Search Results (406)

Background/Objectives: Immunocompromised children undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) for hematologic disorders face a high risk of serious, life-threatening infections caused by multidrug-resistant (MDR) bacteria. Cefiderocol is a novel siderophore cephalosporin, indicated for use in adult patients with MDR Gram-negative infections. Clinical data in immunocompromised children are limited. To report a multicenter real-life experience from the Infection Working Group of the Italian Pediatric Hematology and Oncology Association (IWG-AIEOP) on the use of cefiderocol in treating pediatric onco-hematologic patients with severe, high-risk infections. Methods: Multicenter retrospective collection of infectious episodes treated with cefiderocol, from January 2021 to December 2024, in patients 18 years or younger, after treatment for malignancies or undergoing HSCT in the AIEOP network, part of a prospective, observational study on the etiology and outcome of febrile episodes among 24 AIEOP centers (code NCT06419426). Results: Fifteen episodes of MDR, life-threatening Gram-negative infections treated with cefiderocol in 13 pediatric onco-hematologic patients were collected. There were eight males and five females, mainly affected by acute leukemia (six lymphoblastic and four myeloid, three other hematologic malignancies). The median age was 11.1 years (range 1–17.4 years), and the median weight was 37.8 kg (range 8–65). Bloodstream infection occurred in 10 of 15 episodes. Pseudomonas aeruginosa, Klebsiella pneumoniae, and Stenotrophomonas maltophilia were isolated in 11, 3, and 1 episodes, respectively. Notably, 11 of 15 isolated pathogens carried a metallo-beta-lactamase (MBL) gene (Verona integron-encoded, VIM, n = 10; New Delhi, NDM, n = 1). All patients achieved infection resolution and were alive and infection-free 90 days after infection onset. Conclusions: Cefiderocol was well tolerated and showed encouraging, favorable clinical outcomes, without serious adverse effects. Full article

Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of invasive disease, yet contemporary genomic data from Canada remain scarce. We investigated 56 cases of invasive SDSE infection identified between 2018 and 2022 in two major tertiary care teaching hospitals in Toronto, Ontario, and characterized 49 corresponding isolates by whole-genome sequencing. Nearly three-quarters of infections were caused by the globally expanding ST20 emm type stG62647 lineage. Patients infected with this lineage were significantly older than those infected with non-ST20 lineages across both bloodstream and non-blood infections. Core-genome phylogenetic analysis revealed a highly clonal ST20 cluster, although two isolates had divergent emm types suggesting recombination at the emm locus. Non-ST20 lineages were numerically smaller and genetically more heterogeneous, including distinct sublineages within ST3 and ST34. All isolates were susceptible to β-lactams and vancomycin. Resistance to tetracycline, erythromycin, and clindamycin was detected in a subset of isolates and was associated with genes tetM, tetO, ermA, ermB, and msrD. Several antimicrobial resistance determinants were located on mobile genetic elements, including integrative and conjugative elements. Our findings provide a contemporary genomic view of invasive SDSE in Toronto, highlighting the dominance of the ST20 stG62647 lineage in agreement with recent global observations. Full article

The non-albicans Candida species Candida tropicalis is an opportunistic fungal pathogen that forms a robust gel-like biofilm on polymeric prosthetic materials. These biofilms are embedded in an extracellular polymeric substance that retains large amounts of water, resulting in a hydrogel-like matrix that protects fungal cells, increases antifungal resistance, and contributes to the biofouling of these prosthetic materials. Biofouling is the unwanted colonization and accumulation of microbial communities on material surfaces, which alters their function and compromises clinical performance. Clinically, it is significant because it is linked to recurrent urinary tract infections, bloodstream infections, and persistent device-related infections, which often result in therapeutic failure and device malfunction. Polymers such as silicone elastomer, polypropylene, polystyrene, polyurethane, polyethylene, and polyvinyl chloride are widely used in catheters, surgical meshes, implants, and prostheses because of their durability, flexibility, and biocompatibility, yet their surface properties often encourage microbial adhesion and biofilm formation. This review emphasizes that the gel-like biofilm architecture of C. tropicalis underpins its persistence and resistance, while also highlighting promising antifungal strategies being developed to mitigate these infections. Notably, palmitic acid has been shown to disrupt mature biofilms by lowering ergosterol and inducing oxidative stress, whereas C-10 massoia lactone damages the extracellular matrix and suppresses hyphal growth. Drug repurposing approaches, such as combining minocycline with fluconazole, restore susceptibility in resistant isolates and demonstrate synergistic antibiofilm activity. Additionally, biomaterial-based interventions, such as chitosan coatings on silicone surfaces, significantly reduce fungal adhesion and biofilm formation. Together, these findings reflect a translational shift toward integrating natural products, repurposed drugs, and functionalized biomaterials into antifungal development. Understanding biofouling and these emerging strategies is crucial for developing effective control measures against C. tropicalis biofilms and for guiding the design of infection-resistant prosthetic devices. Full article

Background: We aimed to describe the clinical and microbiological characteristics of biliary-source bloodstream infections (bBSIs) in patients with malignancies and identify risk factors for recurrence. Methods: All bBSI episodes in patients with active solid tumors during 2021–2025 were retrospectively reviewed. Independent risk factors for recurrent bBSI and mortality were identified. A previously published recurrence risk score was externally validated. Results: Overall, 136 patients experienced 199 bBSI episodes. Pancreatic (36.7%) and biliary tract (33.2%) were the most common cancers, and 60.8% had metastatic disease. The main pathogens were Escherichia coli (43.2%), Klebsiella pneumoniae (24.1%), and Enterococcus faecium (19.1%), and multidrug-resistant organisms accounted for 19.1%. Inappropriate empirical antibiotic treatment (IEAT) occurred in 37.2% and was independently associated with increased 30-day mortality, together with metastatic disease and septic shock. Thirty-day mortality was 24.6%. Recurrent bBSI occurred in 35.7% and was independently associated with biliary tract cancer, previous multidrug-resistant isolation, and prior hospitalization for suspected biliary infection. The externally validated recurrence score showed excellent discrimination (AUC 0.815). Conclusions: bBSI in oncology patients is associated with high rates of MDR pathogens, IEAT, recurrence, and mortality. A simple clinical score may identify patients at high risk of recurrence and guide preventive strategies. Full article

Quorum sensing (QS) represents a promising target for anti-virulence therapy; however, effective pharmacological intervention requires a detailed understanding of regulatory network architecture and environmental context. In Klebsiella pneumoniae, the orphan LuxR-type receptor SdiA lacks a cognate LuxI synthase and instead detects exogenous acyl-homoserine lactones (AHLs), positioning it as an inter-species signal integrator. Here, we demonstrate that SdiA functions as a context-dependent regulator whose impact on biofilm formation and virulence gene expression is gated by environmental AHL availability. Using isogenic ΔluxS, ΔsdiA, and ΔluxSΔsdiA mutants in a clinical bloodstream isolate, we show that under AHL-limited conditions, SdiA promotes baseline biofilm development, whereas in the presence of exogenous C6-HSL, it restrains excessive biofilm maturation. Two-way ANOVA confirmed significant genotype, treatment, and interaction effects, establishing that SdiA-mediated regulation is signal contingent. We further investigated the halogenated thiolactone meta-bromo-thiolactone (mBTL), previously described as a QS inhibitor in Pseudomonas aeruginosa. In K. pneumoniae, mBTL acts as a context-selective modulator rather than a simple inhibitor. Under AHL-limited conditions, mBTL phenocopied ΔsdiA, reducing biofilm formation and inducing overlapping transcriptional profiles. In contrast, under AHL-replete conditions, mBTL opposed SdiA-dependent gene expression, consistent with competitive antagonism of ligand-bound receptor. RNA-seq analysis revealed substantial concordance between ΔsdiA and WT + mBTL under AHL-free conditions, with the inversion of transcriptional directionality in the presence of C6-HSL. The findings redefine SdiA as a conditional quorum-sensing integrator and identify mBTL as a ligand-context-dependent modulator of LuxR-type signaling. Our results highlight the necessity of evaluating anti-virulence compounds across relevant signal environments and introduce receptor state-selective modulation as a strategic framework for targeting hybrid quorum-sensing systems in polymicrobial pathogens. Full article

Background: Fungemia caused by non-Candida yeasts is rare but represents an emerging clinical problem that remains less well recognized and studied. These organisms often exhibit intrinsic resistance or reduced susceptibility to commonly used empirical antifungal agents, such as fluconazole and echinocandins. This poses significant challenges for empirical antifungal therapy. Objectives: To describe the clinical characteristics, antifungal treatments, and outcomes of pediatric patients with bloodstream infections due to non-Candida yeasts and to summarize the antifungal susceptibility profiles of available isolates. Methods: This retrospective study reviewed all episodes of fungemia caused by non-Candida yeasts at a tertiary pediatric center between 1 January 2020 and 1 September 2025. Results: Of the 139 yeast-related fungemia episodes identified during the study period, five (3.6%) were caused by non-Candida yeasts: three by Trichosporon spp., one by Rhodotorula mucilaginosa, and one by Magnusiomyces clavatus (formerly Saprochaete clavatus). Two cases occurred as breakthrough infections under ongoing antifungal treatment. Empirical antifungal treatments most often included amphotericin B, fluconazole, or echinocandins. The median time to species-level identification after the first positive culture result was six days (range 4–7), highlighting a considerable delay that may critically affect clinical management. Overall mortality was 40%, while attributable mortality due to non-Candida fungemia was 20%. Conclusions: Non-Candida yeasts, although infrequent, represent clinically important pathogens in pediatric fungemia due to their potential resistance to standard empirical antifungal agents. Early species-level identification and awareness of expected susceptibility patterns are essential to guide appropriate initial therapy and improve outcomes. Full article

Background: Staphylococcus aureus bacteremia (SAB) is a common and life-threatening bloodstream infection often caused by methicillin-resistant SA (MRSA) isolates. Up to 35% of SAB patients fail to clear infection with gold-standard anti-MRSA antibiotics, even if the isolate meets susceptibility breakpoints in conventional assays in vitro. Such outcomes are termed persistent and may involve small colony variant (SCV) adaptation of SA in vivo. Methods: In this study, we assessed virulence phenotypes and mechanisms in persistent (PB) vs. resolving (RB) MRSA isolates from SAB. Results: Overall, PB isolates caused less hemolysis or biofilm formation than RB isolates, but proteolysis was equivalent. Attenuation of these virulence phenotypes increased longitudinally during the course of SAB. Although PB vs. RB isolates had similar human endothelial cell invasion rates, PB isolates more frequently formed SCVs intracellularly and inversely correlated with pH. Study PB and RB isolates exhibited distinct susceptibilities to prototypic human host defense peptides (HDPs), which were influenced by antibiotics and pH. Furthermore, mechanistic signatures of HDPs differed between PB and RB isolates. Conclusions: Together, these results reveal that MRSA isolates from PB vs. RB outcomes of SAB have differential virulence profiles that suggest coordinated immune subversion in PB. Understanding MRSA adaptations that promote persistence in SAB may enable innovative agents and strategies to address these challenging infections. Full article

Streptococcus suis is an emerging zoonotic pathogen that typically causes bacteremia or meningitis in humans, whereas vertebral osteomyelitis with epidural abscess is exceedingly rare and may be missed. We describe a 65-year-old farmer with fever and severe low back pain after long-term bare-handed handling of raw pig lungs. Pre-treatment blood cultures yielded S. suis identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). After transient improvement on empirical therapy, fever recurred with worsening lumbar pain. Contrast-enhanced magnetic resonance imaging (MRI) demonstrated multilevel thoracolumbar pyogenic spondylitis with an epidural abscess and a sub-ligamentous abscess beneath the posterior longitudinal ligament (PLL) extending from L2 to L5. Computed tomography-guided lumbar biopsy followed by tissue metagenomic next-generation sequencing (mNGS) detected S. suis, providing concordant evidence supporting pathogen involvement at the vertebral focus. The bloodstream isolate (SS-JX2025-01) was serotype 2, sequence type 7 (ST7). It remained susceptible to β-lactams and glycopeptides but was resistant to macrolide–lincosamide and tetracycline classes, consistent with erm(B), tet(O), tet(40), and ant(6)-Ia detected by whole-genome sequencing (WGS). Virulence profiling revealed an epf⁺/sly⁺/mrp⁻ pattern with multiple adhesins and immune-evasion factors, whereas canonical 89K pathogenicity island markers were absent. Core-genome phylogeny placed SS-JX2025-01 within the Chinese ST7 lineage associated with previous outbreaks. This biopsy-supported case expands the clinical spectrum of invasive S. suis infection, highlights the value of tissue mNGS as an adjunct for supporting deep-seated foci in zoonotic infections, and underscores the importance of occupational prevention in small-scale farming households. Full article

Background: The goal of this study was to characterize the microbial etiology, antimicrobial susceptibility, and temporal resistance trends of early-onset neonatal sepsis (EOS) pathogens in a tertiary neonatal intensive care unit over 10 years (2014–2023), assessing empirical therapy adequacy and mortality associations. Methods: Retrospective analysis was performed on the positive blood cultures of neonates with confirmed EOS, born between 1 January 2014 and 31 December 2023. Blood was aseptically collected into PEDS Plus/BC bottles, incubated using the BACTEC system, with pathogen identification by biochemical assays or MALDI-TOF MS. Susceptibility testing followed EUCAST disk-diffusion standards, with additional resistance assays. Results: Among 6631 NICU admissions, 39 neonates met EOS criteria (31 preterm, 8 term). In preterm infants, Gram-negative Enterobacterales—mainly E. coli (n = 20)—predominated, while GBS was most common in term infants. All GBS isolates (n = 7) were susceptible to benzylpenicillin and vancomycin. Although 90% of E. coli were ampicillin-resistant, 90–95% remained susceptible to third-generation cephalosporins, piperacillin–tazobactam, and aminoglycosides. Two E. coli isolates produced ESBL but remained susceptible to aminoglycosides and carbapenems. Mortality was higher in E. coli EOS (50%) than in GBS (0%) or other pathogens (25%), with borderline significance (p = 0.0547; adjusted RR 1.55, 95% CI 0.54–4.41). Ampicillin resistance was not associated with increased mortality. No annual resistance trends were observed. Conclusions: In this 10-year NICU cohort, the etiology of EOS differed markedly between preterm and term neonates. Recommended empirical ampicillin–aminoglycoside therapy demonstrated in vitro efficacy against most neonatal bloodstream isolates pending pathogen identification. However, the widespread ampicillin resistance, particularly among E. coli strains, supports consideration of cephalosporin–aminoglycoside combinations or meropenem monotherapy when rapid beta-lactam bactericidal activity is clinically essential. Mortality was higher in E. coli EOS, though not statistically significant, and unrelated to ampicillin resistance. Full article

Background: Antimicrobial resistance (AMR), particularly due to extended-spectrum beta-lactamases (ESBL), is a growing threat to public health in sub-Saharan Africa. This study investigates the prevalence, epidemiological characteristics, resistance patterns and resistance dynamic over time of ESBL-producing non-typhoidal Salmonella (NTS) bacteremia in Kisantu, Democratic Republic of Congo (DRC), from 2019 to 2022. Methods: A retrospective observational study used routine bloodstream infection data from the AMR network at Saint Luc Hospital in Kisantu. Blood cultures from suspected bacteremia cases were processed using standard microbiological techniques. Bacterial identification relied on biochemical reactions. Antibiotic susceptibility testing and ESBL-producing NTS detection were performed by disk diffusion following Clinical and Laboratory Standards Institute guidelines. Associations between ESBL production and patient characteristics (age, sex) were assessed using Pearson’s Chi-square test, and annual temporal trends in ESBL-producing NTS from 2019 to 2022 were analyzed by logistic regression using 2019 as the reference year. Results: Of the 19,430 blood cultures, 1681 NTS isolates were identified, and 1568 of these were screened for ESBL. ESBL prevalence was significantly associated with age (p = 0.007), peaking in children under 2 years, but not with sex (p = 0.570). Compared with 2019, the likelihood of isolating ESBL-producing NTS increased markedly through 2022, with adjusted probabilities rising from 58% to 87%, reflecting a strong upward temporal trend. High levels of extensively drug-resistant (94.1%) were observed. No carbapenem resistance was detected. Conclusions: ESBL-producing NTS bacteremia is rising in Kisantu, DRC, mainly affecting children under 2 years. Rising resistance to key antibiotics limits treatment options and highlights the need for strengthened AMR surveillance, optimized antibiotic use, and vaccination strategies. Full article

Background/Objective: Acinetobacter baumannii is an opportunistic pathogen responsible for various healthcare-associated infections, particularly in critically ill patients. The emergence and rapid spread of multidrug- and extensively drug-resistant strains, notably carbapenem-resistant A. baumannii (CRAB), threaten global health. We aimed to investigate the clonal distribution, antimicrobial resistance profiles, and resistance determinants of CRAB bloodstream isolates in Korean hospitals to identify emerging high-risk clones and their potential clinical impact. Methods: Sequence types (STs) were determined using the Oxford multilocus sequence typing scheme, and antimicrobial susceptibility profiles and resistance determinants were evaluated. Results: We analyzed 812 CRAB bloodstream isolates collected from nine South Korean tertiary hospitals between 2016 and 2020. The isolates were classified into 39 STs, with ST191 (n = 245) and ST369 (n = 192) being the most prevalent. Between 2016 and 2020, ST369 increased from 2.6% to 37.9%, while ST195, first detected in 2018 (0.5%), increased to 19.0%; however, ST191 declined from 45.2% to 19.0%. Most CRAB infections were hospital-acquired (91.6%, 744 of 812), predominantly affecting men aged ≥51 years, particularly the 71–80-year-olds. Resistance rates were ≥80% for ampicillin-sulbactam and ciprofloxacin. bla_OXA-23 was detected in 807 isolates, confirming its central role in carbapenem resistance. ST195 exhibited higher resistance to minocycline (29.4%) than did the other STs. Conclusions: Dynamic clonal shifts and high antimicrobial resistance exist among CRAB isolates in Korean hospitals, with the rapid emergence of ST195 and ST369 increasing clinical challenges. Continuous epidemiological surveillance and targeted infection control measures are essential to control the spread of high-risk CRAB clones. Full article

Elizabethkingia species are rare but increasingly recognised Gram-negative pathogens linked to healthcare-associated transmission, intrinsic multidrug resistance, and severe infection in vulnerable hosts. We performed a comprehensive review of human Elizabethkingia infections by systematically searching PubMed on 18 October 2025 and included English-language case reports, case series, and outbreak investigations; species were analysed as reported (legacy nomenclature retained), and adults were defined as ≥18 years. In total, 374 studies were included (300 case reports, 41 case series, 33 outbreak investigations). Adult infections were predominantly healthcare-related, affected older adults with substantial comorbidities and most often presented as bacteraemia or sepsis and pneumonia; crude mortality in adult case reports was 32.8%. Paediatric disease was concentrated in neonates and Neonatal Intensive Care Unit (NICU) settings, with meningitis and bloodstream infection predominating; crude mortality in paediatric case reports was 23.3%, and neurological sequelae were frequently reported among survivors. Across studies, isolates showed broad resistance to β-lactams and near-universal resistance to carbapenems, with variable activity to fluoroquinolones and trimethoprim–sulfamethoxazole and more consistent in vitro activity to minocycline. Species misidentification (notably Elizabethkingia anophelis as Elizabethkingia meningoseptica) and heterogeneous susceptibility testing limited comparability. Outbreak investigations repeatedly implicated water-associated reservoirs and reusable equipment, underscoring the need for improved diagnostics, susceptibility-guided therapy and water-focused infection prevention. Full article

Daptomycin-resistant Enterococcus faecium (DRE) poses an increasing therapeutic challenge, particularly in immunocompromised patients and solid organ transplant recipients. Surveillance data from the Centers for Disease Control and Prevention indicate that approximately 6.5% of E. faecium isolates are daptomycin-resistant, underscoring the need for heightened clinical vigilance, particularly for prompt identification and treatment. In this case series, three patients with advanced liver disease, including two status post orthotopic liver transplantation, are described who developed DRE during treatment for bloodstream infection. These cases illustrate the dynamic nature of antimicrobial susceptibility under daptomycin exposure and highlight the contributions of persistent source control issues, intravascular infection, and altered host factors to treatment failure. All patients were successfully managed by escalating to combination therapy with high-dose daptomycin and ceftaroline, alongside appropriate source control. This series emphasizes the importance of periodic susceptibility reassessment during daptomycin therapy and cautions clinicians against assuming sustained susceptibility in patients with prolonged bacteremia or complex infections. Early recognition of evolving resistance and timely therapeutic adjustment may improve outcomes in this high-risk population. Full article

Background: While Candida auris is well known to cause hospital outbreaks, other species in the C. haemulonii complex are less well documented but gained attention as opportunistic pathogens. Only one documented outbreak has been published. We describe the second, silent, fungemia outbreak due to antifungal-susceptible C. duobushaemulonii. Methods: We retrospectively genotyped six C. duobushaemulonii bloodstream isolates, collected in a 4-month-period in 2022 (n = 4) and during a week in 2024 (n = 2) in pediatric patients in Brazil. Whole genome sequencing (WGS) was done and compared to n = 33 publicly available genomes, including four cases from an outbreak in Panama. Antifungal susceptibility was performed with the reference CLSI method. Results: MALDI-TOF-MS identified isolates as either C. pseudohaemulonii or C. duobushaemulonii albeit with low scores. ITS sequence analyses confirmed all isolates as C. duobushaemulonii. WGS proved the presence of an outbreak among four pediatric patients in 2022 and a genetically distinct cluster of two cases in 2024. All six isolates were susceptible to azoles and echinocandins and were interpreted as being resistant to amphotericin B with a MIC at breakpoint of 2 µg/mL. Conclusions: This study describes the second documented outbreak due to the rare yeast C. duobushaemulonii, belonging to the C. haemulonii species complex, during 2022–2024 in patients admitted to a pediatric oncology ward in a Brazilian hospital. Full article

Background: Sepsis remains a leading cause of morbidity and mortality worldwide, where timely and accurate pathogen detection is critical for improved outcomes. Conventional blood cultures are the gold standard but are limited by prolonged turnaround times and suboptimal sensitivity, often delaying targeted therapy. Methods: This single-center retrospective study evaluated the diagnostic performance and clinical utility of the T2Bacteria and T2Resistance Panels compared with conventional blood cultures in 30 adult patients admitted to the cardiovascular intensive care unit with a suspected bloodstream infection. Results: The T2Bacteria Panel demonstrated high diagnostic accuracy for on-panel organisms (100%), detecting all cases of Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, while blood cultures detected 9 of 12 on-panel infections. In contrast, two off-panel organisms were isolated from five patients exclusively by blood cultures, highlighting the complementary roles of both methods. Importantly, antimicrobial therapy was modified in 6 of 10 T2-positive patients (60%) based on T2 results, preceding blood culture reporting by a median of more than 100 h. Conclusions: These findings underscore the value of T2 assays in enabling earlier, evidence-based therapeutic decisions and supporting antimicrobial stewardship. While limited by the sample size and single-center design, these findings—consistent with pathogen distributions reported in European ICU settings—suggest that integrating T2-based diagnostics into cardiovascular ICU workflows may enhance early therapeutic decision-making and antimicrobial stewardship. Full article