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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.

Objective: To analyze the clinical and economic impact of community-onset urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae requiring hospitalization. Methods: A retrospective cohort study that included all adults with a UTI caused by K. pneumoniae that were 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 UTIs caused by K. pneumoniae were studied, 112 were non-ESBL-producing and 61 were ESBL-producing. Multivariate analysis identified ESBL production, acute confusional state associated with UTI, shock, and the time taken to obtain adequate treatment as risk factors for clinical failure during the first seven days. An economic analysis showed differences between ESBL-producing and non-ESBL-producing K. pneumoniae for the total cost of hospitalization per episode (mean EUR 6718 vs EUR 3688, respectively). Multivariate analysis of the higher costs of UTI episodes found statistically significant differences for ESBL production and the time taken to obtain adequate treatment. Conclusion: UTIs caused by ESBL-producing K. pneumoniae requiring hospitalization and the time taken to obtain adequate antimicrobial therapy are associated with worse clinical and economic outcomes.

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.

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.

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).