Voriconazole, an antifungal agent, displays high intra- and inter-individual variability. The predictive pharmacokinetic (PK) index requires a minimum plasma concentration (C_min) in patient serum of between 1–5.5 mg/L. It is common to encounter fungal infections in patients undergoing extracorporeal membrane oxygenation (ECMO) support, and data regarding voriconazole PK changes during ECMO are scarce. Our study compared voriconazole PKs in patients with and without ECMO support in a retrospective cohort of critically-ill patients. Fifteen patients with 26 voriconazole C_min determinations in the non-ECMO group and nine patients with 27 voriconazole C_min determinations in the ECMO group were recruited. The ECMO group had lower C_min (0.38 ± 2.98 vs. 3.62 ± 3.88, p < 0.001) and higher infratherapeutic C_min values (16 vs. 1, p < 0.001) than the non-ECMO group. Multivariate analysis identified ECMO support (−0.668, CI₉₅ −0.978–−0.358) and plasma albumin levels (−0.023, CI₉₅ −0.046–−0.001) as risk factors for low C_min values. When comparing pre- and post-therapeutic drug optimisation samples from the ECMO group, the dose required to achieve therapeutic C_min was 6.44 mg/kg twice a day. Therapeutic drug optimisation is essential to improve target attainment.

Background. Some patients previously presenting with COVID-19 have been reported to develop persistent COVID-19 symptoms. While this information has been adequately recognised and extensively published with respect to non-critically ill patients, less is known about the incidence and factors associated with the characteristics of persistent COVID-19. On the other hand, these patients very often have intensive care unit-acquired pneumonia (ICUAP). A second infectious hit after COVID increases the length of ICU stay and mechanical ventilation and could have an influence on poor health post-COVID 19 syndrome in ICU-discharged patients. Methods: This prospective, multicentre, and observational study was carrid out across 40 selected ICUs in Spain. Consecutive patients with COVID-19 requiring ICU admission were recruited and evaluated three months after hospital discharge. Results: A total of 1255 ICU patients were scheduled to be followed up at 3 months; however, the final cohort comprised 991 (78.9%) patients. A total of 315 patients developed ICUAP (97% of them had ventilated ICUAP). Patients requiring invasive mechanical ventilation had more persistent post-COVID-19 symptoms than those who did not require mechanical ventilation. Female sex, duration of ICU stay, development of ICUAP, and ARDS were independent factors for persistent poor health post-COVID-19. Conclusions: Persistent post-COVID-19 symptoms occurred in more than two-thirds of patients. Female sex, duration of ICU stay, development of ICUAP, and ARDS all comprised independent factors for persistent poor health post-COVID-19. Prevention of ICUAP could have beneficial effects in poor health post-COVID-19.

Critically ill patients undergo significant pathophysiological changes that affect antibiotic pharmacokinetics. Piperacillin/tazobactam administered by continuous infusion (CI) improves pharmacokinetic/pharmacodynamic (PK/PD) target attainment. This study aimed to characterize piperacillin PK after CI administration of piperacillin/tazobactam in critically ill adult patients with preserved renal function and to determine the empirical optimal dosing regimen. A total of 218 piperacillin concentrations from 106 patients were simultaneously analyzed through the population PK approach. A two-compartment linear model best described the data. Creatinine clearance (CL_CR) estimated by CKD-EPI was the covariate, the most predictive factor of piperacillin clearance (CL) interindividual variability. The mean (relative standard error) parameter estimates for the final model were: CL: 12.0 L/h (6.03%); central and peripheral compartment distribution volumes: 20.7 L (8.94%) and 62.4 L (50.80%), respectively; intercompartmental clearance: 4.8 L/h (26.4%). For the PK/PD target of 100% fT_>1×MIC, 12 g of piperacillin provide a probability of target attainment > 90% for MIC < 16 mg/L, regardless of CL_CR, but higher doses are needed for MIC = 16 mg/L when CL_CR > 100 mL/min. For 100% fT_>4×MIC, the highest dose (24 g/24 h) was not sufficient to ensure adequate exposure, except for MICs of 1 and 4 mg/L. Our model can be used as a support tool for initial dose guidance and during therapeutic drug monitoring.

Information on the long-term effects of non-restrictive antimicrobial stewardship (AMS) strategies is scarce. We assessed the effect of a stepwise, multimodal, non-restrictive AMS programme on broad-spectrum antibiotic use in the intensive care unit (ICU) over an 8-year period. Components of the AMS were progressively implemented. Appropriateness of antibiotic prescribing was also assessed by monthly point-prevalence surveys from 2013 onwards. A Poisson regression model was fitted to evaluate trends in the reduction of antibiotic use and in the appropriateness of their prescription. From 2011 to 2019, a total of 12,466 patients were admitted to the ICU. Antibiotic use fell from 185.4 to 141.9 DDD per 100 PD [absolute difference, −43.5 (23%), 95% CI −100.73 to 13.73; p = 0.13] and broad-spectrum antibiotic fell from 41.2 to 36.5 [absolute difference, −4.7 (11%), 95% CI −19.58 to 10.18; p = 0.5]. Appropriateness of antibiotic prescribing rose by 11% per year [IRR: 0.89, 95% CI 0.80 to 1.00; p = 0.048], while broad-spectrum antibiotic use showed a dual trend, rising by 22% until 2015 and then falling by 10% per year since 2016 [IRR: 0.90, 95% CI 0.81 to 0.99; p = 0.03]. This stepwise, multimodal, non-restrictive AMS achieved a sustained reduction in broad-spectrum antibiotic use in the ICU and significantly improved appropriateness of antibiotic prescribing.

Background/Objectives: Infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) represent a major therapeutic challenge, particularly in hospitalized and critically ill patients with limited treatment options. Cefiderocol, a novel siderophore cephalosporin, has demonstrated activity against a broad range of resistant Gram-negative pathogens. We aimed to evaluate the effectiveness and safety of cefiderocol for the treatment of MDR-GNB infection. Methods: We conducted a retrospective observational study including all adult patients who received ≥72 h of cefiderocol between November 2020 and October 2024 at a Spanish tertiary-care hospital. The primary outcome was clinical success, defined as survival and absence of clinical recurrence 30 days after cefiderocol initiation. Secondary outcomes included 30- and 90-day mortality, clinical and microbiological recurrence, emergence of resistance, and adverse events. Results: Eighty patients were included (median age 64 years [IQR 56–72]; 81.3% male). Respiratory (26.2%) and abdominal (22.5%) infections were the most common, and 20% presented with bacteremia. At infection onset, 26.2% had septic shock and 45% required intensive care unit admission. The three most frequently isolated pathogen was Pseudomonas aeruginosa (33.9%), followed by Enterobacterales (33%) and Stenotrophomonas maltophilia (30.1%). Clinical success was achieved in 67.5% of patients. Thirty and 90-day mortality rates were 27.5% and 36.5%, respectively. Recurrence within 90 days occurred in 5% of cases. Emergence of resistance was detected in one Klebsiella pneumoniae ST147 isolate, and serious adverse events occurred in 5% of patients. Conclusions: In a cohort including a substantial proportion of critically ill patients, cefiderocol was associated with favorable clinical outcomes and an acceptable safety profile. These findings suggest that cefiderocol may represent a useful therapeutic option for severe MDR-GNB infections in patients with limited treatment alternatives.

Background/Objectives: Antibiotic pharmacokinetics (PK) and pharmacodynamics (PD) are altered during extracorporeal membrane oxygenation (ECMO). Meropenem and piperacillin are among the most commonly prescribed antibiotics for infections in this population. However, guidance on dosage adjustments in the ECMO setting remains limited. We aim to assess differences in meropenem and piperacillin concentrations achieved and identify the clinical, physiological, and mechanical factors influencing antibiotic exposure. Methods: This is a retrospective, single-centre, observational study comparing an ECMO cohort with a population control group from a prior study, without renal dysfunction. Demographic, clinical, PK/PD parameters, and ECMO-related data were analysed using univariate and generalised estimating equations. For both antimicrobials, the PK/PD target was set at 100%fT_>4xMIC. Results: A total of 130 critically ill patients were included: 18 in the ECMO group and 112 in the control group. The mean age was 65 years (23), 67% were male and 26.9% were classified as obese. For meropenem, renal function and ECMO support significantly influenced drug exposure, with PK/PD targets being achieved in 67% of measurements; in contrast, piperacillin exposure exhibited greater variability, primarily driven by renal function and mechanical ventilation. Notably, PK/PD targets for piperacillin were met in only 20% of measurements. Conclusions: Our findings highlight the considerable variability in β-lactam exposures and PK/PD target attainment in critically ill patients. This study underscores the importance of therapeutic drug monitoring and individualised dosing in attempts to improve antimicrobial efficacy and patient outcomes in this challenging setting.