Tuberculosis respiratoria y retraso diagnóstico / Respiratory tuberculosis and diagnostic delay

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Oportunidades perdidas en la detección de la tuberculosis: análisis de las visitas a Urgencias antes del diagnóstico / Missed opportunities for detecting tuberculosis: An analysis of emergency department visits before the diagnosis

Objetivo: Evaluar en pacientes diagnosticados de tuberculosis pulmonar la frecuencia de asistencias en Urgencias en los 6meses previos al diagnóstico, conocer los motivos de la asistencia, el grado de sospecha en Urgencias y los factores a los que se asociaba esta sospecha. Método: Estudio retrospectivo de los casos de tuberculosis pulmonar atendidos en un servicio de Urgencias generales entre 2011 y 2017. Resultados: De los 54 pacientes incluidos, 38 (70%) habían sido atendidos en el servicio de Urgencias en los 6meses previos al diagnóstico: 6 (16%) por procesos sin relación con la tuberculosis y 32 (84%) con relación potencial. En 12 (38%) de estos pacientes se sospechó en Urgencias la posibilidad del diagnóstico de tuberculosis pulmonar, y no se sospechó en los restantes 20 pacientes (62%). El grupo en el que se sospechó tenía más frecuencia de síntomas generales y respiratorios y más frecuencia de cavitación en la radiografía. Conclusiones: Un elevado porcentaje de pacientes con tuberculosis pulmonar han consultado en Urgencias en los 6meses previos al diagnóstico, y con mucha frecuencia esta posibilidad diagnóstica no se sospecha

Objective: To assess the frequency of care in an emergency department in the 6months prior to the diagnosis of tuberculosis and to determine the reasons for the care, the degree of suspicion in the emergency department and the factors associated with this suspicion. Method: A retrospective study was conducted on patients with pulmonary tuberculosis treated in the general emergency department between 2011 and 2017. Results: Of the 54 included patients, 38 (70%) had been treated in the emergency department in the 6months prior to the diagnosis: 6 (16%) patients had been treated for processes unrelated to the tuberculosis, and 32 (84%) were treated for processes that were potentially related to the tuberculosis. Pulmonary tuberculosis was suspected in the emergency department for 12 (38%) of these patients and not suspected in the remaining 20 patients (62%). The group in which pulmonary tuberculosis was suspected had a higher rate of general and respiratory symptoms and cavitation in the radiography. Conclusions: A high percentage of patients with pulmonary tuberculosis were admitted to the emergency department in the 6months prior to the diagnosis, and this diagnostic possibility was often not suspected

Missed opportunities for detecting tuberculosis: An analysis of emergency department visits before the diagnosis. / Oportunidades perdidas en la detección de la tuberculosis: análisis de las visitas a Urgencias antes del diagnóstico.

OBJECTIVE: To assess the frequency of care in an emergency department in the 6months prior to the diagnosis of tuberculosis and to determine the reasons for the care, the degree of suspicion in the emergency department and the factors associated with this suspicion. METHOD: A retrospective study was conducted on patients with pulmonary tuberculosis treated in the general emergency department between 2011 and 2017. RESULTS: Of the 54 included patients, 38 (70%) had been treated in the emergency department in the 6months prior to the diagnosis: 6 (16%) patients had been treated for processes unrelated to the tuberculosis, and 32 (84%) were treated for processes that were potentially related to the tuberculosis. Pulmonary tuberculosis was suspected in the emergency department for 12 (38%) of these patients and not suspected in the remaining 20 patients (62%). The group in which pulmonary tuberculosis was suspected had a higher rate of general and respiratory symptoms and cavitation in the radiography. CONCLUSIONS: A high percentage of patients with pulmonary tuberculosis were admitted to the emergency department in the 6months prior to the diagnosis, and this diagnostic possibility was often not suspected.

Mujeres autoras de artículos editoriales en revistas españolas de Neumología / No disponible

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Detección de la necesidad de cuidados paliativos en pacientes hospitalizados por EPOC / No disponible

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Activity of various drugs alone or in combination against Mycobacterium fortuitum.

Interest in Mycobacterium fortuitum has increased since it was recognized as an emergent pathogen. The objective of this study was to screen a large number of drug combinations in order to evaluate the activity of classical and new potentially useful antibiotics against M. fortuitum. Twenty M. fortuitum clinical isolates were studied with 51 combinations of two drugs and 47 combinations of three drugs belonging to different families: fluoroquinolones, linezolid, macrolides, rifamycins, aminoglycosides, and carbapenems. Activity was determined in Mueller Hinton broth by seeing whether the cultures were negative after 4 days of incubation with the combination of antibiotics. The most active drugs were moxifloxacin and gatifloxacin, which were active against 15 of the 20 strains studied, followed by amikacin (14 of the 20). The combinations of gatifloxacin with rifampicin or rifabutin, moxifloxacin with rifampicin or amikacin, and ciprofloxacin with amikacin were the most useful against M. fortuitum, as they showed activity in 18 of the 20 strains studied. Linezolid, imipenem, and ertapenem showed poor activity in this experimental model when they were used on their own. Larger studies, both in vitro and in vivo, should be done to confirm the true usefulness of the new fluoroquinolones, alone or in combination, in the treatment of M. fortuitum.

Real-time PCR with internal amplification control for detecting tuberculosis: method design and validation.

Real-time PCR has been a major development in the diagnosis of tuberculosis. However, most tests do not include an internal amplification control (IAC), which therefore limits it clinical application. In this study a new, easy to perform real-time PCR test with IAC was designed and validated in clinical samples. The primers amplified a 163-bp fragment of IS6110 of Mycobacterium tuberculosis and the IAC was designed with a fragment of a different microorganism (Chlamydia trachomatis). The interassay and intraassay variation of this test were very low (0.45-1.65% and 0.18-1.80%, respectively). The detection accuracy was validated in 50 samples (25 urine, 25 sputum) with different concentrations of M. tuberculosis, 18 clinical isolates of non-tuberculous mycobacteria and 148 samples with clinical suspicion of pulmonary tuberculosis. The specificity was 100%. The detection limit of this PCR test without IAC was approximately 15 bacteria and with IAC approximately 32 bacteria. This real-time PCR with IAC assay can improve the detection of M. tuberculosis and contribute to standardization of this diagnostic technique.

Screening for sterilizing activity of antibiotic combinations in an acid model of rapidly growing mycobacteria during the stationary phase of growth.

BACKGROUND: In view of the problems of correlation between the data provided by classical microbiological studies and clinical response, we designed an in vitro method to screen for the sterilizing activity of various antibiotics, individually or in combinations, against clinical isolates of various rapidly growing mycobacteria in the stationary phase. MATERIAL AND METHODS: We screened a large number of antibiotic combinations (4-16 microg/ml) for their sterilizing capacity in 26 Mycobacterium fortuitum clinical isolates, 7 Mycobacterium chelonae and 2 Mycobacterium abscessus clinical isolates (10(5) CFU). RESULTS: The best results against M. fortuitum were obtained with moxifloxacin, both on its own (13/26 strains) and in combination. This drug is also very active against M. chelonae (3/7 strains), and in combination with clarithromycin and amikacin exhibits sterilizing activity against all the strains studied. Combinations of clarithromycin with moxifloxacin or linezolid at high doses (16 microg/ml) exhibit activity against M. abscessus. CONCLUSIONS: The most relevant finding of our study is the good activity of moxifloxacin against these microorganisms in the stationary phase. This indicates the need to confirm these data in animal models or clinical trials in order to determine their true clinical importance.

In vitro bactericidal activity of antibiotic combinations against clinical isolates of Mycobacterium chelonae.

Mycobacterium chelonae is one of the most antibiotic-resistant species of the pathogenic, rapidly-growing mycobacteria. The objective of this study was to evaluate the bactericidal activity of classical and new potential drugs, alone and in combinations, against clinical isolates of Mycobacterium chelonae. Clarithromycin was seen to be the most bactericidal drug. In drug combinations, this compound is most useful with gentamicin, fluoroquinolones, rifampicin, linezolid, other aminoglycosides, doxycyline and carbapenems. The combination of tobramycin with ciprofloxacin or moxifloxacin also exhibits similar activity. In conclusion, this study on bactericidal activity of drug combinations against Mycobacterium chelonae confirms the utility of clarithromycin associated with other drugs, and, of the new drugs, the value of moxifloxacin and linezolid.

Incidence of Beijing genotype of Mycobacterium tuberculosis in Elche, Spain: a 13-year surveillance study.

Strains of the Beijing genotype family of Mycobacterium tuberculosis have been associated with outbreaks and multidrug resistance. We performed a retrospective thirteen-year surveillance study (1993 - 2005) on the occurrence of this strain in Elche, Spain. Only one of the available isolates from 332 cases of tuberculosis tested positive for Beijing strain. The case, detected in 2001, was that of an immigrant patient from Senegal with pulmonary tuberculosis. The strain was not drug resistant and besides six close contact persons that were infected no secondary cases of this strain were detected. In the Elche area, the incidence of Beijing strains is very low and there is no evidence of transmission or higher virulence.

Importance of the efflux pump systems in the resistance of Mycobacterium tuberculosis to fluoroquinolones and linezolid.

OBJECTIVE: Our aim was to study the influence of efflux pump systems in the resistance of Mycobacterium tuberculosis to fluoroquinolones and linezolid. METHODS: We studied the mutations in gyrA and gyrB genes and the influence of efflux pump systems with 2 inhibitors (reserpine and MC 207.110). RESULTS: The effect of the active efflux system on the decrease in sensitivity to ciprofloxacin, moxifloxacin, levofloxacin, ofloxacin, gatifloxacin and linezolid was studied by investigating the variation in the in vitro activity of these compounds when assayed in association with reserpine and MC 207.110. These inhibitors exhibit activity both in strains that are resistant and in strains that are susceptible to these antibiotics. However, they are seen to be most active in resistant strains, since the minimum inhibitory concentration of the antibiotics studied in these strains was reduced between 2- and 6-fold. CONCLUSIONS: Therefore, these mechanisms are involved in the resistance to both compounds. It would be of interest to carry out further studies to determine to what extent these active efflux systems influence resistance to the different groups of drugs used in the treatment of tuberculosis, with a view to the possibility of using the inhibitors of these systems in future therapeutic applications.

Frequency of Hoover's sign in stable patients with chronic obstructive pulmonary disease.

Hoover's sign (the inward motion of the lower lateral rib cage with inspiration) is conventionally considered to be a sign of severe disease in chronic obstructive pulmonary disease (COPD). However, no studies have been done regarding the frequency of Hoover's sign in patients with stable COPD. We aim to establish the frequency of Hoover's sign in a large series of stable patients with COPD and to analyse the characteristics associated with its presence. One hundred and fifty-seven consecutive patients with COPD, 150 of whom were men (95%), with a mean (standard deviation) age of 68 (8) years were included. Seventy-one patients had Hoover's sign (45%) on clinical examination. Hoover's sign was not detected in mild COPD patients, and it was present in 36% of moderate, 43% of severe and 76% of very severe COPD patients. In the multivariate analysis, dyspnea, body mass index (BMI), number of exacerbations and number of prescribed drugs were independently associated with the presence of Hoover's sign in COPD. Hoover's sign is a frequent finding in COPD, and the frequency increases with severity. Its presence is independently related to higher values of dyspnea, BMI, number of exacerbations and number of prescribed drugs.

Drug susceptibility of the Mycobacterium genus: in vitro tests and clinical implications.

This review describes the mechanisms of drug resistance of the most clinically relevant mycobacteria and the methods that have been used for studying drug susceptibility (pnenotype, genotype and in vivo tests) and it describes the more important resistance mechanisms to the drugs. Also, this review describes the relationship between microbiological and pharmacological data and the importance of latency -stationary phase- in mycobacteria. Current clinical guidelines on the treatment of tuberculosis (populations of Mycobacterium tuberculosis within the host, drugs and duration, importance of HIV infection in the treatment of tuberculosis, and treatment of latent tuberculosis) and other diseases caused by mycobacteria (specially associated a Mycobacterium kansasii, Mycobacterium avium complex, Mycobacterium fortuitum and Mycobacterium chelonei) are commented in view of drug resistance information, including the more commonly accepted treatments to these diseases. In addition, the impact of pharmacological studies in predicting response to therapy is reviewed. Finally, it describes the new methods of susceptibility testing and the new antituberculous drugs.

Epidemiología molecular de la tuberculosis: principales hallazgos y su aplicación en España / Molecular epidemiology of tuberculosis: main findings and their application in Spain

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[Apolipoprotein A1 and apolipoprotein B in pleural effusions]. / Apolipoproteína A1 y apolipoproteína B en los derrames pleurales.

OBJECTIVE: To determine the levels of apolipoprotein A1 and apolipoprotein B in pleural effusions and analyze their possible diagnostic value. PATIENTS AND METHODS: A total of 117 patients with pleural effusion (30 transudates and 87 exudates) were included. The apolipoproteins were measured by turbidimetry. RESULTS: The apolipoprotein B values in serum were slightly lower in transudates than in exudates, and both apolipoproteins had lower values in patients with benign exudates than in malignant ones. The apolipoprotein levels in pleural fluid were lower in transudates than in exudates. The pleural/serum fluid ratios of both apolipoproteins were significantly lower in malignant effusions compared with benign exudates. No cutoff value was found that would make it possible to differentiate between transudates and exudates or between benign and malignant exudates with sensitivity or specificity levels that had clinical interest. CONCLUSIONS: Apolipoprotein A1 and apolipoprotein B levels in pleural fluid are different in transudates and exudates, and the pleural/serum fluid ratios are also different between benign and malignant exudates. However, their measurement does not supply additional clinical information.