Multidrug-resistant (MDR) Klebsiella pneumoniae (Kp) represents a growing public health threat worldwide. We performed genomic analyses of carbapenem- and/or colistin-resistant Kp isolates recovered from hospitalized patients at Meram Hospital in Konya, Turkey. Forty-four isolates were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry, and resistance phenotypes were confirmed using broth microdilution assays. Whole-genome sequencing (Illumina) and bioinformatic analyses were used to determine sequence types (STs), antimicrobial resistance (AMR) determinants, virulence factors, and plasmid profiles. The isolates belonged to five STs: ST2096 (70.4%), ST377 (13.6%), ST101 (4.5%), ST14 (2.3%), and one novel ST (ST8972), along with two untypeable strains. Clonal group 14 (CG14), comprising ST2096, ST14, and ST8972, was predominant. Global phylogenetic analysis showed that most ST2096 isolates belonged to a clade circulating in Turkey and other countries, suggesting an international spread of these high-risk clones. No plasmid-mediated mcr genes were detected; however, several chromosomal mutations in mgrB and pmrB were identified. Carbapenem resistance was largely driven by blaOXA-48-like genes, with blaKPC-2 co-detected in one isolate. Notably, 77.3% of isolates exhibited convergence of genotypes with high virulence potential and AMR, and only two isolates lacked high virulence potential. These findings highlight the rising burden of MDR Kp in Turkey and demonstrate an urgent need for robust One Health genomic surveillance across clinical and community settings throughout the globe. The spread of carbapenem- and colistin-resistant strains harboring enhanced virulence gene profiles in different geographical locations signals lapses in antimicrobial stewardship and infection control that can be mitigated by coordinated local and global efforts to address AMR.IMPORTANCEThe global rise of Klebsiella pneumoniae (Kp) resistant to last-resort antimicrobials represents a critical threat to public health. Despite this concern, data on the genetic drivers of resistance and virulence in Turkey remain scarce, resulting in significant gaps in local and global surveillance. This study addresses this need by providing a comprehensive genomic analysis of multidrug-resistant clinical Kp isolates, revealing the frequent convergence of antimicrobial resistance and genetic signatures indicative of enhanced virulence in these strains. Notably, most isolates belonged to ST2096, clustering with genomes from Turkey and other countries, highlighting the international spread of these high-risk clones. The emergence of these difficult-to-treat pathogens emphasizes the urgent need for targeted action, including sustained genomic surveillance, stronger infection prevention, and improved antimicrobial stewardship. Policymakers, clinicians, and public health stakeholders must collaborate to enhance diagnostic capacity, surveillance systems, and infection control, particularly in countries where existing gaps exacerbate the spread of multidrug-resistant pathogens with high-virulence genotypes.

AbstractInvasive infections due to Paenibacillus species pose a serious risk to young infants and have a high risk of neurologic sequelae. This report describes two infants with severe neurologic manifestations secondary to Paenibacillus dendritiformis infection who were recently identified in the United States. Clinicians who care for young infants should be aware of this emerging infection.

We describe the case of a young female who presented with apparent human metapneumovirus-associated illness and dehydration, but whose condition rapidly worsened with progression to multiple organ dysfunction syndrome (MODS). Multiple modalities were used to treat the patient, including: 1) extracorporeal life support (ECLS) for refractory shock; 2) anakinra, a human recombinant interleukin (IL)-1 receptor antagonist, for presumed cytokine storm; and 3) therapeutic plasma exchange (TPE) for thrombocytopenia-associated multiple organ failure (TAMOF). The patient’s organ dysfunction rapidly improved. Post hoc cytokine analysis revealed that anakinra administration was associated with marked decreases in interleukin (IL)-6 and IL-8 levels, but not in other cytokine biomarkers, indicating a possible upstream IL-1 effect on IL-6/IL-8 levels. Preclinical cytokine-based sepsis models were used to investigate this possibility. The preclinical results suggest that IL-6 levels are a function of synergistic IL-1 and tumor necrosis factor (TNF) activity. Further study is needed to determine appropriate patient populations, timing, and dosing of anakinra for suppressing IL-1 signaling during cytokine storm-induced MODS.

Introduction:Neonatal mortality remains disproportionately high in sub-Saharan Africa, where an estimated 27 neonatal deaths per 1,000 live births occur annually. Infections, including sepsis and meningitis, account for a substantial proportion of these deaths, while neural tube defects (NTDs) contribute significantly to both neonatal mortality and long-term disability. Existing surveillance systems in the region are predominantly facility-based, missing the substantial proportion of births and deaths that occur in the community. Population-based surveillance platforms that capture community-level data are urgently needed to generate accurate incidence estimates, identify modifiable risk factors, and guide evidence-based interventions. Cohort Description:The Consortium to Reduce Infant Mortality (CONRIM) is a multi-institutional partnership among Ugandan physicians and scientists, Yale University, Penn State University, Boston Children's Hospital/Harvard Medical School, and Uganda's National Planning Authority. CONRIM conducts prospective, community-based neonatal surveillance within the Busoga Kingdom in eastern Uganda. A network of 813 trained Village Health Team members conducts household-level visits using a structured Open Data Kit (ODK)-based mobile questionnaire to capture every birth, assess for danger signs of possible serious bacterial infection (pSBI), screen for NTDs, and record maternal nutrition and folic acid use, water, sanitation and hygiene (WASH) conditions, and health care utilization. Findings to Date:Since surveillance began in June 2025, the platform has registered approximately 22,200 household submissions and over 5,700 newborn encounters across the Jinja District (population 660,000). Early data have identified higher than expected rates of infants with NTDs including encephalocele and spina bifida; documented folic acid non-use in before and during most pregnancies; characterized WASH conditions in birthplaces; and mapped geospatial hotspots of neonatal infection risk in northeastern rural subcounties. Prospective 28-day follow-up of all live births has demonstrated a neonatal mortality rate of 21.5 per 1000 live births. A real-time data quality monitoring system with 21 automated quality control flags maintains a 99% clean-record rate. Future Plans:Ongoing and planned activities include laboratory-based confirmation of neonatal sepsis via blood culture and cerebrospinal fluid analysis with polymerase chain reaction capacity, portable neuroimaging for NTDs, environmental sampling, genomic studies of folate metabolism pathway genes, linkage with facility-based records at Jinja Regional Referral Hospital and Mulago National Referral Hospital, and community-level interventions informed by surveillance findings.

Background:Neonatal disorders such as post-infectious hydrocephalus exhibit a higher incidence in Africa, where the intricate relationships between genetic ancestry, environmental exposures, and other risk factors likely contribute to the increased incidence. Methods:To start to characterize the common genetic architecture of Ugandan infants, we analyzed genome sequencing data from 1,030 Ugandan infants recruited from studies targeting neonatal sepsis and hydrocephalus. We employed genetic admixture analysis and integrated geospatial data to examine the relationships between genetic backgrounds and disease prevalence within this cohort. Results:Our results identified four distinct genetic admixture groups, each correlating strongly with specific geographic distributions across Uganda. Notably, a predominance of one admixture group, most common in northern Uganda, was overrepresented in the participants with post-infectious hydrocephalus. Conclusion:This study underscores the importance of genetic factors in disease manifestation at the population level, and a role for such precision public health approaches in complex neonatal disorders in African populations.

The mobile colistin resistance gene, mcr-1, encodes resistance to colistin, a critically important antibiotic. Resistance to colistin can jeopardize antimicrobial chemotherapy. Here, we report the detection and genomic characterization of mcr-1-carrying Escherichia coli isolated from otherwise healthy children in community daycares. The mcr-1 was located on transferable plasmids. Additionally, the mcr-1 occurred in E coli that mainly belonged to a clonal ST10 lineage, indicating that these mcr-1-carrying strains were spreading across daycares in geographically distant cities.

BACKGROUND:Neonatal infections due to Paenibacillus species have increasingly been reported over the last few years. METHODS:We performed a structured literature review of human Paenibacillus infections in pediatric and adult patients to compare the epidemiology of infections between these distinct patient populations. RESULTS:Forty reports describing 177 infections were included. Two additional cases were brought to our attention by colleagues. There were 38 Paenibacillus infections occurring in adults caused by 23 species. The clinical presentations of infections were quite variable. In contrast, infections in infants were caused primarily by Paenibacillus thiaminolyticus (112/141, 79%). All the infants with Paenibacillus infection presented with sepsis syndrome or meningitis, often complicated by extensive cerebral destruction and hydrocephalus. Outcomes were commonly poor with 17% (24/141) mortality. Cystic encephalomalacia due to brain destruction was common in both Ugandan and American infant cases and 92/141 (65%) required surgical management of hydrocephalus following their infection. CONCLUSIONS:Paenibacillus species seem to cause a clinical syndrome in infants characterized by brain abscesses, hydrocephalus and death. This contrasts with infection in adults, which is sporadic with only rare involvement of the central nervous system and very few deaths.

Importance:Children with growth faltering are more susceptible to infections and may experience cognitive, physical, and metabolic developmental impairments. Objective:To assess whether prenatal and preconception meteorological and environmental factors are associated with village-level rates of childhood growth outcomes in Uganda. Design, Setting, and Participants:This cross-sectional study used data collected between June 20, 2015, and December 16, 2016, from the 2016 Ugandan Demographic and Health Survey for individuals aged 0 to 59 months with available anthropometric measures (weight and length or height). Data analysis was conducted from October 2020 to April 2024. Exposures:Factors assessed included meteorological information, such as drought index (Standardized Precipitation-Evapotranspiration Index [SPEI]), Aridity Index, rainfall, temperature, and vegetation indices; demographic and economic development factors (nighttime light emissions, driving time to the nearest city); and land topography (slope angle, elevation above sea level). Main Outcomes and Measures:The main outcomes were height-for-age z score (HAZ), weight-for-age z score (WAZ), and weight-for-height z score (WHZ). Spatial resolution estimates, at 1 km × 1 km of childhood growth faltering indicators, were created. Results:Of the 5219 individuals aged 0 to 59 months included in the analysis, 2633 (50%) were female; mean (SD) age was 29 (17) months. Of these individuals, 30.22% (95% CI, 29.36%-30.98%) had stunting, 12.23% (95% CI, 11.55%-12.91%) had underweight, and 3.63% (95% CI, 3.46%-3.80%) had wasting. Large disparities in the burden of childhood growth faltering existed within Uganda at smaller and larger spatial scales; villages in the northeastern and southwestern areas of the country had the highest prevalence of all forms of growth faltering (stunting, >40%; underweight, >16%; and wasting, >6%). Higher SPEI at 3 months before birth was positively associated with all childhood growth outcomes: HAZ (β, 0.06; 95% CI, 0.02-0.10), WAZ (β, 0.04; 95% CI, 0.01-0.07), and WHZ (β, 0.03; 95% CI, 0.001-0.06). Higher location mean rainfall 11 months before birth was also positively associated with HAZ (β, 0.06; 95% CI, 0.01-0.10). Aridity Index associations with WAZ (β, 0.09; 95% CI, 0.04-0.13) and WHZ (β, 0.09; 95% CI, 0.02-0.16) were consistent with findings for SPEI. Conclusions and Relevance:In this study of 5219 individuals 0 to 59 months of age in Uganda, rainfall and long-term availability of water at preconception and during gestation were positively associated with nutritional child growth outcomes. Understanding the relative contributions of meteorological environment factors on the spatial distribution of undernutrition at various spatial scales within Uganda (from the village to the district level) may help in the design of more cost-effective delivery of precision public health programs.

BACKGROUND:Prolonged time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) may enable malnourished oesophageal cancer patients' nutritional status to recover better, possibly improving outcomes with fewer complications and better overall survival (OS) after oesophagectomy. METHODS:This is a substudy within a multicentre randomised controlled trial comparing outcomes in patients with oesophageal cancer after standard TTS of 4-6 weeks to prolonged TTS of 10-12 weeks after nCRT. Patients were categorised as malnourished or non-malnourished at baseline and compared regarding weight, dysphagia, postoperative complications, and OS. RESULTS:The mean weight from baseline to time of surgery decreased significantly in patients allocated to standard TTS (p < 0.001) while patients with prolonged TTS recovered during the extended time to similar weight as at baseline (p = 0.131). The mean dysphagia score at the time of surgery improved significantly in both groups (p < 0.001). There were no significant differences between patients allocated to standard versus prolonged TTS regarding postoperative complications, regardless of malnourishment status at baseline. No significant differences in OS after prolonged TTS compared to standard TTS, was observed in neither malnourished patients (hazard ratio, HR 1.72 (95 %, CI: 0.82-3.59, p = 0.147) nor non-malnourished patients (HR 1.26 (95 % CI:0.82-1.94, p = 0.291). CONCLUSIONS:Prolonged TTS was associated with better weight recovery at the time of surgery compared to standard TTS. Patients malnourished at baseline did not benefit in terms of less postoperative complications after prolonged TTS.

OBJECTIVE:The authors previously identified Paenibacillus species in the CSF of 44% of infants presenting for neurosurgical evaluation with findings consistent with postinfectious hydrocephalus (PIH) in Eastern Uganda. Here, they sought to compare outcomes among hydrocephalic infants with and without Paenibacillus detection at the time of hydrocephalus surgery. METHODS:In a prospective observational study of 189 infants with PIH who underwent a CSF diversion prior to 90 days of age, 78 had a positive CSF polymerase chain reaction result for Paenibacillus species (PP), and 111 had a negative result (PN). The primary outcome was diversion failure-free survival, defined as being alive without diversion failure at last patient contact. Secondary outcomes included overall survival and diversion success. RESULTS:After a median follow-up period of 35.7 months, the primary outcome was observed in 42 PP patients (54%) and in 76 PN patients (68%) (adjusted hazard ratio [aHR] 2.45, 95% CI 1.42-4.22; p = 0.001). PP patients who underwent endoscopic diversion had a worse primary event rate (aHR 6.47, 95% CI 2.40-17.42; p < 0.001). Death from any cause occurred in 16 PP patients (21%) and 9 PN patients (8%) (aHR 3.47, 95% CI 1.44-8.37; p = 0.006). Diversion failure occurred in 28 PP patients (36%) and 29 PN patients (26%) (aHR 2.24, 95% CI 1.31-3.85; p = 0.003). CONCLUSIONS:In this study, Paenibacillus detection in the CSF at the time of hydrocephalus surgery was associated with a significantly increased rate of the composite of diversion failure or death, death, and diversion failure, and was particularly increased for patients who had an endoscopic diversion.

Vancomycin-resistant Enterococcus faecium (VRE) poses a global public health threat, with particularly severe ramifications in low-resource settings. While E. faecium is commonly a commensal organism in the human gut, the acquisition of vancomycin resistance has contributed to the emergence of VRE as a major cause of hospital-acquired infections, especially in vulnerable populations. This study investigates the genetic characteristics of VRE isolated from hospitalized patients in Lebanon, focusing on antimicrobial resistance (AMR) phenotypes and the underlying resistome. We collected VRE isolates from patients at the time of admission or during routine screenings for multidrug-resistant pathogens. The isolates were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and screened for antimicrobial susceptibility using the disk diffusion and E-test methods. Whole genome sequencing was conducted using Illumina technology, and bioinformatics analyses were carried out to identify the resistome, sequence types, plasmid types, and virulence genes. Additionally, we analyzed previously GenBank-deposited VRE genomes from Lebanon to assess genetic relationships. Our VRE isolates carried multiple acquired AMR genes and chromosomal mutations, exhibiting resistance to vancomycin, telavancin, ampicillin, erythromycin, norfloxacin, levofloxacin, and nitrofurantoin. The isolates belonged to three subtypes: ST203 (67%), ST612 (22%), and a novel ST2711 (11%), all of which belonged to CC17, a globally prevalent hospital-associated lineage known for high levels of AMR and hospital outbreaks. Core-genome single nucleotide variants (SNVs) phylogenetic analysis revealed that the ST203 isolates clustered with the previously GenBank-deposited ST203 Lebanese genomes. Taken together, these findings highlight the growing VRE burden in low-resource countries, emphasizing the need for enhanced surveillance and alternative treatment strategies. IMPORTANCE:The healthcare system in Lebanon faces substantial challenges due to ongoing economic instability and limited resources, creating a conducive environment for the spread of antimicrobial resistance. Vancomycin-resistant Enterococcus faecium (VRE) represents a growing public health threat, yet studies addressing its genetics in Lebanon are scarce. This study provided critical insights into the genomic features of VRE in clinical settings, highlighting the potential clonal dissemination of multidrug-resistant isolates carrying the vanHAX operon and belonging to CC17, a globally prevalent, hospital-associated lineage. Resistance to novel antimicrobials, such as telavancin, dalbavancin, and eravacycline, is alarming and necessitates immediate action to preserve these critical last-resort interventions. Notably, the identification of clonal spread and a novel sequence type (ST2711) within Lebanese hospitals, alongside resistance to last-resort antimicrobials, highlights the dynamic evolution of VRE and the urgent need to strengthen antimicrobial stewardship programs in Lebanon and beyond. Addressing this challenge requires integrated One Health strategies.

This study aimed to evaluate the role of early effective antibiotic therapy in preventing secondary meningitis as a sequelae of bacterial bloodstream infections (BSI).In this multicenter cohort study, we identified blood cultures that were positive for Group B Streptococcus (GBS), Staphylococcus aureus, Escherichia coli, and other non-E. coli gram-negative bacteria that had a corresponding cerebrospinal fluid sample collected ≤7 days after the positive blood culture among infants discharged from a neonatal intensive care unit managed by the Pediatrix Medical Group 2002 to 2020. The odds of secondary meningitis for early effective antibiotic therapy versus delayed antibiotic therapy were compared using an adjusted logistic regression model. The odds of secondary meningitis following GBS BSI were compared for infections treated with empirical vancomycin versus β-lactam antibiotic.Secondary meningitis was identified in 11% of 5,967 BSI. Early effective antibiotic therapy was not associated with a reduced odds of secondary meningitis for GBS (adjusted odds ratio [aOR]: 1.17; 95% confidence interval [CI]: 0.82-1.66) or E. coli (aOR: 1.06; 95% CI: 0.82-1.38); however, was associated with decreased odds for non-E. coli gram-negative bacteria (aOR: 0.69; 95% CI: 0.49-0.98) and S. aureus (aOR: 0.51; 95% CI: 0.34-0.74). GBS BSIs were more often complicated by meningitis when vancomycin was used empirically compared with β-lactam antibiotic (aOR: 2.01; 95% CI: 1.28-3.14).Early effective antibiotic therapy for BSI in infants did not reduce the odds of secondary meningitis caused by GBS or E. coli; however, early effective antibiotic therapy did reduce episodes due to non-E. coli gram-negative bacteria and S. aureus. · Early effective antibiotic therapy in the setting of non-E. coli gram-negative bacteria and S. aureus BSI was associated with reduced odds of secondary meningitis.. · Early effective antibiotic therapy for BSI in infants was not found to reduce the odds of secondary meningitis caused by GBS or E. coli.. · GBS BSIs were more commonly complicated by meningitis when vancomycin was used empirically compared with a β-lactam antibiotic..

We describe the case of an infant who presented with simple rhinovirus/enterovirus bronchiolitis whose condition worsened with rapid progression to multiple organ dysfunction syndrome (MODS). The patient was presumed to have either primary or secondary hemophagocytic lymphohistiocytosis (HLH), and treatment was initiated using dexamethasone, anakinra, and intravenous immunoglobulin to modulate the immune system. Due to the organ dysfunction, the use of etoposide was avoided and instead, emapalumab, an interferon gamma antagonist, was administered at a dose of 6 mg/kg. The patient's organ failure improved, and the levels of inflammatory markers decreased. The flow cytometry analysis revealed that cytotoxic cells lacked perforin expression, and subsequent genetic analysis confirmed homozygous pathogenic mutations in the perforin gene. This case highlights the potential avoidance of etoposide in cases of primary HLH, the possible benefit of an elevated initial dose of emapalumab, and the contribution offered by a multi-specialty team approach to complex diagnosis.

Resistant and refractory cytomegalovirus (CMV) viremia can limit the provision of chemotherapy due to myelosuppression and end-organ dysfunction. Few therapies are available for children with clinically significant CMV viremia. We successfully used maribavir for a 4-year-old patient with lymphoma to complete his chemotherapy course. Resistance to maribavir did result after many months of therapy.

Abstract Background Dysphagia is the main symptom for patients diagnosed with cancer in the oesophagus or gastro oesophageal junction (GOJ), but there are lack of recent studies confirming this. Several studies have reported relief of dysphagia during neoadjuvant treatment but there might also be side effects affecting nutritional status resulting in weight loss. We wanted to investigate if there are differences between the mainly used neoadjuvant treatments in Sweden today, namely CROSS, FLOT, and other treatments (OT), for example prolonged neoadjuvant treatment due to oligometastatic cancer. Aims of this study was to investigate dysphagia, weight changes, and main causes of healthcare referral. Methods All patients with cancer in the oesophagus or GEJ receiving neoadjuvant treatment followed by subsequent oesophagectomy at Karolinska University hospital in Stockholm, Sweden January 2017 to June 2022 were included in the study. Data were extracted from the local prospective database and the electronic medical records. To grade the severity of dysphagia we used the five graded Ogilvie score. The weight as well as the dysphagia score was evaluated before oncological treatment and before surgery. The patients were divided into three groups, them receiving CROSS, FLOT and OT, respectively. Results There were 69 patients receiving CROSS, 68 receiving FLOT and 28 receiving OT. The patients experienced relief of dysphagia in all groups, CROSS p<0.001, FLOT p<0.001 and OT p<0.001. Patients receiving CROSS lost 1.32 kg weight (-8.5 kg to 6.4 kg), while those receiving FLOT gained 0.08 kg (-5.5 kg to 11.1 kg) and OT lost 0.49 kg (-20 kg to 8 kg). Dysphagia was the main symptom for patients diagnosed with oesophageal cancer or GEJ (65%), other causes (9%), followed by anaemia (8 %), reflux (6%), pain (6%) and au passant (5%). Conclusion All groups experienced statistically significant relief of dysphagia during the neoadjuvant treatments. There were small differences in weight changes between the treatment groups, although patients undergoing chemoradiotherapy treatment lost more weight compared to those only receiving chemotherapy. Main cause of referral is dysphagia. Key words Oesophageal cancer, neoadjuvant therapy, dysphagia, weight

Multisystem inflammatory syndrome in children (MIS-C) has been extensively described in patients following severe acute respiratory syndrome coronavirus 2 infection. There are now questions about what MIS-C may look like in vaccinated children. Multisystem inflammatory syndrome in children has many clinical and laboratory features in common with other inflammatory disorders including Kawasaki disease and toxic shock syndrome. Rheumatologic conditions can present with similar musculoskeletal complaints and elevated inflammatory markers. Laboratory markers and clinical symptoms of MIS-C usually improve once therapy is begun. We describe a child with persistent thrombocytopenia as an example of variable presentation of MIS-C in vaccinated children. This case report discusses an atypical progression of MIS-C in a vaccinated child with a known prior positive COVID-19 polymerase chain reaction (PCR) test. She presented with nonspecific abdominal pain and fever and was found to have elevated inflammatory markers, lymphopenia, and thrombocytopenia. Intravenous immunoglobulin and steroid treatment failed to induce rapid recovery in her clinical condition or thrombocytopenia. Rheumatologic, hematologic, oncologic, and infectious causes were considered and worked up due to the uncertainty of her case and persistence of pancytopenia but ultimately were ruled out with extensive testing and monitoring. It was key to include a broad differential including viral-induced bone marrow suppression, idiopathic thrombocytopenic purpura, secondary hemophagocytic lymphohistiocytosis, systemic juvenile idiopathic arthritis, and malignancy. The spectrum of MIS-C and response to treatment continues to evolve, and prior vaccination in this child’s case complicated the clinical picture further. Additional evaluation of MIS-C in vaccinated cases will permit characterization of the range of MIS-C presentation and response to standard therapy.

Background Paenibacillus thiaminolyticus is a cause of postinfectious hydrocephalus among Ugandan infants. To determine whether Paenibacillus spp is a pathogen in neonatal sepsis, meningitis, and postinfectious hydrocephalus, we aimed to complete three separate studies of Ugandan infants. The first study was on peripartum prevalence of Paenibacillus in mother-newborn pairs. The second study assessed Paenibacillus in blood and cerebrospinal fluid (CSF) from neonates with sepsis. The third study assessed Paenibacillus in CSF from infants with hydrocephalus.Methods In this observational study, we recruited mother-newborn pairs with and without maternal fever (mother- newborn cohort), neonates (aged <= 28 days) with sepsis (sepsis cohort), and infants (aged <= 90 days) with hydrocephalus with and without a history of neonatal sepsis and meningitis (hydrocephalus cohort) from three hospitals in Uganda between Jan 13, 2016 and Oct 2, 2019. We collected maternal blood, vaginal swabs, and placental samples and the cord from the mother-newborn pairs, and blood and CSF from neonates and infants. Bacterial content of infant CSF was characterised by 16S rDNA sequencing. We analysed all samples using quantitative PCR (qPCR) targeting either the Paenibacillus genus or Paenibacillus thiaminolyticus spp. We collected cranial ultrasound and computed tomography images in the subset of participants represented in more than one cohort.Findings No Paenibacillus spp were detected in vaginal, maternal blood, placental, or cord blood specimens from the mother-newborn cohort by qPCR. Paenibacillus spp was detected in 6% (37 of 631 neonates) in the sepsis cohort and, of these, 14% (5 of 37 neonates) developed postinfectious hydrocephalus. Paenibacillus was the most enriched bacterial genera in postinfectious hydrocephalus CSF (91 [44%] of 209 patients) from the hydrocephalus cohort, with 16S showing 94% accuracy when validated by qPCR. Imaging showed progression from Paenibacillus spp-related meningitis to postinfectious hydrocephalus over 1-3 months. Patients with postinfectious hydrocephalus with Paenibacillus spp infections were geographically clustered.Interpretation Paenibacillus spp causes neonatal sepsis and meningitis in Uganda and is the dominant cause of subsequent postinfectious hydrocephalus. There was no evidence of transplacental transmission, and geographical evidence was consistent with an environmental source of neonatal infection. Further work is needed to identify routes of infection and optimise treatment of neonatal Paenibacillus spp infection to lessen the burden of morbidity and mortality.Funding National Institutes of Health and Boston Children's Hospital Office of Faculty Development.Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral infection that emerged in December 2019, leading to the COVID-19 pandemic. Despite significant research, there are still significant knowledge gaps, particularly with regards to COVID-19 in children and the impact of respiratory virus co-infection. Methods A retrospective chart review was conducted at Penn State Children’s Hospital including children who tested positive for SARS-CoV-2 by multiplex polymerase chain reaction from nasopharyngeal swabs between March 2020 and June 2022. Demographics, symptoms, clinical features, and treatments of patients who tested positive for SARS-CoV-2 alone were compared to those who had co-detection of another respiratory virus. Results A total of 464 episodes of SARS-CoV-2 detection were included, with 123 (26.5%) involving of co-detection of another respiratory virus. Patients with viral co-detection more commonly presented with upper respiratory tract infection (URI) symptoms and, cough, and were more likely to require any supplemental oxygen therapy. However, there were no differences in rates of mechanical ventilation, intensive care unit admission, mortality, or receipt of SARS-CoV-2 specific antivirals [Table 1]. Co-detections occurred throughout the study period [Figure 1]. Of the 123 episodes of viral co-detection, 99 (80.5%) had one other virus detected. The most commonly co-detected virus was rhino/enterovirus, which was found in 100 (81.3%) of the co-detection episodes. Outcomes of SARS-CoV-2 and Viral Co-Detection Numbers of SARS-CoV-2 and Viral Co-Detections Conclusion This study provides insight into the impact of respiratory virus co-infections in pediatric COVID-19. Co-infection was more often associated with URI symptoms, but otherwise appeared clinically similar to SARS-CoV-2 mono-detection. Additionally, while children with co-infection more often needed any supplemental oxygen, there were no differences with regard to other markers of clinical severity. As SARS-CoV-2 continues to circulate with other respiratory viruses, ongoing studies will be needed to determine if alternative treatment strategies are needed. Disclosures Jessica E. Ericson, MD, MPH, Abbvie: Advisor/Consultant

Background Paenibacillus thiaminolyticus may be an underdiagnosed cause of neonatal sepsis. Methods We prospectively enrolled a cohort of 800 full-term neonates presenting with a clinical diagnosis of sepsis at 2 Ugandan hospitals. Quantitative polymerase chain reaction specific to P. thiaminolyticus and to the Paenibacillus genus were performed on the blood and cerebrospinal fluid (CSF) of 631 neonates who had both specimen types available. Neonates with Paenibacillus genus or species detected in either specimen type were considered to potentially have paenibacilliosis, (37/631, 6%). We described antenatal, perinatal, and neonatal characteristics, presenting signs, and 12-month developmental outcomes for neonates with paenibacilliosis versus clinical sepsis due to other causes. Results Median age at presentation was 3 days (interquartile range 1, 7). Fever (92%), irritability (84%), and clinical signs of seizures (51%) were common. Eleven (30%) had an adverse outcome: 5 (14%) neonates died during the first year of life; 5 of 32 (16%) survivors developed postinfectious hydrocephalus (PIH) and 1 (3%) additional survivor had neurodevelopmental impairment without hydrocephalus. Conclusions Paenibacillus species was identified in 6% of neonates with signs of sepsis who presented to 2 Ugandan referral hospitals; 70% were P. thiaminolyticus. Improved diagnostics for neonatal sepsis are urgently needed. Optimal antibiotic treatment for this infection is unknown but ampicillin and vancomycin will be ineffective in many cases. These results highlight the need to consider local pathogen prevalence and the possibility of unusual pathogens when determining antibiotic choice for neonatal sepsis.

Neonatal infections due to Paenibacillus species have increasingly been reported over the last few years. We performed a structured literature review of human Paenibacillus infections in infants and adults to compare the epidemiology of infections between these distinct patient populations. Thirty-nine reports describing 176 infections met our inclusion criteria and were included. There were 37 Paenibacillus infections occurring in adults caused by 23 species. The clinical presentations of infections were quite variable. In contrast, infections in infants were caused by only 3 species: P. thiaminolyticus (112/139, 80%), P. alvei (2/139, 1%) and P. dendritiformis (2/139, 1%). All of the infants with Paenibacillus infection presented with a sepsis syndrome or meningitis, often complicated by extensive cerebral destruction and hydrocephalus. Outcomes were commonly poor with 17% (24/139) mortality. Cystic encephalomalacia due to brain destruction was common in both Ugandan and American cases and 92/139 (66%) required surgical management of hydrocephalus following their infection. Paenibacillus infections are likely underappreciated in infants and effective treatments are urgently needed.