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ABSTRACT: This case emphasizes the value of meticulous observation and regular follow-up of patients receiving rifampicin therapy. The prognosis for complete improvement in renal function in such cases was excellent, with prompt recognition and discontinuation of rifampicin. Teaching patients about these possible adverse effects and encouraging immediate reporting of signs and symptoms are likely to be beneficial because acute kidney injury can manifest itself very quickly after rifampicin is started. Even if renal failure can happen with any dose of rifampicin, primary physicians must have awareness about patients on intermittent or irregular therapy and those who have previously used this medication. It is challenging to determine the prevalence of adverse reactions to common antibiotics where a state- or country-wide reporting system is absent. Along with withdrawal of the causative agent patients were treated with corticosteroids (0.5-1 mg/kg/day) for an average period of 4-12 weeks showing significant recovery of renal function.
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Antituberculosos , Nefritis Intersticial , Rifampin , Humanos , Nefritis Intersticial/inducido químicamente , Rifampin/efectos adversos , Rifampin/uso terapéutico , Antituberculosos/efectos adversos , Antituberculosos/uso terapéutico , Masculino , Granuloma/inducido químicamente , Granuloma/tratamiento farmacológico , Adulto , Femenino , Enfermedad AgudaRESUMEN
BACKGROUND: Rifampicin resistant tuberculosis remains a global health problem with almost half a million new cases annually. In high-income countries patients empirically start a standardized treatment regimen, followed by an individualized regimen guided by drug susceptibility test (DST) results. In most settings, DST information is not available or is limited to isoniazid and fluoroquinolones. Whole genome sequencing could more accurately guide individualized treatment as the full drug resistance profile is obtained with a single test. Whole genome sequencing has not reached its full potential for patient care, in part due to the complexity of translating a resistance profile into the most effective individualized regimen. METHODS: We developed a treatment recommender clinical decision support system (CDSS) and an accompanying web application for user-friendly recommendation of the optimal individualized treatment regimen to a clinician. RESULTS: Following expert stakeholder meetings and literature review, nine drug features and 14 treatment regimen features were identified and quantified. Using machine learning, a model was developed to predict the optimal treatment regimen based on a training set of 3895 treatment regimen-expert feedback pairs. The acceptability of the treatment recommender CDSS was assessed as part of a clinical trial and in a routine care setting. Within the clinical trial setting, all patients received the CDSS recommended treatment. In 8 of 20 cases, the initial recommendation was recomputed because of stock out, clinical contra-indication or toxicity. In routine care setting, physicians rejected the treatment recommendation in 7 out of 15 cases because it deviated from the national TB treatment guidelines. A survey indicated that the treatment recommender CDSS is easy to use and useful in clinical practice but requires digital infrastructure support and training. CONCLUSIONS: Our findings suggest that global implementation of the novel treatment recommender CDSS holds the potential to improve treatment outcomes of patients with RR-TB, especially those with 'difficult-to-treat' forms of RR-TB.
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Antituberculosos , Sistemas de Apoyo a Decisiones Clínicas , Aprendizaje Automático , Rifampin , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Rifampin/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Antituberculosos/uso terapéutico , Antituberculosos/administración & dosificación , Mycobacterium tuberculosis/efectos de los fármacos , Medicina de Precisión/métodos , Pruebas de Sensibilidad Microbiana , Masculino , Femenino , AdultoRESUMEN
Introduction. Proper management of multidrug-resistant tuberculosis is a prioritized strategy for tuberculosis control worldwide. Objective. To evaluate differences concerning demographic and clinical characteristics and programmatic indicators of Buenaventura patient cohort with confirmed diagnosis of multidrug-resistant tuberculosis, compared to those of the other municipalities from Valle del Cauca, Colombia, 2013-2016. Materials and methods. We conducted an analytical cohort study to compare records of patients older than 15 years with multidrug-resistant tuberculosis included in the Programa de Tuberculosis de Buenaventura (with para-aminosalicylic acid) versus the other municipalities of Valle del Cauca (without para-aminosalicylic). Results. Ninety-nine cases were recorded with a median age of 40 years (IQR = 26 - 53); in Buenaventura, 56% of the patients were women, while in the other municipalities, men predominated with 67%; 95% had health insurance. The most common comorbidity was diabetes (14%). Adverse reactions to antituberculosis medications in Buenaventura were 1.3 times more frequent than in the other municipalities (OR = 2.3; 95% CI = 0.993 - 5.568; p = 0.04). In Buenaventura, the mortality rate was 5% compared to the 15% reported in the other municipalities. Treatment failures were not reported in Buenaventura, but 35% did not continue with the follow-up. Treatment success was higher in Buenaventura (56 %). Conclusion. A strengthened program in Buenaventura presented better programmatic results than those from the other municipalities of Valle del Cauca. Access to molecular tests, availability of shortened treatments, and continuous monitoring to identify adverse reactions to antituberculosis medications are routes for all other control programs.
Introducción. El manejo adecuado de la tuberculosis multirresistente es una estrategia priorizada para el control de la tuberculosis en el mundo. Objetivo. Evaluar las diferencias entre las características demográficas y clínicas, y los indicadores programáticos de los pacientes con diagnóstico confirmado de tuberculosis pulmonar resistente a rifampicina o multirresistente en Buenaventura, frente a la cohorte de los demás municipios del Valle del Cauca entre 2013 y 2016. Materiales y métodos. Se desarrolló un estudio analítico de cohortes para comparar los registros de pacientes mayores de 15 años con tuberculosis multirresistente, del Programa de Tuberculosis de Buenaventura (con ácido paraaminosalicílico), frente a los demás municipios del Valle del Cauca (sin ácido paraaminosalicílico). Resultados. Se registraron 99 casos con una mediana de edad de 40 años (RIC = 26- 53); en Buenaventura, el 56 % eran mujeres; en los demás municipios, predominaron los hombres (67 %); el 95 % de los evaluados tenía aseguramiento en salud. La comorbilidad más frecuente fue diabetes (14 %). Las reacciones adversas a medicamentos antituberculosos en Buenaventura fueron 1,3 veces más frecuentes que en los demás municipios (OR = 2,3; IC95 %: 0,993 - 5,568; p = 0,04). En Buenaventura falleció el 5 % de los casos frente al 15 % reportado en los demás municipios. No hubo fracasos con el tratamiento en Buenaventura, pero se reportó un 35 % de pérdida del seguimiento. El éxito del tratamiento fue mayor en Buenaventura en el 56 %. Conclusión. El programa fortalecido de Buenaventura presentó mejores resultados programáticos que los demás municipios del Valle del Cauca. El acceso a pruebas moleculares, la disponibilidad de tratamientos acortados y el seguimiento continuo para identificar reacciones adversas a medicamentos antituberculosos son un derrotero para todos los programas de control.
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Rifampin , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Colombia/epidemiología , Adulto , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Rifampin/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Antituberculosos/uso terapéutico , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/epidemiología , Estudios de Cohortes , Ácido Aminosalicílico/uso terapéutico , Adulto Joven , Antibióticos Antituberculosos/uso terapéuticoRESUMEN
BACKGROUND: Drug-resistant tuberculosis (DR-TB) poses a significant threat to global TB control and remains a major public health issue. This study aims to evaluate treatment outcomes and identify risk factors for unfavorable outcomes in patients with multi-DR-TB (MDR-TB) treated at a major reference hospital in Istanbul. METHODS: We conducted a retrospective analysis of 413 patients with rifampicin-resistant and MDR-TB who received treatment between January 1, 2013, and December 31, 2023, at the University of Health Sciences Süreyyapasa Chest Diseases Training and Research Hospital. Patients were treated following the World Health Organization and national guidelines, with regimens tailored to individual drug resistance profiles and side effect management. Demographic data, comorbidities, microbiological follow-up, drug resistance patterns, treatment regimens, and radiological findings were analyzed. RESULTS: Treatment success was achieved in 350 patients (84.74%). Thirty-two patients (7.74%) were lost to follow-up, and 32 patients (7.74%) died. Logistic regression analysis identified several factors associated with unfavorable treatment outcomes: comorbidities (odds ratio [OR]: 7.555, P = 0.001), quinolone resistance (OR: 3.695, P = 0.030), and bronchiectasis (OR: 4.126, P = 0.013). Additional significant factors included male gender (P = 0.007), foreign-born status (P = 0.013), age over 35 years (P = 0.002), previous treatment history (P = 0.058), and drug side effects (P = 0.012). CONCLUSION: The long-term regimen for MDR-TB was found to be highly successful, with an 84.74% treatment success rate. Effective treatment regimens, close patient follow-up, early recognition of side effects, and comprehensive management are crucial for achieving successful outcomes. Identifying and addressing risk factors such as comorbidities, drug resistance, and specific patient demographics can further improve treatment success rates. This study underscores the importance of tailored treatment strategies and robust patient management in combating MDR-TB.
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Antituberculosos , Rifampin , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Masculino , Femenino , Rifampin/uso terapéutico , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Resultado del Tratamiento , Factores de Riesgo , Antituberculosos/uso terapéutico , Antituberculosos/efectos adversos , Mycobacterium tuberculosis/efectos de los fármacos , Adulto Joven , Anciano , Turquía , Farmacorresistencia Bacteriana Múltiple , AdolescenteRESUMEN
Mycobacterium marinum infection often affects the extremities, causing single or multiple skin lesions. With the improvement of molecular detection technology and the clinical application of NGS pathogen detection, the diagnosis rate of Mycobacterium marinum skin disease is gradually increasing. This article reported the case of a 54-year-old man who was stung by a marine fish and gradually developed swelling and nodules on his right hand and right upper limb. He was diagnosed with Mycobacterium marinum infection by detection of the tuberculosis resistance gene dissolution curve of the pus and the identification of the bacteria. Oral rifampicin combined with clarithromycin and minocycline was given for anti-infection treatment. During follow-up, the abscesses and nodules gradually shrank and eventually disappeared. By presenting the diagnosis and treatment of this case, the understanding of this disease among clinicians can be improved to avoid misdiagnosis and missed diagnosis.
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Infecciones por Mycobacterium no Tuberculosas , Mycobacterium marinum , Humanos , Persona de Mediana Edad , Masculino , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium marinum/aislamiento & purificación , Enfermedades Cutáneas Bacterianas/diagnóstico , Enfermedades Cutáneas Bacterianas/microbiología , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Claritromicina/uso terapéutico , Rifampin/uso terapéutico , Antibacterianos/uso terapéuticoRESUMEN
BACKGROUND: Brucellosis is a global public health concern and occurs mainly in young adults and the elderly, with children having a lower incidence, thus often leading to delayed treatment. This study aimed to describe the epidemiologic features and clinical characteristics of brucellosis in children. METHODS: In this retrospective study, the clinical data of five children diagnosed with brucellosis in Anhui Provincial Children's Hospital between January 1, 2021 and December 30, 2022 were analyzed. RESULTS: All five cases were from non-pastoral areas, among which three have a history of livestock exposure and originated from the countryside. All patients had medium-high grade fever, mostly accompanied by night sweats and malaise, and three had joint pains. Laboratory tests showed that their white blood cell count was normal or mildly raised, with lymphocytes as the predominant cell population. Four patients had anemia, four had aspartate aminotransferase and alanine aminotransferase abnormality, and two had elevated ferritin levels. All blood samples were positive for Brucella culture, one of which had positive bone marrow culture, and all had positive serology test results. All patients were treated with rifampicin, in combination with sulfamethoxazole or doxycycline for 6 weeks following diagnosis. Four children had a good prognosis, but one child had recurrent joint pain. CONCLUSIONS: The epidemiologic history of children from non-pastoral areas with brucellosis is often unclear; clinical manifestations and laboratory tests lack specificity; and they are easily delayed diagnosis. Clinicians should remain vigilant regarding the possibility of this disease in children with fever of unknown origin. The epidemiological history should be investigated in detail to improve the diagnostic ability of brucellosis. We recommend emphasizing serological testing. Children with brucellosis who receive timely diagnosis and standardized treatment can expect a favorable prognosis.
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Antibacterianos , Brucelosis , Brucelosis/epidemiología , Brucelosis/diagnóstico , Brucelosis/tratamiento farmacológico , Humanos , Masculino , Femenino , Niño , Estudios Retrospectivos , Antibacterianos/uso terapéutico , Preescolar , Doxiciclina/uso terapéutico , China/epidemiología , Brucella/aislamiento & purificación , Rifampin/uso terapéutico , Sulfametoxazol/uso terapéutico , Fiebre/microbiología , Fiebre/etiología , AdolescenteRESUMEN
BACKGROUND: Among chronic condition problems, tuberculosis still represents a serious public health problem globally. OBJECTIVE: To investigate latent tuberculosis infection in patients with Crohn's disease. Retrospective, descriptive cross-sectional study of quantitative analysis. METHODS: The research was conducted on diagnosed cases of Crohn's disease at the University Hospital located in a city in Northeastern Brazil. All cases of patients with Crohn's disease undergoing isoniazid or rifampicin therapy for latent tuberculosis (LTBI) were included in the study. The data obtained were subsequently subjected to statistical analysis using the Statistical Package for the Social Sciences (SPSS) program. RESULTS: We analyzed 235 medical records, and it was observed that 56% were male, with a mean age of 42.7. Among these, 54% declared themselves as brown, 31% had completed high school, and 47% were residents of the city of Teresina. Regarding the clinical and epidemiological characteristics of the studied patients classified as having ILTB, 34% of the medical records were diagnosed by tuberculin test, 48.51% were investigated by x-ray examination, and the recent location affected the colon with 27%. CONCLUSION: Overall, the health profile of the participants in this study aligns with findings previously established in the literature, particularly studies conducted in other Brazilian states, as well as in other developing countries.
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Enfermedad de Crohn , Hospitales Universitarios , Tuberculosis Latente , Humanos , Masculino , Estudios Retrospectivos , Enfermedad de Crohn/complicaciones , Femenino , Adulto , Estudios Transversales , Tuberculosis Latente/epidemiología , Tuberculosis Latente/complicaciones , Tuberculosis Latente/diagnóstico , Brasil/epidemiología , Hospitales Universitarios/estadística & datos numéricos , Persona de Mediana Edad , Adulto Joven , Adolescente , Rifampin/uso terapéutico , Anciano , Isoniazida/uso terapéutico , Antituberculosos/uso terapéuticoRESUMEN
Clarithromycin extended-release (CLA-ER) was used as companion drug to rifampicin (RIF) for Mycobacterium ulcerans infection in the intervention arm of a WHO drug trial. RIF enhances CYP3A4 metabolism, thereby reducing CLA serum concentrations, and RIF concentrations might be increased by CLA co-administration. We studied the pharmacokinetics of CLA-ER at a daily dose of 15 mg/kg combined with RIF at a dose of 10 mg/kg in a subset of trial participants, and compared these to previously obtained pharmacokinetic data. Serial dried blood spot samples were obtained over a period of ten hours, and analyzed by LC-MS/MS in 30 study participants-20 in the RIF-CLA study arm, and 10 in the RIF-streptomycin study arm. Median CLA Cmax was 0.4 mg/L-and median AUC 3.9 mg*h/L, following 15 mg/kg CLA-ER. Compared to standard CLA dosed at 7.5 mg/kg previously, CLA-ER resulted in a non-significant 58% decrease in Cmax and a non-significant 30% increase in AUC. CLA co-administration did not alter RIF Cmax or AUC. Treatment was successful in all study participants. No effect of CLA co-administration on RIF pharmacokinetics was observed. Based on our serum concentration studies, the benefits CLA-ER over CLA immediate release are unclear.
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Úlcera de Buruli , Claritromicina , Preparaciones de Acción Retardada , Mycobacterium ulcerans , Rifampin , Humanos , Claritromicina/farmacocinética , Claritromicina/administración & dosificación , Masculino , Femenino , Adulto , Rifampin/farmacocinética , Rifampin/administración & dosificación , Rifampin/uso terapéutico , Persona de Mediana Edad , Úlcera de Buruli/tratamiento farmacológico , Úlcera de Buruli/microbiología , Mycobacterium ulcerans/efectos de los fármacos , Preparaciones de Acción Retardada/farmacocinética , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Anciano , Adulto Joven , Área Bajo la Curva , Espectrometría de Masas en TándemRESUMEN
Fluoroquinolone resistance is a major challenge in treating Multidrug-Resistant Tuberculosis globally. The GenoType MTBDRsl Ver 2.0, endorsed by the WHO, was used to characterize fluoroquinolone resistance. The fluoroquinolone resistance rates in the MDR-TB, Rifampicin-Resistant TB, and non-MDR-TB were 33%, 16.5%, and 5.4%, respectively. The most common mutation found in fluoroquinolone-resistant isolates was D94G (49.5%) in the gyrA gene. Of the 150 MDR-TB isolates, the prevalence of Extensively Drug-Resistant Tuberculosis and pre-XDR-TB was 1.33% and 30%, respectively. Among the 139 RR-TB isolates, pre-XDR-TB prevalence was 15.8%. The fluoroquinolone resistance rates were 5.12% among the 1230 isoniazid-monoresistant isolates. The study found that MDR-TB and RR-TB have higher risk of fluoroquinolone resistance than non-MDR tuberculosis. Rifampicin-resistant isolates with a mutation at codon S450L have a higher risk (RR = 12.96; 95%CI: 8.34-20.13) of developing fluoroquinolone resistance than isolates with mutations at other codons in the rpoB gene. Isoniazid-resistant isolates with a mutation at codon S315T have a higher risk (RR = 2.09; 95%CI: 1.25-3.50) of developing fluoroquinolone resistance. The study concludes that rapid diagnosis of fluoroquinolone resistance before starting treatment is urgently needed to prevent the spread and increase of resistance and to achieve better treatment outcomes in areas where it is higher.
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Antituberculosos , Fluoroquinolonas , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Fluoroquinolonas/farmacología , Fluoroquinolonas/uso terapéutico , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efectos de los fármacos , Estudios Retrospectivos , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/transmisión , Tuberculosis Resistente a Múltiples Medicamentos/genética , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Masculino , Femenino , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología , Adulto , Mutación , Medición de Riesgo , Persona de Mediana Edad , Pruebas de Sensibilidad Microbiana , Rifampin/farmacología , Rifampin/uso terapéutico , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Tuberculosis Extensivamente Resistente a Drogas/microbiología , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple/genética , Isoniazida/farmacología , Isoniazida/uso terapéutico , AncianoRESUMEN
Tuberculosis (TB) preventive treatment (TPT) effectively prevents the progression from TB infection to TB disease. This study explores factors associated with TPT non-completion in Cambodia using 6-years programmatic data (2018-2023) retrieved from the TB Management Information System (TB-MIS). Out of 14,262 individuals with latent TB infection (LTBI) initiated with TPT, 299 (2.1%) did not complete the treatment. Individuals aged between 15-24 and 25-34 years old were more likely to not complete the treatment compared to those aged < 5 years old, with aOR = 1.7, p = 0.034 and aOR = 2.1, p = 0.003, respectively. Individuals initiated with 3-month daily Rifampicin and Isoniazid (3RH) or with 6-month daily Isoniazid (6H) were more likely to not complete the treatment compared to those initiated with 3-month weekly Isoniazid and Rifapentine (3HP), with aOR = 2.6, p < 0.001 and aOR = 7, p < 0.001, respectively. Those who began TPT at referral hospitals were nearly twice as likely to not complete the treatment compared to those who started the treatment at health centers (aOR = 1.95, p = 0.003). To improve TPT completion, strengthen the treatment follow-up among those aged between 15 and 34 years old and initiated TPT at referral hospitals should be prioritized. The national TB program should consider 3HP the first choice of treatment.
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Antituberculosos , Isoniazida , Tuberculosis Latente , Rifampin , Humanos , Cambodia/epidemiología , Adolescente , Adulto , Femenino , Masculino , Adulto Joven , Antituberculosos/uso terapéutico , Estudios Retrospectivos , Isoniazida/uso terapéutico , Rifampin/uso terapéutico , Rifampin/análogos & derivados , Niño , Tuberculosis Latente/tratamiento farmacológico , Tuberculosis Latente/epidemiología , Tuberculosis Latente/prevención & control , Preescolar , Tuberculosis/prevención & control , Tuberculosis/epidemiología , Tuberculosis/tratamiento farmacológico , Persona de Mediana Edad , LactanteRESUMEN
BACKGROUND: Rifampicin resistant tuberculosis (RR-TB) poses a growing threat to individuals and communities. This study utilized a seasonal autoregressive integrated moving average (SARIMA) model to quantitatively predict the monthly incidence of RR-TB in Yunnan Province which could guide government health administration departments and the centers for disease control and prevention (CDC) in preventing and controlling the RR-TB epidemic. METHODS: The study utilized routine surveillance reporting data from the infectious Disease Network Surveillance and Reporting System. Monthly incidence rates of RR-TB were collected from January 2019 to December 2022. A time series SARIMA model was used to predict the number of monthly RR-TB cases in Yunnan Province in 2023, and the model was validated using time series plots, seasonal and non-seasonal differencing, autocorrelation and partial autocorrelation analysis, and white noise tests. RESULTS: From 2019 to 2022, the incidence of RR-TB decreases as the incidence of all TB decreases (P < 0.05). There was no significant change in the proportion of RR-TB among all TB cases, which remained within 2.5% (P>0.05). The time series decomposition shows that it presented obvious seasonality, periodicity and randomness after being decomposed. Time series analysis was performed on the original series after 1 non-seasonal difference and 1 seasonal difference, the ADF test showed P < 0.05. According to ACF and PACF, the SARIMA (1, 1, 1) (1, 1, 0)12 model was chosen and statistically significant model parameter estimates (P < 0.05). The predicted seasonal trend of RR-TB incidence in 2019 to 2023 was similar to the actual data. The percentage accuracy in the prediction excesses 80% in 2019 to 2022 and is all within 95% CI. However there was a certain gap between the actual incidence and the predicted value in 2023, and the acutual incidence had increased by 12.4% compared to 2022. The percentage of accuracy in the prediction was only 70% in 2023. CONCLUSIONS: We found the incidence of RR-TB was based on that of all TB in Yunnan. The SARIMA model successfully predicted the seasonal incidence trend of RR-TB in Yunnan Province in 2019 to 2023, but the prediction precision could be influenced by factors such as new infectious disease outbreaks or pandemics, social issues, environmental challenges or other unknown risks. Hence CDCs should pay special attention to the post epidemic effects of new infectious disease outbreaks or pandemics, carry out monitoring and early warning, and better optimize disease prediction models.
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Rifampin , Estaciones del Año , Tuberculosis Resistente a Múltiples Medicamentos , China/epidemiología , Humanos , Incidencia , Rifampin/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Modelos EstadísticosRESUMEN
BACKGROUND: Individuals who were formerly incarcerated have high tuberculosis incidence, but are generally not considered among the risk groups eligible for tuberculosis prevention. We investigated the potential health impact and cost-effectiveness of Mycobacterium tuberculosis infection screening and tuberculosis preventive treatment (TPT) for individuals who were formerly incarcerated in Brazil. METHODS: Using published evidence for Brazil, we constructed a Markov state transition model estimating tuberculosis-related health outcomes and costs among individuals who were formerly incarcerated, by simulating transitions between health states over time. The analysis compared tuberculosis infection screening and TPT, to no screening, considering a combination of M tuberculosis infection tests and TPT regimens. We quantified health effects as reductions in tuberculosis cases, tuberculosis deaths, and disability-adjusted life-years (DALYs). We assessed costs from a tuberculosis programme perspective. We report intervention cost-effectiveness as the incremental costs per DALY averted, and tested how results changed across subgroups of the target population. FINDINGS: Compared with no intervention, an intervention incorporating tuberculin skin testing and treatment with 3 months of isoniazid and rifapentine would avert 31 (95% uncertainty interval 14-56) lifetime tuberculosis cases and 4·1 (1·4-5·8) lifetime tuberculosis deaths per 1000 individuals, and cost US$242 per DALY averted. All test and regimen combinations were cost-effective compared with no screening. Younger age, longer incarceration, and more recent prison release were each associated with significantly greater health benefits and more favourable cost-effectiveness ratios, although the intervention was cost-effective for all subgroups examined. INTERPRETATION: M tuberculosis infection screening and TPT for individuals who were formerly incarcerated appears cost-effective, and would provide valuable health gains. FUNDING: National Institutes of Health. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.
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Análisis Costo-Beneficio , Cadenas de Markov , Tamizaje Masivo , Prisioneros , Tuberculosis , Humanos , Brasil/epidemiología , Prisioneros/estadística & datos numéricos , Tuberculosis/diagnóstico , Tuberculosis/economía , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Tamizaje Masivo/economía , Tamizaje Masivo/métodos , Adulto , Masculino , Femenino , Antituberculosos/uso terapéutico , Antituberculosos/economía , Persona de Mediana Edad , Rifampin/uso terapéutico , Rifampin/economía , Mycobacterium tuberculosis/aislamiento & purificación , Adulto JovenRESUMEN
BACKGROUND: Despite the introduction of bedaquiline (Bdq) containing all-oral regimens for treating patients with rifampicin resistant/multidrug resistant tuberculosis (MDR/RR-TB) in 2019, data on its effectiveness in Pakistan, which has the fifth highest MDR-TB burden, is lacking. This study evaluates treatment outcomes and identifies factors associated with unsuccessful outcomes among MDR/RR-TB patients treated with an all-oral longer treatment regimen (LTR). METHODS: This retrospective record review included all microbiologically confirmed pulmonary MDR/RR-TB patients treated with an all-oral LTR between August 2019 and February 2021 across nine PMDT centres in Pakistan. Sociodemographic and clinical data were retrieved from the Electronic Nominal Recording and Reporting System. Treatment outcomes, defined by WHO criteria, were analysed using SPSS and multivariate binary logistic regression to identify factors associated with unsuccessful outcomes. A p-value < 0.05 was considered statistically significant. RESULTS: The final analysis included 644 MDR/RR-TB patients (mean age 37.9 ± 17.6 years), mostly male (53.0 %), underweight (68.0 %), with TB treatment history (66.1 %), MDR-TB (84.9 %), lung cavitation (71.0 %), and no comorbidities (86.4 %). Fluoroquinolone resistance was found in 41.9 %, 16 % had used second-line drugs, and 9.8 % had previous MDR-TB treatment. A total of 400 (62.1 %) patients were declared cured, 53 (8.2 %) treatment completed, 117 (18.2 %) died, 37 (5.7 %) lost to follow-up (LTFU), and 37 (5.7 %) treatment failures. Overall treatment success rate was 70.3 % (n = 453). In multivariate analysis, history of TB treatment (OR:1.63, 95 %CI:1.09-2.64, p = 0.023), previous SLD use (OR:2.09, 95 %CI: 1.20-3.37, p = 0.012), resistance to Z (OR:0.43, 95 %CI: 0.20-0.81, p = 0.023), and resistance to > 5 drugs (OR:3.12, 95 %CI:1.36-11.64, p = 0.013) were significantly associated with death and treatment failure. Whereas, lung cavitation had statistically significant association with LTFU (OR:2.66, 95 %CI:1.10-7.32, p = 0.045). CONCLUSION: Treatment success rate (70.3 %) in this study fell below the WHO recommended target success rate (>90 %). Enhanced clinical management, coupled with special attention to patients exhibiting identified risk factors could improve treatment outcomes.
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Antituberculosos , Diarilquinolinas , Rifampin , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Femenino , Masculino , Estudios Retrospectivos , Adulto , Pakistán , Antituberculosos/uso terapéutico , Antituberculosos/administración & dosificación , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Diarilquinolinas/uso terapéutico , Diarilquinolinas/administración & dosificación , Persona de Mediana Edad , Rifampin/uso terapéutico , Rifampin/administración & dosificación , Resultado del Tratamiento , Adulto Joven , Administración Oral , Adolescente , AncianoRESUMEN
Brucellosis is a difficult to treat infection that requires antibiotic combinations administered over several weeks for clearance of infection and relapse prevention. This systematic review summarizes current evidence for antibiotic treatment of human brucellosis. PubMed, EMBASE, Scopus, CINAHL, Web of Science, and China Academic Journal databases were searched for prospective studies that had compared different antibiotic regimens for treating human brucellosis in the last 25 years. Thirty-four studies recruiting 4182 participants were eligible. Standard dual therapy with doxycycline + rifampicin had a higher risk of treatment failure compared to triple therapy which added streptomycin (RR: 1.98, 95% CI 1.17-3.35, p = 0.01) or levofloxacin (RR: 2.98, 95% CI 1.67-5.32, p = 0.0002), but a similar or lower risk compared to alternative dual antibiotic combinations (p > 0.05). The same combination had a higher risk of relapses compared to triple therapy which added streptomycin (RR: 22.12, 95% CI 3.48-140.52, p = 0.001), or levofloxacin (RR: 4.61, 95% CI 2.20-9.66, p < 0.0001), but a similar or lower risk compared to other dual antibiotic combinations (p > 0.05). Triple antibiotic therapy is more effective than standard dual therapy with rifampicin and doxycycline. However, the latter is also efficacious and suitable for uncomplicated disease.
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Antibacterianos , Brucelosis , Humanos , Antibacterianos/uso terapéutico , Brucelosis/tratamiento farmacológico , Doxiciclina/uso terapéutico , Quimioterapia Combinada , Levofloxacino/uso terapéutico , Rifampin/uso terapéutico , Estreptomicina/uso terapéutico , Resultado del TratamientoRESUMEN
Periprosthetic joint infections (PJI) pose a significant challenge in orthopaedic surgery, often requiring extensive surgical debridement and prolonged antibiotic treatment to eliminate the causative pathogens. Rifampin, known for its potent activity against biofilms, has been crucial in managing PJI by penetrating and disrupting these formations, thereby improving treatment efficacy. In this sense, antibiotic protocols lacking rifampin have shown increased failure rates. Consequently, the development of rifampin resistance could severely influence the prognosis of PJI. The aim of this clinical study was to assess how rifampin resistance affects the functional outcome in patients with PJI. In this single-centre comparative cohort study, we systematically documented all patients who presented with a PJI during the period spanning from 2018 to 2020. Two distinct groups were established for the study: Group 1 comprised 35 patients with a PJI caused by rifampin-susceptible pathogens and group 2 consisted of 28 patients with PJI caused by rifampin-resistant pathogens. A total of 63 patients (34 females) with a mean age of 68 years and a mean follow up of 37 months were included. The examination of patient-specific parameters did not reveal any identified risk factors as influential. Patients with a rifampin-resistant pathogen underwent a greater number of surgical revisions (6.9 ± 5.1 compared to 3.59 ± 3.39, p = 0.0011) and had extended durations of antibiotic treatment (p = 0.0052). The results of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score revealed significant differences in clinical outcome between both groups in every domain, even when stratified by acute and chronic entities. In total the WOMAC increased significantly from 21.57 ± 14.9 points in group 1 to 71.47 ± 62.7 points in group 2 (p < 0.001). The higher failure rates observed in group 2 were not statistically significant (p = 0.44). The current study demonstrates that PJI caused by rifampin-resistant bacteria are associated with a significantly worse functional outcome in both acute and chronic infection types without significantly affecting total failure rates.
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Antibacterianos , Farmacorresistencia Bacteriana , Infecciones Relacionadas con Prótesis , Rifampin , Humanos , Rifampin/uso terapéutico , Rifampin/farmacología , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/microbiología , Femenino , Masculino , Anciano , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Persona de Mediana Edad , Resultado del Tratamiento , Enfermedad Crónica , Anciano de 80 o más Años , Desbridamiento , Estudios Retrospectivos , Estudios de CohortesRESUMEN
Brucellosis, a zoonotic ailment induced by the Brucella and some patients may present with joint involvement. This report describes a pediatric patient diagnosed with Brucella arthritis, presenting with swelling and pain in the right knee. The patient had a reoccurrence of fever due to sulfamethoxazole-trimethoprim allergy during treatment. Symptoms improved after adjusting the antimicrobial regimen to ceftriaxone and rifampicin. This case emphasizes the importance of the need for brucellosis as a differential diagnosis for arthralgia and fever in brucellosis- endemic areas. Furthermore, it emphasizes the importance of timely recognition that recurrent fever after effective anti-infective therapy must be considered as a possibility of drug fever.
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Antibacterianos , Artritis Infecciosa , Brucelosis , Rifampin , Humanos , Brucelosis/tratamiento farmacológico , Brucelosis/diagnóstico , Brucelosis/microbiología , Artritis Infecciosa/tratamiento farmacológico , Artritis Infecciosa/microbiología , Artritis Infecciosa/diagnóstico , Antibacterianos/uso terapéutico , Rifampin/uso terapéutico , Niño , Masculino , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Fiebre/tratamiento farmacológico , Fiebre/microbiología , Ceftriaxona/uso terapéutico , Fiebre por MedicamentoRESUMEN
INTRODUCTION: Antimicrobial resistance in Mycobacterium tuberculosis (MTB) poses a significant challenge to tuberculosis (TB) management worldwide. Rifampicin resistance (RR) has been associated with the rpoB gene mutation. No study was conducted in Tanzania to determine the commonest mutation. The inconsistent findings from various studies support the need to determine whether reported mutation patterns are applicable in our setting. We determined the frequency of rpoB gene mutation and factors associated with RR, which were detected using GeneXpert MTB/RIF assay. METHODS: We conducted a retrospective cross-sectional study involving data from the National Tuberculosis and Leprosy Program database from 2020 to 2022 for cases investigated using GeneXpert MTB/RIF assay. Descriptive analysis was performed to determine the frequency of categorical variables. The chi-square test and logistic regression analysis assessed the relationship between the independent variables and outcome. The 95% confidence interval and a significance level of p<0.05 were used to assess the strength of association. RESULTS: A total of 56,004 participants had a status of MTB and RR, where 38,705/56,004 (69.11%) were males. Probe E mutation (codon 529-533), 89/219 (40.64%) was predominant. Human immunodeficiency virus (HIV)-positive patients had a higher gene mutation, 134/10601 (1.26%) than HIV-negative, 306/45016 (0.68%) (p<0.001). Patients with both pulmonary and extra-pulmonary TB had about four times greater odds of developing rifampicin resistance (AOR 3.88, 95%CI: 1.80-8.32). RR was nearly nine times higher in previously treated patients than new patients (AOR 8.66, 95% CI: 6.97-10.76). HIV-positive individuals had nearly twice the odds of developing RR than HIV-negative individuals (AOR 1.91, 95%CI: 1.51-2.42). CONCLUSION: The rate of RR was lower compared to other studies in Tanzania, with probe E mutations the most prevalent. Patients with disseminated TB, HIV co-infection and those with prior exposure to anti-TB had more risk of RR. The findings highlight the need to strengthen surveillance of multidrug-resistant TB among high risk patients.
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Proteínas Bacterianas , ARN Polimerasas Dirigidas por ADN , Farmacorresistencia Bacteriana , Mutación , Mycobacterium tuberculosis , Rifampin , Rifampin/farmacología , Rifampin/uso terapéutico , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efectos de los fármacos , Tanzanía/epidemiología , Masculino , Femenino , Adulto , Estudios Retrospectivos , Estudios Transversales , Proteínas Bacterianas/genética , ARN Polimerasas Dirigidas por ADN/genética , Persona de Mediana Edad , Farmacorresistencia Bacteriana/genética , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/genética , Adulto Joven , Adolescente , Pruebas de Sensibilidad Microbiana , Antibióticos Antituberculosos/uso terapéutico , Antibióticos Antituberculosos/farmacología , NiñoRESUMEN
Objectives: This study aimed to investigate the epidemiological and drug resistance (DR) characteristics of extrapulmonary tuberculosis (EPTB) in South-Central China. Methods: EPTB inpatients who were culture-positive for Mycobacterium tuberculosis were retrospectively included in a study at a provincial TB hospital in Hunan, a province in South-Central China, from January 2013 to December 2021. Demographic, clinical, and drug susceptibility data were retrieved from TB treatment records. Descriptive statistical methods and a Chi-squared test were used to analyze the epidemiological and DR characteristics of EPTB patients. A logistic regression model was used to explore the risk factors of rifampicin-resistant/multidrug-resistant (RR/MDR)-EPTB. Results: A total of 1,324 cases were included. The majority of EPTB patients were in the age range of 20-29 years, were predominantly men (male-to-female ratio: 2.03), and were farmers (65.63%). Most EPTB cases were found in 2013 and 2017 from 2013 to 2021. The most prevalent subtypes of EPTB were lymphatic TB (29.83%, 395/1,324), multiple EPTB (20.85%, 276/1,324), and musculoskeletal TB (14.65%, 194/1,324). Musculoskeletal TB and genitourinary TB predominantly presented as exclusive EPTB forms, while lymphatic TB and pharyngeal/laryngeal TB often co-occurred with pulmonary TB (PTB). Drug susceptibility testing results showed that total DR rates (resistance to any of RFP, isoniazid [INH], streptomycin [STR], and/or ethambutol [EMB]) and RR/MDR rates in EPTB were 25.23% and 12.39%, respectively. Musculoskeletal TB exhibited the highest rates of total DR (31.40%), INH resistance (28.90%), STR resistance (20.10%), EMB resistance (6.20%), MDR (13.90%), and poly-DR (6.70%). The multivariable logistic regression model showed that patients aged from 20 to 59 years (compared to those aged 10 years), workers (compared to retirees), and EPTB patients from the south and west of Hunan (compared to those from the east of Hunan) were at an increased risk of developing RR/MDR EPTB (all OR values > 1). Conclusion: Our study provided a detailed account of the epidemiological and DR characteristics of EPTB in Hunan province, China. The significant DR rates, particularly in musculoskeletal TB cases, highlight the need for timely diagnosis, effective drug susceptibility testing, and the development of more effective treatment regimens for EPTB, especially targeting musculoskeletal TB treatments.
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Antituberculosos , Mycobacterium tuberculosis , Tuberculosis Extrapulmonar , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Antituberculosos/uso terapéutico , Antituberculosos/farmacología , China/epidemiología , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/aislamiento & purificación , Mycobacterium tuberculosis/efectos de los fármacos , Estudios Retrospectivos , Rifampin/uso terapéutico , Rifampin/farmacología , Factores de Riesgo , Tuberculosis Extrapulmonar/tratamiento farmacológico , Tuberculosis Extrapulmonar/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológicoRESUMEN
BACKGROUND: In clinical practice guidelines, there is no consensus about the medications that should be initially offered to patients with brucellosis. To provide informative evidence, we compared and ranked brucellosis medications based on their efficacy and safety. METHODS: For this systematic review and network meta-analysis, we searched 4 English databases and 3 Chinese databases, from the date of database inception to December 13, 2023. We included randomized controlled trials (RCTs) involving children and adolescents with brucellosis, comparing different antibiotic regimens. We excluded studies explicitly targeting patients with spondylitis brucellosis, endocarditis brucellosis, and neuro-brucellosis. The primary outcomes were overall failure (efficacy) and side effects (safety). Secondary outcomes were relapse and therapeutic failure. Pairwise meta-analysis was first examined. Data were analyzed using random effects network meta-analysis, with subgroup and sensitivity analyses performed. The Confidence in Network Meta-Analysis (CINeMA) framework was used to assess the certainty of evidence. The protocol was preregistered in PROSPERO (CRD42023491331). RESULTS: Of the 11,747 records identified through the database search, 43 RCTs were included in the network meta-analysis. Compared with standard therapy (Doxycycline + Rifampicin), Rifampicin + Tetracyclines (RR 4.96; 95% CI 1.47 to 16.70; very low certainty of evidence), Doxycycline + TMP/SMX (RR 0.18; 95% CI 0.06 to 0.52; low certainty of evidence), Doxycycline + Quinolones (RR 0.27; 95% CI 0.11 to 0.71; low certainty of evidence), Streptomycin + Tetracyclines (RR 0.04; 95% CI 0.01 to 0.16; low certainty of evidence), and Single (RR 0.05; 95% CI 0.02 to 0.16; moderate certainty of evidence) were less efficacious. Doxycycline + Gentamicin ranked the best in efficacy (SUCRA values: 0.94), the second is Triple (SUCRA values: 0.87), and the third is Doxycycline + Streptomycin (SUCRA values: 0.78). CONCLUSIONS: Brucellosis medications differ in efficacy and safety. Doxycycline + Gentamicin, Triple, and Doxycycline + Streptomycin have superior efficacy and safety. Treatment of brucellosis should strike a balance between efficacy, safety, and cost.
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Antibacterianos , Brucelosis , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Brucelosis/tratamiento farmacológico , Humanos , Antibacterianos/uso terapéutico , Doxiciclina/uso terapéutico , Adolescente , Niño , Estreptomicina/uso terapéutico , Rifampin/uso terapéutico , Quimioterapia CombinadaRESUMEN
In the Perspective, William Burman and colleagues advocate improving the safety and acceptability of treatment, rather than treatment-shortening, of rifampin-susceptible tuberculosis.