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Low serum albumin levels are very common in critically ill patients, with reported incidences as high as 40–50%. This condition appears to be associated with alterations in the degree of protein binding of many highly protein-bound antibacterials, which lead to altered pharmacokinetics and pharmacodynamics, although this topic is infrequently considered in daily clinical practice. The effects of hypoalbuminaemia on pharmacokinetics are driven by the decrease in the extent of antibacterial bound to albumin, which increases the unbound fraction of the drug. Unlike the fraction bound to plasma proteins, the unbound fraction is the only fraction available for distribution and clearance from the plasma (central compartment). Hence, hypoalbuminaemia is likely to increase the apparent total volume of distribution (V d ) and clearance (CL) of a drug, which would translate to lower antibacterial exposures that might compromise the attainment of pharmacodynamic targets, especially for time-dependent antibacterials. The effect of hypoalbuminaemia on unbound concentrations is also likely to have an important impact on pharmacodynamics, but there is very little information available on this area. The objectives of this review were to identify the original research papers that report variations in the highly protein-bound antibacterial pharmacokinetics (mainly V d and CL) in critically ill patients with hypoalbuminaemia and without renal failure, and subsequently to interpret the consequences for antibacterial dosing. All relevant articles that described the pharmacokinetics and/or pharmacodynamics of highly protein-bound antibacterials in critically ill patients with hypoalbuminaemia and conserved renal function were reviewed. We found that decreases in the protein binding of antibacterials in the presence of hypoalbuminaemia are frequently observed in critically ill patients. For example, the V d and CL of ceftriaxone (85–95% protein binding) in hypoalbuminaemic critically ill patients were increased 2-fold. A similar phenomenon was reported with ertapenem (85–95% protein binding), which led to failure to attain pharmacodynamic targets (40% time for which the concentration of unbound [free] antibacterial was maintained above the minimal inhibitory concentration [ f T>MIC] of the bacteria throughout the dosing interval). The V d and CL of other highly protein-bound antibacterials such as teicoplanin, aztreonam, fusidic acid or daptomycin among others were significantly increased in critically ill patients with hypoalbuminaemia compared with healthy subjects. Increased antibacterial V d appeared to be the most significant pharmacokinetic effect of decreased albumin binding, together with increased CL. These pharmacokinetic changes may result in decreased achievement of pharmacodynamic targets especially for time-dependent antibacterials, resulting in sub-optimal treatment. The effects on concentration-dependent antibacterial pharmacodynamics are more controversial due to the lack of data on this topic. In conclusion, altered antibacterial-albumin binding in the presence of hypoalbuminaemia is likely to produce significant variations in the pharmacokinetics of many highly protein-bound antibacterials. Dose adjustments of these antibacterials in critically ill patients with hypoalbuminaemia should be regarded as another step for antibacterial dosing optimization. Moreover, some of the new antibacterials in development exhibit a high level of protein binding although hypoalbuminaemia is rarely considered in clinical trials in critically ill patients. Further research that defines dosing regimens that account for such altered pharmacokinetics is recommended.

PurposeCeftriaxone total and unbound pharmacokinetics (PK) can be altered in critically ill patients with septic shock and hypoalbuminemia receiving continuous veno-venous hemodiafiltration (CVVHDF). The objective of this study was to determine the dosing strategy of ceftriaxone that maximizes the probability of maintaining the concentration above the MIC of the susceptible bacteria (≤2 mg/L by the EUCAST) for a 100% of the dosing interval (100% ƒuT>MIC).MethodsIn a prospective PK study in the intensive care units of two tertiary Spanish hospitals, six timed blood samples were collected per patient; for each sample, ceftriaxone total and unbound concentrations were measured using a liquid chromatography coupled to tandem mass spectrometry method. Population PK analysis and Monte-Carlo simulations were performed using NONMEMv.7.3®.ResultsWe enrolled 8 critically ill patients that met the inclusion criteria (47 blood samples). Median age (range) was 70 years (47-85), weight 72.5 kg (40-95), albumin concentration 24.2 g/L (22-34), APACHE II score at admission 26 (17-36), and SOFA score on the day of study 12 (9-15). The unbound fraction (ƒu) of ceftriaxone was 44%, and total CL was 1.27 L/h, 25-30% higher than the CL reported in septic critically ill patients not receiving renal replacement therapies, and dependent on albumin concentration and weight. Despite this increment in ƒu and CL, Monte-Carlo simulations showed that a dose of 1 g once-daily ceftriaxone is sufficient to achieve a 100% ƒuT>MIC for MICs ≤2 mg/L for any range of weight and albumin concentration.ConclusionOnce-daily 1 g ceftriaxone provides optimal exposure in critically ill patients with septic shock and hypoalbuminemia receiving CVVHDF.

Background: Daptomycin-induced eosinophilic pneumonia (DEP) is a rare but severe adverse effect and the risk factors are unknown. The aim of this study was to determine risk factors for DEP. Methods: A retrospective cohort study was performed at the Bone and Joint Infection Unit of the Hospital Universitari Bellvitge (January 2014–December 2018). To identify risk factors for DEP, cases were divided into two groups: those who developed DEP and those without DEP. Results: Among the whole cohort (n = 229) we identified 11 DEP cases (4.8%) and this percentage almost doubled in the subgroup of patients ≥70 years (8.1%). The risk factors for DEP were age ≥70 years (HR 10.19, 95%CI 1.28–80.93), therapy >14 days (7.71, 1.98–30.09) and total cumulative dose of daptomycin ≥10 g (5.30, 1.14–24.66). Conclusions: Clinicians should monitor cumulative daptomycin dosage to minimize DEP risk, and be cautious particularly in older patients when the total dose of daptomycin exceeds 10 g.

A catheter is a device that is inserted into the venous system to infuse treatment with controlled doses per unit of time. The study of its interaction with blood flow cannot be easily analysed with common analytical methods or different visualization techniques in real life. Computational Fluid Dynamics has become a very useful tool in a wide variety of fields of scientific study and has allowed access to the understanding of the anatomical and physiological functioning of the human body. In this work, Computational Fluid Dynamics is used to study the effects of inserting a catheter on blood flow and the quality of the mixture of blood with the various substances infused through this device. Results show that the insertion of the catheter not only does not worsen the blood circulation but improves it by reducing stagnant zones. Regarding mixture, a homogenization of the fluids in the venous area before their entrance to the heart was observed. Highest quality mixtures correspond to fewer infused fluids and at lower velocity.

Infection after spinal instrumentation (IASI) by Cutibacterium spp. is being more frequently reported. The aim of this study was to analyse the incidence, risk factors, clinical characteristics, and outcome of a Cutibacterium spp. IASI (CG) compared with non-Cutibacterium IASI (NCG) infections, with an additional focus on the role of rifampin in the treatment. All patients from a multicentre, retrospective, observational study with a confirmed IASI between January 2010 and December 2016 were divided into two groups: (CG and NCG) IASI. Baseline, medical, surgical, infection treatment, and follow-up data were compared for both groups. In total, 411 patients were included: 27 CG and 384 NCG. The CG patients were significantly younger. They had a longer median time to diagnosis (23 vs. 13 days) (p = 0.025), although 55.6% debuted within the first month after surgery. Cutibacterium patients were more likely to have the implant removed (29.6% vs. 12.8%; p = 0.014) and received shorter antibiotic regimens (p = 0.014). In 33% of Cutibacterium cases, rifampin was added to the baseline therapy. None of the 27 infections resulted in treatment failure during follow-up regardless of rifampin use. Cutibacterium spp. is associated with a younger age and may cause both early and late IASIs. In our experience, the use of rifampin to improve the outcome in the treatment of a Cutibacterium spp. IASI is not relevant since, in our series, none of the cases had therapeutic failure regardless of the use of rifampin.

Infection after spinal instrumentation (IASI) by Cutibacterium spp. is being more frequently reported. The aim of this study was to analyse the incidence, risk factors, clinical characteristics, and outcome of a Cutibacterium spp. IASI (CG) compared with non-Cutibacterium IASI (NCG) infections, with an additional focus on the role of rifampin in the treatment. All patients from a multicentre, retrospective, observational study with a confirmed IASI between January 2010 and December 2016 were divided into two groups: (CG and NCG) IASI. Baseline, medical, surgical, infection treatment, and follow-up data were compared for both groups. In total, 411 patients were included: 27 CG and 384 NCG. The CG patients were significantly younger. They had a longer median time to diagnosis (23 vs. 13 days) (p = 0.025), although 55.6% debuted within the first month after surgery. Cutibacterium patients were more likely to have the implant removed (29.6% vs. 12.8%; p = 0.014) and received shorter antibiotic regimens (p = 0.014). In 33% of Cutibacterium cases, rifampin was added to the baseline therapy. None of the 27 infections resulted in treatment failure during follow-up regardless of rifampin use. Cutibacterium spp. is associated with a younger age and may cause both early and late IASIs. In our experience, the use of rifampin to improve the outcome in the treatment of a Cutibacterium spp. IASI is not relevant since, in our series, none of the cases had therapeutic failure regardless of the use of rifampin.

The healthcare response to the COVID-19 pandemic in long term care facilities (LTCF), constitutes one of the challenges faced by governments and institutions worldwide. Our aim was to analyze the facilitators and barriers of this response, for the future integrated care model in these facilities. From a retrospective observational study, we present the experience and lessons learned of the implementation of an integrated response at the meso level in LTCF for older people and for people with physical and mental conditions in the North Metropolitan area of Barcelona, in Catalonia, during the COVID-19 pandemic. We analyzed the care provided to 13,369 institutionalized people. The major facilitating points were: the adaptation of proactive care teams, the creation of a tool to improve communication with institutions, and the management of epidemiological data for planning collaboration between different actors. Main barriers were not including users and family members views in the response adaptation, and the lack of LTCF resources to respond to changing needs. Increasing proactivity and adapting interventions based on updated information were key to minimize infections and mortality. Improving the communication and the collaboration between actors, and people involvement in the response planning, need to be considered for the future.

Introduction Acute gastroenteritis (AGE) represents a significant global health burden, with enteric viruses being a leading cause of gastroenteritis worldwide. Despite advances in diagnosis and treatment, there are limited data on adults seeking care due to AGE of viral etiology. This study aimed to describe the etiological, clinical, and epidemiological characteristics of viral AGE in adult patients presenting for medical consultation in a tertiary hospital over a 2-year period. Methods A retrospective cross-sectional study was conducted, with 8886 stool samples from 8356 adult patients presenting acute diarrhea between January 2021 and December 2022. A molecular real-time RT-PCR panel was used to screen for common bacterial, parasitic, and viral pathogens. Clinical and demographic data were collected, and statistical analysis was performed to evaluate possible associations. Results Enteric viruses constituted 10.3% (307 cases) of all AGE of known etiology, with norovirus being the predominant pathogen (196, 63.8%), followed by rotavirus (82, 26.7%) and adenovirus (29, 9.4%). The different viruses showed a distinct seasonal predominance. Coinfection with other microorganisms was common. Most cases exhibited a self-limiting course. Mortality and hospitalization rates were high in patients with higher comorbidity indices, mainly in individuals with immunosuppression. Conclusions Viruses are an important cause of acute gastroenteritis in adults presenting for medical consultation. The new multiplex molecular tests with high sensitivity and specificity allow early differential diagnosis in AGE. It is therefore necessary to identify which special populations particularly with higher comorbidity indices, would benefit from the implementation of these techniques, to guide decision-making related to appropriate treatments and avoid unnecessary interventions.