Impact of Loading Dose of Caspofungin in Pharmacokinetic-Pharmacodynamic Target Attainment for Severe Candidiasis Infections in Patients in Intensive Care Units: the CASPOLOAD Study.

This study evaluated the impact of a high loading dose of caspofungin (CAS) on the pharmacokinetics of CAS and the pharmacokinetic-pharmacodynamic (PK-PD) target attainment in patients in intensive care units (ICU). ICU patients requiring CAS treatment were prospectively included to receive a 140-mg loading dose of CAS. Plasma CAS concentrations (0, 2, 3, 5, 7, and 24 h postinfusion) were determined to develop a two-compartmental population PK model. A Monte Carlo simulation was performed and the probabilities of target attainment (PTAs) were computed using previously published MICs. PK-PD targets were ratios of area under the concentration-time curve from 0 to 24 h (AUC0-24h) divided by the MIC (AUC0-24h/MIC) of 250, 450, and 865 and maximal concentration (Cmax) divided by the MIC (Cmax/MIC) of 5, 10, 15, and 20. Among 13 included patients, CAS clearance was 0.98 ± 0.13 liters/h and distribution volumes were V1 = 9.0 ± 1.2 liters and V2 = 11.9 ± 2.9 liters. Observed and simulated CAS AUC0-24h were 79.1 (IQR 55.2; 108.4) and 81.3 (IQR 63.8; 102.3) mg · h/liter during the first 24 h of therapy, which is comparable to values usually observed in ICU patients at day 3 or later. PTAs were >90% for MICs of 0.19 and 0.5 mg/liter, considering AUC/MIC = 250 and Cmax/MIC = 10 as PK-PD targets, respectively. Thus, a high loading dose of CAS (140 mg) increased CAS exposure in the first 24 h of therapy, allowing early achievement of PK-PD targets for most Candida strains. Such a strategy seems to improve treatment efficacy, though further studies are needed to assess the impact on clinical outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT02413892.).

Perivalvular Mitral Abscess Fistulised to the Pericardial Cavity Revealing Staphylococcal Endocarditis.

BACKGROUND: Fistula to the pericardial cavity is a very rare complication of perivalvular abscess during infective endocarditis, with Staphylococcus aureus being the most commonly associated microorganism. METHODS: We report a fatal septic shock due to a mitral endocarditis revealed by a myocardial abscess fistulised toward the pericardial cavity. RESULTS: A 66-year-old female without previous valvular disease was admitted to intensive care for severe sepsis. A few hours after admission, an unexpected cardiac arrest occurred. Chest computed tomographic-scan and transoesophageal echocardiography revealed a pericardial effusion due to a perivalvular mitral abscess fistulised toward the pericardial cavity. Despite prompt management including surgical debridement and appropriate antibiotics, death occurred 36hours after intensive care admission. All blood cultures as well as native mitral valve and pericardial fluid grew methicillin-sensitive Staphylococcus aureus. CONCLUSIONS: Intensivists should consider this rare complication in patients with staphylococcal infective endocarditis and perivalvular abscess.

Preload dependency determines the effects of phenylephrine on cardiac output in anaesthetised patients: A prospective observational study.

BACKGROUND: Although phenylephrine is widely used in the operating room to control arterial pressure, its haemodynamic effects remain controversial. OBJECTIVE: We hypothesised that the effect of phenylephrine on cardiac output is affected by preload dependency. DESIGN: A prospective observational study. SETTING: Single-centre, University Hospital of Caen, France. PATIENTS: Fifty ventilated patients undergoing surgery were studied during hypotension before and after administration of phenylephrine. MAIN OUTCOME MEASURES: Cardiac index (CI), stroke volume (SV), corrected flow time, mean arterial pressure, pulse pressure variations (PPV) and systemic vascular resistance index were used to assess effects of changes in preload dependency. RESULTS: Twenty seven (54%) patients were included in the preload-dependent group (PPV ≥ 13%) and 23 (46%) in the preload-independent group (PPV < 13%) before administration of phenylephrine. For the whole cohort, phenylephrine increased mean arterial pressure [58 (±8) mmHg vs. 79 (±13) mmHg; P < 0.0001] and calculated systemic vascular resistance index [2010 (1338; 2481) dyn s cm m vs. 2989 (2155; 3870) dyn s cm m; P < 0.0001]. However, CI and SV decreased in the preload-independent group [2.3 (1.9; 3.7) l min m vs. 1.8 (1.5; 2.7) l min m; P < 0.0001 and 65 (44; 81) ml vs. 56 (39; 66) ml; P < 0.0001 for both] but not in the preload-dependent group [respectively 2.1 (1.8; 3.5) l min m vs. 2.1 (1.8; 3.3) l min m; P = 0.168 and 49 (41; 67) ml vs. 53 (41; 69) ml; P = 0.191]. Corrected flow time increased [294 (47) ms vs. 306 (56) ms; P = 0.031], and PPV decreased [17 (15; 19) % vs.12 (14; 16) %; P < 0.0003] only in the PPV at least 13% group. CONCLUSION: The effects of phenylephrine on CI and SV depend on preload. CI and SV decreased in preload-independent patients through increase in afterload, but were unchanged in those preload-dependent through increased venous return.

Semi-quantitative cultures of throat and rectal swabs are efficient tests to predict ESBL-Enterobacterales ventilator-associated pneumonia in mechanically ventilated ESBL carriers.

PURPOSE: In ICU patients with carriage of extended spectrum beta-lactamase producing Enterobacterales (ESBL-E) and suspected Gram-negative bacilli ventilator-associated pneumonia (GNB-VAP), the quantification of the rectal and throat ESBL-E carriage might predict the ESBL-E involvement in GNB-VAP. Our aim was to evaluate whether a semi-quantitative assessment of rectal/throat ESBL-E carriage can predict ESBL-E-associated VAP in medical ICU patients. METHODS: From May 2014 to May 2017, all ESBL-E carriers had a semi-quantitative assessment of ESBL-E density in swabs cultures. For those who developed GNB-VAP (diagnosed using bronchoalveolar lavage or plugged telescopic catheter with significant quantitative culture), the last positive swab collected at least 48 h before GNB-VAP onset was selected. Clinical data were extracted from a prospectively collected database. RESULTS: Among 365 ESBL-E carriers, 82 developed 107 episodes of GNB-VAP (ESBL-E VAP, n = 50; and non-ESBL-E GNB-VAP, n = 57) after 13 days of mechanical ventilation in median. Antimicrobials use before VAP onset was similar between groups. The last swabs were collected 5 days in median before VAP onset. ESBL-E. coli carriers developed ESBL-E VAP less frequently (n = 13, 34%) than others (n = 32, 67.3%, p < .01). Throat swab positivity (39 (78%) vs. 12 (23%), p < .01) was more frequent for ESBL-E VAP. ESBL-E VAP was associated with significantly higher ESBL-E density in rectal swabs. In multivariate models, non-E. coli ESBL-E carriage and rectal ESBL-E carriage density, or throat carriage, remained associated with ESBL-E VAP. CONCLUSION: In carriers of ESBL-E other than E. coli, ESBL-E throat carriage or a high-density ESBL-E rectal carriage are risk factors of ESBL-E VAP in case of GNB-VAP.

Impact of natural light exposure on delirium burden in adult patients receiving invasive mechanical ventilation in the ICU: a prospective study.

OBJECTIVE: To determine whether potential exposure to natural light via windows is associated with reduced delirium burden in critically ill patients admitted to the ICU in a single room. DESIGN: Prospective single-center study. SETTING: Medical ICU of a university hospital, Paris, France. PATIENTS: Adult patients receiving invasive mechanical ventilation. METHODS: Consecutive patients admitted to a single room with (LIGHT group) or without (DARK group) exposure to natural light via windows were evaluated for delirium. The primary endpoint was the incidence of delirium. Main secondary endpoints included incidence of severe agitation intervened with antipsychotics and incidence of hallucinations. RESULTS: A total of 195 patients were included (LIGHT group: n = 110; DARK group: n = 85). The incidence of delirium was similar in the LIGHT group and the DARK group (64% vs. 71%; relative risk (RR) 0.89, 95% CI 0.73-1.09). Compared with the DARK group, patients from the LIGHT group were less likely to be intervened with antipsychotics for agitation episodes (13% vs. 25%; RR 0.52, 95% CI 0.27-0.98) and had less frequent hallucinations (11% vs. 22%; RR 0.49, 95% CI 0.24-0.98). In multivariate logistic regression analysis, natural light exposure was independently associated with a reduced risk of agitation episodes intervened with antipsychotics (adjusted odds ratio = 0.39; 95% CI 0.17-0.88). CONCLUSION: Admission to a single room with potential exposure to natural light via windows was not associated with reduced delirium burden, as compared to admission to a single room without windows. However, natural light exposure was associated with a reduced risk of agitation episodes and hallucinations.

Endovascular cooling versus standard femoral catheters and intravascular complications: A propensity-matched cohort study.

BACKGROUND: Targeted temperature management (TTM) contributes to improved neurological outcome in adults who have been successfully resuscitated after cardiac arrest with shockable rhythm. Endovascular cooling catheters are widely used to induce and maintain targeted temperature in the ICU. The aim of the study was to compare the risk of complications with cooling catheters and standard central venous catheters. MATERIALS AND METHODS: In this prospective single-centre cohort study, we included all patients admitted to an intensive care unit for successfully resuscitated cardiac arrest that required endovascular TTM (Coolgard®, Zoll™ Medical corporation, MA, USA), between August 2012 and November 2014, inclusive. We matched the endovascular cooling catheter cohort with a retrospective historical cohort of 512 central femoral venous catheters from the 3SITES trial to compare thrombotic and infectious complications. RESULTS: Overall, 108 patients were included in the cooling cohort, of which 89 had ultrasound doppler. The duration of catheterization was 4.9 days in the control group versus 4.2 days in the TTM group (p = 0.08). After propensity-score matching, there were significantly more thrombotic complications in the cooling (n = 75) than in the control (n = 75) group (12 of 75 (16%) versus 0 of 75 (0%), respectively, p = 0.005), and 4 patients presented major complications. There were 8 colonized catheters in each group (11%) (p > 0.99), and none of the patients had a catheter-related bloodstream infection. CONCLUSIONS: In our propensity-score matched study, endovascular cooling catheters were associated with an increased risk of venous catheter-related thrombosis compared to standard central venous catheters.