Carbapenem-resistant Gram-negative bacilli (CR-GNB) are a critical public health threat, and carbapenem use contributes to their spread. Antimicrobial stewardship programs (ASPs) have proven successful in reducing antimicrobial use. However, evidence on the impact of carbapenem resistance remains unclear. We evaluated the impact of a multifaceted ASP on carbapenem use and incidence of CR-GNB in a high-endemic hospital. An interrupted time-series analysis was conducted one year before and two years after starting the ASP to assess carbapenem consumption, CR-GNB incidence, death rates of sentinel events, and other variables potentially related to CR-GNB incidence. An intense reduction in carbapenem consumption occurred after starting the intervention and was sustained two years later (relative effect −83.51%; 95% CI −87.23 to −79.79). The incidence density of CR-GNB decreased by −0.915 cases per 1000 occupied bed days (95% CI −1.743 to −0.087). This effect was especially marked in CR-Klebsiella pneumoniae and CR-Escherichia coli, reversing the pre-intervention upward trend and leading to a relative reduction of −91.15% (95% CI −105.53 to −76.76) and −89.93% (95% CI −107.03 to −72.83), respectively, two years after starting the program. Death rates did not change. This ASP contributed to decreasing CR-GNB incidence through a sustained reduction in antibiotic use without increasing mortality rates.

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is currently a serious global concern. Antimicrobial stewardship programs (ASPs) are one of the key strategies to overcome this resistance. However, evidence about the long-term clinical and ecological impacts of ASPs is scarce. A multidisciplinary team conducted a multifaceted intervention in a CR-Kp endemic hospital over a 6-year period. We assessed the monthly long-term impacts of ASPs on carbapenem use, incidence density (ID), and crude death rates of hospital-acquired CR-Kp infections. Other variables potentially related to CR-Kp incidence and healthcare activity indicators were monitored. Carbapenem use showed a sustained reduction over the long term, with a difference of −66.19% (95% CI −87.03 to −45.34) between the expected pre-intervention trend consumption value and that obtained six years after starting the program. The ID of CR-Kp also decreased significantly and was maintained over the long term, with a relative reduction of −88.14% (95% CI; −100.4 to −75.85) at the end of the study period. The crude death rate of CR-Kp at 14 and 28 days decreased significantly after the intervention and remained steady after six years. Infection control indicator trends remained stable. This mixed ASP contributed to reducing the high incidence of infections and mortality rates of CR-Kp, achieving a sustained ecological and clinical effect.

Introduction: High‐dose methotrexate (HDMTX) use can be limited by the development of acute kidney injury (AKI). Early AKI detection is paramount to prevent further renal injury and irreversible toxicities. This study sought to determine whether early elimination patterns of MTX would be useful as a biomarker of AKI in HDMTX treatment.Methods: This retrospective cohort study included two sites that collected ≥2 MTX levels within 16 h from completion of MTX infusion. Early levels were tagged and MTX elimination half‐life (t_½) were calculated from combinations of two of three different early time periods. Receiver operating characteristic (ROC) curves were synthesized for each elimination t_½ (biomarker) with respect to AKI and delayed methotrexate elimination (DME); the biomarker with the highest area under the ROC curve (AUC) was tested in a multiple variable logistic regression model.Results: Data from 169 patients who received a total of 556 courses of HDMTX were analyzed. ROC analysis revealed MTX elimination t_½ calculated from the second and third time periods had the highest AUC for AKI at 0.62 (interquartile range [IQR] 0.56–0.69) and DME at 0.86 (IQR 0.73–1.00). After adjusting for age, sex, dose (mg/m²), infusion duration, HDMTX course, and baseline estimated glomerular filtration rate, it remained significant for AKI with an OR of 1.29 and 95% confidence interval of 1.03–1.65.Conclusion: Early MTX elimination t_½ measured within 16 h of infusion completion was significantly associated with the development of AKI and serves as an early clearance biomarker that may identify patients who benefit from increased hydration, augmented leucovorin rescue, and glucarpidase administration.

Infections caused by KPC-producing Klebsiella pneumoniae (KPC-KP) represent a persistent public health challenge. This prospective study examines ten-year trends, clinical features, and genomic epidemiology of hospital-onset (HOI) and non-hospital-onset (non-HOI, including healthcare-associated [HcAI] and community-acquired [CA]) KPC-KP infections following a 2012 outbreak. We evaluated the impacts of a 2014 antimicrobial stewardship program (ASP) and COVID-19-related infection prevention and control (IPC) measures, with emphasis on hospital-to-community dissemination. We analysed a prospective, longitudinal cohort of patients (2012–2022) in a tertiary referral hospital. Interrupted time series and ARIMA models assessed ASP and IPC impacts on incidence density (ID). Cross-correlation analysis explored temporal associations between HOI and non-HOI trends. Whole-genome sequencing and PERMANOVA evaluated the genomic structure of ST512/KPC-3 isolates. Multivariable regression analysed the association between infection type and clinical outcomes. Among 467 patients, 33.2% had non-HOI (ID 0.53/1,000 admissions/month) and 66.8% HOI (ID 0.30, p = 0.39). Urinary tract infections predominated in non-HOI (52.9%), while bloodstream and respiratory infections were more common in HOI. Incidence density of HOI and non-HOI infections declined significantly following ASP implementation, with a 4-month lag suggesting sequential transmission dynamics. These reductions were maintained during the pandemic. Genomic data confirmed ST512/KPC-3 dominance and hospital-to-community spread, with temporal factors—rather than acquisition type—explaining genetic variation. Adjusted analyses showed similar 30-day mortality and treatment responses across HOI and non-HOI. ASP and COVID-19 IPC measures contributed to maintaining low KPC-KP incidence. Genomic evidence underscores the role of temporal dynamics and clonal expansion in ST512/KPC-3 dissemination. Non-HOI infections are clinically significant and require targeted, system-wide surveillance and control strategies.

While surgical antibiotic prophylaxis (SAP) is a cornerstone of preventing surgical site infections, adherence to clinical guidelines determines its effectiveness. In Spain, nationwide data on SAP appropriateness are scarce. This study evaluated prescribing practices across Spanish hospitals to assess alignment with national standards and identify factors associated with inappropriate antibiotic use. We conducted a multicentre, cross-sectional, point-prevalence survey (PPS) in hospitals nationwide in Spain. Adult and paediatric patients undergoing elective or urgent surgery in 11 surgical areas were included. SAP appropriateness was assessed based on the SEIMC/AEC national consensus and local clinical guidelines, if available. The primary outcome was overall appropriateness, which was defined as adherence to the recommended indication, antimicrobial agent, dose, route of administration, infusion duration, timing of administration and total duration of SAP. Agreement between guidelines was assessed using Gwet's AC1 coefficient. A mixed-effects logistic regression model was used to identify factors associated with SAP inappropriateness, accounting for institutional clustering and ensuring robust variable selection. Among 2198 patients from 91 hospitals, overall SAP appropriateness was 31·8% (n = 699) according to national consensus, increasing to 41·3% (n = 764) when compared with local protocols. According to the national consensus, the primary cause of inappropriateness was SAP duration. Agreement between national and local guidelines was moderate (Gwet's AC1 0·68), with notable discrepancies in cardiac and thoracic surgery. Independent risk factors identified by the mixed-effects logistic regression model included the number of antimicrobial agents prescribed (OR 25·44, 95% CI 17·05-37·27; p < 0·001), and the use of amoxicillin-clavulanic acid (OR 2·64, 1·77-3·90; p < 0·001), or antibiotics classified as "other" (OR 15·03, 4·95-45·60; p < 0·001). SAP appropriateness in Spanish hospitals is suboptimal, with a significant gap between national evidence-based guidelines and clinical practice. These findings underscore opportunities for targeted antimicrobial stewardship interventions. This study was funded by the Spanish Foundation of Hospital Pharmacy (FEFH).