In Vitro Activity of Delafloxacin and Microbiological Response against Fluoroquinolone-Susceptible and Nonsusceptible Staphylococcus aureus Isolates from Two Phase 3 Studies of Acute Bacterial Skin and Skin Structure Infections.

Delafloxacin is an investigational anionic fluoroquinolone antibiotic with broad-spectrum in vitro activity, including activity against Gram-positive organisms, Gram-negative organisms, atypical organisms, and anaerobes. The in vitro activity of delafloxacin and the percent microbiological response in subjects infected with fluoroquinolone-susceptible and nonsusceptible Staphylococcus aureus isolates were determined from two global phase 3 studies of delafloxacin versus vancomycin plus aztreonam in patients with acute bacterial skin and skin structure infections (ABSSSI). Patients from 23 countries, predominately the United States but also Europe, South America, and Asia, were enrolled. The microbiological intent-to-treat (MITT) population included 1,042 patients from which 685 S. aureus isolates were submitted for identification and susceptibility testing per CLSI guidelines at the central laboratory (JMI Laboratories, North Liberty, IA). The comparator fluoroquinolone antibiotics included levofloxacin and ciprofloxacin. Nonsusceptibility to these antibiotics was determined using CLSI breakpoints. S. aureus isolates were 33.7% levofloxacin nonsusceptible (LVX-NS). The delafloxacin MIC90 values against levofloxacin-nonsusceptible S. aureus, methicillin-resistant S. aureus (MRSA), and methicillin-susceptible S. aureus isolates were all 0.25 µg/ml. Delafloxacin demonstrated high rates of microbiological response against LVX-NS isolates as well as isolates with documented mutations in the quinolone resistance-determining region (QRDR). S. aureus was eradicated or presumed eradicated in 98.4% (245/249) of delafloxacin-treated patients. Similar eradication rates were observed for delafloxacin-treated subjects with levofloxacin-nonsusceptible S. aureus isolates (80/81; 98.8%) and MRSA isolates (70/71; 98.6%). Microbiological response rates of 98.6% were observed with delafloxacin-treated subjects with S. aureus isolates with the S84L mutation in gyrA and the S80Y mutation in parC, the most commonly observed mutations in global phase 3 studies. The data suggest that delafloxacin could be a good option for the treatment of infections caused by S. aureus isolates causing ABSSSI, including MRSA isolates, where high rates of ciprofloxacin and levofloxacin nonsusceptibility are observed. (The phase 3 studies described in this paper have been registered at ClinicalTrials.gov under identifiers NCT01984684 and NCT01811732.).

Cholesterol esters (CE) derived from hepatic sterol O-acyltransferase 2 (SOAT2) are associated with more atherosclerosis than CE from intestinal SOAT2.

RATIONALE: Cholesterol esters (CE), especially cholesterol oleate, generated by hepatic and intestinal sterol O-acyltransferase 2 (SOAT2) play a critical role in cholesterol homeostasis. However, it is unknown whether the contribution of intestine-derived CE from SOAT2 would have similar effects in promoting atherosclerosis progression as for liver-derived CE. OBJECTIVE: To test whether, in low-density lipoprotein receptor null (LDLr(-/-)) mice, the conditional knockout of intestinal SOAT2 (SOAT2(SI-/SI-)) or hepatic SOAT2 (SOAT2(L-/L-)) would equally limit atherosclerosis development compared with the global deletion of SOAT2 (SOAT2(-/-)). METHODS AND RESULTS: SOAT2 conditional knockout mice were bred with LDLr(-/-) mice creating LDLr(-/-) mice with each of the specific SOAT2 gene deletions. All mice then were fed an atherogenic diet for 16 weeks. SOAT2(SI-/SI-)LDLr(-/-) and SOAT2(-/-)LDLr(-/-) mice had significantly lower levels of intestinal cholesterol absorption, more fecal sterol excretion, and lower biliary cholesterol levels. Analysis of plasma LDL showed that all mice with SOAT2 gene deletions had LDL CE with reduced percentages of cholesterol palmitate and cholesterol oleate. Each of the LDLr(-/-) mice with SOAT2 gene deletions had lower accumulations of total cholesterol and CE in the liver compared with control mice. Finally, aortic atherosclerosis development was significantly lower in all mice with global or tissue-restricted SOAT2 gene deletions. Nevertheless, SOAT2(-/-)LDLr(-/-) and SOAT2(L-/L-)LDLr(-/-) mice had less aortic CE accumulation and smaller aortic lesions than SOAT2(SI-/SI-)LDLr(-/-) mice. CONCLUSIONS: SOAT2-derived CE from both the intestine and liver significantly contribute to the development of atherosclerosis, although the CE from the hepatic enzyme appeared to promote more atherosclerosis development.

Sport-specific nutrition: practical strategies for team sports.

Implementation of a nutrition programme for team sports involves application of scientific research together with the social skills necessary to work with a sports medicine and coaching staff. Both field and court team sports are characterized by intermittent activity requiring a heavy reliance on dietary carbohydrate sources to maintain and replenish glycogen. Energy and substrate demands are high during pre-season training and matches, and moderate during training in the competitive season. Dietary planning must include enough carbohydrate on a moderate energy budget, while also meeting protein needs. Strength and power team sports require muscle-building programmes that must be accompanied by adequate nutrition, and simple anthropometric measurements can help the nutrition practitioner monitor and assess body composition periodically. Use of a body mass scale and a urine specific gravity refractometer can help identify athletes prone to dehydration. Sports beverages and caffeine are the most common supplements, while opinion on the practical effectiveness of creatine is divided. Late-maturing adolescent athletes become concerned about gaining size and muscle, and assessment of maturity status can be carried out with anthropometric procedures. An overriding consideration is that an individual approach is needed to meet each athlete's nutritional needs.

Molecular epidemiology of cytomegalovirus in a nursery: lack of evidence for nosocomial transmission.

During a 3-year period, cytomegalovirus (CMV) was recovered from the urine of 35 hospitalized newborn infants (15 with congenital and 20 with acquired infections). Two of the infants with acquired infections lacked maternal antibody to CMV (seronegative) and received transfusions from multiple seropositive blood donors. After seronegative blood products were used exclusively for seronegative low birth weight (less than 1300 gm) infants, none of 154 seronegative infants acquired CMV. CMV was recovered from one seronegative nurse who became infected during the study period. EcoRl digestion of the DNA of the nurse's isolate and of 34 of the 35 infant isolates revealed that no two were identical. LBW seropositive infants were randomized to receive either seronegative blood products or blood products from random donors; there was no significant difference in the number of acquired CMV infections. There were no deaths among 18 infants with acquired CMV infection. Hepatosplenomegaly and worsening bronchopulmonary dysplasia developed in one LBW infant. These results prove that nosocomial transmission of CMV did not occur frequently during the 3-year period.