Healthcare-associated pneumonia: a prospective study in Spain

Objective: The aim of the study was to describe the epidemiological characteristics and factors related to outcome in Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated pneumonia (HCAP). Methods: A 3-year prospective observational epidemiological case study of HCAP was conducted in seven Spanish hospitals. Microbiological and patient characteristics and outcomes were collected and classified by causative pathogen into 4 categories: "S. pneumoniae", "MRSA", "Others" and "Unknown". Patients were followed up 30 days after discharge. Results: A total of 258 (84.6%) patients were enrolled (170 were men [65.9%]). Mean age was 72.4 years ± 15 years (95% CI [70.54-74.25]). The etiology of pneumonia was identified in 73 cases (28.3%): S. pneumoniae in 35 patients (13.6%), MRSA in 8 (3.1%), and other microorganisms in 30 patients (11.6%). Significant differences in rates of chronic obstructive pulmonary disease (p < 0.05), previous antibiotic treatment (p<0.05), other chronic respiratory diseases, inhaled corticosteroids (p <0.01), and lymphoma (p < 0.05) were observed among the four groups. Patients with MRSA pneumonia had received more previous antibiotic treatment (87.5%). Thirty-three (12.8%) patients died during hospitalisation; death in 27 (81.2%) was related to pneumonia. Conclusions: The etiology of HCAP was identified in only one quarter of patients, with S. pneumoniae being the most prevalent microorganism. Patients with chronic respiratory diseases more frequently presented HCAP due to MRSA than to S. pneumoniae. Death at hospital discharge was related in most cases to pneumonia.Objetivo: Describir las características epidemiológicas y factores relacionados con la neumonía asociada a cuidados sanitarios (NACS) causada por Streptococcus pneumoniae y Staphylococcus aureus resistente a meticilina (SARM). Pacientes y métodos: Estudio epidemiológico observacional prospectivo de casos a 3 años en siete hospitales españoles. Se recogieron las características microbiológicas y de los pacientes y sus resultados y se clasificaron en función del patógeno causante en 4 categorías: ?S. pneumoniae?, ?SARM?, ?Otros? y ?Desconocido?. Al alta, se realizó un seguimiento de 30 días. Resultados: Se incluyeron 258 (84,6%) pacientes (170 hombres [65.9%]; edad media 72,4 años ± 15 años (95% IC [70,54-74,25]). La etiología de la neumonía se identificó en 73 casos (28,3%):S. pneumoniae en 35 pacientes (13,6%), SARM en 8 (3,1%) y otros microorganismos en 30 pacientes (11,6%). Hubo diferencias significativas en tasas de enfermedad pulmonar obstructiva crónica (p < 0,05), tratamiento antibiótico previo (p < 0,05), otras enfermedades respiratorias crónicas, corticoides inhalados (p < 0,01) y linfoma (p < 0,05) entre los cuatro grupos. Los pacientes con NACS causada por SARM recibieron tratamiento antibiótico previo en mayor medida (87,5%). Treinta y tres (12,8%) pacientes murieron durante la hospitalización; en 27 (81,2%) debido a la neumonía. Conclusiones: Se identificó la etiología de la NACS en solo un cuarto de los pacientes, siendo S. pneumoniae el patógeno más frecuente. En los pacientes con enfermedades respiratorias crónicas fue más frecuente la NACS causada por SARM. La muerte tras el alta hospitalaria se relacionó con la neumonía en la mayoría de los casos

EN-DALBACEN 2.0 Cohort: real-life study of dalbavancin as sequential/consolidation therapy in patients with infective endocarditis due to Gram-positive cocci

Objectives: Infective endocarditis (IE) has high mortality and morbidity and requires long hospital stays to deliver the antibiotic treatment recommended in clinical practice guidelines. We aimed to analyse the health outcomes of the use of dalbavancin (DBV) in the consolidation treatment of IEs caused by Gram-positive cocci and to perform a pharmacoeconomic study. Materials and methods: This observational, retrospective, Spanish multicentre study in patients with IE who received DBV as part of antibiotic treatment in consolidation phase were followed for at least 12 months. The study was approved by the Provincial Committee of the coordinating centre. Results: The study included 124 subjects, 70.2% male, with a mean age of 67.4 years and median Charlson index of 4 (interquartile range: 2.5-6). Criteria for definite IE were met by 91.1%. Coagulase-negative staphylococci (38.8%), Staphylococcus aureus (22.6%), Enterococcus faecalis (19.4%), and Streptococcus Spp. (9.7%) were isolated more frequently, all susceptible to vancomycin. Before DVB administration, 91.2% had undergone surgery; 60.5% had received a second regimen for 24.5 d (16.6-56); and 20.2% had received a third regimen for 14.5 d (12-19.5). DBV was administered to facilitate discharge in 95.2% of cases. At 12 months, the effectiveness was of 95.9%, and there was 0.8% loss to follow-up, 0.8% IE-related death, and 3.2% relapse. Adverse events were recorded in 3.2%. The hospital stay was reduced by 14 d, and there was a mean savings of 5548.57 €/patient vs. conventional treatments. Conclusion: DBV is highly effective, safe, and cost-effective as consolidation therapy in patients with IE by Gram-positive cocci, with few adverse events

Genotypic tropism testing in proviral DNA to guide maraviroc initiation in aviremic subjects: 48‐week analysis of the PROTEST study

Introduction: In a previous interim 24‐week virological safety analysis of the PROTEST study [1], initiation of Maraviroc (MVC) plus 2 nucleoside reverse‐transcriptase inhibitors (NRTIs) in aviremic subjects based on genotypic tropism testing of proviral HIV‐1 DNA was associated with low rates of virological failure. Here we present the final 48‐week analysis of the study. Methods PROTEST was a phase 4, prospective, single‐arm clinical trial (ID: NCT01378910) carried on in 24 HIV care centres in Spain. Maraviroc‐naïve HIV‐1‐positive adults with HIV‐1 RNA (VL) 10% in a singleton), initiated MVC with 2 NRTIs and were followed for 48 weeks. Virological failure was defined as two consecutive VL>50 c/mL. Recent adherence was calculated as: (# pills taken/# pills prescribed during the previous week)*100. Results Tropism results were available from 141/175 (80.6%) subjects screened: 87/141 (60%) were R5 and 74/87 (85%) were finally included in the study. Their median age was 48 years, 16% were women, 31% were MSM, 36% had CDC category C at study entry, 62% were HCV+ and 10% were HBV+. Median CD4+ counts were 616 cells/mm3 at screening, and median nadir CD4+ counts were 143 cells/mm3. Previous ART included PIs in 46 (62%) subjects, NNRTIs in 27 (36%) and integrase inhibitors (INIs) in 1 (2%). The main reasons for treatment change were dyslipidemia (42%), gastrointestinal symptoms (22%), and liver toxicity (15%). MVC was given alongside TDF/FTC in 40 (54%) subjects, ABC/3TC in 30 (40%), AZT/3TC in 2 (3%) and ABC/TDF in 2 (3%). Sixty‐two (84%) subjects maintained VL<50 c/mL through week 48, whereas 12 (16%) discontinued treatment: two (3%) withdrew informed consent, one (1%) had a R5→X4 shift in HIV tropism between the screening and baseline visits, one (1%) was lost to follow‐up, one (1%) developed an ART‐related adverse event (rash), two (3%) died due to non‐study‐related causes (1 myocardial infarction at week 0 and 1 lung cancer at week 36), and five (7%) developed protocol‐defined virological failure, although two of them regained VL<50 c/mL with the same MVC regimen (Table 1). Conclusions Initiation of MVC plus 2 NRTIs in aviremic subjects based on genotypic tropism testing of proviral HIV‐1 DNA is associated with low rates of virological failure up to one year

Genotypic tropism testing in proviral DNA to guide maraviroc initiation in aviremic subjects: 48-week analysis of the PROTEST study

Introduction: In a previous interim 24-week virological safety analysis of the PROTEST study (1), initiation of Maraviroc (MVC) plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs) in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA was associated with low rates of virological failure. Here we present the final 48-week analysis of the study. Methods: PROTEST was a phase 4, prospective, single-arm clinical trial (ID: NCT01378910) carried on in 24 HIV care centres in Spain. Maraviroc-naïve HIV-1-positive adults with HIV-1 RNA (VL) 10% in a singleton), initiated MVC with 2 NRTIs and were followed for 48 weeks. Virological failure was defined as two consecutive VL>50 c/mL. Recent adherence was calculated as: (# pills taken/# pills prescribed during the previous week)*100. Results: Tropism results were available from 141/175 (80.6%) subjects screened: 87/141 (60%) were R5 and 74/87 (85%) were finally included in the study. Their median age was 48 years, 16% were women, 31% were MSM, 36% had CDC category C at study entry, 62% were HCV+ and 10% were HBV+. Median CD4+ counts were 616 cells/mm(3) at screening, and median nadir CD4+ counts were 143 cells/mm(3). Previous ART included PIs in 46 (62%) subjects, NNRTIs in 27 (36%) and integrase inhibitors (INIs) in 1 (2%). The main reasons for treatment change were dyslipidemia (42%), gastrointestinal symptoms (22%), and liver toxicity (15%). MVC was given alongside TDF/FTC in 40 (54%) subjects, ABC/3TC in 30 (40%), AZT/3TC in 2 (3%) and ABC/TDF in 2 (3%). Sixty-two (84%) subjects maintained VL<50 c/mL through week 48, whereas 12 (16%) discontinued treatment: two (3%) withdrew informed consent, one (1%) had a R5→X4 shift in HIV tropism between the screening and baseline visits, one (1%) was lost to follow-up, one (1%) developed an ART-related adverse event (rash), two (3%) died due to non-study-related causes (1 myocardial infarction at week 0 and 1 lung cancer at week 36), and five (7%) developed protocol-defined virological failure, although two of them regained VL<50 c/mL with the same MVC regimen (Table 1). Conclusions: Initiation of MVC plus 2 NRTIs in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure up to one year

Genotypic tropism testing in proviral DNA to guide maraviroc initiation in aviremic subjects: 48-week analysis of the PROTEST study

Introduction: In a previous interim 24-week virological safety analysis of the PROTEST study (1), initiation of Maraviroc (MVC) plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs) in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA was associated with low rates of virological failure. Here we present the final 48-week analysis of the study. Methods: PROTEST was a phase 4, prospective, single-arm clinical trial (ID: NCT01378910) carried on in 24 HIV care centres in Spain. Maraviroc-naïve HIV-1-positive adults with HIV-1 RNA (VL) 10% in a singleton), initiated MVC with 2 NRTIs and were followed for 48 weeks. Virological failure was defined as two consecutive VL>50 c/mL. Recent adherence was calculated as: (# pills taken/# pills prescribed during the previous week)*100. Results: Tropism results were available from 141/175 (80.6%) subjects screened: 87/141 (60%) were R5 and 74/87 (85%) were finally included in the study. Their median age was 48 years, 16% were women, 31% were MSM, 36% had CDC category C at study entry, 62% were HCV+ and 10% were HBV+. Median CD4+ counts were 616 cells/mm(3) at screening, and median nadir CD4+ counts were 143 cells/mm(3). Previous ART included PIs in 46 (62%) subjects, NNRTIs in 27 (36%) and integrase inhibitors (INIs) in 1 (2%). The main reasons for treatment change were dyslipidemia (42%), gastrointestinal symptoms (22%), and liver toxicity (15%). MVC was given alongside TDF/FTC in 40 (54%) subjects, ABC/3TC in 30 (40%), AZT/3TC in 2 (3%) and ABC/TDF in 2 (3%). Sixty-two (84%) subjects maintained VL<50 c/mL through week 48, whereas 12 (16%) discontinued treatment: two (3%) withdrew informed consent, one (1%) had a R5→X4 shift in HIV tropism between the screening and baseline visits, one (1%) was lost to follow-up, one (1%) developed an ART-related adverse event (rash), two (3%) died due to non-study-related causes (1 myocardial infarction at week 0 and 1 lung cancer at week 36), and five (7%) developed protocol-defined virological failure, although two of them regained VL<50 c/mL with the same MVC regimen (Table 1). Conclusions: Initiation of MVC plus 2 NRTIs in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure up to one year

Antibiotic selection in the treatment of acute invasive infections by Pseudomonas aeruginosa: Guidelines by the Spanish Society of Chemotherapy

Pseudomonas aeruginosa is characterized by a notable intrinsic resistance to antibiotics, mainly mediated by the expression of inducible chromosomic β-lactamases and the production of constitutive or inducible efflux pumps. Apart from this intrinsic resistance, P. aeruginosa possess an extraordinary ability to develop resistance to nearly all available antimicrobials through selection of mutations. The progressive increase in resistance rates in P. aeruginosa has led to the emergence of strains which, based on their degree of resistance to common antibiotics, have been defined as multidrug resistant, extended-resistant and panresistant strains. These strains are increasingly disseminated worldwide, progressively complicating the treatment of P. aeruginosa infections. In this scenario, the objective of the present guidelines was to review and update published evidence for the treatment of patients with acute, invasive and severe infections caused by P. aeruginosa. To this end, mechanisms of intrinsic resistance, factors favoring development of resistance during antibiotic exposure, prevalence of resistance in Spain, classical and recently appeared new antibiotics active against P. aeruginosa, pharmacodynamic principles predicting efficacy, clinical experience with monotherapy and combination therapy, and principles for antibiotic treatment were reviewed to elaborate recommendations by the panel of experts for empirical and directed treatment of P. aeruginosa invasive infections

Clinical characteristics and outcome of Spanish patients with ANCA-associated vasculitides Impact of the vasculitis type, ANCA specificity, and treatment on mortality and morbidity

The aim of this study was to describe the clinical characteristics of ANCA-associated vasculitides (AAV) at presentation, in a wide cohort of Spanish patients, and to analyze the impact of the vasculitis type, ANCA specificity, prognostic factors, and treatments administered at diagnosis, in the outcome. A total of 450 patients diagnosed between January 1990 and January 2014 in 20 Hospitals from Spain were included. Altogether, 40.9% had granulomatosis with polyangiitis (GPA), 37.1% microscopic polyangiitis (MPA), and 22% eosinophilic granulomatosis with polyangiitis (EGPA). The mean age at diagnosis was 55.6±17.3 years, patients with MPA being significantly older (P<0.001). Fever, arthralgia, weight loss, respiratory, and ear-nose-throat (ENT) symptoms, were the most common at disease onset. ANCAs tested positive in 86.4% of cases: 36.2% C-ANCA-PR3 and 50.2% P-ANCA-MPO. P-ANCA-MPO was significantly associated with an increased risk for renal disease (OR 2.6, P<0.001) and alveolar hemorrhage (OR 2, P=0.010), while C-ANCA-PR3 was significantly associated with an increased risk for ENT (OR 3.4, P<0.001) and ocular involvement (OR 2.3, P=0.002). All patients received corticosteroids (CS) and 74.9% cyclophosphamide (CYC). The median follow-up was 82 months (IQR 100.4). Over this period 39.9% of patients suffered bacterial infections and 14.6% opportunistic infections, both being most prevalent in patients with highcumulated doses of CYC and CS (P<0.001). Relapses were recorded in 36.4% of cases with a mean rate of 2.5±2.3, and were more frequent in patients with C-ANCA-PR3 (P=0.012). The initial disease severity was significantly associated with mortality but not with the occurrence of relapses. One hundred twenty-nine (28.7%) patients (74 MPA, 41 GPA, 14 EGPA) died. The mean survival was 58 months (IQR 105) and was significantly lower for patients with MPA (P<0.001). Factors independently related to death were renal involvement (P=0.010), cardiac failure (P=0.029) and age over 65 years old (P<0.001) at disease onset, and bacterial infections (P<0.001). An improved outcome with significant decrease in mortality and treatment-related morbidity was observed in patients diagnosed after 2000, and was related to the implementation of less toxic regimens adapted to the disease activity and stage, and a drastic reduction in the cumulated CYC and CS dose

Visceral leishmaniasis caused by Leishmania infantum in a Spanish patient in Argentina: What is the origin of the infection? Case report

BACKGROUND: The question "Where have you been?" is a common one asked by doctors in Northern Europe and America when faced with clinical symptoms not typical of their country. This question must also arise in the clinics of developing countries in which non-autochthonous cases such as the one described here can appear. Important outbreaks of Leishmania infantum have been recorded in the last decade in several Latin American countries but its presence has not yet been recorded in Argentina. We report the first case of visceral leishmaniasis owing to L. infantum in this country. CASE PRESENTATION: A 71-year-old Spanish woman who has been living in Mendoza, Argentina, during the last 40 years presented with a history of high fever and shivering, anemia, leukopenia and splenomegaly over two years. Argentinian doctors did not suspect visceral leishmaniasis even when the histological analysis revealed the presence of "intracytoplasmatic spheroid particles compatible with fungal or parasitic infection". After a serious deterioration in her health, she was taken to Spain where she was evaluated and visceral leishmaniasis was established. Specific identification of the parasite was done by PCR-ELISA, isoenzyme electrophoresis and RAPD-PCR. CONCLUSION: We would like to point out that: i) cases such as the one described here, which appear in non-endemic areas, can pass unnoticed by the clinical physician. ii) in countries in which these introduced cases reside, in-depth parasitological studies are required into vectors and possible reservoirs to rule out the rare case of local infection and, once infection has taken place, to ensure that this does not spread by anthroponotic transmission or a competent reservoir

Budget Impact Analysis of Switching to Darunavir/Ritonavir Monotherapy for HIV-Infected People in Spain

Antiretrovirals, Budget-impact-analysis, Darunavir/ritonavir, HIV-infections