The high cost of fidaxomicin has restricted its use despite the benefit of a lower
Clostridioides difficile
infection (CDI) recurrence rate at 4 weeks of follow-up. This short follow-up represents ...the main limitation of pivotal clinical trials of fidaxomicin, and some recent studies question its benefits over vancomycin. Moreover, the main risk factors of recurrence after treatment with fidaxomicin remain unknown. We designed a multicentre retrospective cohort study among four Spanish hospitals to assess the efficacy of fidaxomicin in real life and to investigate risk factors of fidaxomicin failure at weeks 8 and 12. Two-hundred forty-four patients were included. Fidaxomicin was used in 96 patients (39.3%) for a first episode of CDI, in 95 patients (38.9%) for a second episode, and in 53 patients (21.7%) for a third or subsequent episode. Patients treated with fidaxomicin in a first episode were younger (59.9 years vs 73.5 years), but they had more severe episodes (52.1% vs. 32.4%). The recurrence rates for patients treated in the first episode were 6.5% and 9.7% at weeks 8 and 12, respectively. Recurrence rates increased for patients treated at second or ulterior episodes (16.3% and 26.4% at week 8, respectively). Age greater than or equal to 85 years and having had a previous episode of CDI were identified as recurrence risk factors at weeks 8 and 12. We conclude that the outcomes with fidaxomicin in real life are at least as good as those observed in clinical trials despite a more demanding evaluation. Be it 85 years of age or older, and the use after a first episode appears to be independent factors of CDI recurrence after treatment with fidaxomicin.
Bezlotoxumab is marketed for the prevention of recurrent
infection (rCDI). Its high cost could be determining its prescription to a different population than that represented in clinical trials. The ...objective of the study was to verify the effectiveness and safety of bezlotoxumab in preventing rCDI and to investigate factors related to bezlotoxumab failure in the real world. A retrospective, multicentre cohort study of patients treated with bezlotoxumab in Spain was conducted. We compared the characteristics of cohort patients with those of patients treated with bezlotoxumab in the pivotal MODIFY trials. We assessed recurrence rates 12 weeks after completion of treatment against
, and we analysed the factors associated with bezlotoxumab failure. Ninety-one patients were included in the study. The cohort presented with more risk factors for rCDI than the patients included in the MODIFY trials. Thirteen (14.2%) developed rCDI at 12 weeks of follow-up, and rCDI rates were numerically higher in patients with two or more previous episodes (25%) than in those who had fewer than two previous episodes of
infection (CDI) (10.4%);
= 0.09. There were no adverse effects attributable to bezlotoxumab. Despite being used in a more compromised population than that represented in clinical trials, we confirm the effectiveness of bezlotoxumab for the prevention of rCDI.
Purpose
To evaluate preoperative asymptomatic bacteriuria (ASB) treatment to reduce early-periprosthetic joint infections (early-PJIs) after hip hemiarthroplasty (HHA) for fracture.
Methods
...Open-label, multicenter RCT comparing fosfomycin-trometamol versus no intervention with a parallel follow-up cohort without ASB. Primary outcome: early-PJI after HHA.
Results
Five hundred ninety-four patients enrolled (mean age 84.3); 152(25%) with ASB (77 treated with fosfomycin-trometamol/75 controls) and 442(75%) without. Despite the study closed without the intended sample size, ASB was not predictive of early-PJI (OR: 1.06 95%CI: 0.33–3.38), and its treatment did not modify early-PJI incidence (OR: 1.03 95%CI: 0.15–7.10).
Conclusions
Neither preoperative ASB nor its treatment appears to be risk factors of early-PJI after HHA.
ClinicalTrials.gov
Identifier: Eudra CT 2016-001108-47
Treatment of carbapenemase‐producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to ...predict mortality in solid organ transplant recipients with carbapenemase‐producing Enterobacterales bloodstream infections. A multinational, retrospective (2004‐2016) cohort study (INCREMENT‐SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30‐day all‐cause mortality. The INCREMENT‐SOT‐CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT‐CPE mortality score ≥8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT‐CPE score ≥8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval CI 0.76‐0.88) and classified patients into 3 strata: 0‐7 (low mortality), 8‐11 (high mortality), and 12‐17 (very‐high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very‐high (adjusted hazard ratio HR 2.82, 95% CI 1.13‐7.06, P = .03) and high (HR 9.93, 95% CI 2.08‐47.40, P = .004) mortality risk strata. A score‐based algorithm is provided for therapy guidance.
The authors develop a predictive risk score for a solid organ transplant recipient's for mortality in patients with bloodstream infections due to carbapenemase‐producing Enterobacterales, which is useful to differentiate patients who can be treated with antimicrobial monotherapy from those who should receive combination therapy.
Infection after spinal instrumentation (IASI) by
spp. is being more frequently reported. The aim of this study was to analyse the incidence, risk factors, clinical characteristics, and outcome of a
...spp. IASI (CG) compared with non-
IASI (NCG) infections, with an additional focus on the role of rifampin in the treatment. All patients from a multicentre, retrospective, observational study with a confirmed IASI between January 2010 and December 2016 were divided into two groups: (CG and NCG) IASI. Baseline, medical, surgical, infection treatment, and follow-up data were compared for both groups. In total, 411 patients were included: 27 CG and 384 NCG. The CG patients were significantly younger. They had a longer median time to diagnosis (23 vs. 13 days) (
= 0.025), although 55.6% debuted within the first month after surgery.
patients were more likely to have the implant removed (29.6% vs. 12.8%;
= 0.014) and received shorter antibiotic regimens (
= 0.014). In 33% of
cases, rifampin was added to the baseline therapy. None of the 27 infections resulted in treatment failure during follow-up regardless of rifampin use.
spp. is associated with a younger age and may cause both early and late IASIs. In our experience, the use of rifampin to improve the outcome in the treatment of a
spp. IASI is not relevant since, in our series, none of the cases had therapeutic failure regardless of the use of rifampin.
Background. Infective endocarditis has a high morbidity and mortality and requires a coordinated medical-surgical management. The objective was to analyse the impact of surgery on mortality in a ...hospital without cardiac surgery.
Material and methods. Evaluation of a prospective cohort of patients with infective endocarditis diagnosed between August 2011 and January 2016 according to modified Duke’s criteria.
Results. Sixty-four patients were included, of whom seventeen patients were operated (26.6%). Mortality was 32.8% and it was associated with chronic obstructive pulmonary disease history, staphylococci coagulase-negative and the appearance of complications, as valvular insufficiency and embolisms in the central nervous system; cardiac surgery was not associated with mortality. Four patients (6,6%) were not operated despite indication of cardiac surgery. The main reason for not been intervened was the poor presurgical prognosis (44.7%).
Conclusions. Mortality due to infective endocarditis in a hospital without cardiac surgery is high. The need for interhospital teams is strengthened.
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.
•Late acute prosthetic joint infection (PJI) treated with surgical debridement and implant retention have a high failure rate.•The exchange of mobile components during surgical debridement is the ...most potent predictor for treatment success.•There are several preoperative patient related variables that increase the risk for failure.•Treatment strategies for late acute PJIs should be individualized and optimized according to the preoperative risk for failing.
Debridement, antibiotics and implant retention (DAIR) is the recommended treatment for all acute prosthetic joint infections (PJI), but its efficacy in patients with late acute (LA) PJI is not well described.
Patients diagnosed with LA PJI between 2005 and 2015 were retrospectively evaluated. LA PJI was defined as the development of acute symptoms (≤ 3 weeks) occurring ≥ 3 months after arthroplasty. Failure was defined as: (i) the need for implant removal, (ii) infection related death, (iii) the need for suppressive antibiotic therapy and/or (iv) relapse or reinfection during follow-up.
340 patients from 27 centers were included. The overall failure rate was 45.0% (153/340). Failure was dominated by Staphylococcus aureus PJI (54.7%, 76/139). Significant independent preoperative risk factors for failure according to the multivariate analysis were: fracture as indication for the prosthesis (odds ratio (OR) 5.4), rheumatoid arthritis (OR 5.1), age above 80 years (OR 2.6), male gender (OR 2.0) and C-reactive protein > 150 mg/L (OR 2.0). Exchanging the mobile components during DAIR was the strongest predictor for treatment success (OR 0.35).
LA PJIs have a high failure rate. Treatment strategies should be individualized according to patients’ age, comorbidity, clinical presentation and microorganism causing the infection.
Describir las características clínicas de los pacientes tratados con evolocumab, las razones del inicio de la terapia y los efectos del tratamiento en la fase inicial de disponibilidad de evolocumab ...en las unidades de nefrología de España.
Estudio retrospectivo, observacional y multicéntrico que incluye los pacientes que iniciaron tratamiento con evolocumab (desde febrero de 2016 a agosto de 2018) en 15 unidades de nefrología en España. Se revisaron las características demográficas y clínicas de los pacientes, el tratamiento hipolipemiante y la evolución de los perfiles lipídicos entre 24 semanas antes y 12±4 semanas después del inicio de evolocumab.
Se incluyeron 60 pacientes: 53,3% mujeres, edad media (DE) de 56,9 (12,8) años, el 45,0% con hipercolesterolemia familiar (HF) (5,0% homocigota y 40,0% heterocigota) y el 65,0% con enfermedad cardiovascular aterosclerótica (ECVA) previa. El filtrado glomerular estimado (FGe) medio fue de 62,6 (30,0) ml/min/1,73m2 (51,7% pacientes con FGe<60ml/min/1,73m2 ERC estadio >2), el 50,0% con proteinuria (>300mg/g) y el 10,0% con síndrome nefrótico. Otros factores de riesgo CV fueron: hipertensión (75,0%), diabetes mellitus (25,0%) y hábito tabáquico (21,7%). El 40,0% eran intolerantes a estatinas. Al inicio de evolocumab, el 41,7% tomaban estatinas de alta intensidad, el 18,3% estatinas de moderada intensidad y el 50,0% ezetimiba. Los niveles medios (DE) de c-LDL al inicio de evolocumab fueron de 179,7 (62,9) mg/dl (53,4% pacientes con c-LDL≥160mg/dl y 29,3%≥190mg/dl). Después de 12 semanas del tratamiento con evolocumab se observó una reducción de los niveles de c-LDL del 60,1%. A la semana 12, el 90,0% de los pacientes alcanzó niveles c-LDL<100mg/dl, 70,0%<70mg/dl y 55,0%<55mg/dl, mientras que el FGe medio y el uso de estatinas se mantuvieron estables.
En las unidades de nefrología de España, evolocumab se ha prescrito principalmente en pacientes con HF, enfermedad renal crónica (ERC>2) y prevención secundaria, con niveles de c-LDL muy por encima de los recomendados por las guías. Evolocumab utilizado en práctica clínica, redujo significativamente los niveles de c-LDL en todos los pacientes incluidos en el estudio.
To describe the clinical characteristics, the reasons for initiating therapy and the effects of treatment in the initial phase of evolocumab availability in the Nephrology Units of Spain.
Retrospective, observational and multicentric study that included patients initiating treatment with evolocumab (from February 2016 to August 2018), in 15 Nephrology Units in Spain. The demographic and clinical characteristics of the patients, the lipid lowering treatment and the evolution of the lipid profiles between 24 weeks pre-initiation and 12±4 weeks post-initiation of evolocumab were reviewed.
Sixty patients were enrolled: 53.3% women; mean (SD) age, 56.9 (12.8) years, 45.0% with familial hypercholesterolemia (FH) (5.0% homozygous and 40.0% heterozygous) and 65.0% with atherosclerotic cardiovascular (CV) disease. The mean (SD) eGFR was 62.6 (30.0)ml/min/1.73m2 (51.7% of patients had eGFR<60ml/min/1.73m2 CKD stage>2), 50.0% had proteinuria (>300mg/g) and 10.0% had nephrotic syndrome. Other CV risk factors were hypertension (75.0%), diabetes (25.0%), and smoking (21.7%). A 40.0% of patients were statin intolerant. At evolocumab initiation, 41.7% of patients were on a high-intensity statin, 18.3% on moderate intensity statin and 50.0% were receiving ezetimibe. Mean (SD) LDL-c at evolocumab initiation was 179.7 (62.9)mg/dL (53.4% of patients with LDL-c≥160mg/dL and 29.3%≥190mg/dL). After 12 weeks, evolocumab resulted in LDL-c reductions of 60.1%. At week 12, 90.0% of patients reached LDL-c levels <100mg/dL, 70.0% <70mg/dL, and 55.0% <55mg/dL, while mean eGFR levels and statin use were remained stable.
In Nephrology Units of Spain, evolocumab was predominantly prescribed in patients with FH, chronic renal disease (CRD>2) and secondary prevention, with LDL-c levels above those recommended by the guidelines. Evolocumab used in clinical practice significantly reduced the LDL-c levels in all patients included in the study.
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