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1.
BMC Infect Dis ; 21(1): 401, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33933020

RESUMEN

BACKGROUND: Prosthetic joint infections (PJI) are one of the most serious complication of arthroplasty. The management of PJI needs a multidisciplinary collaboration between orthopaedic surgeon, infectious disease specialist and microbiologist. In France, the management of PJI is organized around reference centres (CRIOACs). Our main objective was to perform an audit through a questionnaire survey based on clinical cases, to evaluate how French physicians manage PJI. Eligible participants were all physicians involved in care of patients presenting a PJI. Physicians could answer individually, or collectively during a multidisciplinary team meeting dedicated to PJI. The survey consisted as three questionnaires organized in a total of six clinical cases. RESULTS: Answers from the CRIOACs to the three questionnaires were 92, 77, and 53%. Between 32 and 39% of respondents did not administer antibiotic prophylaxis despite positive S. aureus pre-operative documentation. One-stage exchange strategy was widely preferred in all clinical cases, with no difference between CRIOACs and other centres. Rifampicin was prescribed for S. aureus PJI, in a situation with (90-92%) or without any prosthesis (70%). There was no consensus for the total antibiotic regimen duration, with prescriptions from six to 12 weeks for a majority of respondents. CONCLUSIONS: Surgical strategy for the management of PJI was homogenous with a preference for a one-stage exchange strategy. Medical management was more heterogenous, which reflects the heterogeneity of those infections and difficulties to perform studies with strong conclusions.


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/prevención & control , Infecciones Relacionadas con Prótesis/cirugía , Antibacterianos/administración & dosificación , Profilaxis Antibiótica , Artritis Infecciosa/tratamiento farmacológico , Artritis Infecciosa/prevención & control , Francia , Hospitales , Humanos , Médicos , Rifampin/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/patogenicidad , Encuestas y Cuestionarios
2.
J Int Med Res ; 49(5): 3000605211011972, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33942632

RESUMEN

Retropharyngeal abscess (RPA) is an acute or chronic deep neck tissue infection. Tuberculous RPA is chronic and extremely rare in adults. A 20-year-old female patient visited the local hospital due to cough and sputum. The sputum smear was positive for acid-fast staining, and lung computed tomography (CT) indicated pulmonary tuberculosis (TB). The patient received the standard regimen of isoniazid+rifampicin+pyrazinamide+ethambutol (HRZE) for 6 months. After HRZE, pulmonary symptoms improved, but some pharyngeal discomfort remained. In another case, a 25-year-old male patient was admitted to our hospital because of a mass on the left side of his neck. Lymph node TB was considered after a puncture biopsy. Lung CT showed no obvious abnormality. After HRZE for 5 months, the mass had progressively enlarged. Both patients underwent B-ultrasonography-guided puncture, and Xpert® MTB/RIF of the abscess was positive and rifampin-sensitive. Tuberculous RPA was diagnosed and treated with isoniazid+rifampicin (HR) for 12 months. After combination anti-TB therapy and surgical drainage, both patients fully recovered. Tuberculous RPA is rare in adults; because of pharyngeal symptoms or progressive enlargement of a neck mass with anti-TB treatment, clinicians need to suspect tuberculous RPA in adults, which is treated with anti-TB therapy and surgery.


Asunto(s)
Mycobacterium tuberculosis , Absceso Retrofaríngeo , Tuberculosis Pulmonar , Adulto , Femenino , Humanos , Masculino , Pirazinamida , Rifampin/uso terapéutico , Adulto Joven
3.
J Int Med Res ; 49(5): 3000605211014999, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33983063

RESUMEN

Female genital tuberculosis (FGTB) is an infection caused by Mycobacterium tuberculosis and usually occurs secondary to pulmonary tuberculosis (TB) through the blood circulation, lymph circulation, or direct spreading from abdominal TB. FGTB is an uncommon type of TB that can destroy genital organs, and lead to menstrual disorders and infertility. The diagnosis of FGTB is often made by detection of acid-fast bacilli under microscopy, culture with endometrial biopsy, or histopathological examination of epithelioid granuloma on a biopsy. A multidrug anti-TB regimen is the major management of FGTB, including rifampicin, isoniazid, pyrazinamide, and ethambutol, while surgery is proposed in more deteriorated cases. However, the conception rate in infertile women with FGTB is still low, even after multidrug anti-TB therapy. Additionally, the risk of complications, such as ectopic pregnancy or miscarriage, remains high. In this review, we summarize the characteristics of FGTB, present current epidemiological data, and focus on its early diagnosis and effective management.


Asunto(s)
Infertilidad Femenina , Mycobacterium tuberculosis , Tuberculosis de los Genitales Femeninos , Antituberculosos/uso terapéutico , Femenino , Humanos , Infertilidad Femenina/diagnóstico , Isoniazida , Embarazo , Rifampin/uso terapéutico , Tuberculosis de los Genitales Femeninos/diagnóstico , Tuberculosis de los Genitales Femeninos/tratamiento farmacológico
5.
BMC Infect Dis ; 21(1): 394, 2021 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-33926375

RESUMEN

BACKGROUND: Whole-genome sequencing has shown that the Mycobacterium tuberculosis infection process can be more heterogeneous than previously thought. Compartmentalized infections, exogenous reinfections, and microevolution are manifestations of this clonal complexity. The analysis of the mechanisms causing the microevolution -the genetic variability of M. tuberculosis at short time scales- of a parental strain into clonal variants with a patient is a relevant issue that has not been yet completely addressed. To our knowledge, a whole genome sequence microevolution analysis in a single patient with inadequate adherence to treatment has not been previously reported. CASE PRESENTATION: In this work, we applied whole genome sequencing analysis for a more in-depth analysis of the microevolution of a parental Mycobacterium tuberculosis strain into clonal variants within a patient with poor treatment compliance in Argentina. We analyzed the whole-genome sequence of 8 consecutive Mycobacterium tuberculosis isolates obtained from a patient within 57-months of intermittent therapy. Nineteen mutations (9 short-term, 10 fixed variants) emerged, most of them associated with drug resistance. The first isolate was already resistant to isoniazid, rifampicin, and streptomycin, thereafter the strain developed resistance to fluoroquinolones and pyrazinamide. Surprisingly, isolates remained susceptible to the pro-drug ethionamide after acquiring a frameshift mutation in ethA, a gene required for its activation. We also found a novel variant, (T-54G), in the 5' untranslated region of whiB7 (T-54G), a region allegedly related to kanamycin resistance. Notably, discrepancies between canonical and phage-based susceptibility testing to kanamycin were previously found for the isolate harboring this mutation. In our patient, microevolution was mainly driven by drug selective pressure. Rare short-term mutations fixed together with resistance-conferring mutations during therapy. CONCLUSIONS: This report highlights the relevance of whole-genome sequencing analysis in the clinic for characterization of pre-XDR and MDR resistance profile, particularly in patients with incomplete and/or intermittent treatment.


Asunto(s)
Farmacorresistencia Bacteriana Múltiple/genética , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Adulto , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Argentina , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Femenino , Humanos , Isoniazida/uso terapéutico , Cumplimiento de la Medicación , Pruebas de Sensibilidad Microbiana , Mutación , Mycobacterium tuberculosis/aislamiento & purificación , Filogenia , Pirazinamida/uso terapéutico , Rifampin/uso terapéutico , Estreptomicina/farmacología , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología , Secuenciación Completa del Genoma
6.
Artículo en Inglés | MEDLINE | ID: mdl-33799350

RESUMEN

Tuberculosis patients "resistant to isoniazid and susceptible to rifampicin (Hr-TB)" remain neglected, despite a high burden and poor outcomes. The World Health Organization (WHO) recommends a 6 month regimen consisting of levofloxacin, rifampicin, ethambutol, and pyrazinamide (LRZE) to treat Hr-TB. In contrast, Uzbekistan uses a 9 month regimen (LRZE plus a second-line injectable in the first 3 months). We aimed to assess the treatment outcomes of this novel regimen among Hr-TB patients treated in two regions of Uzbekistan (Fergana and Bukhara) in 2017-2018. We conducted a cohort study involving secondary analysis of routine surveillance data. Of 132 Hr-TB patients, 105 (80%) were successfully treated. Death was the predominant unsuccessful outcome (13, 10%) followed by "treatment failure" (10, 8%) and "lost to follow-up" (4, 2%). High treatment success is an indicator of the potential effectiveness of the novel regimen and adds to the limited global evidence on this issue. However, the sample size was small and there was no comparison group. Since the study was conducted in two regions of Uzbekistan only, the findings have limited generalizability. We recommend future research using an adequate sample size and an appropriate study design (randomized controlled trial or prospective cohort with a control group receiving the WHO-recommended regimen).


Asunto(s)
Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Antituberculosos/uso terapéutico , Estudios de Cohortes , Humanos , Isoniazida/uso terapéutico , Estudios Prospectivos , Rifampin/uso terapéutico , Resultado del Tratamiento , Tuberculosis/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Uzbekistán/epidemiología
7.
J Am Vet Med Assoc ; 258(6): 648-653, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33683955

RESUMEN

OBJECTIVE: To compare soil concentrations of macrolide- and rifampicin-resistant Rhodococcus equi strains (MRRE) on horse-breeding farms that used thoracic ultrasonographic screening (TUS) to identify foals with subclinical pneumonia combined with subsequent administration of macrolides and rifampin to affected foals (TUS farms) versus soil concentrations on farms that did not (non-TUS farms), determine whether the combined use of TUS and antimicrobial treatment of subclinically affected foals was associated with soil concentration of MRRE, and assess whether there were temporal effects on soil concentrations of MRRE during the foaling season. SAMPLES: 720 soil samples and 20 completed questionnaires from 20 horse-breeding farms (10 TUS farms and 10 non-TUS farms) in central Kentucky. PROCEDURES: A questionnaire was used to gather information from participating farms about their 2019 foaling season. Soil samples were collected during January, March, May, and July 2019 for bacterial culture and antimicrobial susceptibility testing to identify any isolates of MRRE. Results were compared for TUS farms versus non-TUS farms. Linear mixed-effects modeling was used to evaluate for potential associations between the soil concentration of MRRE and the use of TUS. RESULTS: Overall, the sum of the mean soil concentrations of MRRE was significantly higher for TUS farms (8.85 log10-transformed CFUs/g) versus non-TUS farms (7.37 log10-transformed CFUs/g). CONCLUSIONS AND CLINICAL RELEVANCE: Our findings indicated that farms that use TUS to identify foals with subclinical pneumonia for antimicrobial treatment select for antimicrobial-resistant R equi strains. Because prognosis is worse for foals infected with resistant versus nonresistant strains of R equi, prudent use of antimicrobials to treat foals with subclinical pulmonary lesions attributed to R equi is recommended.


Asunto(s)
Infecciones por Actinomycetales , Enfermedades de los Caballos , Rhodococcus equi , Rhodococcus , Infecciones por Actinomycetales/tratamiento farmacológico , Infecciones por Actinomycetales/veterinaria , Animales , Granjas , Enfermedades de los Caballos/tratamiento farmacológico , Caballos , Kentucky/epidemiología , Macrólidos/uso terapéutico , Rifampin/uso terapéutico
8.
BMJ Case Rep ; 14(3)2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33692068

RESUMEN

Brucellosis is a common zoonotic disease worldwide. It has protean clinical manifestation and sometimes may has a life-threatening complication. A 4-year-old boy presented with a history of fever, myalgia and appetite loss for 3 weeks. On examination, he had hepatosplenomegaly. The initial working diagnosis was an infection, autoimmune disease and malignancy. Investigations showed positive Brucella serology, and he was started on rifampicin and cotrimoxazole. He was further investigated because of persistent fever, which revealed evidence of haemophagocytic lymphohistiocytosis (HLH). He continued treatment for brucellosis, except rifampicin which was replaced with doxycyclin due to a worsening liver function. The child showed complete clinical and biochemical improvement after 6 weeks of therapy. HLH is a life-threatening condition and should be suspected in children with brucellosis, who did not respond to appropriate antibiotics treatment. Secondary HLH does not always require specific therapy; it may improve with adequate treatment of the underlying condition.


Asunto(s)
Brucelosis , Linfohistiocitosis Hemofagocítica , Animales , Brucelosis/complicaciones , Brucelosis/diagnóstico , Brucelosis/tratamiento farmacológico , Niño , Preescolar , Doxiciclina , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Linfohistiocitosis Hemofagocítica/etiología , Masculino , Rifampin/uso terapéutico , Zoonosis
9.
Int J Tuberc Lung Dis ; 25(2): 134-141, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33656425

RESUMEN

BACKGROUND: Xpert® MTB/RIF was expected to revolutionise the management of rifampicin-resistant TB (RR-TB) by enabling rapid and decentralised diagnosis of rifampicin (RIF) resistance.METHODS: We performed a care cascade analysis for a cohort of RR-TB patients managed under programmatic conditions. Cumulative incidences of time to completion of the RR-TB care cascade steps were estimated, reasons for delay or attrition from the cascade investigated and WHO programme indicators for monitoring of RR-TB programmes calculated.RESULTS: Of 502 patients diagnosed with RR-TB using Xpert, 64% initiated multidrug-resistant TB (MDR-TB) treatment immediately, 20% after some first-line treatment, 16% never initiated MDR-TB treatment, mainly because of death (44%) or loss to follow-up (26%) soon after diagnosis. A supplementary sputum sample was collected within 14 days of treatment in 58.8% of cases. Only 63% of RR-TB cases were assessed for isoniazid resistance, and only 65% of MDR-TB cases were evaluated for pre-XDR-TB (extensively drug-resistant TB). Treatment was individualised in 57% of pre-XDR and 68% of XDR-TB patients. Only 8% completed the entire RR-TB care cascade as intended.CONCLUSION: Fidelity to the RR-TB algorithm was poor, with substantial losses at each step of the cascade, highlighting the fact that implementation of novel technologies needs to be accompanied by health system strengthening to maximise impact.


Asunto(s)
Antibióticos Antituberculosos , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Antibióticos Antituberculosos/farmacología , Antibióticos Antituberculosos/uso terapéutico , Farmacorresistencia Bacteriana , Humanos , Rifampin/uso terapéutico , Sudáfrica/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología
10.
BMC Infect Dis ; 21(1): 261, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33711936

RESUMEN

BACKGROUND: Tuberculosis is a devastating and a deadly disease despite the novel advances in its diagnostic tools and drug therapy. Drug resistant Mycobacterium contributes a great share to tuberculosis mortality. Status of drug resistance and patients' awareness toward the disease is unknown in northeastern Ethiopia. Thus, the aim of this study was to determine the phenotypic and genotypic drug sensitivity patterns and associated factors in Oromia Special Zone and Dessie Town, northeastern Ethiopia. METHODS: In a cross-sectional study, 384 smear positive tuberculosis cases were recruited and Löwenstein-Jensen culture was done. The performance of GenoTypic MTBDRplus assay using the conventional BACTEC MGIT 960 as a "gold standard" was determined. Drug resistant strains were identified using spoligotyping. Pearson Chi-square test was used to determine the association of drug sensitivity test and tuberculosis type, lineages, dominant strains and clustering of the isolates. RESULTS: The 384 smear positive Mycobacterium samples were cultured on LJ media of which 29.2% (112/384) as culture positive. A fair agreement was found between MTBDRplus assay and the conventional MGIT test in detecting the Mycobacterium tuberculosis with sensitivity, specificity, positive and negative predictive value of 94.2, 30.2, 68.4 and 76.5%, respectively. Among LJ culture positive samples 95 of them gave valid result for MTBDRplus assay and 16.8% (16/95) as drug resistant. Similarly, MGIT subculture was made for the 112 isolates and 69 of them gave positive result with 15.9% (11/69) as drug resistant. Cohen's kappa value showed almost a perfect agreement between the two testing methods in detecting rifampicin (sensitivity 100% and specificity 98.3%) and multi-drug resistance (sensitivity 83.3% and specificity 100%). Spoligotyping identified 76.5% (13/17) of the drug resistant isolates as Euro-American and family 33 as the predominant family. Significant association was observed between drug resistant isolates and the dominant strains (χ2: 34.861; p = 0.040) of the Mycobacterium. CONCLUSION: Higher magnitude of drug resistance was found in the study area. The GenoTypic MDRTBplus assay had an acceptable drug sensitivity testing performance.


Asunto(s)
Mycobacterium tuberculosis/genética , Tuberculosis/diagnóstico , Adolescente , Adulto , Anciano , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Estudios Transversales , Farmacorresistencia Bacteriana/efectos de los fármacos , Farmacorresistencia Bacteriana/genética , Etiopía , Femenino , Genotipo , Humanos , Isoniazida/farmacología , Isoniazida/uso terapéutico , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Fenotipo , Juego de Reactivos para Diagnóstico , Rifampin/farmacología , Rifampin/uso terapéutico , Tuberculosis/tratamiento farmacológico , Adulto Joven
11.
BMC Infect Dis ; 21(1): 205, 2021 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-33627075

RESUMEN

BACKGROUND: Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs). METHODS: As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations in test availability. RESULTS: Three hundred eight adults with reported RR/MDR-TB were enrolled from 16 participating sites in 8 countries. Their median age was 36 years, and 36% were HIV-infected. Routine testing on all 308 were confirmed as having RR-TB, but only 75% were documented as having MDR-TB. The majority of those not classified as having MDR-TB were because only rifampicin resistance was tested. At study entry (median 59 days after MDR-TB treatment initiation), 280 participants (91%) were able to produce sputum for the study, of whom 147 (53%) still had detectable MTB. All but 2 of these 147 had rifampicin DST done, with resistance detected in 89%. Almost half (47%) of the 147 specimens had INH DST done, with 83% resistance. Therefore, 20% of the 280 study specimens had MDR-TB confirmed. Overall, DST for second-line drugs were available in only 35% of the 308 routine specimens and 15% of 280 study specimens. CONCLUSIONS: RR-TB was detected in all routine specimens but only 75% had documented MDR-TB, illustrating the need for expanded DST beyond Xpert MTB/RIF to target preventive therapy for HHC.


Asunto(s)
Isoniazida/uso terapéutico , Mycobacterium tuberculosis/aislamiento & purificación , Rifampin/uso terapéutico , Esputo/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Antituberculosos/uso terapéutico , Estudios Transversales , Estudios de Factibilidad , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología
12.
Medicine (Baltimore) ; 100(7): e24787, 2021 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-33607832

RESUMEN

RATIONALE: Tuberculosis is a common cause of phlyctenular keratoconjunctivitis, especially for patients who live in a high endemic area of tuberculosis. We report a rare case of pediatric phlyctenular keratoconjunctivitis associated with primary sinonasal tuberculosis. PATIENT CONCERNS: A 7-year-old boy presented with a 5-month history of redness of the left eye accompanied by mild visual impairment. Physical examination revealed elevated pinkish-white nodules with a circumcorneal hypervascularized lesion on the left conjunctiva. DIAGNOSIS: Computed tomography revealed an enhancing soft tissue mass in the left maxillary sinus with bone destruction. Histopathology of maxillary tissue showed chronic inflammation without granuloma. Special stain, culture and polymerase chain reaction for mycobacterium were initially negative. Left maxillary sinus tuberculosis was diagnosed by positive Mycobacterium tuberculosis polymerase chain reaction from formalin-fixed paraffin-embedded maxillary tissue. INTERVENTIONS: Two month of oral isoniazid, rifampicin, pyrazinamide, and ethambutol, followed by 10 months of oral isoniazid and rifampicin without topical eye drops agent were prescribed. OUTCOMES: Two months after initiation of treatment, the phlyctenular lesion had significantly improved. A follow-up computed tomography showed a significant reduction in the size of the maxillary sinus lesion and the extent of adjacent bone destruction. LESSONS: Primary sinonasal tuberculosis is an uncommon cause of phlyctenular keratoconjunctivitis in children. When microbiological and histopathological evidences are absent, polymerase chain reaction analysis has a crucial role in the diagnosis of tuberculosis, especially in patient with uncommon presentation.


Asunto(s)
Queratoconjuntivitis/etiología , Enfermedades de los Senos Paranasales/diagnóstico , Tuberculosis/diagnóstico , Antibióticos Antituberculosos/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Isoniazida/uso terapéutico , Masculino , Mycobacterium tuberculosis/aislamiento & purificación , Órbita/diagnóstico por imagen , Órbita/patología , Enfermedades de los Senos Paranasales/complicaciones , Enfermedades de los Senos Paranasales/tratamiento farmacológico , Rifampin/uso terapéutico , Tomografía Computarizada por Rayos X , Tuberculosis/complicaciones , Tuberculosis/tratamiento farmacológico
13.
Med Clin (Barc) ; 156(8): 393-401, 2021 04 23.
Artículo en Inglés, Español | MEDLINE | ID: mdl-33531151

RESUMEN

Drug-resistant tuberculosis, especially those with resistance to rifampicin (RR-TB), has become one of the main obstacles to achieving the dream of eradicating tuberculosis. Furthermore, it is necessary to combine three or four different drugs in the attempt to cure TB, however, unfortunately, there are few available that can be considered genuinely effective. Fortunately, the notable worldwide increase in RR-TB in recent years has led to the investment of resources in the development of new drugs for TB, and other drugs investigated for other diseases have been successfully tested on TB. This has resulted in a clear change in the clinical management of these patients over the last 3-4 years, and it is now easier to design therapeutic regimens and achieve higher success rates. All these changes are updated in this review.


Asunto(s)
Tuberculosis Extensivamente Resistente a Drogas , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Antituberculosos/uso terapéutico , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Humanos , Rifampin/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología
14.
An Bras Dermatol ; 96(2): 224-227, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33637399

RESUMEN

Leprosy is one of the neglected diseases in the world and Brazil is the second country with more cases. A retrospective study was conducted based on the medical records of 196 leprosy patients diagnosed during the course of 13 years at a university hospital. The aim was to describe the adverse effects of polychemotherapy, as well the most prevalent and most vulnerable populations. In the study, dapsone was the most implicated drug, especially in women, and the risk increased with age. The authors conclude that with this patient profile, greater vigilance should be taken regarding possible adverse effects, especially anemia.


Asunto(s)
Leprostáticos , Lepra , Brasil , Clofazimina/uso terapéutico , Dapsona/efectos adversos , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Leprostáticos/efectos adversos , Lepra/tratamiento farmacológico , Estudios Retrospectivos , Rifampin/uso terapéutico
15.
BMC Infect Dis ; 21(1): 123, 2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33509114

RESUMEN

BACKGROUND: Xpert MTB/RIF (Xpert) has been recommended by WHO as the initial diagnostic test for TB and rifampicin-resistance detection. Existing evidence regarding its uptake is limited to public health systems and corresponding resource and infrastructure challenges. It cannot be readily extended to private providers, who treat more than half of India's TB cases and demonstrate complex diagnostic behavior. METHODS: We used routine program data collected from November 2014 to April 2017 from large-scale private sector engagement pilots in Mumbai and Patna. It included diagnostic vouchers issued to approximately 150,000 patients by about 1400 providers, aggregated to 18,890 provider-month observations. We constructed three metrics to capture provider behavior with regards to adoption of Xpert and studied their longitudinal variation: (i) Uptake (ordering of test), (ii) Utilization for TB diagnosis, and (iii) Non-adherence to negative results. We estimated multivariate linear regression models to assess heterogeneity in provider behavior based on providers' prior experience and Xpert testing volumes. RESULTS: Uptake of Xpert increased considerably in both Mumbai (from 36 to 60.4%) and Patna (from 12.2 to 45.1%). However, utilization of Xpert for TB diagnosis and non-adherence to negative Xpert results did not show systematic trends over time. In regression models, cumulative number of Xpert tests ordered was significantly associated with Xpert uptake in Patna and utilization for diagnosis in Mumbai (p-value< 0.01). Uptake of Xpert and its utilization for diagnosis was predicted to be higher in high-volume providers compared to low-volume providers and this gap was predicted to widen over time. CONCLUSIONS: Private sector engagement led to substantial increase in uptake of Xpert, especially among high-volume providers, but did not show strong evidence of Xpert results being integrated with TB diagnosis. Increasing availability and affordability of a technically superior diagnostic tool may not be sufficient to fundamentally change diagnosis and treatment of TB in the private sector. Behavioral interventions, specifically aimed at, integrating Xpert results into clinical decision making of private providers may be required to impact patient-level outcomes.


Asunto(s)
Técnicas de Diagnóstico Molecular/estadística & datos numéricos , Mycobacterium tuberculosis/aislamiento & purificación , Sector Privado/estadística & datos numéricos , Tuberculosis/diagnóstico , Antibióticos Antituberculosos/uso terapéutico , Farmacorresistencia Bacteriana/genética , Humanos , India/epidemiología , Mycobacterium tuberculosis/genética , Proyectos Piloto , Pautas de la Práctica en Medicina/estadística & datos numéricos , Rifampin/uso terapéutico , Tuberculosis/tratamiento farmacológico
16.
BMC Infect Dis ; 21(1): 90, 2021 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-33478428

RESUMEN

BACKGROUND: Ending the global tuberculosis (TB) epidemic requires a focus on treating individuals with latent TB infection (LTBI) to prevent future cases. Promising trials of shorter regimens have shown them to be effective as preventative TB treatment, however there is a paucity of data on self-administered treatment completion rates. This pilot trial assessed treatment completion, adherence, safety and the feasibility of treating LTBI in the UK using a weekly rifapentine and isoniazid regimen versus daily rifampicin and isoniazid, both self-administered for 12 weeks. METHODS: An open label, randomised, multi-site pilot trial was conducted in London, UK, between March 2015 and January 2017. Adults between 16 and 65 years with LTBI at two TB clinics who were eligible for and agreed to preventative therapy were consented and randomised 1:1 to receive either a weekly combination of rifapentine/isoniazid ('intervention') or a daily combination of rifampicin/isoniazid ('standard'), with both regimens taken for twelve weeks; treatment was self-administered in both arms. The primary outcome, completion of treatment, was self-reported, defined as taking more than 90% of prescribed doses and corroborated by pill counts and urine testing. Adverse events were recorded. RESULTS: Fifty-two patients were successfully enrolled. In the intervention arm 21 of 27 patients completed treatment (77.8, 95% confidence interval [CI] 57.7-91.4), compared with 19 of 25 (76.0%, CI 54.9-90.6) in the standard of care arm. There was a similar adverse effect profile between the two arms. CONCLUSION: In this pilot trial, treatment completion was comparable between the weekly rifapentine/isoniazid and the daily rifampicin/isoniazid regimens. Additionally, the adverse event profile was similar between the two arms. We conclude that it is safe and feasible to undertake a fully powered trial to determine whether self-administered weekly treatment is superior/non-inferior compared to current treatment. TRIAL REGISTRATION: The trial was funded by the NIHR, UK and registered with ISRCTN ( 26/02/2013-No.04379941 ).


Asunto(s)
Antituberculosos/uso terapéutico , Tuberculosis Latente/tratamiento farmacológico , Rifampin/análogos & derivados , Rifampin/uso terapéutico , Adolescente , Adulto , Antituberculosos/administración & dosificación , Antituberculosos/efectos adversos , Esquema de Medicación , Quimioterapia Combinada , Femenino , Humanos , Isoniazida/administración & dosificación , Isoniazida/efectos adversos , Isoniazida/uso terapéutico , Londres , Masculino , Persona de Mediana Edad , Proyectos Piloto , Rifampin/administración & dosificación , Rifampin/efectos adversos , Autoadministración , Resultado del Tratamiento , Adulto Joven
17.
BMJ Case Rep ; 14(1)2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33509870

RESUMEN

Anti-interferon-gamma (IFN-γ) autoantibodies has been recognised as an adult-onset immunodeficiency in the past decade in people who originate from Southeast Asia. These patients are susceptible to particular opportunistic infections, especially non-tuberculous mycobacteria (NTM). We present the case of a woman whom originally came from Thailand with disseminated Mycobacterium avium complex infection (pleural, pericardium, bloodstream and lung parenchymal involvement). Her infection continued to progress while receiving proper antibiotic treatment. Once high titre neutralising anti-IFN-γ autoantibodies were detected, rituximab was added as adjunctive treatment. The patient had remarkable clinical improvement against persistence of anti-IFN-γ autoantibodies. Although her lung disease has improved, the patient continues on triple therapy for NTM. The kinetics of anti-IFN-γ autoantibodies in the context of clinical progression, indication and length for rituximab and triple therapy is discussed in view of the current literature.


Asunto(s)
Autoanticuerpos/inmunología , Síndromes de Inmunodeficiencia/inmunología , Interferón gamma/inmunología , Infección por Mycobacterium avium-intracellulare/inmunología , Adulto , Antibacterianos/uso terapéutico , Grupo de Ascendencia Continental Asiática , Azitromicina/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/inmunología , Progresión de la Enfermedad , Etambutol/uso terapéutico , Femenino , Humanos , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Pericarditis/tratamiento farmacológico , Pericarditis/inmunología , Pleuresia/tratamiento farmacológico , Pleuresia/inmunología , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/inmunología , Recurrencia , Rifampin/uso terapéutico , Rituximab/uso terapéutico , Tailandia/etnología
18.
Lancet Infect Dis ; 21(3): 354-365, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33508224

RESUMEN

BACKGROUND: Targeted preventive therapy for individuals at highest risk of incident tuberculosis might impact the epidemic by interrupting transmission. We tested performance of a transcriptomic signature of tuberculosis (RISK11) and efficacy of signature-guided preventive therapy in parallel, using a hybrid three-group study design. METHODS: Adult volunteers aged 18-59 years were recruited at five geographically distinct communities in South Africa. Whole blood was sampled for RISK11 by quantitative RT-PCR assay from eligible volunteers without HIV, recent previous tuberculosis (ie, <3 years before screening), or comorbidities at screening. RISK11-positive participants were block randomised (1:2; block size 15) to once-weekly, directly-observed, open-label isoniazid and rifapentine for 12 weeks (ie, RISK11 positive and 3HP positive), or no treatment (ie, RISK11 positive and 3HP negative). A subset of eligible RISK11-negative volunteers were randomly assigned to no treatment (ie, RISK11 negative and 3HP negative). Diagnostic discrimination of prevalent tuberculosis was tested in all participants at baseline. Thereafter, prognostic discrimination of incident tuberculosis was tested in the untreated RISK11-positive versus RISK11-negative groups, and treatment efficacy in the 3HP-treated versus untreated RISK11-positive groups, during active surveillance through 15 months. The primary endpoint was microbiologically confirmed pulmonary tuberculosis. The primary outcome measures were risk ratio [RR] for tuberculosis of RISK11-positive to RISK11-negative participants, and treatment efficacy. This trial is registered with ClinicalTrials.gov, NCT02735590. FINDINGS: 20 207 volunteers were screened, and 2923 participants were enrolled, including RISK11-positive participants randomly assigned to 3HP (n=375) or no 3HP (n=764), and 1784 RISK11-negative participants. Cumulative probability of prevalent or incident tuberculosis disease was 0·066 (95% CI 0·049 to 0·084) in RISK11-positive (3HP negative) participants and 0·018 (0·011 to 0·025) in RISK11-negative participants (RR 3·69, 95% CI 2·25-6·05) over 15 months. Tuberculosis prevalence was 47 (4·1%) of 1139 versus 14 (0·78%) of 1984 in RISK11-positive compared with RISK11-negative participants, respectively (diagnostic RR 5·13, 95% CI 2·93 to 9·43). Tuberculosis incidence over 15 months was 2·09 (95% CI 0·97 to 3·19) vs 0·80 (0·30 to 1·30) per 100 person years in RISK11-positive (3HP-negative) participants compared with RISK11-negative participants (cumulative incidence ratio 2·6, 95% CI 1·2 to 5·9). Serious adverse events related to 3HP included one hospitalisation for seizures (unintentional isoniazid overdose) and one death of unknown cause (possibly temporally related). Tuberculosis incidence over 15 months was 1·94 (95% CI 0·35 to 3·50) versus 2·09 (95% CI 0·97 to 3·19) per 100 person-years in 3HP-treated RISK11-positive participants compared with untreated RISK11-positive participants (efficacy 7·0%, 95% CI -145 to 65). INTERPRETATION: The RISK11 signature discriminated between individuals with prevalent tuberculosis, or progression to incident tuberculosis, and individuals who remained healthy, but provision of 3HP to signature-positive individuals after exclusion of baseline disease did not reduce progression to tuberculosis over 15 months. FUNDING: Bill and Melinda Gates Foundation, South African Medical Research Council.


Asunto(s)
Antituberculosos/uso terapéutico , Biomarcadores/metabolismo , Isoniazida/uso terapéutico , Rifampin/análogos & derivados , Tuberculosis/prevención & control , Adulto , Esquema de Medicación , Femenino , Seronegatividad para VIH , Humanos , Incidencia , Masculino , Mycobacterium tuberculosis/genética , ARN Bacteriano/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rifampin/uso terapéutico , Sudáfrica/epidemiología , Resultado del Tratamiento , Tuberculosis/epidemiología , Tuberculosis/genética , Tuberculosis/metabolismo , Adulto Joven
19.
Nat Commun ; 12(1): 424, 2021 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-33462224

RESUMEN

There have been notable advances in the development of vaccines against active tuberculosis (TB) disease for adults and adolescents. Using mathematical models, we seek to estimate the potential impact of a post-exposure TB vaccine, having 50% efficacy in reducing active disease, on global rifampicin-resistant (RR-) TB burden. In 30 countries that together accounted for 90% of global RR-TB incidence in 2018, a future TB vaccine could avert 10% (95% credible interval: 9.7-11%) of RR-TB cases and 7.3% (6.6-8.1%) of deaths over 2020-2035, with India, China, Indonesia, Pakistan, and the Russian Federation having the greatest contribution. This impact would increase to 14% (12-16%) and 31% (29-33%) respectively, when combined with improvements in RR-TB diagnosis and treatment relative to a scenario of no vaccine and no such improvements. A future TB vaccine could have important implications for the global control of RR-TB, especially if implemented alongside enhancements in management of drug resistance.


Asunto(s)
Antituberculosos/farmacología , Carga Global de Enfermedades , Profilaxis Posexposición/métodos , Vacunas contra la Tuberculosis/administración & dosificación , Tuberculosis/epidemiología , Adolescente , Adulto , Antituberculosos/uso terapéutico , Simulación por Computador , Farmacorresistencia Bacteriana/inmunología , Humanos , Incidencia , Modelos Estadísticos , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/aislamiento & purificación , Rifampin/farmacología , Rifampin/uso terapéutico , Tuberculosis/tratamiento farmacológico , Tuberculosis/microbiología , Tuberculosis/prevención & control
20.
BMJ Case Rep ; 14(1)2021 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-33495169

RESUMEN

Infective endocarditis is associated with a variety of clinical signs, but its association with multisystem vasculitis is rarely reported. A high index of suspicion is necessary to differentiate a primary autoimmune vasculitis from an infectious cause as the wrong treatment can lead to significant morbidity and mortality. We present a 71-year-old female patient with negative blood cultures, on antibiotics for recent bacteraemia, who presented with cutaneous and renal leucocytoclastic vasculitis. Workup revealed a vegetation adjacent to her right atrial pacemaker lead consistent with infective endocarditis and her vasculitis completely resolved with appropriate antibiotics.


Asunto(s)
Lesión Renal Aguda/diagnóstico , Endocarditis Bacteriana/diagnóstico , Enfermedades Cutáneas Vasculares/diagnóstico , Infecciones Estafilocócicas/diagnóstico , Vasculitis/diagnóstico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/inmunología , Lesión Renal Aguda/terapia , Anciano , Antibacterianos/uso terapéutico , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Bacteriemia/complicaciones , Bacteriemia/tratamiento farmacológico , Ceftriaxona/uso terapéutico , Endocarditis Bacteriana/complicaciones , Endocarditis Bacteriana/tratamiento farmacológico , Femenino , Humanos , Edema Pulmonar/etiología , Edema Pulmonar/terapia , Diálisis Renal , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Rifampin/uso terapéutico , Enfermedades Cutáneas Vasculares/etiología , Enfermedades Cutáneas Vasculares/inmunología , Enfermedades Cutáneas Vasculares/patología , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/tratamiento farmacológico , Vasculitis/etiología , Vasculitis/inmunología , Vasculitis/patología
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