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.
Abstract only
206
Background: Methadone (M) is frequently used for severe cancer pain using the parenteral and oral route. The most commonly used dose ratio (DR) parenteral: oral is 1:2. However, ...methadone is highly bioavailable and a lower ratio might result in similar analgesia with less toxicity. The main objective of this RCT is to compare success and side effects with 2 ratios of parenteral to oral M: 1:2 vs 1:1.2 in hospitalized patients with cancer pain. Methods: Inpatients with cancer pain well controlled with parenteral M requiring rotation to the oral route. Double blind RCT. Outcomes included pain intensity (BPI), opioid toxicity (CTCAE), and M dose. Success was defined as good pain control with no toxicity at 72hs. Results: 39/44 randomized patients were evaluable (89%): 21 in DR 1:2 and 18 in DR 1:1.2. 71% male, median age 65. No significant difference between DR1:2 and DR1:1.2 in frequency of neuropathic pain (64 Vs 68%), Papscore A/B (100 Vs 91%), CAGE + (23 Vs 18%). Median M dose pre/post was 24.5mg±13.5 y 49 mg±27.3 for DR 1:2, Vs 23.3mg±9.4 (p: NS) y 28mg±11.3 (p < 0.01) for DR 1:1.2. The DR1:2 group developed more cumulative toxicity at dasy 1, 2 and 3 (p < 0.015, p < 0.006 y p < 0.001 respectively). Pain intensity pre/ post was: 1.58±1.3 and 0.87±1.0, ns for DR 1:2, Vs 1.13±0.7 (p:NS) and 1.07±0.9 (p:NS) for DR 1:1.2. Success was observed in 12 pts in DR1:2 Vs 18 in DR 1:1.2, p < 0.001. Side effects related to M were observed in 33/46 pts in DR 1:2 (mainly neurotoxicity symptoms) Vs 1/6 in DR 1:1.2. Conclusions: DR 1:1.2 when changing from parenteral to oral M resulted in lower toxicity and no difference in analgesia. More conservative dose adjustment during M route change should be considered. Granted by Spanish Ministry of Health EC10-133. EUDRACT Number: 2010-024092-39. Clinical trial information: 2010-024092-39.
Background
Lumen-apposing metal stents (LAMS) have displaced double-pigtail plastic stents (DPS) as the standard treatment for walled-off necrosis (WON),β but evidence for exclusively using LAMS is ...limited. We aimed to assess whether the theoretical benefit of LAMS was superior to DPS.
Methods
This multicenter, open-label, randomized trial was carried out in 9 tertiary hospitals. Between June 2017, and Oct 2020, we screened 99 patients with symptomatic WON, of whom 64 were enrolled and randomly assigned to the DPS group (
n
= 31) or the LAMS group (
n
= 33). The primary outcome was short-term (4-weeks) clinical success determined by the reduction of collection. Secondary endpoints included long-term clinical success, hospitalization, procedure duration, recurrence, safety, and costs. Analyses were by intention-to-treat. ClinicalTrials.gov, NCT03100578.
Results
A similar clinical success rate in the short term (RR, 1.41; 95% CI 0.88–2.25;
p
= 0.218) and in the long term (RR, 1.2; 95% CI 0.92–1.58;
p
= 0.291) was observed between both groups. Procedure duration was significantly shorter in the LAMS group (35 vs. 45-min,
p
= 0.003). The hospital admission after the index procedure (median difference, − 10 95% CI − 17.5, − 1;
p
= 0.077) and global hospitalization (median difference − 4 95% CI − 33, 25.51;
p
= 0.82) were similar between both groups. Reported stent-related adverse events were similar for the two groups (36 vs.45% in LAMS vs. DPS), except for de novo fever, which was significantly 26% lower in LAMS (RR, 0.26 0.08–0.83,
p
= 0.015).
Conclusions
The clinical superiority of LAMS over DPS for WON therapy was not proved, with similar clinical success, hospital stay and similar safety profile between both groups, yet a significant reduction in procedure time was observed.
Trial registration number
ClinicalTrials.gov, NCT03100578.
Graphical abstract
Abstract
Background
Daptomycin plus fosfomycin combination has demonstrated synergistic and bactericidal effect in animal models of methicillin-resistant Staphylococcus aureus bacteremia (MRSAB), but ...there is lack of data in humans.
Method
A randomized (1:1), open-label, clinical trial involving adults with MRSAB was conducted at 18 medical centers in Spain. Patients were assigned to receive daptomycin, 10 mg/kg IV daily plus fosfomycin, 2 g IV/6 hour (combination therapy) or to receive daptomycin 10 mg/kg/24 h IV (monotherapy) during 10 up to 14 days for uncomplicated bacteremia and 28 up to 42 days for complicated bacteremia. The primary efficacy endpoints were: (a) treatment success at Test-of-Cure visit (ToC: 6 weeks after end of therapy) and (b) treatment success at 7 days (defined as alive at day 7 and clearance of bacteremia without relapse from 8 to 90 days after randomization), according with the proposed primary endpoints for use in clinical trials in bloodstream infections in adults.
Result
Between December 2013 and November 2017, 674 patients with MRSAB were evaluated and 155 patients were randomized: 74 received combination therapy and 81 monotherapy. In intention-to-treat analysis, (a) at ToC visit successful outcome was achieved in 40 of 74 patients (54,1%) who received combination therapy as compared with 34 of 81 patients (42%) who were given monotherapy (54.1% vs. 42.0%; absolute difference, 12.1%; 95% confidence interval, 0%-27.0%); (b) at 7 days after starting the therapy: a successful outcome was achieved in 69 of 74 patients who received combination therapy as compared with 62 out of 81 patients who received monotherapy (93.2% vs. 76.5%; absolute difference, 16.7%; 95% confidence interval, 5.4%–27.7%). Combination therapy was associated with lower rates of microbiologic failure than monotherapy at ToC visit (0 vs. 9 patients, P = 0.009). Combination therapy, as compared with daptomycin monotherapy, was associated with a nonsignificantly higher rate of adverse events due to study medication leading to treatment failure and discontinuation of therapy: 6/74 (8.1%) vs. 3/81 (3.7%) (P = 0.31).
Conclusion
The combination of daptomycin plus fosfomycin was more effective than daptomycin alone for treating MRSAB (NCT01898338).
Disclosures
All authors: No reported disclosures.
Evaluar la prevalencia de inactividad física y el riesgo de sarcopenia en los pacientes de atención primaria y en sus acompañantes.
Estudio transversal. Se realizó una encuesta anónima a usuarios y ...acompañantes de atención primaria en consulta y en estand dentro de los centros de atención primaria (CAP) coincidiendo con una actividad de salud comunitaria para el día Mundial de la Actividad Física.
Cinco CAP de la región sanitaria Metropolitana Sud: en Cornellà de Llobregat (CAP Jaume Soler), en l’Hospitalet de Llobregat (CAP Florida Nord, CAP Florida Sud y CAP Bellvitge) y en Viladecans (CAP Maria Bernades) entre el 27 de marzo y el 6 de abril de 2023.
La población de atención primaria formada por paciente y sus acompañantes mayores de 18 años.
Los sanitarios administraron cuestionarios a los usuarios y sus acompañantes.
Se valoró la presencia de inactividad física con el cuestionario BPAAT y el riesgo de sarcopenia con el test SARC-F, además del sexo y el tramo de edad. Se realizó un análisis descriptivo univariante para la descripción de las prevalencias.
En 998 participantes observamos inactividad física en un 38,9% de los encuestados (33,8% hombres y 42,3% mujeres). Entre los mayores de 50 años (665 participantes), un 15,4% presentó riesgo de sarcopenia (9,58% varones y 19,2% mujeres).
La prevalencia de inactividad física y riesgo de sarcopenia (en mayores de 50 años) en la población estudiada es elevada. Las mujeres presentan mayor inactividad física y mayor riesgo de sarcopenia que los varones.
Assess the prevalence of physical inactivity and risk of sarcopenia in primary care patients and their companions.
Cross-sectional study. We carried out an anonymous survey of primary care users (patients and companions) in primary care consultations and stands coinciding with a community health activity for World Physical Activity Day.
Five primary care centers (CAPs) of the South Metropolitan health region: in Cornellà de Llobregat (CAP Jaume Soler), in l’Hospitalet de Llobregat (CAP Florida Nord, CAP Florida Sud and CAP Bellvitge) and in Viladecans (CAP Maria Bernades) between 27 March to April 6, 2023 (coinciding with World Physical Activity Day).
Primary care population consists of patients and their companions over 18 years of age.
The health workers administered questionnaires to users and companions.
We evaluated physical inactivity with the BPAAT questionnaire, risk of sarcopenia with SARC-F screening test, sex and age range. We performed an univariate descriptive analysis to report prevalence.
Nine hundred ninety-eight participants were surveyed. Physical inactivity was present in 38.9% of the participants. Among those over 50 years (665 participants), 15.4% were at risk of sarcopenia (9.58% men, 19.2% women).
The prevalence of physical inactivity and risk of sarcopenia (in individuals over 50 years old) in the studied population is high. Women have greater physical inactivity and a greater risk of sarcopenia than men.
Assess the prevalence of physical inactivity and risk of sarcopenia in primary care patients and their companions.OBJECTIVESAssess the prevalence of physical inactivity and risk of sarcopenia in ...primary care patients and their companions.Cross-sectional study. We carried out an anonymous survey of primary care users (patients and companions) in primary care consultations and stands coinciding with a community health activity for World Physical Activity Day. SITE: Five primary care centers (CAPs) of the South Metropolitan health region: in Cornellà de Llobregat (CAP Jaume Soler), in l'Hospitalet de Llobregat (CAP Florida Nord, CAP Florida Sud and CAP Bellvitge) and in Viladecans (CAP Maria Bernades) between 27 March to April 6, 2023 (coinciding with World Physical Activity Day).DESIGNCross-sectional study. We carried out an anonymous survey of primary care users (patients and companions) in primary care consultations and stands coinciding with a community health activity for World Physical Activity Day. SITE: Five primary care centers (CAPs) of the South Metropolitan health region: in Cornellà de Llobregat (CAP Jaume Soler), in l'Hospitalet de Llobregat (CAP Florida Nord, CAP Florida Sud and CAP Bellvitge) and in Viladecans (CAP Maria Bernades) between 27 March to April 6, 2023 (coinciding with World Physical Activity Day).Primary care population consists of patients and their companions over 18 years of age.PARTICIPANTSPrimary care population consists of patients and their companions over 18 years of age.The health workers administered questionnaires to users and companions.INTERVENTIONSThe health workers administered questionnaires to users and companions.We evaluated physical inactivity with the BPAAT questionnaire, risk of sarcopenia with SARC-F screening test, sex and age range. We performed an univariate descriptive analysis to report prevalence.MAIN MEASUREMENTSWe evaluated physical inactivity with the BPAAT questionnaire, risk of sarcopenia with SARC-F screening test, sex and age range. We performed an univariate descriptive analysis to report prevalence.Nine hundred ninety-eight participants were surveyed. Physical inactivity was present in 38.9% of the participants. Among those over 50 years (665 participants), 15.4% were at risk of sarcopenia (9.58% men, 19.2% women).RESULTSNine hundred ninety-eight participants were surveyed. Physical inactivity was present in 38.9% of the participants. Among those over 50 years (665 participants), 15.4% were at risk of sarcopenia (9.58% men, 19.2% women).The prevalence of physical inactivity and risk of sarcopenia (in individuals over 50 years old) in the studied population is high. Women have greater physical inactivity and a greater risk of sarcopenia than men.CONCLUSIONSThe prevalence of physical inactivity and risk of sarcopenia (in individuals over 50 years old) in the studied population is high. Women have greater physical inactivity and a greater risk of sarcopenia than men.
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