Sticking to minimum standards: implementing antibiotic stewardship in intensive care.

BACKGROUND: In Australia, antimicrobial stewardship programmes are a compulsory component of hospital accreditation. Good documentation around anti-microbial prescribing aids communication and can improve prescribing practice in environments with multiple decision makers. AIM: This study aims to develop and implement an intervention to improve antimicrobial prescribing practice in a 24-bed intensive care unit in a tertiary referral adult hospital. METHODS: We conducted a four-phase (observation, reflection, implementation, evaluation) prospective collaborative before-after quality improvement study. Baseline audits and surveys of antimicrobial prescribing practices identified barriers to and enablers of good prescribing practice. A customised intervention was then implemented over 6 weeks and included a yellow medication record sticker, quarterly education sessions and intensive care unit-specific empiric antimicrobial prescribing guidelines. Post-implementation, the effects were monitored by serial antimicrobial prescribing audits for 1 year. The primary outcomes were clear documentation of the start date, the planned stop date or review date and the indication for an antibiotic. These were all considered the 'minimum standards' for an antimicrobial prescription on the medication record. RESULTS: Documentation of minimum standards specifically addressed by the sticker improved (start date (72% to 90%, P < 0.001), stop date (16% to 63%, P < 0.001), antimicrobial indication documented on medication chart (58% to 83%, P < 0.01)). Overall, adherence to all three minimum standards (start date, stop date and indication) improved from 41/306 (13%) to 306/492 (63%) (P < 0.001). One-year post-implementation, the yellow sticker had become embedded into daily practice. CONCLUSION: A systematic approach to quality improvement combined with the implementation of a tailored, multi-faceted intervention can improve antimicrobial prescribing practices.

Analysis of knowledge and attitude surveys to identify barriers and enablers of appropriate antimicrobial prescribing in three Australian tertiary hospitals.

BACKGROUND: Antimicrobial stewardship programmes aim to optimise use of antibiotics and are now mandatory in all Australian hospitals. AIM: We aimed to identify barriers to and enablers of appropriate antimicrobial prescribing among hospital doctors. METHODS: Two paper-based and one web-based surveys were administered at three Australian university teaching hospitals from March 2010 to May 2011. The 18-item questionnaire recorded doctors' level of experience, their knowledge regarding the use of common antimicrobials and their attitudes regarding antimicrobial prescribing. Local survey modifications allowed inclusion of specific questions on: infections in intensive care unit patients, clinical microbiology and use of local guidelines. RESULTS: The respondents (n = 272) were comprised of 96 (35%) registrars, 67 (25%)residents, 57 (21%) interns and 47 (17%) consultant hospital doctors. Forty-one per cent were working in a medical specialty. Identified barriers included: gaps in antimicrobial prescribing knowledge (especially among interns), a lack of awareness about which antimicrobials were restricted and a reliance on senior colleagues to make antimicrobial prescribing decisions. Enablers of optimal prescribing included: an acknowledgement of the need for assistance in prescribing and reported readiness to consult national prescribing guidelines. These results were used to help guide and prioritise interventions to improve prescribing practices. CONCLUSION: A transferable knowledge and attitudes survey tool can be used to highlight barriers and facilitators to optimal hospital antimicrobial prescribing in order to inform tailored antimicrobial stewardship interventions.

Oxidative and osmotolerant effects in Salvator merianae (Squamata: Teiidae) red blood cells during hibernation.

Hibernation is a natural condition of animals that lives in the temperate zone, although some tropical lizards also experience hibernation annually, such as the lizard native from South America, Salvator merianae, or "tegu" lizard. Even though physiological and metabolic characteristic associated with hibernation have been extensively studied, possible alterations in the red blood cells (RBC) integrity during this period remains unclear. Dehydration and fasting are natural consequences of hibernating for several months and it could be related to some cellular modifications. In this study, we investigated if the osmotic tolerance of RBCs of tegu lizard under hibernation is different from the cells obtained from animals while normal activity. Additionally, we indirectly investigated if the RBCs membrane of hibernating tegus could be associated with oxidation by quantifying oxidized biomolecules and the activity of antioxidant enzymes. Our findings suggest that RBCs are more fragile during the hibernation period, although we did not find evidence of an oxidative stress scenario associated with the accentuated fragility. Even though we did not exclude the possibility of oxidative damage during hibernation, we suggested that an increased RBCs volume as a consequence of hypoosmotic blood during hibernation could also affect RBCs integrity as noted.

Oxidative and osmotolerant effects in Salvator merianae (Squamata: Teiidae) red blood cells during hibernation / Efeitos de oxidação e osmotolerância dos eritrócitos de Salvator merianae (Squamata: Teiidae) durante a hibernação

Abstract Hibernation is a natural condition of animals that lives in the temperate zone, although some tropical lizards also experience hibernation annually, such as the lizard native from South America, Salvator merianae, or "tegu" lizard. Even though physiological and metabolic characteristic associated with hibernation have been extensively studied, possible alterations in the red blood cells (RBC) integrity during this period remains unclear. Dehydration and fasting are natural consequences of hibernating for several months and it could be related to some cellular modifications. In this study, we investigated if the osmotic tolerance of RBCs of tegu lizard under hibernation is different from the cells obtained from animals while normal activity. Additionally, we indirectly investigated if the RBCs membrane of hibernating tegus could be associated with oxidation by quantifying oxidized biomolecules and the activity of antioxidant enzymes. Our findings suggest that RBCs are more fragile during the hibernation period, although we did not find evidence of an oxidative stress scenario associated with the accentuated fragility. Even though we did not exclude the possibility of oxidative damage during hibernation, we suggested that an increased RBCs volume as a consequence of hypoosmotic blood during hibernation could also affect RBCs integrity as noted.

Resumo A hibernação é uma condição natural dos animais que vivem na zona temperada, embora alguns lagartos tropicais também experenciem hibernação anualmente, como é o caso do lagarto nativo da América do Sul, Salvator merianae ou "teiú". Embora as características fisiológicas e metabólicas associadas à hibernação tenham sido amplamente estudadas, possíveis alterações na integridade das hemácias durante esse período ainda permanecem obscuras. A desidratação e o jejum são consequências naturais da hibernação por vários meses e podem estar relacionadas a algumas modificações celulares. Neste estudo, investigamos se a tolerância osmótica de hemácias do lagarto teiú sob hibernação são diferentes das células obtidas de animais em atividade normal. Além disso, investigamos indiretamente por meio da quantificação de biomoléculas oxidadas e da atividade de enzimas antioxidantes se a membrana das hemácias dos teiús em hibernação poderia estar associada à oxidação. Nossos resultados sugerem que as hemácias possuem maior fragilidade durante o período de hibernação, embora não tenhamos encontrado evidências de um cenário de estresse oxidativo associado à essa fragilidade acentuada. Embora não tenhamos excluído a possibilidade de dano oxidativo durante a hibernação, sugerimos que um aumento no volume das hemácias como consequência de sangue hipoosmótico durante a hibernação também poderia afetar a integridade de hemácias, tal como foi observado.

Oxidative and osmotolerant effects in Salvator merianae (Squamata: Teiidae) red blood cells during hibernation

Abstract Hibernation is a natural condition of animals that lives in the temperate zone, although some tropical lizards also experience hibernation annually, such as the lizard native from South America, Salvator merianae, or tegu lizard. Even though physiological and metabolic characteristic associated with hibernation have been extensively studied, possible alterations in the red blood cells (RBC) integrity during this period remains unclear. Dehydration and fasting are natural consequences of hibernating for several months and it could be related to some cellular modifications. In this study, we investigated if the osmotic tolerance of RBCs of tegu lizard under hibernation is different from the cells obtained from animals while normal activity. Additionally, we indirectly investigated if the RBCs membrane of hibernating tegus could be associated with oxidation by quantifying oxidized biomolecules and the activity of antioxidant enzymes. Our findings suggest that RBCs are more fragile during the hibernation period, although we did not find evidence of an oxidative stress scenario associated with the accentuated fragility. Even though we did not exclude the possibility of oxidative damage during hibernation, we suggested that an increased RBCs volume as a consequence of hypoosmotic blood during hibernation could also affect RBCs integrity as noted.

Resumo A hibernação é uma condição natural dos animais que vivem na zona temperada, embora alguns lagartos tropicais também experenciem hibernação anualmente, como é o caso do lagarto nativo da América do Sul, Salvator merianae ou teiú. Embora as características fisiológicas e metabólicas associadas à hibernação tenham sido amplamente estudadas, possíveis alterações na integridade das hemácias durante esse período ainda permanecem obscuras. A desidratação e o jejum são consequências naturais da hibernação por vários meses e podem estar relacionadas a algumas modificações celulares. Neste estudo, investigamos se a tolerância osmótica de hemácias do lagarto teiú sob hibernação são diferentes das células obtidas de animais em atividade normal. Além disso, investigamos indiretamente por meio da quantificação de biomoléculas oxidadas e da atividade de enzimas antioxidantes se a membrana das hemácias dos teiús em hibernação poderia estar associada à oxidação. Nossos resultados sugerem que as hemácias possuem maior fragilidade durante o período de hibernação, embora não tenhamos encontrado evidências de um cenário de estresse oxidativo associado à essa fragilidade acentuada. Embora não tenhamos excluído a possibilidade de dano oxidativo durante a hibernação, sugerimos que um aumento no volume das hemácias como consequência de sangue hipoosmótico durante a hibernação também poderia afetar a integridade de hemácias, tal como foi observado.

rEnolase maternal immunization confers caries protection on offspring.

Therapeutic vaccination with Streptococcus sobrinus recombinant enolase (rEnolase) protects rats from dental caries. Here, we investigated the effect that maternal rEnolase vaccination before pregnancy had on the offspring's immune response to S. sobrinus oral infection and dental caries progression. Female Wistar rats were immunized by intranasal and subcutaneous routes with rEnolase adsorbed onto aluminum hydroxide as adjuvant or similarly treated with the adjuvant alone (sham-immunized). Ten days after the last administration, the immunized females were paired with a male rat. The oral immune responses to S. sobrinus infection and dental caries in the offspring were evaluated. The results showed that pups born from rEnolase-immunized mothers had higher levels of rEnolase-specific salivary IgA and IgG antibodies (indicating a placental antibody transfer) and lower sulcal and proximal enamel caries scores than rats born from sham-immunized mothers. In conclusion, rEnolase maternal immunization before pregnancy provides offspring with protection against S. sobrinus-induced dental caries.

Estudo clínico e histológico das pálpebras e conjuntiva hígidas submetidas ao tratamento tópico com soluções anestésicas em coelhos / Clinical and histological evaluation of healthy eyelid and conjunctiva subject to local treatment with anesthetic solutions in rabbits

Avaliaram-se as apresentações comerciais de colírios anestésicos aplicados em 63 coelhos da raça Nova Zelândia, distribuídos em três grupos (G1, G2 e G3) de 21 animais cada e que receberam instilação de uma gota em cada olho seis vezes ao dia. Os animais do G1 foram tratados com colírio de cloridrato de proparacaína a 0,5%; os do G2, com colírio de cloridrato de tetracaína a 1% associado à fenilefrina a 0,1%; e os do G3, com solução fisiológica. Cada grupo foi subdividido em três subgrupos com sete animais cada, os quais foram tratados por três, sete e 15 dias. No final de cada tratamento, dois animais de cada subgrupo foram sacrificados para exame histológico de fragmentos retirados da conjuntiva, da terceira pálpebra e das pálpebras. Observou-se, ao exame clínico, episclerite em graus diversos em 100% dos animais do G1, no terceiro, sétimo e 15º dia, e em apenas 17,8% nos do G2, nestes mesmos dias. Ao exame microscópico, observaram-se aumento do número de células califormes, proliferação de folículos linfoides, aumento do número de eosinófilos e aumento do espaço intersticial nas pálpebras dos animais do G1. Pôde-se concluir que o colírio de tetracaína a 1% associado à fenilefrina a 0,1% promoveu maior toxicidade à conjuntiva ocular e às pálpebras de coelhos quando comparado ao colírio de proparacaína a 0,5%.

This work aimed to evaluate commercial presentations of anesthetic eye drops in sixty three New Zealand rabbits which were separated equally in three groups (G1, G2 and G3). The G1 group was treated with 0.5% proparacaine chloridrate eye drop, G2 group with 1% tetracaine chloridrate associated with 0.1% phenylephrine eye drop and G3 group with 0.9% physiologic solution eye drop. All of them received one drop in each eye six times a day. Each group was subdivided into three subgroups (seven rabbits), which are treated for 3, 7 and 15 days. At the end of each treatment, two animals in each subgroup were subject to euthanasia, for the purpose of conjunctiva, eyelids and third eyelids histological evaluation. At the clinical exam, different grades of episcleritis were found in all rabbits in G2 group and only in 17.8% of the rabbits in G1 group. Eye and eyelid histologic evaluation of G2 group revealed an upgrade of goblet cells and eosinophil number, lymphoid follicle proliferation and increase of interstitial space in the eyelids. We could conclude that 1% tetracaine associated with 0.1% phenylephrine eye drop caused more eyelid and ocular conjunctiva toxicity than 0.5% proparacaine eye drop.

Seasonal variation of exudate ofCistus ladanifer.

The production of labdanum exudate byCistus ladanifer L. is highly seasonal, reaching a maximum concentration during summer and a minimum concentration in winter. Because this exudate strongly absorbs in the wavelength range of 260-400 nm (the near-UV-visible range), it may be important biologically as an UV-visible filter. Separation of exudate components has been achieved by reverse-phase high-performance liquid chromatography (HPLC).The retention times of HPLC chromatograms and the spectral characteristics (absorption and fluorescence) of the exudate identify flavonoids as the most relevant chromophores regarding the potency of the exudate as a UV-visible filter. HPLC studies show that kaempferol-3-(O)methyl, kaempferol-3,7-di(O)methyl, and apigenin-4'-(O)methyl are the most enriched flavonoids in the exudate.Other flavonoids [apigenin, apigenin-7-(O)methyl, apigenin-7,4'-di(O)methyl, kaempferol-3,4'-di(O)methyl and kaempferol-3,7,4'-tri(O)methyl] are present in the exudate as minor components, e.g., each contributes by less than 10% to total flavonoids.The ratio of kaempferols to apigenins of the exudate also shows seasonal variation (maximum value in summer and minimum in spring). However, due to the similar absorption spectra of both groups of flavonoids, this has a minor influence on the exudate's ability to filter near-UV-visible radiation.

Redescription of Rhamnocercus stichospinus Seamster and Monaco, 1956 (Monogenea: Diplectanidae), parasitic on Menticirrhus americanus (Osteichthyes: Sciaenidae) from the coastal zone of the State of Rio de Janeiro, Brazil.

Rhamnocercus stichospinus Seamster and Monaco, 1956 (Diplectanidae) parasitic on the sciaenid fish Menticirrhus americanus from the coastal zone of the State of Rio de Janeiro, is redescribed and recorded for the first time in the South American Atlantic Ocean. The generic diagnosis of Rhamnocercus is emended to accommodate the presence of confluent intestinal ceca in R. stichospinus.

Plant growth inhibiting flavonoids in exudate of Cistus ladanifer and in associated soils.

Of the aglycone flavonoids identified in the exudate of cistus ladanifer, two, the flavone apigenin-4'-(O)-methyl and the flavonol kaempferol-3,7-di(O)-methyl inhibit development of the seedlings of Rumex crispus at 0.5 and 1 mM. Additive effects were observed between the major flavonols of the exudate kaempferol-3-(O)-methyl and kaempferol-3,7-di-(O)-methyl in inhibiting the size of the cotyledons and delaying the germination and cotyledon emergence. The presence of apigenin-4'-(O)-methyl, kaempferol-3,7-di-(O)-methyl, and kaempferol-3-(O)-methyl was detected in the soils associated with C. ladanifer during the summer and autumn months. That these compounds are present in the soil and are not restricted to the leaves provides support for the hypothesis that C. ladanifer has allelopathic potential.

Identification and effects of interaction phytotoxic compounds from exudate of Cistus ladanifer leaves.

Eleven allelochemicals (ferulic acid, cinnamic acid, 4-hydroxybenzoic acid, hydroxycinnamic acid, methyl propionate, oxalic acid, methylmalonic acid, p-anisic acid, butyric acid, 3-hydroxybutyric acid, and azulene) were identified in the exudate of Cistus ladanifer L. We studied the effect of each on germination, cotyledon emergence, root length, and cotyledon length of Rumex crispus. Three groups were distinguished with respect to phytotoxic activity: compounds with low activity (ferulic acid, 4-hydroxybenzoic acid, oxalic acid, methylmalonic acid, p-anisic acid, hydroxybutyric acid, and azulene), with intermediate activity (cinnamic acid and hydroxycinnamic acid), and with high activity (methyl propionate and butyric acid). The effect of the interaction of the compounds was studied. When acting conjointly, all combinations tested produced a more negative effect on both germination and seedling growth than when acting alone. The interaction affected cotyledon emergence and root length more negatively than germination and cotyledon length. When hydroxycinnamic acid and cinnamic acid were added to these mixtures there was an enhancement in the phytotoxic activity, accentuating the effect of the other allelochemicals.

Inhibition of mouth skeletal muscle relaxation by flavonoids of Cistus ladanifer L.: a plant defense mechanism against herbivores.

Cistus ladanifer exudate is a potent inhibitor of the sarcoplasmic reticulum Ca2+-ATPase (Ca2+-pump) of rabbit skeletal muscle, a well-established model for active transport that plays a leading role in skeletal muscle relaxation. The low concentration of exudate needed to produce 50% of the maximum inhibition of the sarcoplasmic reticulum Ca2+-ATPase activity, 40-60 microg/ml, suggests that eating only a few milligrams of C. ladanifer leaves can impair the relaxation of the mouth skeletal muscle of herbivores, as the exudate reaches up to 140 mg/g of dry leaves in summer season. The flavonoid fraction of the exudate accounts fully for the functional impairment of the sarcoplasmic reticulum produced by the exudate (up to a dose of 250-300 microg/ml). The flavonoids present in this exudate impair the skeletal muscle sarcoplasmic reticulum function at two different levels: (i) by inhibition of the Ca2+-ATPase activity, and (ii) by decreasing the steady state ATP-dependent Ca2+-accumulation. Among the exudate flavonoids, apigenin and 3,7-di-O-methyl kaempferol are the most potent inhibitors of the skeletal muscle sarcoplasmic reticulum. We conclude that the flavonoids of this exudate can elicit an avoidance reaction of the herbivores eating C. ladanifer leaves through impairment of mouth skeletal muscle relaxation.

[Influence of nutrition on hormone secretion. II. Study in Ribeirão, Pernambuco, Brazil (author's transl)]. / Influência da nutrição sobre a secreção hormonal. II Estudo em Ribeirão, Pernambuco, Brasil

1. Ten children from Ribeirão of both sexes, aged 1 to 6 years, suffering from 2nd and 3rd degree malnutrition were studied. The mean circulating growth hormone levels were significantly higher in both groups before dietary therapy, but the highest values were found in children with 3rd degree malnutrition. It was demonstrated that serum growth hormone levels were significantly related to the severity of malnutrition. A positive correlation was found between the nutritional status and the growth hormone levels. 2. The mean circulating insulin levels were lower before dietary therapy, but a significant correlation was not noted between the nutritional status and the insulin levels. 3. After the dietary therapy the hormone levels progressively returned to normal. These children showed a better recovery than those of the previous study, Agua Preta. This observation may be due to the active participation of the mothers in the nutritional recuperation of their children.