Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19.

Rationale: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome with fatal outcomes. Evidence suggests that dysregulated immune responses, including autoimmunity, are key pathogenic factors. Objectives: To assess whether IgA autoantibodies target lung-specific proteins and contribute to disease severity. Methods: We collected 147 blood, 9 lung tissue, and 36 BAL fluid samples from three tertiary hospitals in Switzerland and one in Germany. Severe COVID-19 was defined by the need to administer oxygen. We investigated the presence of IgA autoantibodies and their effects on pulmonary surfactant in COVID-19 using the following methods: immunofluorescence on tissue samples, immunoprecipitations followed by mass spectrometry on BAL fluid samples, enzyme-linked immunosorbent assays on blood samples, and surface tension measurements with medical surfactant. Measurements and Main Results: IgA autoantibodies targeting pulmonary surfactant proteins B and C were elevated in patients with severe COVID-19 but not in patients with influenza or bacterial pneumonia. Notably, pulmonary surfactant failed to reduce surface tension after incubation with either plasma or purified IgA from patients with severe COVID-19. Conclusions: Our data suggest that patients with severe COVID-19 harbor IgA autoantibodies against pulmonary surfactant proteins B and C and that these autoantibodies block the function of lung surfactant, potentially contributing to alveolar collapse and poor oxygenation.

Autoreactive T cells targeting type II pneumocyte antigens in COVID-19 convalescent patients.

BACKGROUND: The role of autoreactive T cells on the course of Coronavirus disease-19 (COVID-19) remains elusive. Type II pneumocytes represent the main target cells of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Autoimmune responses against antigens highly expressed in type II pneumocytes may influence the severity of COVID-19 disease. OBJECTIVE: The aim of this study was to investigate autoreactive T cell responses against self-antigens highly expressed in type II pneumocytes in the blood of COVID-19 patients with severe and non-severe disease. METHODS: We collected blood samples of COVID-19 patients with varying degrees of disease severity and of pre-pandemic controls. T cell stimulation assays with peptide pools of type II pneumocyte antigens were performed in two independent cohorts to analyze the autoimmune T cell responses in patients with non-severe and severe COVID-19 disease. Target cell lysis assays were performed with lung cancer cell lines to determine the extent of cell killing by type II PAA-specific T cells. RESULTS: We identified autoreactive T cell responses against four recently described self-antigens highly expressed in type II pneumocytes, known as surfactant protein A, surfactant protein B, surfactant protein C and napsin A, in the blood of COVID-19 patients. These antigens were termed type II pneumocyte-associated antigens (type II PAAs). We found that patients with non-severe COVID-19 disease showed a significantly higher frequency of type II PAA-specific autoreactive T cells in the blood when compared to severely ill patients. The presence of high frequencies of type II PAA-specific T cells in the blood of non-severe COVID-19 patients was independent of their age. We also found that napsin A-specific T cells from convalescent COVID-19 patients could kill lung cancer cells, demonstrating the functional and cytotoxic role of these T cells. CONCLUSIONS: Our data suggest that autoreactive type II PAA-specific T cells have a protective role in SARS-CoV-2 infections and the presence of high frequencies of these autoreactive T cells indicates effective viral control in COVID-19 patients. Type II-PAA-specific T cells may therefore promote the killing of infected type II pneumocytes and viral clearance.

Pediatric hospital admissions, case severity, and length of hospital stay during the first 18 months of the COVID-19 pandemic in a tertiary children's hospital in Switzerland.

BACKGROUND: SARS-CoV-2 directly contributes to the burden of respiratory disease in children, but indirect effects of protective measures also need to be considered to assess the overall impact of the pandemic on children's health. METHODS: We retrospectively compared pre-pandemic and pandemic data of main admission diagnoses, sorted by ICD-10 diagnosis groups, in a tertiary children's hospital in Switzerland from 2017 until August 2021. Hospital admission rates, severity, and length of stay (LOS) of the individual ICD-10 groups during the pandemic were compared with three previous years accounting for seasonal differences. RESULTS: Among 20,168 hospital admissions (n = 13'950 in pre-pandemic years; n = 3'120 in 2020 and n = 3'098 in 2021), there were significant decreases in numbers of admissions for respiratory diseases during the early pandemic with a rebound in summer 2021. During the pandemic, admissions for non-respiratory infections, neoplasms, and skin diseases decreased but increased for trauma. Particularly, a drop in admissions for different respiratory infections [e.g. respiratory syncytial virus (RSV) and bronchiolitis] was pronounced after introduction of strict measures, but admissions increased again after restrictions were loosened. While disease severity was lower for respiratory and neurologic diseases and bronchiolitis throughout the pandemic, gastrointestinal disease admissions had longer LOS and in the first pandemic year greater severity. For RSV and pneumonia, disease severity and LOS were higher in the first pandemic year and lower in the second pandemic year. CONCLUSION: The pandemic and associated protective measures had a significant effect on respiratory and non-respiratory admissions, particularly with decreases in hospital admissions for respiratory infections followed by a rebound after loosening of measures.

Validation of sTREM-1 and IL-6 based algorithms for outcome prediction of COVID-19.

BACKGROUND: A prospective observational cohort study of COVID-19 patients in a single Emergency Department (ED) showed that sTREM-1- and IL-6-based algorithms were highly predictive of adverse outcome (Van Singer et al. J Allergy Clin Immunol 2021). We aim to validate the performance of these algorithms at ED presentation. METHODS: This multicentric prospective observational study of PCR-confirmed COVID-19 adult patients was conducted in the ED of three Swiss hospitals. Data of the three centers were retrospectively completed and merged. We determined the predictive accuracy of the sTREM-1-based algorithm for 30-day intubation/mortality. We also determined the performance of the IL-6-based algorithm using data from one center for 30-day oxygen requirement. RESULTS: 373 patients were included in the validation cohort, 139 (37%) in Lausanne, 93 (25%) in St.Gallen and 141 (38%) in EOC. Overall, 18% (93/373) patients died or were intubated by day 30. In Lausanne, 66% (92/139) patients required oxygen by day 30. The predictive accuracy of sTREM-1 and IL-6 were similar compared to the derivation cohort. The sTREM-1-based algorithm confirmed excellent sensitivity (90% versus 100% in the derivation cohort) and negative predictive value (94% versus 100%) for 30-day intubation/mortality. The IL-6-based algorithm performance was acceptable with a sensitivity of 85% versus 98% in the derivation cohort and a negative predictive value of 60% versus 92%. CONCLUSION: The sTREM-1 algorithm demonstrated good reproducibility. A prospective randomized controlled trial, comparing outcomes with and without the algorithm, is necessary to assess its safety and impact on hospital and ICU admission rates. The IL-6 algorithm showed acceptable validity in a single center and need additional validation before widespread implementation.

Remdesivir in Coronavirus Disease 2019 patients treated with anti-CD20 monoclonal antibodies: a case series.

PURPOSE: COVID-19 patients on anti-CD20 treatment can suffer a delayed viral clearance and worse clinical outcome. We aim to present our experience with remdesivir treatment in anti-CD20-treated patients with prolonged symptoms, a patient population for which no data from randomized controlled trials are available. METHODS: From the beginning of the pandemic until February 2021, we included all consecutive patients from our healthcare network on anti-CD20 treatment with prolonged COVID-19 symptoms, who received remdesivir. Patient informed consent was gathered and patients' charts were reviewed to collect baseline data, COVID-19 history including time of symptom onset, diagnosis, data on treatment and disease course. Patients or their next of kin were contacted in March 2022 to assess long-term outcomes. RESULTS: We included 11 patients, who received remdesivir at a median of 33 days after diagnosis. Eight patients showed clinical improvement along with reductions in viral loads, one patient with relapsing infection recovered after administration of convalescent plasma, and two patients died. No clinical relapses were reported (median follow-up 13 months), while follow-up PCRs were not performed. One patient died of underlying malignancy 8 months after recovery from COVID-19. CONCLUSIONS: We observed a benefit of antiviral therapy in a majority of COVID-19 patients on anti-CD20 treatment, without any clinical relapses in the 1-year follow-up. Although these data suggest that remdesivir might be a promising management option in patients with delayed viral clearance, the lack of a control group is an important limitation of the study design. TRIAL REGISTRATION: Ethikkommission Ostschweiz, Scheibenackerstrasse 4, CH-9000 St. Gallen approved this case series. Project-ID 2021-00349 EKOS 21/027.

No evidence of harmful effects of steroids in severe exacerbations of COPD associated with influenza.

PURPOSE: COPD has large impact on patient morbidity and mortality worldwide. Acute exacerbations (AECOPD) are mostly triggered by respiratory infections including influenza. While corticosteroids are strongly recommended in AECOPD, they are potentially harmful during influenza. We aimed to evaluate if steroid treatment for AECOPD due to influenza may worsen outcomes. METHODS: A retrospective analysis of a Swiss nation-wide hospitalization database was conducted identifying all AECOPD hospitalisations between 2012 and 2017. In separate analyses, outcomes concerning length-of-stay (LOS), in-hospital mortality, rehospitalisation rate, empyema and aspergillosis were compared between AECOPD during and outside influenza season; AECOPD with and without laboratory-confirmed influenza; and AECOPD plus pneumonia with and without laboratory-confirmed influenza. RESULTS: Patients hospitalized for AECOPD during influenza season showed shorter LOS (11.3 vs. 11.6 day, p < 0.001) but higher rehospitalisation rates (33 vs 31%, p < 0.001) compared to those hospitalized outside influenza season. Patients with confirmed influenza infection had lower in-hospital mortality (3.3 vs. 5.5%, p = 0.010) and rehospitalisation rates (29 vs. 37%, p < 0.001) than those without confirmed influenza. CONCLUSION: Using different indicators for influenza as the likely cause of AECOPD, we found no consistent evidence of worse outcomes of AECOPD due to influenza for hospitalized patients. Assuming that most of these patients received corticosteroids, as it is accepted standard of care in Switzerland, this study gives no evidence to change the current practice of using corticosteroids for hospitalized AECOPD independent of the influenza status.

Severe Coronavirus Disease 2019 (COVID-19) is Associated With Elevated Serum Immunoglobulin (Ig) A and Antiphospholipid IgA Antibodies.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) frequently entails complications that bear similarities to autoimmune diseases. To date, there are little data on possible immunoglobulin (Ig) A-mediated autoimmune responses. Here, we aim to determine whether COVID-19 is associated with a vigorous total IgA response and whether IgA antibodies are associated with complications of severe illness. Since thrombotic events are frequent in severe COVID-19 and resemble hypercoagulation of antiphospholipid syndrome, our approach focused on antiphospholipid antibodies (aPL). METHODS: In this retrospective cohort study, clinical data and aPL from 64 patients with COVID-19 were compared from 3 independent tertiary hospitals (1 in Liechtenstein, 2 in Switzerland). Samples were collected from 9 April to 1 May 2020. RESULTS: Clinical records of 64 patients with COVID-19 were reviewed and divided into a cohort with mild illness (mCOVID; 41%), a discovery cohort with severe illness (sdCOVID; 22%) and a confirmation cohort with severe illness (scCOVID; 38%). Total IgA, IgG, and aPL were measured with clinical diagnostic kits. Severe illness was significantly associated with increased total IgA (sdCOVID, P = .01; scCOVID, P < .001), but not total IgG. Among aPL, both cohorts with severe illness significantly correlated with elevated anticardiolipin IgA (sdCOVID and scCOVID, P < .001), anticardiolipin IgM (sdCOVID, P = .003; scCOVID, P< .001), and anti-beta 2 glycoprotein-1 IgA (sdCOVID and scCOVID, P< .001). Systemic lupus erythematosus was excluded from all patients as a potential confounder. CONCLUSIONS: Higher total IgA and IgA-aPL were consistently associated with severe illness. These novel data strongly suggest that a vigorous antiviral IgA response, possibly triggered in the bronchial mucosa, induces systemic autoimmunity.

Characteristics of patients with Coronavirus Disease 2019 (COVID-19) and seasonal influenza at time of hospital admission: a single center comparative study.

BACKGROUND: In the future, co-circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses A/B is likely. From a clinical point of view, differentiation of the two disease entities is crucial for patient management. We therefore aim to detect clinical differences between Coronavirus Disease 2019 (COVID-19) and seasonal influenza patients at time of hospital admission. METHODS: In this single-center observational study, we included all consecutive patients hospitalized for COVID-19 or influenza between November 2019 and May 2020. Data were extracted from a nationwide surveillance program and from electronic health records. COVID-19 and influenza patients were compared in terms of baseline characteristics, clinical presentation and outcome. We used recursive partitioning to generate a classification tree to discriminate COVID-19 from influenza patients. RESULTS: We included 96 COVID-19 and 96 influenza patients. Median age was 68 vs. 70 years (p = 0.90), 72% vs. 56% (p = 0.024) were males, and median Charlson Comorbidity Index (CCI) was 1 vs. 2 (p = 0.027) in COVID-19 and influenza patients, respectively. Time from symptom onset to hospital admission was longer for COVID-19 (median 7 days, IQR 3-10) than for influenza patients (median 3 days, IQR 2-5, p < 0.001). Other variables favoring a diagnosis of COVID-19 in the classification tree were higher systolic blood pressure, lack of productive sputum, and lack of headache. The tree classified 86/192 patients (45%) into two subsets with ≥80% of patients having influenza or COVID-19, respectively. In-hospital mortality was higher for COVID-19 patients (16% vs. 5%, p = 0.018). CONCLUSION: Discriminating COVID-19 from influenza patients based on clinical presentation is challenging. Time from symptom onset to hospital admission is considerably longer in COVID-19 than in influenza patients and showed the strongest discriminatory power in our classification tree. Although they had fewer comorbidities, in-hospital mortality was higher for COVID-19 patients.

Antimicrobial resistance and antibiotic consumption in intensive care units, Switzerland, 2009 to 2018.

BackgroundIntensive care units (ICU) constitute a high-risk setting for antimicrobial resistance (AMR).AimWe aimed to describe secular AMR trends including meticillin-resistant Staphylococcus aureus (MRSA), glycopeptide-resistant enterococci (GRE), extended-spectrum cephalosporin-resistant Escherichia coli (ESCR-EC) and Klebsiella pneumoniae (ESCR-KP), carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA) from Swiss ICU. We assessed time trends of antibiotic consumption and identified factors associated with CRE and CRPA.MethodsWe analysed patient isolate and antibiotic consumption data of Swiss ICU sent to the Swiss Centre for Antibiotic Resistance (2009-2018). Time trends were assessed using linear logistic regression; a mixed-effects logistic regression was used to identify factors associated with CRE and CRPA.ResultsAmong 52 ICU, MRSA decreased from 14% to 6% (p = 0.005; n = 6,465); GRE increased from 1% to 3% (p = 0.011; n = 4,776). ESCR-EC and ESCR-KP increased from 7% to 15% (p < 0.001, n = 10,648) and 5% to 11% (p = 0.002; n = 4,052), respectively. CRE, mostly Enterobacter spp., increased from 1% to 5% (p = 0.008; n = 17,987); CRPA remained stable at 27% (p = 0.759; n = 4,185). Antibiotic consumption in 58 ICU increased from 2009 to 2013 (82.5 to 97.4 defined daily doses (DDD)/100 bed-days) and declined until 2018 (78.3 DDD/100 bed-days). Total institutional antibiotic consumption was associated with detection of CRE in multivariable analysis (odds ratio per DDD: 1.01; 95% confidence interval: 1.0-1.02; p = 0.004).DiscussionIn Swiss ICU, antibiotic-resistant Enterobacterales have been steadily increasing over the last decade. The emergence of CRE, associated with institutional antibiotic consumption, is of particular concern and calls for reinforced surveillance and antibiotic stewardship in this setting.

In vitro virucidal activity of Echinaforce®, an Echinacea purpurea preparation, against coronaviruses, including common cold coronavirus 229E and SARS-CoV-2.

BACKGROUND: Coronaviruses (CoVs) were long thought to only cause mild respiratory and gastrointestinal symptoms in humans but outbreaks of Middle East Respiratory Syndrome (MERS)-CoV, Severe Acute Respiratory Syndrome (SARS)-CoV-1, and the recently identified SARS-CoV-2 have cemented their zoonotic potential and their capacity to cause serious morbidity and mortality, with case fatality rates ranging from 4 to 35%. Currently, no specific prophylaxis or treatment is available for CoV infections. Therefore we investigated the virucidal and antiviral potential of Echinacea purpurea (Echinaforce®) against human coronavirus (HCoV) 229E, highly pathogenic MERS- and SARS-CoVs, as well as the newly identified SARS-CoV-2, in vitro. METHODS: To evaluate the antiviral potential of the extract, we pre-treated virus particles and cells and evaluated remaining infectivity by limited dilution. Furthermore, we exposed cells to the extract after infection to further evaluate its potential as a prophylaxis and treatment against coronaviruses. We also determined the protective effect of Echinaforce® in re-constituted nasal epithelium. RESULTS: In the current study, we found that HCoV-229E was irreversibly inactivated when exposed to Echinaforce® at 3.2 µg/ml IC50. Pre-treatment of cell lines, however, did not inhibit infection with HCoV-229E and post-infection treatment had only a marginal effect on virus propagation at 50 µg/ml. However, we did observe a protective effect in an organotypic respiratory cell culture system by exposing pre-treated respiratory epithelium to droplets of HCoV-229E, imitating a natural infection. The observed virucidal activity of Echinaforce® was not restricted to common cold coronaviruses, as both SARS-CoV-1 and MERS-CoVs were inactivated at comparable concentrations. Finally, the causative agent of COVID-19, SARS-CoV-2 was also inactivated upon treatment with 50µg/ml Echinaforce®. CONCLUSIONS: These results show that Echinaforce® is virucidal against HCoV-229E, upon direct contact and in an organotypic cell culture model. Furthermore, MERS-CoV and both SARS-CoV-1 and SARS-CoV-2 were inactivated at similar concentrations of the extract. Therefore we hypothesize that Echinacea purpurea preparations, such as Echinaforce®, could be effective as prophylactic treatment for all CoVs due to their structural similarities.

Author Correction: In vitro virucidal activity of Echinaforce®, an Echinacea purpurea preparation, against coronaviruses, including common cold coronavirus 229E and SARS-CoV-2.

The original version of the acknowledgement unfortunately contained a mistake.

Species specificity preliminary evaluation of an IL-4-based test for the differential diagnosis of human echinococcosis.

The diagnosis of cystic echinococcosis (CE) is based on imaging, while serology is a complementary test of particular use when imaging is inconclusive. Serology has several limitations. Among them, false-positive results are often obtained in subjects with alveolar echinococcosis (AE), rendering difficult the differential diagnosis. We set up an immune assay based on IL-4-specific production after stimulating whole blood with an antigen B (AgB)-enriched fraction from E granulosus that associates with CE and CE cysts in active stage. We aimed to evaluate potential cross-reactivity of this test using samples from patients with AE. Twelve patients with AE were recruited; IL-4 levels ranged from 0 to 0.07 pg/mL. Based on the previously identified cut-off of 0.39 pg/mL using samples from patients with CE, none of samples from AE patients scored positive. In contrast, almost 80% of samples from AE patients scored positive in serology tests based on different E granulosus-derived antigenic preparations. Our preliminary data show that this experimental whole-blood assay has no cross-reactivity in our cohort of patients with AE, in turn indicating a high specificity of the assay for CE diagnosis. This result supports further work towards the development of improved diagnostic tests for CE.

Influenza-associated aspergillosis in critically-ill patients-a retrospective bicentric cohort study.

Influenza was recently reported as a risk factor for invasive aspergillosis (IA). We aimed to describe prognostic factors for influenza-associated IA (IAA) and poor outcome and mortality in critically ill patients in Switzerland. All adults with confirmed influenza admitted to the ICU at two Swiss tertiary care centres during the 2017/2018 influenza season were retrospectively evaluated. IAA was defined by clinical, mycological and radiological criteria: a positive galactomannan in bronchoalveolar lavage or histopathological or cultural evidence in respiratory specimens of Aspergillus spp., any radiological infiltrate and a compatible clinical presentation. Poor outcome was defined as a composite of in-hospital mortality, ICU length of stay (LOS), invasive ventilation for > 7 days or extracorporeal membrane oxygenation. Of 81 patients with influenza in the ICU, 9 (11%) were diagnosed with IAA. All patients with IAA had poor outcome compared to 26 (36%) patients without IAA (p < 0.001). Median ICU-LOS and mortality were 17 vs. 3 days (p < 0.01) and 3/9 (33%) vs. 13/72 (18%; p = 0.37) in patients with vs. without IAA, respectively. Patients with IAA had significantly longer durations of antibiotic therapy, vasoactive support and mechanical ventilation. Aspergillus was the most common respiratory co-pathogen (9/40, 22%) followed by classical bacterial co-pathogens. IAA was not associated with classical risk factors. Aspergillus is a common superinfection in critically ill influenza patients associated with poor outcome and longer duration of organ supportive therapies. Given the absence of classical risk factors for aspergillosis, greater awareness is necessary, particularly in those requiring organ supportive therapies.

Effect of C-Reactive Protein-Guided Antibiotic Treatment Duration, 7-Day Treatment, or 14-Day Treatment on 30-Day Clinical Failure Rate in Patients With Uncomplicated Gram-Negative Bacteremia: A Randomized Clinical Trial.

Importance: Antibiotic overuse drives antibiotic resistance. Gram-negative bacteremia is a common infection that results in substantial antibiotic use. Objective: To compare the clinical effectiveness of C-reactive protein (CRP)-guided, 7-day, and 14-day antibiotic durations 30, 60, and 90 days after treatment initiation. Design, Setting, and Participants: Multicenter, noninferiority, point-of-care randomized clinical trial including adults hospitalized with gram-negative bacteremia conducted in 3 Swiss tertiary care hospitals between April 2017 and May 2019, with follow-up until August 2019. Patients and physicians were blinded between randomization and antibiotic discontinuation. Adults (aged ≥18 years) were eligible for randomization on day 5 (±1 d) of microbiologically efficacious therapy for fermenting, gram-negative bacteria in blood culture(s) if they were afebrile for 24 hours without evidence for complicated infection (eg, abscess) or severe immunosuppression. Intervention: Randomization in a 1:1:1 ratio to an individualized CRP-guided antibiotic treatment duration (discontinuation once CRP declined by 75% from peak; n = 170), fixed 7-day treatment duration (n = 169), or fixed 14-day treatment duration (n = 165). Main Outcomes and Measures: The primary outcome was the clinical failure rate at day 30, defined as the presence of at least 1 of the following, with a non-inferiority margin of 10%: recurrent bacteremia, local suppurative complication, distant complication (growth of the same organism causing the initial bacteremia), restarting gram-negative-directed antibiotic therapy due to clinical worsening suspected to be due to the initial organism, or death due to any cause. Secondary outcomes included the clinical failure rate on day 90 of follow-up. Results: Among 504 patients randomized (median [interquartile range] age, 79 [68-86] years; 306 of 503 [61%] were women), 493 (98%) completed 30-day follow-up and 448 (89%) completed 90-day follow-up. Median antibiotic duration in the CRP group was 7 (interquartile range, 6-10; range, 5-28) days; 34 of the 164 patients (21%) who completed the 30-day follow-up had protocol violations related to treatment assignment. The primary outcome occurred in 4 of 164 (2.4%) patients in the CRP group, 11 of 166 (6.6%) in the 7-day group, and 9 of 163 (5.5%) in the 14-day group (difference in CRP vs 14-day group, -3.1% [1-sided 97.5% CI, -∞ to 1.1]; P < .001; difference in 7-day vs 14-day group, 1.1% [1-sided 97.5% CI, -∞ to 6.3]; P < .001). By day 90, clinical failure occurred in 10 of 143 patients (7.0%) in the CRP group, 16 of 151 (10.6%) in the 7-day group, and 16 of 153 (10.5%) in the 14-day group. Conclusions and Relevance: Among adults with uncomplicated gram-negative bacteremia, 30-day rates of clinical failure for CRP-guided antibiotic treatment duration and fixed 7-day treatment were noninferior to fixed 14-day treatment. However, interpretation is limited by the large noninferiority margin compared with the low observed event rate, as well as low adherence and wide range of treatment durations in the CRP-guided group. Trial Registration: ClinicalTrials.gov Identifier: NCT03101072.

Influence of biofilms on morbidity associated with short-term indwelling ureteral stents: a prospective observational study.

PURPOSE: To evaluate the influence of biofilms on morbidity associated with short-term ureteral stenting using contemporary methods of biofilm examination and validated assessment of symptoms. METHODS: Patients undergoing temporary ureteral stenting for secondary ureterorenoscopy due to urinary calculi were prospectively included. The German Ureteral Stent Symptoms Questionnaire (USSQ) was used to assess stent-associated morbidity. Biofilms were removed from stents using 'pinhole extraction', a novel, validated, abrasion-based technique. Extracted biofilms were analyzed for total mass, bacterial load and mineral components. Correlation between total biofilm mass and USSQ total score was the primary outcome variable analyzed using Spearman correlation. Secondary outcomes included correlations between various biofilm characteristics and symptoms. RESULTS: 94 patients were included in the analysis. Extracted biofilm mass had a median of 37.0 mg (0-310.2 mg) per stent. No correlation between total biofilm mass and USSQ total score was found (Spearman r = 0.012; p = 0.911). Correlations between biofilm characteristics and morbidity were generally weak and not significant. Significant correlations could be found between biofilm mass and hematuria (r = 0.280; p = 0.007), and between the number of bacteria (qPCR) and the USSQ subscore for pain (r = 0.243; p = 0.019) and the intake of analgesics (r = 0.259; p = 0.012). CONCLUSION: Based on elaborated biofilm examination methods and validated self-reported outcome measures, our findings indicate that biofilms might aggravate some lower urinary tract symptoms but are not the main trigger for stent-associated morbidity in short-term ureteral stenting.

Septic arthritis due to streptococci and enterococci in native joints: a 13 year retrospective study.

OBJECTIVES: Streptococcal species are the second most common cause of native joint septic arthritis (SA). However, there are few systematic data about streptococcal SA. METHODS: The medical records of adults with SA caused by streptococci, pneumococci, and enterococci at our tertiary care centre between 2003 and 2015 were reviewed. RESULTS: 71 patients (34% female) with 83 affected joints were included. Median age was 62 years. A single joint was involved in 62 patients (87%). One or more comorbidities were present in 58 patients (82%). 16 patients (23%) had a concomitant soft-tissue infection overlying the affected joint. The hematogenous route was the dominating pathogenesis (42/71, 59%). 9 (13%) patients were diagnosed with endocarditis. The knee was the most commonly affected joint (27/83, 33%) followed by shoulder (13/83, 16%). ß-haemolytic streptococci were most commonly identified (37/71, 52%) followed by polymicrobial infections (12/71, 17%). Surgical interventions included arthroscopic irrigation and debridement in 31 (44%), arthrotomy in 23 (32%), and amputation in five patients (7%). Median duration of antimicrobial therapy was 42 days. Antibiotic treatment without any surgical intervention was performed in 5 (7%) patients. Outcome was good in 55 (89%) patients; mortality was 13% with four of nine deaths attributed to joint infection. Age and pathogen group independently predicted poor outcome in recursive partitioning analysis. CONCLUSIONS: Streptococcal SA was mostly due to ß-haemolytic streptococci in older and polymorbid patients. Old age, anginosus group streptococci, enterococci, and polymicrobial infections predicted poor outcome, while antibiotic treatment duration can likely be shortened.

Detection of microbial colonization of the urinary tract of patients prior to secondary ureterorenoscopy is highly variable between different types of assessment: results of a prospective observational study.

This study compares the findings of different detection methods for microorganisms in patients with ureteral stents undergoing secondary ureterorenoscopy including the use of a novel validated examination pipeline for biofilms on ureteral stents. Of the included 94 patients, 21.3% showed bacteriuria in preoperative urine cultures. Intraoperative urine culture showed bacteriuria in four (4.3%) of the patients. Stent biofilm cultures were positive in 12.9% and qPCR detected bacterial DNA in 18.1%. The findings of the different examinations were poorly correlated with each other. Detection of microorganisms in the urinary tract of patients with indwelling ureteral stents is highly dependent on timing (i.e. pre- vs intraoperative) and method of assessment. Preoperative routine urine cultures are not predictive for intraoperative urine- and stent culture. These results cast doubt on the clinical relevance of enterococcal species, staphylococci, and streptococci if identified preoperatively prior to stent removal. The timing of oral preoperative antibiotic prophylaxis might need to be reconsidered.

Multiplex Urinary Antigen Detection for 13 Streptococcus pneumoniae Serotypes Improves Diagnosis of Pneumococcal Pneumonia in South African HIV-Infected Adults.

A serotype-specific urinary antigen detection (UAD) assay for 13 serotypes included in the pneumococcal conjugate vaccine (PCV13) was recently reported as a useful diagnostic tool for pneumococcal pneumonia. We aimed to assess the diagnostic accuracy of the UAD in HIV-infected South African adults. Urine specimens from a well-defined cohort of HIV-infected South African adults with pneumonia were evaluated retrospectively in the UAD assay. Pneumonia was considered pneumococcal if either sputum Gram stain, sputum culture, blood culture, or the immunochromatographic (ICT) BinaxNow S. pneumoniae test (composite diagnostic) was positive. Among 235 enrolled pneumonia patients, the UAD assay was more frequently positive (104 [44.3%]) than the composite diagnostic (71 [30.2%]; P < 0.001) and increased the pneumococcal etiology from 30.2% by an additional 22.6% to 52.8%. The UAD assay detected more pneumococcal etiologies (45.0%) than the serotype-independent ICT (23.4%, P < 0.001). UAD identified 6/7 patients with PCV13 serotype bacteremia without misclassification of bacteremia episodes due to non-PCV13 serotypes. UAD was positive for 5.1% of asymptomatic HIV-infected persons, with higher rates among those with nasopharyngeal carriage. Concordance between serotypes identified by UAD and by Quellung reaction and PCR serotyping was 70/86 (81.4%). UAD identified the dominant serotype in multiple serotype carriage. This study confirms the utility of the UAD assay for HIV-infected adults comparing favorably with other diagnostic tests. A highly valent UAD may become a new standard for detection of pneumococcal pneumonia in adults. Prior to PCV introduction, at least 53% of pneumonia cases were due to pneumococci in HIV-infected South African adults.