Antibiotic use in non-university regional acute care general hospitals in southwestern Germany, 2001-2002.

BACKGROUND: A previous study from Germany showed high antibiotic use in university hospitals, particularly in intensive care units (ICU) and hematology-oncology services, but there has been no information about recent antibiotic use in non-university hospitals. In the present study, we collected data from 40 non-university regional general hospitals located in the southwestern part of the country, and analyzed use density in the medical and surgical services of these hospitals. MATERIALS AND METHODS: Hospital pharmacy records for the calendar years 2001 and 2002 were evaluated. The number of defined daily doses (DDD, definition according to the WHO/ATC 2001 index) and prescribed daily doses (PDD) per 100 patient days (DDD/100 or PDD/100, respectively) were calculated to compare antibiotic use densities in medical and surgical services. Data for surgery included various subspecialties and gynecology. RESULTS: Antibiotic use in the participating hospitals increased minimally between 2001 and 2002 both in medicine as well as in surgery. Use density in internal medicine (ICU areas excluded) in the year 2002 ranged between 13.5 and 93.7 DDD/100 with a weighted mean of 49.9 DDD/100 (corresponding to 28.6 PDD/100, respectively). Values for surgery were lower with a weighted mean of 43.4 DDD/100 (corresponding to 26.1 PDD/100, range, 10 to 65.4 DDD/100), respectively. Hospital size was not a strong predictor of use density, while large differences were observed between intensive care areas and normal wards. Mean use densities in intensive care areas in 2002 were 105.6 DDD/100 (or 49.7 PDD/100) in medical intensive care units, 116.9 DDD/100 (or 61.2 PDD/100) in surgical intensive care units, and 112.7 DDD/100 (or 66.7 PDD/100) in mixed, interdisciplinary intensive care units. Betalactams made up > 50% of all PDDs, while fluoroquinolones were the second most frequently prescribed drugs (15% of all PDDs). Fluoroquinolones were usually given orally. Overall glycopeptide and aminoglycoside use was < 1 PDD/100. CONCLUSION: This recent data from a large regional nonuniversity acute care hospital sample confirms that hospital antibiotic use density largely depends on patient care areas and less on hospital size. Surprisingly low use was observed for glycopeptides and aminoglycosides. The data may be useful as a benchmark for further pharmaco-epidemiologic evaluation and focused drug use control interventions.

An arrestin homolog of blowfly photoreceptors stimulates visual-pigment phosphorylation by activating a membrane-associated protein kinase.

An arrestin homolog (Arr2, 49-kDa protein) of blowfly (Calliphora erythrocephala) retinae undergoes light-dependent reversible binding to the photoreceptor membrane. In order to characterize this arrestin homolog and to study its function in a well-defined experimental system, we developed a purification scheme which used microvillar photoreceptor membranes as an affinity binding matrix. Additional purification steps included ammonium sulfate precipitation, gel filtration and binding to heparin-agarose. The molecular mass of purified Arr2, as judged by SDS/PAGE, is in the range 45-49 kDa. The isoelectric point, as judged by gel isoelectric focussing, is 8.7. Arr2 is specific to the retina, where it is subject to phosphorylation at multiple sites. Binding of purified Arr2 to isolated photoreceptor membranes efficiently activates the light-induced phosphorylation of visual pigment. Since the assay system used is deficient in rhodopsin phosphatase activity, the arrestin-stimulated phosphate incorporation into rhodopsin results solely from the activation of a protein kinase. Phosphorylation experiments with highly purified membrane preparations indicate that rhodopsin kinase is tightly associated with the rhabdomeric membrane or the microvillar cytoskeleton. Rhodopsin kinase is released from the membrane or inactivated upon treatment with urea. It is concluded that this arrestin is a regulator protein that controls visual-pigment phosphorylation by affecting the interaction of metarhodopsin and rhodopsin (metarhodopsin) kinase.

Mechanism of arrestin 2 function in rhabdomeric photoreceptors.

Arrestins have emerged as one family of proteins that mediate the inactivation of G-protein-coupled receptors. We have isolated cDNA clones encoding two arrestin isoforms of the dipteran visual system, Calliphora arrestin 1 (Arr1) and arrestin 2 (Arr2). Microsequencing established that the arr2 gene encodes the Calliphora 49-kDa protein characterized previously as a photoreceptor-specific protein that undergoes reversible binding to light-activated rhodopsin and thereby activates the phosphorylation of metarhodopsin. Ultrastructural localization of Arr2 to the rhabdomeral part of the photoreceptor cell and quantitation of the amount of Arr2 bound suggest that Arr2 directly interacts with light-activated rhodopsin. In a reconstituted system containing affinity purified Arr2 and isolated rhabdomeric membranes, Arr2 binds to non-phosphorylated and phosphorylated metarhodopsin with comparable affinity. Reaction time courses reveal that Arr2 binding precedes phosphorylation of metarhodopsin, contrary to what has been reported so far for vertebrate photoreceptors. The phosphorylation-independent binding of Arr2 to metarhodopsin provides a mechanism for the rapid inactivation of the long-lived activated rhodopsin state which is characteristic for invertebrate photoreceptors. The dephosphorylation of rhodopsin is catalyzed by a Ca(2+)-dependent protein phosphatase which is shown here for the first time to exist in a membrane-associated form. Only metarhodopsin molecules with bound Arr2 are resistant to dephosphorylation. Thus, in fly photoreceptors, Arr2 acts as a regulatory protein that controls the phosphorylation as well as the dephosphorylation of the light-activated visual pigment.