Results of a monocentric field study: value of histology compared to sonication method and conventional tissue culture in the diagnosis of periprosthetic joint infection (PJI).

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.

Peripartal anti-SARS-CoV-2-IgA/IgG in asymptomatic pregnant women during regional SARS-CoV-2-outbreak.

OBJECTIVES: The Severe Acute Respiratory Distress Corona Virus 2 (SARS-CoV-2) pandemic poses special challenges for the society and especially the medical staff. Even if a rather mild course is assumed among pregnant women the measures to prevent transmission of the infection are of outstanding importance. METHODS: To screen asymptomatic pregnant women during admission to our university maternal hospital we focused on anti-SARS-CoV-2-specific IgG and IgA antibody responses. Hundred and fifty one women admitted to the hospital for childbirth or caesarean delivery were included. In case of suspicious anti-SARS-CoV-2-antibody levels an RT-PCR was performed to confirm an ongoing infection with SARS-CoV-2. RESULTS: A total of 89% showed negative results for anti-SARS-CoV-2-IgA antibodies, whereas 3% were borderline and 7% positive (both labeled as suspicious). In only one patient with suspicious serology we detected SARS-CoV-2-RNA in the following RT-PCR. 2% presented anti-SARS-CoV-2-IgG antibodies, all being positive for anti-SARS-CoV-2-IgA. The observed positive rate of our study collective of 10.6% seemed much higher than the expected one (1.3%) based on the reports of the Robert Koch Institute and the specifications given by the test's manufacturer. The expected positive predictive value (PPV) was 4.3-6.7 times higher than the observed one. CONCLUSIONS: To our knowledge this is the first report of anti-SARS-CoV-2-antibody levels in the peripartum period of asymptomatic women. As the positive anti-SARS-CoV-2 serology poorly correlated with the confirmatory RT-PCR and the fact that mainly the detection of the virus by PCR correlates with the patient's infectiousness we suggest to rather perform a SARS-CoV-2-PCR-based admission screening in perinatal centers to prevent the spread of the disease.

SARS-CoV-2 in pregnancy and possible transfer of immunity: assessment of peripartal maternal and neonatal antibody levels and a longitudinal follow-up.

OBJECTIVES: In the current Severe Acute Respiratory Distress Coronavirus 2 (SARS-CoV-2) pandemic there is still great uncertainty about the effects of an infection in pregnancy especially regarding a possible fetal transmission of antibodies to SARS-CoV-2 and the longevity of this immunity. METHODS: Sixteen women who were infected with SARS-CoV-2 during pregnancy and their offspring were included. The antibody response to SARS-CoV-2 was measured in mother and umbilical cord blood peripartum and in a follow-up examination 6-11 weeks after birth. Medical history, symptoms regarding SARS-CoV-2, obstetric and neonatal information were queried following recommendations by the WHO. RESULTS: A total of 73% of the women and one third of the infants developed antibodies to SARS-CoV-2 spike (S) protein receptor binding domain (RBD), with a long interval between infection and birth proving favorable for a transplacentar transfer of antibodies to the neonates. All infants showed declining or vanishing antibody-titers in the follow-up examination, while the titers of their mothers were stable or even increased. CONCLUSIONS: Our results demonstrate that transplacental transfer of SARS-CoV-2-specific antibodies is possible, but also indicate that the immunity that may be gained as a result might decrease in newborns postpartum. This provides important evidence that could be useful for further studies covering vaccination during pregnancy.

SARS-CoV-2 antibody testing-questions to be asked.

Severe acute respiratory syndrome coronavirus 2 infection and development of coronavirus disease 2019 presents a major health care challenge of global dimensions. Laboratory diagnostics of infected patients, and the assessment of immunity against severe acute respiratory syndrome coronavirus 2, presents a major cornerstone in handling the pandemic. Currently, there is an increase in demand for antibody testing and a large number of tests are already marketed or are in the late stage of development. However, the interpretation of test results depends on many variables and factors, including sensitivity, specificity, potential cross-reactivity and cross-protectivity, the diagnostic value of antibodies of different isotypes, and the use of antibody testing in identification of acutely ill patients or in epidemiological settings. In this article, the recently established COVID-19 Task Force of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL) addresses these issues on the basis of currently available data sets in this rapidly moving field.

Successful containment of Covid-19 outbreak in a large maternity and perinatal center while continuing clinical service.

With increasing number of SARS-CoV-2 infections and COVID-19 patients to be taken care of by the health system, more and more health workers become affected by the disease. It has been reported that right from the beginning of the outbreak in Lombardy up to 20% of the doctors and nurses became infected. Under these circumstances, the regular operation of health institutions already suffering from a shortage of staff becomes difficult. This has led to complete or partial shutdowns of hospitals, either due to a lack of uninfected personnel or because of uncontrollable chains of infection endangering patients. In one of the largest university perinatal center in Bavaria with more than 3000 births per year, an outbreak of COVID-19 occurred in March 2020, affecting 36 staff members, including doctors, nurses, and midwives. Here, we describe the outbreak and present the measures contributing to the successful containment of the outbreak within three weeks. At the same time, clinical services could be maintained, however, not without deployment of personnel exposed to employees infected with SARS-CoV-2. Apart from massive testing of personnel in pre-defined phases and increased hygiene measures, including a general obligation to wear surgical face masks, we identified the need to monitor cases of illness across all groups of employees, to ensure social distancing within personnel and to evaluate contacts of clinical personnel outside of the hospital environment, in order to be able to interpret chains of infections and to disrupt them. Overall, only a bundle of measures is needed to contain such an outbreak.

Symptoms and immunoglobulin development in hospital staff exposed to a SARS-CoV-2 outbreak.

BACKGROUND: Worldwide, the number of SARS-CoV-2 infections is increasing. Serological immunoglobulin tests may help to better understand the development of immune mechanisms against SARS-CoV-2 in COVID-19 cases and exposed but asymptomatic individuals. The aim of this study was to investigate exposure to SARS-CoV-2, symptoms, and antibody responses in a large sample of healthcare workers following a COVID-19 outbreak. METHODS: A COVID-19 outbreak among staff members of a major German children's and women's hospital was followed by massive RT-PCR SARS-CoV-2 tests and provided the opportunity to study symptoms, chains of infection, and SARS-CoV-2-specific antibody responses (IgG and IgA) by ELISA. Study participants were classified as COVID-19 cases, and persons with close, moderate, or no exposure to SARS-CoV-2 in the clinical setting, respectively. RESULTS: Out of 201 study participants, 31 were COVID-19 cases. While most study participants experienced many symptoms indicative for SARS-CoV-2 infection, anosmia and coughing were remarkably more frequent in COVID-19 cases. Approximately 80% of COVID-19 cases developed some specific antibody response (IgA and IgG) approximately 3 weeks after onset of symptoms. Subjects in the non-COVID-19 groups had also elevated IgG (1.8%) and IgA values (7.6%) irrespective of contact history with cases. CONCLUSION: We found that a significant number of diseased did not develop relevant antibody responses three weeks after symptom onset. Our data also suggest that exposure to COVID-19 positive co-workers in a hospital setting is not leading to the development of measurable immune responses in a significant proportion of asymptomatic contact persons.

An epidemic CC1-MRSA-IV clone yields false-negative test results in molecular MRSA identification assays: a note of caution, Austria, Germany, Ireland, 2020.

We investigated why a clinical meticillin-resistant Staphylococcus aureus (MRSA) isolate yielded false-negative results with some commercial PCR tests for MRSA detection. We found that an epidemic European CC1-MRSA-IV clone generally exhibits this behaviour. The failure of the assays was attributable to a large insertion in the orfX/SCCmec integration site. To ensure the reliability of molecular MRSA tests, it is vital to monitor emergence of new SCCmec types and junction sites.

Clinimetric properties and suitability of selected quality indicators for assessing antibiotic use in hospitalized adults: a multicentre point prevalence study in 24 hospitals in Germany.

OBJECTIVES: The capability to measure and monitor the quality of antibiotic prescribing is an important component of antibiotic stewardship (ABS) programmes. Several catalogues of consensus-based structure and process-of-care quality indicators (QIs) have been proposed, but only a few studies have tested and validated ABS QIs in practice tests. This multicentre study determined the clinimetric properties and suitability of a set of 33 process QIs for ABS that had earlier been developed and in part recommended in a German-Austrian hospital ABS practice guideline. METHODS: Two point prevalence surveys were conducted in a convenience sample of 24 acute care hospitals throughout Germany, and data of all screened adult inpatients with prescription of a systemic antibiotic at a given day (n=4310) were included in the study. For each QI, the following clinimetric properties were assessed: applicability, feasibility, performance, case mix stability and interobserver reliability. RESULTS: Eighteen QIs were considered sufficiently feasible, applicable and reliable, and had adequate room for improvement. The finally selected QIs primarily cover antibiotic therapy of common infections (bloodstream infection, pneumonia and urinary tract infection), while two of the QIs each address surgical prophylaxis and general aspects of antibiotic administration. CONCLUSIONS: Practice tests may be important to test the suitability of consensus process-of-care QIs in the field of hospital ABS. The 18 selected QIs considered suitable enough for hospital ABS in this study should be regarded as priority QIs useful for internal quality control and assurance. More research and additional practice tests may be needed to confirm their suitability for external quality assessment schemes.

Validation of adapted daily dose definitions for hospital antibacterial drug use evaluation: a multicentre study.

Background: The WHO/ATC (Anatomical Therapeutic Chemical) index DDD (WHO-DDD) is commonly used for drug consumption measurement. Discrepancies between WHO-DDD and actual prescribed daily doses (PDD) in hospitals have prompted alternative dose definitions adapted to doses recommended in hospital practice guidelines [recommended daily doses (RDD)]. Methods: In order to validate RDD we performed modified point prevalence surveys in 24 acute care hospitals and recorded 20620 PDD of antibiotics given to 4226 adult patients on the day of the survey and the 6 preceding days. We calculated RDD and WHO-DDD and compared them with PDD. Results: The rate of RDD corresponding to PDD was higher than the corresponding rate for WHO-DDD (pooled data, 55% versus 30%) and the differences were similar across the hospital sample, but varied according to drug/drug class, route of administration, indication and renal function. RDD underestimated actual consumption by 14% overall, while WHO-DDD overestimated total antibacterial consumption by 28% (pooled data; median values RDD -10% versus WHO-DDD +32%). The deviations of estimated from actual drug use volumes were largest for ß-lactams (RDD -11% versus WHO-DDD +49%), in particular for penicillins (-11% versus +64%), if WHO-DDD were used. Conclusions: Hospital antibiotic consumption surveillance systems using current WHO-DDD should address the uneven discrepancies between actual prescribing and consumption estimates according to drug class that may lead to misclassification in benchmark analyses. We recommend using validated RDD as a supplementary measure to the WHO-DDD for detailed analyses.

Focusing on severe infections with the respiratory syncytial virus (RSV) in adults: Risk factors, symptomatology and clinical course compared to influenza A / B and the original SARS-CoV-2 strain.

BACKGROUND: The role and impact of RSV in the adult population is not well understood and comparative data of RSV infection, influenza A/B and SARS-CoV-2 in the elderly hospitalized for respiratory infections is limited. METHODS: In a retrospective, monocentric study we analyzed data of adult patients with respiratory infections tested positive by PCR for RSV, Influenza A/B and SARS-CoV-2 over a four-year period from 2017 to 2020. Symptoms on admission, laboratory results, and risk factors were assessed, and the clinical course and outcomes were studied. RESULTS: A total of 1541 patients hospitalized with respiratory disease and PCR positive for one of the 4 viruses were enrolled in the study. RSV was the second most prevalent virus before the COVID-19 pandemic and RSV patients represent the oldest group in this study with an average age of 75 years. Neither clinical nor laboratory characteristics differ clearly between RSV, Influenza A / B and SARS-CoV-2 infections. Up to 85% of patients had risk factors, with COPD and kidney disease found particularly frequently in RSV infections. Hospital stay was 12.66 days for RSV patients and thus significantly longer than for influenza A / B (10.88 and 8.86, respectively, p < 0.001), but shorter than for SARS-CoV-2 (17.87 days, p < 0.001). The risk for ICU admission and the rate of mechanical ventilation were also higher for RSV than for influenza A (OR 1.69 (p = 0.020) and 1.59 (p = 0.050)) and influenza B: (1.98 (p = 0.018) and 2.33 (p < 0.001)), but lower than for SARS-CoV-2 (0.65 (p < 0.001) and 0.59 (p = 0.035)). The risk of hospital mortality for RSV was increased compared with influenza A (1.55 (p = 0.050)) and influenza B (1.42 (p = 0.262)), but lower compared to SARs-CoV-2 (0.37 (p < 0.001). CONCLUSION: RSV infections in elderly are frequent and more severe than those with influenza A/B. While the impact of SARS-CoV-2 most likely decreased in the elderly population due to vaccination, RSV can be expected to continue to be problematic for elderly patients, especially those with comorbidities and thus, more awareness on the disastrous impact of RSV in this age group is urgently needed.

Comparative analysis of RSV-related hospitalisations in children and adults over a 7 year-period before, during and after the COVID-19 pandemic.

BACKGROUND: RSV is an important cause for respiratory illness in children and the elderly. We analysed RSV seasons since 2016 in both age groups for differences, similarities and timely associations before, during and after the COVID-19 pandemic. METHODS: We studied epidemiological and clinical features of seven consecutive RSV seasons since 2016 retrospectively in children and adults who were systematically monitored for RSV infections by PCR when hospitalized in Regensburg, Germany. RESULTS: Data from 1903 RSV positive, hospitalised patients were analysed (1446 children, 457 adults). We observed a complete absence of RSV associated hospitalizations in season 2020/2021. While in the season of 2021/2022, RSV associated hospitalizations in children returned to considerable numbers earlier than expected, hospitalizations in the elderly were still mitigated during that season in temporal association with the continuation of NPI measures for COVID-19 in the elderly until summer of 2022. Overall, children were hospitalized more often for RSV, while the elderly showed more severe outcomes. RSV hospitalisations continuously increase in both age groups, following a bi-annual pattern of severe and less severe seasons, which was not altered by the COVID-19 pandemic. CONCLUSION: We demonstrate the relation between RSV waves in children and the elderly. NPI measures may protect the elderly from RSV infections and epidemiological data could be used to predict RSV waves early enough to prepare countermeasures.

Analysis of COVID-19 Infection Chains in a School Setting: Data From a School-Based rRT-PCR-Gargle Pool Test System.

BACKGROUND: School testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was implemented in some countries to monitor and prevent SARS-CoV-2 transmissions. Here, we analyze infection chains in primary schools and household members of infected students based on systematic real-time reverse-transcriptase polymerase-chain-reaction (rRT-PCR)-gargle pool testing. METHODS: Students and school staff (N = 4300) of all 38 primary schools in the rural county of Cham, Germany, were tested twice per week with a gargle pool rRT-PCR system from April to July of 2021. Infection chains of all 8 positive cases identified by school testing were followed up. RESULTS: In total, 8 positive cases were found by gargle pool PCR testing based on 96,764 school tests. While no transmissions occurred in the school setting, 20 of 27 household members of the 8 cases tested positive. The overall attack rate was 74.1% in families. CONCLUSIONS: No school outbreaks occurred during the study period. All cases but 1 were initially picked up by school testing. No transmission from school to families was observed.

Serum Neurofilament light chain (NfL) levels in children with and without neurologic diseases.

BACKGROUND/OBJECTIVE: Serum neurofilament light chain (sNfL) is a specific biomarker of neuronal damage. Elevated sNfL levels have been reported in numerous neurologic diseases in adults, whereas data on sNfL in the pediatric population are incomplete. The aim of this study was to investigate sNfL levels in children with various acute and chronic neurologic disorders and describe the age dependence of sNfL from infancy to adolescence. METHODS: The total study cohort of this prospective cross-sectional study consisted of 222 children aged from 0 to 17 years. Patients' clinical data were reviewed and patients were assigned to the following groups: 101 (45.5%) controls, 34 (15.3%) febrile controls, 23 (10.4%) acute neurologic conditions (meningitis, facial nerve palsy, traumatic brain injury, or shunt dysfunction in hydrocephalus), 37 (16.7%) febrile seizures, 6 (2.7%) epileptic seizures, 18 (8.1%) chronic neurologic conditions (autism, cerebral palsy, inborn mitochondrial disorder, intracranial hypertension, spina bifida, or chromosomal abnormalities), and 3 (1.4%) severe systemic disease. sNfL levels were measured using a sensitive single-molecule array assay. RESULTS: There were no significant differences in sNfL levels between controls, febrile controls, febrile seizures, epileptic seizures, acute neurologic conditions, and chronic neurologic conditions. In children with severe systemic disorders, by far the highest NfL levels were found with an sNfL of 429 pg/ml in a patient with neuroblastoma, 126 pg/ml in a patient with cranial nerve palsy and pharyngeal Burkitt's lymphoma, and 42 pg/ml in a child with renal transplant rejection. The relationship between sNfL and age could be described by a second order polynomial with an R2 of 0.153 with a decrease of sNfL by 3.2% per year from birth to age 12 years and thereafter an increase by 2.7% per year until age 18 years. CONCLUSIONS: In this study cohort, sNfL levels were not elevated in children with febrile or epileptic seizures, or various other neurologic diseases. Strikingly high sNfL levels were detected in children with oncologic disease or transplant rejection. A biphasic sNfL age-dependency was documented, with highest levels in infancy and late adolescence and the lowest levels in middle school age.

Effects of infection control measures towards preventing SARS-CoV-2 outbreaks in a German choir boarding school from March 2020 to April 2022.

Background: Singing in a choir was associated with larger outbreaks in the beginning of the SARS-CoV-2 pandemic. Materials and methods: We report on the effect and acceptance of various infection control measures on the occurrence of SARS-CoV-2 infections in the world famous Domspatzen boys' choir from March 2020 to April 2022. Results: In addition to basic general hygiene measures, systematic rRT-PCR testing and scientifically approved concepts of distancing during singing were applied. While single infections of choir members could not be avoided, singing-related outbreaks were not observed. Until the Omicron variant emerged, potential transmission of SARS-CoV-2 in the school was limited to only one case. Incidences at the school were never higher than in the comparable general population until then. While the impact of the pandemic on daily life and singing was rated as severe, especially by staff members, most students agreed with the usefulness of protection measures and rated them as acceptable. Students viewed regular testing as the most important tool to increase safety in the school. Discussion: A bundle of infection control measures including regular testing can prevent outbreaks of SARS-CoV-2 even in the setting of choir singing. Measures are acceptable for choir members if they allow to continue with singing and performing.

Evaluation of a rapid culture-based screening test for detection of methicillin resistant Staphylococcus aureus.

The performance of a culture based assay, BacLite Rapid MRSA for the rapid detection (5 hours) of methicillin resistant Staphylococcus aureus (MRSA) from specimens (n = 377) obtained from nares, throat, wounds and perineum was investigated. Compared to culture based reference methods (chromogenic MRSA ID (bioMerieux)), selective enrichment broth, PBP2' latex agglutination (Oxoid) and VITEK 2 identification (bioMerieux), an overall sensitivity of 71% with a 82% specificity and a negative predictive value (NPV) of 95% was provided. The Baclite test is rapid and easy to use and has the advantage of a culture-based detection method for MRSA.

Diabetic foot infections: microbiological aspects, current and future antibiotic therapy focusing on methicillin-resistant Staphylococcus aureus.

Diabetic patients are at increased risk of complicated skin, skin structure and bone infections including infections of diabetic foot ulcerations (DFU). Analyses of epidemiology and microbial pathogenicity show that staphylococci seem to be predestined to induce such infections. In addition, multidrug resistance particularly due to an increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) seems to be the challenge for effective antibiotic therapy. With regard to infections with MRSA, classical agents like vancomycin, linezolid, fosfomycin or trimethroprim-sulphametoxazol might be agents of choice in DFU. New-generation drugs including broad-spectrum tetracyclines like tigecycline, first and second generation of cyclic lipopeptides, anti-MRSA ß-lactams including ceftobiprole and anti-MRSA antibodies are developed or in progress and the hope for the future.

Performance evaluation of the Roche Elecsys Anti-SARS-CoV-2 S immunoassay.

The Elecsys® Anti-SARS-CoV-2 S immunoassay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) has been developed for the detection of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein. We evaluated the assay performance using samples from seven sites in Germany, Austria, and Switzerland. For specificity and sensitivity analyses, 7880 presumed negative pre-pandemic samples and 827 SARS-CoV-2 PCR-confirmed single or sequential samples from 272 different patients were tested, respectively. The overall specificity and sensitivity (≥14 days post-PCR) for the Elecsys Anti-SARS-CoV-2 S immunoassay were 99.95% (95% confidence interval [CI]: 99.87-99.99; 7876/7880) and 97.92% (95% CI: 95.21-99.32; 235/240), respectively. The Elecsys Anti-SARS-CoV-2 S immunoassay had significantly higher specificity compared with the LIAISON® SARS-CoV-2 S1/S2 IgG (99.95% [2032/2033] vs 98.82% [2009/2033]), ADVIA Centaur® SARS-CoV-2 Total (100% [928/928] vs 86.96% [807/928]), ARCHITECT SARS-CoV-2 IgG (99.97% [2931/2932] vs 99.69% [2923/2932]), iFlash-SARS-CoV-2 IgM (100.00% [928/928] vs 99.57% [924/928]), and EUROIMMUN Anti-SARS-CoV-2 IgG (100.00% [903/903] vs 97.45% [880/903]) and IgA (100.00% [895/895] vs 95.75% [857/895]) assays. The Elecsys Anti-SARS-CoV-2 S immunoassay had significantly higher sensitivity (≥14 days post-PCR) compared with the ARCHITECT SARS-CoV-2 IgG (98.70% [76/77] vs 87.01% [67/77]), iFlash-SARS-CoV-2 IgG (100.00% [76/76] vs 93.42% [71/76]) and IgM (100.00% [76/76] vs 35.53% [27/76]), and EUROIMMUN Anti-SARS-CoV-2 IgG (98.26% [113/115] vs 93.91% [108/115]) assays. Therefore, the Elecsys Anti-SARS-CoV-2 S assay demonstrated a reliable performance across various sample populations for the detection of anti-S antibodies.