Infection最新文献

Purpose: This study aims to evaluate the burden of respiratory syncytial virus (RSV) infections in patients with haematological diseases. It seeks to analyse the relevance of prevention, diagnosis and treatment of RSV infections.

Methods: A multi-centre, retrospective study was conducted across University Hospitals in Cologne, Düsseldorf, Bonn, and the University Medical Centre Hamburg-Eppendorf between Jan 2016 and Aug 2023. All haematological patients with diagnosed RSV infection were included. The study focused on the incidence of RSV, underlying conditions, comorbidities, coinfections and clinical outcomes such as hospitalization, intensive care unit (ICU) admission and mortality.

Results: Of 166 patients, 89 (53.6%) had signs of pneumonia and 37 (22.3%) were admitted to ICU due to RSV infection, while 20 (54%) of those were mechanically ventilated with median duration of 11 days (1,33; IQR:18). Mean age was 60 years (range 14-88). Sixteen patients (9.6%) were treated as outpatients, while 52 (31.3%) were hospitalized due to RSV infection; the median hospital stay was 16 days (IQR 25.25, range 0-97). 79 (47.6%) of patients presented with leukopenia and 57 (34.3%) with neutropenia. In total, 22 patients (13.3%) died within 30 days and 29 (17.5%) died within 90 days. Highest mortality rates were seen in patients with aggressive lymphoma (23.5%) and acute leukaemia (18%).

Conclusion: RSV significantly impacts patients with haematological diseases, leading to high rates of hospitalization, ICU admission, and mortality. Preventive measures, such as vaccination, alongside early diagnosis and individualized management, are essential to reduce RSV-associated morbidity and mortality in this high-risk population.

Purpose: Anidulafungin is recommended as a first-line treatment for invasive Candida infections in critically ill patients. Pharmacokinetic (PK) variability is large in critically ill patients, potentially compromising pharmacokinetic-pharmacodynamic (PKPD) target attainment under standard dosing. We aimed to assess anidulafungin exposure, PKPD target attainment, and population (pop)PK in critically ill patients.

Methods: Adult ICU patients receiving standard anidulafungin dosing [200 mg on day 1, then 100 mg daily] were included (NCT04045366). We performed rich blood sampling on an early (day 2 ± 1) and/or late (day 5 ± 1) treatment day. Using total anidulafungin plasma concentrations, we developed a popPK model (NONMEM7.5) and conducted Monte Carlo simulations (n = 1,000 per virtual patient) to evaluate the impact of patient factors on PKPD target attainment (AUC_24h target 83.5 mg×h/L).

Results: Twenty patients contributed 188 anidulafungin concentrations. PKPD target attainment was 45% and 65% on early and late sampling days, respectively. A two-compartment popPK model with first-order elimination described the data. Anidulafungin clearance increased with bodyweight and central volume of distribution increased as serum albumin decreased. Both bodyweight and serum albumin had a clinically relevant impact on PKPD target attainment at day 1 (area under the ROC curve; AUROC 0.82 and 0.62, respectively), and bodyweight on PKPD target attainment at day 14 (AUROC 0.94). Standard anidulafungin dosing regimen fails to achieve adequate target attainment throughout the treatment period.

Conclusion: Standard anidulafungin dosing is insufficient for achieving adequate exposure in critically ill patients. An interactive simulation tool is provided to aid dose-finding research and explore different dosing strategies and targets.

Purpose: To describe the clinical characteristics and outcomes of patients with nosocomial pneumonia (NP) caused by carbapenem-resistant Gram-negative bacilli (CR-GNB) and to compare them to patients with NP caused by carbapenem-susceptible (CS)-GNB.

Methods: Prospective observational multicenter study including patients with bacteremic NP caused by GNB from the ALARICO Network (June 2018-January 2020). The primary outcome measure was 30-day mortality. A Cox regression analysis was performed to identify factors independently associated with 30-day mortality. Hazard ratio (HR) and 95% confidence intervals (CI) were calculated.

Results: Overall, 167 patients with GNB NP were included: 101 with bacteremic NP caused by CR-GNB (n = 39 by KPC-producing Klebsiella pneumoniae, n = 29 by carbapenem-resistant Acinetobacter baumannii, n = 28 by carbapenem-resistant Pseudomonas aeruginosa, n = 5 by MBL-producing Klebsiella pneumoniae) and 66 cases of bacteremic CS-GNB NP. Thirty-day mortality rate was higher in patients with NP caused by CR-GNB compared to those with NPcaused by CS-GNB (46.5% vs 30.3%, p = 0.036). On multivariable analysis, age (HR 1.044, 95% CI 1.021-1.067, p < 0.001), hematological malignancy (HR 4.307, 95% CI 1.924-9.643, p < 0.001) and septic shock (HR 3.668, 95% CI 2.001-6.724, p < 0.001) were factors independently associated with 30-day mortality, while the receipt of adequate antibiotic therapy within 24 h from infection onset (HR 0.495, 95% CI 0.252-0.969, p = 0.04) was a protective factor. Carbapenem resistance was not associated with increased risk of mortality (HR 1.075, 95% CI 0.539-2.142, p = 0.837).

Conclusions: Patients with bacteremic NP caused by CR-GNB have high mortality rate. Strategies to reduce the time from infection to the administration of adequate antibiotic therapy should be implemented in patients with NP.

Background: The best treatment for bloodstream infections (BSI) due to chromosomal AmpC (c-AmpC) producing Enterobacterales is not clearly defined.

Objectives: To describe the clinical and microbiological outcomes of patients treated with piperacillin/tazobactam, cefepime or carbapenems for bloodstream infections (BSIs) due to c-AmpC beta-lactamase-producing strains.

Data sources: We searched MEDLINE, the Cochrane Library and EMBASE to screen original reports published up to January 2024.

Study eligibility criteria: RCTs and observational studies investigating all-cause mortality, clinical failure, microbiological failure or rate of ADRs of patients treated with piperacillin/tazobactam, cefepime or carbapenems.

Participants: Patients with bloodstream infections due to c-AmpC producing bacteria.

Interventions: Piperacillin/tazobactam, cefepime or carbapenems as targeted treatment.

Assessment of risk of bias: We used the Cochrane Risk of Bias Tool for RCTs, and the Newcastle Ottawa scale for observational studies.

Methods of data synthesis: We conducted a meta-analysis pooling Risk ratios (RRs) through random effect models.

Results: We screened 1,720 original reports, and 20 studies (1 RCTs, 1 case-control study, 18 cohort studies) were included in the analysis, for a total of 2,834 patients. When comparing piperacillin/tazobactam with alternative treatments (cefepime or carbapenems), no significant difference in mortality rate was observed between the treatment groups (RR: 1.1; 95% CI: 0.76-1.58, p = 0.61), while an higher rate of microbiological failure (RR: 1.80; 95% CI: 1.15-2.82, p = 0.01) and clinical failure (RR: 1.54; 95% CI: 1.00-2.40, p = 0.05) was observed among patients receiving piperacillin/tazobactam. No difference was observed in microbiological and clinical failure rate among patients treated with cefepime or carbapenems, with a lower mortality rate in those receiving cefepime (RR: 0.74; 95% CI: 0.59-0.94, p = 0.014).

Conclusions: Cefepime represents an excellent alternative to carbapenems for BSI due to AmpC-producing strains, whereas piperacillin/tazobactam is associated with a higher rate of clinical and microbiological failure. There is an urgent need for randomized clinical trials that aim to define the best carbapenem-sparing strategy in these infections.

Purpose: Infective endocarditis (IE) is a heterogeneous disease undergoing epidemiological changes. Whether those changes have an impact on the correlates of embolic events (EE) remains unclear. We analyzed the correlates of EE and proposed a diagnostic score model in a large contemporary cohort.

Methods: This is a retrospective observational study including patients with definite valve IE admitted between 2000 and 2023. EE were defined as acute complications causing overt clinical manifestations. The study primary aim was to identify independent correlates of EE.

Results: 715 valve-IE cases were included. EE occurred in 41.4% (n = 296) of patients. S. aureus etiology (OR 2.708[1.268-5.786]; p = 0.010), C-reactive protein > 6.7 mg/dL (OR 2.415[1.371-4.252]; p = 0.002), and splenomegaly (OR 2.858[1.620-5.403]; p < 0.001) were independently associated with EE. VS ≥ 14 mm (OR 1.575[0.925-2.682]; p = 0.061) and D-dimers > 747 ng/mL (OR 1.677[0.976-2.881]; p = 0.061) showed a trend for independent association. These variables were included in a diagnostic score model. A stepwise increase of EE occurrence was found stratifying patients into 3 categories (score 0-2-22%; score 3-5-53%; score 6-8-78%;p < 0.001). A cut-off of 2 (< 2 vs. ≥ 2) showed a sensitivity of 83% and a specificity of 50% (AUROC 0.732; p < 0.001).

Conclusion: EE were independently associated to Staphylococcus aureus, C-reactive protein and splenomegaly and less strongly linked to vegetation size in our cohort. These results may be explained by a change in embolic complications correlates linked to the epidemiological shift. The discriminative ability of our score was only fair. At present, clinicians should rely upon clinical and imaging data to diagnose EE.

mRNA-based vaccines played a key role in fighting the global COVID-19 pandemic by saving millions of lives. In rare cases, however, the BNT162b2 vaccine has been associated with severe adverse reactions e.g. myocarditis (OE ratio 2.78; 95% CI 2.61; 2.95) [Faksova in Vaccine 42(9):2200-2211, 2024, https://doi.org/10.1016/j.vaccine.2024.01.100 , Schwab in Clin Res Cardiol 112(3):431-440, 2022, https://doi.org/10.1007/s00392-022-02129-5 ]. Here, we describe the case of a 38-year-old man who developed a wide variety of long-term symptoms (fatigue, dizziness, palpitations with recurrent syncopes, paresthesia, paresis and fasciculations) following his first mRNA-based BNT162b2 COVID-19 vaccination. 143 days after vaccination, a subsequent COVID-19 infection was associated with exacerbation of paresis and a temporary loss of vision. After ruling out other causes and due to the immediate temporal association, an adverse reaction to vaccination appears likely. The fact that these symptoms worsened after a subsequent acute COVID 19 infection hints at the possibility of a common underlying pathophysiology. This case combines two clinical phenomena that have emerged during the COVID 19 pandemic, side effects associated with novel vaccines and Post-COVID Syndrome.

Background: To confirm the diagnosis of periprosthetic joint infection (PJI), the Infectious Diseases Society of America (IDSA) and the International Consensus Meeting (ICM) have defined criteria that include histology as a minor criterion and the sonication method only as an additional criterion. The aim of this monocentric, retrospective study was to investigate the value of histology and whether sonication leads to a more accurate diagnosis.

Materials and methods: All revision surgeries for knee and hip arthroplasty between 2017 and 2020 were included. With regard to microbiological diagnostic, conventional culture of periprosthetic biopsies and sonication of explant material were performed. In addition, histology and non-specific inflammatory markers (CRP, leukocytes) were recorded.

Results: A total of 78 patients with PJI and 62 aseptic controls were included. From both microbiological methods (conventional culture / sonication), Staphyloccus (S.) epidermidis and S. aureus were detected most frequently. However, compared to the conventional microbiology, a higher sensitivity was calculated for sonication, albeit with a lower specificity in relation to a PJI. In two logistic regression models for the significance of all diagnostic parameters in PJI, the AUC was 0.92 and 0.96 with histology in particular making the decisive contribution in both models (p < 0. 001, both models).

Conclusion: Since histology showed the highest accuracy in the current study, its importance in the PJI criteria should be reevaluated. Sonication shows a high sensitivity for germ detection with a lower specificity and should only be used in combination with the conventional culture for microbiolgical diagnostics.

Purpose: We aimed to develop and implement dosing recommendations for antimicrobials in obese and underweight patients within an academic hospital, and assess their impact on antibiotic prescribing.

Methods: A multi-step approach project was performed. First, obese and underweight patient prevalence and antimicrobial prescription frequency was determined in a point prevalence study. Second and third, a literature review and e-survey provided dosing evidence. Fourth, a consensus meeting was organized to formulate dosing recommendations. Fifth, these were implemented in our clinical validation service as six clinical rules continuously screening patients' records for potentially inappropriate prescriptions (PIPs). Uptake was evaluated by documenting the number of advices and acceptance rate. Last, an interrupted time series analysis (ITS) compared pre- and post-implementation periods to measure the impact of the intervention on residual PIPs/day. A residual PIP was defined as a PIP which persisted up to 48 h.

Results: First, 41% of 15.896 hospitalized patients received antimicrobials over 20 days; of which 12% were obese and 9% underweight. Antibiotics were predominantly prescribed according to standard dosing regimens, adjusted to renal function. Next, six dosing recommendations, derived from literature, survey, and consensus, were implemented. In the fifth step, during an 18-week period, 219 advices were given, with 86% acceptance rate. Last, in the ITS analysis, at preintervention, a median of 75% residual PIPs/day existed, reduced to 0% postintervention. Use of clinical rules resulted in a significant immediate 84% relative reduction in residual PIPs (95% CI 0.55-0.94).

Conclusion: After conducting a literature review, e-survey, and seeking consensus from a panel of experts, dosing recommendations for antimicrobial treatment in both obese and underweight patients were developed. These recommendations have been successfully implemented into clinical practice, addressing the specific needs of these patient populations.

Purpose: Sulbactam (SBT) is one of the most significant treatments for patients with extensively drug-resistant Acinetobacter baumannii (XDR-AB). However, the efficacy and safety of SBT and its high dose regimen has not been well documented. This retrospective study aimed to assess the efficacy and safety of SBT-based treatment, particularly at high-dose (≥ 6 g/day), for XDR-AB infection.

Method: A total of 52 XDR-AB infected patients treated with intravenous SBT at Peking Union Medical College Hospital were included. The primary outcome was 28-day all-cause mortality, while the secondary outcome was 14-day clinical response and the time of response. The formulation of SBT in our study is 0.5 g per vial.

Results: Among the patients, the 28-day all-cause mortality rate was 36.5% (19/52), and the favorable 14-day clinical response rate was 59.6% (31/52). The 28-day mortality was independently associated coinfection with gram-positive bacteria (GPB) and a shorter duration of therapy. Patients with intracranial infection might have a longer survival time. A favorable 14-day clinical response was associated with the dose of SBT, and a longer treatment duration. However, the higher creatinine clearance (CrCl) associated with a worse clincal response. In addition, a higher SBT dosage was significantly correlated with a shorter time to clinical response. No adverse effects related were reported.

Conclusion: The single-agent formulation of SBT emerges as a promising alternative for the treatment of XDR-AB infection, such as intracranial infection, particularly at high doses (≥ 6 g/day). Besides, longer duration of treatment correlates with higher survival rate and better favorable clinical response. Higher CrCl negatively correlates with favorable clinical response.

Purpose: Early diagnosis of surgical site infections (SSIs) could prevent surgical revision. Inflammatory markers (IMs), such as procalcitonin (PCT), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α), seem more accurate in diagnosing SSI than C-reactive protein (CRP) and white blood cell (WBC) count. The aim was to compare the predictive values of CRP, WBC count, PCT, IL-6, and TNF-α in SSI detection.

Methods: A total of 130 patients undergoing dorsal spondylodesis from 2019 to 2024 were enrolled in a prospective diagnostic study at a maximum care spine center. IMs were measured preoperatively and on the postoperative days (PODs) 1, 2, 3, 5, and 7. Patients with high suspicion of SSI underwent revision surgery. SSI was diagnosed when the microbiological evidence was positive. Patients were divided a posteriori into the non-infection and infection groups.

Results: IMs of 118 patients (66.9 ± 13.0 years, 61.0% females) were measured. Fifteen of the 118 patients (12.7%) developed an SSI. The groups differed with respect to existing hypertension, number of instrumented segments, region of surgery, CRP_POD1,7, PCT_POD7, and IL-6_POD3,5,7. Binary logistic regression for SSI detection including these parameters showed an area under the curve (AUC) of 0.88 (95% CI 0.79-0.98; P < 0.001). The main effect for SSI detection was maintained by IL-6_POD7 (odds ratio = 1.13; 95% CI 1.05-1.23; P = 0.001), which itself showed an AUC of 0.86 (95% CI 0.75-0.97).

Conclusion: Compared to CRP, WBC count, PCT, and TNF-α, IL-6 seems to be the critical IM for the early detection of an SSI.

Trial registration: drks.de: DRKS00033773, date of registration: 29.02.2024, retrospectively registered; Postoperative Markers of Inflammation in Spine Surgery (POMIS) Trial.