Inpatient antibiotic consumption in a regional secondary hospital in New Zealand.

BACKGROUND: Reporting of antibiotic consumption in hospitals is a crucial component of antibiotic stewardship, but data from Australasian secondary hospitals are scarce. The hypothesis of this audit is that antibiotic consumption in secondary hospitals would be lower than in tertiary centres. AIMS: The study aims to present the first published audit of antibiotic consumption from a secondary hospital in New Zealand compared with two tertiary centres. METHODS: Hospital population-level data were retrospectively accessed to identify all systemic antibiotics dispensed to adult inpatients at Taranaki District Health Board during 2011. Consumption was calculated in defined daily doses per 100 inpatient-days and per 100 admissions, stratified by drug class. Comparison was against published data from two tertiary centres. RESULTS: Total consumption was lower, but that of high-risk antibiotic classes was higher than both tertiary centres. The relative consumption of lincosamides was 4.0 and 2.6 times higher than the two tertiary centres, with an associated 14% incidence of Clostridium difficile associated diarrhoea within 3 months. CONCLUSION: Our secondary hospital appears to consume the wrong types of antibiotic rather than too much. Data from all Australasian hospitals, stratified by clinical service area and hospital level, are required for clinically relevant benchmarking.

Genetic map construction and QTL mapping of resistance to blackleg (Leptosphaeria maculans) disease in Australian canola (Brassica napus L.) cultivars.

Genetic map construction and identification of quantitative trait loci (QTLs) for blackleg resistance were performed for four mapping populations derived from five different canola source cultivars. Three of the populations were generated from crosses between single genotypes from the blackleg-resistant cultivars Caiman, Camberra and (AV)Sapphire and the blackleg-susceptible cultivar Westar(10). The fourth population was derived from a cross between genotypes from two blackleg resistant varieties (Rainbow and (AV)Sapphire). Different types of DNA-based markers were designed and characterised from a collection of 20,000 EST sequences generated from multiple Brassica species, including a new set of 445 EST-SSR markers of high value to the international community. Multiple molecular genetic marker systems were used to construct linkage maps with locus numbers varying between 219 and 468, and coverage ranging from 1173 to 1800 cM. The proportion of polymorphic markers assigned to map locations varied from 70 to 89% across the four populations. Publicly available simple sequence repeat markers were used to assign linkage groups to reference nomenclature, and a sub-set of mapped markers were also screened on the Tapidor x Ningyou (T x N) reference population to assist this process. QTL analysis was performed based on percentage survival at low and high disease pressure sites. Multiple QTLs were identified across the four mapping populations, accounting for 13-33% of phenotypic variance (V (p)). QTL-linked marker data are suitable for implementation in breeding for disease resistance in Australian canola cultivars. However, the likelihood of shifts in pathogen race structure across different geographical locations may have implications for the long-term durability of such associations.

Interdependence of spinal adenosinergic, serotonergic and noradrenergic systems mediating antinociception.

The present investigations examined possible interdependence among serotonergic, noradrenergic and adenosinergic pathways as spinal antinociceptive systems. ED50 values for antinociception induced by intrathecal injections of noradrenergic, serotonergic or adenosinergic agonists in mice were determined. These results were compared to ED50 values determined when an antagonist or a sub-antinociceptive dose of a second agonist was coadministered i.t. with agonists. Interactions observed when serotonergic and adenosinergic agents were coadministered suggest that antinociception induced by serotonin (i.t.) is mediated, in part, via serotonin-stimulated release of adenosine. The mechanism by which norepinephrine administered i.t. induced antinociception, however, appeared to be independent of serotonergic and adenosinergic pathways.

Involvement of A2 adenosine receptors in spinal mechanisms of antinociception.

Preliminary investigations suggest that spinal adenosine induces significant behavioral effects and may interact with descending antinociceptive systems stimulated by morphine administered intracerebroventricularly (i.c.v.). In the present study, rank order potencies for antinociception induced by adenosine agonists administered intrathecally (i.t.) were determined. Interactions of adenosine agonists (i.t.) with morphine (i.c.v.)-induced antinociception were also examined. Dose-dependent antinociception, as measured in tail flick and hot plate assays, was observed in mice administered adenosine or adenosine agonists i.t. Rank order potencies were 5'-N6-ethylcarboxamidoadenosine (NECA) greater than N6-(R-phenylisopropyl)-adenosine (R-PIA) greater than 2-chloroadenosine (CADO) greater than N6-(S-phenylisopropyl)-adenosine (S-PIA) greater than adenosine. Rank order potencies were identical for adenosine agonist (i.t.) synergism with morphine (i.c.v.)-induced antinociception. Further, i.t. injections of NECA or nitrobenzylthioinosine (NBI), an adenosine reuptake inhibitor, were able to potentiate morphine (i.c.v.)-induced antinociception. Hind limb paralysis induced by high doses of adenosine agonists (i.t.) was dissociated from antinociceptive effects. Rank order potencies determined in our studies support involvement of A2 adenosine receptors in spinal mechanisms of antinociception. In addition, these results confirm spinal adenosine interactions with antinociceptive systems stimulated by i.c.v. injections of morphine.

Spinal adenosine modulates descending antinociceptive pathways stimulated by morphine.

Adenosine-mediated analgesia and interactions between opioids and adenosine in the brain have been observed by several researchers. Our investigations were designed to examine opioid-adenosine interactions at spinal sites and possible modulation of opioid-stimulated descending antinociceptive pathways by adenosine in the spinal cord. Methylxanthines administered intrathecally (i.t.) were used as adenosine receptor antagonists to determine possible interactions between opioids and endogenous adenosine. Theophylline administered i.t. dose-dependently antagonized analgesia induced by morphine administered i.t. or i.c.v. as measured by tail-flick and hot-plate assays. Analgesia induced by i.t. injections of 2-chloroadenosine, an adenosine agonist, was also antagonized by theophylline. However, doses of naloxone (i.t.) that antagonized analgesia induced by i.t. injections of morphine had no effect on 2-chloroadenosine (i.t.)-induced analgesia. These data support morphine-stimulated release of adenosine in the spinal cord. Antagonism of morphine (i.c.v.)-induced analgesia by theophylline was mimicked by caffeine and isobutylmethylxanthine. The results could not be explained as a consequence of effects on phosphodiesterease enzymes, drug-induced hyperalgesia or spinal redistribution of i.c.v. administered morphine. Therefore, our studies suggest that endogenous adenosine in the spinal cord is involved in analgesia mediated by opioid-stimulated descending antinociceptive pathways.