
Objective To analyze the clinical characteristics of patients diagnosed with Streptococcus suis meningitis in Dehong Prefecture People’s Hospital from 2016 to 2023 for better diagnosis, treatment and prevention of S. suis meningitis. Methods A retrospective study was conducted on 22 cases of S. suis meningitis. The demographic and clinical data of patients, clinical manifestations of S. suis meningitis, laboratory tests, auxiliary examination results, treatment and outcomes were analyzed. Results The 22 patients with S. suis meningitis included 21 males and 1 female. The average age of patients was 51.5 (39-66) years old. All patients had a history of contact with pork or pigs before the onset of symptoms, and some of them had a history of ingesting raw pork. The peak incidence of S. suis meningitis was in the period from May to October (72.7%), The common clinical manifestations included fever (100%), headache (77.3%), neck stiffness (77.3%), and change in consciousness (68.2%). Some patients also experienced hearing loss (31.8%). Laboratory test results upon admission showed elevation in leucocyte count, procalcitonin (PCT) and C-reactive protein (CRP) (100%). The pressure of cerebrospinal fluid elevated in 10 patients (50.0%). Cerebrospinal fluid tests of 20 patients showed elevation in protein (100%), leucocyte (90.0%), and reduction in glucose (55.0%) and chloride (30.0%). Blood culture was positive in 21 patients. Cerebrospinal fluid culture was positive in 6 patients. Metagenomic next-generation sequencing of cerebrospinal fluid suggested S. suis in 1 case. CT or MRI examination showed abnormal changes in 8 patients. After diagnosis, ceftriaxone, penicillin or vancomycin combined with dexamethasone, dehydration was used. The condition was improved in 21 patients. One patient died after voluntary cessation of treatment. Conclusions S. suis meningitis has a clear association with pig, pork contact and ingesting raw pork in Dehong Prefecture. Diagnosis of S. suis meningitis is primarily based on epidemiological history, clinical symptoms, aetiological examination and related auxiliary examinations. Clinicians should be aware of the possibility of S. suis meningitis, prescribe aetiological test to confirm the diagnosis, and timely administer effective antibiotics.
Objective To elucidate the clinical manifestations, diagnostic approaches, treatment modalities, and prognostic outcomes of toxoplasmosis. Methods We retrospectively analyzed the clinical data of 16 patients diagnosed with toxoplasmosis who were admitted to the Affiliated Hospital of Southwest Medical University between November 2018 and October 2024. The analysis aimed to investigate their clinical features, diagnostic approaches, and prognostic outcomes. The patients were assigned to superficial lymph node or neurological form of toxoplasmosis based on the site of infection. Subsequently, a comparative analysis was conducted to evaluate the differences in clinical manifestations and therapeutic responses between the two subgroups. Results Sixteen patients, aged 8 to 71 years, median age 41 years, were enrolled in the study. 15 cases had a confirmed history of exposure to cats, while 1 case had a confirmed history of exposure to dogs. The duration of illness varied from 7 days to 24 months. Enlarged lymph nodes were observed in 14 cases (87.5%), while two cases presented with headaches. Increased eosinophil count was reported in one case, decreased hemoglobin levels in 4 cases, decreased albumin levels in two cases, increased erythrocyte sedimentation rate in two cases, and elevated high-sensitivity C-reactive protein levels in two cases. Elevated IgG antibody titer was reported in all cases while increased IgM antibody titer was reported in 12 cases. Ultrasound and cranial magnetic resonance imagin were the primary imaging modalities used for diagnosis. Ultrasound revealed enlargement of multiple lymph nodes in the affected regions in 14 cases, while cranial magnetic resonance imaging demonstrated multiple patchy and enhanced intracranial lesions in two cases. All superficial lymph node form of toxoplasmosis underwent histopathological examination, characterized by reactive lymph node hyperplasia and follicular nodular hyperplasia, microgranulomas in some cases. All patients received sulfamethoxazole-trimethoprim-folinic acid treatment, 6-8 weeks for the superficial lymph node form of toxoplasmosis and 10-12 weeks for the neurological form toxoplasmosis. One patient with neurological toxoplasmosis experienced left limb dyskinesia post-treatment, whereas the remaining patients achieved clinical cure. Conclusions The clinical presentation of toxoplasmosis is multifaceted and diverse. A comprehensive investigation of the epidemiological background and relevant laboratory tests is crucial for definitive diagnosis. Treatment is primarily pharmacological interventions. The outcomes are generally favorable for the majority of patients. Controlling infected felines and canines, reducing exposure to such animals, and stringent personal hygiene protocols are key preventive strategies.
Objective To assess the impact of nirmatrelvir/ritonavir on the trough concentration of voriconazole based on therapeutic drug monitoring (TDM) for adjusting the dosing regimens when voriconazole was co-administered with nirmatrelvir/ritonavir. Methods Data were collected from patients at Quanzhou First Hospital Affiliated to Fujian Medical University, who had received both voriconazole and nirmatrelvir/ritonavir between January 2023 and August 2024 and received TDM for voriconazole. The baseline data of patients, dosing regimens of nirmatrelvir/ritonavir and voriconazole, other concomitant medications, and the results of voriconazole TDM were summarized and analyzed. Results A total of 9 patients were included. The mean trough concentration of voriconazole was (3.96 ± 2.54) mg/L (range: 0.7-7.1 mg/L). The trough concentration of voriconazole was within the target range for 4 patients, above the upper limit for 4 patients, and below the lower limit for 1 patient. Six patients underwent TDM for voriconazole for more than one time. The mean trough concentration increased from 2.94 mg/L to 4.48 mg/L in 5 of the 6 patients when voriconazole was coadministered with nirmatrelvir/ritonavir. The trough concentration decreased slightly from 1.0 mg/L to 0.7 mg/L when coadministered with nirmatrelvir/ritonavir in one patient. Conclusions Co-administration with nirmatrelvir/ritonavir does not significantly decrease the trough concentration of voriconazole. The trough concentration of voriconazole increased to some extent when coadministered with nirmatrelvir/ritonavir. Voriconazole coadministered with nirmatrelvir/ritonavir is appropriate under the guidance of voriconazole TDM.
Objective To examine the clinical characteristics and treatment strategies for bloodstream infections caused by Trichosporon asteroides. Methods The clinical data of 8 patients undergoing hematopoietic stem cell transplantation (HSCT) complicated with T. asteroides bloodstream infection who were treated at Aerospace Center Hospital from April 2021 to December 2023 were retrospectively analyzed. Results The patients included 6 males and 2 females. The median age of patients was 34 years (range: 17-57 years). None of the primary diseases achieved remission before HSCT. T. asteroides bloodstream infection occurred during neutropenic phase after HSCT in 7 cases, and secondary to complex bacterial infection after HSCT in one case. 7 patients received combination antifungal therapy, including amphotericin B or liposomal amphotericin B plus voriconazole/posaconazole. Two patients achieved negative blood cultures for T. asteroides (one died from pulmonary complications 22 months later). The time to positivity (TTP) was longer than 40 hours for both cases. The remaining 6 patients died due to treatment failure, with a TTP < 40 hours. Conclusions Patients undergoing HSCT who develop T. asteroides bloodstream infections are associated with an extremely poor prognosis. Early combination antifungal therapy, granulocyte transfusion, and immune reconstitution therapy are critical interventions for improving outcomes post-positivity.
Objective To investigate the clinical features, risk factors and prognosis of Streptococcus mitis bloodstream infection in children with acute myeloid leukemia (AML). Methods A retrospective analysis was conducted on the clinical data of 82 children with AML complicated with bloodstream infection, who were admitted to Department of Hematology and Oncology of Hunan Children’s Hospital from December 2018 to July 2024. The patients were assigned to case group (S. mitis bloodstream infection, n = 32) or control group ( bloodstream infection due to other pathogens, n = 50) based on pathogens. The clinical characteristics of patients were compared betwen groups and the risk factors for S. mitis bloodstream infection were analyzed by logistic regression. Results Logistic regression analysis showed that FLAG regimen (fludarabine, cytarabine, idarubicin and granulocyte colony stimulating factor) was an independent risk factor for S. mitis bloodstream infection in AML patients (OR = 6.631, 95% CI: 2.075 - 21.195). All the children in case group presented with high fever as the initial symptom, accompanied by symptoms such as cough (37.5%, 12/32), oral ulcers (25.0%, 8/32), red and swollen gums (9.4%, 3/32), and perianal skin ulcers (3.1%, 1/32). The median (P25, P75) duration of fever was 5.0 (3.5, 10.5) days. Overall, 61.9% (13/21) of bronchopneumonia cases progressed to severe pneumonia. Antimicrobial susceptibility testing showed that all of the 31 S. mitis strains were susceptible to vancomycin and linezolid, while 96.8%, 90.3%, 74.2%, 67.7%, 51.6%, and 29.0% of the strains were susceptible to meropenem, ceftriaxone, clindamycin, levofloxacin, penicillin, erythromycin, respectively. The 30-day overall mortality rate was 6.2% (2/32). Conclusions The FLAG regimen for AML significantly increases the risk for S. mitis bloodstream infection in children with AML. Such infections are characterized by persistent fever and are prone to complications such as severe pneumonia. S. mitis is highly resistant to penicillin. It is recommended to preferentially use highly active beta-lactam antibiotics, such as ceftriaxone, to effectively reduce the risk of infection and improve treatment outcomes.
Objective To analyze the risk factors for hospital-acquired multidrug-resistant Klebsiella pneumoniae infection and antibiotic resistance profiles of the pathogen. Methods Patients were screened for those with non-multidrug resistant Klebsiella pneumoniae isolated from the specimens submitted for the first time in a tertiary A hospital from January 2018 to December 2022. Overall, 82 patients were identified with multidrug resistant K. pneumoniae after treatment for some time. These patients were included as observation group. Another 82 patients were identified with non-multidrug resistant K. pneumoniae isolated from the specimen before and after treatment in the same period in the same ward. These patients were studied as control group. The demographic and clinical data of patients were compared between the two groups. The significant factors for hospital-acquired multidrug resistant K. pneumoniae infection identified from univariate analysis were input into into multivariate logistic regression analysis. Results No significant difference was found in gender, age, department, and primary disease between the observation group and control group (P > 0.05). Statistically significant difference was found in the length of hospital stay, hospital stay before the first detection of multidrug resistant K. pneumoniae or the last detection of non-multidrug resistant K. pneumoniae, number of underlying diseases, comorbidity of heart disease, chronic lung disease or neurological disease, history of blood transfusion, history of surgery as well as the following variables between two specimen submissions: length of ICU stay, days of ventilator use, days of drainage tube use, episodes of sputum suction, days of urinary catheter use, modality of antibiotic use, use of broad-spectrum cephalosporins, fluoroquinolones, aminogly-cosides, and glycylcyclines (P < 0.05). Logistic regression analysis showed that the number of underlying diseases, comorbidity of neurological disease, days of hospital stay before the first detection of multidrug resistant K. pneumoniae or the last detection of non-multidrug resistant K. pneumoniae, days of drainage tube use between two specimen submissions, and modality of antibiotics use were independent risk factors for the acquisition of multidrug-resistant K. pneumoniae in the hospital (P < 0.05). Conclusions The days of hospital stay before the first detection of multidrug resistant K. pneumoniae or the last detection of non-multidrug resistant K. pneumoniae, the number of underlying diseases, comorbidity of neurological disease and the days of drainage tube use between two specimen submissions, and modality of antibiotics use were independent risk factors for hospital-acquired multidrug resistant K. pneumoniae infections. Timely control of these factors is critical for reducing the incidence of multi-drug resistant K. pneumoniae infection. Rational use of antibacterial drugs is beneficial for improving the outcomes of patients.
Objective To investigate the clinical features, pathogenesis, diagnosis, treatment, and prognosis of patients with hepatitis B virus (HBV) reactivation secondary to BCR-ABL tyrosine kinase inhibitors (BCR-ABL-TKIs). Methods We reported two cases of dasatinib-induced HBV reactivation in leukaemia patients in the Second Affiliated Hospital of Bengbu Medical University. Relevant literature reports were identified from PubMed, Wanfang Data, VIP, and CNKI databases since 2000, using search terms “hepatitis B virus”, “reactivation”, “imatinib”, “dasatinib”, “nilotinib”, “flumatinib”, “olverembatinib”, “bosutinib”, “ponatinib”, “BCR-ABL”, “tyrosine kinases inhibitor” and “chronic myeloid leukemia”. We examined the clinical features of patients with HBV reactivation secondary to BCR-ABL-TKIs to further understand the pathogenesis, diagnosis, prevention,treatment and prognosis of such diseases. Results The data were collected from 28 patients with HBV reactivation secondary to BCR-ABL-TKIs, including 23 males and 5 females. The average age of patients was (51.6 ± 13.1) years. Among the 28 patients, 82.1% (23/28) were HBsAg carriers. The median time from initiation of BCR-ABL-TKIs to HBV reactivation was 7.0 (4.3, 12.0) months. The BCR-ABL-TKIs used were mostly first-generation imatinib (19 cases), followed by second-generation dasatinib (7 cases) and nilotinib (2 cases). Timely antiviral therapy resulted in favourable survival outcomes, with an overall survival rate of 82.1% (23/28). Conclusions The risk of HBV reactivation caused by BCR-ABL-TKIs is high. Clinicians should be vigilant about this potential complication during treatment. Preemptive measures and timely antiviral therapy in case of HBV reactivation can significantly improve patient outcomes.
YANG Xinyi, CHEN Xinfei, LI Jin, ZHANG Han, WANG Qing, DENG Changzi, SUN Ziyong, CHEN Zhongju, HAO Qiaoxin, LIU Zhenjia, CHENG Bin, WANG Ziran, DAI Rongchen, HUANG Yuyan, ZHU Huiqing, LIU Feiyi, ZHAO Yiying, XU Yingchun, XIAO Meng
Objective To assess the diagnostic performance of a novel domestic chromogenic medium for Candida auris. Methods This study utilized 184 Candida strains, including 5 reference strains, 65 strains of C. auris, 16 strains from 5 species of the C. haemulonii complex, and 98 clinical isolates of 14 other Candida species. Species identification was performed using a domestic C. auris chromogenic medium (ATAU), with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and ribosomal DNA internal transcribed spacer sequencing serving as gold standards. In addition, the consistency in diagnostic efficacy was compared between ATAU and imported traditional Candida chromogenic agar media (CRCA) for common Candida species. The difference in species identification capability was also assessed between ATAU and novel imported C. auris chromogenic agar media (CRAU) for the C. auris-C. haemulonii complex. Results Under the culture conditions of 35°C for 48 hours, compared with the results of the gold standard identification, the sensitivity of ATAU for the identification of C. auris was 100%, the specificity was 97.4%, and the overall coincidence rate was 98.3%. One strain of C. vulturna, which belongs to the C. auris - C. haemulonii complex, was misidentified as C. auris. In addition, the strains of C. pseudohaemulonii grow slowly at the culture temperature of 35°C even if their chromogenic features were similar to those of C. auris. Therefore, they can be distinguished. However, at 30°C, it was difficult to distinguish C. duobushaemulonii and C. haemulonii from C. auris. In addition, one strain each of C. metapsilosis (1/10) and one strain C. parapsilosis (1/10) were misidentified as C. auris. The sensitivity and specificity of both ATAU and CRCA for the identification of C. albicans and C. krusei were 100%, and the agreement rate between the two methods was 100%. The sensitivity of both methods was 90.0% for identification of C. tropicalis, and the specificity was 100% and 99.4%, respectively. Both methods missed the same strain of C. tropicalis, but one strain of C. catenulata (1/7) was misidentified as C. tropicalis on CRCA. The sensitivities of both methods were 100% for identification of C. glabrata. The identification specificity was 100% for CRCA, but 99.4% for ATAU, because a strain of C. orthopsilosis (1/10) was misidentified. Both ATAU and CRAU accurately detected C. auris, performed similarly in identifying the C. haemulonii complex and the strains that are easily misidentified on ATAU. It showed lower specificity in identifying C. glabrata. Conclusions ATAU has good diagnostic performance for C. auris and common Candida species (C. albicans, C. tropicalis, C. glabrata, C. krusei). The coincidence rate with the gold standard method is greater than 97%. Especially, the sensitivity for C. auris reaches 100%. Therefore, this chromogenic medium is suitable for the screening of nosocomial infections caused by C. auris and preliminary identification of common Candida species. However, identification based on mass spectrometry can be used to confirm the results of ATAU.
Objective To explore the diagnostic value of nanopore targeted sequencing technology (NTS) for detecting non-tuberculous Mycobacterium (NTM) pulmonary disease in bronchoalveolar lavage fluid (BALF). Methods This study enrolled 89 patients who were suspected of NTM infection and admitted to Anhui Chest Hospital from January 2022 to April 2025. NTS, PCR fluorescent probe, and BACTEC MGIT 960 fully automated rapid liquid culture (BD960 method) were performed on BALF samples to detect NTM. The diagnostic performance of the three techniques were compared. Results Among 89 suspected NTM pulmonary disease patients, 76 were diagnosed. The sensitivity of NTS, PCR fluorescent probe, and BD960 method for diagnosing NTM was 86.8% (66/76), 52.6% (40/76), and 26.3% (20/76), respectively. Compared with PCR fluorescence probe and BD960, NTS showed significant differences (P < 0.05) with χ2 values of 21.073 and 56.665, respectively. NTS testing had significantly shorter turn around time than PCR and BD960 liquid culture method (t=11.94, t=117.65, P < 0.05). The area under the receiver operating characteristic curve (AUC) of the three methods for detecting NTM in BALF was 0.93, 0.76, and 0.63, respectively. The AUC of NTS method was significantly higher than PCR fluorescent probe and BD960 method. Conclusions NTS technology is promising for clinial use to diagnose NTM-related pulmonary disease.
Objective To evaluate the bioequivalence of locally produced lefamulin acetate tablets and imported lefamulin acetate tablets in healthy subjects. Methods A total of 38 healthy subjects were divided into two groups using an open, random, two-cycle, two-sequence, crossover design. Subjects in both groups took 0.6 g test preparation and reference preparation orally on day 1 and day 8 in sequence, with a washout period of at least 1 week. The concentration of lefamulin in plasma was determined by liquid chromatography-tandem mass spectrometry. The main pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.4 software. Results The mean values of main pharmacokinetic parameters Cmax, AUC0-t, and AUC0-inf of the test preparation of lefamulin were 1 481 μg/L, 8 100 μg·h/L, and 8 346 μg·h/L, respectively. The mean values of the corresponding parameters of the reference preparation were 1 518 μg/L, 8 271 μg·h/L, and 8 520 μg·h/L, respectively. The 90% confidence interval of geometric mean ratio between test and reference preparation of lefamulin for the main pharmacokinetics parameters Cmax, AUC0-t and AUC0-inf all fell in the range of 80.0% to 125.0%. Conclusions The test preparation and the reference preparation of lefamulin acetate tablets are bioequivalent in healthy Chinese adult subjects.
Objective A hypervirulent Klebsiella pneumoniae (hvKP)-induced liver abscess mice model was established by oral gavage to mimick human natural infection. The model was compared with that established by the traditional intraperitoneal injection method. The mice model successfully established by oral gavage enabled research into hvKP pathogenesis and clinical interventions. Methods The hvKP liver abscess mice model was established using both oral gavage and intraperitoneal injection methods. For the oral gavage method, the standard hvKP strain RJF293 was administered orally. Mice mortality, colony counts and histopathological changes in liver tissue were observed. The intraperitoneal injection method served as a control, with the same strain administered intraperitoneally. The expression levels of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α in liver tissue were measured by ELISA. Results The hvKP liver abscess model was established successfully by oral gavage method. The modeling success rate was 66.7% at 48 hours post-infection. Colony counts in liver tissue peaked at 48 hours (1.73×104 CFU/g tissue). Apparent abscess formation and inflammatory responses were observed in liver tissue. The intraperitoneal injection method achieved a modeling success rate of 83.3%. Colony counts in liver tissue peaked at 72 hours (2.46×108 CFU/g tissue). ELISA results showed that the concentrations of IL-1β, IL-6, and TNF-α in the liver significantly increased from 24 to 72 hours post-infection, indicating that hvKP infection activated local inflammatory responses in the liver. Conclusions A hvKP liver abscess mice model was effectively established by oral gavage method to mimick natural infection. This method is ideal for studying hvKP pathogenesis and immune responses, offering a stable and clinically reliable mice model for hvKP research, while the intraperitoneal injection method is more appropriate for antimicrobial screening and animal PK/PD studies.
Objective To analyze the types and characteristics of drug-resistant gene mutations in rifampicin-resistant tuberculosis (RR-TB) by whole-genome sequencing (WGS) and compared with the performance of the Xpert MTB/XDR assay. Methods Sixty-nine RR-TB strains isolated from Yunnan Provincial Hospital of Infectious Diseases and characterized by WGS and Xpert MTB/XDR testing between September 2020 and September 2023 were selected for analysis of drug resistance gene mutations. Results Among the 69 RR-TB strains, the resistance mutation rates for isoniazid, ethambutol, pyrazinamide, streptomycin, and fluoroquinolones were 65.2%, 52.2%, 21.7%, 47.8%, and 33.3%, respectively. Among the 45 isoniazid-resistant strains, mutations in katG gene were the most common (86.7%, 39/45). Among the 36 ethambutol-resistant strains, mutations in embB gene were predominant (91.7%, 33/36). All 15 pyrazinamide-resistant strains harbored mutations in pncA gene. Among the 33 streptomycin-resistant strains, mutations in rpsL gene were the most prevalent (72.7%, 24/33). All of the 23 fluoroquinolone-resistant strains exhibited mutations in gyrA gene. No amikacin resistance gene mutations were detected. The predominant mutation types were katG S315T, embB codon 306 mutations, pncA mutations, rpsL K43R, and gyrA mutations at codons 90, 91, or 94. Taking WGS as the reference standard, Xpert MTB/XDR testing demonstrated good sensitivity for detecting isoniazid resistance and favorable sensitivity and specificity for detecting fluoroquinolone resistance. Conclusions RR-TB strains showed relatively high rate of fluoroquinolone resistance. Xpert MTB/XDR testing has demonstrated good sensitivity and specificity for detecting fluoroquinolone resistance. It is appropriate for rapid diagnosis.