Infective endocarditis (IE) has high mortality and morbidity and requires long hospital stays to deliver the antibiotic treatment recommended in clinical practice guidelines. We aimed to analyse the health outcomes of the use of dalbavancin (DBV) in the consolidation treatment of IEs caused by Gram-positive cocci and to perform a pharmacoeconomic study. This observational, retrospective, Spanish multicentre study in patients with IE who received DBV as part of antibiotic treatment in consolidation phase were followed for at least 12 months. The study was approved by the Provincial Committee of the coordinating centre. The study included 124 subjects, 70.2% male, with a mean age of 67.4 years and median Charlson index of 4 (interquartile range: 2.5-6). Criteria for definite IE were met by 91.1%. Coagulase-negative staphylococci (38.8%), Staphylococcus aureus (22.6%), Enterococcus faecalis (19.4%), and Streptococcus Spp. (9.7%) were isolated more frequently, all susceptible to vancomycin. Before DVB administration, 91.2% had undergone surgery; 60.5% had received a second regimen for 24.5 d (16.6-56); and 20.2% had received a third regimen for 14.5 d (12-19.5). DBV was administered to facilitate discharge in 95.2% of cases. At 12 months, the effectiveness was of 95.9%, and there was 0.8% loss to follow-up, 0.8% IE-related death, and 3.2% relapse. Adverse events were recorded in 3.2%. The hospital stay was reduced by 14 d, and there was a mean savings of 5548.57 €/patient vs. conventional treatments. DBV is highly effective, safe, and cost-effective as consolidation therapy in patients with IE by Gram-positive cocci, with few adverse events.

Carbapenem antibiotics are considered the treatment of choice for serious extended-spectrum beta-lactamase-producing Gram-negative bacteria infections. Our objectives were to analyze the results of carbapenem de-escalation therapy in complicated urinary tract infections (UTIs) attended in a third-level Spanish hospital and to evaluate the impact of pharmacist recommendation in this practice, the outcomes obtained, and associated factors. This prospective observational study of carbapenem prescriptions and de-escalation performance was conducted in a third-level hospital between August 1 2013 and July 31, 2014. Data were gathered on carbapenem treatment duration, de-escalation, length of hospital stay, mortality rate, and associated re-admissions. De-escalation, which was only ordered for patients with positive cultures, was conducted in 49.7% of the 163 patients with complicated UTI. More than half (69.1%) of pharmacist interventions were accepted. De-escalation reduced the median hospital stay by five days (p=0.030). Crude hospital mortality was lower in the de-escalation group (7.4% vs. 29.3%, p<0.001), although their exposure to carbapenems was lower (4 vs 6 days, p<0.001). Factors associated with de-escalation were ICU stay for at least 48h, pharmacist recommendation and ESBL or AmpC producing Enterobacteriaceae. Factors associated with in-hospital mortality were age, previous admission and duration of hospital stay, but not pharmacist recommendation. Otherwise, carbapenem de-escalation was associated as a protective factor against in-hospital mortality. Carbapenem de-escalation in accordance with pharmacist recommendation proved to be a safe approach in complicated UTI, reducing the hospital stay of patients without affecting the re-admission rate.

The aim of this study was to evaluate the safety and efficacy of de-escalation in patients under treatment with carbapenems and its impact on clinical outcomes. A prospective observational study was conducted for 1year. Patients administered active carbapenems for at least 24h were included. Primary outcomes were in-hospital mortality, mortality at 30 days after carbapenem prescription, and infection-related readmission within 30 days. De-escalation was defined as the substitution of carbapenem with narrower spectrum antimicrobial agents or its discontinuation during the first 96h of treatment. The study included 1161 patients, and de-escalation was performed in 667 (57.5%) of these. In the de-escalation group, 54.9% of cultures were positive. After propensity score matching, 30-day mortality was lower (17.4% vs. 25.7%, p=0.036), carbapenem treatment was 4 days shorter (4 vs. 8 days, p<0.001), total antibiotic therapy duration was 2 days longer (12 vs. 10 days, p=0.003), and length of hospital stay was 5 days shorter (8 vs. 13 days, p=0.008) in the de-escalated versus non-de-escalated patients. In-hospital mortality and 30-day readmission rates did not differ significantly between these groups. Carbapenem de-escalation is a safe strategy that does not compromise the clinical status of patients.

Colistimethate sodium (CMS) is the inactive prodrug of colistin, CMS has a narrow antibacterial spectrum with concentration-dependent bactericidal activity against multidrug-resistant gram-negative bacteria, including Pseudomonas aeruginosa and Acinetobacter baumannii. This study aimed to analyze potential correlations between clinical features and the development of CMS-induced nephrotoxicity. This retrospective cohort study was conducted in a tertiary-care university hospital between 1 January 2015 and 31 December 2019. A total of 163 patients received CMS therapy. 75 patients (46%) developed nephrotoxicity attributable to colistin treatment, although only 14 patients (8.6%) discontinued treatment for this reason. 95.7% of CMS were prescribed as target therapy. Acinetobacter baumannii spp. was the most commonly identified pathogen (72.4%) followed by P. aeruginosa (19.6%). Several risk factors associated with nephrotoxicity were identified, among these were age (HR 1.033, 95%CI 1.016–1.052, p < 0.001), Charlson Index (HR 1.158, 95%CI 1.0462–1.283; p = 0.005) and baseline creatinine level (HR 1.273, 95%CI 1.071–1.514, p = 0.006). In terms of in-hospital mortality, risk factors were age (HR 2.43, 95%CI 1.021–1.065, p < 0.001); Charlson Index (HR 1.274, 95%CI 1.116–1.454, p = 0.043), higher baseline creatinine levels (HR 1.391, 95%CI 1.084–1.785, p = 0.010) and nephrotoxicity due to CMS treatment (HR 5.383, 95%CI 3.126–9.276, p < 0.001). In-hospital mortality rate were higher in patients with nephrotoxicity (log rank test p < 0.001). In conclusion, the nephrotoxicity was reported in almost half of the patients. Its complex management, continuous renal dose adjustment and monitoring creatinine levels at least every 48 h leads to a high percentage of inappropriate use and treatment failure.

Background: Ceftobiprole is a fifth-generation cephalosporin that has been approved in Europe solely for the treatment of community-acquired and nosocomial pneumonia. The objective was to analyze the use of ceftobiprole medocaril (Cefto-M) in Spanish clinical practice in patients with infections in hospital or outpatient parenteral antimicrobial therapy (OPAT). Methods: This retrospective, observational, multicenter study included patients treated from 1 September 2021 to 31 December 2022. Results: A total of 249 individuals were enrolled, aged 66.6 ± 15.4 years, of whom 59.4% were male with a Charlson index of four (IQR 2–6), 13.7% had COVID-19, and 4.8% were in an intensive care unit (ICU). The most frequent type of infection was respiratory (55.8%), followed by skin and soft tissue infection (21.7%). Cefto-M was administered to 67.9% of the patients as an empirical treatment, in which was administered as monotherapy for 7 days (5–10) in 53.8% of cases. The infection-related mortality was 11.2%. The highest mortality rates were identified for ventilator-associated pneumonia (40%) and infections due to methicillin-resistant Staphylococus aureus (20.8%) and Pseudomonas aeruginosa (16.1%). The mortality-related factors were age (OR: 1.1, 95%CI (1.04–1.16)), ICU admission (OR: 42.02, 95%CI (4.49–393.4)), and sepsis/septic shock (OR: 2.94, 95%CI (1.01–8.54)). Conclusions: In real life, Cefto-M is a safe antibiotic, comprising only half of prescriptions for respiratory infections, that is mainly administered as rescue therapy in pluripathological patients with severe infectious diseases.

Enterococcal endocarditis (EIE) affects elderly patients, with high rates of complications and mortality, and dalbavancin (DBV) exhibits significant antimicrobial activity against most enterococci. However, data are lacking on the use of DBV in EIE. The main objective was to evaluate the outcomes of treatment with DBV in the consolidation therapy of IE by Enterococcus spp. Spanish-French retrospective observational study of patients with EIE enrolled between November 2016 and June 30, 2022 receiving DBV in consolidation phase and followed for ≥12 months. Ninety-eight patients were enrolled, 69.4 % male, with mean age of 71.2 (±12.51) years and median Charlson index of 5 (IQR 3-7). Criteria for definite IE were met by 84.7%; 60.2 % had IE on native valve, 26.5 % late prosthetic IE, 8.2 % early prosthetic IE, 2 % cardiovascular implantable electronic-IE (CIE-IE), and 3.1 % CIE-IE and valve. Aortic valve involvement was observed in 66.3 %. E. faecalis was isolated in 86.7 %, E. faecium in 11.2 %; 32.6 % underwent surgery, and these had a higher cure rate (100 % vs 75.8 %; p = 0.005) and lower mortality (0 vs 13.6 %; p = 0.029). DBV was administered to facilitate discharge in 88.8 %. Total dose was 2500 mg (1500-3000) over 3.5 weeks (2-4). Loss to follow-up was 0 %, relapse rate 8.2 %, 1-year IE-related mortality 3.1 %, and clinical cure rate 81.2 %. Severe adverse events affected 1 % (acute tubular necrosis). Hospital stay was reduced by 21 days (14-28). DBV appears to be highly effective, safe, and cost-effective as consolidation therapy in patients with IE caused by Enterococcus spp., with minimal adverse events.