RESUMEN

INTRODUCTION: Infections caused by multidrug-resistant gram-negative bacilli (MDR-GNB) in critically ill patients present a challenge for timely and appropriate antibiotic treatment. This is particularly important in patients undergoing extracorporeal life support techniques such as renal replacement therapy and extracorporeal membrane oxygenation. These techniques can introduce additional pharmacokinetic alterations, potentially leading to suboptimal exposure to antibiotics. This study aims to outline dosing strategies and therapeutic drug monitoring protocols for new ß-lactam antibiotics effective against MDR-GNB in critically ill patients undergoing extracorporeal life support techniques at a national level. Additionally, the study seeks to develop a consensus document, based on available evidence. METHODS: The project will comprise two main phases: I) A national survey, and II) the development of a consensus document. This consensus document, undertaken according to ACCORD guidelines, will encompass: a) establishment of a multidisciplinary panel of experts, b) prospective registration of the consensus, c) evidence synthesis, d) modified Delphi rounds. The antimicrobials to be included will be: meropenem, ceftazidime/avibactam, ceftolozane/tazobactam, cefiderocol, meropenem/vaborbactam, imipenem/relebactam, and aztreonam. Extracorporeal life support techniques will include continuous renal replacement therapy, conventional intermittent hemodialysis, and extracorporeal membrane oxygenation. DISCUSSION: The availability of extracorporeal life support techniques has expanded significantly in recent years, alongside a rise in the prevalence of infections caused by multidrug-resistant gram-negative bacilli (MDR-GNB). There is a need to develop evidence-based tools of high quality to standardize dosing and monitoring strategies for new ß-lactam antibiotics.

RESUMEN

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.

RESUMEN

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.

Asunto(s)

RESUMEN

Nosocomial infections caused by non-fermenting Gram-negative bacteria are a real challenge for clinicians, especially concerning the accuracy of empirical treatment. This study aimed to describe the clinical characteristic, empirical antibiotic therapy, accuracy of these prescriptions for appropriate coverage and risk factor for clinical failure of bloodstream infections due to non-fermenting Gram-negative bacilli. This retrospective, observational cohort study was conducted between January 2016 and June 2022. Data were collected from the hospital's electronic record. The statistic tests corresponding to each objective were applied. A multivariate logistic regression was performed. Among the total 120 patients included in the study, the median age was 63.7 years, and 79.2% were men. Considering the appropriate empirical treatment rate by species, inappropriate treatment for S. maltophilia was 72.4% (p = 0.088), for A. baumanii 67.6% and 45.6% for P. aeruginosa. Clinical success was achieved in 53.3%, and overall, 28-day mortality was 45.8%. ICU admission, sepsis or shock septic, age, previous antibiotic treatment and contact with healthcare facilities were independently associated with clinical failure. In conclusion, bloodstream infection produced by multidrug-resistant non-fermenting Gram-negative bacteria is a significant therapeutic management challenge for clinicians. The accuracy of empirical treatment is low due to the fact that it is not recommended to cover these microorganisms empirically, especially S. maltophilia and A. baumanii.

RESUMEN

Two-drug regimens (2DRs) are emerging in clinical practice guidelines as treatment option for both naive and treatment-experienced people living with HIV (PLHIV). Objectives: To determine the real-life effectiveness of 2DR with 25 mg RPV plus 50 mg DTG in a single-tablet regimen (RPV/DTGSTR) and its impact on viral and immune status, lipid profile, and inflammatory markers. Methods: This observational study included 291 treatment-experienced PLHIV, starting 2DR with RPV/DTGSTR between 29 January 2019 and 2 February 2022, who were followed up for at least six months. Participants gave verbal informed consent for the switch in antiretroviral therapy (ART) to RPV/DTGSTR. Results: The mean age of the 291 participants was 51.3 years; 77.7% were male; and 42.9% were in the AIDS stage with a CD4 nadir of 283.5 ± 204.6 cells/uL. The median time since HIV diagnosis was 19.7 years (IQR: 10.6-27). Before 2DR, patients received a median of five ART lines (IQR: 3-7) for 22.2 years (IQR: 14-26), with 34.4% (n = 100) receiving a three-drug regimen (3DR), 31.3% (n = 91) receiving monotherapy, and 34.4% (n = 100) receiving 2DR. The median time on RPV/DTGSTR was 14 months (IQR: 9.5-21); 1.4% were lost to the follow-up. Effectiveness was 96.2% by intention-to-treat (ITT) analysis, 97.5% by modified ITT, and 99.3% by per-protocol analysis. Virological failure was observed in 0.69%, blips in 3.5%, and switch to another ART in 1.4%. The mean lipid profile improved, with reductions in TC/HDLc ratio (3.9 ± 0.9 vs. 3.6 ± 0.9; p = 0.0001), LDLc (118.3 ± 32.2 mg/dL vs. 106.2 ± 29.8 mg/dL, p = 0.0001), TG (130.9 ± 73.9 mg/dL vs. 115.9 ± 68.5 mg/dL, p = 0.0001), and CD4/CD8 ratio increase (0.99 ± 0.58 vs. 1.01 ± 0.54; p = 0.0001). The cost-effectiveness of 2DR with RPV/DTGSTR was similar to that of DTG/3TC and superior to those of BIC/TAF/FTC and DRV/c/TAF/FTC, with higher virological suppression and lower annual costs. Conclusions: The switch to RPV plus DTG in STR is a cost-effective, long-lasting, and robust strategy for PLHIV, with a very long experience of treatment, which improves the lipid profile without affecting inflammatory markers.

Asunto(s)

RESUMEN

The current morbimortality of serious infections is unacceptable and there is a need to promote the increase in the efficacy of empirical and targeted antibiotherapy. This could be achieved by initiatives coming from ASP teams aimed at promoting increased efficacy of antibiotic therapy .In the optimization of the antibiotic therapy there are several critical points in which an adequate timing could achieve benefits in the survival of patients with severe infections: prompt initiation of empirical treatment; de-escalation performance, appropriate targeted treatment; and finally, curtail antibiotic duration. (AU)

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

The aim of this study was to describe the differences in antimicrobial susceptibility to moxifloxacin between European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) in anaerobic microorganisms. Overall, resistance to moxifloxacin appears to be high in almost all groups of anaerobes, but enormous differences in susceptibility rates between these two committees could be observed.

Asunto(s)

RESUMEN

OBJECTIVE: To validate a Russian-language version of the World Health Organization's Alcohol Use Disorders Identification Test (AUDIT). METHODS: We invited 2173 patients from 21 rural and urban primary health-care centres in nine Russian regions to participate in the study (143 declined and eight were excluded). In a standardized interview, patients who had consumed alcohol in the past 12 months provided information on their sociodemographic characteristics and completed the Russian AUDIT, the Kessler Psychological Distress Scale and the Composite International Diagnostic Interview to identify problem drinking and alcohol use disorders. We assessed the feasibility of administering the test, its internal consistency and its ability to predict hazardous drinking and alcohol use disorders in primary health care in the Russian Federation. FINDINGS: Of the 2022 patients included in the study, 1497 were current drinkers with Russian AUDIT scores. The test was internally consistent with good psychometric properties (Cronbach's α : 0.842) and accurately predicted alcohol use disorders and other outcomes (area under the curve > 75%). A three-item short form of the test correlated well with the full instrument and had similar predictive power (area under the curve > 80%). We determined sex-specific thresholds for all outcomes, as non-specific thresholds resulted in few women being identified. CONCLUSION: With the validated Russian AUDIT, there is no longer a barrier to introducing screening and brief interventions into primary health care in the Russian Federation to supplement successful alcohol control policies.

Asunto(s)

RESUMEN

Understanding changes in environmental mercury concentrations is important for assessing the risk to human and wildlife populations from this potent toxicant. Here, we use herring gull (Larus argentatus) eggs to evaluate temporal changes in total mercury (THg) availability from two locations on Great Slave Lake (GSL), Northwest Territories, Canada. Egg THg concentrations increased through time, but this change was due to shifts in gull diets. Stable nitrogen isotopes allowed adjustment of egg THg concentrations for dietary changes. Diet-adjusted egg THg concentrations showed no long-term trend. Consistent with that result, new statistical analysis of THg concentrations in three species of GSL fish showed minor or no temporal changes. Although a long-term trend was absent, inter-year differences in adjusted egg THg concentrations persisted. Contributions of environmental variables (i.e., river flow, lake level, air temperature, precipitation, and wildfire) to these differences were investigated. Egg THg concentrations were greater following years of lower lake levels and greater wildfire extent. Lake level could have affected mercury methylation. Increased wildfire could have enhanced terrestrial Hg releases to the atmosphere where it was transported long distances to GSL. Climate change may increase wildfire extent with impacts on Hg bioaccumulation in northern ecosystems. Egg Hg levels reported here are unlikely to pose health risks to gulls, but in light of ongoing environmental change, monitoring should continue. Our study emphasizes the importance of ancillary datasets in elucidating Hg trends; such information will be critical for evaluating the effectiveness of Hg mitigation strategies implemented as part of the Minamata Convention.

Asunto(s)

Asunto(s)

RESUMEN

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Asunto(s)

RESUMEN

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Carbapenem de-escalation is a safe strategy that does not compromise the clinical status of patients.

Asunto(s)

RESUMEN

Levels of biomagnifying contaminants are greatest in high-trophic level biota (e.g., predatory birds such as gulls). Gull eggs have been used to assess contaminant spatial patterns and sources, but such assessments must consider how organism trophic position may influence spatial inferences. Stable nitrogen isotopes (δ15 N) in bulk tissue are routinely used in this context. However, bulk δ15 N values are only useful if spatial differences in baseline δ15 N values are considered. Amino acid compound-specific stable nitrogen isotope analysis can generate estimates of baseline δ15 N values and trophic position from the same sample. In the present study, eggs (n = 428) of California (Larus californicus), herring (Larus argentatus smithsonianus), and ring-billed (Larus delawarensis) gulls were used to assess spatial patterns in mercury (Hg) availability in 12 western Canadian lakes located over 14 degrees of latitude, with amino acid compound-specific stable isotope analysis adjustment of egg Hg levels for trophic position. Mean trophic position-adjusted egg Hg levels (micrograms per gram, dry wt) were greatest at sites in receiving waters of the Athabasca River (X¯ = 0.70) compared to southern (X¯ = 0.39) and northern (X¯ = 0.50) regions. Research is required to investigate factors (e.g., local Hg released as a result of human activities, processes influencing Hg methylation) which may be responsible for greater Hg availability in the lower Athabasca River basin. However, it is clear that amino acid compound-specific stable isotope analysis is a valuable tool for assessing contaminant spatial patterns. Environ Toxicol Chem 2018;37:1466-1475. © 2018 SETAC.

Asunto(s)

RESUMEN

Bird eggs are often used to monitor levels and trends of mercury (Hg) in the environment. Logistical issues in such studies sometimes require the use of eggs at different stages of development. Therefore, it is important to understand how embryonic age may affect egg Hg concentrations. Studies using dry weight Hg concentrations in eggs assume that dry mass (e.g., lipids) does not change through embryonic development and thus expressing concentrations on a dry weight basis adjusts for any changes that may occur in egg mass throughout development. That assumption is tested in the present study by injecting chicken eggs with Hg and measuring Hg concentrations in embryonic contents at different stages of artificial incubation. The results indicate that dry weight Hg concentrations in eggs at later stages of development are statistically greater than in undeveloped eggs. To address this issue, we developed a method of standardizing egg Hg concentrations for embryonic age based on egg contents density (egg contents mass/egg contents volume). A combined dataset (n = 225) from precocial and semi-precocial birds was used to demonstrate that egg contents density declines with increasing embryonic development. Based on this finding, we applied a formula to adjust egg dry weight Hg concentrations for stage of development: adjusted egg [Hg] = unadjusted [Hg] × (egg contents density). The application of this approach to adjust data from the chicken egg Hg injection study resulted in there being no statistically significant difference in dry weight Hg levels in eggs at different stages of embryonic development. The adjustment approach described in the present study is a straightforward method to account for stage of development when assessing Hg levels in avian eggs and should be widely applicable to studies of this nature. Environ Toxicol Chem 2018;37:1168-1174. © 2017 SETAC.

Asunto(s)