Abstract
Background
We aimed at constructing a composite score based on Epstein-Barr virus DNAemia (EBVd) and simple clinical and immunological parameters to predict late severe infection (LI) beyond ...month 6 in solid organ transplantation (SOT) recipients.
Methods
Kidney and liver transplant recipients between May 2014 and August 2016 at 4 participating centers were included. Serum immunoglobulins and complement factors, peripheral blood lymphocyte subpopulations, and whole blood EBVd were determined at months 1, 3, and 6. Cox regression analyses were performed to generate a weighted score for the prediction of LI.
Results
Overall, 309 SOT recipients were followed-up for a median of 1000 days from transplant (interquartile range, 822–1124). Late severe infection occurred in 104 patients (33.6%). The CLIV Score consisted of the following variables at month 6: high-level EBVd (>1500 IU/mL) and recurrent infection during the previous months (6 points); recipient age ≥70 years and chronic graft dysfunction (5 points); cytomegalovirus mismatch (4 points); and CD8+ T-cell count <400 cells/μL (2 points). The area under receiver operating characteristics curve was 0.77 (95% confidence interval, 0.71–0.84). The risk of LI at day 1000 was as follows: score 0, 12.6%; score 2–5, 25.5%; score 6–9, 52.7%; score ≥10, 73.5%.
Conclusions
While waiting for further external validation, the CLIV Score based on clinical and immune-virological parameters is potentially useful to stratify the risk of LI after SOT.
The CLIV Score consisted of the following variables at month 6: high-level EBVd and recurrent infection during the previous months; recipient age ≥70 years and chronic graft dysfunction; CMV mismatch; and CD8+ T-cell count <400 cells/μL.
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.
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
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.
Abstract Background Clostridioides difficile infection (CDI) occurs in various contexts and care settings and is managed by multiple specialists who are not experts in its management. While there are ...many initiatives to improve the diagnosis and avoid overdiagnosis, there is less focus on the overall management of the infection. Methods We studied a cohort of patients with a positive test result for toxigenic C difficile in 2 hospitals. Hospital A has a program that provides advice from an infectious disease specialist (IDS) and promotes continuity of care by providing a phone number to contact the IDS. Hospital B does not have any specific CDI program. The evaluation assessed the proportion of patients not treated (carriers or self-limited disease), adherence to Infectious Diseases Society of America guidelines, access to novel therapies, recurrence and mortality rates, and readmission and emergency department visits due to CDI. We assessed the program's effectiveness through a logistic regression model adjusted for covariates chosen by clinical criteria. Results Hospital A avoided more unnecessary treatments (19.3% vs 11.5%), provided access to novel therapies more frequently (35.3% vs 13%), and adhered more closely to current guidelines (95.8% vs 71.3%). Although the mortality and recurrence rates did not differ, the absence of an intervention program was associated with greater odds of admission due to recurrence (odds ratio, 4.19; P = .037) and more visits to the emergency department due to CDI (odds ratio, 8.74; P = .001). Conclusions Implementation of a CDI intervention program based on recommendations from IDSs and improved access to specialized care during the follow-up is associated with enhanced quality of CDI management and potential reductions in hospital resource utilization.
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.
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.
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.
•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.
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