Clinical Predictive Model of Multidrug Resistance in Neutropenic Cancer Patients with Bloodstream Infection Due to Pseudomonas aeruginosa.

We aimed to assess the rate and predictive factors of bloodstream infection (BSI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa in neutropenic cancer patients. We performed a multicenter, retrospective cohort study including oncohematological neutropenic patients with BSI due to P. aeruginosa conducted across 34 centers in 12 countries from January 2006 to May 2018. A mixed logistic regression model was used to estimate a model to predict the multidrug resistance of the causative pathogens. Of a total of 1,217 episodes of BSI due to P. aeruginosa, 309 episodes (25.4%) were caused by MDR strains. The rate of multidrug resistance increased significantly over the study period (P = 0.033). Predictors of MDR P. aeruginosa BSI were prior therapy with piperacillin-tazobactam (odds ratio [OR], 3.48; 95% confidence interval [CI], 2.29 to 5.30), prior antipseudomonal carbapenem use (OR, 2.53; 95% CI, 1.65 to 3.87), fluoroquinolone prophylaxis (OR, 2.99; 95% CI, 1.92 to 4.64), underlying hematological disease (OR, 2.09; 95% CI, 1.26 to 3.44), and the presence of a urinary catheter (OR, 2.54; 95% CI, 1.65 to 3.91), whereas older age (OR, 0.98; 95% CI, 0.97 to 0.99) was found to be protective. Our prediction model achieves good discrimination and calibration, thereby identifying neutropenic patients at higher risk of BSI due to MDR P. aeruginosa The application of this model using a web-based calculator may be a simple strategy to identify high-risk patients who may benefit from the early administration of broad-spectrum antibiotic coverage against MDR strains according to the local susceptibility patterns, thus avoiding the use of broad-spectrum antibiotics in patients at a low risk of resistance development.

Role of nitric oxide on motor behavior.

The present review paper describes results indicating the influence of nitric oxide (NO) on motor control. Our last studies showed that systemic injections of low doses of inhibitors of NO synthase (NOS), the enzyme responsible for NO formation, induce anxiolytic effects in the elevated plus maze whereas higher doses decrease maze exploration. Also, NOS inhibitors decrease locomotion and rearing in an open field arena. These results may involve motor effects of this compounds, since inhibitors of NOS, NG-nitro-L-arginine (L-NOARG), N(G)-nitro-L-arginine methylester (L-NAME), N(G)-monomethyl-L-arginine (L-NMMA), and 7-Nitroindazole (7-NIO), induced catalepsy in mice. This effect was also found in rats after systemic, intracebroventricular or intrastriatal administration. Acute administration of L-NOARG has an additive cataleptic effect with haloperidol, a dopamine D2 antagonist. The catalepsy is also potentiated by WAY 100135 (5-HT1a receptor antagonist), ketanserin (5HT2a and alfal adrenergic receptor antagonist), and ritanserin (5-HT2a and 5HT2c receptor antagonist). Atropine sulfate and biperiden, antimuscarinic drugs, block L-NOARG-induced catalepsy in mice. L-NOARG subchronic administration in mice induces rapid tolerance (3 days) to its cataleptic effects. It also produces cross-tolerance to haloperidol-induced catalepsy. After subchronic L-NOARG treatment there is an increase in the density NADPH-d positive neurons in the dorsal part of nucleus caudate-putamen, nucleus accumbens, and tegmental pedunculupontinus nucleus. In contrast, this treatment decreases NADPH-d neuronal number in the substantia nigra compacta. Considering these results we suggest that (i) NO may modulate motor behavior, probably by interfering with dopaminergic, serotonergic, and cholinergic neurotransmission in the striatum; (ii) Subchronic NO synthesis inhibition induces plastic changes in NO-producing neurons in brain areas related to motor control and causes cross-tolerance to the cataleptic effect of haloperidol, raising the possibility that such treatments could decrease motor side effects associated with antipsychotic medications. Finally, recent studies using experimental Parkinson's disease models suggest an interaction between NO system and neurodegenerative processes in the nigrostriatal pathway. It provides evidence of a protective role of NO. Together, our results indicate that NO may be a key participant on physiological and pathophysiological processes in the nigrostriatal system.

Os desafios da implantação da notificação de uso de antimicrobianos em um hospital de grande porte

INTRODUÇÃO: Visando implantar um método de vigilância epidemiológica ativa das infecções hospitalares e promover o uso racional de antimicrobianos (AM), foi desenvolvido um modelo de ficha de notificação de uso de antimicrobiano de forma a garantir que todo tratamento iniciado fosse notificado à Comissão de Controle de Infecção Hospitalar (CCIH).OBJETIVOS: Implantar um método ativo de vigilância epidemiológica, conjugando ações da CCIH e do SF; Promover o uso racional de antimicrobianos.MÉTODO: A CCIH juntamente com o SF desenvolveu um novo modelo de ficha de notificação de AM que incluiu as informações sobre o esquema antimicrobiano empregado no rodapé da própria prescrição médica. O novo modelo foi aprovado em reunião com a direção médica do hospital, todos os chefes de clínica e a supervisão da enfermagem. Foi idealizado bloco de prescrição em duas vias, onde a primeira (branca) ficasse na clínica e a segunda (amarela) fosse encaminhada ao SF. Todas as prescrições contendo notificação são separadas ao fim do dia para serem fotocopiadas no dia seguinte e então encaminhadas à CCIH. RESULTADOS:A exigência da notificação de AM forneceu uma série de vantagens para o SF e para a CCIH: acesso à notificação do AM; controle de estoque dos AMs notificados; análise criteriosa de todo o esquema terapêutico empregado, intervenção da CCIH e SF em esquemas desnecessários ou incompatíveis com estoque do AM, patologia ou justificativa. DISCUSSÃO E CONCLUSÕES: A mudança na maneira de se notificar o esquema antimicrobiano proposto foi suficiente para a criação do hábito da notificação por parte da equipe médica, apesar da grande resistência e dos questionamentos surgidos no início da implantação do protocolo. A exigência da notificação gerou benefícios não só para o hospital, como também para o paciente, uma vez que a CCIH passou a emitir seu parecer para cada notificação encaminhada, identificando erros e sugerindo modificações no tratamento proposto. Para o SF, este protocolo permitiu uma redução nos custos e garantiu o uso racional desses medicamentos. Todavia, o modelo ideal de notificação de AMs ainda está para ser encontrado, já que no modelo desenvolvido, as notificações dos AMs só chegam à CCIH um dia após o início do tratamento em dias úteis ou em até três dias nos casos de feriados e finais de semana e, portanto, um tratamento iniciado com AM inadequado, demora a sofrer intervenção por parte da CCIH, aumentando as chances de seleção de resistência microbiana e também o custo para o SF

Effects of electrolytic and 6-hydroxydopamine lesions of rat nigrostriatal pathway on nitric oxide synthase and nicotinamide adenine dinucleotide phosphate diaphorase.

The aim of the present study was to assess degenerative changes in the nitric oxide (NO) system of basal ganglia in animals with experimentally induced Parkinson's disease. In one procedure, rats were stereotaxically injected with 6-hydroxydopamine (6-OHDA) in the right medial forebrain bundle; in a second procedure, electrodes were implanted in the right substantia nigra pars compacta (SNc). After 15 and 30 days animals were tested for rotational asymmetry induced by apomorphine. Apomorphine induced rotation in lesioned animals, towards the ipsilateral side after electrolytic lesion and towards contralateral side in 6-OHDA animals. Structural deficits in basal ganglia were quantified by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry and by nitric oxide synthase (NOS) immunoreactivity. 6-OHDA and electrolytic lesions induced a significant decrease in the number of NADPH-d/NOS positive cells in the lesion ipsilateral to SNc, in contrast with cell number increase in the ipsilateral dorsal striatum. By contrast, 6-OHDA-treated animals showed a decrease in the number of NOS immunoreactive cells in the contralateral nucleus accumbens. We conclude that populations of NO-synthesizing neurons are differentially regulated in Parkinson's disease induced by different experimental procedures.