We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis.
A ...randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy.
Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 95% confidence interval, .93-1.8; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018).
Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events.
NCT01898338.
To evaluate the prevalence of transmitted drug resistance (TDR) and non-B subtypes in patients with acute/recent HIV-1 infection in Barcelona during the period 1997-2012.
Patients from the "Hospital ...Clínic Primary HIV-1 Infection Cohort" with a genotyping test performed within 180 days of infection were included. The 2009 WHO List of Mutations for Surveillance of Transmitted HIV-1 Drug Resistance was used for estimating the prevalence of TDR and phylogenetic analysis for subtype determination.
189 patients with acute/recent HIV-1 infection were analyzed in 4 time periods (1997-2000, n=28; 2001-4, n=42; 2005-8, n=55 and 2009-12, n=64). The proportion of patients with acute/recent HIV-1 infection with respect to the total of newly HIV-diagnosed patients in our center increased over the time and was 2.18%, 3.82%, 4.15% and 4.55% for the 4 periods, respectively (p=0.005). The global prevalence of TDR was 9%, or 17.9%, 9.5%, 3.6% and 9.4% by study period (p=0.2). The increase in the last period was driven by protease-inhibitor and nucleoside-reverse-transcriptase-inhibitor resistance mutations while non-nucleoside-reverse-transcriptase inhibitor TDR and TDR of more than one family decreased. The overall prevalence of non-B subtypes was 11.1%, or 0%, 4.8%, 9.1% and 20.3 by study period (p=0.01). B/F recombinants, B/G recombinants and subtype F emerged in the last period. We also noticed an increase in the number of immigrant patients (p=0.052). The proportion of men-who-have-sex-with-men (MSM) among patients with acute/recent HIV-1 infection increased over the time (p=0.04).
The overall prevalence of TDR in patients with acute/recent HIV-1 infection in Barcelona was 9%, and it has stayed relatively stable in recent years. Non-B subtypes and immigrants proportions progressively increased.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To analyse the effectiveness of dalbavancin (DBV) in clinical practice as consolidation therapy in patients with bloodstream infection (BSI) and/or infective endocarditis (IE) produced by ...gram-positive cocci (GPC), as well as its safety and pharmacoeconomic impact.
A multicentre, observational and retrospective study was conducted of hospitalised patients with IE and/or BSI produced by GPC who received at least one dose of DBV. Clinical response was assessed during hospitalization, at 3 months and at 1 year.
Eighty-three patients with median age of 73 years were enrolled; 73.5% were male; 59.04% had BSI and 49.04% IE (44.04% prosthetic valve IE, 32.4% native IE, 23.5% pacemaker lead). The most frequently isolated microorganism was Staphylococcus aureus in BSI (49%) and coagulase-negative staphylococci in IE (44.1%). All patients with IE were clinically cured in hospital; at 12 months, there was 2.9% loss to follow-up, 8.8% mortality unrelated to IE, and 2.9% therapeutic failure rate. The percentage effectiveness of DBV to treat IE was 96.7%. The clinical cure rate for BSI was 100% during hospital stay and at 3 months; there were no recurrences or deaths during the follow-up. No patient discontinued treatment for adverse events. The saving in hospital stay was 636 days for BSI (315,424.20€) and 557 days for IE (283,187.45€).
DBV is an effective consolidation antibiotic therapy in clinically stabilized patients with IE and/or BSI. It proved to be a cost-effective treatment, reducing the hospital stay, thanks to the pharmacokinetic/pharmacodynamic profile of this drug.
The presence of neutralizing antibodies (NAbs) is a major correlate of protection for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Thus, different in vitro ...pseudoviruses‐based assays have been described to detect NAbs against SARS‐CoV‐2. However, the determination of NAbs against SARS‐CoV‐2 in people living with HIV (PLWH) through HIV‐based pseudoparticles could be influenced by cross‐neutralization activity or treatment, impeding accurate titration of NAbs. Two assays were compared using replication‐defective HIV or VSV‐based particles pseudotyped with SARS‐CoV‐2 spike to measure NAbs in COVID‐19‐recovered and COVID‐19‐naïve PLWH. The assay based on HIV‐pseudoparticles displayed neutralization activity in all COVID‐19‐recovered PLWH with a median neutralizing titer 50 (NT50) of 1417.0 (interquartile range IQR: 450.3−3284.0), but also in 67% of COVID‐19‐naïve PLWH (NT50: 631.5, IQR: 16.0−1535.0). Regarding VSV‐pseudoparticles system, no neutralization was observed in COVID‐19‐naïve PLWH as expected, whereas in comparison with HIV‐pseudoparticles assay lower neutralization titers were measured in 75% COVID‐19‐recovered PLWH (NT50: 100.5; IQR: 20.5−1353.0). Treatment with integrase inhibitors was associated with inaccurate increase in neutralization titers when HIV‐based pseudoparticles were used. IgG purification and consequent elimination of drugs from samples avoided the interference with retroviral cycle and corrected the lack of specificity observed in HIV‐pseudotyped assay. This study shows methodological alternatives based on pseudoviruses systems to determine specific SARS‐CoV‐2 neutralization titers in PLWH.
•Non-HACEK endocarditis affects elderly patients with high comorbidity.•There are difference between Enterobacterales and NF-GNB cases.•Advanced age and prosthetic valve confer a worse ...prognosis.•Surgery may not be indicated in all cases.
Infective endocarditis (IE) due to non-HACEK bacilli (Haemophilus species, Actinobacillus, Cardiobacterium, Eikenella, or Kingella) is uncommon and poorly described. The objectives of this study were to describe non-HACEK Gram-Negative Bacilli (GNB) IE cases and compare characteristic of IE produced by Enterobacterales and non-fermenting (NF) GNB.
From January 2008 to December 2018, 3910 consecutive patients with definitive IE diagnosis, defined with Modified Duke criteria, either clinical or pathological criteria (e.g. demonstration of non-HACEK GNB in valve culture)were prospectively included.
A total of 104 IE cases were caused by non-HACEK GNB (2.6%). Compared to IE due to other microorganisms (excluding HACEK GNB), patients with non-HACEK GNB IE presented with higher age (71 years IQR 62–78 vs 68 years IQR: 57–77; p = 0.026), higher proportion of women (52% vs 31.5%, p < 0.001), higher Charlson Index (5 IQR: 4–8 vs 4 IQR 3–7, p = 0.003) and higher in-hospital mortality (36.5% vs 27.1%, p = 0.034). Enterobacterales cases were more frequently associated with genitourinary focus (32.8% vs 5.0%, p = 0.001). NFGNB endocarditis more frequently affected right valves (20.0% vs. 6.3%, p = 0.033), had more common healthcare-related acquisition (67.5% vs. 43.7%, p = 0.030) and venous catheter as focus (40.0% vs. 17.2%, p = 0.019). In the multivariant model, factors related with hospital mortality were: age (OR 1.05, 95%CI 1.00–1.09, p = 0.042), prosthetic valve (OR 2.31, 95%CI 0.90–5.88, p = 0.080), and not performing surgery when indicated (OR 3.60, 95%CI 1.17–11.05, p = 0.025).Patients treated with quinolone combination had lower mortality (OR 0.29; 95%CI 0.09–0.96; p = 0.043).
Non-HACEK GNB IE is a rare infection characterized by affecting elderly patients with high comorbidity, nosocomial acquisition and unfavorable outcome. Age, prosthetic valve and not performing surgery when indicated are associated with mortality.
The objective of the study is to quantify the effect of climate change on the climatic risks associated with droughts and diminished water resources in the eastern Iberian Peninsula. For this ...purpose, this work analyses the 70-year historical series (1952–2021) of daily rainfall data from 353 meteorological stations. They are located in a key recharge area of the hydrological system, the Sierra de Albarracín, where three important rivers originate, namely the Tagus, the Júcar and the Turia, as do several tributaries of the Guadiana and Ebro rivers. It analyses trends in: annual and seasonal rainfall volumes with specific studies about their intensity according to certain percentiles; the number of rainy days, dry spell duration (< 1 mm/day) and drought evolution with the Standardized Precipitation Evaporation Index. The most relevant results are: (1) the second 35 years of the study period (1987–2021) were notably drier than the first part (1952–1986), with smaller volumes and fewer days with recorded precipitation; (2) summer and winter were most affected by pluviometric decrease, with losses of >50% of rainfall volume at some stations; (3) moderate rainfall significantly reduced between the 50th and 95th percentiles, which were more important in the system's water recharge; (4) the stations with a negative precipitation trend predominated; (5) the medium- and long-term analyses (12 and 36 months) highlighted the drought situation in which the headwaters of the analyzed basins are immersed. The trend indicates that the situation will become critical.
Graphical abstract Display omitted
•The study shows a serious situation for a key area of the hydrological system of the Iberian Peninsula.•Negative trends predominate. Comparing two 35-year periods, the most recent one shows less precipitation.•The most affected seasons are summer and winter, with rainfall reductions of over 50% in some areas.•Drought analysis reveals that the negative SPEI phase initiated in the 1980s tends to be prolonged.•The situation in the Tagus headwater is of concern and should be taken into account in future plans.
Given the increasing need for complete rainfall data networks, in recent years have been proposed diverse methods for filling gaps in observed precipitation series, progressively more advanced that ...traditional approaches to overcome the problem. The present study has consisted in validate 10 methods (6 linear, 2 non-linear and 2 hybrid) that allow multiple imputation, i.e., fill at the same time missing data of multiple incomplete series in a dense network of neighboring stations. These were applied for daily and monthly rainfall in two sectors in the Júcar River Basin Authority (east Iberian Peninsula), which is characterized by a high spatial irregularity and difficulty of rainfall estimation. A classification of precipitation according to their genetic origin was applied as pre-processing, and a quantile-mapping adjusting as post-processing technique. The results showed in general a better performance for the non-linear and hybrid methods, highlighting that the non-linear PCA (NLPCA) method outperforms considerably the Self Organizing Maps (SOM) method within non-linear approaches. On linear methods, the Regularized Expectation Maximization method (RegEM) was the best, but far from NLPCA. Applying EOF filtering as post-processing of NLPCA (hybrid approach) yielded the best results.
•Ten methods for automatic gap filling in dense networks of observed rainfall data have been validated and compared.•The study has been applied for daily and monthly data in Eastern of Spain, where rainfall presents very high irregularity.•Methods based on NLPCA approach were the best. A synoptic based pre-classification and a post-process QM were necessary.•These methods (NLPCA-QM and NLPCA+EOF-QM) are applied in a novel way for the specific purpose of rainfall gap filling.
•Infective endocarditis (IE) has high mortality and morbidity and requires long hospital stays to deliver the antibiotic treatment recommended in clinical practice guidelines.•Dalbavancin (DBV) is a ...highly effective and safe consolidation therapy for patients with IE due to Gram-positive cocci, with a very low frequency of adverse events.•DBV is an especially cost-effective approach of IE because it facilitates the discharge of patients, reducing their hospital stay.
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.
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.
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.
DBV is highly effective, safe, and cost-effective as consolidation therapy in patients with IE by Gram-positive cocci, with few adverse events.
IFN-based therapy against hepatitis C recurrence after liver transplantation (LT) has poor effectiveness and tolerability. In HIV/HCV-coinfected liver transplant recipients, the results are even ...poorer. Here, we report our experience using direct antiviral agents (DAAs) in 11 consecutive coinfected patients within the LT setting.
Four patients with compensated cirrhosis and hepatocellular carcinoma were treated while awaiting LT and seven patients received antiviral therapy due to severe hepatitis C recurrence after LT fibrosing cholestatic hepatitis (n = 1), fibrosis stage ≥F3 (n = 2) and decompensated cirrhosis (n = 4). Patients were treated with different sofosbuvir-based regimens with or without ribavirin for 12 or 24 weeks.
Sustained virological response (SVR) was achieved in all patients. Two of the four patients treated while awaiting LT reached the time of transplant with undetectable HCV-RNA that remained undetectable 12 weeks after LT, one patient had detectable HCV-RNA at the time of transplant but achieved SVR after completing 12 weeks of therapy after LT and the last patient is still on the waiting list. Seven patients with severe post-LT hepatitis C recurrence were treated within 11-120 months after LT. In these patients, viral eradication was associated with an improvement in liver function and clinical decompensation. Tolerance to antiviral therapy was good and only four patients reported mild adverse events.
IFN-free regimens are effective and well tolerated in HIV/HCV-coinfected patients within the LT setting, but more data are needed to confirm our promising results and to establish the best treatment option in this population.
Interventions during primary HIV infection (PHI) can modify the clinical course during the chronic phase. The long-term effect of structured treatment interruptions (STI) followed by low doses of ...interleukin-2 (IL-2) in treated PHI patients is unknown.
Twelve PHI patients with viral load (VL) <20 copies/mL, CD4 cells >500 cells/mm3, and CD4/CD8 ratio >1, on antiretroviral therapy (ART) initiated within the first 90 days of infection and continued for at least 12 months were included. They underwent four STI and were then allocated (week 0 of the study) to ART alone or ART plus low doses of IL-2. ART was stopped once VL <20 copies/mL ('final stop'). Primary endpoints were VL<3000 copies/mL and CD4 cells >500 cells/mm3 at 48 weeks; secondary endpoints were immune activation, inflammatory markers until 48 weeks and the time before resuming ART (CD4 <350 cells/mm3 or AIDS) after 'final stop', compared between groups.
Ten out of 12 patients were males, median age was 35 years and the main risk was men-who-have-sex-with-men. Only one out of 12 patients (in the STI group) maintained VL<3000 copies/mL and CD4 cells >500 cells/mm3 without ART at 48 weeks. All other virological and immunological parameters were comparable between groups at week 0, 'final stop' and week 48. However, the proportion of CD8-CD38+ cells, tumor necrosis factor and srIL-2 were higher in the IL-2 group at 'final stop' and week 24. All these differences vanished during follow-up. At 5 years after the final stop 3 out of 6 patients in the IL-2 group and 6 out of 6 patients in the STI group have resumed ART (P = 0.19).
STI and IL-2 failed to achieve virological control after ART interruption. STI were not deleterious in long-term follow-up, an important issue for eradication and functional cure trials.
ClinicalTrials.gov NCT02300623.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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