Clinical relevance of Staphylococcus saccharolyticus detection in human samples: a retrospective cohort study.

PURPOSE: To characterize the clinical relevance of S. saccharolyticus and to identify criteria to distinguish between infection and contamination. METHODS: We retrospectively investigated clinical features of patients with S. saccharolyticus detection between June 2009 and July 2021. Based on six criteria, infection was considered likely for patients with a score from 3 to 6 points, infection was considered unlikely for patients with a score from 0 to 2 points. We performed group comparison and logistic regression to identify factors than are associated with likely infection. In addition, whole genome sequencing (WGS) of 22 isolates was performed. RESULTS: Of 93 patients in total, 44 were assigned to the group "infection likely" and 49 to the group "infection unlikely". Multiple regression analysis revealed "maximum body temperature during hospital stay" to have the strongest predictive effect on likely infection (adjusted odds ratio 4.40, 95% confidence interval 2.07-9.23). WGS revealed two different clades. Compared to isolates from clade A, isolates from clade B were more frequently associated with implanted medical devices (3/10 vs. 9/12, p = 0.046) and a shorter time to positivity (TTP) (4.5 vs. 3, p = 0.016). Both clades did neither differ significantly in terms of causing a likely infection (clade A 7/10 vs. clade B 5/12, p = 0.23) nor in median length of hospital stay (28 vs. 15.5 days, p = 0.083) and length of stay at the ICU (21 vs. 3.5 days, p = 0.14). CONCLUSION: These findings indicate that S. saccharolyticus can cause clinically relevant infections. Differentiation between infection and contamination remains challenging.

Study draft: "UVC-You Will See" study: longer vs. shorter umbilical venous catheter (UVC) dwell time (6-10 vs. 1-5 days) in very premature infants with birth weight < 1250 g and/or gestational age < 30 weeks.

BACKGROUND: Umbilical venous catheters (UVCs) are often used in preterm infants. Their use is associated with complications (infections, clot formation, organ injury). Very preterm infants with acquired bloodstream infection are at a higher risk for death and important morbidities (e.g., adverse neurodevelopmental outcomes). It is standard clinical practice to remove UVCs in the first days of life. Replacement of intravenous access is often performed using percutaneously inserted central catheters (PICCs). It is unclear whether serial central line use affects the rates of catheter-related complications. METHODS: A multicenter randomized controlled trial (random group assignment) was performed in 562 very premature (gestational age < 30 weeks) and/or very low birth weight infants (< 1250 g) requiring an UVC for administration of parenteral nutrition and/or drugs. Group allocation was random. HYPOTHESIS: A UVC dwell time of 6-10 days (281 infants) is not associated with an increased rate of central venous catheter (UVC, PICC)-related complications compared to 1-5 days (281 infants), and a longer UVC dwell time will significantly reduce the number of painful, invasive procedures associated with the need for vascular access as well as radiation exposure, use of antibiotics, and medical costs. PRIMARY OUTCOME PARAMETER: The number of catheter-related bloodstream infections and/or catheter-related thromboses and/or catheter-associated organ injuries related to the use of UVC/PICC was the primary outcome. CONCLUSION: Extending the UVC dwell time may significantly reduce the number of painful invasive procedures, with the potential to positively impact not only long-term pain perception but also important social competencies (attention, learning, and behavior). Thus, the "UVC-You Will See" study has the potential to substantially change current neonatal intensive care practice.

Combinatorial host-response biomarker signature (BV score) and its subanalytes TRAIL, IP-10, and CRP in children with Mycoplasma pneumoniae community-acquired pneumonia.

BACKGROUND: Host-response biomarkers to differentiate bacterial from viral etiology in children with respiratory infections have shown high accuracies, but are understudied in Mycoplasma pneumoniae (Mp) infections. METHODS: We compared BV scores (0-34 indicating viral, and 66-100 indicating bacterial etiology), TRAIL (pg/mL), IP-10 (pg/mL), and CRP (mg/L) serum levels between Mp positive (Mp+) and negative (Mp-) community-acquired pneumonia (CAP). We performed receiver operating characteristic (ROC) curve analyses for clinical features and biomarkers. RESULTS: Of 80 CAP patients (median age 6.3 years, 57.5% male), 26 were Mp + CAP. By comparing Mp + CAP with Mp-CAP patients, BV scores were lower (median 14.0, IQR 3.0-27.8 vs. 54.0, IQR 12.0-84.8; P = 0.0008), TRAIL levels were higher (86.5, IQR 67.4-123.0 vs. 65.5, IQR 42.5-103.9; P = 0.025), CRP levels were lower (12.9, IQR 4.0-22.3 vs. 36.7, IQR 13.0-132.8; P = 0.0019), and IP-10 levels were comparable (366.0, IQR 150.2-603.8 vs. 331.0, IQR 154.3-878.8; P = 0.73). ROC analyses yielded a comparable discriminatory accuracy for the combination of age, fever duration, respiratory symptoms duration, with either procalcitonin or BV (AUC 0.87 vs. 0.86, P = 0.94). CONCLUSIONS: Children with Mp + CAP have atypically low, viral levels of the BV score, underscoring the complementary role of microbiological testing.

Association of viral load with TRAIL, IP-10, CRP biomarker signature and disease severity in children with respiratory tract infection or fever without source: A prospective, multicentre cohort study.

BACKGROUND: To investigate the association of viral load (VL) with (i) tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10, C-reactive protein, and a combinatorial score (BV score), and (ii) clinical severity. STUDY DESIGN: In this prospective, multicentre cohort substudy, children with respiratory tract infection or fever without source were enrolled. VL for influenza virus, rhinovirus, respiratory syncytial virus, and adenovirus was measured from nasopharyngeal swabs. The reference standard diagnosis was established based on expert panel adjudication. RESULTS: Of 1140 recruited patients, 333 had a virus monodetection. VL for the aggregated data set correlated with TRAIL and IP-10 levels, with the length of oxygen therapy, and inversely with the BV score. At a single viral level, only the influenza VL yielded a correlation with TRAIL, IP-10 levels, and the BV score. Children with a viral reference standard diagnosis had significantly higher VL than those with bacterial infection (p = 0.0005). Low TRAIL (incidence rate ratio [IRR] 0.6, 95% confidence interval [CI] 0.39-0.91) and young age (IRR 0.62, 95% CI 0.49-0.79) were associated with a longer hospital stay, while young age (IRR 0.33, 95% CI 0.18-0.61), low TRAIL (IRR 0.25, 95% CI 0.08-0.76), and high VL (IRR 1.16, 95% CI 1.00-1.33) were predictive of longer oxygen therapy. CONCLUSION: These findings indicate that VL correlates with biomarkers and may serve as a complementary tool pertaining to disease severity.

An immune-protein score combining TRAIL, IP-10 and CRP for predicting severe COVID-19 disease.

COVID-19 patients are oftentimes over- or under-treated due to a deficit in predictive management tools. This study reports derivation of an algorithm that integrates the host levels of TRAIL, IP-10, and CRP into a single numeric score that is an early indicator of severe outcome for COVID-19 patients and can identify patients at-risk to deteriorate. 394 COVID-19 patients were eligible; 29% meeting a severe outcome (intensive care unit admission/non-invasive or invasive ventilation/death). The score's area under the receiver operating characteristic curve (AUC) was 0.86, superior to IL-6 (AUC 0.77; p = 0.033) and CRP (AUC 0.78; p < 0.001). Likelihood of severe outcome increased significantly (p < 0.001) with higher scores. The score differentiated severe patients who further deteriorated from those who improved (p = 0.004) and projected 14-day survival probabilities (p < 0.001). The score accurately predicted COVID-19 patients at-risk for severe outcome, and therefore has potential to facilitate timely care escalation and de-escalation and appropriate resource allocation.

Expression of TRAIL, IP-10, and CRP in children with suspected COVID-19 and real-life impact of a computational signature on clinical decision-making: a prospective cohort study.

PURPOSE: We evaluated the host-response marker score "BV" and its components TRAIL, IP-10, and CRP in SARS-CoV-2 positive children, and estimated the potential impact on clinical decision-making. METHODS: We prospectively analyzed levels of TRAIL, IP-10, CRP, and the BV score, in children with suspected COVID-19. Classification of infectious etiology was performed by an expert panel. We used a 5-point-questionnaire to evaluate the intention to treat with antibiotics before and after receiving test results. RESULTS: We screened 111 children, of whom 6 (5.4%) were positive for SARS-CoV-2. A total of 53 children were included for the exploratory analysis. Median age was 3.1 years (interquartile range [IQR] 1.3-4.3), and 54.7% (n = 29) were girls. A viral and a bacterial biomarker pattern was found in 27/53 (50.9%) and 15/53 (28.3%), respectively. BV scores differed between COVID-19, children with other viral infections, and children with bacterial infections (medians 29.5 vs. 9 vs. 66; p = 0.0006). Similarly, median TRAIL levels were different (65.5 vs. 110 vs. 78; p = 0.037). We found no differences in IP-10 levels (555 vs. 504 vs. 285; p = 0.22). We found a concordance between physicians' "unlikely intention to treat" children with a viral test result in most cases (n = 19/24, 79.2%). When physicians expressed a "likely intention to treat" (n = 15), BV test revealed 5 bacterial, viral, and equivocal scores each. Antibiotics were withheld in three cases (20%). Overall, 27/42 (64%) of pediatricians appraised the BV test positively, and considered it helpful in clinical practice. CONCLUSION: Host-response based categorization of infectious diseases might help to overcome diagnostic uncertainty, support clinical decision-making and reduce unnecessary antibiotic treatment.

Umbilical venous catheter- and peripherally inserted central catheter-associated complications in preterm infants with birth weight < 1250 g : Results from a survey in Austria and Germany.

BACKGROUND AND OBJECTIVE: Umbilical venous catheters (UVC) and peripherally inserted central catheters (PICC) are commonly used in preterm infants but have been associated with a number of serious complications. We performed a survey in Austria and Germany to assess the use of UVCs and PICCs in preterm infants with a birth weight < 1250 g and associated rates of catheter-related adverse events. METHODS: Electronic survey of participating centers of the NeoVitaA trial. Main outcome parameter was the reported rates of UVC- and PICC-associated complications (infection, thrombosis, emboli, organ injury, arrhythmia, dislocation, miscellaneous). RESULTS: In total, 20 neonatal intensive care units (NICU) providing maximal intensive care in Austria and Germany (level I) were contacted, with a senior neonatologist response rate of 12/20 (60%). The reported rates for UVC with a dwell time of 1-10 days were bacterial infection: 4.2 ± 3.4% (range 0-10%); thrombosis: 7.3 ± 7.1% (0-20%); emboli: 0.9 ± 2.0% (0-5%); organ injury: 1.1 ± 1.9% (0-5%); cardiac arrhythmia: 2.2 ± 2.5% (0-5%); and dislocation: 5.4 ± 8.7% (0-30%); and for PICCs with a dwell time of 1-14 days bacterial infection: 15.0 ± 3.4% (range 2.5-30%); thrombosis; 4.3 ± 3.5% (0-10%); emboli: 0.8 ± 1.6% (0-5%); organ injury: 1.5 ± 2.3% (0-5%); cardiac arrhythmia: 1.5 ± 2.3% (0-5%), and dislocation: 8.5 ± 4.6% (0-30%). CONCLUSION: The catheter-related complication rates reported in this survey differed between UVCs and PICCs and were higher than those reported in the literature. To generate more reliable data on this clinically important issue, we plan to perform a large prospective multicenter randomized controlled trial investigating the non-inferiority of a prolonged UVC dwell time (up to 10 days) against the early change (up to 5 days) to a PICC.

Staphylococcus massiliensis isolated from human blood cultures, Germany, 2017-2020.

Clinical and laboratory data on newly described staphylococcal species is rare, which hampers decision-making when such pathogens are detected in clinical specimens. Here, we describe Staphylococcus massiliensis detected in three patients at a university hospital in southwest Germany. We report the discrepancy of microbiological findings between matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, 16S-rRNA polymerase chain reaction, and whole-genome sequencing for all three isolates. Our findings highlight the diagnostic pitfalls pertinent to novel and non-model organisms in daily microbiological practice, in whom the correct identification is dependent on database accuracy.

[Prospektives Audit des Gentamicin Drug Monitorings in einem Kinderkrebszentrum]. / Prospective Audit of Gentamicin Drug Monitoring Practice in a Pediatric Cancer Center.

BACKGROUND: Many pediatric cancer centers still use Gentamicin as first line combination treatment in patients with fever and neutropenia. Since 2011, our center has implemented a dosing regimen with 250 mg/m2 BSA (max. 10 mg/kg, max. 400 mg) as a single daily infusion according to the German guideline. PATIENTS AND METHODS: In this prospective audit (February 2011 to December 2019), 105 Gentamicin treatment cycles were analyzed in 66 pediatric cancer patients, focusing on adherence to the dosing regimen and the drug monitoring results. RESULTS: Adherence to the dosing regimen was high (89%). In 64% of all cycles, the Cmax (drawn 1 h after the 2nd dose) reached the target of 10-20 µg/ml. Cmax significantly correlated with dosing in mg/m2 BSA (p=0,007), but not with dosing in mg/kg (p=0,366). Age below 6 years did not influence these results. The Gentamicin Ctrough (drawn 8-10 h after the second dose) was < 2 µg/ml in 93% of all cycles without any dose correlation. None of the patients experienced Gentamicin-associated nephrotoxicity. DISCUSSION AND CONCLUSION: This prospective audit of single daily infusion Gentamicin in pediatric cancer patients without impaired renal function elicits the feasibility and safety of the dosing regimen in mg/m2 BSA according to the German guideline. Since indications for first-line gentamicin are limited, a multicenter prospective study would be advantageous to confirm these observations.

Human infections caused by Staphylococcus argenteus in Germany: genetic characterisation and clinical implications of novel species designation.

We report a series of Staphylococcus argenteus infections from Saarland, Germany. Travel histories were unremarkable for extra-European sojourns, indicating an autochthonous transmission mode. Multilocus sequence typing revealed that all isolates were members of the clonal complex CC2250. In only one case, guideline-adherent treatment with an isoxazolyl penicillin was prescribed. Our report illustrates the perils of novel species designations, which may lead to misconceptions and suboptimal treatment choices among clinicians.

Antibiotic utilization in hospitalized children under 2 years of age with influenza or respiratory syncytial virus infection - a comparative, retrospective analysis.

BACKGROUND: Infections due to Respiratory Syncytial Virus (RSV) and Influenza virus (FLU) are leading causes of hospitalization in young children. Yet, there is little data on factors associated with antibiotic use in these patients. METHODS: We conducted a retrospective, single-center study of all patients below 2 years of age hospitalized between 2014 and 2018. We compared children with RSV infection to children with FLU infection analyzing clinical characteristics and factors contributing to an increased rate of antimicrobial utilization. RESULTS: RSV infection was diagnosed in 476/573 (83.1%), FLU in 95/573 (16.6%), and RSV-FLU-co-infection in 2/573 (0.3%) patients. Median age was lower for RSV compared to FLU (4 vs. 12 months; p < 0.0001). Children with RSV had longer hospitalization (5 vs. 4 days; p = 0.0023) and needed oxygen more frequently (314/476 vs. 23/95; p < 0.0001) than FLU patients. There was no significant difference in the overall antibiotic utilization between RSV and FLU patients (136/476 vs. 21/95; p = 0.2107). Logistic regression analyses revealed that septic appearance on admission (odds ratio [OR] 8.95, 95% confidence interval [CI] 1.5-54.1), acute otitis media (OR 4.5, 95% CI 2.1-9.4), a longer oxygen therapy (OR 1.40; 95% CI 1.13-1.74) and a higher C-reactive protein (CRP) (OR 1.7, 95% CI 1.5-2.0) were significantly associated with antibiotic use in both groups, but not age or pneumonia. CONCLUSIONS: In our cohort, the rate of antibiotic utilization was comparable between RSV and FLU patients, while for both groups distinct clinical presentation and a high CRP value were associated with higher antibiotic use.

Infectious causes of peripheral facial nerve palsy in children-a retrospective cohort study with long-term follow-up.

The aim of this study was to analyze the clinical and laboratory characteristics of children with peripheral facial nerve palsy (pFP) with a focus on identifying infectious etiology and long-term outcome. We conducted an ICD-10-based retrospective chart review on children hospitalized with pFP between January 1, 2006, and December 31, 2016. Furthermore, a telephone-based follow-up survey was performed. A total of 158 patients were identified, with a median age of 10.9 years (interquartile range 6.4-13.7). An infectious disease was associated with pFP in 82 patients (51.9%); 73 cases were classified as idiopathic pFP (46.2%). Three cases occurred postoperatively or due to a peripheral tumor. Among the infectious diseases, we identified 33 cases of neuroborreliosis and 12 viral infections of the central nervous system (CNS), caused by the varicella-zoster virus, human herpesvirus 6, herpes simplex virus, enterovirus, and Epstein-Barr virus. Other infections were mainly respiratory tract infections (RTIs; 37 cases). Children with an associated CNS infection had more often headache and nuchal rigidity, a higher cerebrospinal fluid cell count, and a longer length of hospital stay. Long-term follow-up revealed an associated lower risk of relapse in CNS infection-associated pFP. Among all groups, permanent sequelae were associated with female sex, a shorter length of hospitalization, and a lower white blood cell count at presentation. pFP is frequently caused by an CNS infection or is associated with concurrent RTIs, with a potential impact on the short- and long-term clinical course.

Evaluation of the multiplex PCR based assay Unyvero implant and tissue infection application for pathogen and antibiotic resistance gene detection in children and neonates.

BACKGROUND: Skin and soft tissue infections have a high disease burden in children. The emergence of multidrug-resistant bacteria over the last decades has heavily influenced hospitalization rates, morbidity and mortality. In addition, with increased survival rates in neonatology and oncology, health-care associated infections are more frequently encountered. There is a growing need for fast and feasible diagnostic tools for the recognition of microorganisms and drug resistances. METHODS: In this prospective study, we compared results of routine culture with the multiplex PCR based Unyvero Implant and Tissue Infection (ITI) application. Specimens were obtained from different sources from neonates and children. RESULTS: We analyzed specimens from 29 patients (72.4% male) with a median age of 8.1 years (range 0.03-15.2). Concordance between Unyvero ITI and culture was reached in 16 of 29 samples (55.2%). Unyvero ITI yielded an overall sensitivity and specificity of 76.3% and 96.5%, respectively. Accuracies were best for non-fermenting bacteria, for which sensitivity was 100% and specificity 98.2%. Detection rates were lower for Gram-positive bacteria (68.8 and 95.2%, respectively). Unyvero correctly detected one blaOXA-24/40 producing Acinetobacter baumannii, while none of the six gyrA87 had a correlate in antimicrobial susceptibility testing. CONCLUSIONS: Unyvero ITI quickly provides additional information relevant for clinical decision-makers. Sensitivity of the PCR must be improved especially for Gram-positive bacteria, and further studies are needed to assess the impact on clinical decision-making and outcome.

[Update Hygiene: Prevention of Vascular Catheter-Associated Infections in Premature and Newborn Infants]. / Update Hygiene: Prävention von Gefäßkatheter-assoziierten Infektionen bei Früh- und Neugeborenen.

BACKGROUND: In May 2018, the commission on infection prevention and control in Germany (KRINKO) of the RKI published a guidance document providing recommendations on the prevention of catheter-associated infections in premature children and newborns. AIM: Summarized presentation, explanation and discussion of the KRINKO recommendations. METHODS: The recommendations of the KRINKO were summarized and discussed with reference to the original sources. RESULTS: In particular, statements were formulated for the insertion and maintenance of vascular catheters and for the preparation of infusions. Overall, however, the evidence of the recommendations is low. About 26% (19 out of 74) are classified under category IA or IB. However, 40% of the recommendations are category II only and therefore based on indicative clinical or epidemiological studies or comprehensible theoretical justifications. Accordingly, there is a lack of urgently needed clinical trials. DISCUSSION: Prevention strategies were discussed in detail and practical issues were addressed. The high number of recommendations, sometimes with low evidence levels, suggests a shared assessment of the infection control team and clinicians to ensure a successful implementation in practice and a focus on key content adapted to the local situation.

Identification and Containment of a Cluster of Two Bacillus cereus Infections in a Neonatal Intensive Care Unit.

We report a cluster of invasive Bacillus cereus infections in a neonatal intensive care unit. We describe the clinical course of two infected patients, one of whom died of severe pneumonia after successfully being weaned from ECMO. Environmental analyses failed to yield a common source. Molecular characterization confirmed the homogeneity of both isolates. Rigorous hygiene control and adequate therapy enabled the containment of the cluster.

Assessment of the multiplex PCR-based assay Unyvero pneumonia application for detection of bacterial pathogens and antibiotic resistance genes in children and neonates.

BACKGROUND: Pneumonia is a major healthcare problem. Rapid pathogen identification is critical, but often delayed due to the duration of culturing. Early, broad antibacterial therapy might lead to false-negative culture findings and eventually to the development of antibiotic resistances. We aimed to assess the accuracy of the new application Unyvero P50 based on multiplex PCR to detect bacterial pathogens in respiratory specimens from children and neonates. METHODS: In this prospective study, bronchoalveolar lavage fluids, tracheal aspirates, or pleural fluids from neonates and children were analyzed by both traditional culture methods and Unyvero multiplex PCR. RESULTS: We analyzed specimens from 79 patients with a median age of 1.8 (range 0.01-20.1). Overall, Unyvero yielded a sensitivity of 73.1% and a specificity of 97.9% compared to culture methods. Best results were observed for non-fermenting bacteria, for which sensitivity of Unyvero was 90% and specificity 97.3%, while rates were lower for Gram-positive bacteria (46.2 and 93.9%, respectively). For resistance genes, we observed a concordance with antibiogram of 75% for those specimens in which there was a cultural correlate. CONCLUSIONS: Unyvero is a fast and easy-to-use tool that might provide additional information for clinical decision making, especially in neonates and in the setting of nosocomial pneumonia. Sensitivity of the PCR for Gram-positive bacteria and important resistance genes must be improved before this application can be widely recommended.

Pott's disease: a major issue for an unaccompanied refugee minor.

The incidence of TB in children in Germany has been on a rise since 2008, especially among foreign-born individuals. With rapidly increasing numbers of refugees from the numerous areas of conflict, this increase in incidence is not expected to halt, neither in Germany nor in Europe in general. We report a case of insufficient tracking in a 16-year-old unaccompanied refugee minor from Somalia who had a positive interferon γ release assay on arrival in Germany. No actions were undertaken, until 6 months later, an X-ray showed prominent hilar enlargement. Nine  months later, the patient presented to our hospital with abdominal pain, vomiting and B symptoms. Workup revealed a paravertebral abscess due to Pott's disease, a skeletal manifestation of Mycobacterium tuberculosis disease. The patient made a full recovery after a combination therapy for a total of 9 months.