J.M. Nicolás

Comparison of antimicrobial cycling and mixing strategies in two medical intensive care units.

Objective:To compare a mixing vs. a cycling strategy of use of anti-Pseudomonas antibiotics on the acquisition of resistant Gram-negative bacilli in the critical care setting. Design:Prospective, open, comparative study of two strategies of antibiotic use. Setting:Two medical intensive care units of a university hospital. Patients:A total of 346 patients admitted for ≥48 hrs to two separate medical intensive care units during an 8-month period. Interventions:Patients, who according to the attending physician’s judgment required an anti-Pseudomonas regimen, were assigned to receive cefepime/ceftazidime, ciprofloxacin, a carbapemen, or piperacillin-tazobactam in this order. “Cycling” was accomplished by prescribing one of these antibiotics during 1 month each. “Mixing” was accomplished by using the same order of antibiotic administration on consecutive patients. Interventions were carried out during two successive 4-month periods, starting with mixing in one unit and cycling in the other. Measurements and Main Results:Swabbing of nares, pharynx, and rectum and culture of respiratory secretions were obtained thrice weekly. The main outcome variable was the proportion of patients acquiring enteric or nonfermentative Gram-negative bacilli resistant to the antibiotics under intervention. The scheduled cycling of antibiotics was only partially successful. Although the expected antibiotic was the most prevalent anti-Pseudomonas agent used within the corresponding period, it never accounted for >45% of all anti-Pseudomonas antimicrobials administered. During mixing, a significantly higher proportion of patients acquired a strain of Pseudomonas aeruginosa resistant to cefepime (9% vs. 3%, p = .01), and there was a trend toward a more frequent acquisition of resistance to ceftazidime (p = .06), imipenem (p = .06), and meropenem (p = .07). No differences in the rate of acquisition of potentially resistant Gram-negative bacilli or incidence of intensive care unit-acquired infections and infections due to particular organisms were observed. Conclusions:In critically ill medical patients, a strategy of monthly rotation of anti-Pseudomonas &bgr;-lactams and ciprofloxacin may perform better than a strategy of mixing in the acquisition of P. aeruginosa resistant to selected &bgr;-lactams.

Significance of type II fiber atrophy in chronic alcoholic myopathy.

To determine the significance of type II fiber atrophy in alcoholic myopathy and its relationship with ethanol-related diseases a prospective study was carried out in 100 chronic alcoholics who showed clinical suspicion of skeletal myopathy. Measurement of muscle strength, laboratory analysis, nutritional assessment and open biopsy of deltoid muscle were performed in each case, as well as electrophysiological testing for peripheral neuropathy. Hepatic ultrasonography and liver biopsy, echocardiography and radionuclide cardiac scanning were carried out in selected subjects. According to histomorphometric analysis, type II fiber atrophy was found in 33 cases (33%), being selective for type II B fiber in 23 (70%). Skeletal myopathy was diagnosed in 61 cases, alcoholic cardiomyopathy in 26, peripheral neuropathy in 23 and cirrhosis in 12. Patients with type II fiber atrophy had a significantly higher total lifetime dose of ethanol, presented a greater incidence of skeletal myopathy and peripheral neuropathy, and exhibited significantly lower values of percentage of ideal body weight and lean body mass than their counterparts. However, the only independent factors for developing type II fiber atrophy were the coexistence of caloric malnutrition (p = 0.004) and the presence of skeletal myopathy (p = 0.043). Selective type II fiber atrophy is a non-specific finding in alcohol-induced muscle damage appearing, overall, in the patients with caloric malnutrition as well as in those with histologic evidence of myopathy.

Sudden Death in Staphylococcus aureus-associated Infective Endocarditis Due to Perforation of a Free-wall Myocardial Abscess

Free-wall myocardial abscess perforation with hemopericardium and sudden death is an extremely infrequent complication of infective endocarditis (IE). We describe a case of Staphylococcus aureus-associated native aortic and tricuspid valve endocarditis complicated by a septic myocardial infarction and abscess formation of embolic origin, with fatal rupture into the pericardium. To our knowledge, only 2 cases of myocardial abscess rupture have previously been reported in relation to IE.Free-wall myocardial abscess perforation with hemopericardium and sudden death is an extremely infrequent complication of infective endocarditis (IE). We describe a case of Staphylococcus aureus-associated native aortic and tricuspid valve endocarditis complicated by a septic myocardial infarction and abscess formation of embolic origin, with fatal rupture into the pericardium. To our knowledge, only 2 cases of myocardial abscess rupture have previously been reported in relation to IE.

Myocardial Antioxidant Status in Chronic Alcoholism

BACKGROUND Excessive ethanol intake is one of the most frequent causes of acquired dilated cardiomyopathy in developed countries. The pathogenesis is multifactorial, with the antioxidant imbalance of cardiac muscle being a potential factor. The current study evaluates myocardial antioxidant status in ethanol consumers and its relation to cardiac damage. METHODS The authors assessed superoxide dismutase, glutathione peroxidase, and glutathione reductase enzyme activities as well as the total antioxidant status capacity in myocardial samples obtained from organ donors with sudden death of traumatic or neurological origin. They studied 23 high-dose chronic alcohol consumers, 27 individuals with long-standing hypertension, and 11 healthy controls. Cardiomyopathy was defined according to standard functional and histological criteria. RESULTS Patients with dilated cardiomyopathy, either of alcoholic or hypertensive origin, showed increased myocardial superoxide dismutase activities compared with patients without cardiomyopathy (p < 0.001, both) and controls (p < 0.05, both). Total antioxidant status capacity and the activity of glutathione peroxidase and glutathione reductase enzymes were similar in all groups. Superoxide dismutase activity was related to the presence of cardiac enlargement and the degree of cardiac histological damage. The amount and type of alcoholic beverages as well as the nutritional status of the patients were not related to myocardial antioxidant activity. CONCLUSIONS The presence of dilated cardiomyopathy, of either alcoholic or hypertensive origin, is related to an increase in myocardial superoxide dismutase activity.

Is eosinopenia a reliable marker of sepsis

We have read with interest the article by Abidi and colleagues [1] in which the authors point out that eosinopenia could be useful to differentiate between noninfection and infection in patients recently admitted to an intensive care unit (ICU). The association of eosinopenia with infections is not new and has been described previously [2]. To test this hypothesis, we reviewed 191 patients (age >18 years, with a minimum ICU stay of 24 hours) admitted to the medical ICU of our hospital. We exuded HIV-infected patients and those with hematological malignancies. Total leukocyte and eosinophil count (EC) were measured at ICU admission. The results are shown in Table ​Table1.1. Although the EC was lower and the proportion of patients with eosinopenia (<40 cells/ml) was higher in the noninfectious systemic inflammatory response syndrome (SIRS) group compared with the infectious SIRS group, these differences were not statistically significant. Therefore, the EC was not useful to distinguish between infection and noninfection. Although one limitation of our study was the absence of a non-SIRS group, the EC of our noninfectious SIRS group was similar to the EC found in the non-SIRS group in the study by Abidi and colleagues [1]. Another study failed to observe an association between eosinopenia and bacteremia [3]. Table 1 Baseline characteristics of the ICU patients included in the study In conclusion, eosinopenia was not a reliable marker of infection. Other analytical parameters, such as C-reactive protein, have demonstrated to be helpful not only for the diagnosis of infection but also as a marker of severity of organ dysfunction in sepsis [4].

Genotypes Coding for Low Serum Levels of Mannose-Binding Lectin Are Underrepresented among Individuals Suffering from Noninfectious Systemic Inflammatory Response Syndrome

ABSTRACT Gene polymorphisms, giving rise to low serum levels of mannose-binding lectin (MBL) or MBL-associated protease 2 (MASP2), have been associated with an increased risk of infections. The objective of this study was to assess the outcome of intensive care unit (ICU) patients with systemic inflammatory response syndrome (SIRS) regarding the existence of functionally relevant MBL2 and MASP2 gene polymorphisms. The study included 243 ICU patients with SIRS admitted to our hospital, as well as 104 healthy control subjects. MBL2 and MASP2 single nucleotide polymorphisms were genotyped using a sequence-based typing technique. No differences were observed regarding the frequencies of low-MBL genotypes (O/O and XA/O) and MASP2 polymorphisms between patients with SIRS and healthy controls. Interestingly, ICU patients with a noninfectious SIRS had a lower frequency for low-MBL genotypes and a higher frequency for high-MBL genotypes (A/A and A/XA) than either ICU patients with an infectious SIRS or healthy controls. The existence of low- or /high-MBL genotypes or a MASP2 polymorphism had no impact on the mortality rates of the included patients. The presence of high-MBL-producing genotypes in patients with a noninfectious insult is a risk factor for SIRS and ICU admission.

22 – Gender Differences in Alcohol Pathology

This chapter discusses the gender differences in alcohol-induced disease. Women clearly exhibit some different responses to the pathological effects of alcohol consumption compared to men. The chapter explains differences in the health of men and women, exploring reductionist assumptions and biological sources of these differences. The pharmacokinetics of alcohol determines the time course of alcohol concentration in blood after the ingestion of an alcoholic beverage and the degree of the exposure of organs to its effects. It has been established that, on an average, women have a higher blood alcohol level than men for a similar intake of ethanol. The reason for this higher alcohol concentration in women is multi-factorial in origin, with body weight, small water volume, lesser first-pass gastric or hepatic effects, and other genetic and hormonal effects mainly being involved. This higher alcohol concentration produces differences in the pathological expression of alcohol-induced organ damage in women manifested by the involvement of several organs. With respect to cardiac damages, in preclinical alcohol-induced ventricular dysfunctions, women are more sensitive to the toxic effects of ethanol than men.

29 – Nutritional Status in Alcoholics

This chapter discusses the nutritional status in chronic alcoholics. The prevalence of malnutrition among chronic alcoholics varies from 5 to 80%, depending on the population studied. In the past, many cross-sectional studies included indigent skid rows subjects or patients with severe somatic complications—such as liver cirrhosis, hence, the general belief that alcoholics have advanced malnutrition. However, later studies have revealed that nutritional deficiencies are rare among middle-class alcoholics without significant somatic complications. Therefore, although chronic alcoholism continues to be the main cause of malnutrition in the Western countries, nutritional deficiencies are usually found among low-income and homeless alcoholic populations, or in those with ethanol-related complications—especially liver disease or neurological disorders. Moreover, alcoholism and malnutrition is discussed jointly with regards to the pathogenesis, the prognosis, and even the therapy of ethanol-related diseases. Experimental, epidemiological and clinical studies suggest that ethanol has a direct effect on most body tissues. Nevertheless, because not all heavy drinkers exhibit all types of ethanol-related complications, other factors such as—nutritional deficiencies, environmental circumstances or genetic predisposition may enhance or prevent the effects of ethanol on cells.

86 – Adhesion Molecules and Alcohol Consumption

This chapter gives an overview of the effects of ethanol consumption or ethanol exposure on adhesion molecule expression and function and its possible relationship with ethanol-related diseases. Adhesion molecules are proteins expressed on the cell surface, which participate in a myriad of physiological processes—such as organogenesis, immune response and angiogenesis. On the other hand, ethanol exposure/consumption is associated with changes in the cell function including changes in adhesion molecule expression or function. Previous studies have suggested that alcohol may alter cellular and tissue adhesion molecules, and thereby, alter the processes in which they are involved. Thus, frequent alcohol-related health problems such as infectious diseases (for example pneumonia) may be explained by disturbances in immune response in which adhesion molecules have a key role. Alcohol-related diseases such as alcoholic hepatitis may also be explained, at least partially, by an excessive immune response of circulating leukocytes against the liver tissue in which adhesion molecules on hepatic endothelium and their counter-receptors on leukocytes are up-regulated. Moderate alcohol consumption seems to be a protector against atherosclerosis; the modification of monocyte-endothelial interactions, which is an early event in atheroma plaque formation, may be another potential mechanism to explain the lower incidence of atherosclerosis in alcohol drinkers.

53 – Alcoholic Myopathy: Clinical Aspects

This chapter describes the clinical aspects of alcoholic myopathy. Ethanol consumption may cause acute and chronic deleterious effect on skeletal muscle, inducing muscle weakness, atrophy, and myocyte death. Acute myopathy has and sporadic presentation among binge consumers. Chronic alcoholic myopathy has a prevalence of 40–60% in a population of alcohol misusers. Muscle weakness, myalgia and swelling are the main features of acute myopathy. In chronic myopathy, the most relevant features are proximal progressive muscle weakness and atrophy. There are more subclinical cases, which can be detected evaluating muscle weakness by myometry. Skeletal muscle involvement in alcoholism is related to other systemic diseases—such as dilated cardiomyopathy, peripheral neuropathy, malnutrition and liver cirrhosis. Myocytolysis and Type II fiber atrophy are the most prominent features in alcoholic myopathy. Because of the lack of a specific histological pattern, the diagnosis of alcoholic myopathy requires a characteristic clinical pattern and careful exclusion of other causes of myopathy. The physiopathological mechanisms that determine the muscle damage induced by ethanol are still not completely understood. Studies have shown that ethanol has a toxic direct effect, that is, producing muscle damage by altering membrane fluidity, channels, pumps and ionic transients, depression of muscle contractility, and protein synthesis or mitochondrial function.