We analyzed the attainment of early pharmacological targets of continuous infusion meropenem and piperacillin/tazobactam and the use and effect of a real-time therapeutic drug monitoring (TDM) program on subsequent dosing and target attainment in patients who are critically ill. This was a single-center, retrospective study among patients hospitalized in the intensive care unit in a Swiss tertiary care hospital from 2017 to 2020. The primary outcome was target attainment [100% tT _{≥ 4xECOFF (Pseudomonas aeruginosa)}] of continuous infusion meropenem and piperacillin/tazobactam within 72 hours after initiation of treatment. A total of 234 patients were included. Median first meropenem (n = 186 of 234) and piperacillin (n = 48 of 234) concentration was 21 mg/L (interquartile range [IQR], 15.6–28.6) and 100.7 mg/L (IQR, 64.0–160.2), respectively. Pharmacological target was attained in 95.7% (95% confidence interval [CI], 91.7–98.1) of patients receiving meropenem and 77.0% (95% CI, 62.7–87.9) treated with piperacillin/tazobactam. In the univariable and multivariable logistic regression, body weight and estimated glomerular filtration rate were negatively associated with target attainment. Subsequently, meropenem dosage was decreased or stopped in 35 of 186 (18.8%) and 89 of 186 (47.9%) patients, respectively, and increased in 2 of 186 (1.1%) patients. Continuous infusion meropenem and piperacillin/tazobactam yielded excellent and moderate early pharmacological target attainment in critically ill patients, respectively. The TDM was mainly used to decrease meropenem dosage.

Fungal antigens such as β-(1→3)-D-glucan (BDG) or mannan (Mn) are useful for detection of candidemia. However, detailed data on serum levels before diagnosis and during treatment are scarce. We conducted a prospective study at two German tertiary care centers for 36 months. Sera from adult patients with candidemia were tested for BDG (Fungitell assay) and Mn (Platelia Candida Ag-Plus assay). For each patient, the clinical course and biomarker kinetics were closely followed and compared. 1,243 sera from 131 candidemia episodes and 15 relapses were tested. In 35% of episodes, empirical therapy included an antifungal drug. Before blood culture sampling, BDG and Mn levels were elevated in 62.4% and 30.8% of patients, respectively. Sensitivity at blood culture sampling was 78.6% (BDG) and 35.1% (Mn). BDG levels of non-survivors were significantly higher than those of survivors. During follow-up, a therapeutic response was associated with decreasing BDG and Mn levels in 84.3% or 70.5% of episodes, respectively. A median increase of 513 pg BDG/mL and 390 pg Mn/mL indicated a relapse of candidemia with a sensitivity of 80% or 46.7%, respectively. In 72.9% and 46.8% of patients, increasing BDG or Mn levels were associated with a fatal outcome. Prior to discharge, BDG and Mn levels had dropped or normalized in 65.7% or 82.1% of patients, respectively. Summarising, in patients with candidemia, biomarker positivity usually precedes culture positivity. Relapses are mostly accompanied by secondary biomarker increases. Rising concentrations of BDG and Mn predict lethality, whereas decreasing levels suggest a favorable outcome in the majority of patients.

Guidance for blood culture (BC) collection is limited. Inappropriate BC collection may be associated with potentially harmful consequences for the patient such as unnecessary laboratory testing, treatment and additional costs. The aim of the study was to assess the appropriateness of BC collection and related knowledge and attitude of precribers. We conducted a single-center quality control study to assess the appropriateness of BC collection according to the local guidelines in a Swiss university hospital in 2020 by combining three different approaches: point prevalence, patient-individual longitudinal and diseases-related analysis. Second, we conducted a survey regarding BC collection practices and knowledge among physicians in two non-university and one university hospital using an 18-item electronic questionnaire. We analyzed 1114 BC collected in 344 patients. Approximately 40% of the BCs were collected inappropriately, in particular in diseases with low pretest probability of bacteremia such as non-severe community acquired pneumonia (CAP). Follow-up blood culture (FUBC) collection was inappropriate in 60%. Growth of a relevant pathogen was more frequently observed in appropriately than in inappropriately collected BCs (18% vs. 3%, p < 0.001). In the survey, uncertainty concerning the need of index BC collection was high in non-severe CAP and uncomplicated cellulitis. Almost half of the BCs was not collected according to the guidelines, especially in non-severe CAP and in case of FUBCs. Substantial uncertainty among physicians regarding BC ordering practices was identified. The implementation of diagnostic stewardship programs may improve BC collection practices, increase adherence to local guidelines, and may help reducing unnecessary diagnostics and treatment.

Syndromic multiplex panel testing enables simultaneous detection of multiple respiratory pathogens, but limited data is available on the comparative diagnostic performance of different testing systems. In this multicenter prospective study, we aimed to compare the QIAstat‐Dx Respiratory Panel 2.0 (QIAstat‐Dx‐RP2.0) with the widely used BioFire‐RP2.1, using 269 respiratory clinical specimens. Concordant test results were obtained in 232 (86.3%) cases. Discordant test results included 33 BioFire‐RP2.1(+)/QIAstat‐Dx‐RP2.0(−) and 4 BioFire‐RP2.1(‐)/QIAstat‐Dx‐RP2.0(+) results. Discordant samples showed significantly lower pathogen loads than concordant ones (p < 0.01). Overall, the QIAstat‐Dx‐RP2.0 showed an analytical sensitivity of 50%–100% depending on the respiratory target, with an analytical specificity ≥ 99.0%. Most significant differences were found for the detection of adenovirus, human coronaviruses, respiratory syncytial virus, human rhinovirus/enterovirus and SARS‐CoV‐2 (kappa‐score: 0.67–0.91). Co‐detections of respiratory pathogens were identified in 47 cases by BioFire‐RP2.1 and 29 by QIAstat‐Dx‐RP2.0. Agreement rates between the two multiplex panel tests decreased from 91.8% for single pathogen detections to 65.0% and 42.9% for co‐detecting two and three pathogens, respectively. Pathogen loads were significantly lower in co‐detections compared to single pathogen detections (p < 0.01), potentially explaining the lower detection rates with the QIAstat‐Dx‐RP2.0 in cases of multiple pathogens. In conclusion, our prospective multicenter evaluation showed good diagnostic performance of the QIAstat‐Dx‐RP2.0 assay, but lower detection rates for some respiratory targets compared to BioFire‐RP2.1. As QIAstat‐Dx‐RP2.0 offers advantages in handling, noise emission, cost effectiveness, and provides semi‐quantitative results compared to BioFire‐RP2.1 an updated version with enhanced analytical sensitivity would be a viable alternative syndromic testing system for detecting respiratory pathogens.

Needlestick accidents while handling of infectious material in research laboratories can lead to life-threatening infections in laboratory personnel. In laboratories working with the lymphocytic choriomeningitis virus (LCMV), the virus can be transmitted to humans through needlestick injury and lead to serious acute illness up to meningitis. We report of a case of LCMV meningitis in a laboratory worker who sustained a penetrating needlestick injury with a LCMV-contaminated hollow needle whilst disposing of a used syringe into the sharps waste bin. Four days after needlestick injury the laboratory worker developed a systemic disease: 11 days after exposure, she was diagnosed with meningitis with clinical signs and symptoms of meningismus, photophobia, nausea and vomiting, requiring hospitalisation. The PCR was positive for LCMV from the blood sample. 18 days after exposure, seroconversion confirmed the diagnosis of LCMV-induced meningitis with an increase in specific LCMV-IgM antibodies to 1:10′240 (day 42: 1:20′480). Ten weeks after exposure, a follow-up titre for IgM returned negative, whereas IgG titre increased to 1:20′480. This is the first case report of a PCR-documented LCMV meningitis, coupled with seroconversion, following needlestick injury. It highlights the importance of infection prevention practices that comprise particularly well established safety precaution protocols in research laboratories handling this pathogenic virus, because exposure to even a small amount of LCMV can lead to a severe, life-threatening infection.

We investigated the clinical relevance of Dermabacter hominis isolated from samples of 108 patients. Polymicrobial growth was evident in 88% of specimens. Isolation of D. hominis was of definitive or possible significance in only 14% of patients. Vancomycin remains the drug of choice given a penicillin resistance rate of 84%.