Incidence of nephrotoxicity associated with intravenous colistimethate sodium administration for the treatment of multidrug‑resistant gram‑negative bacterial infections

Colistimethate sodium (CMS) is the inactive prodrug of colistin, CMS has a narrow antibacterial spectrum with concentration-dependent bactericidal activity against multidrug-resistant gramnegative 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

EN-DALBACEN 2.0 Cohort: real-life study of dalbavancin as sequential/consolidation therapy in patients with infective endocarditis due to Gram-positive cocci

Objectives: 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. Materials and methods: 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. Results: 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. Conclusion: DBV is highly effective, safe, and cost-effective as consolidation therapy in patients with IE by Gram-positive cocci, with few adverse events

Seguimiento y análisis de la realización de la desescalada en el tratamiento con carbapenemes

1. La prescripción de los carbapenemes es apropiada en más de la mitad de los casos. La desescalada en tratamientos con carbapenemes se realiza en casi más de la mitad de las prescripciones en total y en la mitad de las prescripciones apropiadas. 2. La realización de la desescalada no afecta la mortalidad intrahospitalaria ni la mortalidad a los 30 días. 3. La realización de la desescalada en los tratamientos con carbapenemes no alarga la estancia hospitalaria y ni aumenta la tasa de reingreso a los 30 días. 4. Las recomendaciones no impositivas por parte de la farmacéutica para la realización de la desescalada en ITU complicada son seguras y no empeoran los resultados clínicos de los pacientes. La realización de la desescalada en la ITU acorta la duración de la estancia hospitalaria. 5. Las recomendaciones consensuadas con el equipo PROA tienen buena aceptación por parte de los médicos prescriptores y son uno de los factores asociados a la realización de la desescalada, además de la prescripción apropiada de los carbapenemes.1. The prescription of carbapenems is appropriate in more than half of the cases. De-escalation in carbapenem therapy is performed in almost half of the total prescriptions and half of the appropriate prescriptions. 2. De-escalation does not affect in-hospital mortality or 30-day mortality rates. 3. De-escalation in carbapenem therapy does not extend hospital stay nor increases the rate of readmission after 30 days. 4. Pharmacist recommendations for carbapenem de-escalation in complicated UTIs are safe and do not worsen the patient’s clinical outcomes. Performing de-escalation in patients with UTI reduces the duration of hospital stay. 5. Recommendations agreed with the PROA team are well accepted by prescribing physicians and are one of the factors associated with the performance of de-escalation, together with the appropriate carbapenem prescription.Tesis Univ. Granada

Pharmacist recommendations for carbapenem de-escalation in urinary tract infection within an antimicrobial stewardship program.

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 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

Clinical outcomes of carbapenem de-escalation regardless of microbiological results: A propensity score analysis.

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 Carbapenem de-escalation is a safe strategy that does not compromise the clinical status of patients

EN-DALBACEN 2.0 Cohort: real-life study of dalbavancin as sequential/consolidation therapy in patients with infective endocarditis due to Gram-positive cocci

Objectives 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. Materials and methods 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. Results 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. Conclusion DBV is highly effective, safe, and cost-effective as consolidation therapy in patients with IE by Gram-positive cocci, with few adverse events

Clinical outcomes of carbapenem de-escalation regardless of microbiological results: A propensity score analysis

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 Carbapenem de-escalation is a safe strategy that does not compromise the clinical status of patients