Reappraisal of the outcome of healthcare-associated and community-acquired bacteramia: a prospective cohort study.

BACKGROUND: Healthcare-associated (HCA) bloodstream infections (BSI) have been associated with worse outcomes, in terms of higher frequencies of antibiotic-resistant microorganisms and inappropriate therapy than strict community-acquired (CA) BSI. Recent changes in the epidemiology of community (CO)-BSI and treatment protocols may have modified this association. The objective of this study was to analyse the etiology, therapy and outcomes for CA and HCA BSI in our area. METHODS: A prospective multicentre cohort including all CO-BSI episodes in adult patients was performed over a 3-month period in 2006-2007. Outcome variables were mortality and inappropriate empirical therapy. Adjusted analyses were performed by logistic regression. RESULTS: 341 episodes of CO-BSI were included in the study. Acquisition was HCA in 56% (192 episodes) of them. Inappropriate empirical therapy was administered in 16.7% (57 episodes). All-cause mortality was 16.4% (56 patients) at day 14 and 20% (71 patients) at day 30. After controlling for age, Charlson index, source, etiology, presentation with severe sepsis or shock and inappropriate empirical treatment, acquisition type was not associated with an increase in 14-day or 30-day mortality. Only an stratified analysis of 14th-day mortality for Gram negatives BSI showed a statically significant difference (7% in CA vs 17% in HCA, p = 0,05). Factors independently related to inadequate empirical treatment in the community were: catheter source, cancer, and previous antimicrobial use; no association with HCA acquisition was found. CONCLUSION: HCA acquisition in our cohort was not a predictor for either inappropriate empirical treatment or increased mortality. These results might reflect recent changes in therapeutic protocols and epidemiological changes in community pathogens. Further studies should focus on recognising CA BSI due to resistant organisms facilitating an early and adequate treatment in patients with CA resistant BSI.

Impact of inadequate empirical therapy on the mortality of patients with bloodstream infections: a propensity score-based analysis.

The impact of the adequacy of empirical therapy on outcome for patients with bloodstream infections (BSI) is key for determining whether adequate empirical coverage should be prioritized over other, more conservative approaches. Recent systematic reviews outlined the need for new studies in the field, using improved methodologies. We assessed the impact of inadequate empirical treatment on the mortality of patients with BSI in the present-day context, incorporating recent methodological recommendations. A prospective multicenter cohort including all BSI episodes in adult patients was performed in 15 hospitals in Andalucía, Spain, over a 2-month period in 2006 to 2007. The main outcome variables were 14- and 30-day mortality. Adjusted analyses were performed by multivariate analysis and propensity score-based matching. Eight hundred one episodes were included. Inadequate empirical therapy was administered in 199 (24.8%) episodes; mortality at days 14 and 30 was 18.55% and 22.6%, respectively. After controlling for age, Charlson index, Pitt score, neutropenia, source, etiology, and presentation with severe sepsis or shock, inadequate empirical treatment was associated with increased mortality at days 14 and 30 (odds ratios [ORs], 2.12 and 1.56; 95% confidence intervals [95% CI], 1.34 to 3.34 and 1.01 to 2.40, respectively). The adjusted ORs after a propensity score-based matched analysis were 3.03 and 1.70 (95% CI, 1.60 to 5.74 and 0.98 to 2.98, respectively). In conclusion, inadequate empirical therapy is independently associated with increased mortality in patients with BSI. Programs to improve the quality of empirical therapy in patients with suspicion of BSI and optimization of definitive therapy should be implemented.

Efficacy and safety of pegylated interferon plus ribavirin in HIV and hepatitis C virus-coinfected patients with advanced immunosuppression.

BACKGROUND: The aim of this study was to assess the efficacy and safety of pegylated interferon (IFN) plus ribavirin (RBV) in human immunodeficiency virus (HIV) and hepatitis C virus (HCV)-coinfected patients with severe immunodeficiency in a clinical cohort. BACKGROUND. A total of 542 HIV-infected patients receiving treatment with pegylated IFN plus RBV from June 2001 through April 2007 were included in this study. The outcome variables were sustained virologic response (SVR) rate and the emergence of AIDS-defining events during HCV infection therapy. SVR rates among patients with a CD4 cell count 250 cells/mm(3). The association between SVR and potential predictors was analyzed. RESULTS: Ten (26%) of 39 individuals with a baseline CD4 cell count 250 cells/mm(3) and 198 (39%) of 503 with baseline CD4 cell counts >or=250 CD4 cells/mm(3) achieved SVR (P = .09). In a nested case-control study with populations matched at a 1:2 ratio, the SVR rate was 26% in the CD4 cell count 250 cells/mm(3) group and 32% in the CD4 cell count >250 cells/mm(3) group (P = .5). Baseline CD4 cell count (250 cells/mm(3) vs >250 cells/mm(3)) was not associated with SVR in the multivariate analysis. Two (5%) individuals in the CD4 cell count 250 cells/mm(3) group experienced opportunistic events during follow-up. In the CD4 cell count 250 cells/mm(3) group, severe hematological toxicity and pegylated IFN or RBV dosage reductions occurred in 16 (41%) and 12 (31%) patients, respectively. In the CD4 cell count >250 cells/mm(3) group, severe hematological toxicity and pegylated IFN or RBV dosage reductions occurred in 29% (P = .1) and 20% (P = .1) of patients, respectively. CONCLUSIONS: The efficacy of pegylated IFN plus RBV in HIV-HCV-coinfected patients with advanced immunosuppression is substantial and not significantly different to that observed in the overall coinfected population. HCV therapy is generally safe in the population of coinfected patients with advanced immunosuppression.

Etiology of spontaneous pneumothorax in 105 HIV-infected patients without highly active antiretroviral therapy.

INTRODUCTION: Spontaneous pneumothorax (SP) is a frequent complication in non-treated HIV-infected patients as a complication of opportunistic infections and tumours. OBJECTIVE: To analyse the aetiology of SP in non-treated HIV patients. PATIENTS AND METHODS: Observational study of SP cases observed in a cohort of 9831 of non-treated HIV-infected patients attended in seven Spanish hospitals. RESULTS: 105 patients (1.06%) developed SP. The aetiological cause was identified in 89 patients. The major causes identified were: bacterial pneumonia (36 subjects, 34.3%); Pneumocystis jiroveci pneumonia (PJP) (31 patients, 29.5%); and pulmonary tuberculosis (17 cases, 15.2%). The most common cause of SP in drugs users was bacterial pneumonia (40%), whereas PJP was more common (65%) in sexual transmitted HIV-patients. The most common cause of bilateral SP was PJP (62.5%) whereas unilateral SP was most commonly associated with bacterial pneumonia (40.2%). The most common cause of SP in patients with a CD4+ lymphocyte count >200 cells/ml and in patients without AIDS criteria was bacterial pneumonia. PJP was the more common cause in patients with a CD4+ lymphocyte count <200 cells/ml or with AIDS. CONCLUSION: The incidence of SP in non-treated HIV-infected patients was 1.06%. The aetiology was related to the patients risk practices and to their degree of immunosuppression. Bacterial pneumonia was the most common cause of SP.

Efficacy of pegylated interferon plus ribavirin treatment in HIV/hepatitis C virus co-infected patients receiving abacavir plus lamivudine or tenofovir plus either lamivudine or emtricitabine as nucleoside analogue backbone.

OBJECTIVES: To compare the response to hepatitis C virus (HCV) therapy among human immunodeficiency virus (HIV)/HCV co-infected patients receiving a nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] backbone consisting of abacavir plus lamivudine with that observed in subjects who receive tenofovir plus lamivudine or emtricitabine. METHODS: A total of 256 subjects, enrolled in a cohort of 948 HIV-infected patients who received pegylated interferon and ribavirin from October 2001 to January 2006, were included in this study. All patients were taking one protease inhibitor or one non-nucleoside reverse transcriptase inhibitor and abacavir plus lamivudine or tenofovir plus lamivudine or emtricitabine as N(t)RTI backbone during HCV therapy. Sustained virological response (SVR) rates in both backbone groups were compared. RESULTS: In an intention-to-treat analysis, 20 out of 70 (29%) individuals under abacavir and 83 out of 186 (45%) under tenofovir showed SVR (P = 0.02). N(t)RTI backbone containing tenofovir was an independent predictor of SVR in the multivariate analysis [adjusted odds ratio (95% CI), 2.6 (1.05-6.9); P = 0.03]. The association between abacavir use and lower SVR was chiefly seen in patients with plasma HCV-RNA load higher than 600 000 IU/mL and genotype 1 or 4. Among patients treated with ribavirin dose <13.2 mg/kg/day, 3 (20%) of those under abacavir versus 22 (52%) under tenofovir reached SVR (P = 0.03), whereas the rates were 31% and 38% (P = 0.4), respectively, in those receiving >/=13.2 mg/kg/day. CONCLUSIONS: HIV-infected patients who receive abacavir plus lamivudine respond worse to pegylated interferon plus ribavirin than those who are given tenofovir plus lamivudine or emtricitabine as N(t)RTI backbone, especially in those receiving lower ribavirin doses.

[Immunological, virological and clinical response in patients infected with HIV after highly active antiviral therapy with nelfinavir: prospective cohort study]. / Respuesta inmunológica, virológica y clínica en pacientes infectados por el VIH tras terapia antirretroviral de gran eficacia con nelfinavir: estudio sobre una cohorte prospectiva.

INTRODUCTION: To assess the long-term effectiveness, safety and response-related factors in a cohort of HIV-infected persons receiving antiretroviral therapy containing nelfinavir. Design and setting. Prospective, non-randomized multicenter study. METHOD: A total of 792 patients were included: 254 (32.1%) treatment-naive patients and 538 (67.9%) patients previously treated with protease inhibitors who were switched to a nelfinavir-containing regimen due to virological failure or intolerance. Factors related to virological response and to treatment failure were assessed by standard survival techniques and Cox proportional risk models. RESULTS: Nelfinavir was well tolerated; treatment had to be interrupted in only 57 patients (7.1%) because of toxicity. During a median follow-up of 12 months, 31 patients (3.9%) experienced a new AIDS-defining event or death, and 463 (58.4%) showed immunological response. Overall, 52% patients achieved plasma HIV-1 RNA levels below 500 copies/mL (57% of naive and 49% of previously treated patients), but a high rate of virological rebound (24% and 49%, respectively) was observed. Low baseline viral load and few prior treatments were factors related to virological response. Naive treatment status and a high increase in CD4 cell count were predictive of longer viral response. CONCLUSIONS: Highly active antiretroviral therapy with a nelfinavir-containing regimen was associated with favorable virological response in nearly half of previously treated patients, and most experienced clinical and immunological benefits. Nevertheless, the limited duration of virological response indicates the need for new alternative drugs.

Respuesta inmunológica, virológica y clínica en pacientes infectados por el VIH tras terapia antirretroviral de gran eficacia con nelfinavir: estudio sobre una cohorte prospectiva / Immunological, virological and clinical response in patients infected with HIV after highly active antiviral therapy with nelfinavir: prospective cohort study

INTRODUCCIÓN. Evaluar la eficacia, tolerancia y factores asociados a la respuesta a largo plazo en una cohorte de pacientes infectados por el virus de la inmunodeficiencia humana (VIH) con un tratamiento que incluya nelfinavir. DISEÑO. Estudio prospectivo y multicéntrico, no aleatorizado. MÉTODO. Se incluyeron un total de 792 pacientes: 254 (32,1 por ciento) sin ningún tratamiento previo y 538 (67,9 por ciento) previamente tratados con inhibidores de la proteasa (IP) que cambiaron a un régimen con nelfinavir. El análisis se realizó mediante el método de curvas actuariales de Kaplan-Meier y modelos de riesgo proporcional de Cox. RESULTADOS. Nelfinavir fue bien tolerado y tan sólo 57 pacientes (7,1 por ciento) interrumpieron el tratamiento debido a efectos secundarios. Tras un año de seguimiento medio, 31 pacientes (3,9 por ciento) tuvieron un nuevo episodio definitorio de sida o muerte y se observó respuesta inmunológica en 463 (58,4 por ciento). Globalmente, el 52 por ciento de los pacientes alcanzó una carga viral indetectable (57 por ciento de vírgenes y 49 por ciento de pretratados), pero un alto porcentaje de ellos (24 y 49 por ciento, respectivamente) experimentó un rebrote tras una favorable respuesta inicial. Los factores relacionados con la respuesta virológica fueron una baja carga viral al inicio y un menor número de tratamientos previos. Los pacientes sin tratamiento previo y con una respuesta inmunológica mayor tuvieron una respuesta viral más duradera. CONCLUSIONES. El tratamiento antirretroviral con nelfinavir consigue una respuesta viral favorable en casi la mitad de los pacientes pretratados y la mayoría experimentan un beneficio clínico e inmunológico. Sin embargo, la limitada durabilidad de la respuesta virológica pone de manifiesto la necesidad de nuevos fármacos alternativos (AU)

Epidemiological, clinical, and prognostic differences between the diseases caused by Mycobacterium kansasii and Mycobacterium tuberculosis in patients infected with human immunodeficiency virus: a multicenter study.

A multicenter, comparative study was performed to determine the epidemiological, clinical, and prognostic differences between the diseases caused by Mycobacterium tuberculosis and Mycobacterium kansasii in human immunodeficiency virus (HIV)-infected patients. From 1 January 1995 through 31 December 1999, 25 HIV-infected patients received diagnoses of M. kansasii infection, and another 75 were selected as control subjects from among patients who had M. tuberculosis infection. Variables associated with M. tuberculosis disease in the multivariate analysis were previous intravenous drug use (odds ratio [OR], 8; 95% confidence interval [CI], 1.5-41.4) and interstitial radiologic pattern (OR, 12.7; 95% CI, 1.7-94.3). Variables associated with M. kansasii were previous diagnosis of acquired immunodeficiency syndrome (OR, 15.8; 95% CI, 4.2-59.6) and concomitant opportunistic infections (OR, 14.2; 95% CI, 2-105.7). Clinical and radiologic features were similar for both groups, but epidemiological characteristics and prognosis were different. M. kansasii disease was associated more closely with level of immunosuppression and progression of HIV infection than was disease caused by M. tuberculosis.

Prognosis and clinical evaluation of infection caused by Rhodococcus equi in HIV-infected patients: a multicenter study of 67 cases.

OBJECTIVE: To assess the clinical characteristics and the factors that influenced the prognosis of patients with HIV and infection caused by Rhodococcus equi. DESIGN: Observational, multicenter study in 29 Spanish general hospitals. SETTING: These hospitals comprised a total of 20,250 beds for acute patients and served a population of 9,716,880 inhabitants. PATIENTS: All patients with HIV and diagnosed R equi infection until September 1998. RESULTS: During the study period, 19,374 cases of AIDS were diagnosed. Sixty-seven patients were included (55 male patients; mean +/- SD age, 31.7 +/- 5.8 years). At the time of diagnosis of R equi infection, the mean CD4+ lymphocyte count was 35/ micro L (range, 1 to 183/ micro L) and the stage of HIV infection was A3 in 10.4% of patients, B3 in 31.3%, C3 in 56.7%, and unknown in 1.5%. R equi was most commonly isolated in sputum (52.2%), blood cultures (50.7%), and samples from bronchoscopy (31.3%). Chest radiographic findings were abnormal in 65 patients (97%). Infiltrates were observed in all of them, with cavitations in 45 patients. The most active antibiotics against the strains isolated were vancomycin, amikacin, rifampicin, imipenem, ciprofloxacin, and erythromycin. After a mean follow-up of 10.7 +/- 12.8 months, 23 patients (34.3%) died due to causes related to R equi infection and 6 other patients showed evidence of progression of the infection. The absence of highly active antiretroviral therapy (HAART) was independently associated with mortality related to R equi infection (relative risk, 53.4; 95% confidence interval, 1.7 to 1,699). Survival of patients treated with HAART was much higher than that of patients who did not receive this therapy. CONCLUSIONS: Infection by R equi is an infrequent, opportunistic complication of HIV infection and occurs during advanced stages of immunodepression. In these patients, it leads to a severe illness that usually causes a bacteremic, cavitary pneumonia, although HAART can improve the prognosis.

Disminución de la frecuencia anual de endocarditis infecciosa en usuarios de drogas intravenosas en el sur de España / Decrease in the annual frequency of infections endocarditis among intravenous drug users in southern Spain

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