Isavuconazole Pharmacokinetics in Critically Ill Patients: Relationship with Clinical Effectiveness and Patient Safety.

Isavuconazole is used to treat fungal infections. This study aims to describe isavuconazole pharmacokinetics in critically ill patients and evaluate their relationship with clinical efficacy and patient safety. We conducted a prospective, observational study in patients treated with intravenous isavuconazole. Samples were collected at predose (Cmin), 1 h (Cmax) and 12 h (C50) after the last dose. The plasma concentration was determined by high-performance liquid chromatography. The relationship between plasma concentration and clinical and microbiological outcomes and safety was evaluated. The influence of covariates (age, sex, weight, SAPS3, creatinine, liver enzymes and extracorporeal devices: continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO)) was analysed. Population pharmacokinetic modelling was performed using NONMEN®. A total of 71 isavuconazole samples from 24 patients were analysed. The mean Cmin was 1.76 (1.02) mg/L; 87.5% reached the optimal therapeutic target and 12.5% were below 1 mg/L. Population pharmacokinetics were best described by a one-compartment model with first-order elimination. No factor had a significant impact on the plasma concentration or pharmacokinetic parameters. Thus, isavuconazole could be safely used in a critically ill population, even in those treated with CRRT and ECMO, from a pharmacokinetic standpoint. Therefore, routine therapeutic drug monitoring may not be strictly necessary in daily clinical practice.

Severe community-acquired Streptococcus pneumoniae bacterial meningitis: clinical and prognostic picture from the intensive care unit.

BACKGROUND: Severe community-acquired pneumococcal meningitis is a medical emergency. The aim of the present investigation was to evaluate the epidemiology, management and outcomes of this condition. METHODS: This was a retrospective, observational and multicenter cohort study. Sixteen Spanish intensive care units (ICUs) were included. Demographic, clinical and microbiological variables from patients with Streptococcus pneumoniae meningitis admitted to ICU were evaluated. Clinical response was evaluated at 72 h after antibiotic treatment initiation, and meningitis complications, length of stay and 30-day mortality were also recorded. RESULTS: In total, 255 patients were included. Cerebrospinal fluid (CSF) culture was positive in 89.7%; 25.7% were non-susceptible to penicillin, and 5.2% were non-susceptible to ceftriaxone or cefotaxime. The most frequent empiric antibiotic regimen was third-generation cephalosporin (47.5%) plus vancomycin (27.8%) or linezolid (12.9%). A steroid treatment regimen was administered to 88.6% of the patients. Clinical response was achieved in 65.8% of patients after 72 h of antibiotic treatment. Multivariate analysis identified two factors associated with early treatment failure: invasive mechanical ventilation (OR 10.74; 95% CI 3.04-37.95, p < 0.001) and septic shock (OR 1.18; 95% CI 1.03-1.36, p = 0.017). The 30-day mortality rate was 13.7%. Only three factors were independently associated with 30-day mortality: delay in start of antibiotic treatment (OR 18.69; 95% CI 2.13-163.97, p = 0.008), Sepsis-related Organ Failure Assessment (SOFA) score (OR 1.36; 95% CI 1.12-1.66, p = 0.002) and early treatment failure (OR 21.75 (3.40-139.18), p = 0.001). Neurological complications appeared in 124 patients (48.63%). CONCLUSIONS: Mortality rate in critically ill patients with pneumococcal meningitis is lower than previously reported. Delay in antibiotic treatment following admission is the only amendable factor associated with mortality.

Impact of the "Zero Resistance" program on acquisition of multidrug-resistant bacteria in patients admitted to Intensive Care Units in Spain. A prospective, intervention, multimodal, multicenter study.

OBJECTIVE: To assess the impact of a multimodal interventional project ("Zero Resistance") on the acquisition of multidrug-resistant bacteria (MDR-B) during the patient's ICU stay. DESIGN: Prospective, open-label, interventional, multicenter study. SETTING: 103 ICUs. PATIENTS: Critically ill patients admitted to the ICUs over a 27-month period. INTERVENTIONS: Implementation of a bundle of 10 recommendations to prevent emergence and spread of MDR-B in the ICU. MAIN VARIABLE OF INTEREST: Rate of patients acquiring MDR-B during their ICU stay, with differentiation between colonization and infection. RESULTS: A total of 139,505 patients were included. In 5409 (3.9%) patients, 6020 MDR-B on ICU admission were identified, and in 3648 (2.6%) patients, 4269 new MDR-B during ICU stay were isolated. The rate of patients with MDR-B detected on admission increased significantly (IRR 1.43, 95% CI 1.31-1.56) (p<0.001) during the study period, with an increase of 32.2% between the initial and final monthly rates. On the contrary, the rate of patients with MDR-B during ICU stay decreased non-significantly (IRR 0.93, 95% CI 0.83-1.03) (p=0.174), with a 24.9% decrease between initial and final monthly rates. According to the classification into colonization or infection, there was a highly significant increase of MDR-B colonizations detected on admission (IRR 1.69, 95% CI 1.52-1.83; p<0.0001) and a very significant decrease of MDR-B-infections during ICU stay (IRR 0.67, 95% CI 0.57-0.80, p<0.0001). CONCLUSIONS: The implementation of ZR project-recommendations was associated with a significantly reduction an infection produced by MDR-B acquired during the patient's ICU stay.

Determination of meropenem in endotracheal tubes by in-tube solid phase microextraction coupled to capillary liquid chromatography with diode array detection.

Meropenem is a widely used antimicrobial for the treatment of infections associated with the use of invasive medical devices in intensive care unit patients. These treatments are not always effective, in fact, in-vitro studies have demonstrated the difficulty of antimicrobials to penetrate into the biofilm, however in-vivo studies of the effect of these compounds is a trend, mostly because of the complexity of pulmonary samples extracted from ETTs. Therefore, the objective of this study was to evaluate in-tube solid phase microextraction (in-tube SPME) coupled to capillary liquid chromatography (CapLC) with DAD to determine meropenem in ETTs in order to estimate the penetration capability into the biofilm. Firstly, different parameter affecting in-tube SPME, such as processed sample volume, capillary length, flow and capillary coating were studied. The best analytical response was achieved by processing 500 µL of standards/samples at 9 µL/seg with a 60-cm capillary column coated with 35%-diphenyl 65%-polydimethylsiloxane. Under these conditions, the analytical performance of in-tube SPME-CapLC-DAD, using acetonitrile-water in gradient mode as mobile phase, showed satisfactory results for estimation of meropenem in terms of sensitivity (LOD = 3 µg/L) and precision (RSD < 10%). Once the experimental conditions were stablished for in-tube SPME, the extraction of meropenem from the ETTs was studied. Liquid extraction, vortex-assisted liquid extraction (VALE) and ultrasound-extraction (UAE) extraction were tested. The results indicated that meropenem could be quantitatively extracted (91 ±â€¯6%) from ETTs, for its subsequent determination by in-tube SPME-CapLC-DAD using water as extraction solvent and 1 min as extraction time. Finally, samples from ETTs used for critically ill patients with different antimicrobial treatments were analysed with successful results.

Mobiluncus curtisii bacteremia.

Mobiluncus curtisii was isolated from the blood of a 35-year-old man with a medical history of ulcerative colitis who was admitted unconscious to the Intensive Care Unit (ICU). A CT scan revealed massive intracerebral hemorrhage in the left hemisphere. Temperature remained constant over 38.5 degrees C; therefore, two sets of blood cultures were collected. One anaerobic bottle BacT/ALERT SN (bioMerieux, France) was detected as positive after 5 days of incubation and a Gram stain confirmed a gram variable curved-shaped rod. The patient died 18 h after being admitted to the hospital.