Impact of Swabbing Location, Self-Swabbing, and Food Intake on SARS-CoV-2 RNA Detection.

This study compared SARS-CoV-2 RNA loads at different anatomical sites, and the impact of self-swabbing and food intake. Adult symptomatic patients with SARS-CoV-2 or non-SARS-CoV-2 respiratory tract infection were included between 2021 and 2022. Patients performed a nasal and buccal swab before a professionally collected nasopharyngeal/oropharyngeal swab (NOPS). Buccal swabs were collected fasting and after breakfast in a subgroup of patients. SARS-CoV-2 RNA loads were determined by nucleic acid testing. Swabbing convenience was evaluated using a survey. The median age of 199 patients was 54 years (interquartile range 38-68); 42% were female and 52% tested positive for SARS-CoV-2. The majority of patients (70%) were hospitalized. The mean SARS-CoV-2 RNA load was 6.6 log10 copies/mL (standard deviation (SD), ±1.5), 5.6 log10 copies/mL (SD ± 1.9), and 3.4 log10 copies/mL (SD ± 1.9) in the professionally collected NOPS, and self-collected nasal and buccal swabs, respectively (p < 0.0001). Sensitivity was 96.1% (95% CI 90.4-98.9) and 75.3% (95% CI 63.9-81.8) for the nasal and buccal swabs, respectively. After food intake, SARS-CoV-2 RNA load decreased (p = 0.0006). Buccal swabbing was the preferred sampling procedure for the patients. In conclusion, NOPS yielded the highest SARS-CoV-2 RNA loads. Nasal self-swabbing emerged as a reliable alternative in contrast to buccal swabs. If buccal swabs are used, they should be performed before food intake.

Exploring the Impact of Model-Informed Precision Dosing on Procalcitonin Concentrations in Critically Ill Patients: A Secondary Analysis of the DOLPHIN Trial.

Model-informed precision dosing (MIPD) might be used to optimize antibiotic treatment. Procalcitonin (PCT) is a biomarker for severity of infection and response to antibiotic treatment. The aim of this study was to assess the impact of MIPD on the course of PCT and to investigate the association of PCT with pharmacodynamic target (PDT) attainment in critically ill patients. This is a secondary analysis of the DOLPHIN trial, a multicentre, open-label, randomised controlled trial. Patients with a PCT value available at day 1 (T1), day 3 (T3), or day 5 (T5) after randomisation were included. The primary outcome was the absolute difference in PCT concentration at T1, T3, and T5 between the MIPD and the standard dosing group. In total, 662 PCT concentrations from 351 critically ill patients were analysed. There was no statistically significant difference in PCT concentration between the trial arms at T1, T3, or T5. The median PCT concentration was highest in patients who exceeded 10× PDT at T1 [13.15 ng/mL (IQR 5.43-22.75)]. In 28-day non-survivors and in patients that exceeded PDT at T1, PCT decreased significantly between T1 and T3, but plateaued between T3 and T5. PCT concentrations were not significantly different between patients receiving antibiotic treatment with or without MIPD guidance. The potential of PCT to guide antibiotic dosing merits further investigation.

What every intensivist should know about: The value of limitations in clinical research.

Not applicable.

Detailed ß-(1→3)-D-glucan and mannan antigen kinetics in patients with candidemia.

Fungal antigens such as ß-(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.

Early Target Attainment With Continuous Infusion Meropenem and Piperacillin/Tazobactam and Utilization of Therapeutic Drug Monitoring in Critically Ill Patients: A Retrospective Cohort Study From 2017 to 2020.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Antibiotic treatment durations for common infectious diseases in Switzerland: comparison between real-life and local and international guideline recommendations.

OBJECTIVES: Shortening the duration of antibiotic therapy (DAT) for common infectious diseases may be an effective strategy to tackle antimicrobial resistance. Shorter DAT has been proven safe and effective for community-acquired pneumonia (CAP), cellulitis, and cholangitis. METHODS: In a retrospective multicentre quality-control study, medical records of 770 patients hospitalized with CAP, cellulitis, and cholangitis at three tertiary care hospitals in Switzerland during 2017-2018 were randomly selected. Appropriateness of antibiotic treatment duration was assessed according to international and local guidelines. RESULTS: Records of 271, 260, and 239 patients with CAP, cellulitis, and cholangitis were included, respectively. Median DAT was seven days (interquartile range [IQR] 6-9), ten days (IQR 8-13), and nine days (IQR 6-13) in CAP, cellulitis, and cholangitis, respectively. DAT longer than recommended by local and international guidelines was observed in 32% and 37% of CAP patients, 23% and 70% of cellulitis patients, and 33% and 37% of cholangitis patients, respectively. Positive blood cultures (odds ratio [OR] = 2.42 (95% confidence interval [CI] 1.33-4.34]), infectious diseases consultation (OR = 1.79 [95% CI 1.05-2.78]), impaired renal function (OR = 0.99 [95% CI 0.98-1.00] per 1 ml/min / 1.73 m2 increase in estimated glomerular filtration rate) and a higher degree of inflammation on admission (OR = 1.0 [95% CI 1.001-1.005] per 10 mg/L increase in C-reactive protein) were independently associated with a DAT longer than recommended in international guidelines. CONCLUSIONS: DAT exceeded recommendations in a significant proportion of patients with mostly community-acquired infections.

Antibiotic treatment duration in diverticulitis, complicated urinary tract infection, and endocarditis: a retrospective, single-center study.

OBJECTIVES: Despite the availability of international guidelines advocating shorter treatment durations, nonadherence to them is common. We assessed duration of antibiotic treatment for diverticulitis, complicated urinary tract infection (UTI), and endocarditis. METHODS: Medical records of patients hospitalized with the previously stated diseases in 2017 and 2018 were randomly selected at a Swiss tertiary care hospital. The appropriateness of antibiotic treatment duration was assessed according to international and local guidelines. RESULTS: A total of 243 patients were included in the study: 100 with diverticulitis, 200 with complicated UTI, and 43 with endocarditis. The dherence to local and international guidelines was 11% and 18% in diverticulitis, 39% and 40% in complicated UTI, and 84% and 86% in endocarditis, respectively. Nonadherence was primarily due to the prolonged treatment in diverticulitis and complicated UTI with a median duration of antibiotic treatment of 11 days (interquartile range 10-13) and 14 days (interquartile range 10-15), respectively. When pooling diverticulitis and complicated UTI cases, the identification of a pathogen in any microbiological sample was associated with an improved adherence to local guidelines in addition to hospitalization in a medical ward and infectious diseases consultation. CONCLUSION: Prolonged courses of antibiotic treatment were common and the treatment adherence to guidelines were poor in diverticulitis, moderate in complicated UTI, and excellent in endocarditis.

Do we need blood culture stewardship programs? A quality control study and survey to assess the appropriateness of blood culture collection and the knowledge and attitudes among physicians in Swiss hospitals.

BACKGROUND: 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. MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.

Comparing Immunoassays for SARS-CoV-2 Antibody Detection in Patients with and without Laboratory-Confirmed SARS-CoV-2 Infection.

Commercially available SARS-CoV-2-directed antibody assays may assist in diagnosing past exposure to SARS-CoV-2 antigens. We cross-compared the following eight immunoassays detecting antibodies against SARS-CoV-2 nucleocapsid (N) or spike (S) antigens in three cohorts consisting of 859 samples from 622 patients: (#1) EDI novel coronavirus COVID-19 (Epitope), (#2) RecomWell SARS-CoV-2 (Mikrogen), (#3) COVID-19 ELISA (VirCell), (#4) Elecsys anti-SARS-CoV-2 N (Roche), (#5) Liaison SARS-CoV-2 S1/S2 (DiaSorin), (#6) anti-SARS-CoV-2 ELISA (EuroImmun), (#7) Elecsys anti-SARS-CoV-2 S (Roche), and (#8) Liaison SARS-CoV-2 TrimericS (DiaSorin). In cross-sectional cohort 1 (68 sera from 38 patients with documented SARS-CoV-2 infection), agreement between assays #1 to #6 ranged from 75% to 93%, whereby discordance mostly resulted from N-based assays #1 to #4. In cross-sectional cohort 2 (510 sera from 510 patients; 56 documented, 454 unknown SARS-CoV-2 infection), assays #4 to #6 were analyzed further together with assays #7 and #8, revealing 94% concordance (44 [9%] positives and 485 [85%] negatives). Discordance was highest within 2 weeks after SARS-CoV-2/COVID-19 diagnosis and confirmed in the longitudinal cohort 3 (281 sera from 74 COVID-19 patients), using assays #4, #6, #7, and #8. Subanalysis of 20 (27%) initially seronegative cohort 3 patients revealed assay-dependent 50% and 90% seroconversion rates after 8 to 11 days and 14 to 18 days, respectively. Increasing SARS-CoV-2 antibodies were significantly associated with declining levels of viral loads, lactate dehydrogenase, interleukin-6, and C-reactive protein and preceded clearance of SARS-CoV-2 detection in the upper respiratory tract by approximately 1 week. SARS-CoV-2-specific antibody assays show substantial agreement, but interpretation of qualitative and semiquantitative results depends on the time elapsed postdiagnosis and the choice of viral antigen. Mounting of systemic SARS-CoV-2-specific antibodies may predict recovery from viral injury and clearance of mucosal replication.

Association of mannose-binding lectin, ficolin-2 and immunoglobulin concentrations with future exacerbations in patients with chronic obstructive pulmonary disease: secondary analysis of the randomized controlled REDUCE trial.

BACKGROUND: The innate and adaptive immune system is involved in the airway inflammation associated with acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). We evaluated the association of mannose-binding lectin (MBL), immunoglobulin (Ig) and ficolin-2 concentrations with COPD exacerbations and according to the glucocorticoid treatment duration for an index exacerbation. METHODS: Post-hoc analysis of the randomized, double-blind, placebo-controlled REDUCE trial of 5 vs. 14 days of glucocorticoid treatment for an index exacerbation. MBL, ficolin-2 and total IgG/IgA and subclass concentrations were determined in stored samples drawn (n = 178) 30 days after the index exacerbation and associated with the risk of re-exacerbation during a 180-day follow-up period. RESULTS: IgG and subclass concentrations were significantly lower after 14 days vs. 5 days of glucocorticoid treatment. Patients with higher MBL concentrations were more likely to suffer from a future exacerbation (multivariable hazard ratio 1.03 per 200 ng/ml increase (95% confidence interval (CI) 1.00-1.06), p = 0.048), whereas ficolin-2 and IgG deficiency were not associated. The risk was most pronounced in patients with high MBL concentrations, IgG deficiency and 14 days of glucocorticoid treatment pointing towards an interactive effect of MBL and IgG deficiency in the presence of prolonged glucocorticoid treatment duration [Relative excess risk due to interaction 2.13 (95% CI - 0.41-4.66, p = 0.10)]. IgG concentrations were significantly lower in patients with frequent re-exacerbations (IgG, 7.81 g/L vs. 9.53 g/L, p = 0.03). CONCLUSIONS: MBL modified the short-term exacerbation risk after a recent acute exacerbation of COPD, particularly in the setting of concurrent IgG deficiency and recent prolonged systemic glucocorticoid treatment. Ficolin-2 did not emerge as a predictor of a future exacerbation risk.

Probability of pharmacological target attainment with flucloxacillin in Staphylococcus aureus bloodstream infection: a prospective cohort study of unbound plasma and individual MICs.

OBJECTIVES: MSSA bloodstream infections (BSIs) are associated with considerable mortality. Data regarding therapeutic drug monitoring (TDM) and pharmacological target attainment of the ß-lactam flucloxacillin are scarce. PATIENTS AND METHODS: We determined the achievement of pharmacokinetic/pharmacodynamic targets and its association with clinical outcome and potential toxicity in a prospective cohort of 50 patients with MSSA-BSI. Strain-specific MICs and unbound plasma flucloxacillin concentrations (at five different timepoints) were determined by broth microdilution and HPLC-MS, respectively. RESULTS: In our study population, 48% were critically ill and the 30 day mortality rate was 16%. The median flucloxacillin MIC was 0.125 mg/L. The median unbound trough concentration was 1.7 (IQR 0.4-9.3), 1.9 (IQR 0.4-6.2) and 1.0 (IQR 0.6-3.4) mg/L on study day 1, 3 and 7, respectively. Optimal (100% fT>MIC) and maximum (100% fT>4×MIC) target attainment was achieved in 45 (90%) and 34 (68%) patients, respectively, throughout the study period. Conversely, when using the EUCAST epidemiological cut-off value instead of strain-specific MICs, target attainment was achieved in only 13 (26%) patients. The mean unbound flucloxacillin trough concentration per patient was associated with neurotoxicity (OR 1.12 per 1 mg/L increase, P = 0.02) and significantly higher in deceased patients (median 14.8 versus 1.7 mg/L, P = 0.01). CONCLUSIONS: Flucloxacillin pharmacological target attainment in MSSA-BSI patients is frequently achieved when unbound flucloxacillin concentrations and strain-specific MICs are considered. However, currently recommended dosing regimens may expose patients to excessive flucloxacillin concentrations, potentially resulting in drug-related organ damage.

Relevance of Dermabacter hominis isolated from clinical samples, 2012-2016: a retrospective case series.

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%.

Predictive Value of Sudden Olfactory Loss in the Diagnosis of COVID-19.

INTRODUCTION: Recent reports suggest that sudden smell loss might be a symptom of SARS-CoV-2 infection. The aim of this study was to investigate the frequency of olfactory loss in an outpatient population who presented to a coronavirus testing center during a 2-week period and to evaluate the diagnostic value of the symptom "sudden smell loss" for screening procedures. METHODS: In this cross-sectional controlled cohort study, 500 patients who presented with symptoms of a common cold to a corona testing center and fulfilled corona testing criteria completed a standardized diagnostic questionnaire which included the patients' main symptoms, time course, and an additional self-assessment of the patients' current smell, taste function, and nasal breathing compared to the level before the onset of symptoms. RESULTS: Out of the 500 patients, 69 presented with olfactory loss. Twenty-two of them subsequently tested positive for SARS-CoV-2. Only 12 out of the patients without olfactory loss tested positive, resulting in a frequency of 64.7% for the symptom "sudden smell loss" in COVID-19 patients. Compared to COVID-19 patients without smell loss, they were significantly younger and less severely affected. Changes in nasal airflow were significantly more pronounced in SARS-CoV-2 negative patients with olfactory complaints compared to the patients with smell loss who tested positive for SARS-CoV-2. By excluding patients with a blocked nose, the symptom "sudden smell loss" can be attested a high specificity (97%) and a sensitivity of 65% with a positive predictive value of 63% and negative predictive value of 97% for COVID-19. CONCLUSION: Considering the high frequency of smell loss in non-hospitalized COVID-19 patients, acute olfactory impairment should be recognized as an early symptom of the disease and should be tested for on a regular basis. In contrast to other acute viral smell impairment, COVID-19-associated smell loss seems to be only rarely accompanied by a severely blocked nose.

[Hematochezia and right-sided upper abdominal pain after puncture of a liver abscess in a 75-year-old male]. / Hämatochezie und rechtsseitiger Oberbauchschmerz nach Punktion eines Leberabszesses bei einem 75-Jährigen.

This article presents the case of a 75-year-old male patient, who underwent a percutaneous abscess puncture of a liver abscess. A few days after the puncture and drainage there was a sudden onset of right upper quadrant abdominal pain accompanied by hematochezia. The patient presented with markedly elevated liver enzyme levels and a significant drop in hemoglobin concentration. After gastroscopy and abdominal computed tomography (CT) in the portal venous phase no bleeding source could be identified. A false aneurysm of the cystic artery was identified only after a CT angiography of the abdomen. Due to spontaneous cessation of the bleeding a cholecystectomy was subsequently performed for definitive treatment of the false aneurysm.

The financial burden of an influenza outbreak in a small rehabilitation centre.

We report an influenza outbreak in a 75-bed rehabilitation centre and present the detailed microeconomic impact that it had during the season 2016/2017. The direct medical, direct non-medical and indirect costs were calculated. The outbreak included 18 patients with influenza and 8 contact patients, leading to 86 days with isolation precautions. During the outbreak month, 25 (15%) employees were absent from work for 89 days (mean 3.6 days, SD ± 1.8), and during the entire influenza season 33 for 175 (5.3 ± SD 4.6) days, respectively. The economic burden related to the outbreak was 114 373 CHF (106 890 €, 112 131 $).

Correction to: Lymphocytic choriomeningitis virus meningitis after needlestick injury: a case report.

[This corrects the article DOI: 10.1186/s13756-019-0524-4.].

Lymphocytic choriomeningitis virus meningitis after needlestick injury: a case report.

Background: 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. Case presentation: 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. Conclusions: 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.