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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.

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional ‘surges’ in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI., COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and is an independent risk factor for all-cause in-hospital death in patients with COVID-19. This Consensus Statement from the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI and for areas of future research, with the aim of improving understanding of the underlying processes and outcomes for patients with COVID-19 AKI.

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional 'surges' in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.

Highlights • Dexamethasone, or alternative steroids, are recommended in severe COVID-19. • The use of tocilizumab in COVID-19, with or without steroids, is still controversial. • Risk for mortality was assessed in 186 COVID-19 patients receiving tocilizumab. • Mortality was associated with older age, chronic heart failure and liver disease. • In tocilizumab-treated patients, the additional use of steroids was beneficial., Objectives To assess the characteristics and risk factors for mortality in patients with severe COVID-19 treated with tocilizumab (TCZ), alone or in combination with corticosteroids (CS). Methods From March 17 to April 7, 2020, a real-world observational retrospective analysis of consecutive hospitalized adult patients receiving TCZ to treat severe COVID-19 was conducted at our 750-bed university hospital. The main outcome was all-cause in-hospital mortality. Results A total of 1,092 COVID-19 patients were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186, 155 (83.3 %) patients were receiving non-invasive ventilation when TCZ was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (± 4.3) and 4.3 days (± 3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR = 1.09, p

Background: Critically ill surgical patients remain at a high risk of adverse outcomes as a result of secondary peritonitis (SP). The risk is even higher if tertiary peritonitis (TP) develops. Factors related to the development of TP, however, are scarce in the literature. The main aim of our study was to identify factors associated with the development of TP in patients with SP in the intensive care unit (ICU), and also to report differences in microbiologic patterns and antibiotic therapy in patients with the two conditions. Patients and Methods: A prospective, observational study was conducted at our institution from 2010 to 2014. Baseline characteristics on admission, outcomes, microbiologic results, and antibiotic therapy were recorded for analysis. Results: We included 343 patients with SP, of whom TP developed in 185 (53.9%). Almost two-thirds (64.4%) were male; mean age was 63.7 +/- 14.3 years, and mean APACHE was 19.4 +/- 7.8. In-hospital death was 42.6% (146). Multivariable analysis showed that longer ICU stay (odds ratio [OR]: 1.019; 95% confidence interval [CI]: 1.004-1.034; p = 0.010), urgent operation on hospital admission (OR: 3.247; 95% CI: 1.392-7.575; p = 0.006), total parenteral nutrition (TPN) (OR: 3.079; 95% CI: 1.535-6.177; p = 0.002) and stomachduodenum as primary infection site (OR: 4.818; 95% CI: 1.429-16.247; p = 0.011) were factors associated with the development of TP, whereas patients with localized peritonitis were less prone to have TP develop (OR: 0.308; 95% CI: 0.152-0.624; p = 0.001). Higher incidences of Candida spp. (OR: 1.275; 95% CI: 1.096-1.789; p = 0.016), Enterococcus faecium (OR: 1.085; 95% CI: 1.018-1.400; p = 0.002), and Enterococcus spp. (OR: 1.370; 95% CI: 1.139-1.989; p = 0.047) were found in TP, and higher rates of cephalosporin use in SP (OR: 3.51; 95% CI: 1.139-10.817; p = 0.035). Conclusions: Complicated peritonitis remains a cause of a high numbers of deaths in the ICU. The need for TPN, urgent operation on hospital admission, and particularly surgical procedures in the proximal gastrointestinal tract were factors associated with development of TP and may potentially help to identify patients with SP at risk for development of TP. Physicians should be aware concerning multi-drug-resistant germs when treating these patients.

Background The administration of β-lactam antibiotics in continuous infusion could let optimize the pharmacokinetic/pharmacodynamic parameters, especially in the treatment of serious bacterial infections. In this context, and also due to variability in their plasmatic concentrations, therapeutic drug monitoring (TDM) may be useful to optimize dosing and, therefore, be useful for the clinicians. Material and methods We developed and validated a measurement procedure based on ultra-high performance liquid chromatography-tandem mass spectrometry for simultaneous measurement of amoxicillin, ampicillin, cloxacillin, piperacillin, cefepime, ceftazidime, cefuroxime, aztreonam and meropenem concentrations in plasma. The chromatographic separation was achieved using an Acquity®-UPLC® BEH™ (2.1 × 100 mm id, 1.7 μm) reverse-phase C18 column, with a water/acetonitrile linear gradient containing 0.1% formic acid at a 0.4 mL/min flow rate. β-Lactam antibiotics and their internal standards were detected by electrospray ionization mass spectrometry in multiple reaction monitoring mode. Results Chromatography run time was 7.0 min and β-lactam antibiotics eluted at retention times ranging between 1.08 and 1.91 min. The lower limits of quantification were between 0.50 and 1.00 mg/L. Coefficients of variation and relative bias absolute values were

Background The impact of Surviving Sepsis Campaign (SSC) care bundles in reducing sepsis-associated acute kidney injury (SA-AKI) was evaluated. Methods We conducted an observational single-center cohort study. Accomplishment of SSC care bundles was registered in all patients with severe sepsis admitted to the critical care department of a university hospital during three different periods. The main outcome measured was SA-AKI incidence defined as any worsening of AKI stage within the first 7 days from onset of sepsis. Results Among 260 patients with severe sepsis or septic shock finally meeting inclusion criteria, 82 (31.5%) patients developed SA-AKI. None of the SSC care tasks significantly decreased SA-AKI incidence, although a trend was observed with an initial better blood glucose control as well as with a more protective ventilation strategy. Hypotension requiring fluid challenge (hazard ratio (HR), 2.3; 95% confidence interval (CI), 1.2 - 4.2) and the presence of an abdominal sepsis etiology (HR, 1.8; 95% CI, 1.1 - 3.1) were independently associated with SA-AKI. Patients who developed SA-AKI had a higher 90-day mortality rate (62.2 vs. 40.4%). Conclusion In a cohort of septic patients, none of the SSC care tasks significantly decreased SA-AKI incidence within the first week after onset of sepsis. .

Purpose: Identify clinical variables associated with mortality in patients with sepsis-associated acute kidney injury (SA-AKI) receiving continuous renal replacement therapy (CRRT) and examine timing of initiation of CRRT in reference to those variables identified. Methods: Retrospective study conducted at two tertiary care hospitals including 939 septic shock patients with SA-AKI who received CRRT in the intensive care unit (ICU). Cox regression models were used to identify variables associated with 90-day mortality. Timing of CRRT initiation was assessed in relationship to significant clinical variables identified. Results: Overall 90-day mortality was 62.9%. Variables prior to CRRT associated with 90-day mortality included: age (aHR, 1.02; 95% CI, 1.01-1.02, p < 000.1), APS-III score (1.01, 1.0-1.0, p < 0.048), days from hospital admission to CRRT initiation (1.01, 1.0-1.0, p < 0.01), blood urea nitrogen (1.01, 1.0-1.0, p < 0.04), medical admission (1.76, 1.5-2.1, p < 0.0001), creatinine (0.99, 0.9-1.0, p < 0.001), and urine output (0.77, 0.6-0.9, p = 0.049). In patients with advanced SA-AKI at ICU admission receiving CRRT within the first 5 days (n = 433), urine output during the 24 h prior to CRRT initiation was a strong predictor of survival (2.6, 1.6-4.3, p < 0.001). Conclusions: In patients with SA-AKI, survival is lower when CRRT is started in the setting of low urine output. (C) 2017 Elsevier Inc. All rights reserved.

Meropenem is a broad-spectrum antibiotic, often used for the empirical treatment of infections in critically ill patients with acute kidney injury. Meropenem has clinically insignificant protein binding and, as a carbapenem antibiotic, shows time-dependent bacterial killing, meaning that the unbound or free antibiotic concentration in blood should be maintained above the minimal inhibitory concentration of the pathogen for at least 40 % of the dosing interval. We developed and validated simple chromatographic methods by ultra-performance liquid chromatography-tandem mass spectrometry to measure plasma, filtrate-dialysate, and urine concentrations of meropenem. Chromatographic separation was achieved using an Acquity(®) UPLC(®) BEH(TM) (2.1 × 100 mm id, 1.7 μm) reverse-phase C(18) column, with a water/acetonitrile linear gradient containing 0.1 % formic acid at a 0.4-mL/min flow rate. Meropenem and its internal standard (ertapenem) were detected by electrospray ionization mass spectrometry in positive ion multiple reaction monitoring mode. The limits of quantification were 0.27, 0.24, and 1.22 mg/L, and linearity was observed between 0.27-150, 0.24-150, and 1.22-2,000 mg/L for plasma, filtrate-dialysate, and urine samples, respectively. Coefficients of variation and relative biases were less than 13.5 and 8.0 % for all biological fluids. Recovery values were greater than 68.3 %. Evaluation of the matrix effect showed ion suppression for meropenem and ertapenem. No carry-over was observed. The validated methods are useful for both therapeutic drug monitoring and pharmacokinetic studies. It could be applied to daily clinical laboratory practice to measure the concentration of meropenem in plasma, filtrate-dialysate, and urine.