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Morbidity and mortality from serious infections are common in intensive care units (ICUs). The appropriateness of the antibiotic treatment is essential to combat sepsis. We aimed to evaluate pharmacokinetic/pharmacodynamic target attainment of meropenem and piperacillin/tazobactam administered at standard total daily dose as continuous infusion in critically ill patients without renal dysfunction and to identify risk factors of non-pharmacokinetic/pharmacodynamic target attainment. We included 118 patients (149 concentrations), 47% had microorganism isolation. Minimum inhibitory concentration (MIC) [median (interquartile range, IQR) values in isolated pathogens were: meropenem: 0.05 (0.02–0.12) mg/l; piperacillin: 3 (1–4) mg/l]. Pharmacokinetic/pharmacodynamic target attainments (100%fCss≥1xMIC, 100%fCss≥4xMIC and 100%fCss ≥ 8xMIC, respectively) were: 100%, 96.15%, 96.15% (meropenem) and 95.56%, 91.11%, 62.22% (piperacillin) for actual MIC; 98.11%, 71.70%, 47.17% (meropenem, MIC 2 mg/l), 95.83%, 44.79%, 6.25% (piperacillin, MIC 8 mg/l), 83.33%, 6.25%, 1.04% (piperacillin, MIC 16 mg/l) for EUCAST breakpoint of Enterobacteriaceae spp. and Pseudomonas spp. Multivariable linear analysis identified creatinine clearance (CrCL) as a predictive factor of free antibiotic concentrations (fCss) of both therapies (meropenem [β = − 0.01 (95% CI − 0.02 to − 0.0; p = 0.043)] and piperacillin [β = − 0.01 (95% CI − 0.02 to 0.01, p 8 mg/l. CrCL was the most powerful factor predictive of fCss in both therapies.

Background: Debridement, antibiotic agents, and implant retention (DAIR) is a currently accepted approach for the treatment of early prosthetic joint infections (PJI). The success of a DAIR procedure has shown variable results throughout the published literature. Scoring systems such as the Kidney, Liver, Index surgery, Cemented prosthesis, and C-reactive protein value (KLIC) score for the selection of patients that are likely to benefit from DAIR have proved to be helpful in decision making. Our study aims to further validate the KLIC score using a large external multicentric cohort and to evaluate other risk factors for failure. Patients and Methods: A retrospective analysis of patients with an early acute PJI who were treated with DAIR and recorded in a database of eight Spanish university hospitals was performed. According to pre-operative variables of the KLIC study, patients were categorized into five groups: group A, =2 points; group B, 2.5-3.5 points; group C, 4-5 points; group D, 5.5-6.5 points; and group E, =7 points. Failure rates were compared between groups at 60 days and after 60 days of DAIR. Further variables for risk of failure were also analyzed. Results: A total of 455 patients with early acute PJI were included in the analyses. At 60 days, patients presenting with pre-operative elevated C-reactive protein serum levels, Staphylococcus aureus, and polymicrobial infections were associated with failure. Failure rates recorded were 12% for group A (n = 210), 18% for group B (n = 83), 26% for group C (n = 89), 24% for group D (n = 66), and 0% for group E (n = 7). Univariable analysis between consecutive groups of the KLIC score showed no differences for failure before 60 days of the DAIR procedure. Scheduled surgery and having the procedure performed by a specialized unit were also identified as important factors for DAIR success. Conclusions: Our results suggest the KLIC score was not useful for predicting failure in our cohort. Furthermore, our results indicate a specialized unit should conduct DAIR procedures.

Background Several observational studies demonstrated the passage of postvaccine antibodies through breast milk in women vaccinated against coronavirus disease 2019 (COVID-19), mostly with messenger RNA (mRNA)–based vaccines, but lacked long-term data. Methods A 6-month prospective cohort study was performed to determine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine–induced antibody levels in the breast milk of 33 lactating healthcare workers at different timepoints after mRNA BNT162b2 Pfizer-BioNTech COVID-19 vaccination. Moreover, we examined the correlation of SARS-CoV-2 antibody levels between serum and breast milk, adverse events related to vaccination, and rate of SARS-CoV-2 infections. Results Mothers’ median age was 38 (interquartile range [IQR], 36–39) years and 15 (IQR, 10–22) months for infants. Median (IQR) SARS-CoV-2 immunoglobulin G (IgG) spike protein subunit S1 (S1) vaccine–induced levels at different timepoints for serum–milk pairs were 519 (234–937) to 1 (0–2.9) arbitrary units (AU)/mL at 2 weeks after first dose and 18 644 (9923–29 264) to 78 (33.7–128), 12 478 (6870–20 801) to 50.4 (24.3–104), 4094 (2413–8480) to 19.9 (10.8–51.9), 1350 (831–2298) to 8.9 (7.8–31.5) AU/mL at 2, 4, 12 and 24 weeks after second dose, respectively. We observed a positive correlation of antibody levels between serum and breast milk, no serious adverse events related to vaccination, and 2 (6%) COVID-19 vaccine breakthrough infections. Conclusions Women vaccinated with Pfizer-BioNTech transmit antibodies into breast milk with a positive correlation with serum levels. Both decreased over time in a 6-month follow-up.

ImportanceTo our knowledge, this is the first study to analyze long–term passage (6 months after immunization) of specific antibodies induced by BNT162b2 COVID-19 vaccine through breast milk.ObjectivesMain objective: to determine SARS-CoV-2 vaccine induced antibody levels in the breast milk of lactating women 4 weeks after mRNA BNT162b2 Pfizer-BioNTech COVID-19 complete vaccination.Secondary objectives: to analyze SARS-CoV-2 antibody levels (breast milk and serum) at different time-points after vaccination, examine the correlation of SARS-CoV-2 antibody levels between serum and breast milk, describe adverse events related to vaccination (AErV) in both mothers and infants and determine the rate of COVID-19 infections.DesignProspective cohort study between February and September 2021.SettingParc Sanitari Sant Joan de Déu, an urban hospital in Spain.ParticipantsDuring our health worker vaccination campaign at our hospital between January and March 2, we recruited 33 lactating women vaccinated with BNT162b2 Pfizer-BioNTech COVID-19.ResultsA total of 33 volunteers were included in the study. The median (IQR) age of mothers was 38 (36-39) years and 15 (10-22) months for the infants.Primary end-point: at 4 w after second dose median (IQR) IgG-S1 levels for serum–milk pairs were 12,478 (6,870-20,801) to 50.4 (24.3-104) arbitrary units (AU) per mL.Secondary end-pointsSARS-CoV-2 antibody levels at different time-points were (serum-milk): 519 (234-937) to 1 (0-2.9) AU/mL at 2w after first dose, 18,644 (9,923-29,264) to 78 (33.7-128) AU/mL at 2w, 4,094 (2,413-8,480) to 19.9 (10.8-51.9) AU/mL at 12w, and 1,350 (831-2,298) to 8.9 (7.8-31.5) at 24w after second dose.We found a positive correlation of SARS-CoV-2 antibody levels between serum and breast milk (Pearson correlation coefficient 0.68).No serious AErV were observed.We found two (6%) COVID-19 vaccine breakthrough infections.ConclusionsPfizer-BioNTech COVID-19 vaccination is safe during breastfeeding and it transmits antibodies into breast milk with a positive correlation with serum levels, and both decrease over time in a 6-month follow-up. Infants of breastfeeding vaccinated women could be protected for at least six months after vaccination and serum determination of SARS-CoV-2 IgG-S1 could indicate the breastmilk levels of antibodies during this period.

The COVID-19 pandemic has raised questions among individuals who are breastfeeding, both because of the possibility of viral transmission to infants during breastfeeding and, more recently, of the potential risks and benefits of vaccination in this specific population. Previous studies have reported the presence of anti–SARS-CoV-2 antibodies in breast milk of COVID-19–infected lactating women,1 and recently several studies have demonstrated the passage of postvaccine antibodies through breast milk in women vaccinated with novel mRNA-based vaccines.1,2 In the present study, conducted between February and March 2021 at Parc Sanitari Sant Joan de Deu, an urban hospital in Spain, we sought to characterize the levels of specific SARS-CoV-2 antibodies in the breast milk of mRNA-vaccinated women across time, as well as their correlation with serum antibody levels.

Morbidity and mortality from serious infections are common in intensive care units (ICUs). The appropriateness of the antibiotic treatment is essential to combat sepsis. We aimed to evaluate pharmacokinetic/pharmacodynamic target attainment of meropenem and piperacillin/tazobactam administered at standard total daily dose as continuous infusion in critically ill patients without renal dysfunction and to identify risk factors of non-pharmacokinetic/pharmacodynamic target attainment.We included 118 patients (149 concentrations), 47% had microorganism isolation. Minimum inhibitory concentration (MIC) [median (interquartile range, IQR) values in isolated pathogens were: meropenem: 0.05 (0.02-0.12) mg/l; piperacillin: 3 (1-4) mg/l]. Pharmacokinetic/pharmacodynamic target attainments (100%fCStandard total daily dose of meropenem allowed achieving pharmacokinetic/pharmacodynamic target attainments in ICU patients without renal dysfunction. Higher doses of piperacillin/tazobactam would be needed to cover microorganisms with MIC8 mg/l. CrCL was the most powerful factor predictive of fC

Objective: To analyze the clinical and economic impact of community-onset urinary tract infections (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae requiring hospitalization. Methods: A retrospective cohort study included all adults with UTI caused by K. pneumoniae admitted to a tertiary care hospital in Barcelona, Spain, between 2011 and 2015. Demographic, clinical and economic data were analyzed. Results: One hundred and seventy-three episodes of UTI caused by K. pneumoniae were studied; 112 were non-ESBL-producing and 61 ESBL-producing. Multivariate analysis identified ESBL production, acute confusional state associated with UTI, shock, and time to adequate treatment as risk factors for clinical failure during the first 7 days. Economic analysis showed differences between ESBL-producing and non-ESBL-producing K. pneumoniae for the total cost of hospitalization per episode (mean 6,718 € vs 3,688 € respectively). Multivariate analysis of the higher costs of UTI episodes found statistically significant differences for ESBL production and time to adequate treatment. Conclusion: UTI caused by ESBL-producing K. pneumoniae requiring hospitalization, and time to adequate antimicrobial therapy are associated with worse clinical and economic outcomes.

This cohort study assesses the concentration of SARS-CoV-2 antibodies in the breast milk of women who received vaccines for COVID-19 and their correlation with serum antibody levels.

Resumen Objetivo Describir las caracteristicas clinicas y respiratorias de una cohorte de 43 pacientes con COVID-19 tras 28 dias de evolucion. Diseno Prospectivo, observacional en un solo centro. Ambito Medicina intensiva. Pacientes Pacientes ingresados por COVID-19 e insuficiencia respiratoria. Intervenciones Ninguna. Variables Se obtuvieron de forma automatica variables demograficas, de gravedad, de laboratorio, de asistencia ventilatoria recibida (oxigenoterapia alto flujo [OAF] y ventilacion mecanica invasiva [VMI]), de oxigenacion (PaO2, PaO2/FiO2) y de complicaciones. Los pacientes se dividieron en 3 grupos: supervivientes (G1), fallecidos (G2) y aquellos que continuaban ingresados (G3). Se utilizo la prueba de Chi-cuadrado o de Fisher (variables categoricas) y la U de Mann-Whitney o Wilcoxon para analizar la diferencia entre medianas. Se considero significativo un valor de p Resultados Se incluyeron 43 pacientes (G1 = 28 [65,1%]; G2 = 10 [23,3%] y G3 = 5 [11,6%]), edad 65 (52-72) anos, 62% varones, APACHE II 18 (15-24), SOFA 6 (4-7), hipertension arterial (30,2%) y obesidad (25,6%) fueron las comorbilidades mas frecuentes. La OAF fue usada en el 62,7% de pacientes, el 85% fracaso. El 95% de los pacientes necesito VMI y el 85% ventilacion en prono. En la poblacion general, la PaO2/FiO2 inicial mejoro a los 7 dias (165 [125-210] vs. 194 [153-285]; p = 0,02), al igual que en el G1 (164 [125-197] vs. 207 [160-294]; p = 0,07), pero no en el G2 (163 [95-197] vs. 135 [85-177]). No se observo co-infeccion bacteriana. El desarrollo de neumonia asociada a la VMI fue elevado (13 episodios/1.000 dias de VMI). Conclusiones Los pacientes con COVID-19 requieren VMI precoz, elevada frecuencia de ventilacion en prono y presentan alta prevalencia de fracaso a la OAF. La falta de mejoria de la PaO2/FiO2 a los 7 dias podria ser un marcador de pronostico.

Introduction International travelers have grown significantly over last years, as well as imported diseases from tropical areas. Information in pediatric population is scarce. We describe demographic and clinical characteristics of febrile children coming from the tropics. Methods Retrospective review of patients under 18 years old, presenting at a tertiary hospital and surrounding primary health care centers between July 2002 and July 2018 with a stay in a tropical region during the previous year. Patients were selected from microbiological charts of thick smears for malaria or dengue serologies. Results 188 patients were studied: 52.7% were born in Spain with a median age of 3.0 years old (IQR 1.5–8.0). Main regions of stay were Sub-Saharan Africa (54.8%) and Latin America (29.8%), mostly for visiting their friends and relatives (56.3%), followed by recent arrival migrants (32.4%). Only 34% of travelers attended pre-travel consultation. More than 80% of these febrile children attended directly the Emergency Room. The most frequent diagnoses were febrile syndrome without source (56.4%), respiratory condition (15.4%) and acute diarrhea (11.7%). Around a half (52.1%) were managed as outpatients, but 46.2% were hospitalized and 7.4% were admitted to Intensive Care Unit. No specific diagnosis was achieved in 24% of cases. However, 29.7% were diagnosed with malaria. Conclusion Children with fever coming from tropical areas were at risk of severe infectious diseases. Malaria was diagnosed in one out of four and 7% required admission in PICU. This information emphasizes the need of reinforcing training about tropical diseases among first line physicians.

Cardiovascular risk (CVR) assessment helps to identify patients at high CVR. The Framingham CVR score (FRS) is the most widely used methods but may overestimate risk in regions with low incidence of cardiovascular disease. The objective was to compare the 10-year performance of the original and the adapted REGICOR - Framingham CVR functions in HIV-infected individuals.We carried out a longitudinal study of HIV-infected patients with CVR evaluation in a hospital in Barcelona between 2003 and 2013.Risk probability was calculated using the FRAMINGHAM function and REGICOR adaptation to the Spanish population, and individuals were categorized in three groups (low, 0 5%; moderate, 5-10%; and high,10%). For each risk group, the number of events over 10 years was calculated using the Kaplan-Meier method, and the expected number of events was calculated by multiplying the frequency of participants in the group by the mean of the probabilities from the risk function. We used the X(2) goodness-of-fit test to assess agreement between observed and expected.Six hundred and forty-one patients were followed up for a median of 10.2 years, and 20 ischemic heart events (IHE) were observed. The mean (95% CI) number of IHEs per 1000 person-years was 3.7 (2.06-5.27). The estimates from the Framingham and REGICOR functions were 40 and 14 IHEs, respectively. The estimate from the original Framingham function differed significantly from the observed incidence (p 0.001), whereas that from the REGICOR-adapted function did not (p = 0.15). In terms of the number of cardiovascular events (38 events observed), the REGICOR function significantly underestimated risk (p = 0.01), whereas the estimate from the Framingham function was similar to observed (p:0.93).The FRS significantly overestimates risk of IHE events in our HIV-infected patients, while the REGICOR function is a better predictor of these events. In terms of cardiovascular events, the REGICOR function significantly underestimates risk, whereas the FRS is a better estimator. We recommend using CVR scales and adjusting them to the origin of the population being studied.

Nephrotoxicity limits the effective use of colistin for the treatment of multidrug-resistant Gram-negative bacteria (MDR-GNB) infections. We previously defined a steady-state colistin plasma concentration (C-ss) of 2.42 mg/L that predicted nephrotoxicity at end of treatment (EOT). The objective of this study was to validate this breakpoint in a prospective cohort. This was a multicentre, prospective, observational study conducted at three hospitals with a cohort of patients treated for MDR-GNB infection with colistin methanesulfonate from September 2011 until January 2015. Nephrotoxicity was evaluated at Day 7 and at EOT using the RIFLE criteria. C-ss values were measured and analysed using HPLC. Taking the previously defined breakpoint for colistin concentration as a criterion, patients were divided into two groups (C-ss, 2.42 mg/L). Sixty-four patients were included. Seven patients (10.9%) had a C-ss > 2.42 mg/L and were compared with the remaining patients. Bivariate analysis showed that patients with a C-ss > 2.42 mg/L were older and had a significantly higher incidence of nephrotoxicity at Day 7 and EOT. Although not statistically significant, nephrotoxicity occurred earlier in these patients (6.2 days vs. 9.2 days in patients with lower C-ss; P = 0.091). Multivariate analysis of nephrotoxicity showed that C-ss > 2.42 mg/L was the only predictive factor. Nephrotoxicity was more frequent and occurred earlier in patients with colistin plasma concentrations higher than the previously defined breakpoint (2.42 mg/L). Colistin therapeutic drug monitoring should be routinely considered to avoid reaching this toxicity threshold and potential clinical consequences. (C) 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Resumen Fundamento y objetivo La vitamina D (vitD) interviene en el metabolismo fosfocalcico y la enfermedad osea, pero tambien en procesos inflamatorio-infecciosos como la tuberculosis. En el presente estudio se evaluan aspectos clinicos y epidemiologicos de enfermos e infectados por Mycobacterium tuberculosis en quienes se obtuvieron concentraciones plasmaticas de vitD para determinar si existe relacion entre el deficit de vitD y el riesgo de desarrollar tuberculosis activa, especialmente las formas mas graves. Metodo Estudio observacional retrospectivo que incluyo a 86 pacientes con tuberculosis activa y 80 contactos con infeccion latente, visitados en una unidad especializada, en un periodo de 2 anos. Resultados Al comparar enfermos con infectados, el deficit de vitD (valores de vitD Conclusion A pesar del limitado numero de sujetos estudiados, se ha detectado una asociacion entre el deficit grave de vitD y la forma de presentacion de la tuberculosis.

Background: Colistin has a narrow therapeutic window with nephrotoxicity being the major dose-limiting adverse effect. Currently, the optimal doses and therapeutic plasma levels are unknown. Methods: Prospective observational cohort study, including patients infected by colistin-susceptible P. aeruginosa treated with intravenous colistimethate sodium (CMS). Clinical data and colistin plasma levels at steady-state (Css) were recorded. The primary and secondary end points were clinical cure and 30-day all-cause mortality. Results: Ninety-one patients were included. Clinical cure was observed in 72 (79%) patients. The mean (SD) Css was 1.49 (1.4) mg/L and 2.42 (1.5) mg/L (p = 0.01) in patients who achieved clinical cure and those who not, respectively. Independent risk factors for clinical failure were male sex (OR 5.88; 95% CI 1.09–31.63), APACHE II score (OR 1.15; 95% CI 1.03–1.27) and nephrotoxicity at the EOT (OR 9.13; 95% CI 95% 2.06–40.5). The 30-day mortality rate was 30.8%. Risk factors for 30-day mortality included the APACHE II score (OR 1.98; 95% CI 1–1.20), the McCabe score (OR 2.49; 95% CI 1.14–5.43) and the presence of nephrotoxicity at the end of treatment (EOT) (OR 3.8; 95% CI 1.26–11.47). Conclusion: In this series of patients with infections caused by XDR P. aeruginosa infections, Css is not observed to be related to clinical outcome. This work was supported by Fondo de Investigación Sanitaria (FIS) from Instituto de Salud Carlos III, Spanish Ministry of Health, Grant number PS09/01634 and from Spanish Ministry of Health and Social Policy, General Pharmacy Subdirection, Grant numbers EC10-165 and EC11-318. This study also received funding from European Regional Development Fund (FEDER: “A way of making Europe”). NB was funded by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III and cofinanced by the European Development Regional Fund "A way to achieve Europe", Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015).

ABSTRACT Aim: We reviewed the clinical use of daptomycin in daily practice. Materials & methods: Efficacy and safety were assessed in 175 consecutive patients given daptomycin for at least 72 h. Results: Daptomycin was given as rescue treatment in 50.9% of cases. Bloodstream infection (34.8%) and skin/soft-tissue infection (19.4%) were the most frequent. In 62.3% of patients, the dose of ≤ 6 mg/kg/day was administered. Staphylococcus spp. were isolated in 52.6% of cases (MRSA in 9.5%, CoNS in 34.3%) and Enterococcus spp. in 8.7%. Clinical success was 75% and microbiological eradication 48.6%. Two patients discontinued daptomycin due to hemolytic anemia of unlikely and possible relationship with daptomycin, respectively. Conclusion: Daptomycin was effective and well tolerated in patients with severe Gram-positive infections.