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: Early diagnosis of ventilator-associated pneumonia (VAP) remains a challenge due to subjective clinical criteria and the low discriminative power of diagnostic tests. We assessed whether rapid molecular diagnostics in combination with Clinically Pulmonary Index Score (CPIS) scoring, microbiological surveillance and biomarker measurements of PTX-3, SP-D, s-TREM, PTX-3, IL-1β and IL-8 in the blood or lung could improve the accuracy of VAP diagnosis and follow-up in critically ill children. Methods: A prospective pragmatic study in a Pediatric Intensive Care Unit (PICU) was conducted on ventilated critically ill children divided into two groups: high and low suspicion of VAP according to modified Clinically Pulmonary Index Score (mCPIS). Blood and bronchial samples were collected on days 1, 3, 6 and 12 after event onset. Rapid diagnostics were used for pathogen identification and ELISA for PTX-3, SP-D, s-TREM, IL-1β and IL-8 measurements. Results: Among 20 enrolled patients, 12 had a high suspicion (mCPIS > 6), and 8 had a low suspicion of VAP (mCPIS < 6); 65% were male; and 35% had chronic disease. IL-1β levels at day 1 correlated significantly with the number of mechanical ventilation days (r_s = 0.67, p < 0.001) and the PICU stay (r = 0.66; p < 0.002). No significant differences were found in the levels of the other biomarkers between the two groups. Mortality was recorded in two patients with high VAP suspicion. Conclusions: PTX-3, SP-D, s-TREM, IL-1β and IL-8 biomarkers could not discriminate patients with a high or low suspicion of VAP diagnosis.

Background: Multi/extensively drug-resistant bacterial infections have recently increased and new antimicrobial options are needed for difficult-to-treat infections. Ceftazidime/avibactam (CZA) has been approved for patients 3 months to 18 years of age, but real-life data on its off-label use in neonates and young infants are still scarce. Materials: : We report demographic, clinical and microbiologic data as well as outcome and safety of all cases of infants treated with CZA between January 1, 2021 and September 30, 2022 in a tertiary neonatal intensive care unit. We also review all neonatal cases previously reported. Results: Twenty-one patients [17 males, with median gestational age 29⁺² (IQR 6⁺⁶) weeks] received 31 CZA courses at a dose of 20–50 mg/kg/dose of ceftazidime q8h for suspected or proved multi/extensively drug-resistant infections. Median postnatal age at the onset of treatment was 44 days (IQR: 94 days). Twelve bacteremias, 2 urinary tract infections and 1 ventilator-acquired pneumonia were recorded. Twelve (39%) treatments were targeted, while 19 (61%) were empirically started due to known colonization with Klebsiella pneumoniae carbapenemase-producing Gram-negative bacteria. All patients had received multiple antibiotics prior and concomitantly with CZA. The most common pathogen identified at targeted administrations was carbapenem-resistant Klebsiella pneumoniae (83%). No serious adverse events attributed to the drug were detected. Twenty-one courses of CZA administration to 20 neonates with a median gestational age of 28.5 (IQR 3.5) weeks were previously reported without significant related adverse events. Conclusions: Favorable clinical and microbiologic responses in neonatal intensive care unit patients treated with CZA off-label were observed without significant and unexpected adverse events in critically ill neonates.

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.

Ventilator-associated pneumonia (VAP) is a common and serious complication of patients at intensive care units (ICUs), contributing to increased morbidity and mortality. Current diagnostic approaches for VAP rely on clinical, radiological, and invasive methods, which are time-consuming, carry risks, and may result in delayed or inconclusive findings. The need for rapid, reliable, and non-invasive diagnostic tools is critical. Biomarkers and specifically volatile organic compounds (VOCs) in exhaled breath have emerged as promising candidates for this purpose. In this study, we applied gas chromatography-mass spectrometry (GC-MS) with solid-phase microextraction (SPME) to analyze breath VOC profiles in critically ill children and explore their potential as early indicators of VAP. Results reveal significant challenges in breath volatilomics, including batch effects and variability in VOC detection. However, normalization strategies allowed for meaningful comparisons across multiple time points, revealing subtle trends in VOC profiles that could differentiate patients with high and low suspicion of VAP. Notably, VOCs such as octanol and benzyl alcohol showed reduced levels in patients with higher suspicion of VAP at Day 6, suggesting potential associations with respiratory infection severity. While preliminary, these findings support further investigation into breath-based VOC signatures as a non-invasive, early diagnostic tool for VAP in pediatric ICUs. This approach could enhance diagnostic accuracy and inform timely clinical decisions, improving patient outcomes.