Invasive fungal infections (IFIs) represent a significant cause of morbidity and mortality in critically ill children admitted to pediatric intensive care units (PICUs). Despite the variation of the incidence of candidemia and invasive candidiasis (IC) and Candida species distribution between different PICU settings, increasing rates of non-albicans Candida species and emerging antifungal resistant strains are observed. Antifungals are prescribed in PICUs mainly for empiric treatment, with limited use of diagnostic-driven strategies despite availability of fungal biomarkers in many settings. Data on antifungal prophylaxis in PICU outside traditional highrisk populations are scarce with no official guidance on administration of prophylaxis and to which patients. Diagnostic challenges, heterogeneity and complexity of PICU patients, and the absence of specific guidelines on prophylaxis contribute to increased and/or inappropriate antifungal use. Although antifungals are frequently used in PICU, antifungal stewardship (AFS) activities reported particularly in this population remain limited. Shift from empiric to pre-emptive treatment, systematic use of therapeutic drug monitoring, new diagnostic tests and fungal biomarkers and limiting the group of patients outside the high-risk groups on prophylaxis are the key targets for AFS in critically ill children. Only nine AFS interventions including PICU patients were found in the English literature; seven were part of hospital-wide stewardship programs and only three were targeted to antifungals. Audit with feedback was mainly used as a strategy, while various designs and outcomes were observed. Antifungal stewardship programs are essential to optimize antifungal use in PICUs; however, standardized frameworks tailored to these settings should be developed. This review describes the epidemiology of IFIs in PICUs, current antifungal prescribing practices, and summarizes AFS interventions implemented in PICUs up to now in order to propose recommendations for future antifungal stewardship initiatives in these patients.

OBJECTIVES:Colistin is an essential antibiotic against carbapenem-resistant Gram-negative bacilli. Pharmacokinetic and pharmacodynamic limitations impact its efficacy, and susceptibility breakpoints equivocate regarding interpretation of MIC values. This post hoc analysis of the OVERCOME trial investigated the association between colistin MIC and outcomes. METHODS:OVERCOME, a randomized, double-blind, placebo-controlled trial, compared colistin monotherapy with colistin plus meropenem for treatment of carbapenem-resistant Gram-negative bacilli pneumonia and/or bloodstream infections. Outcomes were compared between participants whose infections were caused by pathogens with colistin MIC values ≤1 mg/L and those with MIC values of 2 mg/L. RESULTS:Among 369 included participants, the mean age was 67.7 ± 15.9 years, 246 (67%) were in the intensive care unit, 251 (68%) had pneumonia, and 286 (78%) were infected with Acinetobacter baumannii. Overall, no association between an infecting pathogen with an MIC of 2 mg/L and either clinical failure (adjusted odds ratio [aOR]: 1.59 [95% CI: 0.72-3.52]) or 28-day mortality (aOR: 1.62 [95% CI: 0.85-3.09]) was demonstrated. Among participants receiving monotherapy, an infecting pathogen with an MIC of 2 mg/L was independently associated with both clinical failure (aOR: 3.59 [95% CI: 1.10-11.77]) and 28-day mortality (aOR: 3.22 [95% CI: 1.32-7.84]). Among participants receiving combination therapy, no association was demonstrated between MIC and outcomes. CONCLUSIONS:When using colistin-based therapy for pathogens with an MIC of 2 mg/L, these findings support colistin and meropenem combination therapy over colistin monotherapy, particularly for pneumonia due to A. baumannii.

BACKGROUND:Imipenem/cilastatin/relebactam (IMI/REL), a fixed-dose combination of imipenem/cilastatin with the β-lactamase inhibitor relebactam, has broad gram-negative coverage. Prospectively obtained safety and efficacy data in neonates and children are needed. METHODS:Children (birth to <18 years old) with hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP), complicated intra-abdominal infection (cIAI) and complicated urinary tract infection (cUTI), including pyelonephritis, were enrolled in an open-label, randomized, active-controlled, multinational phase 2/3 trial (ClinicalTrials.gov: NCT03969901). Participants were randomized 3:1 to IMI/REL or active-control, standard-of-care antibacterial therapy for 7-14 days (HABP/VABP; intravenous [IV] only) or 5-14 days (cIAI, cUTI; with oral step-down permitted after 3 days of IV). The primary endpoint was safety, assessed through 14 days after the end of therapy (EOT) as adverse events (AEs) and AE-related discontinuations of IV therapy. Clinical and microbiologic responses were also assessed at EOT and follow-up visits. This was an estimation study without hypothesis testing. RESULTS:Eighty-six children were randomized to IMI/REL and 29 to active control. AEs were reported in 67.1% of IMI/REL versus 50.0% of active control arm participants (treatment difference: 17.1% [95% confidence interval: -3.5, 37.2]), leading to 3 versus 0 discontinuations of IV therapy, respectively. Treatment outcomes were generally comparable at all time points; at EOT, clinical response was 78.8% versus 75.0% and microbiologic response 95.6% versus 90.9% with IMI/REL and active control, respectively, with no mortality in either arm. CONCLUSIONS:IMI/REL was generally well tolerated in neonates and older pediatric patients with HABP/VABP, cIAI, or cUTI, with safety and efficacy profiles comparable to standard-of-care antibacterial therapy.

Background. Colistin, a last-line treatment for carbapenem-resistant Gram-negative bacilli (CRGNB), is frequently used in combination with meropenem because these agents often demonstrate in vitro synergy. Using data from the OVERCOME trial comparing colistin + meropenem to colistin + placebo for treatment of pneumonia or bloodstream infection due to CRGNB, we evaluated the impact of synergistic therapy on outcomes. Methods. In vitro synergy testing between colistin and meropenem was conducted using 24-hour time-kill analysis; synergy was defined as >2-log reduction in colony-forming units/mL compared to the most active single agent. Patients receiving synergistic combination therapy were compared to patients receiving functional colistin monotherapy (colistin alone or combination therapy without synergy). Outcomes included mortality, clinical failure, and microbiologic cure. Adjusted analyses controlled for variables on which randomization was stratified and confounders. Results. A total of 146 subjects receiving synergistic combination therapy and 261 subjects receiving functional monotherapy were included. Most had pneumonia (70%), CR Acinetobacter baumannii infection (79%) and were in intensive care (69%). Acinetobacter baumannii was more common in those receiving synergistic combination therapy than functional monotherapy (P < .001). Mortality rates were similar (38.3% and 41.4%, respectively). In adjusted analyses, synergistic combination therapy was associated with significantly lower clinical failure rates (55.3%, 64.3%, adjusted odds ratio [aOR] 0.62, P = .049), with consistent findings in pneumonia (62.6%, 71.8%, aOR 0.55, P = .04) and A. baumannii subgroups (57.4%, 69.4%, aOR 0.60, P = .06). Microbiologic cure rates were similar. Conclusions. Colistin-based, synergistic combination treatment with meropenem (compared to nonsynergistic colistin-based therapy) was associated with decreased clinical failure, particularly in people with pneumonia and A. baumannii.

BACKGROUND:Invasive fungal disease remains a major cause of morbidity and mortality among children with malignancies and those undergoing hematopoietic stem cell transplantation (HSCT). Real-world data that describe antifungal prescribing practices in pediatric hematology-oncology units are very limited. METHODS:A national prospective observational study from June 2016 through December 2019 in 5 pediatric hematology-oncology units and the single pediatric HSCT unit in Greece was conducted. The first 15 children per month admitted to these units who required initiation of new antifungal agents for prophylaxis or treatment were recorded. Demographics, presence of a central venous line, type of underlying disease, absolute neutrophil count on the first day of antifungal therapy, presence of invasive fungal disease, days of therapy, microbiologic findings and outcomes were recorded. RESULTS:Among 1838 anti-infective courses, 737 (40.1%) involved antifungal agents. Antifungal use was predominantly prophylactic (47.6%) or empiric (50.7%), with targeted therapy accounting for only 1.5%. Prophylaxis was more common in the HSCT unit, whereas empiric therapy predominated in pediatric hematology-oncology units. Fluconazole was the most frequently used prophylactic agent, followed by micafungin and voriconazole. Proven fungemia was uncommon; Candida albicans was the most frequently isolated pathogen. Overall mortality was 1.8%, with slightly higher mortality among patients receiving antifungal therapy. CONCLUSIONS:Antifungal use in pediatric oncology and HSCT settings was extensive and heterogeneous, characterized by heavy reliance on prophylactic and empiric strategies and minimal targeted therapy. These findings support the need for structured antifungal stewardship programs to optimize antifungal exposure while preserving favorable outcomes.

BACKGROUND:Cefiderocol is a novel siderophore-conjugated cephalosporin with activity against antimicrobial-resistant Gram-negative bacteria. Despite increasing off-label use in critically ill neonates and children, data on its safety and effectiveness remain limited. METHODS:We performed a retrospective case series of neonatal and pediatric patients (≤18 years) who received off-label cefiderocol across 3 tertiary-care hospitals in Greece for suspected or documented infections due to multidrug-resistant Gram-negative bacteria. We also conducted a systematic review of pediatric cases published through June 2025. RESULTS:Fifteen patients [median age 65 months (range 4-183)] received 21 cefiderocol courses. The systematic review identified 37 additional treatment courses (32 patients, 6 of them <3 months of age), primarily for bloodstream infections (86%), pneumonia (24.3%) and febrile neutropenia (18.9%). Most patients had received multiple antibiotics before and concomitantly with cefiderocol for extensively resistant Gram-negative bacteria. Clinical response occurred in 16/21 (76.2%) courses in the case series study and 22/28 (78.6%) courses in the systematic review. Microbiologic clearance was observed in 7/9 (78%) courses in the case series. Cefiderocol was well-tolerated without serious adverse events in all cases. Most isolates (14/18, 78%) were susceptible to cefiderocol according to current breakpoints, with a single instance of resistance emergence. CONCLUSIONS:This is the largest pediatric cohort to date combining real-world and published cefiderocol cases, suggesting that cefiderocol is a safe, well-tolerated and potentially effective option for severe, difficult-to-treat antimicrobial-resistant Gram-negative infections in neonates and children. These results support cautious off-label use in critically ill patients, while underscoring the urgent need for further pediatric trials.

Acinetobacter baumannii has been characterized by CDC, WHO and most National Healthcare Systems worldwide as a critical nosocomial pathogen, and classified as an ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) pathogen. Mortality of invasive infections due to A. baumannii exceeds 40%. To highlight its impact on public health, ECDC has organized a special project on national lab co-ordination to accurately detect and report carbapenem-resistant strains, to identify epidemiological factors for infection (or colonization) with carbapenem-resistant A. baumanii at clonal and sub-genomic level. This review aims to describe the history, epidemiology, and evolution of resistance of A. baumannii, and stress the caveats associated with the management of systemic infections. Available active antimicrobials and drugs in the pipeline are listed, and available clinical evidence on their pharmacokinetics and efficacy in various types of infections are described. Clinician’s choice of treatment (drug, and monotherapy vs. combination treatment) depends on the patients’ profile, site of infection and antimicrobial resistance profile. Emphasis is laid on specific patient subpopulations, whose management is discussed.

Respiratory viral infections (RVIs) have been described traditionally as clinically important infectious complications in pediatric patients with immunosuppression, particularly in those with malignancies (hematological or solid) and recipients of hematopoietic cell or solid organ transplantation. Specifically, advances in the field of cancer therapy and novel immune-based pharmaceuticals have significantly expanded the population of children with prolonged and complex immunosuppression, whereas the widespread use and availability of molecular diagnostics have increased the detection of respiratory viruses. Additionally, these developments have improved the etiologic identification of RVIs, while introducing important challenges in clinical interpretation, mainly in differentiating incidental viral identification from clinically significant diseases. Furthermore, RVIs in immunocompromised children are characterized by heterogeneous and diverse clinical manifestations, with a range from mild upper respiratory tract involvement to severe lower respiratory tract disease, which can lead to substantial morbidity and mortality. Diagnostic strategies in this field are primarily based on nucleic acid amplification tests, requiring careful interpretation because of the possible prolonged viral shedding, co-detection, and overlapping infectious syndromes. Beyond direct clinical consequences, viral detection has an impact on infection control measures, antimicrobial stewardship decisions, and the timing of therapies. In this literature review, we offer an overview of current evidence on the epidemiology, clinical manifestations, diagnostic approaches, and management of RVIs in immunocompromised pediatric populations, underscoring the unmet need for structured, risk-adapted integration of virologic data into pediatric oncology care.

Importance Clesrovimab is a long-acting monoclonal antibody approved for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants who are born during or entering their first RSV season; data concerning clesrovimab from a second RSV season among children who remain at risk for severe disease are needed. Objective To evaluate the safety and tolerability of clesrovimab (105 mg) vs palivizumab in RSV season 1 in infants at increased risk for severe RSV disease. Key secondary objectives include describing the safety of 210 mg of clesrovimab in RSV season 2 in children who remain at increased risk for severe RSV disease, clesrovimab pharmacokinetics, and the incidence of RSV-associated disease. Design, Setting, and Participants SMART (MK-1654-007) was a randomized, partially masked, palivizumab-controlled, phase 3 clinical trial, conducted at 110 sites in 27 countries and territories between November 30, 2021, and November 20, 2025. The population constituted palivizumab-eligible infants, including those with prematurity, chronic lung disease of prematurity, or hemodynamically significant congenital heart disease. Interventions Participants, randomized 1:1 and stratified by region and condition, received clesrovimab (105 mg) on day 1 followed by placebo on day 28 or monthly palivizumab (15 mg/kg) up to 5 doses (1 dose per month). Eligible infants received open-label clesrovimab (210 mg) before their second RSV season. Main Outcomes and Measures The primary outcome was the observed proportions of participants experiencing adverse events (AEs) after clesrovimab or palivizumab in season 1. Results Overall, 997 infants (500 [50.2%] male; median age, 2.6 [range, 0.0-12.0] months) received clesrovimab, 105 mg (n = 498) or palivizumab (n = 499) in season 1; 276 received clesrovimab, 210 mg open-label in season 2. In season 1, the proportions of participants experiencing AEs were comparable between treatment groups. In season 2, clesrovimab, 210 mg was well tolerated. Incidence rates of RSV-associated medically attended lower respiratory infection (MALRI) were comparable between clesrovimab and palivizumab (3.2% [95% CI, 1.8%-5.2%] and 3.4% [95% CI, 2.0%-5.6%], respectively) through day 150 in season 1; total RSV-associated MALRI incidence through day 180 after a 210-mg dose in season 2 was 7.3% (95% CI, 4.4%-11.4%). Conclusions and Relevance In this randomized clinical trial, clesrovimab was well tolerated in infants at increased risk for severe RSV disease through 2 RSV seasons. These findings support the use of clesrovimab in children who remain at risk for severe RSV disease in their second RSV season. Trial Registration ClinicalTrials.gov Identifier: NCT04938830

Acute respiratory infections (ARIs) are the most common infectious diseases during childhood, responsible for significant morbidity and mortality in the pediatric population worldwide. Metabolomics, the global analysis of small metabolites, is a novel tool that offers insights into diagnostics and prognostics of viral respiratory infections. This review summarizes the existing literature on metabolomic studies in viral acute respiratory infections (ARIs) within the pediatric population. Metabolomic research on patients with bronchiolitis has addressed several clinical questions, such as discrimination by causative agent, i.e. respiratory syncytial virus or rhinovirus, and most importantly prognosis, predicting disease severity and long-term outcomes. In pneumonia, studies have focused on discriminating viral from bacterial etiology and from healthy controls but also predicting disease severity. There is a growing number of studies on metabolomics in ARIs providing a strong foundation for addressing remaining challenges and allowing for more comparable results and greater impact on clinical practice.

The European Confederation of Medical Mycology Candida III was a pan-European, multicenter observational study of adult patients with blood culture-proven candidemia. Among a total of 632 patients with candidemia across 64 institutions in 20 European countries, a subanalysis of 396 (63%) cases occurring outside the intensive care unit (ICU) was conducted. Compared with ICU patients, non-ICU patients had a higher comorbidity burden (median Charlson comorbidity index [CCI] 6 vs 5 in ICU patients, P = .006). Hematologic and oncologic malignancies were more frequent among non-ICU cases (45.5% vs 28.4%, P < .001), whereas both chronic kidney and cardiovascular disease were more prevalent in ICU patients (P < .001). Non-ICU patients had significantly lower mortality in Kaplan-Meier survival analysis (P > .001). Postsurgical non-ICU patients (n = 45) had the highest survival rate (73.3%, P = .003) and the longest hospital stay, even after excluding all cases with a fatal outcome before day 30. In non-ICU patients, older age, hemato-oncologic malignancies, chronic liver disease, and COVID-19 were all independently associated with mortality risk, while treatment consultation by an infectious disease or clinical microbiology consultant, and initial treatment with an echinocandin, respectively, higher EQUAL Candida scores were associated with lower mortality risk in the multivariable Cox regression models. In conclusion, despite higher comorbidity rates, non-ICU patients with candidemia had higher survival rates.

Candidozyma auris (previously named Candida auris) has been recognized as a significant public health threat due to its extensive transmission in hospital settings, high mortality rates, and multidrug resistance. Evidence regarding optimal antifungal treatment in children remains limited. The present systematic review aims to synthesize available evidence on pediatric C. auris infections, focusing on antifungal treatment, resistance profiles, and clinical outcomes. A systematic search was conducted across PubMed, Scopus, and Web of Science, identifying case reports and case series of pediatric patients with confirmed C. auris infection. Data were extracted on demographics, comorbidities, infection site, antifungal therapy, and outcomes. Risk of bias was assessed using JBI Critical Appraisal checklists. Fourteen studies comprising 62 patients were included, with most cases being bloodstream infections. C. auris showed widespread fluconazole resistance and variable susceptibility to amphotericin B. Echinocandins were the most commonly used agents, generally associated with survival. Overall mortality was 35%, similar to that reported for adults. Combination therapy showed numerically higher survival, although given the small sample size and heterogeneity of treatment regimens, no comparative inferences can be made. Pediatric C. auris infections mirror adult patterns of antifungal resistance and mortality. Echinocandins remain first line therapy; however, the emergence of echinocandin resistance underscores the urgent need for antifungal stewardship, standardized pediatric guidelines, and novel antifungal development.

BACKGROUND:Klebsiella spp. are a major cause of antimicrobial-resistant hospital-acquired infections. This study aimed to identify possible risk factors for Klebsiella spp. infection during the first180 days post-transplantation. METHODS:A multi-centre, retrospective, case-control study was conducted in three hospitals in Greece and Italy between 2016 and 2021, including patients aged >50 years who had undergone solid organ transplantation. RESULTS:In total, 202 transplant patients (115 liver, 79 kidney, seven heart and four pancreas) were included in this study, of which 120 (59.4%) suffered from at least one infection due to Klebsiella spp. (141 infections). The most common site of infection was the urinary tract (48/141, 34%), and the most common species was Klebsiella pneumoniae (132/141, 93.6%). Among all Klebsiella spp. isolates, 40.3% were carbapenem-resistant. History of cardiovascular disease [odds ratio (OR) 2.06, 95% confidence interval (CI) 1.14-3.8; P=0.019] and post-transplant intensive care unit (ICU) hospitalization for ≥3 days (OR 2.08, 95% CI 1.18-3.72; P=0.012) were independently associated with Klebsiella spp. infection among all organ recipients. In liver transplant patients, post-transplant ICU hospitalization for ≥3 days (OR 2.87, 95% CI 1.25-6.78; P=0.014) was associated with Klebsiella spp. infection, and in kidney transplant patients, history of cardiovascular disease was associated with Klebsiella spp. infection (OR 2.84, 95% CI 1.12-7.48; P=0.03). CONCLUSION:Post-transplant ICU stay for ≥3 days and history of cardiovascular disease are associated with increased risk of Klebsiella spp. infection in solid organ transplant recipients aged >50 years.

Candidemia is a life-threatening invasive fungal infection, particularly in patients admitted to intensive care units (ICUs). Epidemiology of candidemia and antifungal resistance have been significantly affected in COVID-19 pandemic. We analysed candidemia cases in neonatal, paediatric, and adult ICUs at Hippokration General Hospital in Thessaloniki, Greece (site 1) and Kayseri City Training and Research Hospital in Kayseri, Türkiye (site 2) from January 2020 to December 2023. Epidemiology, species distribution, and antifungal susceptibility of cases were compared. A total of 388 patients from site 1 and 379 patients from site 2 were included. A significant increase in the incidence of candidemia was observed in both hospitals during the COVID-19 pandemic. Candida parapsilosis was the most common species in all ICUs at Site 1, while Candida albicans was predominant at Site 2. C. parapsilosis became the most frequent species at Site 2 after 2021. C. glabrata was isolated more frequently in Site 1, whereas C. tropicalis was more frequently isolated in Site 2. A total of 14 C. auris strains were isolated, 13 of which were at the site 1. Over 90

This phase 2a study evaluated pharmacokinetics and safety of ceftazidime-avibactam (CAZ/AVI; combination dosed as fixed 4:1 ratio) in neonates and young infants with suspected/confirmed infections due to Gram-negative pathogens requiring intravenous antibiotics. Hospitalized neonates and infants (gestational age ≥ 26 weeks to < 3 months), enrolled sequentially into 3 age cohorts, received CAZ/AVI single dose (Part A) or multiple dose every 8 h (Part B) by 2-h intravenous infusions. Infants > 28 days (Cohort 1) received CAZ/AVI 37.5 mg/kg/dose (CAZ 30 mg/kg and AVI 7.5 mg/kg). Full-term neonates ≤ 28 days (Cohort 2) and preterm neonates ≤ 28 days (Cohort 3) received 25 mg/kg/dose (CAZ 20 mg/kg and AVI 5 mg/kg). Pharmacokinetics, safety, and clinical and microbiological outcomes (Part B only) were assessed descriptively. Forty-six patients received CAZ/AVI, 25 in Part A and 21 in Part B. Sepsis (39.1%) and urinary tract infection (15.2%) were the predominant diagnoses. Observed drug plasma-concentration time profiles were generally similar across cohorts. Overall, 23 patients (50%) had ≥ 1 adverse event (AE), 8 patients (17.4%) had ≥ 1 serious AE (SAE), and 2 patients (4.3%) died; no SAE or death was treatment related. In Part B, ≥ 80% of patients had favorable clinical and microbiological responses. Plasma exposures after single and multiple CAZ/AVI doses in neonates and young infants < 3 months old (37.5 [30/7.5] mg/kg/dose for > 28 days; 25 [20/5] mg/kg/dose for ≤ 28 days) were similar to approved doses for older children. The safety profile of CAZ/AVI was as expected based on previous observations. Study funded by Pfizer. Trial registration: NCT04126031.

Chimeric antigen receptor (CAR)-T immunotherapy has revolutionized the management of patients with relapsed/refractory B-cell hematological malignancies. There is emerging evidence that CAR-engineered cells—not only T cells, but also natural killers and macrophages—might have a crucial role in the treatment of autoimmune disorders and solid tumors. Moreover, given the burden of chronic infectious diseases, the mortality and morbidity of infections in immunocompromised individuals, and the development of multidrug-resistant pathogens, including bacteria, fungi, and mycobacteria, a need for novel and personalized therapeutics in this field is emerging. To this end, the development of CAR cells for the management of chronic infections has been reported. In this literature review, we summarize the ongoing clinical and pre-clinical data about CAR cell products in the field of infectious diseases. Currently, clinical studies on CAR immunotherapy for infections mainly concern human immunodeficiency virus infection treatment, and data regarding other infections largely originate from preclinical in vitro and in vivo models. In the era of personalized medicine, effective and safe therapies for the management of chronic infections and infectious complications in immunocompromised patients are crucial.

Objectives: A post hoc analysis used pooled STRIVE/ReSTORE trial data to determine outcomes with rezafungin versus caspofungin by Candida species and antifungal susceptibility. Methods: The efficacy and safety of once weekly rezafungin 400/200 mg versus once daily caspofungin 70/50 mg was demonstrated in the randomized, double-blind phase 2 STRIVE (NCT02734862) and phase 3 ReSTORE (NCT03667690) trials involving adults with candidaemia and/or invasive candidiasis. In this analysis, data were pooled for patients with a documented Candida infection within 96 hours of randomization who also received >1 dose of study drug. Treatment outcomes were evaluated by Candida species and baseline MICs. Susceptibility was determined using European Committee on Antimicrobial Susceptibility Testing E.Def 7.4 broth microdilution methodology, with Tween 20-supplemented medium for rezafungin. Results: A total of 294 patients were included (rezafungin: N = 139, caspofungin: N = 155). Susceptibility testing at baseline identified three rezafungin non-susceptible isolates. Day 14 global cure rates were numerically similar between groups for C. albicans (rezafungin: 61.0% [36/59], caspofungin: 65.2% [45/69]) and C. tropicalis (rezafungin: 70.4% [19/27], caspofungin: 63.6% [14/22]), but higher with rezafungin than caspofungin for C. glabrata (rezafungin: 71.1% [27/38], caspofungin: 60.0% [21/35]) and C. parapsilosis (rezafungin: 78.6% [11/44], caspofungin: 55.6% [15/27]). Day 30 all-cause mortality rates were numerically similar between groups for C. albicans (rezafungin: 22.0% [13/59], caspofungin: 18.8% [13/69]) and C. glabrata (rezafungin: 15.8% [6/38], caspofungin: 11.4% [4/35]), but higher with caspofungin than rezafungin for C. tropicalis (rezafungin: 18.5% [5/27], caspofungin: 31.8% [2/22]) and C. parapsilosis (rezafungin: 7.1% [1/14], caspofungin: 29.6% [8/27]). Day 5/14 mycological eradication rates were numerically similar between treatments for C. albicans and C. parapsilosis, but higher with rezafungin for C. glabrata and C. tropicalis. Outcomes by Candida species were not associated with treatment-specific MICs. Discussion: Rezafungin appears to be an effective treatment for candidaemia/invasive candidiasis irrespective of baseline Candida species. Alex Soriano, Clin Microbiol Infect 2025;31:250 (c) 2024 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/).

Introduction: The epidemiology of candidemia has shifted in the past few decades; drug-resistant non-albicans Candida species have become more prevalent worldwide. The aim of this retrospective study was to determine the epidemiology of Candida species isolated from hospitalized neonates, children and adults, and to investigate a potential changing susceptibility pattern in a large general tertiary hospital. Methods: All unique Candida strains isolated from candidemia cases between 1 January 2020 and 15 October 2024 were identified, and their susceptibility profile was characterized. The distribution pattern in different ward types (medical, surgical, pediatric and ICU) was recorded. Cumulative annual susceptibility profiles were compared. Results: Candidemia incidence increased during the COVID-19 pandemic, from 0.63/1000 patient-days in 2020 to 0.96/1000 patient-days in 2022, and has since slightly decreased (0.83 and 0.89 in 2023 and 2024, respectively). Candidemia-associated mortality was high (>50%) in 2020 and peaked during the pandemic. During the study period, Candida parapsilosis remained the most frequent Candida spp. However, since the first isolation of Candida auris from the bloodstream in late 2022, and despite intense infection control measures taken, its frequency sharply climbed to the second position after only C. parapsilosis in the first 10 months of 2024 (33.6% vs. 25.2% for C. parapsilosis and 21.0% for C. albicans). While C. albicans has remained highly susceptible to fluconazole (1% resistance rate), C. parapsilosis manifested significant resistance to fluconazole during 2022–2024 (52%). C. auris was universally resistant to azoles and one isolate also resistant to echinocandins. Conclusions: A high prevalence of azole resistance of C. parapsilosis, the most frequently isolated Candida species, persists, and a significant rise of C. auris was recorded in nosocomial bloodstream infections with severe implications on public health.

BACKGROUND:Hospital-acquired infections with Klebsiella spp. and emerging multi-drug-resistant strains are a persistent concern. Identifying high-risk groups is crucial for the evaluation of preventive interventions such as vaccines. We determined the incidence and developed prediction models for postsurgical klebsiella infections in adult elective surgery patients. METHODS:This multi-centre retrospective case-control study, in seven European hospitals, included patients ≥50 years old who underwent elective surgery between 2012 and 2021. Using multi-variable logistic regression, we modelled the risk of postsurgical klebsiella infection and investigated trial enrichment scenarios. RESULTS:Of 139,778 eligible surgeries identified, 1781 were included: 840 patients with postsurgical klebsiella infection and 941 without. The incidence of postsurgical klebsiella infection was 1.38% (95% confidence interval 1.24-1.54%). Pre-surgical klebsiella colonization, gastrointestinal surgery, abdominal surgery, trauma surgery and chronic cardiovascular disease were independent predictors of postoperative klebsiella infection. Minimally invasive surgery and peri-operative antibiotic prophylaxis predicted a lower risk. Trial enrichment simulation indicated a 72% reduction in required participants when enrolling patients with a predicted risk above 2%. CONCLUSIONS:A multi-variable model incorporating klebsiella colonization status and clinical factors can accurately predict klebsiella infections in elective surgery patients. This model can select high-risk patients, enhancing the efficiency of phase-III trials of preventive interventions, including vaccination.