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Toxoplasma gondii infection was one of the most frequent AIDS-defining conditions in HIV-infected individuals until the advent of combination antiretroviral therapy. We aimed to assess the clinical load, coinfection, and mortality, as well as time trends for people living with HIV and hospitalized with Toxoplasma gondii infection, in Spain from 1997 to 2015. Retrospective observational analysis using the Spanish National Registry of Hospital Discharges. Information was retrieved for the study period using the International Classification of Diseases, 9th revision. There were 66,451,094 hospital admissions in Spain from 1997 to 2015, including 472,269 (0.71%) in people living with HIV. Toxoplasma gondii infection was registered in 9006 of these (overall prevalence 1.91%), making it the fifth most common opportunistic infection in hospitalized HIV-positive patients. Prevalence of Toxoplasma gondii infection declined in this group from 4.2% in 1997 to 0.8% in 2015 (p < 0.001), while mean age increased, from 35 years in 1997 to 44 years in 2015. The overall in-hospital mortality rate declined from 13.5% in 1997 to 8.9% in 2015, and it was higher in the concomitant presence of bacterial pneumonia (28.9% vs. 10.2%, p < 0.001), cryptosporidiosis (26.9% vs. 11.5%; p = 0.03), cytomegalovirus disease (18.2% vs. 11.2%, p < 0.001), Pneumocystis jiroveci pneumonia (31.5% vs. 10.5%, p < 0.001), leukoencephalopathy (19.8% vs. 11.78% p < 0.001), and wasting syndrome (29.3% vs 10.9%; p < 0.001). Toxoplasma gondii infection prevalence has significantly declined among hospitalized HIV-infected patients in Spain during the last two decades, coinciding with the widespread use of combination antiretroviral therapy.

African histoplasmosis is defined as the fungal infection caused by Histoplasma capsulatum var. duboisii (Hcd). Studies focused on distinguishing Hcd and H. capsulatum var. capsulatum (Hcc), which coexist in Africa, are scarce or outdated, and African strains are continuously underrepresented. In this work, 13 cases of African patients with histoplasmosis diagnosed in the Spanish Mycology Reference Laboratory have been reviewed showing that 77% had disseminated disease and AIDS as underlying disease although Hcd infection has been classically considered a rare presentation in AIDS patients. Strains isolated from these patients and other clinical and reference strains were studied by assessing classical identification methods and performing a three-loci multi-locus sequence analysis (MLSA). Classical identification methods based on biochemical tests and measurement of yeast size proved to be useless in distinguishing both varieties. The MLSA defined an African cluster, with a strong statistical support, that included all strains with African origin. Finally, mating type was also determined by using molecular methods revealing an unequal mating type distribution in African strains. In conclusion, historical statements and classical identification methods were useless to distinguish between varieties, whereas molecular analyses revealed that all strains with African origin grouped together suggesting that traditional classification should be revised. Further investigation is required in order to unravel traditional concepts about Hcd infection and support results obtained in this work., (© The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: It is unclear whether optimal immunological recovery reduces the risk of tuberculosis (TB) in human immunodeficiency virus (HIV) infected patients receiving antiretroviral therapy (ART), in whom it is still significantly higher than in the general population., Methods: Retrospective cohort study in ART-treated patients without a previous diagnosis of TB. TB was microbiologically proven. Multivariate analyses were performed to identify risk factors associated with TB., Results: This study included 1824 patients; the median follow-up was 473 days. The median CD4 count was 207 cells/μl (90-363.8); 339 (18.6%) were tuberculin skin test positive. Increased CD4 count gain after ART initiation was a protective factor against active TB (per each 100 cells/μl increase, OR 0.683, 95%CI 0.522-0.894). Maximal protection was observed in patients reaching increments ⩾150 cells/μl after 12 months of ART (OR 0.29, 95%CI 0.11-0.8) or ⩾300 cells/μl after 24 months (OR 0.73, 95%CI 0.71-0.75). There was no association between achieving HIV RNA <50 copies/ml and risk of active TB (OR 1.43, 95%CI 0.68-2.49)., Conclusions: The risk of TB in patients starting ART is reduced among those with better immunological response, and is unrelated to the virological response. Our results emphasise the need for adjunctive strategies in immunological non-responders to minimise any residual risk of TB.

Histoplasmosis is a systemic infection caused by the dimorphic fungus Histoplasma capsulatum. In immunocompromised patients, primary pulmonary infection can spread to the skin and meninges. Clinical manifestations appear in patients with a CD4(+) lymphocyte count of less than 150 cells/μL. Coccidioidomycosis is a systemic mycosis caused by Coccidioides immitis and Coccidioides posadasii. It can present as diffuse pulmonary disease or as a disseminated form primarily affecting the central nervous system, the bones, and the skin. Cryptococcosis is caused by Cryptococcus neoformans (var. neoformans and var. grubii) and Cryptococcus gattii, which are members of the Cryptococcus species complex and have 5 serotypes: A, B, C, D, and AD. It is a common opportunistic infection in patients with human immunodeficiency virus (HIV)/AIDS, even those receiving antiretroviral therapy. Histopathologic examination and culture of samples from any suspicious lesions are essential for the correct diagnosis of systemic fungal infections in patients with HIV/AIDS., (Copyright © 2011 Elsevier España, S.L. and AEDV. All rights reserved.)

Background: There may be an interaction between the CD4 count and the tuberculin skin test (TST) for the development of tuberculosis (TB) in human immunodeficiency virus (HIV) infected patients receiving highly active antiretroviral therapy (HAART)., Methods: Observational, cohort study of patients treated with HAART during the course of HIV infection in whom TB was confirmed by a positive culture result. Patients were stratified by TST and CD4 count. Univariate and multivariate analyses were performed to identify risk factors associated with the development of TB., Results: The study included 1824 patients starting HAART, 339 (18.6%) of whom were TST-positive. After a median 473 days, 45 cases of TB had developed (1.9 cases per 100 person-years, 95%CI 1.38-2.54). The risk of developing TB increased significantly among patients with a positive TST (2.81, 95%CI 1.11-7.15), and in individuals with > or < 200 cells/μ l (1.37, 95%CI 0.44-4.21). By contrast, in the TST-negative group, the risk was significantly higher in patients with < 200 cells/μ l (16.64, 95%CI 2.16-127.6)., Conclusions: TST-positive patients are at high risk of developing TB, irrespective of CD4 count. However, among TST-negative patients only those with a CD4 count < 200 cells/μ l have an appreciable risk of developing the disease.

The aim of our study was to determine the usefulness of pneumococcal urinary antigen (UA) collected in the emergency department (ED) for the microbiologic diagnosis of community-acquired pneumonia (CAP) in HIV patients and to compare it with other diagnostic tests. Prospective study from 1 January 2007 to 31 December 2008 included HIV-infected patients admitted at the ED with respiratory symptoms and who were diagnosed of CAP. UA, two blood cultures and sputum sample for culture determination were collected from every patient. Sixty-four patients were included. The mean age was 42 years. A total of 31 (48%) UA tests, 12 (19%) blood cultures and 21 (33%) sputum cultures tested positive. A microbiological diagnosis was obtained in 38 (59%) cases. Pneumococcal pneumonia was diagnosed in 32 cases. The statistical analysis showed that the test with best performance was the UA, both in relation to blood and sputum cultures (P<0.05). Two patients died during hospitalization (series mortality of 3%). In conclusion, given its good diagnostic performance, UA should be requested in the ED for the aetiological diagnosis of CAP.

The objective of this study was to determine whether the prevalence of Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations has changed since the introduction of combined antiretroviral therapy (cART) and whether the mutations are associated with poor outcome in Spanish HIV-1-infected patients with Pneumocystis pneumonia (PcP). We studied 167 PcP episodes in HIV-1-infected patients diagnosed during the pre-cART (1989-1995) and cART (2001-2004) periods. Molecular genotyping of DHPS was successfully performed in 98 patients (43 pre-cART and 55 cART). Seventeen patients (17/98, 17%; 95% confidence interval [CI], 10-25%) had mutations in the DHPS gene: 14 patients (14/43, 33%; 95% CI, 19-49%) from the pre-cART period and 3 patients (3/55, 5.5%; 95% CI, 1.3-16%) from the cART period (P < 0.01). In the multivariate analysis, the pre-cART period, previous PcP prophylaxis with sulfa drugs, and homosexuality as an HIV risk factor were found to be associated with a higher risk of presenting DHPS mutations. Overall, 95% of patients were treated with trimethoprim and sulfamethoxazole (TMP-SMX). In-hospital mortality was similar in patients with (out) mutations (6% versus 11%, P = 0.84). DHPS gene mutations were more common during the pre-cART period and were associated with previous sulfa exposure and homosexuality. However, their presence did not worsen prognosis of PcP. The response to TMP-SMX with therapeutic doses was successful in most cases.

Background: Fever of unknown origin (FUO) is common among HIV-infected patients with a CD4+ T-lymphocyte cell count below 200 cells/ml. The use of HAART has transformed the evolution of AIDS and related diseases., Design and Method: Case-control study, nested on a historical cohort of 3777 HIV-infected patients who were attended at "12 de Octubre" University Hospital in Madrid, Spain, between 1994 and 2000., Results: 276 FUO episodes were recorded, 58 of which occurred in patients receiving HAART. The significant decrease on the accumulated FUO incidence along the study period of 7.3 episodes per 100 HIV-infected patients after 1997 corresponded with the introduction of HAART. FUO was more frequent in patients who did not receive HAART. The aetiological spectrum of FUO was transformed by the introduction of HAART: the incidence of tuberculosis decreased while that of leishmaniasis increased. The four year survival in the non-FUO group increased when compared to that of patients who had had FUO. Similarly, this four year survival increased in patients who received HAART at the time of FUO versus those not receiving it., Conclusions: Our results confirm that the incidence of FUO has significantly decreased with the introduction of HAART. HAART has also transformed the aetiological spectrum related to FUO considerably. The most frequent cause of FUO in non-HAART patients on this study was the disseminated infection by Mycobacterium avium intracellulare (MAI), followed by tuberculosis, while leishmaniasis was its most common cause in patients receiving HAART. Survival decreased in patients who developed FUO; however, patients who received HAART at the time of FUO had longer survival than patients who did not., (2009 European Federation of Internal Medicine.)

Objectives: Despite a recent decrease, bacterial pneumonia (BP) is still the most common admission diagnosis in HIV patients. We analyse BP incidence, characteristics and prevention measures., Methods: Observational study of all patients hospitalized for BP in a tertiary hospital in Barcelona, Spain, from January 2000 to December 2005. Demographic and HIV-related data, BP risk factors, characteristics of BP and outcomes are analysed., Results: One hundred and eighty-six BP episodes in 161 patients were included; patients were mainly male (73.7%) and intravenous drug users (73.7%). A decrease in BP incidence was seen during the study period, especially in vaccinated patients. The most commonly isolated microorganism was Streptococcus pneumoniae (31.7%), followed by Legionella pneumophila (5.9%). Legionella pneumophila was more likely in patients with undetectable viral load, higher CD4 cell counts or prior vaccination. Highly active antiretroviral therapy, cotrimoxazole prophylaxis and pneumococcal vaccination did not have a significant influence on bacteraemia rate, in-hospital complications or BP mortality. High Pneumonia Severity Index (PSI) predicted mortality accurately [relative risk 15.2, 95% confidence interval 3.2-71.7; P=0.001]. Mortality was 9.1%, but was significantly higher in patients with CD4 counts under 200 cells/microL (P=0.022)., Conclusions: A decline in BP incidence was seen during the study period. Combining CD4 cell count and PSI score could become a good strategy in deciding which patients have to be hospitalized.

The incidence of Pneumocystis jirovecii pneumonia (PCP) in HIV-infected patients has decreased thanks to sulfa prophylaxis and combined antiretroviral therapy. The influence of P. jirovecii dihydropteroate synthase (DHPS) gene mutations on survival is controversial and has not been reported in Spain. This prospective multicenter study enrolled 207 HIV-infected patients with PCP from 2000 to 2004. Molecular genotyping was performed on stored specimens. Risk factors for intensive care unit (ICU) admission and mortality were identified using a logistic regression model. Seven patients (3.7%; 95% confidence interval [CI], 1.5-7.5%) had DHPS mutations. Overall mortality was 15% (95% CI, 10-21%), rising to 80% (95% CI, 61-92%) in patients requiring mechanical ventilation. None of the patients with DHPS mutants died, nor did they need ICU admission or mechanical ventilation. PaO(2) <60 mm Hg at admission was a predictor of ICU admission (P = 0.01), and previous antiretroviral therapy predicted non-ICU admission (P = 0.009). PaO(2) <60 mm Hg at admission and ICU admission during the 1st week were predictors of mortality (P = 0.03 and P < 0.001, respectively). The prevalence of DHPS mutants in Spain is low and is not associated with a worse outcome. Severe respiratory failure at admission is the strongest predictor of PCP outcome.

Pneumonia caused by the opportunistic organism Pneumocystis jirovecii is a clinically important infection affecting AIDS and other immunocompromised patients. The present study aimed to compare and characterise the frequency pattern of DNA sequences from the P. jirovecii mitochondrial large-subunit rRNA (mtLSU rRNA) gene, the dihydropteroate synthase (DHPS) gene and the internal transcribed spacer (ITS) regions of the nuclear rRNA operon in specimens from Lisbon (Portugal) and Seville (Spain). Total DNA was extracted and used for specific molecular sequence analysis of the three loci. In both populations, mtLSU rRNA gene analysis revealed an overall prevalence of genotype 1. In the Portuguese population, genotype 2 was the second most common, followed by genotype 3. Inversely, in the Spanish population, genotype 3 was the second most common, followed by genotype 2. The DHPS wild-type sequence was the genotype observed most frequently in both populations, and the DHPS genotype frequency pattern was identical to distribution patterns revealed in other European studies. ITS types showed a significant diversity in both populations because of the high sequence variability in these genomic regions. The most prevalent ITS type in the Portuguese population was Eg, followed by Cg. In contrast to other European studies, Bi was the most common ITS type in the Spanish samples, followed by Eg. A statistically significant association between mtLSU rRNA genotype 1 and ITS type Eg was revealed.

We report a case of disseminated histoplasmosis in a 33-year old Ecuadorian patient with AIDS and a CD4 lymphocyte count of 39 cells/microl. He presented with prolonged fever and cough, was diagnosed with hemophagocytic syndrome and multiple organ failure and died 18 days after admission. Histoplasma capsulatum was isolated post-mortem from bone marrow biopsy and blood culture. In a literature review we found 22 published cases of disseminated histoplasmosis in patients with AIDS in Spain since 1988. All but two were men under 50 years old. Nineteen had been born or had lived in endemic areas. The diagnosis of histoplasmosis was established by culture of bone marrow biopsy in 10 cases. Itraconazole was introduced as a second drug after amphotericin B in ten of the thirteen patients who survived.

Objective: Evaluation of the usefulness of a quantitative real-time polymerase chain reaction-based (RT-PCR) technique for clinical diagnosis of histoplasmosis., Methods: Primers and probes were designed on the basis of sequences from the ITS regions of ribosomal DNA of 20 clinical strains of Histoplasma capsulatum. LightCycler procedures (Roche Applied Science) were used with probes marked by fluorescence resonance energy transfer (FRET). Reproducibility, sensitivity, and specificity were analyzed. In addition, an internal control was designed to identify false negative results by PCR inhibition. The RT-PCR assay was tested in 22 clinical samples from 14 patients with proven histoplasmosis. In addition, 30 samples from patients with febrile neutropenia or mycoses other than histoplasmosis, and from healthy volunteers were analyzed as controls., Results: The limit of detection of the assay was 1 fg of genomic DNA per microl of sample. The PCR-based technique was reproducible and highly specific. Positive results were obtained in 11/14 (78.6%) patients and in 17/22 (77.3%) clinical samples. RT-PCR was positive in 100% of respiratory secretions and bone marrow samples, but only 70% of sera (p < 0.01). Mean fungal DNA value was 23.1 fg/microl in serum and 4.85 x 10(3) fg/microl in respiratory and bone marrow samples. RT-PCR results were positive in serum from three HIV patients for which antibody detection by immunodiffusion was negative. Specificity was 100%, since PCR results were negative for all the control samples., Conclusion: Thes RT-PCR technique is a sensitive, specific method for early diagnosis of histoplasmosis, particularly when respiratory secretions or bone marrow samples are analyzed. The reliability is lower in serum, but it can be used as an additional, complementary technique to culture and serology in HIV patients.

The antifungal drug susceptibility of 70 Cryptococcus neoformans isolates obtained in Spain from 1994 to 1996 (23 isolates) and from 1997 to 2005 (47 isolates) was investigated. The MICs of fluconazole, itraconazole and voriconazole were determined by the modified Clinical and Laboratory Standards Institute (CLSI; formerly National Committee for Clinical Laboratory Standards) broth microdilution method. The MIC(50) and MIC(90) for itraconazole and voriconazole did not change significantly from 1994 to 2005. The MIC(50) of fluconazole remained stable and the MIC(90) decreased by 2 log(2) dilution in the isolates collected from 1997 to 2005. We conclude that the in vitro resistance to fluconazole decreased over an 11-year period. In addition, a tendency for the development of possible cross-resistance between the three triazoles was observed., (Copyright 2007 S. Karger AG, Basel.)

Three hundred and ten Cryptococcus neoformans strains isolated from AIDS patients in five different countries (151 from Brazil, 23 from Italy, 28 from Spain, 104 from Thailand and four from Turkey) were tested by the API-ZYM kit to detect their extracellular enzymatic activity. The enzymes esterase (C4) (no 3), esterase lipase (C8) (no 4), leucine arylamidase (no 6) and acid phosphatase (no 11) were commonly positive in most of the strains (more than 95%). These enzymes could be considered a useful tool not only for C. neoformans identification, but in particular for their possible relationship to new C. neoformans virulence factors and also for epidemiological research. Interestingly, it is also the high positive percentage of alpha-glucosidase and beta-glucosidase detected in all isolates. The serotype A was the most predominant serotype in all countries, except for Italy where the serotype D was predominant. Further studies are needed to draw a clear correlation between the API-ZYM profile and serotype.

Objectives: The Hospital Universitario Germans Trias i Pujol is a 600-bed center serving 700,000 inhabitants including 1800 patients with HIV infection in Catalonia (Spain). Highly active antiretroviral therapy (HAART) became available at the end of 1996. Thus, the period 1995 1997 was considered appropriate for evaluating possible epidemiological changes in bloodstream infections (BSI) in HIV-infected patients., Methods: All significant bloodstream infections, including mycobacteremia and fungemia, observed in HIV-positive patients from January, 1995 to December, 1997 have been included in the study., Results: One hundred and eighty six cases were evaluated, in whom a decrease in BSI was observed (68 in 1995, 86 in 1996, 32 in 1997). Over time, we observed an improvement in the immunologic situation of the patients (1995: CD4 <50/mm3 73.8% vs 1997: CD4 <50/mm3 45.5% (P=0.05)). The source of BSI was known in 80.7% of the episodes. BSI secondary to catheter and respiratory infections prevailed in 1995, whereas an increase in bacteremias related to intravenous drug use, with or without endocarditis, was seen in 1997. The most frequent isolates were Mycobacterium avium intracellulare (23) (MAI), M. tuberculosis (20), Staphylococcus aureus (20), coagulase-negative staphylococci (16), Salmonella spp. (16) and Streptococcus pneumoniae (15). In 1997, a decrease was observed in the isolation of Gram-negatives and Mycobacterium spp. with S. aureus and enterococci prevailing., Conclusions: The prevalence of bloodstream infections in HIV-positive patients has decreased since the introduction of HAART and the immunologic state has improved. Furthermore there is a trend to a decrease or disappearance of microorganisms, such as Pseudomonas spp., Mycobacterium tuberculosis, MAI or fungi related to severe immunosuppression. Lastly, bacteremia caused by the active use of intravenous drugs remains stable with the highest percentage in Spain.

We present the genomic characterization of a Spanish isolate of Mycobacterium malmoense. Identification and molecular characterization of the microorganism were performed using the technique of PCR-restriction fragment length polymorphism analysis (PRA) and sequencing of the 16S and the ITS spacer (16S-23S rDNA intergenic spacer region). It was seen that our isolate is very similar to the strain described in Sweden, but differs in the sequencing of the ITS from the isolate in Great Britain. Molecular techniques facilitate a rapid diagnosis and enable a better understanding of the epidemiology of this microorganism.

We present a study of a nosocomial outbreak of multidrug-resistant tuberculosis caused by Mycobacterium bovis in 31 patients, 30 of whom were infected with human immunodeficiency virus; all 31 died of progressive tuberculosis. All M. bovis strains had identical spoligotyping patterns and showed resistance to 12 antituberculosis drugs. Reinfection was suggested in 11 cases and confirmed in 4 by molecular typing methods. The causative strain was named "B strain."

Severity criteria for community-acquired pneumonia (CAP) have always excluded patients with human immunodeficiency virus (HIV) infection. A 1-yr, multicenter, prospective observational study of HIV-infected patients with bacterial CAP was done to validate the criteria used in the American Thoracic Society (ATS) guidelines for CAP, and to determine the prognosis-associated factors in the HIV-infected population with bacterial CAP. Overall, 355 cases were included, with an attributable mortality of 9.3%. Patients who met the ATS criteria had a longer hospital stay (p = 0.01), longer duration of fever (p < 0.001), and higher attributable mortality (13.1% versus 3.5%, p = 0.02) than those who did not. Three factors were independently related to mortality: CD4(+) cell count < 100/microl, radiologic progression of disease, and shock. Pleural effusion, cavities, and/or multilobar infiltrates at admission were independently associated with radiologic progression. A prognostic rule based on the five criteria of shock, CD4(+) cell count < 100/microl, pleural effusion, cavities, and multilobar infiltrates had a high negative predictive value for mortality (97.1%). The attributable mortality for severe pneumonia was 11.3%, as compared with 1.3% for nonsevere disease (p = 0.008). The ATS severity criteria are valid in HIV-infected patients with bacterial CAP. Our study provides the basis for identification of patients who may require hospitalization determined by clinical judgment and the five clinical criteria of shock, a CD4(+) cell count < 100/microl, pleural effusion, cavities, and multilobar involvement. These prognostic factors should be validated in independent cohort studies.

From 1973 to 1995, 29 new and reemerging pathogenic microbes were recognized. However, in discussions about emerging infectious diseases, the focus is often on the clinical effects of the host-parasite relationship, rather than the examination of the biology of the pathogen. Many of what we refer to as emerging diseases are characterized better as 'diseases of human progress'. Thus, the aerosolization of water has played an important role in the emergence of Legionella pneumophila infections. New diseases are superimposed on endemic diseases such as diarrhoeal diseases, malaria and tuberculosis. In addition, many pathogens are becoming increasingly resistant to standard antimicrobial drugs, making treatment difficult and in some cases impossible. We summarize our experience on emerging parasitic diseases (primary amoebic meningoencephalitis, respiratory cryptosporidiosis, and diplogonoporiasis), and selected problems of bacterial resistance (MDR tuberculosis caused by Mycobacterium bovis and macrolide-resistance mechanisms of Streptococcus pneumoniae and S. pyogenes).

Background: We have studied the incidence of tuberculosis++ disease, HIV infection and their association during a period of 6 years using samples analysed in a third level hospital laboratory., Material and Method: 21,242 samples for mycobacteria and 63,425 for HIV antibodies were analysed between 1993 and 1998. The protocol used for mycobacteria consisted of Lowenstein-Jensen, hemoculture, biochemical tests for identification and DNA probe. The diagnosis of HIV was performed using screening with mix EIA HIV 1 + 2, confirmed with Western-blot. Spearman coefficient correlation was used for study of tendency., Results: 1,613 samples (7.5%) positive for mycobacteria from 566 patients (98 females and 428 males) aging between 31 and 40 years (46.9%) were detected. The highest incidence for tuberculosis was observed in 1995 (49.2 x 10(5) and was followed by a decreasing linear tendency. Mycobacterium tuberculosis (96%) and M. bovis (2.7%) were most frequent agents. 2,295 samples (3.6%) showed anti-HIV (406 females and 1,889 males). 54.1% of the infected patients belonged to the age interval 21 to 40 years. The highest incidence was observed in 1994 and was followed by a significant decrease (p < 0.05). The percentage of patients co-infected with tuberculosis-HIV was 39.7% with a maximum in 1995 followed by a linear decrease., Conclusions: The incidence of both infections and co-infection was very high in the first triennium and was followed by a progressive decrease. The decrease of HIV preceded tuberculosis. The result suggest a possible epidemiological correlation between both infections.

Antigen fingerprinting based on surface glycolipid antigens was applied to the epidemiology of clinical isolates of the Mycobacterium avium complex from 128 acquired immunodeficiency syndrome (AIDS) and 31 non-AIDS patients from several different regions of Spain. The application of thin-layer chromatography, gas chromatography-mass spectrometry and monoclonal antibodies, combined with ELISA, allowed a facile identification, differentiation and classification of the isolates. The cumulative results demonstrate that, among the clinical isolates, serovar 4 was predominant in both AIDS (33.6%) and non-AIDS (22.6%) isolates. In general, the results demonstrate geographical as well as disease-related differences in the distribution of Myco. avium complex serovars of clinical importance.

Objective: To determine the predictive factors of non-completion of tuberculosis (TB) treatment among patients infected with the human immunodeficiency virus (HIV)., Design: Between 1987 and 1996, 2201 HIV-infected TB patients were detected by the Barcelona Tuberculosis Prevention and Control Programme. Patients who completed treatment were compared to those who abandoned. Bivariate analysis was made by chi(2) test to compare qualitative variables. Associations were measured by means of odds ratios (OR) with 95% confidence intervals (CI). Variables showing a statistically significant association were analysed at multivariate level by means of a logistic regression model., Results: Treatment was carried to completion by 1065 patients (48.4%), 289 (13.1%) abandoned, 648 (29.5%) died during treatment, and 142 (6.5%) moved out of the city. Final outcome could not be established in 57 (2.5%). Intravenous drug users (IDU) represented 76.2% of patients. The rate of non-completion between 1987 and 1992 was 26.3% and for 1993-1996 it was 15.1%, a decrease of 42.6%. Living in neighbourhoods of a low socio-economic level (OR 1.61; 95% CI 1.222.13), homelessness (OR 3.56; 95% CI 2.01-6.31), history of TB (OR 1.61; 95% CI 1.12-2.33), and having presented with a current TB episode in 1987-1992 (OR 1.42; 95% CI 1.01-2.00), were risk factors for abandoning TB treatment., Conclusions: Social and health factors together influence non-completion of TB treatment in HIV-infected patients, while health interventions can improve treatment completion.

A prospective analysis of 43 episodes of Pseudomonas aeruginosa bacteremia in HIV-1-infected subjects was performed and the results compared with the incidence and outcome of Pseudomonas aeruginosa bacteremia in other high-risk patients, such as transplant recipients, leukemia patients, or patients hospitalized in the intensive care unit. The incidence of bacteremia/fungemia as a whole and of gram-negative and Pseudomonas aeruginosa bacteremia in particular was greater in HIV-1-infected subjects than in the unselected general population admitted. In contrast, the incidence of Pseudomonas aeruginosa bacteremia in HIV-1-infected patients did not differ from that in patients with other high-risk conditions. In patients with HIV-1 infection, independent risk factors for presenting Pseudomonas aeruginosa bacteremia were nosocomial origin (OR, 2.7; 95% CI, 1.3-5.7), neutropenia (OR, 2.7; 95% CI, 1.07-6.8), previous treatment with cephalosporins (OR, 3.6; 95% CI, 1.1-11.6), and a CD4+ cell count lower than 50 cells/mm3 (OR, 3.1; 95% CI, 1.7-8.6). Primary bacteremia and pneumonia were the most common forms of presentation. Fourteen (33%) patients died as a consequence of the bacteremia. The presence of severe sepsis (OR, 17.5; 95% CI, 3.2-68) and the institution of inappropriate definitive antibiotic therapy (OR, 2.7; 95% CI, 1.1-13) were independently associated with a poor outcome. One year after the development of bacteremia, only eight (19%) patients remained alive.

We determined biovars and serotypes of 154 isolates of Cryptococcus neoformans from clinical and environmental sources from different areas of Spain. All clinical isolates belonged to C. neoformans var. neoformans. Serotypes showed an irregular distribution. C. neoformans var. gattii serotype B was isolated from necropsy specimens from goats with pulmonary disease.

Background: As prisons have a high prevalence of tuberculosis and HIV infection, we studied the possibility of multiple tuberculosis infections in a selected population of HIV-infected inmates., Methods: Two groups of patients with special characteristics were selected from 226 HIV-infected inmates diagnosed with tuberculosis in the prisons of Madrid (Spain) between 1993 and 1994. The first group contained nine patients who remained culture positive 4 months after the initiation of therapy and the second group contained 28 patients with Mycobacterium tuberculosis isolated from different anatomical sites. DNA typing with IS6110 was performed on all isolates from these patients. In some patients a secondary DNA typing with the plasmid pTBN12 was performed., Results: Two patients from group A had a second M. tuberculosis strain obtained 4 and 18 months after the initial isolate, with different IS6110 and pTBN12 patterns. In one patient the second strain was multidrug resistant and in the other patient both strains had the same drug-susceptible pattern. The clinical and microbiologic evidence in both patients was consistent with the presence of active tuberculosis caused by a new strain of M. tuberculosis. In group B, the isolates from 27 patients shared similar fingerprint pattern; however, in one patient isolates from sputum and urine showed different IS6110 and pTBN12 patterns, although both strains showed the same drug-susceptible phenotype., Conclusion: This study provides evidence that HIV-infected inmates living under conditions of high environmental infectivity can be infected with two different strains of M. tuberculosis. This finding has implications for the tuberculosis-control programs in prison.

Objective: To analyze the characteristics of the patients died from tuberculosis (TB) in our hospital., Method: We retrospectively reviewed the records of the 46 patients died in-hospital from TB between january, 1992 and june, 1997. MEAN AGE: 55 +/- 19 years (19-85). 35 (76%) males and 11 (24%) females., Diagnosis: pulmonary (63%), disseminated (26%) and extrapulmonary (11%) TB. 87% of the patients had previous comorbidity (35% were seropositive for HIV). The only differences between HIV-infected and non-HIV-infected cases were a greater proportion of normal chest roentgenograms and of toxicity from therapy in seropositive patients. The disease was diagnosed at death in 17% of cases. Chemoprophylaxis had not been used in 5 patients, although they fulfilled criteria for receiving it. Poor compliance with treatment was noted in 6 (13%) patients., Conclusions: We have found a high prevalence of comorbidity in these patients, which might account for the mortality. Delays in diagnosis, misuse of chemoprophylaxis and poor compliance with therapy might also be implicated in some cases.

Background: Immunosuppression caused by human immunodeficiency virus 1 (HIV) infection appears to modify the clinical characteristics and to increase the severity of several bacterial infections. The impact of HIV infection and the degree of immunosuppression on the clinical characteristics and outcome of infective endocarditis (IE) in intravenous (IV) drug users has not been well characterized., Methods: Prospective cohort study among 292 consecutive IV drug users with IE diagnosed in 2 academic institutional hospitals in Barcelona, Spain, from January 1, 1984, to October 31, 1995. Serostatus of HIV infection was documented in 283 patients. We measured demographics, clinical and biological data, cause, echocardiographic findings, HIV serostatus and classification, CD4 cell count, complications, and mortality., Results: Among the 283 episodes of IE, 216 (76.3%) were in HIV-infected patients and 67 (23.7%) in non-HIV-infected patients. Rate of IE per 1000 admissions ranged from 0.17 to 0.82 per year, peaking in 1989. Characteristics of IE independently associated with HIV infection were right-side involvement (odds ratio [OR], 7.6; 95% confidence interval [CI], 3.5-16.7), a micro-organism different from viridans streptococci (OR, 2.5; 95% CI, 1.1-5.9), duration of drug abuse longer than 5 years (OR, 5.0; 95% CI, 2.4-10.3), and white blood cell count of no more than 10 X 10(9)/L (OR, 2.2; 95% CI, 1.1-4.2). There were no significant differences in mortality due to IE according to HIV serostatus. Among the 216 patients with HIV infection, the variables independently associated with worse outcome were CD4 cell count lower than 0.200 x 10(9)/L and left-sided or mixed IE., Conclusions: Although there is a difference in clinical presentation in IE in IV drug users, outcome was similar according to their HIV status. However, among HIV-infected patients, severe immunosuppression and mixed or left-side valvular involvement were strong risk factors for mortality.

To assess and compare epidemiological factors, clinical and radiological signs, laboratory results and drug resistance in patients with tuberculosis (TB) with and without AIDS. Retrospective study of TB diagnosed bacteriologically between January 1993 and December 1996 at Hospital Universitario La Fe. Annual rates were 41.7, 47.1, 34.6 and 43.8 per 100,000 inhabitants in 1993 to 1996, respectively. AIDS was present in 22.4%. TB was pulmonary in 87% and 49.4% in patients without and with AIDS, respectively. Incidence was higher in the 25 to 34 age range. Prior contact with TB patients was established in 19.2% of cases. Pulmonary TB in patients with AIDS presented with normal lung X-rays in 30.1%; 16.2% of these had positive sputum cultures. Pulmonary cavitation was evident in 32.6% of TB patients without AIDS and 6.8% of those with AIDS. Pulmonary TB was diagnosed by culture of sputum taken at the time of admission in 25.9% of non AIDS patients and in 12.4% of patients with AIDS. Extrapulmonary TB was diagnosed by culture in most cases. Such forms predominated among TB plus AIDS patients, with most cases being ganglial and urogenital. Overall drug resistance was 8.3% (7.4% non-AIDS/11.5% AIDS). Primary resistance (PR) was 6.3% and 7.1%, PR to hydrazides was 5% and 5.4%, and secondary resistance was 32.4% and 33.3%. Drug resistance in non-AIDS and AIDS patients, was associated with a history of TB and past treatment (p < 0.009), prior contact with TB patients (p < 0.004) and pulmonary cavitatin (p < 0.02). TB with AIDS tends to occur in a younger population, is often extrapulmonary or with atypical lung involvement. Drug resistance is similar in patients with and without AIDS.

Setting: The incidence of tuberculosis (TB) in Spain is one of the highest in Europe. In Zaragoza region the incidence rate of tuberculosis and the acquired immune deficiency syndrome (AIDS) are close to the national average., Objective: To better define the molecular epidemiology of tuberculosis in an area of Europe where this has not been previously studied., Design: A retrospective epidemiological study on tuberculosis was conducted in Zaragoza, a region of Spain, in 1993. The study population consisted of 226 patients from whom positive culture and complete clinical and demographic data were available. Mycobacterium tuberculosis strains were typed by standard restriction fragment length polymorphism (RFLP). A cluster was defined as two or more isolates with identical RFLP patterns when five or more copies of IS6110 are present. The 137 non-clustered patients were compared with the 89 clustered patients and studied by using univariate analysis., Results: Thirty-nine percent of the patients were clustered, suggesting possible recent transmission. Infection with drug-resistant M. tuberculosis was associated with a decreased risk of being in a cluster. The strains isolated from human immunodeficiency virus (HIV)-positive patients were not associated with clustering. We found that immigration was not a major determinant in the total number of TB cases., Conclusion: Immigration, HIV and drug resistance were not associated with recent transmission. More than 50% of the clusters contained two or three patients, indicating that small outbreaks were responsible for most of the tuberculosis cases. Our RFLP typing results indicate that a TB control programme should be implemented in Spain in order to lower transmission of TB.

Background: Since 1990, several nosocomial outbreaks of multidrug-resistant (MDR) tuberculosis have occurred, none of which have involved Mycobacterium bovis. We describe an epidemic of nosocomial and primary MDR M bovis tuberculosis from December, 1993, to February, 1995, among HIV-1-infected patients in a district of Madrid., Methods: We undertook genetic characterisation of the M bovis strain and investigated its presence in a tuberculosis epidemic in a Madrid hospital in a case-controlled study. We assessed 19 cases diagnosed with MDR tuberculosis due to M bovis during the study period. For the control group, we randomly selected 33 patients with HIV-1 infection and isolation of a strain of M tuberculosis susceptible to isoniazid, rifampicin, or both, who were treated in Ramón y Cajal Hospital. Infection-control policies and practices were implemented., Findings: We detected 19 cases in HIV-1-infected patients of primary MDR tuberculosis produced by M bovis resistant to 11 antituberculosis drugs. We found phenotypic and genotypic similarities in the strains of M bovis. In the case group, the index case and two other cases had had previous contact with another hospital that had had an MDR tuberculosis outbreak. All patients died after a mean of 44 days (range 2-116), despite multidrug treatment with first-line and second-line antituberculosis drugs. The cases with M bovis MDR tuberculosis were significantly more likely than controls to have been admitted to a hospital ward at the same time as patients already infected with MDR tuberculosis during the 10 months before their diagnosis (adjusted odds ratio 94.6 [95% CI 9.4-956.3], p < 0.0001). Advanced HIV-1 immunosuppression was associated with the development of MDR tuberculosis. Implementation of control measures stopped the epidemic., Interpretation: An M bovis primary MDR tuberculosis epidemic that cannot be treated effectively and with high mortality has emerged in Europe and has been transmitted between hospitals.

Between 1988 and 1995, 1832 HIV positive patients were evaluated in our institution. We studied the epidemiologic, immunologic and bacteriologic data, laboratory tests, and X-Ray films in those with musculoskeletal infection. We reviewed twenty-one cases of musculoskeletal infection in twenty patients aged 23-35 years (mean 28,6 years, M:F= 15:5). In all of them risk factor for HIV was intravenous drug abuse. The number of CD4 positive lymphocytes ranged from 0,003 to 0,5 10(9)/l. Staphylococcus aureus was the organism responsible of the infection in twelve cases, all active intravenous drug abusers at the time the diagnosis was done. The remaining causative agents were: Mycobacterium tuberculosis (3 cases), Candida albicans (2 cases), Salmonella subgroup 1 (1 case), Neisseria gonorrhoeae (1 case), Pseudomona aeruginosa (1 case) and Streptococcus agalactiae (1 case). Fifteen infections were diagnosed between 1988 and 1991 and 6 between 1992 and 1995. Musculoskeletal infectious lesions in HIV positive patients in our country are related in the majority of cases to intravenous drug abuse. In the last four years due to a National medical health care plan conducted to educate this group of people the number of musculoskeletal infections is decreasing.

Nineteen multidrug-resistant (MDR) Mycobacterium complex strains isolated in a nosocomial outbreak were characterized at the molecular level. The strains were microbiologically characterized as Mycobacterium bovis. The mpt40 sequence was not present in chromosomal DNA from these strains, supporting the fact that they were M. bovis. All of the isolates were resistant to isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin, para-aminosalicylic acid, clarithromycin, cycloserine, ethionamide, ofloxacin, capreomycin, and amikacin. By performing the standardized IS6110 fingerprinting by restriction fragment length polymorphism (RFLP) analysis, we were able to differentiate two groups (groups A and B) containing two (16 isolates) and three (3 isolates) IS6110 copies, respectively. These strains were typed by spoligotyping, developed to distinguish M. bovis strains and also to distinguish them from M. tuberculosis strains (J. Kamerbeek et al., J. Clin. Microbiol. 35:907-914, 1997). All the strains were confirmed to be M. bovis. In addition, spoligotyping showed a difference in only 1 of 43 spacers between RFLP groups A and B. The rpo beta region of several strains representative of each identified group was cloned and sequenced, and identical mutations (Ser-531 to Leu) responsible for the rifampin resistance phenotype were found. To our knowledge, this is the first characterization at the molecular level of an MDR M. bovis strain responsible for a nosocomial outbreak.

Background: Nocardia usually infects immunosuppressed patients, particularly with cellular immunity deficiency. Nevertheless, despite severe immunosuppression in patients infected with HIV, nocardiosis is rare among these patients. We report here two cases of nocardiosis in patients with HIV infection and review spanish literature up to 1993, with an analysis of the characteristics of this infection in our country., Methods and Results: The two patients consumed drugs parenterally and Nocardia organism were recovered in blood cultures after 48 hours of inoculation in standard culture media. The source of the infection was cutaneous in one patient, over an area of venipuncture, and pulmonary in the other patient. Previously, eleven cases of nocardiosis had been reported in the spanish literature in patients infected with HIV. Eighty-four percent were males, and all of them consumed drugs parenterally and displayed a severe cellular immunodepression; the total CD4 lymphocyte count was lower than 100/mm3 in patients when this finding was available (6/13). At diagnosis only one patient received prophylaxis against other type of infection with antibiotics theoretically effective against Nocardia at diagnosis. The Nocardia species recovered more frequently was asteroides (77%) and the most common location was the skin (54%). Treatments more frequently employed were sulfametoxazole-trimethoprim (45%) and sulfadiazine (36%), with a good response except in those with cerebral involvement., Conclusions: Nocardiosis in patients with HIV infection is rare in Spain. In contrast with other geographical areas skin involvement was the more common form of infection. Prophylaxis with sulfametoxazole-trimethoprim against other infections could be responsible for a lower than expected incidence among this type of patients.

From January 1988 to October 1992, the primary resistance to first-line antituberculous drugs in 501 tuberculous patients was evaluated prospectively. Three-hundred and seventeen patients were HIV-negative and 184 were HIV-positive; these patients had several different clinical forms of tuberculosis. Moreover, the acquired resistance to antituberculous drugs was studied in 295 non-AIDS patients and in 42 AIDS patients with evidence of antecedent tuberculosis treatment. The data indicated that during these five years there was no consistent and clear-cut trend toward greater frequency of primary drug resistance to any of the first-line antituberculous drugs. Primary drug resistance in HIV-positive patients (7.1%) did not differ significantly (p > 0.05) from that found in HIV-negative patients (8.2%). Among HIV-positive patients, the acquired drug resistance pattern was similar to that detected in HIV-negative patients although the frequency of resistance in the former (69%) was significantly higher (p < 0.01). During the study, resistance to isoniazid was almost constant in the acquired-resistance cases and was frequently associated with resistance to other drugs. Furthermore, the acquired resistance to isoniazid was often of a higher level (1 to 10 mg/l) than the primary resistance (0.2 mg/l), and those strains were usually catalase and peroxidase negative.

Study Objective: To evaluate the safety and efficacy of transthoracic aspiration with an ultrathin needle in the microbiologic diagnosis of pulmonary infections in HIV-infected patients., Design: Retrospective review of cases., Setting: A 500-bed teaching hospital in Lleida, Spain., Patients: Forty-five HIV-infected patients admitted between March 1989 and March 1993 with clinical and roentgenographic evidence of pulmonary infection and without contraindications for transthoracic needle aspiration (TNA)., Interventions: Forty-seven TNAs were performed in the emergency room (20) or during hospitalization (27). The TNA procedures were done without premedication and without fluoroscopic guidance. Specimens were processed using routine microbiologic and cytologic techniques; in addition, polymerase chain reaction (PCR) for Pneumocystis carinii was carried out since March 1992. Development of adverse effects was carefully evaluated., Results: The TNA was effective in 29 (62 percent) out of 47 procedures. The diagnosis was obtained for 14 of 15 patients with P carinii pneumonia, 8 out of 14 patients with bacterial pneumonia, and 4 out of 12 patients with tuberculosis. Other pathogens recovered were Nocardia asteroides, Cryptococcus neoformans, Rhodococcus equi, and Mycobacterium avium. No false-positive results were obtained. Pneumothorax developed in eight (17 percent) procedures, but only one procedure resulted in a pleural drainage; the incidence of other adverse effects was low and clinically irrelevant., Conclusion: Our study suggests that TNA can be a useful technique in establishing the etiologic diagnosis of pulmonary infections in HIV-infected patients, with a good sensitivity, high specificity, and relatively low incidence of serious complications, with TNA appearing as a reliable alternative to more uncomfortable methods.

Background: Since the appearance of AIDS, bacteremia by Mycobacterium tuberculosis is an event described with ever greater frequency. The isolation of M. tuberculosis in blood cultures in patients coinfected by the human immunodeficiency virus and M. tuberculosis may vary the initial clinical diagnosis and confirm the picture as disseminated tuberculosis., Methods: The clinical records of patients admitted to the General Penitentiary Hospital of Madrid with significant bacteremia during the study period (March 1, 1991-September 1992) were retrospectively and prospectively reviewed. Special attention was given to the bacteremias by M. tuberculosis with the most significant clinical evolutive data being collected. The blood cultures were performed according to the routine technique using a non radiometric system with 10-day incubation and posterior processing of the sample for visualization and culture for mycobacteria., Results: In an 18 moth period and out of a total of 284 positive blood cultures (154 significant isolations) 14 episodes of bacteremia by M. tuberculosis were studied in 12 prison patients coinfected by the human immunodeficiency virus with associated severe immunosuppression (mean of CD4 = 0.068 x 10(9)/l). All the patients were intravenous drug addicts. Likewise, 37 other significant bacteremias were reviewed. The positivity of the blood culture as the sole sample or associated to respiratory isolations, changed the initial diagnosis and classified the picture as disseminated tuberculosis on 6 occasions (43%). All the patients presented pictures of disseminated tuberculosis although only four had been previously diagnosed of AIDS., Conclusions: Bacteremia by M. tuberculosis is frequent in patients infected by the human immunodeficiency virus. M. tuberculosis (27.4%) was the most frequently isolated microorganism in blood cultures in this study. The processing of blood cultures for mycobacteria may be useful in patients positive for the human immunodeficiency virus with tuberculosis in order to confirm the diagnosis of disseminated tuberculosis. The isolation of M. tuberculosis in the blood may vary the initial diagnosis and could modify the prevalence of AIDS cases in Spain.

We analyze the cases of 215 adult patients affected from tuberculosis (TB) and infection due to human immunodeficiency virus (HIV) in the study period from December 6th, 1986 to January 31st of 1992. Disease affected specially the group of drug addict patients (DAP) with a 74.88%, followed by paid plasma donors (PPD) from our city with a 12.09%. Sexual transmission was the route of contamination with the HIV in 16 cases. In five cases atypical mycobacteria were detected. First-line anti-tuberculostatics drugs activity against Mycobacterium tuberculosis was excellent. A total of 17 cases with toxicity to any of these drugs were described. TB was located in the lung in 108 cases (50.23%), in 74 cases out of the lung (34.41%) and in 33 cases there was intrapulmonary as well as extrapulmonary affectation (15.34%). TB was diagnosed at the same time that a disease which met AIDS criteria in 13.49% of cases, TB was diagnosed first in 32.55% of cases, and AIDS was diagnosed before TB in only 7.91% of cases. Fever was the predominant symptom (88.84%), together with toxic status at admittance (80.47%) and deteriorated immune situation with lymphocytes count decrease (mean 1240/mm) and CD4 (mean value 134.5/mm) together with a mean raised IgA (492.85 mg/dl). Thorax radiography was normal in 34.88%. In 33 of these patients TB was localized in the lung, in 27.91% primary radiologic types were observed while in 31.16% reactivation types. In 51 cases (23.72%) tuberculosis was detected in patients (DAP) who were forwarded from the penitentiary system.(ABSTRACT TRUNCATED AT 250 WORDS)

We report the case of a 25-year-old, HIV-positive patient (group IV, A, C2 clinical stage) with a widespread dermatophyte infection. He was a male gypsy with a known history of intravenous drug abuse. After an episode of cerebral toxoplasmosis for which he was treated with systemic steroids (because of cerebral oedema) he developed, over 16 days, a remarkably extensive ringworm of the trunk due to an unusual zoophilic dermatophyte, Microsporum (Trichophyton) gallinae. Human infection with this dermatophyte species is unusual: there are as few as seven proven reported cases, all of whom had localized lesions. This is the first widespread and severe case reported in man and also the first reported from Spain.