Vancomycin pharmacokinetic/pharmacodynamic (PK/PD) targets have not been validated in the neonatal population as no specifically designed studies are available. The main goal of this study was to ...analyze the therapeutic vancomycin regimen, the 24-h area under the curve (AUC
), and the trough plasma concentration (
) obtained that achieved clinical and microbiological effectiveness in a cohort of neonates. This was an observational, prospective, single-center study covering a period of 2 years. Eligible patients were neonates and young infants who were undergoing treatment with intravenous vancomycin for ≥72 h with ≥1
available. The primary outcome was the association of
and AUC
with clinical and microbiological efficacy at the beginning (early clinical evolution ECE) and the end (late clinical evolution LCE) of treatment with vancomycin. A total of 43 patients were included, 88.4% of whom were cured. In ECE, the cutoff points of the receiver operating characteristic (ROC) curve were 238 mg · h/L (sensitivity of 61% and specificity of 88%) for AUC
and 6.8 μg/mL (sensitivity of 61% and specificity of 92%) for
. In LCE, the
value was 11 μg/mL, with a sensitivity of 80% and a specificity of 92%. In this analysis, AUC
was not considered a good predictor. Logistic regression showed that a vancomycin
of ≤6.8 μg/mL was associated with an unfavorable ECE (
= 0.001), being 18 times more likely to progress poorly compared to those with higher levels. AUC
and
are good predictors of ECE in this population. Concentrations close to 7 μg/mL and an AUC
of around 240 mg · h/L 48 h after antibiotic initiation seem to be sufficient to achieve clinical cure in most cases.
Pharmacokinetic nomograms, equations, and software are considered the main tools available for Therapeutic Drug Monitoring (TDM). Model-informed precision dosing (MIPD) is an advanced discipline of ...TDM that allows dose individualization, and requires a software for knowledge integration and statistical calculations. Due to its precision and extensive applicability, the use of these software is widespread in clinical practice. However, the currently available evidence on these tools remains scarce.
To review and summarize the available evidence on MIPD software tools to facilitate its identification, evaluation, and selection by users.
An electronic literature search was conducted in MEDLINE, EMBASE, OpenAIRE, and BASE before July 2022. The PRISMA-ScR was applied. The main inclusion criteria were studies focused on developing software for use in clinical practice, research, or modelling.
Twenty-eight software were classified as MIPD software. Ten are currently unavailable. The remaining 18 software were described in depth. It is noteworthy that all MIPD software used Bayesian statistical methods to estimate drug exposure and all provided a population model by default, except NONMEN.
Pharmacokinetic software have become relevant tools for TDM. MIPD software have been compared, facilitating its selection for use in clinical practice. However, it would be interesting to standardize the quality and validate the software tools.
Real-life data on doravirine (DOR) in different drug combinations are limited. We evaluated the effectiveness of DOR plus two nucleos(t)ide reverse transcriptase inhibitors (NRTI), mainly ...abacavir/lamivudine, and dual therapies in people with HIV (PWH), mostly virologically suppressed. Ambispective observational study that enrolled adults PWH who initiated a DOR-based regimen from September 2020 to February 2022 at a referral center in Spain. Participants were grouped as follows: A, received DOR plus two NRTI; B, dual therapy (DT) with DOR plus dolutegravir (DTG) or darunavir/cobicistat (DRVc); C, DOR plus ≥two antiretroviral drugs. The primary endpoints were treatment effectiveness at week 48 by intention-to-treat (ITT) and per-protocol analysis (OT). A cohort of 187 participants, 91% virologically suppressed, were analyzed after a median follow-up of 112 weeks (80–136). Group A received DOR plus abacavir/lamivudine (ABV/3TC) (n = 109) or tenofovir/emtricitabine (TFV/3TC) (n = 45). At week 48, the effectiveness of DOR plus ABV/3TC by ITT was 90.8% (CI95, 88.0–93.6), better than with TFV/FTC 73.3% (66.7–79.9); P = 0.003. Only one virologic failure was observed. Mild adverse effects were the cause of treatment discontinuation in 7.8%, followed by switching to a single-tablet regimen. In group B, the effectiveness by ITT was 92.9% (CI95, 88.0–97.8) at week 48. No adverse effects or virologic failure were registered in this group. DOR plus two NRTI or DT have long-term effectiveness and safety as a switching option for PWH, mostly virologically suppressed. The DOR plus ABV/3TC combination has shown even better effectiveness than TFV/FTC.IMPORTANCEDOR-based regimens have shown long-term effectiveness and safety in PWH, mostly virologically suppressed. The combination of DOR plus ABV/3TC has shown even better safety and effectiveness than TFV/FTC. DOR plus two NRTI offers cost benefits compared to other regimens.
Vancomycin is commonly used as a treatment for neonatal infections. However, there is a lack of consensus establishing the optimal vancomycin therapeutic regimen and defining the most appropriate ...PK/PD parameter correlated with the efficacy. A recent guideline recommends AUC-guided therapeutic dosing in treating serious infections in neonates. However, in clinical practice, trough serum concentrations are commonly used as a surrogate PKPD index for AUC24. Despite this, target serum concentrations in a neonatal population remain poorly defined. The objective is to describe the relationship between therapeutic regimens and the achievement of clinical or pharmacokinetic outcomes in the neonatal population. The review was carried out following PRISMA guidelines. A bibliographic search was manually performed for studies published on PubMed and EMBASE. Clinical efficacy and/or target attainment and the safety of vancomycin treatment were evaluated through obtaining serum concentrations. A total of 476 articles were identified, of which 20 met the inclusion criteria. All of them evaluated the target attainment, but only two assessed the clinical efficacy. The enormous variability concerning target serum concentrations is noteworthy, which translates into a difficulty in determining which therapeutic regimen achieves the best results. Moreover, there are few studies that analyze clinical efficacy results obtained after reaching predefined trough serum concentrations, this information being essential for clinical practice.
Deprescription is the revision of the therapeutic plan with the aim of simplifying it, taking into account patient preferences, prognosis and environment. This strategy is particularly relevant in ...older patients, mostly polymedicated individuals, since they are exposed to numerous adverse effects and interactions and tend to have less adherence to treatments.
To identify the deprescribing tools for older patients available in the scientific literature, classify them according to their design and describe their main features and potential applicability in clinical practice.
A search was conducted in PubMed and EMBASE for relevant literature published before July 2021. The PRISMA-ScR method was applied, extracting variables related to study and tool characteristics as well as potential clinical applicability. The main inclusion criteria were studies focused on designing or developing deprescribing tools for older patients and those that indicated the features of the deprescribing tool used in detail.
Fourteen of 723 papers met the inclusion criteria, and 12 tools were identified: 6 “algorithm-based tools” and 6 “criterion-based tools”. Though all tools are aimed at older patients, there are certain peculiarities regarding their design, population, application setting and variables included. Of the 6 criterion-based tools found, 4 used the Delphi method for their design and development. Furthermore, most of them agree on the pharmacological groups that are likely to be deprescribed.
Taking into account the importance of the clinical situation and priorities in the care plan in the deprescribing process, the authors believe that tools which help to evaluate these aspects are the most suitable for application in clinical practice. However, it is necessary to continue studying applicability in real-life clinical scenarios and to obtain health results.
•The presence of “criterion-based” and “algorithm-based” tools in the literature is balanced, with six algorithms and six criteria identified.•Tools identified differ in the target population, the design used for their development, their potential setting of application and the variables included in each tool.•There are many deprescribing tools available in the literature, but it is still critical to identify its real usefulness in specific populations.
LESS-CHRON (List of Evidence-Based Deprescribing for Chronic Patients) and STOPPFrail (Screening Tool of Older Persons' Prescriptions in Frail adults with limited life expectancy) are criterion-based ...deprescribing tools. This study aimed to identify the prevalence of potentially inappropriate medications (PIMs) with these tools in an outpatient, polymedicated, older population with multimorbidity.
Single-center cross-sectional observational study.
PIMs and criteria subject to deprescribing identified by each tool were collected in patients who were being followed up on outpatient internal medicine consultation.
PIMs were identified by STOPPFrail and LESS-CHRON criteria reviewing medical histories and pharmacologic treatments of the patients in the electronic health card system. Sociodemographic, clinical, and pharmacologic variables were recorded. A correlation analysis between treatment tools and clinical values was performed using the nonparametric Spearman rho correlation.
Eighty-three patients with a median of 14.4 (interquartile range 12-17) prescribed drugs were included. The total number of PIMs identified with LESS-CHRON was 158 vs 127 with STOPPFrail. Eight of the 27 criteria (29.6%) for LESS-CHRON and 15 of the 25 for STOPPFrail were found to be not applicable. A significant correlation was obtained for both tools with the number of prescribed drugs at the time of inclusion. The Profund, Barthel, and Frail-VIG index only showed a significant correlation with LESS-CHRON.
Both tools have shown the capacity to identify PIMs that can be deprescribed in the population studied. However, LESS-CHRON appears to have a greater detection potential in the subgroup of patients analyzed. STOPPFrail brings a certain complementarity in other areas of therapy not covered by LESS-CHRON.
This study explored the feasibility of a bundle of indicators aimed at assessing the quality of antimicrobial use in intensive care units (ICUs) through an observational prospective study spanning 12 ...quarters (January 2019–December 2021) in a 1290-bed teaching hospital in Spain. Members of the antimicrobial stewardship programme team selected the indicators to analyse the quality of antimicrobial use based on consumption data from a list proposed in a previous study. Antimicrobial use in the ICU was measured as defined daily dose (DDD) per 100 occupied bed-days. Trends and points of change were analysed with segmented regression. The intravenous macrolides/intravenous respiratory fluoroquinolones ratio in the ICU increased progressively, although not significantly, by 11.14% per quarter, likely related to prioritization of the use of macrolides in serious community-acquired pneumonia and the coronavirus disease 2019 pandemic. A remarkable upward trend of 2.5% per quarter was detected in the anti-methicillin-susceptible Staphylococcus aureus/anti-methicillin-resistant S. aureus agents ratio in the ICU, which could be explained by the low prevalence of methicillin-resistant S. aureus at the study centre. Patterns of amoxicillin-clavulanic acid/piperacillin-tazobactam ratio and diversification of anti-pseudomonal beta-lactams showed an increment in use over the study. The use of these novel indicators provides additional information for the current analysis of DDD. Implementation is feasible, and led to the detection of patterns that agree with local guidelines and cumulative antibiogram reports, and foster targeted improvement actions within antimicrobial stewardship programmes.
In 2017, a questionnaire was developed in Italian with the aim of determining clinicians' perceptions of deprescription in the elderly population. The objective was to translate and cross-culturally ...adapt this deprescription questionnaire to Spanish.
Forward and blind-back translations, followed by a synthesis and adaptation by a third translator. Development of an expert panel to evaluate the adequacy of the translation, the understandability of the translated question and the usefulness of each question. A comprehensibility analysis was carried out on physicians familiar with deprescription.
The Spanish version of the questionnaire was obtained, where the average degree of difficulty in the direct and the back-translation was low/moderate. In the first phase of the panel of experts, 4 questions had sections considered "indeterminate" and one question was "doubtful". After the second phase, all the questions were considered "adequate" except for one.
This is the first cross-cultural adaptation to Spanish of this questionnaire, which will provide a tool to assess clinicians' perception of this practice and establish improvements to carry out this activity.
There are barriers to deprescription that hinder its implementation in clinical practice. The objective of this study was to analyse the main barriers and limitations of the deprescription process ...perceived by physicians who care for multipathological patients.
The "
" was adapted to an online format and sent to physicians in geriatrics. Question 1 is a reference to establish agreement or disagreement with this practice. The influence of different aspects of deprescription was analysed via the demographic characteristics of the clinicians and perceptions of the various barriers (questions 2-9) by means of bivariate analysis. Based on the latter, a multivariate model was carried out to demonstrate the relationship between barriers and the degree of deprescription agreement among respondents.
Of the 72 respondents, 72.2% were in favour of deprescribing. Regarding the analyses, the demographic characteristics did not influence rankings. The deprescription of preventive drugs and consensus with patients were associated with a positive attitude towards deprescribing, while withdrawing drugs prescribed by other professionals, time constraints and patient reluctance emerged as possible barriers. The only factor independently associated with deprescribing was lack of time.
Time was found to be the main barrier to deprescription. Training, the creation of multidisciplinary teams and integrated health systems are key facilitators.
We aimed to define a novel indicator for monitoring antimicrobial use specifically in the Emergency Department Observation Unit (EDOU) and to assess the long-term impact of an institutional ...education-based antimicrobial stewardship program (ASP) on the antimicrobial prescribing pattern and clinical outcomes in this setting. A quasi-experimental interrupted time-series study was performed from 2011 to 2022. An educational ASP was implemented at the EDOU in 2015. To estimate changes in antimicrobial use, we designed an indicator adjusted for patients at risk of antimicrobial prescribing: defined daily doses (DDDs) per 100 patients transferred from the Emergency Department to the Observation Unit (TOs) per quarter. The number of bloodstream infections (BSIs) and the crude all-cause 14-day mortality were assessed as clinical outcomes. Antimicrobial use showed a sustained reduction with a trend change of -1.17 DDD per 100 TO and a relative effect of -45.6% (CI95% -64.5 to -26.7), particularly relevant for meropenem and piperacillin-tazobactam, with relative effects of -80.4% (-115.0 to -45.7) and -67.9% (-93.9 to -41.9), respectively. The incidence density of all BSIs increased significantly during the ASP period, with a relative effect of 123.2% (41.3 to 284.7). The mortality rate remained low and stable throughout the study period, with an absolute effect of -0.7% (-16.0 to 14.7). The regular monitoring of antimicrobial use in the EDOU by using this new quantitative indicator was useful to demonstrate that an institutional education-based ASP successfully achieved a long-term reduction in overall antimicrobial use, with a low and steady BSI mortality rate.
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