Epidemiology of Non-Tuberculous Mycobacteria isolated from clinical specimens in Madrid, Spain, from 2013 to 2017.

The epidemiology of non-tuberculous mycobacteria (NTM) in Spain is largely unknown because systematic reporting is not compulsory. The aim of our study was to describe the frequency and diversity of NTM species in our region and their distribution according to the source sample, gender, and age of the patients. We performed a multicenter study of all NTM isolated in 24 public hospitals in Madrid from 2013 to 2017. A total of 6.923 mycobacteria were isolated: 4535 (65.5%) NTM, and 2.388 (34.5%) Mycobacterium tuberculosis complex (MTB). Overall, 61 different NTM species were identified. The most frequently isolated species were Mycobacterium avium complex (47.7%), M. lentiflavum (12.2%), M. gordonae (9.2%), M. fortuitum (8.9%), and M. abscessus (3.9%). Whereas MTB cases were stable during the study period, the number of NTM isolates increased considerably from 930 isolates in 2013 to 1012 in 2017; a sharp increase occurred in the last year. The rise in NTM isolates was mostly due to M. lentiflavum, M. kansasii, and M. abscessus mainly isolated from respiratory specimens in patients older than 60. The increase in isolation rate of NTM in our region is consistent with the increasing rates reported worldwide in the last decades. The rise in NTM isolates was mainly attributed to M. lentiflavum but it also should be noted the increasing of species with high pathogenic potential such as M. kansasii and M. abscessus.

Staphylococcus aureus meningitis in adults: A comparative cohort study of infections caused by meticillin-resistant and meticillin-susceptible strains.

BACKGROUND: Staphylococcus aureus meningitis is an uncommon nosocomial infection usually associated with neurosurgical procedures, but spontaneous infections may occasionally appear. AIMS: To compare the features of meningitis caused by meticillin-resistant (MRSA) and meticillin-susceptible (MSSA) S. aureus and examine the prognostic factors for mortality, including MRSA infection and combined antimicrobial therapy. METHODS: Retrospective cohort study of 350 adults with S. aureus meningitis admitted to 11 hospitals in Spain (1981-2015). Logistic regression and propensity score matching were used to analyse prognostic factors. RESULTS: There were 118 patients (34%) with MRSA and 232 (66%) with MSSA. Postoperative infection (91% vs 73%) and nosocomial acquisition (93% vs 74%) were significantly more frequent in MRSA than in MSSA meningitis (P < 0.001). Combined therapy was given to 118 (34%) patients. Overall 30-day mortality rate was 23%. On multivariate analysis, mortality was associated with severe sepsis or shock (odds ratio (OR) 9.9, 95% confidence interval (CI) 4.5-22.0, P < 0.001), spontaneous meningitis (OR 4.2, 95% CI 1.9-9.1, P < 0.001), McCabe-Jackson score rapidly or ultimately fatal (OR 2.8, 95% CI 1.4-5.4, P = 0.002), MRSA infection (OR 2.6, 95% CI 1.3-5.3, P = 0.006), and coma (OR 2.6, 95% CI 1.1-6.1, P < 0.029). In postoperative cases, mortality was related to retention of cerebrospinal devices (OR 7.9, 95% CI 3.1-20.3, P < 0.001). CONCLUSIONS: Clinical and epidemiological differences between MRSA and MSSA meningitis may be explained by the different pathogenesis of postoperative and spontaneous infection. In addition to the severity of meningitis and underlying diseases, MRSA infection was associated with increased mortality. Combined antimicrobial therapy was not associated with increased survival.

Papel de la infección en la exacerbación de la EPOC / Role of infection in chronic obstructive pulmonary disease (COPD) exacerbations

El mecanismo patogénico de la exacerbación de la EPOC no es bien conocido por las dificultades para utilizar técnicas agresivas durante los episodios. Se trata de un complejo proceso inflamatorio en el que la infección parece ser la responsable de hasta el 70- 80% de los episodios. Las bacterias se aíslan en el 40-60% de los cultivos de esputo de estos enfermos, encontrándose, sobre todo, Haemophilus influenzae, Streptococcus pneumoniae y Moraxella catarrhalis. En pacientes con EPOC basal más grave se pueden aislar también Pseudomonas aeruginosa, Haemophilus parainfluenzae y enterobacterias. Cada vez se aíslan con más frecuencia bacterias atípicas, especialmente Chlamydia pneumoniae, que además puede permanecer de forma indefinida, jugando un papel en el mantenimiento de la inflamación bronquial. Los virus pueden ser responsables del 30% de las exacerbaciones y favorecen la infección bacteriana. Los principales virus implicados son ARN (rhinovirus, influenza, parainfluenza, coronavirus y virus respiratorio sinticial) y menos virus ADN (adenovirus y citomegalovirus). Se discuten los mecanismos patogénicos por los que los microorganismos pueden dar lugar a la exacerbación y las evidencias que existen de ello (AU)

Role of infection in chronic obstructive pulmonary disease (COPD) exacerbations The pathogenetic mechanism of chronic obstructive pulmonary disease (COPD) exacerbation is not fully known because of the difficulties implicit in the use of aggressive techniques and procedures in the course of acute episodes. In general terms, it is a complex inflammatory event in which infection appears to be responsible for up to 70 or 80% of the episodes. Bacteria are isolated in 40-60% of the sputum cultures of these patients, with predominance of Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. In patients with more severe baseline COPD, Pseudomonas aeruginosa, Haemophilus parainfluenzae and enterobacteriae may also be isolated. Atypical bacteria are isolated with increasing frequence, particularly Chlamydia pneumoniae, which may furthermore persist indefinitely and play a significant role in the maintenance of bronchial inflammation. Viruses may be responsible in up to 30% of exacerbations and they favour bacterial infection. The main involved viruses are of the RNA type (rhinovirus, influenzavirus, parainfluenzavirus, coronavirus and Respiratory Syncitial virus) and, to a lesser extent, DNA viruses (adenovirus and cytomegalovirus). The pathogenetic mechanisms whereby microorganisms may cause exacerbation are discussed, together with the supporting evidence (AU)

Manejo de la infección respiratoria en los servicios de urgencias hospitalarios. Opinión de los médicos españoles / Management of respiratory tract infection at hospitalary Emergency Services. The Spanish physicians' opinion

Objetivos: Conocer la opinión y establecer un debate sobre el manejo clínico de la infección respiratoria en los servicios de urgencia hospitalarios (SUH).Métodos: Se distribuyeron unas recomendaciones realizadas por un Comité de Expertos sobre el manejo de la infección respiratoria (bronquitis aguda, exacerbación de EPOC y neumonía) y una encuesta a facultativos de Atención Primaria, Medicina Intensiva, Medicina Interna, Microbiología, Neumología y Urgencia Hospitalaria sobre las exploraciones complementarias a realizar y criterios de ingreso en las diferentes unidades desde los SUH. Se celebraron 61 reuniones en 61 áreas sanitarias españolas para acordar la respuesta a la encuesta. Resultados: En bronquitis aguda un 53 por ciento consideró necesario hacer radiografía de tórax y un 20 por ciento hemograma. Más del 80 por ciento no consideró útil la observación de urgencias. El 97 por ciento cree que deben ingresar los enfermos con descompensación grave de enfermedad crónica por la bronquitis aguda. El 68 por ciento cree que no existe indicación de ingreso en la UCI. En exacerbación de EPOC se considera necesario realizar radiografía de tórax (100 por ciento), gasometría arterial (90 por ciento) y hemograma (89 por ciento). Un 34 por ciento cree necesaria la pulsioximetría y un 14 por ciento la espirometría. Hubo acuerdo casi unánime en las indicaciones de ingreso. Un 92 por ciento consideró útil la observación en urgencias. En la neumonía más de 93 por ciento considera necesario hacer radiografía de tórax, hemograma y bioquímica elemental, un 55 por ciento gasometría arterial, un 49 por ciento hemocultivos. Un 72 por ciento cree que la observación de urgencias es útil para el manejo de la neumonía. Hubo acuerdo mayoritario para las indicaciones de ingreso. El grado de acuerdo fue menor para la edad avanzada (75 por ciento) y neoplasia (72 por ciento) como indicación de hospitalización. Conclusiones: Las opiniones expresadas por los participantes en el estudio son bastante homogéneas y de acuerdo con las recomendaciones de la literatura en cuanto al manejo de la neumonía y de la exacerbación de EPOC en los SUH. En el manejo de la bronquitis aguda el grado de acuerdo es menor y parecen oportunas unas recomendaciones de actuación en estas situaciones (AU)

La infección respiratoria en los servicios de urgencias hospitalarios. Estudio DIRA / Respiratory tract infection in hospitalary emergency outpatient clinics: the DIRA study

La infección respiratoria (IR) es uno de los motivos de consulta más frecuentes en los servicios de urgencia hospitalaria (SUH), en los que constituye la infección más diagnosticada. Objetivos: 1. Estudiar la prevalencia y formas de presentación de la IR en urgencias. 2. Conocer las prácticas actuales de manejo de la IR en los SUH. Metodología: Se analizaron prospectivamente en los SUH de 50 hospitales repartidos por toda España las IR atendidas los días 21 de octubre de 1998, 21 de enero, de abril y de julio de 1999 recogiéndose los datos epidemiológicos y clínicos y de manejo de la infección en un cuestionario. Los datos recogidos fueron analizados mediante el análisis de varianza (ANOVA) en variables continuas y test de chi cuadrado en comparación de proporciones. Se utilizó el programa estadístico SPSS v 9.0.Resultados: Se recogieron datos de 1.248 pacientes mayores de 14 años, de los cuales 737 eran varones (59,1 por ciento); la edad media fue de 58,5 años (DS 22,8). El 63,9 por ciento de los enfermos padecían una enfermedad de base. El diagnóstico más frecuente fue bronquitis aguda (28,4 por ciento), seguido de neumonía (22,1 por ciento) y agudización de EPOC (20,4 por ciento). No se observaron diferencias en cuanto al destino final del enfermo o el uso de antibióticos. Un 81 por ciento de los enfermos fueron tratados con antibióticos, siendo el más utilizado en todos los cortes amoxicilina-clavulánico. Un tercio de los enfermos (416) ingresaron; de ellos el 51 por ciento padecía una neumonía, un 27 por ciento una agudización de EPOC y un 19 por ciento una bronquitis aguda. Conclusiones: 1) La IR más frecuente en los SUH es la bronquitis aguda, lo que sugiere una utilización inadecuada del SUH. 2) La mayoría de las IR son tratadas con antibióticos. 3) Los hábitos de manejo de la IR no varían significativamente en las cuatro estaciones del año (AU)

[Use of non-conventional amphotericin B at the San Carlos Clinical Hospital]. / Utilización de anfotericina B no convencional en el hospital clínico de San Carlos.

BACKGROUND: Amphotericin B is the treatment of choice for systemic fungal infections, however, its clinical usefulness is limited by its toxicity. The lipid formulations appear to be equally effective and safer, but are more costly. The increase in the consumption of, and expenditure on these formulas led us to undertake a study in order to identify their profile of use (quantitative and qualitative) and to assess the financial repercussions when used inappropriately. METHODS: A set of rules were developed for the use of amphotericin B, and the quality of the prescription of non-conventional amphotericin B (amphotericin B notC) was evaluated retrospectively together with the financial repercussions of its inappropriate use. RESULTS: In 54% of the treatments studied, a poor selection of amphotericin B was made; in 3.5%, the use of amphotericin B was not indicated. The excess expenditure derived from the inappropriate use amounted to 42 million pesetas, 35% of the total expenditure on medicines; the expenditure due to unnecessary prescription was 1,720,327 pesetas. CONCLUSIONS: The retrospective evaluation has shown that there is a high percentage of treatments that do not conform with the recommendations contained in the prescription rules. The holding of information sessions would assist in achieving a more efficient selection of the amphotericin B notC; this would improve prescription quality, which might also deliver significant financial savings.

The central nervous system and infection by Candida species.

In this paper we have reviewed the main clinico-pathologic disease groups of neurocandidiasis: the microabscesses, the macroabscesses, and the meningitis. Special attention has been paid to the predisposing conditions for the appearance of neurocandidiasis, the neuroimaging techniques, and the study of the cerebrospinal fluid, needed for diagnosis. We have also discussed the differential diagnosis with other illnesses. Treatment should be given with amphotericin-B and 5-fluorocytosine. The use of other antifungal drugs for neurocandidiasis is also discussed.

Economic impact of HIV protease inhibitor therapy in the global use of health-care resources.

OBJECTIVE: To evaluate the clinical and economical impact of the introduction of HIV protease inhibitor (PI) therapy in the current clinical care of HIV-infected patients. METHODS: Cohort study with 155 HIV-infected patients with a full year of follow-up before and after the introduction of PI by June 1998. The setting was a large urban tertiary teaching hospital in Madrid, Spain. The main outcomes measures were clinical and immunological evolution, pharmacy, out-patient, emergency room and in-patient medical costs evaluated by diagnostic-related group classification, and the global economic costs of clinical care in HIV-infected patients (AIDS and non-AIDS). RESULTS: The cost of PI therapy was compensated fully by savings related to reduction of the number, length and severity of hospital admissions in AIDS cases. In contrast, more modest clinical effects with increased costs were observed in non-AIDS cases. Globally, there was an increase of about 20% in the total health-care costs of HIV-infected patients (P < 0.01). CONCLUSIONS: PI therapy is highly cost-effective in AIDS patients. Its value in less severely immunosuppressed patients requires further evaluation.

Infection of the central nervous system by Mycobacterium tuberculosis in patients infected with human immunodeficiency virus (the new neurotuberculosis).

Neurologic complications of HIV infection are numerous. This review focuses on the clinical presentation, diagnostic particularities and therapeutic issues of neurotuberculosis. The pertinent literature describing this important infection is succinctly summarized with a particular emphasis on the discussion of differences in clinical presentation between HIV-infected and -uninfected patients.

Intracerebral mass lesions in patients with human immunodeficiency virus infection and cryptococcal meningitis.

The frequency of intracerebral mass lesions (ICML) in patients with human immunodeficiency virus (HIV) infection and cryptococcal meningitis (CM) is not well established. Cryptococcoma seems to be a rare affliction. The objective of this study was to analyze the etiology of ICML in patients with HIV infection and CM. The methodology was a retrospective review of cases diagnosed in two Spanish hospitals between September 1988 and April 1995. Eighteen cases of CM were identified. Computed tomography was performed on presentation in 17 cases. Only one patient had ICML, which progressed while on antifungal treatment and regressed when anti-Toxoplasma treatment was established. During follow-up, two additional patients developed ICML and were successfully treated as toxoplasmosis. Overall, 3 out of 17 patients (18%) developed ICML and all three were cured when anti-Toxoplasma treatment was implemented. In our study, cerebral toxoplasmosis was the only presumed cause of ICML. In areas of high prevalence of toxoplasmosis, ICML in patients with CM may not be cryptococcomas. Consequently, in these areas of high prevalence, a trial of toxo-therapy should be strongly considered for patients with CM and ICML.

Tuberculous meningitis. Clinical characteristics and comparison with cryptococcal meningitis in patients with human immunodeficiency virus infection.

OBJECTIVE: To determine the prevalence and causes of meningitis in patients with human immunodeficiency virus (HIV) infection. DESIGN: A prospective study of HIV-associated neurologic complications carried out from 1988 to 1992. SETTING: A tertiary care university hospital in Madrid, Spain. PATIENTS. A total of 142 patients, 65% of whom were injecting drug users. RESULTS: Thirty-six episodes of meningitis were diagnosed in 33 patients (23%). Of these, 17 cases (47%) were tuberculous meningitis (5 definite and 12 probable) and 7 (19%) corresponded to cryptococcal meningitis. Comparative studies of the tuberculous and cryptococcal meningitis cases showed injecting drug use as the most common form of HIV transmission in the tuberculous meningitis (P = .03) and a lower mean CD4+ cell count in the cryptococcal meningitis group (P = .02). CONCLUSIONS: Tuberculous meningitis was the prime type of meningitis, which was associated with HIV transmission by injecting drug use. Cryptococcal meningitis appears in more advanced stages of HIV infection, which determines its characteristic presentation.

AIDS dementia complex: incidence, clinical profile and impact of zidovudine treatment*.

This study aimed to determine the incidence of AIDS dementia complex (ADC), the clinical data which distinguish it from other neurological complications of HIV infection, and the impact of zidovudine (AZT) therapy on the appearance and course of this condition. Data on the neurological complications of HIV patients treated at a community hospital from 1988 to 1992 were collected prospectively. Out of 500 AIDS patients treated at the hospital, there were 142 patients with neurological complications, with an average of 1.42 complications/patient There were 23 patients diagnosed as having ADC; with an estimated incidence of 4.6%, it was the most frequent neurological complication, after cerebral toxoplasmosis. Age was higher in patients with ADC as first manifestation of AIDS with respect to ADC patients with previous AIDS diagnosed. Compared with the group of patients suffering from other neurological complications, patients with ADC showed significant differences in several biological markers of progression to AIDS, such as hemoglobin, hematocrit, global lymphocyte count, serum ß2-microglobulin and serum IgA. CD4 count was similar in both groups. Ten ADC patients had been treated previously with AZT. Dementia continued progressing in seven of these patients and remained stable in three. Of the other 13 cases not treated previously with the drug, eight received AZT therapy, and a favourable response was obtained in three patients (p = 0.068). ADC represents a major neurological complication in AIDS patients. AZT therapy may delay the appearance of ADC, but not prevent it. A trend towards a favourable response to AZT was observed in ADC patients who had not been treated with it previously.

[Alpha tumor necrosis factor in central nervous system disease associated with HIV infection]. / El factor de necrosis tumoral alfa en la afectación del sistema nervioso central asociada a la infección por el VIH.

The aim of the present study is to evaluate the relationship between the alpha tumor necrosis factor (TNF-alpha), interleukin 1 beta (IL-1 beta) and the neurological disease associated to the HIV-1 infection and different neurological manifestations (15 infections of the CNS and 11 AIDS-dementia complexes) and 14 from a control group. The mean value of TNF-alpha in CSF of patients with HIV-1 infection and AIDS-dementia complex was 19.8 +/- 30.6 pg/ml, superior to that of the control group (p < 0.05). The group of patients with HIV-1 and opportunistic CNS infection has a TNF-alpha value of 28.5 +/- 37.8 pg/ml, that is superior to that of the patients with the AIDS-dementia complex (TNF-alpha = 7.9 +/- 9.4 pg ml; p < 0.05). Within the group of patients with a CNS infection, the value of TNF-alpha was greater in those in the acute phase (44.2 +/- 42.4 pg/ml) than in those in the chronic phase (6.8 +/- 7.6 pg/ml; p < 0.05). The TNF-alpha in the CSF is a good marker of infection of the CNS in the HIV-1 infection.

Candida cerebrospinal fluid shunt infection. Report of two new cases and review of the literature.

In this case report, we describe two patients with Candida shunt infection and review 22 cases from the previous literature. All of them had ventriculoperitoneal shunts, except one who had an external ventricular drain. The more outstanding predisposing factors were recent bacterial meningitis and/or neurosurgery (different from the shunt placement) and abdominal complications (intestinal perforation in three cases, and gastrostomy and lengthening of the distal catheter in one each). The clinical manifestations were hydrocephalus in 36%, fever in 31%, meningoencephalitis in 21%, and abdominal symptoms in 10%. The mean cerebrospinal fluid count was 78 cells/mm3 (with 77% lymphocytic predominance). Two patients died (9%); one of them was the only case in which the catheter was not removed. The recommended treatment is the replacement of the shunt and antifungal therapy with intravenous amphotericin B; in cases of poor clinical condition, the latter should also be given intraventricularly.

[Candida albicans meningitis in 2 parenteral drug addicts. Review of the literature]. / Meningitis por Candida albicans en 2 adictos a drogas por vía parenteral. Revisión de la literatura.

BACKGROUND: HIV infection and parenteral drug abuse (PDA) are frequently associated conditions. Both are at increased risk of developing specific types of Candida infections. Localized CNS infection is an exceptional finding. METHODS: We report two cases of meningitis in PDA due to Candida albicans--one of them HIV positive, and review the literature emphasizing the characteristics of 8 HIV positive patients 4 of them PDA. RESULTS: Most frequent presentation symptoms were fever and headache for more than two weeks. Three patients were found normal on neurologic examination. In two cases CT scan showed hydrocephalus. In one case CNS infarcts were demonstrated on MRI. Median CSF cell counts were 109, mostly lymphocytic. Two cases had elevated adenosine deaminase levels in CSF. Two cases were treated with fluconazole, one improved and the other was cured. Four patients died due to the infection, one of them received no specific treatment. CONCLUSIONS: Candida meningitis can be a manifestation of HIV related immunosuppression. Clinical and CSF findings are mild. Mortality is high. Probably a maintenance therapy is required.

[Comparative study of pneumococcal bacteremia in patients with and without HIV infection]. / Estudio comparativo de la bacteriemia por neumococo en pacientes con y sin infección por VIH.

A retrospective study of bacteriemias due to S. pneumoniae in adults is performed, from all the cases observed in our hospital during the 1989-1990 period. We compare the clinical characteristics of the disease depending if the affected patients were infected or not by the human immunodeficiency virus (HIV). In the considered period bacteriemia due to S. pneumoniae has been diagnosed in 12 patients with HIV infection and 29 without it. Ten of the twelve patients with HIV infection (83.3%) were in Stage IV (CDC) of the disease, staying the rest in a less developed phase of the disease. Age was significantly higher in non-HIV patients (p < 0.001) and a high percentage of patients in this group (75%) showed some disease considered as predisposing to bacteriemia due to S. pneumoniae. When a respiratory foci was present, VIH positive individuals showed more frequently bilateral radiologic infiltrates and less frequently pleural effusion. Leucocyte count when diagnosis was done were significantly higher in non-HIV group. Sensibility of isolated S. pneumoniae was similar in the two groups, being the immediate mortality related with bacteriemia due to S. pneumoniae higher in the non-HIV group. In our center 29.3% of bacteriemias due to S. pneumoniae are diagnosed in patients with HIV infection. This disease in itself could constitute an added risk factor in the development of bacteriemia due to S. pneumoniae.

[Bacteremic pneumonia caused by Rhodococcus equi and HIV infection. Report of a new case and review of the literature]. / Neumonía bacteriémica por Rhodococcus equi e infección por VIH. Comentario de un nuevo caso y revisión de la literatura.

Rhodococcus equi (Corynebacterium equi) is able to produce infections not only in animals but also in patients, usually immunosuppressed ones. We report a new case of bacteremic pneumonia in a drug addict who was also infected by HIV. X-ray film of the chest showed a cavitated infiltrate in right upper lobe. R. equi was recovered from blood, respiratory secretions and lung tissue. The patient was with a prolonged course of antibiotics and also surgical treatment. In spite of both therapies, the patient died. We believe that this infection has to be considered in HIV infected patients with cavitated pneumonia and that early surgical treatment, combined with a prolonged course of multiple antibiotics, is advisable. Finally, in view of the severity of this infection, and its relation with other opportunistic infections, we believe that could be included as AIDS diagnostic criteria.

[Bacteremia caused by Streptococcus pneumoniae and HIV infection]. / Bacteriemia por Streptococcus pneumoniae e infección por VIH.

We analyze seven patients with HIV infection that developed community-acquired bacteremic pneumonia due to Streptococcus pneumoniae. Six patients were drug addicts and one was a male homosexual. Five patients have been previously diagnosed of having AIDS. All patients had fever with respiratory tract symptoms and abnormal X-ray films of the chest, in five cases the lesions were located in both lungs. Only four patients showed a pattern of consolidation. The remaining cases showed an interstitial pattern. All but one patient have a CD4 lymphocyte count equal or less than 50 cells/mm3. Clinical evolution was good with antibiotic treatment. In two cases a relapse occur. No deaths were seen directly related to pneumococcal infection. We want to highlight the relative lack of severity of this infection and we suggest the use of antibiotic treatment for at least 14 days.