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1.
Medicine (Baltimore) ; 103(40): e39995, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39465692

RESUMEN

Despite widespread application during the coronavirus disease-19 pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection using patient-performed rapid antigen tests (RATs) is limited, especially regarding the Delta and Omicron variants. Therefore, in this study, we evaluated the performance of RATs in identifying Delta and Omicron infections in self-test settings. In this multicenter clinical performance study conducted in Korea between November 2021 and February 2022, we included participants without prior diagnostic device experience. Using 2 RAT types, we compared the results with real-time reverse transcriptase-polymerase chain reaction testing, focusing on clinical sensitivity and specificity. Reverse transcriptase-polymerase chain reaction helped confirm 77 SARS-CoV-2 infections among 280 participants. RATs exhibited high positive agreement for Omicron detection but lower rates for Delta, especially among partially vaccinated individuals. This study provides direct evidence that RATs, originally developed for ancestral strains of SARS-CoV-2, effectively detect major variants such as Delta and Omicron in real patient/clinical settings. By confirming variant presence through sequencing, our research offers significant and novel insights into the performance of RATs, particularly in the context of breakthrough infections postvaccination, with precise data on vaccination status and timing obtained from government records.


Asunto(s)
COVID-19 , SARS-CoV-2 , Sensibilidad y Especificidad , SARS-CoV-2/inmunología , COVID-19/diagnóstico , Humanos , Estudios Prospectivos , Masculino , Femenino , Prueba Serológica para COVID-19/métodos , Persona de Mediana Edad , Adulto , República de Corea , Anciano , Antígenos Virales
2.
Artículo en Inglés | MEDLINE | ID: mdl-39343425

RESUMEN

BACKGROUND: This study aimed to determine whether a shorter high-dose rifampicin regimen is non-inferior to the standard 6-month tuberculosis regimen. METHOD: This multicenter, randomized, open-label, non-inferiority trial enrolled participants with respiratory specimen positivity by Xpert MTB/RIF assay or Mycobacterium tuberculosis culture without rifampicin-resistance. Participants were randomized at 1:1 to the investigational or control group. The investigational group received high-dose rifampicin (30 mg/kg/day), isoniazid, and pyrazinamide until culture conversion, followed by high-dose rifampicin and isoniazid for 12 weeks. The control group received the standard 6-month regimen. The primary outcome was the rate of unfavorable outcomes at 18 months post-randomization. The non-inferiority margin was set at <6% difference in unfavorable outcomes rates. RESULTS: Between 4 November 2020 and 3 January 2022, 76 participants were enrolled. Of these, 58 were included in the modified intention-to-treat analysis. Unfavorable outcomes occurred in 10 (31.3%) of 32 in the control group and 10 (38.5%) of 26 in the investigational group. The difference was 7.2% (95% confidence interval, ∞ to 31.9%), failing to prove non-inferiority. Serious adverse events and grade 3 or higher adverse events did not differ between the groups. CONCLUSIONS: The shorter high-dose rifampicin regimen failed to demonstrate non-inferiority but had an acceptable safety profile. Trial registration ClinicalTrials.gov NCT04485156.

3.
Korean J Intern Med ; 39(4): 640-649, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38910510

RESUMEN

BACKGROUND/AIMS: This study aimed to investigate the timing and predictors of death during treatment among patients with multidrug/rifampin-resistant tuberculosis (MDR/RR-TB) in South Korea. METHODS: This was a retrospective cohort study that included MDR/RR-TB cases notified between 2011 and 2017 in South Korea. RESULTS: Among 7,226 MDR/RR-TB cases, 699 (9.7%) died at a median of 167 days (IQR 51-358 d) from the initiation of MDR-TB treatment. The cumulative proportion of all-cause death was 35.5% at 90 days and 52.8% at 180 days from treatment initiation. TB-related deaths occurred at a median of 133 days (IQR 32-366 d), which was significantly earlier than the median of 184 days (IQR 68-356 d) for non-TB-related deaths (p = 0.002). In a multivariate analysis, older age was the factor most strongly associated with death, with those aged ≥ 75 years being 68 times more likely to die (aHR 68.11, 95% CI 21.75-213.26), compared those aged ≤ 24 years. In addition, male sex, comorbidities (cancer, human immunodeficiency virus, and end stage renal disease), the lowest household income class, and TB-specific factors (previous history of TB treatment, smear positivity, and fluoroquinolone resistance) were identified as independent predictors of all-cause death. CONCLUSION: This nationwide study highlights increased deaths during the intensive phase and identifies high-risk groups including older people and those with comorbidities or socioeconomic vulnerabilities. An integrated and comprehensive strategy is required to reduce mortality in patients with MDR/RR-TB, particularly focusing on the early stages of treatment and target populations.


Asunto(s)
Antituberculosos , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Masculino , República de Corea/epidemiología , Estudios Retrospectivos , Femenino , Tuberculosis Resistente a Múltiples Medicamentos/mortalidad , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Persona de Mediana Edad , Adulto , Anciano , Factores de Tiempo , Factores de Riesgo , Adulto Joven , Antituberculosos/uso terapéutico , Antituberculosos/efectos adversos , Rifampin/uso terapéutico , Factores de Edad , Comorbilidad , Adolescente , Resultado del Tratamiento , Causas de Muerte , Medición de Riesgo
4.
Sci Rep ; 14(1): 13162, 2024 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-38849439

RESUMEN

Predicting outcomes in pulmonary tuberculosis is challenging despite effective treatments. This study aimed to identify factors influencing treatment success and culture conversion, focusing on artificial intelligence (AI)-based chest X-ray analysis and Xpert MTB/RIF assay cycle threshold (Ct) values. In this retrospective study across six South Korean referral centers (January 1 to December 31, 2019), we included adults with rifampicin-susceptible pulmonary tuberculosis confirmed by Xpert assay from sputum samples. We analyzed patient characteristics, AI-based tuberculosis extent scores from chest X-rays, and Xpert Ct values. Of 230 patients, 206 (89.6%) achieved treatment success. The median age was 61 years, predominantly male (76.1%). AI-based radiographic tuberculosis extent scores (median 7.5) significantly correlated with treatment success (odds ratio [OR] 0.938, 95% confidence interval [CI] 0.895-0.983) and culture conversion at 8 weeks (liquid medium: OR 0.911, 95% CI 0.853-0.973; solid medium: OR 0.910, 95% CI 0.850-0.973). Sputum smear positivity was 49.6%, with a median Ct of 26.2. However, Ct values did not significantly correlate with major treatment outcomes. AI-based radiographic scoring at diagnosis is a significant predictor of treatment success and culture conversion in pulmonary tuberculosis, underscoring its potential in personalized patient management.


Asunto(s)
Inteligencia Artificial , Esputo , Tuberculosis Pulmonar , Humanos , Masculino , Femenino , Persona de Mediana Edad , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/diagnóstico por imagen , Estudios Retrospectivos , Resultado del Tratamiento , Anciano , Esputo/microbiología , Adulto , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Rifampin/uso terapéutico , República de Corea , Tomografía Computarizada por Rayos X/métodos , Antituberculosos/uso terapéutico , Radiografía Torácica/métodos
5.
J Clin Med ; 13(10)2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38792481

RESUMEN

Background/Objectives: This study explores the impact of QMAC-DST, a rapid, fully automated phenotypic drug susceptibility test (pDST), on the treatment of tuberculosis (TB) patients. Methods: This pre-post comparative study, respectively, included pulmonary TB patients who began TB treatment between 1 December 2020 and 31 October 2021 (pre-period; pDST using the Löwenstein-Jensen (LJ) DST (M-kit DST)) and between 1 November 2021 and 30 September 2022 (post-period; pDST using the QMAC-DST) in five university-affiliated tertiary care hospitals in South Korea. We compared the turnaround times (TATs) of pDSTs and the time to appropriate treatment for patients whose anti-TB drugs were changed based on these tests between the groups. All patients were permitted to use molecular DSTs (mDSTs). Results: A total of 182 patients (135 in the M-kit DST group and 47 in the QMAC-DST group) were included. The median TAT was 36 days for M-kit DST (interquartile range (IQR), 30-39) and 12 days for QMAC-DST (IQR, 9-15), with the latter being significantly shorter (p < 0.001). Of the total patients, 10 (5.5%) changed their anti-TB drugs based on the mDST or pDST results after initiating TB treatment (8 in the M-kit DST group and 2 in the QMAC-DST group). In the M-kit DST group, three (37.5%) patients changed anti-TB drugs based on the pDST results. In the QMAC-DST group, all changes were due to mDST results; therefore, calculating the time to appropriate treatment for patients whose anti-TB drugs were changed based on pDST results was not feasible. In the QMAC-DST group, 46.8% of patients underwent the first-line line probe assay compared to 100.0% in the M-kit DST group (p < 0.001), indicating that rapid QMAC-DST results provide quicker assurance of the ongoing treatment by confirming susceptibility to the current anti-TB drugs. Conclusions: QMAC-DST delivers pDST results more rapidly than LJ-DST, ensuring faster confirmation for the current treatment regimen.

6.
Clin Infect Dis ; 78(6): 1690-1697, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38563246

RESUMEN

BACKGROUND: Improving health-related quality of life (HRQOL) has emerged as a priority in the management of nontuberculous mycobacterial pulmonary disease (NTM-PD). We aimed to evaluate HRQOL and its changes after 6 months' treatment in patients with NTM-PD. METHODS: The NTM-KOREA is a nationwide prospective cohort enrolling patients initiating treatment for NTM-PD in 8 institutions across South Korea. We conducted the Quality of Life-Bronchiectasis (QOL-B) at 6-month intervals and evaluated baseline scores (higher scores indicate better quality of life) and changes after 6 months' treatment. Multivariate logistic regression was performed to identify factors associated with improvement in the QOL-B physical functioning and respiratory symptoms domains. RESULTS: Between February 2022 and August 2023, 411 patients were included in the analysis. Baseline scores (95% confidence interval [CI]) for physical functioning and respiratory symptoms were 66.7 (46.7-86.7) and 81.5 (70.4-92.6), respectively. Among 228 patients who completed the QOL-B after 6 months' treatment, improvements in physical functioning and respiratory symptoms were observed in 61 (26.8%) and 71 (31.1%) patients, respectively. A lower score (adjusted odds ratio; 95% CI) for physical functioning (0.93; 0.91-0.96) and respiratory symptoms (0.92; 0.89-0.95) at treatment initiation was associated with a greater likelihood of physical functioning and respiratory symptom improvement, respectively; achieving culture conversion was not associated with improvement in physical functioning (0.62; 0.28-1.39) or respiratory symptoms (1.30; 0.62-2.74). CONCLUSIONS: After 6 months of antibiotic treatment for NTM-PD, HRQOL improved in almost one-third, especially in patients with severe initial symptoms, regardless of culture conversion. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT03934034.


Asunto(s)
Antibacterianos , Infecciones por Mycobacterium no Tuberculosas , Calidad de Vida , Humanos , Masculino , Femenino , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/microbiología , República de Corea , Antibacterianos/uso terapéutico , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Micobacterias no Tuberculosas/efectos de los fármacos , Resultado del Tratamiento
7.
Tuberc Respir Dis (Seoul) ; 87(3): 302-308, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38547859

RESUMEN

In cases where pulmonary tuberculosis (PTB) is not microbiologically diagnosed via sputum specimens, bronchoscopy has been the conventional method to enhance diagnostic rates. Although the additional benefit of bronchoscopy in diagnosing PTB is well-known, its overall effectiveness remains suboptimal. This review introduces several strategies for improving PTB diagnosis via bronchoscopy. First, it discusses how bronchoalveolar lavage or an increased number of bronchial washings can increase specimen abundance. Second, it explores how thin or ultrathin bronchoscopes can achieve specimen acquisition closer to tuberculosis (TB) lesions. Third, it highlights the importance of conducting more sensitive TB-polymerase chain reaction tests on bronchoscopic specimens, including the Xpert MTB/RIF assay and the Xpert MTB/RIF Ultra assay. Finally, it surveys the implementation of endobronchial ultrasound with a guide sheath for tuberculomas, collection of post-bronchoscopy sputum, and reduced use of lidocaine for local anesthesia. A strategic combination of these approaches may enhance the diagnostic rates in PTB patients undergoing bronchoscopy.

8.
Respirology ; 29(4): 333-339, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38379178

RESUMEN

BACKGROUND AND OBJECTIVE: Next-generation sequencing (NGS) analysis is considered standard for lung cancer diagnosis in clinical practice. Little is known about the feasibility of NGS using tumour tissue sampled with a 1.1 mm-diameter cryoprobe. We aimed to investigate the suitability of specimens obtained by transbronchial cryobiopsy (TBC) using a 1.1 mm-diameter cryoprobe for NGS analysis. METHODS: Patients with lung cancer who underwent TBC using a 1.1 mm-diameter cryoprobe for NGS testing between October 2020 and April 2023 were enrolled. A 4.0- or 3.0 mm-diameter bronchoscope with radial probe endobronchial ultrasound and virtual bronchoscopic navigation was used to detect peripheral lung lesions. All procedures were performed under fluoroscopic guidance. Data were analysed retrospectively. RESULTS: A total of 56 patients underwent TBC using a 1.1 mm cryoprobe for NGS testing, during the study period. Most patients (98%) were in the advanced stage of lung cancer (recurrent or inoperable disease of stages III or IV). The diagnostic yield of NGS for DNA and RNA sequencing was 95% each (53 of 56). Moderate bleeding was noted in three patients (5%) and none of the study patients developed life-threatening complications, such as pneumothorax or lung infection. CONCLUSION: TBC using a 1.1 mm-diameter cryoprobe is a useful and safe tool for NGS analysis, for both DNA and RNA sequencing.


Asunto(s)
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Estudios Retrospectivos , Broncoscopía/métodos , Pulmón/diagnóstico por imagen , Pulmón/patología , Secuenciación de Nucleótidos de Alto Rendimiento , ADN , Biopsia/métodos
9.
Korean J Intern Med ; 39(2): 306-317, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38317270

RESUMEN

BACKGROUND/AIMS: To determine whether metformin, which is considered a host-directed therapy for tuberculosis (TB), is effective in improving the prognosis of patients with TB and diabetes mellitus (DM), who have higher mortality than those without DM. METHODS: This cohort study included patients who were registered as having TB in the National Tuberculosis Surveillance System. The medical and death records of matched patients were obtained from the National Health Information Database and Statistics Korea, respectively, and data from 2011 to 2017 were collected retrospectively. We classified patients according to metformin use among participants who used diabetes drugs for more than 28 days. The primary outcome was all-cause mortality during TB treatment. Double propensity score adjustment was applied to reduce the effects of confounding and multivariable Cox proportional hazard models were used to estimate adjusted hazard ratio (aHR) with 95% confidence interval (CI). RESULTS: The all-cause mortality rate during TB treatment was lower (9.5% vs. 12.4%, p < 0.01) in the metformin user group. The hazard of death due to all causes after double propensity score adjustment was also lower in the metformin user group (aHR 0.76, 95% CI 0.67-0.86, p < 0.01). There was no significant difference in mortality between metformin users and non-users for TB-related deaths (p = 0.22); however, there was a significant difference in the non-TB-related deaths (p < 0.01). CONCLUSION: Metformin use in patients with TB-DM co-prevalence is associated with reduced all-cause mortality, suggesting the potential for metformin adjuvant therapy in these patients.


Asunto(s)
Diabetes Mellitus Tipo 2 , Metformina , Tuberculosis , Humanos , Metformina/efectos adversos , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Estudios Retrospectivos , Tuberculosis/tratamiento farmacológico , Hipoglucemiantes/efectos adversos
11.
PLoS One ; 18(12): e0295556, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38096233

RESUMEN

Despite its significant impact on mortality, tuberculosis (TB)-diabetes mellitus (DM) co-prevalence has not been well-elucidated for the cause of death. We investigated the impact of DM on TB-related and non-TB-related deaths in patients with TB. This retrospective nationwide cohort study included patients diagnosed with TB between 2011 and 2017 in South Korea. We performed Fine and Gray regression model analyses to assess the mortality risk of DM classified by cause of death. Of 239,848 patients, 62,435 (26.0%) had DM, and 20,203 died during anti-TB treatment. Of all deaths, 47.9% (9,668) were caused by TB, and the remaining 52.1% (10,535) was attributed to various non-TB-related causes. The mortality rate was higher in the DM than in the non-DM groups in both men and women. DM was associated with a higher risk of TB-related (adjusted hazard ratio [aHR] 1.07, 95% confidence interval [CI] 1.01-1.13) and non-TB-related (aHR 1.21, 95% CI 1.15-1.27) deaths in men; however, only a higher risk of non-TB-related deaths (aHR 1.29, 95% CI 1.20-1.38) in women. Our findings indicate that DM is independently associated with a greater risk of death during anti-TB treatment among patients with TB for both TB-related and non-TB-related deaths.


Asunto(s)
Diabetes Mellitus , Tuberculosis , Masculino , Humanos , Femenino , Estudios de Cohortes , Estudios Retrospectivos , Causas de Muerte , Tuberculosis/diagnóstico , Factores de Riesgo
12.
ERJ Open Res ; 9(4)2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37583964

RESUMEN

Background: This study evaluated the risk factors of long-term mortality in patients with multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) in South Korea who were lost to follow-up (LTFU). Methods: This was a retrospective longitudinal follow-up study using an integrated database constructed by data linkage of the three national databases, which included 7226 cases of MDR/RR-TB notified between 2011 and 2017 in South Korea. Post-treatment outcomes of patients who were LTFU were compared with those of patients who achieved treatment success. Results: Of the 7226 MDR/RR-TB cases, 730 (10.1%) were LTFU. During a median follow-up period of 4.2 years, 101 (13.8%) of the LTFU patients died: 25 deaths (3.4%) were TB related and 76 (10.4%) were non-TB related. In the LTFU group, the adjusted hazard ratio (aHR) of all-cause mortality (aHR 2.50, 95% CI 1.99-3.15, p<0.001), TB-related mortality (aHR 5.38, 95% CI 3.19-9.09, p<0.001) and non-TB-related mortality (HR 2.21, 95% CI 1.70-2.87, p<0.001) was significantly higher than that in the treatment success group. Independent risk factors for all-cause mortality in the LTFU group were age >55 years, fluoroquinolone resistance, cancer and no retreatment. In the LTFU patients who did not receive retreatment, the risk of non-TB-related mortality (aHR 5.00, 95% CI 1.53-16.37, p=0.008) and consequent all-cause mortality (aHR 2.18, 95% CI 1.08-4.40, p=0.030) was significantly higher than that of patients who received retreatment. Conclusion: Non-TB-related mortality was the main cause of death and might be reduced by retreatment in LTFU patients with MDR/RR-TB.

13.
Infect Drug Resist ; 16: 5233-5242, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37589016

RESUMEN

Purpose: Isoniazid-monoresistant tuberculosis (Hr-TB) has emerged as a global challenge, necessitating detailed guidelines for its diagnosis and treatment. We aim to consolidate the Korean guidelines for Hr-TB management by gathering expert opinions and reaching a consensus. Patients and Methods: A conventional Delphi method involving two rounds of surveys was conducted with 96 experts selected based on their clinical and research experience and involvement in nationwide tuberculosis studies and development of the Korean guidelines on tuberculosis. The survey consisted of three sections of questionnaires on diagnosis, treatment, and general opinions on Hr-TB. Results: Among the 96 experts, 72 (75%) participated in the two rounds of the survey. A majority of experts (96%) strongly agreed on the necessity of molecular drug susceptibility testing (DST) for isoniazid and rifampin resistance in all tuberculosis patients and emphasized the importance of interpreting mutation types (inhA or katG) and additional molecular DST for fluoroquinolones for confirmed isoniazid-resistant cases. Over 95.8% of experts recommended treating Hr-TB with a combination of rifampin, ethambutol, pyrazinamide, and levofloxacin for six months, without exceeding 12 months unless necessary. They also acknowledged the drawbacks of long-term pyrazinamide use due to its side effects and agreed on shortening its duration by extending the duration of the rest of the treatment with a modified combination of choice. Conclusion: This Delphi survey enabled Korean tuberculosis experts to reach a consensus on diagnosing and treating Hr-TB. These findings will be valuable for developing the upcoming revised Korean guidelines for Hr-TB management.

14.
Respir Med ; 217: 107338, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37380091

RESUMEN

OBJECTIVES: Transbronchial cryobiopsy (TBCB) is a novel technique for the diagnosis of peripheral lung lesions (PLLs). We aim to evaluate the clinical outcomes of TBCB using a new 1.1-mm diameter cryoprobe for the diagnosis of PLLs. MATERIALS AND METHODS: We performed a prospective observational pilot study on the diagnosis of PLLs (diameter ≤30 mm) by TBCB, using a 1.1-mm diameter cryoprobe with radial endobronchial ultrasound (RP-EBUS), virtual bronchoscopic navigation and fluoroscopy from December 2021 to July 2022. Primary outcome was the pathological diagnostic yield of TBCB, and secondary outcome was adverse event. RESULTS: A total of 50 patients were enrolled (mean lesion size, 21 mm). TBCB was performed in 49 patients up to three times except for the one with "invisible" finding on RP-EBUS. The overall diagnostic yield of TBCB was 90% (45/50). There was no difference in the diagnostic yield between size (20 mm vs. 20-30 mm; 88% [22/25] vs. 92% [23/25]; P = 1.000), RP-EBUS findings (concentric vs. others; 97% [28/29] vs. 81% [17/21]; P = 0.148), and acute angle location (apical segment of both upper lobes vs. others; 92% [12/13] vs. 89% [33/37]; P = 1.000). The cumulative diagnostic yields of the first, second, and third TBCB were 82% (41/50), 88% (44/50), and 90% (45/50), respectively. Mild bleeding was developed in 56% (28/50), and moderate bleeding was found in 26% (13/50). CONCLUSION: TBCB using a 1.1-mm diameter cryoprobe is an effective, reasonable method for the diagnosis of PLLs regardless of its size, RP-EBUS finding, and anatomical location without serious complication. TRIAL REGISTRATION: Clinical Trials.Gov (NCT05046093).


Asunto(s)
Broncoscopía , Neoplasias Pulmonares , Humanos , Proyectos Piloto , Estudios Prospectivos , Biopsia/efectos adversos , Biopsia/métodos , Broncoscopía/efectos adversos , Broncoscopía/métodos , Pulmón/diagnóstico por imagen , Pulmón/patología , Neoplasias Pulmonares/patología
15.
Int J Antimicrob Agents ; 62(2): 106840, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37160240

RESUMEN

BACKGROUND: The ability of ethambutol (EMB) to suppress bacterial resistance has been demonstrated in a time-dependent manner. Through the development of a population pharmacokinetics (PK) model, this study aimed to suggest the PK/pharmacodynamics (PD) target and identify the significant covariates that influence interindividual variability (IIV) in the PK of EMB. METHODS: In total, 837 patients from 20 medical centres across Korea were enrolled in this study. The non-linear mixed-effect method was used to establish and validate the population PK model. RESULTS: A two-compartment model with transit compartment absorption was sufficient to describe the PK of EMB. Body weight and renal function were identified as significant covariates that affect IIV of the apparent clearance (CL/F) of EMB. Patients with moderate renal function showed 35% and 55% lower CL/F (CL/F 89.9 L/h) compared with those with mild and normal renal function, respectively. All the renal function groups with simulated doses ranging from 800 to 1200 mg achieved area under the curve over minimum inhibitory concentration (MIC) >119, and maintained T>MIC for >23 h for MIC of 0.5 µg/mL. Based on our simulation result, it is suggested that doses of 800, 1000, and 1200 mg should obtain the T>MIC target of 4, 6, and 8 h, respectively. This model was validated internally and externally. CONCLUSION: This study provides insight into the PK/PD indexes of EMB for three different renal function groups and T>MIC targets for different doses. The results could be used to provide optimal-dose suggestions for EMB.


Asunto(s)
Infecciones Bacterianas , Tuberculosis , Humanos , Etambutol/farmacología , Estudios Prospectivos , Tuberculosis/tratamiento farmacológico , Infecciones Bacterianas/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Antibacterianos/uso terapéutico
16.
Tuberc Respir Dis (Seoul) ; 86(3): 234-244, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37254489

RESUMEN

BACKGROUND: Effective treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis (FQr-MDR-TB) is difficult because of the limited number of available core anti-TB drugs and high rates of resistance to anti-TB drugs other than FQs. However, few studies have examined anti-TB drugs that are effective in treating patients with FQr-MDR-TB in a real-world setting. METHODS: The impact of anti-TB drug use on treatment outcomes in patients with pulmonary FQr-MDR-TB was retrospectively evaluated using a nationwide integrated TB database (Korean Tuberculosis and Post-Tuberculosis). Data from 2011 to 2017 were included. RESULTS: The study population consisted of 1,082 patients with FQr-MDR-TB. The overall treatment outcomes were as follows: treatment success (69.7%), death (13.7%), lost to follow-up or not evaluated (12.8%), and treatment failure (3.9%). On a propensity-score-matched multivariate logistic regression analysis, the use of bedaquiline (BDQ), linezolid (LZD), levofloxacin (LFX), cycloserine (CS), ethambutol (EMB), pyrazinamide, kanamycin (KM), prothionamide (PTO), and para-aminosalicylic acid against susceptible strains increased the treatment success rate (vs. unfavorable outcomes). The use of LFX, CS, EMB, and PTO against susceptible strains decreased the mortality (vs. treatment success). CONCLUSION: A therapeutic regimen guided by drug-susceptibility testing can improve the treatment of patients with pulmonary FQr-MDR-TB. In addition to core anti-TB drugs, such as BDQ and LZD, treatment of susceptible strains with later-generation FQs and KM may be beneficial for FQr-MDR-TB patients with limited treatment options.

17.
Tuberc Respir Dis (Seoul) ; 86(2): 133-141, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37005092

RESUMEN

BACKGROUND: The present study evaluated the association between participation in a rehabilitation program during a hospital stay and 1-year survival of patients requiring at least 21 days of mechanical ventilation (prolonged mechanical ventilation [PMV]) with various respiratory diseases as their main diagnoses that led to mechanical ventilation. METHODS: Retrospective data of 105 patients (71.4% male, mean age 70.1±11.3 years) who received PMV in the past 5 years were analyzed. Rehabilitation included physiotherapy, physical rehabilitation, and dysphagia treatment program that was individually provided by physiatrists. RESULTS: The main diagnosis leading to mechanical ventilation was pneumonia (n=101, 96.2%) and the 1-year survival rate was 33.3% (n=35). One-year survivors had lower Acute Physiology and Chronic Health Evaluation (APACHE) II score (20.2±5.8 vs. 24.2±7.5, p=0.006) and Sequential Organ Failure Assessment score (6.7±5.6 vs. 8.5±2.7, p=0.001) on the day of intubation than non-survivors. More survivors participated in a rehabilitation program during their hospital stays (88.6% vs. 57.1%, p=0.001). The rehabilitation program was an independent factor for 1-year survival based on the Cox proportional hazard model (hazard ratio, 3.513; 95% confidence interval, 1.785 to 6.930; p<0.001) in patients with APACHE II scores ≤23 (a cutoff value based on Youden's index). CONCLUSION: Our study showed that participation in a rehabilitation program during hospital stay was associated with an improvement of 1-year survival of PMV patients who had less severe illness on the day of intubation.

18.
BMJ Open ; 13(3): e069642, 2023 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-36889835

RESUMEN

OBJECTIVES: This study aimed to identify the prevalence of diabetes mellitus (DM) among patients with tuberculosis (TB) using a nationwide cohort in South Korea. DESIGN: A retrospective cohort study. SETTING: This study used the Korean Tuberculosis and Post-Tuberculosis cohort, which was constructed by linking the Korean National Tuberculosis Surveillance, National Health Information Database (NHID) and Statistics Korea data for the causes of death. PARTICIPANTS: During the study period, all notified patients with TB with at least one claim in the NHID were included. Exclusion criteria were age less than 20 years, drug resistance, initiation of TB treatment before the study period and missing values in covariates. OUTCOME MEASURES: DM was defined as having at least two claims of the International Classification of Diseases (ICD) code for DM or at least one claim of the ICD code for DM and prescription of any antidiabetic drugs. Newly diagnosed DM (nDM) and previously diagnosed DM (pDM) were defined as DM diagnosed after and before TB diagnosis, respectively. RESULTS: A total of 26.8% (70 119) of patients were diagnosed with DM. The age-standardised prevalence increased as age increased or income decreased. Patients with DM were more likely to be men, older, had the lowest income group, had more acid-fast bacilli smear and culture positivity, had a higher Charlson Comorbidity Index score and had more comorbidities compared with patients without DM. Approximately 12.5% (8823) patients had nDM and 87.4% (61 296) had pDM among those with TB-DM. CONCLUSIONS: The prevalence of DM among patients with TB was considerably high in Korea. To achieve the goal of TB control and improve the health outcomes of both TB and DM, integrated screening of TB and DM and care delivery in clinical practice are necessary.


Asunto(s)
Diabetes Mellitus , Tuberculosis , Masculino , Humanos , Adulto Joven , Adulto , Femenino , Estudios de Cohortes , Estudios Retrospectivos , Prevalencia , Factores de Riesgo , Diabetes Mellitus/epidemiología , Diabetes Mellitus/diagnóstico , Tuberculosis/complicaciones , Tuberculosis/epidemiología , Tuberculosis/diagnóstico , República de Corea/epidemiología
19.
Thorac Cancer ; 14(9): 834-839, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36724807

RESUMEN

OBJECTIVE: For thoracoscopy, the usefulness of a dye mixture of indigo carmine and Lipiodol for localizing lung lesions has been reported. However, little is known about the stability and safety of this dye mixture injected on the visceral pleura through a bronchoscope. METHODS: Porcine models were divided into three groups according to the detection time of the dye mixture: group A with a detection time of 4 h; group B, 8 h; and group C, 24 h. A dye mixture of indigo carmine and Lipiodol (0.5 mL each) was sprayed onto the visceral pleura both in the ventral and dorsal regions via a spray catheter. RESULTS: Twelve markings were created on the visceral pleura of the porcine lung (six ventral and six dorsal) in the six porcine models. At predetermined detection times, all 12 dye markings (100%) were visible on the visceral pleura. The mean longest diameter of the dye marking in the ventral and dorsal regions was 18.8 mm and 24.3 mm, respectively. In groups B and C, pathological changes in the lymphatic system, such as lymphatic dilatations, were found; minimal changes were found in group B, however, these changes with oval-shaped lymphatic cysts and Lipiodol accumulation, were more evident in group C. CONCLUSIONS: The dye mixture of indigo carmine and Lipiodol had reliable stability and visibility. In terms of safety, it may be necessary to check the dye mixture on the lung surface within 8 h.


Asunto(s)
Colorantes , Carmin de Índigo , Humanos , Porcinos , Animales , Aceite Etiodizado , Toracoscopía
20.
J Korean Med Sci ; 38(5): e33, 2023 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-36747362

RESUMEN

BACKGROUND: The treatment outcomes of patients with multidrug/rifampin-resistant (MDR/RR) tuberculosis (TB) are important indicators that reflect the current status of TB management and identify the key challenges encountered by TB control programs in a country. METHODS: We retrospectively evaluated the treatment outcomes as well as predictors of unfavorable outcomes in patients with MDR/RR-TB notified from 2011 to 2017, using an integrated TB database. RESULTS: A total of 7,226 patients with MDR/RR-TB were included. The treatment success rate had significantly increased from 63.9% in 2011 to 75.1% in 2017 (P < 0.001). Among unfavorable outcomes, the proportion of patients who failed, were lost to follow up, and were not evaluated had gradually decreased (P < 0.001). In contrast, TB-related death rate was not significantly changed (P = 0.513), while the non-TB related death rate had increased from 3.2% in 2011 to 11.1% in 2017 (P < 0.001). Older age, male sex, immigrants, low household income, previous history of TB treatment, and comorbidities were independent predictors of unfavorable outcomes. Of the 5,308 patients who were successfully treated, recurrence occurred in 241 patients (4.5%) at a median 18.4 months (interquartile range, 9.2-32.4) after completion treatment. CONCLUSION: The treatment outcomes of patients with MDR/RR-TB has gradually improved but increasing deaths during treatment is an emerging challenge for MDR-TB control in Korea. Targeted and comprehensive care is needed for vulnerable patients such as the elderly, patients with comorbidities, and those with low household incomes.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Masculino , Anciano , Rifampin/uso terapéutico , Estudios Retrospectivos , Antituberculosos/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Resultado del Tratamiento , República de Corea/epidemiología
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