Vancomycin and phage COP-80B combination therapy for Staphylococcus epidermidis periprosthetic joint infections: a preclinical mouse studyŠtilec, Vida; Marušić, Monika; Motaln, Helena; Gregorič, Klara; Draksler, Urška; Čater, Maša; Izlakar, Jani; Janež, Nika; Trebše, Rihard; Horvat, Simon; Peterka, Matjaž
doi: 10.1007/s10096-026-05561-xpmid: 42298263
The increasing number of joint replacement surgeries has led to an increase in periprosthetic joint infections (PJI). Chronic PJI caused by Staphylococcus epidermidis is very common and challenging to treat, prompting interest in bacteriophage therapy. Preclinical studies are essential for optimizing phage administration routes and dosages. Here, phage replication and bacterial growth inhibition using phage and vancomycin were first assessed in vitro. Then, chronic PJI was induced in mice using biofilm-coated titanium implants inoculated with S. epidermidis COB-SE3 to evaluate the efficacy of phage COP-80B and vancomycin therapy. Mice received one intra-articular and two intraperitoneal phage doses over three days, along with vancomycin administered twice daily for five days. Four weeks after implantation, we quantified and compared bacterial loads in periarticular tissues and implants across four groups: untreated controls, phage monotherapy, vancomycin monotherapy, and phage-vancomycin combination. Infection persistence was lower than expected, limiting the ability to detect treatment effects and assess therapeutic efficacy in this low-virulence model. Intra-articular administration of 1010 PFU of COP-80B did not alter plasma alanine aminotransferase levels, indicating no hepatotoxicity. Bacterial isolates remained susceptible to both phage and vancomycin, while phage-neutralizing antibodies developed during treatment. Overall, this study evaluates phage-vancomycin therapy while also contributing a murine model that advances methodological development for chronic S. epidermidis PJI research, with additional refinement of infection kinetics needed to reliably assess therapeutic efficacy.
Risk factors associated with apyrexia during bacteraemia: a prospective multicenter cohort studyRoger, Pierre-Marie; Bocquillon, Lucie; Lemasson, Arnaud; Arcese, Guillaume; Arhire, Andréi; Strzelecki, Anne-Claire; Darmon, Anne; Keita-perse, Olivia
doi: 10.1007/s10096-026-05567-5pmid: N/A
Apyrexia during bacteraemia is not rare and is associated with diagnostic uncertainty. Our aim was to search for risk factors of apyrexia in patients with bacteraemia. This was a prospective bicentric study including all positive blood cultures (PBC) over twenty-seven months. The laboratory gave the PBC results to the infectious disease specialist in real-time. Data was collected from digital medical files. Contaminated blood cultures were not included. Apyrexia was defined by the absence of fever in recent medical history, associated with a body temperature < 38 °C at the initiation of clinical management, confirmed at the time of blood sampling, and constantly observed until PBC. We used logistic regression to figure out the risk factors of apyrexia despite bacteraemia. From January 2023 to March 2025, 423 PBCs were communicated to ID specialists, from which we excluded 71 contaminated ones (17%). Among 352 bacteraemia mainly due to Enterobacterales (n = 165, 47%) and Staphylococcus spp. (n = 83, 24%), apyrexia was observed in 72 cases (20%). The latter were without antibiotic prescription before PBC compared to patients with fever: 35 vs. 13% respectively (p < 0.001). In a multivariate analysis, apyrexia was associated with three risk factors: admission in oncology: adjusted odds ratio (aOR) [95% CI]: 2.03 [1.10–3.73], an enterococcal bacteraemia: 4.01 [1.43–11.36], while urinary infections were protective of apyrexia: 0.16 [0.07–0.39]. Apyrexia during bacteraemia was not rare except in urinary-tract infections and was associated with admission in oncology and Enterococcus spp.
Risk factors for multidrug resistance and mortality in healthcare-associated neonatal gram-negative bloodstream infectionsTurgut, Hatice; Özdemir, Ramazan; Memişoğlu, Funda
doi: 10.1007/s10096-026-05565-7pmid: 42260230
PurposeThis study aimed to characterize pathogen distribution and antimicrobial resistance patterns of gram-negative bloodstream infections in a tertiary neonatal intensive care unit and to determine which factors were associated with multidrug resistance (MDR) and 28-day mortality.MethodsIn this retrospective cohort study, 197 neonates with healthcare-associated gram-negative bloodstream infections diagnosed between January 2010 and December 2025 were included. Demographic, perinatal, clinical, and microbiological data were extracted from electronic medical records. Factors associated with MDR infection and 28-day mortality were evaluated using univariable and multivariable logistic regression analyses.ResultsOf the 197 neonates, 114 (57.9%) had MDR gram-negative bloodstream infections. Klebsiella spp. was the most frequently isolated pathogen (51.3%), followed by Acinetobacter spp. (23.9%) and Escherichia coli (14.7%). Extended-spectrum beta-lactamase production was detected in 68.6% of isolates, MDR in 57.9%, and carbapenem resistance in 39.1%. Acinetobacter spp. showed the highest rates of carbapenem resistance (95.7%) and MDR (97.9%). In multivariable analysis, older postnatal age at infection onset, mechanical ventilation, and previous carbapenem exposure were independently associated with MDR infection, whereas appropriate empirical therapy was protective. Overall, 83 neonates (42.1%) died within 28 days. Mechanical ventilation and inotropic support were independently associated with mortality, while appropriate empirical therapy remained independently protective. MDR status and pathogen distribution were not independently associated with mortality.ConclusionNeonatal gram-negative bloodstream infections were characterized by a high burden of MDR. Mortality was more strongly related to indicators of illness severity than to microbiological resistance profiles. Appropriate empirical therapy was protective against both MDR infection and 28-day mortality.
Congenital tuberculosis transmitted via the placenta: identification by metagenomic next-generation sequencingGao, Xingchen; Qin, Ruiqi; Li, Shengjin; Yang, Yanli; He, Jing
doi: 10.1007/s10096-026-05564-8pmid: N/A
Background: Congenital tuberculosis (CTB) is a rare disease with high mortality in neonates. Early diagnosis is crucial but often delayed due to atypical clinical and imaging manifestations. Case presentation: We report a 36-day-old female infant presenting with recurrent fever. Laboratory data showed leukocytosis and neutrophilia with mildly elevated C-reactive protein. Chest computed tomography revealed extensive ground-glass opacities, multiple subpleural nodules, and necrotic hilar and mediastinal lymphadenopathy. The asymptomatic mother was subsequently found to have diffuse miliary nodules on chest CT. Conventional tuberculosis tests (acid-fast smear, culture, GeneXpert, T-SPOT.TB) were negative in both the infant and mother. Metagenomic next-generation sequencing (mNGS) of the placental tissue detected 10 specific Mycobacterium tuberculosis sequences, and Ziehl-Neelsen staining confirmed acid-fast bacilli. Both mother and infant responded well to anti-tuberculosis therapy. Conclusions: CTB should be considered in neonates with persistent pulmonary infection unresponsive to broad-spectrum antibiotics. Examination of placental tissue using mNGS is a valuable diagnostic tool for confirming transplacental tuberculosis transmission.
RAST+: pre-positivity application of EUCAST RAST using BACTEC FX growth detection plots — a proof-of-concept studyDemirel, Kutay; Anıl, Ali Fazıl; Kibar, Neşe İnal; Atik, Tuğba Kula; Şener, Aslı Gamze; Sancak, Banu
doi: 10.1007/s10096-026-05511-7pmid: N/A
BackgroundTimely antimicrobial susceptibility testing (AST) from blood cultures is crucial to optimize antimicrobial therapy.PurposeThe aim of this study is to accelerate AST results by applying EUCAST RAST method before blood culture positivity (RAST+) by utilizing Growth and Detection Plots (GDPs) generated by the BD BACTEC FX (Becton Dickinson, Sparks, MD, USA) system.MethodsQuality control strains and 20 clinical isolates were inoculated into BACTEC™ Plus Aerobic bottles and incubated in the BD BACTEC FX system. GDPs were continuously monitored to detect the steeping phase indicative of early bacterial growth prior to signal positivity. Bottles were removed at the beginning of the steeping phase and RAST+ was performed using 300 µL inoculum. Zone diameters were interpreted according to EUCAST RAST guidelines.ResultsThe RAST+ method yielded inhibition zones within acceptable ranges both for 150 µL and 300 µL inocula for quality control strains, with improved readability at 300 µL. Of 185 antibiotic disks tested, 159 (85.9%) produced interpretable results by using a 300 µL inoculum. When compared to the reference method, RAST+ achieved a categorical agreement of 96.2%. The rates of very major, major, and minor errors were each 1.3%, indicating a high level of concordance and diagnostic reliability.ConclusionsTo the best of our knowledge, this is the first study to analyze GDPs in order to predict blood culture positivity. Furthermore, it is also the first to apply rapid AST directly from blood culture bottles (RAST) before the positivity signal appears. RAST+ is a proof-of-concept approach for detecting bacterial growth and performing antimicrobial susceptibility testing directly from blood cultures before they signal positive, potentially reducing turnaround times (TAT) and supporting earlier clinical decision-making.
Human parvovirus B19 infection in a Spanish healthcare area: epidemiology, clinical spectrum, and factors associated with hospitalizationMuela-Molinero, Alberto; Romero-Calvo, Alicia; Ortiz-de-Urbina-Fernández, Pablo; Calvo-Rubio, Lara Victoria; Cuellar-de-la-Rosa, Alejandro; Pintor-Rey, Marino; Dios-Diez, Paula
doi: 10.1007/s10096-026-05560-ypmid: N/A
PurposeTo describe the epidemiological, clinical, laboratory, and healthcare-related characteristics of human parvovirus B19 (PVB19) infection diagnosed in a Spanish healthcare area during 2019–2024, and to identify factors associated with hospitalization, particularly in adult patients.MethodsWe performed a retrospective, single-center cohort study in the León healthcare area, Spain, including all hospital-attending patients with microbiologically confirmed acute PVB19 infection diagnosed between January 2019 and December 2024. Acute infection was defined by positive PVB19 IgM and/or PVB19 DNA detection by qualitative PCR in a compatible clinical episode; isolated IgG positivity or incomplete serology without microbiological confirmation was not considered sufficient. Adult and pediatric patients were compared according to clinical manifestations, laboratory findings, and hospitalization status. A multivariate binary logistic regression model was used to identify factors associated with hospitalization in adults.ResultsA total of 81 patients were included, 51 adults (63%) and 30 pediatric patients (37%). Most cases occurred during spring and summer, with a marked rebound after 2020 and a peak in 2024. Fever, arthromyalgias, and cutaneous manifestations were the most frequent clinical findings. Lymphopenia and anemia were the most common laboratory abnormalities. Hospitalization was required in 31 patients (38.3%), more frequently in adults than in children (47.1% vs. 23.3%). In adults, hospitalization was associated with cytopenias and higher C-reactive protein levels. In exploratory adjusted analysis, relevant cytopenia was associated with hospitalization (adjusted OR 7.31, 95% CI 1.07–49.73; p = 0.042).ConclusionsPVB19 infection may impose a relevant healthcare burden, particularly in adults. Cytopenias appear to define a more severe hematological phenotype associated with hospitalization and may help identify patients requiring closer clinical monitoring.