To Örebro University

OBJECTIVES: Optimal antibiotic treatment is important in the treatment of sepsis. However, patients with sepsis are at risk of suboptimal antibiotic concentrations. This study aimed to evaluate β-lactam antibiotic concentrations during the first 48 h in patients with community-acquired sepsis admitted to the ICU, and to identify variables associated with antibiotic concentrations that were too low or too high.

METHODS: This prospective, observational, single-centre study included patients aged ≥18 years with a high likelihood of infection, a SOFA score of ≥2p, planned β-lactam antibiotic treatment, and ICU admission. The exclusion criteria were ongoing antibiotic treatment and/or nosocomial infections. β-Lactam concentrations were measured up to seven times during the first 48 h. The estimated trough concentrations were divided by the predetermined MIC to generate MIC-multiples for comparison. Patients were allocated to three groups based on the MIC-multiple (MIC× < 1, 1-8 or >8).

RESULTS: Fifty patients were included, with a median of seven samples per patient (257 samples). The group with MIC-multiples of <1 (n = 16) was associated with younger age, lower Charlson comorbidity index, Simplified Acute Physiology Score 3, creatinine concentration, and need for noradrenaline. The group with MIC-multiples of >8 (n = 15) had higher creatinine and noradrenaline levels.

CONCLUSIONS: ICU patients with sepsis are at risk of either too low or too high antibiotic concentrations, and specific patient characteristics may be predictable. Therapeutic drug monitoring in combination with model-informed precision dosing may also help to optimize antibiotic dosing in the early phase of community-acquired sepsis to prevent treatment failure and toxicity.

Background: Body temperature and peripheral blood inflammatory markers are often elevated in acute stroke. Whether the increase in inflammatory markers is caused by the stroke itself or is attributable to a complication, is incompletely understood. This uncertainty may hamper the diagnosis and treatment of infections. We aimed to describe the dynamics of inflammatory parameters in a cohort of stroke patients free from complications.

Methods: Acute stroke patients were prospectively included within 48 h of symptom onset and monitored through daily questions of symptoms and clinical examinations to detect complications. Inflammatory parameters in blood and body temperature were measured daily for up to ten days and the 97.5th percentile calculated. Values were compared with paired t-test to measurements at a 90-day follow up.

Results: 70 stroke patients were included. 51 of them were considered complication-free and sampled for a total of 282 days. Body temperature, CRP and WBC were all significantly elevated the first days after stroke, compared to 90-days post stroke. Mean body temperature was highest at 24-48h at 37.1 degrees C, mean WBC was highest at 0-24h at 8.1 x 10<^>9/L, compared to 36.7 degrees C and 6.0 x 10<^>9/L at the 90-day follow-up (p-values < 0.01). Median CRP peaked at 7.0 mg/L 120-144 h after stroke, compared to 0.9 mg/L at follow-up (p-value < 0.01).

Conclusions: Acute stroke may cause mildly elevated levels of CRP, WBC and body temperature. Except for WBC during the first 24h, higher levels (such as CRP > 50mg/L, WBC > 11 x 10<^>9/L or body temp > 38 degrees C) are very uncommon (< 2.5%) and are likely to reflect a complication.

Blood stream infections are associated with high mortality and morbidity. NEWS2 is a quick scoring system including bedside measurable vital signs. This study aimed to investigate the ability of NEWS2 ≥ 5p to identify sepsis, per Sepsis-3 criteria, among adult patients with community-acquired infection and positive blood cultures. It also explored if NEWS2 ≥ 5p could indicate infection etiology based on bacterial species in blood culture. This retrospective study included 555 patients with positive blood cultures. 425 of 555 (76.6%) patients had sepsis. The sensitivity of NEWS2 ≥ 5p for detecting sepsis was 86.6% and was not statistically associated with infection etiology. Patients with S. pneumoniae had a higher median NEWS2 score than those with other bacterial species. The 28-day mortality rate was 12.1%, and the sensitivity of NEWS2 ≥ 5p for detecting 28-day mortality was 91.0%. NEWS2 ≥ 5p was detected in a high proportion of sepsis cases among patients with blood stream infections, independent of bacterial species, and is a quick tool for identifying high sepsis likelihood in the emergency department.

BACKGROUND: The purpose of this study was to prospectively investigate the incidence of influenza-associated pulmonary aspergillosis (IAPA) in influenza patients admitted to intensive care units in Sweden.

METHODS: The study included consecutive adult patients with PCR-verified influenza A or B in 12 Swedish intensive care units (ICUs) over four influenza seasons (2019-2023). Patients were screened using serum galactomannan and β-d-glucan tests and fungal culture of a respiratory sample at inclusion and weekly during the ICU stay. Bronchoalveolar lavage was performed if clinically feasible. IAPA was classified according to recently proposed case definitions.

RESULTS: The cohort included 55 patients; 42% were female, and the median age was 59 (IQR 48-71) years. All patients had at least one galactomannan test, β-d-glucan test and respiratory culture performed. Bronchoalveolar lavage was performed in 24 (44%) of the patients. Five (9%, 95% CI 3.8% - 20.4%) patients were classified as probable IAPA, of which four lacked classical risk factors. The overall ICU mortality was significantly higher among IAPA patients than non-IAPA patients (60% vs 8%, p = 0.01).

CONCLUSIONS: The study represents the first prospective investigation of IAPA incidence. The 9% incidence of IAPA confirms the increased risk of invasive pulmonary aspergillosis among influenza patients admitted to the ICU. Therefore, it appears reasonable to implement a screening protocol for the early diagnosis and treatment of IAPA in influenza patients receiving intensive care.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04172610, registered November 21, 2019.

BACKGROUND: Blood stream infection (BSI) and sepsis are serious clinical conditions and identification of the disease-causing pathogen is important for patient management. The RISE (Rapid Identification of SEpsis) study was carried out to collect a cohort allowing high-quality studies on different aspects of BSI and sepsis. The aim of this study was to identify patients at high risk for BSI who might benefit most from new, faster, etiological testing using neutrophil to lymphocyte count ratio (NLCR) and Shapiro score.

METHODS: Adult patients (≥ 18 years) presenting at the emergency department (ED) with suspected BSI were prospectively included between 2014 and 2016 at Örebro University Hospital. Besides extra blood sampling, all study patients were treated according to ED routines. Electronic patient charts were retrospectively reviewed. A modified Shapiro score (MSS) and NLCR were extracted and compiled. Continuous score variables were analysed with area under receiver operator characteristics curves (AUC) to evaluate the ability of BSI prediction.

RESULTS: The final cohort consisted of 484 patients where 84 (17%) had positive blood culture judged clinically significant. At optimal cut-offs, MSS (≥3 points) and NLCR (> 12) showed equal ability to predict BSI in the whole cohort (AUC 0.71/0.74; sensitivity 69%/67%; specificity 64%/68% respectively) and in a subgroup of 155 patients fulfilling Sepsis-3 criteria (AUC 0.71/0.66; sensitivity 81%/65%; specificity 46%/57% respectively). In BSI cases only predicted by NLCR> 12 the abundance of Gram-negative to Gram-positive pathogens (n = 13 to n = 4) differed significantly from those only predicted by MSS ≥3 p (n = 7 to n = 12 respectively) (p < 0.05).

CONCLUSIONS: MSS and NLCR predicted BSI in the RISE cohort with similar cut-offs as shown in previous studies. Combining the MSS and NLCR did not increase the predictive performance. Differences in BSI prediction between MSS and NLCR regarding etiology need further evaluation.

Background: Combination therapy in the treatment of sepsis, especially the value of combining a beta-Lactam antibiotic with an aminoglycoside, has been discussed. This retrospective cohort study including patients with sepsis or septic shock aimed to investigate whether one single dose of gentamicin at admittance (SGA) added to beta-Lactam antibiotic could result in a lower risk of mortality than beta-Lactam monotherapy, without exposing the patient to the risk of nephrotoxicity.

Methods and findings: All patients with positive blood cultures were evaluated for participation (n = 1318). After retrospective medical chart review, a group of patients with community-acquired sepsis with positive blood cultures who received beta-Lactam antibiotic with or without the addition of SGA (n = 399) were included for the analysis. Mean age was 74.6 yrs. (range 19-98) with 216 (54%) males. Sequential Organ Failure Assessment score (SOFA score) median was 3 (interquartile range [IQR] 2-5) and the median Charlson Comorbidity Index for the whole group was 2 (IQR 1-3). Sixty-seven (67) patients (17%) had septic shock. The 28-day mortality in the combination therapy group was 10% (20 of 197) and in the monotherapy group 22% (45 of 202), adjusted HR 3.5 (95% CI (1.9-6.2),p= < 0.001. No significant difference in incidence of acute kidney injury (AKI) was detected.

Conclusion: This retrospective observational study including patients with community-acquired sepsis or septic shock and positive blood cultures, who meet Sepsis-3 criteria, shows that the addition of one single dose of gentamicin to beta-lactam treatment at admittance was associated with a decreased risk of mortality and was not associated with AKI. This antibiotic regime may be an alternative to broad-spectrum antibiotic treatment of community-acquired sepsis. Further prospective studies are warranted to confirm these results.

OBJECTIVE: In the pathogenesis of sepsis, activation of both pro- and anti-inflammatory responses are key components, but knowledge is lacking on the association between bacterial etiology and development of dysregulated responses with sustained immunosuppression. The aim of this study was to evaluate how the immunosupression marker HLA-DR on monocytes (mHLA-DR) is associated with bacterial etiology and markers of inflammation during the clinical trajectory of bloodstream infection (BSI).

METHODS: Ninety-one adults, predominantly non-ICU patients, with BSI caused by Streptococcus pneumoniae (n = 27), Staphylococcus aureus (n = 22), Escherichia coli/Klebsiella pneumoniae (n = 23), and other species (n = 19) were prospectively included, and sampled on admission (day 0) and on days 1-2, 3, 7±1, 14±2, and 28±4.

RESULTS: The dynamics of mHLA-DR, measured by flow cytometry, differed significantly between etiology groups (p<0.001). Patients with S. pneumoniae and S. aureus BSI demonstrated low initial mHLA-DR, with the S. aureus group showing delayed recovery over time. Eleven patients (55% S. aureus) had negative outcome (secondary bacteremia or death) and they demonstrated sustained C-reactive protein elevation, neutrophilia, lymphocytopenia, and loss of mHLA-DR.

CONCLUSIONS: Dynamics of mHLA-DR varied according to the bacterial etiology of infection, with delayed recovery in patients with S. aureus BSI. Patients with negative outcome showed sustained CRP elevation, neutrophilia, lymphocytopenia, and low levels of mHLA-DR, supporting the theory of a dysregulated host response with persistent inflammation and immunosuppression in late stages of deleterious sepsis.

Propionibacterium spp. are a rare cause of infective endocarditis (IE). The diagnosis is difficult because the bacteria are slow-growing and growth in blood cultures is often misinterpreted as contamination from the skin flora. The aim of this study was to describe all cases of Propionibacterium spp. endocarditis in the Swedish national registry of IE. The registry was searched for all cases of IE from 1995 to 2016 caused by Propionibacterium spp. Data concerning clinical characteristics, treatment, and outcome were registered. A total of 51 episodes of definitive prosthetic valve endocarditis (PVE) caused by Propionibacterium spp. were identified, comprising 8% of cases of PVE during the study period. Almost all cases (n = 50) were male. The median time from surgery to diagnosis of IE was 3 years. Most patients were treated mainly with beta-lactams, partly in combination with aminoglycosides. Benzyl-penicillin was the most frequently used beta-lactam. A total of 32 patients (63%) underwent surgery. Overall, 47 patients (92.1%) were cured, 3 (5.9%) suffered relapse, and 1 (2.0%) died during treatment. IE caused by Propionibacterium spp. almost exclusively affects men with a prosthetic valve and findings of Propionibacterium spp. in blood cultures in such patients favors suspicion of a possible diagnosis of IE. In patients with prosthetic valves, prolonged incubation of blood cultures up to 14 days is recommended. The prognosis was favorable, although a majority of patients required cardiac surgery during treatment. Benzyl-penicillin should be the first-line antibiotic treatment option for IE caused by Propionibacterium spp.

To improve management of Staphylococcus aureus bacteremia (SAB), better understanding of host-pathogen interactions is needed. In vitro studies have shown that S. aureus bacteria induce dose-dependent immunosuppression that is evidenced by reduced expression of major histocompatibility complex (MHC) class II on antigen presenting cells. Thus, the aim of this study was to determine whether expression of the MHC class II-related genes HLA-DRA and CD74 is more greatly reduced in complicated SAB, with its probable higher loads of S. aureus, than in uncomplicated SAB. Adult patients with SAB were prospectively included and blood samples taken on the day of confirmation of SAB (Day 1) and on Days 2, 3, 5 and 7. HLA-DRA and CD74 mRNA expression was determined by quantitative reverse transcription PCR. Sepsis was defined according to the Sepsis-3 classification and SAB was categorized as complicated in patients with deep-seated infection and/or hematogenous seeding. Twenty patients with SAB were enrolled and samples obtained on all assessment days. HLA-DRA and CD74 expression did not differ significantly between patients with SAB and sepsis (n=13) and those without sepsis (n=7) on any assessment day. However, patients with complicated SAB (n=14) had significantly weaker HLA-DRA expression on all five assessment days than patients with uncomplicated SAB (n=6). Additionally, they tended to have weaker CD74 expressions. Neutrophil, monocyte and leukocyte counts did not differ significantly between complicated and uncomplicated SAB. In conclusion, patients with complicated SAB show weaker HLA-DRA expression than those with uncomplicated SAB during the first week of bacteremia.

INTRODUCTION: Cat bite infections usually involve a mix of anaerobic and aerobic bacteria including species of Pasteurella, Streptococcus, Staphylococcus, Bacteroides, and Fusobacterium. We report a case of Pasteurella multocida infection from cat bites leading to endocarditis and subsequent aortic valve replacement.

PRESENTATION OF CASE: A 70-year-old male was admitted because of fever, tachycardia, and malaise. He had a history of alcohol abuse and was living alone with a cat in a rural area. A sepsis of unknown origin was suspected, and intravenous treatment with gentamicin and cefotaxime was initiated. Blood cultures yielded Pasteurella multocida, and the patient history revealed repeated cat bites. After four days, the patient was discharged with oral penicillin V treatment. Two weeks later, the patient returned with fever and a new systolic murmur. An aortic valve endocarditis was diagnosed, and it became clear that the patient had not completed the prescribed penicillin V treatment. The patient underwent a biological aortic valve replacement with debridement of an annular abscess, and the postoperative course was uneventful.

DISCUSSION: Endocarditis due to Pasteurella is extremely rare, and there are only a few reports in the literature. Predisposing factors in the present case were alcohol abuse and reduced compliance to treatment.

CONCLUSION: Cat bites are often deep, and in rare circumstances can lead to life-threatening endocarditis. Proper surgical revision, antibiotic treatment, and patient compliance are necessary components in patient care to avoid this complication.