Linezolid serum trough (
) and peak (
) levels were determined prospectively in 90 patients. Adequate exposure was defined as a
of 2 to 8 mg/liter. Therapy was empirical (73.3%) or targeted (26.7%). ...Wide interindividual variability in linezolid
levels was recorded (0.1 to 25.2 μg/ml). Overall, 65.5% of the patients had out-of-range, 41.1% had subtherapeutic, and 24.4% had supratherapeutic trough levels. We did not find a correlation between abnormal levels and adverse events, in-hospital mortality, or overall poor outcome.
Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was ...to identify variables associated with septic shock development in a large population of patients with candidemia.
A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3).
Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03-6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04-4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12-0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08-4.24, p = 0.02).
Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms.
•Nocardiosis mainly affects elderly patients with chronic respiratory conditions and those under corticosteroid treatment.•Infections in HIV and solid organ transplantation patients have practically ...disappeared.•Nocardiosis most commonly affects the lungs.•Nocardiosis caused by N. farcinica is apparently a risk factor for poor clinical outcome.
To analyse relevant changes in incidence, clinical and microbiological characteristics of nocardiosis over the last 24 years at the current institution.
The clinical records of patients with nocardiosis (2006–2018) were reviewed and then compared with a previous cohort (1995–2006). Nocardia isolates were identified by 5’-end-16S-rRNA-gene-PCR targeting the first 500 bp of the gene and sequencing. Susceptibility tests were determined by broth microdilution (CLSI guidelines).
Forty-two patients (64.3% male) with nocardiosis were evaluated in the recent cohort: 51.2% had COPD, 43.9% were on corticosteroid therapy and 31.7% had cancer. The incidence of nocardiosis varied from 6.3 to 7.1/100,000 admissions (p = 0.62). There was a decrease in HIV patients (27% vs. 4.9%, p = 0.01) and solid organ transplantation (SOT) recipients (18.9% vs. 2 .4%, p = 0.01). Cases with pulmonary involvement had increased (70.3% vs. 90.5%, p = 0.04). Nocardia species were similar but the most common were N. cyriacigeorgica (32.4% vs. 40.5%, p = 0.49) and N. farcinica (24.3% vs. 14.3%, p = 0.39). Antibiotic resistance remained stable: cotrimoxazole (10.8% vs. 5.7%, p = 0.68), imipenem (5.4% vs. 5.6%, p = 1.0); amikacin and linezolid were 100% active. No differences were found in breakthrough nocardiosis (21.6% vs. 9.8%, p = 0.21) or related mortality (21.6% vs. 21.4%, p = 1.0). The multivariate analysis confirmed that nocardiosis caused by N. farcinica is a risk factor for poor outcome (p = 0.045).
Nocardiosis incidence has remained stable. It mainly affected elderly patients with chronic respiratory conditions and those on corticosteroid treatment. Infections in HIV and SOT patients have practically disappeared. Pulmonary involvement remains the most common area to be affected. Nocardiosis caused by N. farcinica is apparently a risk factor for poor clinical outcome.
Enterococcus faecalis infective endocarditis (EFIE) is a severe disease of increasing incidence. The objective was to analyze whether the outcome of patients with native valve EFIE (NVEFIE) treated ...with a short course of ampicillin plus ceftriaxone (4wAC) was similar to patients treated according to international guidelines (6wAC). Between January 2008 and June 2018, 1,978 consecutive patients with definite native valve IE were prospectively included in a national registry. Outcomes of patients with NVEFIE treated with 4wAC were compared to those of patients who received 6wAC. Three hundred and twenty-two patients (16.3%) had NVEFIE. One hundred and eighty-three (56.8%) received AC. Thirty-nine patients (21.3%) were treated with 4wAC for four weeks and 70 patients (38.3%) with 6wAC. There were no differences in age or comorbidity. Patients treated 6wAC presented a longer duration of symptoms before diagnosis (21 days, IQR 7-60 days vs. 7 days, IQR 1-22 days; p = 0.002). Six patients presented perivalvular abscess and all of these received 6wAC. Surgery was performed on 14 patients (35.9%) 4wAC and 34 patients (48.6%) 6wAC (p = 0.201). In-hospital mortality, one-year mortality and relapses among 4wAC and 6wAC patients were 10.3% vs. 11.4% (p = 0.851); 17.9% vs. 21.4% (p = 0.682) and 5.1% vs. 4.3% (p = 0.833), respectively. In conclusion, a four-week course of AC may be considered as an alternative regimen in NVEFIE, notably in patients with shorter duration of symptoms and those without perivalvular abscess. These results support the performance of a randomized clinical trial to evaluate the efficacy of this short regimen.
There is scarce information on the actual incidence of candidemia in COVID-19 patients. In addition, comparative studies of candidemia episodes in COVID-19 and non-COVID-19 patients are ...heterogeneous. Here, we assessed the real incidence, epidemiology, and etiology of candidemia in COVID-19 patients, and compared them with those without COVID-19 (2020 vs. 2019 and 2020, respectively). We also genotyped all
,
, and
isolates (
= 88), causing candidemia in both groups, providing for the first time a genotypic characterization of isolates gathered in patients with either COVID-19 or non-COVID-19. Incidence of candidemia was higher in patients with COVID-19 than non-COVID-19 (4.73 vs. 0.85 per 1000 admissions; 3.22 vs. 1.14 per 10,000 days of stay). No substantial intergroup differences were found, including mortality. Genotyping proved the presence of a low number of patients involved in clusters, allowing us to rule out rampant patient-to-patient
transmission. The four patients, involved in two clusters, had catheter-related candidemia diagnosed in the first COVID-19 wave, which demonstrates breaches in catheter management policies occurring in such an overwhelming situation. In conclusion, the incidence of candidemia in patients with COVID-19 is significantly higher than in those without COVID-19. However, genotyping shows that this increase is not due to uncontrolled intrahospital transmission.
Long-term immunity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in immunosuppressed patients is not well characterized. We aimed to explore the long-term natural ...immunity against SARS-CoV-2 in liver transplant (LT) recipients compared to the non-transplanted population (control group).
Fifteen LT recipients and 15 controls matched according to variables associated with disease severity were included at 12 months following the coronavirus disease 2019 (COVID-19) onset. Peripheral blood mononuclear cells were stimulated with peptide pools covering spike (S), nucleocapside (N), and membrane (M) proteins. Reactive CD4+ and CD8+ T cells were identified using flow cytometry, and cytokine production was evaluated in the culture supernatants using cytometric bead array. Serum anti-N and anti-S IgG antibodies were detected with chemiluminescence.
The percentage of patients with a positive response in both CD4+ and CD8+ T cells against each viral protein and IL2, IL10, TNF-α, and IFN-γ levels was similar between LT recipients and controls. IFN-γ levels were positively correlated with the percentage of reactive CD4+ (p = 0.022) and CD8+ (p = 0.043) T cells to a mixture of M + N + S peptide pools. The prevalence and levels of anti-N and anti-S IgG antibodies were slightly lower in the LT recipients, but the difference was not statistically significant.
LT recipients exhibited a similar T cell response compared to non-transplanted individuals one year after COVID-19 diagnosis.
Candidemia acquired outside critical care or hematological areas has received much attention in recent years; however, data on candidemia in surgical departments are very scarce. Our objectives were ...to describe episodes of candidemia diagnosed in surgical wards and to compare them with episodes occurring in medical wards. We performed a post hoc analysis of a prospective, multicenter study implemented in Spain during 2010-2011 (CANDIPOP project). Of the 752 episodes of candidemia, 369 (49.1%) occurred in patients admitted to surgical wards (165, 21.9%) or medical wards (204, 27.2%). Clinical characteristics associated with surgical patients were solid tumor as underlying disease, recent surgery, indwelling CVC, and parenteral nutrition. Candidemia was more commonly related to a CVC in the surgical than in the medical wards. The CVC was removed more frequently and early management was more appropriate within 48 hours of blood sampling in the surgical patients. Overall, 30-day mortality in the surgical departments was significantly lower than in medical wards (37.7% vs. 15.8%, p<0.001). Multivariate analysis revealed admission to a surgical ward and appropriate early management of candidemia as factors independently associated with a better outcome. We found that approximately 50% of episodes of candidemia occurred in non-hematological patients outside the ICU and that clinical outcome was better in patients admitted to surgical wards than in those hospitalized in medical wards. These findings can be explained by the lower severity of underlying disease, prompt administration of antifungal therapy, and central venous catheter removal.
At some point in their lives, many people will require major heart surgery (MHS). Patients are generally older adults with various risk factors for infection. However, the incidence of infection ...after MHS is poorly known, as reported infection data are frequently biased due to different factors like the surgical procedure, postoperative timing, and infectious syndromes or etiologic agents, among others. In addition, most patient data are retrospectively obtained.
Data were prospectively collected regarding the incidence of all nosocomial infections produced from the time of surgery to hospital discharge in a cohort of 800 adults consecutively undergoing a MHS procedure.
During postoperative hospitalization, 124 of the 800 participants developed one or more infections (15.5%): during their ICU stay in 68 patients (54.8%), during their stay on the general ward post ICU in 50 (40.3%), and during their stay in both wards in 6 (4.8%). The most common infections were pneumonia (related or not to mechanical ventilation), surgical site and bloodstream. As etiological agents, 193 pathogens were isolated: mostly Gram-negative bacilli (54.4%), followed by Gram-positive bacteria (30%), viruses (4.6%) and fungi (1.5%). In our cohort, all-cause mortality was recorded in 33 participants (4.1%) and 9 infection-related deaths (1.1%) were produced. Among subjects who developed infections, overall mortality was 13.7% and in those who did not, this was only 2.3%.
Infection following MHS remains frequent and severe. Our data suggest that hospital-acquired infection studies should consider episodes of infection in all populations during their entire hospital stay and not only those related to specific clinical syndromes or acquired while the patient is in intensive care.
Abstract
The objective of this study was to analyse the mechanisms of resistance to carbapenems and other extended-spectrum-β-lactams and to determine the genetic relatedness of multidrug-resistant
...Enterobacterales
(MDR-E) causing colonization or infection in solid-organ transplantation (SOT) recipients. Prospective cohort study in kidney (n = 142), liver (n = 98) or kidney/pancreas (n = 7) transplant recipients between 2014 and 2018 in seven Spanish hospitals. We included 531 MDR-E isolates from rectal swabs obtained before transplantation and weekly for 4–6 weeks after the procedure and 10 MDR-E from clinical samples related to an infection. Overall, 46.2%
Escherichia coli
, 35.3%
Klebsiella pneumoniae
, 6.5%
Enterobacter cloacae
, 6.3%
Citrobacter freundii
and 5.7% other species were isolated. The number of patients with MDR-E colonization post-transplantation (176; 71.3%) was 2.5-fold the number of patients colonized pre-transplantation (71; 28.7%). Extended-spectrum β-lactamases (ESBLs) and carbapenemases were detected in 78.0% and 21.1% of MDR-E isolates respectively. In nine of the 247 (3.6%) transplant patients, the microorganism causing an infection was the same strain previously cultured from surveillance rectal swabs. In our study we have observed a low rate of MDR-E infection in colonized patients 4–6 weeks post-transplantation.
E. coli
producing
bla
CTX-M-G1
and
K. pneumoniae
harbouring
bla
OXA-48
alone or with
bla
CTX-M-G1
were the most prevalent MDR-E colonization strains in SOT recipients.
Introduction
To evaluate the clinical impact of a comprehensive care bundle for the management of candidemia.
Methods
A quasi-experimental pre-post study was implemented. During the pre-intervention ...period (May 2014–September 2015), a non-mandatory antifungal stewardship program (ASP) was implemented, and patients with candidemia were visited by an infectious disease specialist who provided diagnostic and therapeutic advice according to standard of care as soon as possible. During the post-intervention period (October 2015–May 2017), patients were managed according to a candidemia care bundle with clear and structured recommendations written in their medical history.
Results
Overall, 109 patients were included, 56 in the pre-intervention and 53 in the post-intervention period. Overall, compliance with the
Candida
bundle significantly improved between the pre- 27/56 (48.2%) and post-intervention 43/53 (81.1%);
p
= 0.01 period. Individual bundle components that significantly improved in the post-intervention period were early adequate antifungal therapy 47/56 (83.9%) vs. 51/53 (96.2%),
p
= 0.05, early adequate source control of the infection 37/56 (82.2%) vs. 41/53 (97.6%),
p
= 0.03 and appropriate duration of therapy 27/56 (48.2%) vs. 43/53 (81.1%),
p
= 0.01. Adherence to follow-up blood cultures, ophthalmologic examination and echocardiography improved in the post-intervention period, but the difference was not statistically significant. Multivariate analysis revealed that being managed according to candidemia bundle had a favorable impact on 14-day mortality (HR 0.08, 95% CI 0.01–0.45,
p
= 0.02) and 30-day mortality (HR 0.40, 95% CI 0.18–0.89,
p
= 0.02).
Conclusions
A simple bundle focused on increasing adherence to a few evidence-based interventions contributed to a significant reduction in 14- and 30-day mortality in patients with candidemia.
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