Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis

OBJECTIVES: Among patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant. DESIGN: Secondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722). SETTING: One hundred-fifty-three ICUs in 13 countries. PATIENTS: Altogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p < 0.001). The median time to RRT initiation among patients allocated to the standard strategy was longest in Europe compared with North America and ANZ (p < 0.001; p < 0.001). Continuous RRT was the initial RRT modality in 60.8% of patients in North America and 56.8% of patients in Europe, compared with 96.4% of patients in ANZ (p < 0.001). After adjustment for predefined baseline characteristics, compared with North American and European patients, those in ANZ were more likely to survive to ICU (p < 0.001) and hospital discharge (p < 0.001) and to 90 days (for ANZ vs. Europe: risk difference [RD], -11.3%; 95% CI, -17.7% to -4.8%; p < 0.001 and for ANZ vs. North America: RD, -10.3%; 95% CI, -17.5% to -3.1%; p = 0.007). CONCLUSIONS: Among STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions

Fungal colonization of soil-buried plasticized polyvinyl chloride (pPVC) and the impact of incorporated biocides

Plasticized polyvinyl chloride (pPVC) with or without incorporated biocides was buried in grassland and forest soil for up to 10 months. The change with time in viable counts of fungi on the plastic surface was followed, together with the percentage capable of clearing the two plasticizers dioctyl adipate (DOA) and dioetyl phthalate (DOP). With time fungal total viable counts (TVC) on control pPVC increased and the fraction able to clear DOA was considerably higher than the average estimated in both soil types. A total of 92 fungal morphotypes were isolated from grassland soil and 42 from forest soil with the greatest variety of fungal isolates observed on control pPVC. The incorporation of biocides into pPVC affected both fungal TVC and the richness of species isolated. The biocides NCMP [n-(trichloromethylthio)phthalimide], OBPA (10,10′-oxybisphenoxarsine) and OIT (2-n-octyl-4-isothiazolin-3-one) were the most effective in grassland soil, and TCMP [2,3,5,6-tetrachloro-4-(methylsulphonyl)pyridine] and NCMP the most effective in forest soil. In grassland soil, Penicillium janthinellum established as a principal colonizer and was recovered from all pPVC types. DOP clearers were found at much lower levels than DOA clearers, with Doratomyces spp. being the most efficient. At the end of 10 months the physical properties of the pPVC were altered; changes in stiffness were the most significant for heavily colonized grassland-buried pPVC samples, whereas in forest soil, the extensibility of the pPVC was affected more than the stiffness. These results suggest that fungi are important colonizers of pPVC buried in soil and that enrichment of soil fungi capable of clearing DOA occurs during colonization of the plastic surface. The results also demonstrate that incorporated biocides have a marked impact on the richness of species colonizing the pPVC surface. © 2006 SGM

In situ quantification of biocide efficacy using GFP transformed Aureobasidium pullulans

Aims: To develop a real-time in situ method to quantify loss of viability of Aureobasidium pullulans PRAFS8 cells attached to plasticized polyvinyl chloride (pPVC) with incorporated biocides, and to use the method to compare biocide efficacy in situ. Methods and Results: A. pullulans PRAFS8, transformed with green fluorescent protein (GFP), was used to quantify the efficacy of a range of biocides incorporated into pPVC. Experimentally, it was found that a density of 1.53 × 106 yeast cells per cm2 of pPVC was optimal as increasing the density of the yeast cells to 6.12 × 10 6 cm-2 attached to pPVC containing the biocide 2-n-octyl-4-isothiazolin-3-one (OIT) decreased the rate of fluorescence loss. A strong positive correlation between fluorescence and viable yeast cell number was observed and fluorescence was used as a direct indicator of cell viability. The effectiveness of five commercial biocides, commonly incorporated into pPVC at their in-use concentrations, was tested against yeast cells attached to the pPVC surface. The loss of fluorescence and hence viability in situ was quantified using image analysis. The biocides N-(trichloromethylthio) phthalimide (NCMP), 10,10′-oxybisphenoxarsine (OBPA), OIT and 2,3,5,6-tetrachloro-4-(methylsulphonyl) pyridine (TCMP) caused complete loss of fluorescence within 30-50 h. In contrast the biocide dichloro-octyl- isothiazoline caused only 55 ± 15% fluorescence loss after 50 h. Starvation of the yeast cells in suspension for 24 h prior to attachment reduced their initial sensitivity to OBPA, NCMP, OIT and TCMP by 15-20%, but eventually the fluorescence was also completely lost. Conclusions: The use of A. pullulans expressing cytosolic GFP enables the in situ quantification of loss of viability when cells are attached to pPVC with incorporated biocides. Significance and Impact of the Study: GFP fluorescence was used as a real-time indicator of cell viability and thus can be applied for direct quantification of the effectiveness of a broad range of biocides, incorporated into the polymer mass and used to protect a variety of plastics or other materials from microbial growth

Influence of starvation, surface attachment and biofilm growth on the biocide susceptibility of the biodeteriogenic yeast Aureobasidium pullulans

Aims: To investigate the effect of starvation, surface attachment and growth in a biofilm on the susceptibility of Aureobasidinm pullulans to the biocides 2-n-octyl-4-isothiazolin-3-one (OIT) and sodium hypochlorite (NaOCl). Methods and Results: Fluorescence loss from a green fluorescent protein (GFP)-transformed strain was used to monitor real-time loss in viability as previously described in situ in 96-well plates. Exponential phase, yeast-like (YL) cells were settled in the bottom of the wells as a low-density monolayer (LDM) and were susceptible to all biocide concentrations (25-100 μg ml -1). The exponential phase YL cells were either starved for 48 h in suspension or starved for 48 h as LDMs in the wells. Starvation in both cases led to a small reduction in susceptibility to the biocides. In contrast, 48-h biofilms grown in malt extract broth showed an apparent lack of susceptibility to 25 and 50 μg ml-1 OIT and to 25-100 μg ml-1 NaOCl. However, when the OIT concentration was increased to compensate for the higher cell density in the biofilm, the biofilms were found to be equally susceptible to the LDM. Conclusions: Starvation of A. pullulans YL cells either in suspension or as attached LDM resulted in a decrease in susceptibility to low concentrations of both OIT and NaOCl while the apparent reduced susceptibility of mature biofilms was due to the increase in biofilm cell density rather than true biofilm resistance per se. Significance and Impact of the Study: Monitoring fluorescence loss from the GFP-transformed strain of A. pullulans can be used as a fast and reliable method for monitoring cell death in real time as a response to biocide and antimicrobial challenge. © 2006 The Authors