National and international guidelines were recently published regarding the treatment of Enterobacteriaceae resistant to third-generation cephalosporins infections. We aimed to assess the implementation of the French guidelines in critically ill patients suffering from extended-spectrum β-lactamase-producing Enterobacteriaceae bloodstream infection (ESBL-E BSI). We conducted a retrospective observational cohort study in the ICU of three French hospitals. Patients treated between 2018 and 2022 for ESBL-E BSI were included. The primary assessment criterion was the proportion of adequate empirical carbapenem prescriptions, defined as prescriptions consistent with the French guidelines. Among the 185 included patients, 175 received an empirical anti-biotherapy within 24 h of ESBL-E BSI onset, with a carbapenem for 100 of them. The proportion of carbapenem prescriptions consistent with the guidelines was 81%. Inconsistent prescriptions were due to a lack of prescriptions of a carbapenem, while it was recommended in 25% of cases. The only factor independently associated with adequate empirical carbapenem prescription was ESBL-E colonization (OR: 107.921 [9.303-1251.910], p = 0.0002). The initial empirical anti-biotherapy was found to be appropriate in 83/98 patients (85%) receiving anti-biotherapy in line with the guidelines and in 56/77 (73%) patients receiving inadequate anti-biotherapy (p = 0.06). Our results illustrate the willingness of intensivists to spare carbapenems. Promoting implementation of the guidelines could improve the proportion of initial appropriate anti-biotherapy in critically ill patients with ESBL-E BSI.

OBJECTIVE: A simplified therapeutic guideline (STG) was established in our urology ward in 2019 for urinary infections. Our aim was to describe the level of physician adherence to STG and the impact of a limited number of antibiotic compounds on the rate of multidrug-resistant (MDR) bacteria. As guidelines should improve patient care, unfavorable outcomes were also reported.
METHODS: The STG for community-acquired and nosocomial urinary infections, including six antibiotics, was established in November 2019 and has been officially applied since January 2020. Treatment duration has to be ≤14 days. We conducted a before-after study to measure physician adherence to the STG for bacteremia treatment between January 2017 and December 2022. Adherence was defined as exclusive use of STG antibiotics. All isolated bacteria from blood cultures were recorded, including MDR Enterobacterales, defined as AmpC β-lactamase- or ESBL-producing strains. Unfavorable outcomes were defined as uncontrolled infection, a second surgical procedure, ICU requirement, and/or death.
RESULTS: Seventy-six cases of bacteremia occurred between January 2017 and December 2019, and ninety between January 2020 and December 2022. The main comorbid condition was urological cancer (46%). The main reason for surgery was ureteral stent (32%). Antibiotic management in accordance with STG increased from 18% to 52%, p < 0.001, and treatments > 14 days decreased from 53% to 28%, p < 0.001. MDR Enterobacterales bacteremia was reduced from 52% to 35%, p = 0.027. The rate of unfavorable outcomes was unchanged.
CONCLUSIONS: STG adherence in urology was satisfactory and associated with reduced MDR Enterobacterales bacteremia.

Optimal coverage of Pseudomonas aeruginosa is challenging in febrile neutropenic patients due to a progressive increase in antibiotic resistance worldwide. We aimed to detail current rates of resistance to antibiotics recommended by international guidelines for P. aeruginosa isolated from bloodstream infections (BSI) in patients with hematologic malignancies. Secondarily, we aimed to describe how many patients received inappropriate empirical antibiotic treatment (IEAT) and its impact on mortality. We conducted a retrospective, multicenter cohort study of the last 20 BSI episodes caused by P. aeruginosa in patients with hematologic malignancies from across 14 university hospitals in Spain. Of the 280 patients with hematologic malignancies and BSI caused by P. aeruginosa, 101 (36%) had strains resistant to at least one of the β-lactam antibiotics recommended in international guidelines, namely, cefepime, piperacillin-tazobactam, and meropenem. Additionally, 21.1% and 11.4% of the strains met criteria for MDR and XDR P. aeruginosa, respectively. Even if international guidelines were followed in most cases, 47 (16.8%) patients received IEAT and 66 (23.6%) received inappropriate β-lactam empirical antibiotic treatment. Thirty-day mortality was 27.1%. In the multivariate analysis, pulmonary source (OR 2.22, 95% CI 1.14 to 4.34) and IEAT (OR 2.67, 95% CI 1.37 to 5.23) were factors independently associated with increased mortality. We concluded that P. aeruginosa-causing BSI in patients with hematologic malignancies is commonly resistant to antibiotics recommended in international guidelines, which is associated with frequent IEAT and higher mortality. New therapeutic strategies are needed. IMPORTANCE Bloodstream infection (BSI) caused by P. aeruginosa is related with an elevated morbidity and mortality in neutropenic patients. For this reason, optimal antipseudomonal coverage has been the basis of all historical recommendations in the empirical treatment of febrile neutropenia. However, in recent years the emergence of multiple types of antibiotic resistances has posed a challenge in treating infections caused by this microorganism. In our study we postulated that P. aeruginosa-causing BSI in patients with hematologic malignancies is commonly resistant to antibiotics recommended in international guidelines. This observation is associated with frequent IEAT and increased mortality. Consequently, there is a need for a new therapeutic strategy.

In the absence of procalcitonin, the American Academy of Pediatrics\' clinical practice guideline (CPG) for evaluating and managing febrile infants recommends using previously untested combinations of inflammatory marker thresholds. Thus, CPG performance in detecting invasive bacterial infections (IBIs; bacteremia, bacterial meningitis) is poorly understood.
To evaluate CPG performance without procalcitonin in detecting IBIs in well-appearing febrile infants 8 to 60 days old.
For this cross-sectional, single-site study, we manually abstracted data for febrile infants using electronic health records from 2011 to 2018. We used CPG inclusion/exclusion criteria to identify eligible infants and stratified IBI risk with CPG inflammatory marker thresholds for temperature, absolute neutrophil count, and C-reactive protein. Because the CPG permits a wide array of interpretations, we performed 3 sensitivity analyses, modifying age and inflammatory marker thresholds. For each approach, we calculated area-under-the-receiver operating characteristic curve, sensitivity, and specificity in detecting IBIs.
For this study, 507 infants met the inclusion criteria. For the main analysis, we observed an area-under-the-receiver operating characteristic curve of 0.673 (95% confidence interval 0.652-0.694), sensitivity of 100% (66.4%-100%), and specificity of 34.5% (30.4%-38.9%). For the sensitivity analyses, sensitivities were all 100% and specificities ranged from 9% to 38%.
Findings suggest that the CPG is highly sensitive, minimizing missed IBIs, but specificity may be lower than previously reported. Future studies should prospectively investigate CPG performance in larger, multisite samples.

A quasi-experimental study was conducted on the implementation of locally developed clinical practice guidelines (CPGs) for empirical antibiotic (ATB) therapy of common infections (bacteremia, urinary tract infection (UTI), pneumonia) in the hospitals from January 2019 to December 2020. The CPGs were developed using data from patients with these infections at individual hospitals. Relevant CPG data pre- and post-implementation were collected and compared. Of the 1644 patients enrolled in the study, 808 and 836 were in the pre- and post-implementation periods, respectively, and patient outcomes were compared. Significant reductions in the mean durations of intensive care unit stay (3.44 ± 9.08 vs. 2.55 ± 7.89 days; p = 0.035), ventilator use (5.73 ± 12.14 vs. 4.22 ± 10.23 days; p = 0.007), piperacillin/tazobactam administration (0.954 ± 3.159 vs. 0.660 ± 2.217 days, p = 0.029), and cefoperazone/sulbactam administration (0.058 ± 0.737 vs. 0.331 ± 1.803 days, p = 0.0001) occurred. Multivariate analysis demonstrated that CPG-implementation was associated with favorable clinical outcomes (adjusted odds ratio 1.286, 95% confidence interval: 1.004-1.647, p = 0.046). Among patients who provided follow-up cultures (n = 284), favorable microbiological responses were significantly less frequent during the pre-implementation period than the post-implementation period (80.35% vs. 91.89%; p = 0.01). In conclusion, the locally developed CPG implementation is feasible and effective in improving patient outcomes and reducing ATB consumption. Hospital antimicrobial stewardship teams should be able to facilitate CPG development and implementation for antimicrobial therapy for common infections.

To describe current resistance to the β-lactams empirically recommended in the guidelines in bloodstream infection (BSI) episodes caused by Gram-negative bacilli (GNB).
Retrospective, multicentre cohort study of the last 50 BSI episodes in haematological patients across 14 university hospitals in Spain. Rates of inappropriate empirical antibiotic therapy (IEAT) and impact on mortality were evaluated.
Of the 700 BSI episodes, 308 (44%) were caused by GNB, mainly Escherichia coli (141; 20.1%), Klebsiella spp. (56; 8%) and Pseudomonas aeruginosa (48; 6.9%). Among GNB BSI episodes, 80 (26%) were caused by MDR isolates. In those caused by Enterobacterales, 25.8% were ESBL producers and 3.5% were carbapenemase producers. Among P. aeruginosa BSI episodes, 18.8% were caused by MDR isolates. Overall, 34.7% of the isolated GNB were resistant to at least one of the three β-lactams recommended in febrile neutropenia guidelines (cefepime, piperacillin/tazobactam and meropenem). Despite extensive compliance with guideline recommendations (91.6%), 16.6% of BSI episodes caused by GNB received IEAT, which was more frequent among MDR GNB isolates (46.3% versus 6.1%; P < 0.001). Thirty day mortality was 14.6%, reaching 21.6% in patients receiving IEAT.
Current resistance to empirical β-lactams recommended in febrile neutropenia guidelines is exceedingly high and IEAT rates are greater than desired. There is an urgent need to adapt guidelines to current epidemiology and better identify patients with a high risk of developing MDR GNB infection.

Cardiovascular implantable electronic device (CIED) implantation has markedly increased over the past 2 decades. Staphylococcus aureus bacteremia (SAB) occurs in patients with CIED, and determination of device infection often is difficult.
The purpose of this study was to examine the rate and clinical characteristics of SAB in patients living with CIED using the 2019 European Heart Rhythm Association (EHRA) international consensus document.
We conducted a retrospective study of patients with CIED who were hospitalized at Mayo Clinic, Rochester, with SAB from 2012 to 2019. Patients who met CIED infection criteria after SAB based on EHRA criteria were identified. A descriptive statistic and time-dependent Cox model were used.
Overall, 110 patients with CIED developed SAB, of whom 92 (83.6%) underwent transesophageal echocardiogram (TEE). Fifty-seven (51.8%) and 31 (28.2%) patients met criteria for definite and possible CIED infections, respectively. At 30-day follow-up, the cumulative rate of patients undergoing complete device extraction was 80.0% in the definite CIED infection group, compared with 38.8% and 32.9% in the possible and rejected CIED infection groups, respectively. We found that CIED extraction was associated with an 83% reduction in risk of 1-year mortality in the definite CIED infection group.
The rate of CIED infections after SAB was higher than that reported previously. Increased use of TEE and a novel case definition with broader diagnostic criteria likely were operative, in part, in accounting for the higher rate of CIED infections complicating SAB. Complete device removal is critical in patients with definite CIED infection to improve 1-year mortality.

BACKGROUND: New randomized controlled trials have been conducted since publication of the 2016 ASPEN/SCCM critical care nutrition guideline. This guideline updates recommendations for foundational questions central to critical care nutrition support.
METHODS: The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process was used to develop and summarize evidence for clinical practice recommendations. Clinical outcomes were assessed for (1) higher vs lower energy dose (2) higher vs lower protein dose (3) exclusive isocaloric PN vs EN (4) supplemental PN (SPN) plus EN vs EN alone (5a) mixed oil lipid injectable emulsions (ILE) vs soybean oil, and (5b) Fish oil (FO) containing ILE vs non-FO ILE. To assess safety, weight based energy intake was plotted against hospital mortality when study heterogeneity precluded meaningful Forest plot inferences.
RESULTS: Between 1/1/2001 and 07/15/2020, 2,320 citations were identified and data were abstracted from 39 trials, including 20,578 participants. Patients receiving FO had decreased pneumonia rates of uncertain clinical significance. Otherwise, there were no differences for any outcome in any question. Due to lack in certainty regarding harm, the energy prescription recommendation was decreased to 12-25kcal/kg/day.
CONCLUSIONS: No differences in clinical outcomes were identified among numerous nutritional interventions, including higher energy or protein intake, isocaloric PN or EN, supplemental PN, or different ILEs. As more consistent critical care nutrition support data become available, more precise recommendations will be possible. In the meantime, clinical judgment and close monitoring are needed. This paper was approved by the ASPEN Board of Directors.  This article is protected by copyright. All rights reserved.

UNASSIGNED: Guidance on the recommended durations of antibiotic therapy, the use of oral antibiotic therapy, and the need for repeat blood cultures remain incomplete for gram-negative bloodstream infections. We convened a panel of infectious diseases specialists to develop a consensus definition of uncomplicated gram-negative bloodstream infections to assist clinicians with management decisions.
UNASSIGNED: Panelists, who were all blinded to the identity of other members of the panel, used a modified Delphi technique to develop a list of statements describing preferred management approaches for uncomplicated gram-negative bloodstream infections. Panelists provided level of agreement and feedback on consensus statements generated and refined them from the first round of open-ended questions through 3 subsequent rounds.
UNASSIGNED: Thirteen infectious diseases specialists (7 physicians and 6 pharmacists) from across the United States participated in the consensus process. A definition of uncomplicated gram-negative bloodstream infection was developed. Considerations cited by panelists in determining if a bloodstream infection was uncomplicated included host immune status, response to therapy, organism identified, source of the bacteremia, and source control measures. For patients meeting this definition, panelists largely agreed that a duration of therapy of ~7 days, transitioning to oral antibiotic therapy, and forgoing repeat blood cultures, was reasonable.
UNASSIGNED: In the absence of professional guidelines for the management of uncomplicated gram-negative bloodstream infections, the consensus statements developed by a panel of infectious diseases specialists can provide guidance to practitioners for a common clinical scenario.

In recent years, important epidemiologic changes have been described in hematopoietic stem cell transplantation (HSCT) recipients with bloodstream infection (BSI), with increases in gram-negative bacilli and multidrug resistant (MDR) gram-negative bacilli. These changes have been linked to a worrisome increase in mortality. We aimed to define the risk factors for mortality of HSCT patients experiencing BSI. All episodes of BSI in patients with HSCT between 2008 and 2017 were prospectively collected. Multivariate analyses were performed. A total of 402 BSI episodes were documented in 293 patients who had undergone HSCT (75.4% allogenic, 32.3% autologous, 19.3% second HSCT). The median time from HSCT to BSI was 62 days (interquartile range, 9 to 182 days). Gram-positive cocci accounted for 56.7% of the episodes; gram-negative bacilli, for 42%. The most common microorganisms were coagulase-negative staphylococci (30.6%) and Pseudomonas aeruginosa (15.9%). MDR gram-negative bacilli caused 11.9% of all episodes. Clinical characteristics, source of BSI, etiology, and outcomes changed depending on time since HSCT. Globally, 26.6% of episodes were treated with inappropriate empiric antibiotic therapy, more frequently in BSI episodes caused by P. aeruginosa, MDR P. aeruginosa, and MDR gram-negative bacilli. The 30-day mortality was 19.2%. Independent risk factors for mortality were BSI occurring ≥30 days after HSCT (odds ratio [OR], 11.21; 95% confidence interval [CI], 4.63 to 27.19), shock (OR, 7.10; 95% CI, 2.98 to 16.94), BSI caused by MDR P. aeruginosa (OR, 4.45; 95% CI, 1.12 to 17.72), and inappropriate empiric antibiotic therapy for gram-negative bacilli or Candida spp. (OR, 3.73; 95% CI, 1.27 to 10.89). HSCT recipients experiencing BSI have high mortality related to host and procedure factors, causative microorganism, and empiric antibiotic therapy. Strategies to identify HSCT recipients at risk of MDR P. aeruginosa and reducing inappropriate empiric antibiotic therapy are paramount to reduce mortality.