Free-living amoebae promote Candida auris survival and proliferation in water.

Candida auris is an emerging species responsible for life-threatening infections. Its ability to be resistant to most systemic antifungal classes and its capacity to persist in a hospital environment have led to health concerns. Currently, data about environmental reservoirs are limited but remain essential in control of C. auris spread. The aim of our study was to explore the interactions between C. auris and two free-living amoeba (FLA) species, Vermamoeba vermiformis and Acanthamoeba castellanii, potentially found in the same water environment. Candida auris was incubated with FLA trophozoites or their culture supernatants. The number of FLA and yeasts was determined at different times and transmission electron microscopy (TEM) was performed. Supernatants of FLAs promoted yeast survival and proliferation. Internalization of viable C. auris within both FLA species was also evidenced by TEM. A water environmental reservoir of C. auris can therefore be considered through FLAs and contamination of the hospital water networks would consequently be possible.

Mucormycosis treatment: Recommendations, latest advances, and perspectives.

Mucormycosis are life-threatening fungal infections especially affecting immunocompromised or diabetic patients. Despite treatment, mortality remains high (from 32 to 70% according to organ involvement). This review provides an update on mucormycosis management. The latest recommendations strongly recommend as first-line therapy the use of liposomal amphotericin B (≥5mg/kg) combined with surgery whenever possible. Isavuconazole and intravenous or delayed-release tablet forms of posaconazole have remained second-line. Many molecules are currently in development to fight against invasive fungal diseases but few have demonstrated efficacy against Mucorales. Despite in vitro efficacy, combinations of treatment have failed to demonstrate superiority versus monotherapy. Adjuvant therapies are particularly complex to evaluate without prospective randomized controlled studies, which are complex to perform due to low incidence rate and high mortality of mucormycosis. Perspectives are nonetheless encouraging. New approaches assessing relationships between host, fungi, and antifungal drugs, and new routes of administration such as aerosols could improve mucormycosis treatment.

Antifungal susceptibility testing practices in mycology laboratories in France, 2018.

A survey of mycology laboratories for antifungal susceptibility testing (AFST) was undertaken in France in 2018, to better understand the difference in practices between the participating centers and to identify the difficulties they may encounter as well as eventual gaps with published standards and guidelines. The survey captured information from 45 mycology laboratories in France on how they perform AFST (number of strains tested, preferred method, technical and quality aspects, interpretation of the MIC values, reading and interpretation difficulties). Results indicated that 86% of respondents used Etest as AFST method, with a combination of one to seven antifungal agents tested. Most of the participating laboratories used similar technical parameters to perform their AFST method and a large majority used, as recommended, internal and external quality assessments. Almost all the participating mycology laboratories (98%) reported difficulties to interpret the MIC values, especially when no clinical breakpoints are available. The survey highlighted that the current AFST practices in France need homogenization, particularly for MIC reading and interpretation.

In vitro activity of isavuconazole against three species of Acanthamoeba.

Acanthamoeba keratitis due to a genus of free-living amoebae is a severe corneal infection. Treatment of this disease is based on the combined use of antiseptics and other drugs, including azoles. We tested isavuconazole, the latest marketed azole, in vitro, against A. castellanii, A. lenticulata and A. hatchetti. Our results show that isavuconazole presents slight amoebistatic activity against A. castellanii trophozoites but no cysticidal activity. Isavuconazole could be used only in association for management of AK due to A. castellanii.

Twenty-four-hour intragastric measurements in twenty healthy subjects: effect of enisoprost, a novel and potent antisecretory and antipeptic synthetic E1 prostaglandin.

Gastric aspiration was performed continuously overnight and at hourly intervals during the daytime in 20 healthy male volunteers. Medications used included enisoprost 100, 200 or 400 micrograms, misoprostol 200 micrograms and placebo, given at bedtime. Each dose of enisoprost markedly inhibited nocturnal mean acid output, hydrogen ion activity, pH and peptic activity. The duration of these effects was up to 10 h. Misoprostol, given at bedtime, also decreased acid secretion, but the effect was significantly less than that observed with any of the doses of enisoprost. A dose-response effect for enisoprost was found for the mean nocturnal hydrogen ion activity and pH, as well as for maximum pH attained. Although enisoprost, given at bedtime, had a marked inhibitory effect on acid and pepsin secretion for the overnight interval, this did not result in rebound hyperacidity or a rise in serum total gastrin concentration. The results of this study suggest that enisoprost should be tested by clinical trial for the treatment of peptic ulcer disease.

Comparison of cimetidine and ranitidine on 24-hour intragastric acidity and serum gastrin profile in patients with esophagitis.

Twenty-four-hour intragastric pH and serum gastrin profiles were monitored in six male asymptomatic patients who previously were found to have esophagitis on endoscopy and biopsy. They received cimetidine 300 mg qid (C), ranitidine 150 mg bid (R), or placebo (P) for one week each, utilizing the Latin-square design. The mean BAO was 0.4 +/- 0.2 mmol/hr, and the pentagastrin-stimulated MAO was 21.2 +/- 3.2 mmol/hr. In the P-treated patients, the pH fluctuated between 1.8 and 3.5 and over 90% of the readings were less than pH 4. As compared to P, both C and R significantly suppressed H+ after breakfast, overnight, and over the 24-hr period. The mean pH after lunch was significantly higher in R than in P, but not in C. Over the 24-hr period, a higher percentage of the readings were above pH 4.0 in R as compared to C. During the night, 50% of the pH readings were above pH 4.0 in C and R, whereas in P 50% of the pH readings were less than pH 2.0. The integrated gastrin responses after each meal were similar in C and R and were greater than in P. The biphasic response of the ratio of H+ and gastrin (H+/G) following each meal was suppressed by both H2-receptor antagonists, with numerically lower values obtained in R than in C. This study suggests that ranitidine 150 mg bid is superior to cimetidine 300 mg qid in suppressing the 24-hr intragastric acidity.

Postprandial changes in serum concentrations of gastrin-17, gastrin-34, and total gastrin in patients with duodenal or gastric ulcers and in normal subjects.

The fasting concentrations of total gastrin and gastrin-17 (G-17) were similar in healthy volunteers and in asymptomatic patients with gastric ulcers or duodenal ulcers. However, the fasting serum concentration of gastrin-34 (G-34) was higher in patients with gastric ulcers than in normal subjects, in whom it was higher than in patients with duodenal ulcers. In response to food, the increases in G-17, G-34, and total gastrin were greater in ulcer patients than in healthy subjects. Cimetidine administration was associated with further increases in G-17, G-34, and total gastrin in normal subjects and gastric ulcer patients after meals. The ratio G-17/G-34 was similar in placebo-treated normal subjects and placebo-treated patients with gastric or duodenal ulcers. Cimetidine produced an increase in G-17/G-34 in placebo-treated normal subjects and placebo-treated patients with gastric or duodenal ulcers, but the ratio G-17/G-34 was greater in patients with gastric ulcers than in normal subjects. These results indicate that: differences in serum gastrin concentrations between patient groups, treatment regimens, and time of day are better detected by measuring G-17 and G-34 rather than total gastrin; there are differences in fasting and food-stimulated gastrin concentrations between normal subjects and patients with gastric or duodenal ulcers; the fasting concentration of G-34 is higher than G-17 in normal subjects and patients with gastric ulcers but not in patients with duodenal ulcers; food increases G-17 in all subjects but G-34 only in subjects with gastric ulcers; cimetidine increases the fasting concentration of total gastrin in normal subjects and patients with gastric ulcers and increases G-17 and G-34 in normal subjects; cimetidine increases the ratio G-17/G-34 in normal subjects and patients with gastric ulcers, but decreases G-17/G-34 in patients with duodenal ulcers. It is proposed: that measurements of total gastrin concentration should be replaced by measurements of G-17 and G-34 and that such measurements of G-17 and G-34 indicate differences in serum gastrin concentrations between normal subjects and those with peptic ulcers and between those with gastric versus duodenal ulcers. The role of altered gastrin metabolism in the pathogenesis of ulcers needs to be established.