Clostridium difficile infections (CDI) in hospitalized patients are known to be closely related to antibiotic exposure. Although several substances can cause CDI, the risk differs between individual agents. In Vienna and other eastern parts of Austria, CDI ribotype 027 is currently highly prevalent. This ribotype has the characteristic of intrinsic moxifloxacin resistance. Therefore, we hypothesized that moxifloxacin restriction can decrease the number of CDI cases in hospitalized patients. Our antibiotic stewardship (ABS) group applied an information campaign on CDI and formal restriction of moxifloxacin in Wilhelminenspital (Vienna, Austria), a 1,000-bed tertiary care hospital. The preintervention period (period 1) was January through May 2013, and the intervention period (period 2) was June through December 2013. We recorded the defined daily doses (DDD) of moxifloxacin and the number of CDI patients/month. Moxifloxacin use was reduced from a mean (؎ standard error of the mean [SEM]) of 1,038 ؎ 109 DDD per month (period 1) to 42 ؎ 10 DDD per month (period 2) (P ‫؍‬ 0.0045). Total antibiotic use was not affected. The mean (؎SEM) numbers of CDI cases in period 1 were 59 ؎ 3 per month and in period 2 were 32 ؎ 3 per month (46% reduction; P ‫؍‬ 0.0044). Reducing moxifloxacin use in combination with providing structured information on CDI was associated with an immediate decrease in CDI rates in this large community teaching hospital.C lostridium difficile infection (CDI) is a common side effect of antimicrobial therapy, and C. difficile is endemic in hospitals due to health care-associated transmissions. CDI is associated with increased mortality rates and economic burden (1, 2). Although several substances can cause CDI, the risk differs between individual antibiotics. A recent meta-analysis of community-associated CDI comprising 30,184 patients (3) showed that the risk for CDI was greatest with clindamycin (odds ratio [OR], 20.43; 95% confidence interval [CI], 8.50 to 49.09), followed by fluoroquinolones (OR, 5.65; 95% CI, 4.38 to 7.28).

In a hospital-based, prospective cohort study, the effects of the three standard treatment regimens for mild Clostridium difficile infection (CDI), oral (p.o.) metronidazole at 500 mg three times/day, intravenous (i.v.) metronidazole at 500 mg three times/day, and oral (p.o.) vancomycin at 250 mg four times/day, were compared with respect to the risk of occurrence of complications, sequelae, and all-cause death within 30 days after the date of starting treatment. Differences in the incidence of these outcomes were tested by 2 or Fisher's exact tests. A Poisson regression model was performed to control for possible confounding effects of sex, age, and severity of comorbidity categorized according to the Charlson comorbidity index. The highest mortality was observed in the metronidazole i.v. group, with a mortality rate 38.1% (16/42) compared to mortality rates of 7.4% (9/121) in the metronidazole p.o. group and 9.5% (4/42) in the vancomycin p.o. group (P < 0.001). After adjustment for possible effects of sex, age (>65 years), and severity of comorbidity, the relative risk of a 30-day fatal outcome for patients receiving metronidazole i.v. was 4.3 (95% confidence interval [CI] ‫؍‬ 1.92 to 10; P < 0.0001) compared to patients treated with metronidazole p.o. and 4.0 (95% CI ‫؍‬ 1.31 to 5.0; P < 0.015) compared to patients treated with vancomycin p.o. There were no significant differences in the risk of complications between the three treatment groups. This study generates the hypothesis that treatment with i.v. metronidazole is inferior to the oral alternatives metronidazole and vancomycin.

We recommend 8 mg/kg daptomycin every 48 h in patients on CVVHDF and therapeutic drug monitoring, if possible.

SummaryReparixin, a CXCR 1/2 antagonist, has been shown to mitigate ischaemiareperfusion injury (IRI) in various organ systems in animals, but data in humans are scarce. The aim of this double-blinded, placebo-controlled pilot study was to evaluate the safety and efficacy of reparixin to suppress IRI and inflammation in patients undergoing on-pump coronary artery bypass grafting (CABG). Patients received either reparixin or placebo (n = 16 in each group) after induction of anaesthesia until 8 h after cardiopulmonary bypass (CPB). We compared markers of systemic and pulmonary inflammation, surrogates of myocardial IRI and clinical outcomes using Mann-Whitney Uand Fisher's exact tests. Thirty-and 90-day mortality was 0% in both groups. No side effects were observed in the treatment group. Surgical revision, pleural and pericardial effusion, infection and atrial fibrillation rates were not different between groups. Reparixin significantly reduced the proportion of neutrophil granulocytes in blood at the beginning [49%, interquartile range (IQR) = 45-57 versus 58%, IQR = 53-66, P = 0·035], end (71%, IQR = 67-76 versus 79%, IQR = 71-83, P = 0·023) and 1 h after CPB (73%, IQR = 71-75 versus 77%, IQR = 72-80, P = 0·035). Reparixin patients required a lesser positive fluid balance during surgery (2575 ml, IQR = 2027-3080 versus 3200 ml, IQR = 2928-3778, P = 0·029) and during ICU stay (2603 ml, IQR = 1023-4288 versus 4200 ml, IQR = 2313-8160, P = 0·021). Numerically, more control patients required noradrenaline ≥ 0·11 μg/kg/min (50 versus 19%, P = 0·063) and dobutamine (50 versus 25%, P = 0·14). Therefore, administration of reparixin in CABG patients appears to be feasible and safe. It concurrently attenuated postoperative granulocytosis in peripheral blood.

BackgroundDuring the influenza pandemic of 2009/10, the whole-virion, Vero-cell-derived, inactivated, pandemic influenza A (H1N1) vaccine Celvapan® (Baxter) was used in Austria. Celvapan® is adjuvant-free and was the only such vaccine at that time in Europe. The objective of this observational, non-interventional, prospective single-center study was to evaluate the immunogenicity and tolerability of two intramuscular doses of this novel vaccine in HIV-positive individuals.Methods and FindingsA standard hemagglutination inhibition (HAI) assay was used for evaluation of the seroconversion rate and seroprotection against the pandemic H1N1 strain. In addition, H1N1-specific IgG antibodies were measured using a recently developed ELISA and compared with the HAI results. Tolerability of vaccination was evaluated up to one month after the second dose. A total of 79 HIV-infected adults with an indication for H1N1 vaccination were evaluated. At baseline, 55 of the 79 participants had an HAI titer ≥1∶40 and two patients showed a positive IgG ELISA. The seroconversion rate was 31% after the first vaccination, increasing to 41% after the second; the corresponding seroprotection rates were 92% and 83% respectively. ELISA IgG levels were positive in 25% after the first vaccination and in 37% after the second. Among the participants with baseline HAI titers <1∶40, 63% seroconverted. Young age was clearly associated with lower HAI titers at baseline and with higher seroconversion rates, whereas none of the seven patients >60 years of age had a baseline HAI titer <1∶40 or seroconverted after vaccination. The vaccine was well tolerated.ConclusionThe non-adjuvanted pandemic influenza A (H1N1) vaccine was well tolerated and induced a measurable immune response in a sample of HIV-infected individuals.