Use of probiotics to prevent ventilator-associated pneumonia: A survey of pharmacists' attitudes.

PURPOSE: The primary objective of this survey was to describe pharmacists' attitudes regarding probiotic use in the intensive care unit (ICU); secondary objectives were to evaluate pharmacists' knowledge and use of probiotics for critically ill patients. METHODS: The survey instrument was rigorously designed and pretested, then distributed in both English and French to Canadian ICU pharmacists. The online survey was open for 5 weeks, and 3 follow-up emails were sent to maximize response rates. RESULTS: Of 303 eligible surveys, 191 were returned (63.0%). Probiotics were available in the hospitals of 69.8% (113/162) of respondents, and 62.0% (101/163) indicated that they had used probiotics for at least 1 ICU patient in the previous year. Most pharmacists (137/171, 80.1%) said that they would "never" consider recommending probiotics for prevention of ventilator-associated pneumonia in ICU patients, and this response was more common (P = .0074) among pharmacists who were "unsure" about the safety of probiotics in this population when compared to those who felt that they knew how safe probiotics are. CONCLUSIONS: Most Canadian ICU pharmacists have used probiotics at least once in the ICU in the last year. However, based on uncertain efficacy and safety, most ICU pharmacists would not currently recommend probiotics for the prevention of ventilator-associated pneumonia.

Influence of arylamine N-acetyltransferase, sex, and age on 4-aminobiphenyl-induced in vivo mutant frequencies and spectra in mouse liver.

One model for cancer initiation by 4-aminobiphenyl (ABP) involves N-oxidation by cytochrome P450 CYP1A2 followed by O-conjugation by N-acetyltransferase(s) NAT1 and/or NAT2 and decomposition to a DNA-binding nitrenium ion. We recently observed that neonatal ABP exposure produced liver tumors in male but not in female mice, and that NAT deficiency reduced liver tumor incidence. However, ABP-induced liver tumor incidence did not correlate with liver levels of N-(deoxyguanosin-8-yl)-ABP adducts 24 hr after exposure. In this study, we compared in vivo ABP-induced DNA mutant frequencies and spectra between male and female wild-type and NAT-deficient Muta™Mouse using both the tumor-inducing neonatal exposure protocol and a 28-day repetitive dosing adult exposure protocol. ABP produced an increase in liver DNA mutant frequencies in both neonates and adults. However, we observed no sex or strain differences in mutant frequencies in neonatally exposed mice, and higher frequencies in adult females than males. Neonatal ABP exposure of wild-type mice increased the proportion of G-T transversions in both males and females, while exposure of Nat1/2(-/-) mice produced increased G-T transversions in males and a decrease in females, even though females had higher levels of N-(deoxyguanosin-8-yl)-4-ABP adducts. There was no correlation of mutant frequencies or spectra between mice dosed as neonates or as adults. These results suggest that observed sex- and NAT-dependent differences in ABP-induced liver tumor incidence in mice are not due to differences in either mutation rates or mutational spectra, and that mechanisms independent of carcinogen bioactivation, covalent DNA binding and mutation may be responsible for these differences.