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A Torres

Publications and source records attributed to A Torres.

At least 199 records · Page 11Linked to original sources

Regression of left ventricular hypertrophy by lisinopril after renal transplantation: role of ACE gene polymorphism.

BACKGROUND: Cardiac complications are the main cause of death in renal transplantation (RT), and left ventricular hypertrophy (LVH) may play an important role in these patients. The unfavorable genotype of the angiotensin-converting enzyme (ACE) gene has been associated with cardiovascular disease, including LVH. ACE inhibitors (ACEIs) reduce LVH, but little is known about the effects of ACEIs on LVH in RT patients with different insertion/deletion (I/D) genotypes of the ACE gene. METHODS: We prospectively studied 57 stable nondiabetic RT patients with hypertension and echocardiographic LVH as well as a functional graft for 69.5 +/- 5.6 months. Patients randomly received either lisinopril 10 mg/day (group A, N = 29; 5 were excluded due to reversible acute renal failure) or placebo (group B, N = 28) for 12 months. Echocardiography (M-mode, 2-B, and color flow Doppler) was performed at baseline and 6 and 12 months later by the same examiner without previous knowledge of the genetic typing. The ACE genotype (I or D alleles) was ascertained by polymerase chain reaction (PCR; group A, DD = 10 and ID/II = 14; group B, DD = 15 and ID/II = 13). RESULTS: All patients maintained a good renal function (serum creatinine <2.5 mg/dL) during the follow-up and both groups received a similar proportion of antihypertensive drugs (beta-blockers 83 vs. 79%; Ca antagonists 66 vs. 68%; alpha1-adrenoreceptor antagonists 50 vs. 67%) during the study. As expected, mean arterial blood pressure and hemoglobin levels showed a higher percentage reduction in group A versus group B (-4 +/- 2.8 vs. 2.1 +/- 2.6%, P = 0.07, and -11.5 +/- 1.5 vs. -0.5 +/- 2.3%, P < 0.01, respectively). Group A patients showed a significantly higher decrement in LV mass index (LVMI) than group B at the end of follow-up, after adjusting for age, baseline LVMI, time after grafting and changes in systolic blood pressure, renal function, and hemoglobin levels (group A, -9.5 +/- 3.5% vs. group B, 3 +/- 3.2%, P < 0.05). As a result, 46% of group A and only 7% of group B patients showed a reduction of LVMI >/=15% (P < 0.01). The beneficial effect of lisinopril on LVMI reduction was more evident in DD patients (placebo DD, 8.4 +/- 4.1% vs. lisinopril DD, -7.2 +/- 5.3, P < 0.05), and a trend was observed in patients with other genotypes (placebo ID/II, 2.8 +/- 5.4% vs. lisinopril ID/II, -11.4 +/- 5%, P = 0.33). CONCLUSIONS: Lisinopril decreases LVM in renal transplant patients with hypertension and LVH, and the ACE gene polymorphism may predict the beneficial effect of this therapy. This finding may be important in targeting prophylactic interventions in this population.

Acute Kidney Injury↗

Ventilator-associated pneumonia: incidence, risk factors, and microbiology.

Ventilator-associated pneumonia (VAP) is a pulmonary infection that occurs after at least 48 hours of mechanical ventilation (MV). The incidence depends on several factors, although the most important are those related to the host and duration of MV. VAP can be differentiated into early-onset (<5 days) and late-onset types (> or =5 days). The overall incidence of VAP varies between 9% and 70% (average, 20% to 25%), and the majority of episodes occur within the first 5 days. Risk factors for VAP include prolonged MV, older age, supine body position, and type of comorbidity. Oropharyngeal colonization appears to be a risk factor for early-onset pneumonia, whereas prolonged MV and antibiotic pretreatment, especially with broad-spectrum drugs, increase the risk for late-onset VAP Microaspiration of colonized oropharyngeal secretions is a major cause of early-onset VAP, most frequently caused by community-type pathogens. After 5 days of MV, pathological colonization with gram-negative bacteria may occur, and late-onset VAP is more likely to be attributable to this group of microorganism. Incidence, risk factors, and microbiology depend strongly on the time frame in which the episode develops. However, initial and pathological colonization during the intensive care unit stay can modify this concept.

Age Factors↗

Cardiac afferents and neurohormonal activation in congestive heart failure.

Cardiac chambers have afferent connections to the brainstem and to the spinal cord. Vagal afferents mediate depressor responses and become activated by volume expansion, increased myocardial contractility and atrial natriuretic factor. Sympathetic afferents, on the contrary, are activated by metabolic mediators, myocardial ischemia and cardiac enlargement. These opposite behaviors may lead to activation or suppression of the sympathetic nervous system and of the renin-angiotensin-aldosterone system. As cardiac diseases progress, the heart dilates, plasma norepinephrine increases, atrial natriuretic factor is released and the renin-angiotensin-aldosterone system is suppressed to maintain water and sodium excretion. This dissociation of the neurohormonal profile of cardiac patients, may be explained by coactivation of sympathetic afferents, by cardiac dilatation, and of vagal afferents by atrial natriuretic factor. In more advanced stages, atrial natriuretic factor suppression of the renin-angiotensin-aldosterone system is overridden by overt sympathetic activation and sodium and water retention ensues. Digitalis, angiotensin-converting enzyme inhibitors and beta-blockers selectively decrease cardiac adrenergic drive. A common mechanism of action, to all three groups of drugs, would be attenuation of sympathetic afferents and partial normalization of vagal afferents. Consequently, heart size and cardiac afferents emerge as the key factors to understand the pathophysiology and treatment of the syndrome of congestive heart failure.

Afferent Pathways↗

Estimating the burden of disease in one Swiss canton: what do disability adjusted life years (DALY) tell us?

BACKGROUND: Examining life expectancy and general mortality rates, the health of the population of Geneva can be described as one of the best in the world. However, in some areas Geneva fares worse than the rest of Switzerland or Europe. To re-appraise the current health priorities of the Genevan population, we analysed the relative importance of specific diseases and injuries calculating DALYs. METHODS: We followed the procedures developed for the Global Burden of Disease (GBD) study to ensure comparability. Some adaptations were made for mortality coding. Disability was estimated based on data for countries classified as Established Market Economies (EME) in the GBD study. RESULTS: Non-communicable diseases accounted for 79% of the disability adjusted life years (DALY), injuries represented 12%, and communicable diseases and other disorders 9%. Ischaemic heart disease was the largest single contributor to DALY, followed by unipolar major depression. Neuropsychiatric disorders and mental health accounted for more than 23% of DALY. CONCLUSIONS: Some of the most important problems identified-depression, osteoarthritis and alcohol abuse-would have been overlooked in an analysis based solely on mortality data. The most striking finding is the importance of mental health problems. The main limitation is the lack of morbidity data for Geneva.

Adolescent↗

Evaluation of antimicrobial treatment in mechanically ventilated patients with severe chronic obstructive pulmonary disease exacerbations.

OBJECTIVE: To study microbial and susceptibility patterns and antimicrobial treatment responses in patients with severe, acute exacerbations of chronic obstructive pulmonary disease requiring mechanical ventilation. DESIGN: Microbial investigation using tracheobronchial aspirates, bronchoscopy with a protected specimen brush, and bronchoalveolar lavage, as well as paired serologies. Evaluation of antimicrobial treatment by results of the initial investigation, susceptibility testing, and a repeated microbial investigation (tracheobronchial aspirates, bronchoscopy with a protected specimen brush, and bronchoalveolar lavage) after 72 hrs. SETTING: A respiratory intensive care unit of a 1,000-bed teaching hospital. PATIENTS: Fifty severely exacerbated and mechanically ventilated patients with chronic obstructive pulmonary disease. INTERVENTIONS: Initial empirical antimicrobial treatment according to clinical judgment. MEASUREMENTS AND MAIN RESULTS: Overall, 36 of 50 patients (72%) had evidence of a microbial origin. Community-acquired endogenous pathogens were present in 70% of patients, and Gram-negative enteric bacilli and Pseudomonas/Stenotrophomonas species were present in 30%. All five isolates of Streptococcus pneumoniae were resistant to penicillin (three intermediately and two highly), and three were resistant to multiple antibiotics. Pseudomonas species revealed multiresistance in four of nine isolates (44%), and Stenotrophomonas maltophilia revealed multiresistance in one of two isolates. Antimicrobial treatment was modified according to diagnostic results in 11 of 31 patients (36%) with potentially pathogenic microorganisms. In patients who underwent a repeat investigation after 72 hrs, 24% of the initially present and potentially pathogenic microorganisms persisted. Inappropriate initial antimicrobial therapy was associated significantly with bacterial persistence (p < .002). CONCLUSIONS: Considering the diversity of microbial pathogens and the resistance rates especially to S. pneumoniae in this patient population, antimicrobial treatment should be based on the constant study of local microbial and susceptibility patterns along with routine microbial investigation of the individual patient.

Aged↗

Sampling methods for ventilator-associated pneumonia: validation using different histologic and microbiological references.

OBJECTIVE: To validate sampling techniques (tracheobronchial aspirates, protected specimen brush, and bronchoalveolar lavage, both conventional and protected) for the detection of ventilator-associated pneumonia (VAP) and causative microorganisms according to different histologic and microbiological references. DESIGN: Immediate, multiple bilateral lung biopsy, postmortem study. SETTING: Respiratory intensive care unit of a 1,000-bed teaching hospital. PATIENTS: Twenty-five mechanically ventilated patients (>72 hrs) who died in our intensive care unit. MEASUREMENTS: Lung tissue histologic examination and quantitative cultures (16 specimens/patient). The following four references for the diagnostic techniques were used: histology of guided lung biopsy, histology of blind lung biopsy, combined guided and blind lung biopsy histology and microbiology of lung tissue, and microbiology of lung tissue. RESULTS: Sensitivities when histologic reference tests were used ranged from 16% to almost 40%, whereas specificity rates were always <80%. When we combined both lung histology of guided or blind specimens and microbiology of lung tissue, all diagnostic techniques achieved considerably higher but still limited diagnostic yields (sensitivity range 43% to 83%; specificity range 67% to 91%). Causative organisms were missed in a significant number of cases by all techniques (17% to 83%). CONCLUSIONS: The diagnostic performances of different diagnostic techniques strongly depend on the reference used. All techniques for detecting VAP are of limited value. Finding a balance between clinical judgment and microbiological results is crucial to appropriately manage patients with VAP.

Biopsy↗

Method for intraoperative positioning of the nipple-areola complex in vertical scar reduction mammaplasty.

The desired shape and position of the nipple-areola complex may be difficult to achieve in vertical scar reduction mammaplasty when using the standard technique of preoperative marking of the so-called mosque-shaped areolar pattern of excision. We describe our modified approach of intraoperative final positioning of the nipple-areola complex by hiding the nipple-areola complex behind the closed vertical incision. Individual positioning at the final part of the operation allows for more predictable results and also for a calculated lower positioning, which enables balance of the potential bottoming-out of the breast, particularly in previously large ptotic breasts. We believe that this modification helps to further improve the results of vertical scar reduction mammaplasty by adding more possibilities for shaping and "last-minute" modifications intraoperatively.

Adult↗

Severity assessment in children hospitalized with bronchiolitis using the pediatric component of the Comprehensive Severity Index.

OBJECTIVE: Practice variation in the management of children hospitalized with bronchiolitis may result in significant differences in resource utilization. Determination of cost-effective care requires an objective means of adjusting for severity. We examined the correlation of the pediatric component of the Comprehensive Severity Index (CSI) with resource utilization in children hospitalized with bronchiolitis at ten children's medical centers. DESIGN: Demographics, clinical findings, laboratory results, interventions, and outcomes were retrospectively extracted from the charts of 804 consecutive children with International Classification of Disease, Ninth Revision codes for bronchiolitis from 10 children's medical centers. Comorbidities of prematurity, heart disease, and a prior history of wheezing or hospitalization, and the viral etiology of the illness were specifically examined. CSI scoring was performed at admission and maximum and correlated with patient variables and measures of resource utilization (hospital costs, length of stay, pediatric intensive care unit admission, and intubation). The performance of CSI relative to the Pediatric Risk of Mortality III was also evaluated. SETTING: Ten tertiary children's medical centers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One child died and >99% of children returned to their baseline state of health. Admission CSI was comparable to the aggregate of all patient variables in its correlation with hospital costs (r2 = 0.23 vs. r2 = 0.24, respectively) and lengths of stay (r2 = 0.23 vs. r2 = 0.24, respectively). Maximum CSI had the highest correlation coefficient with hospital costs (r2 = 0.42) and lengths of stay (r2 = 0.41), whereas the correlation of admission Pediatric Risk of Mortality III scores with costs was r2 = 0.12 and with lengths of stay was r2 = 0.07. CSI scores also correlated well with measures of resource utilization in subgroups of bronchiolitis patients with comorbidities or other risk factors for severe disease. CONCLUSIONS: CSI scores correlate well with resource use in pediatric patients hospitalized with bronchiolitis. This severity scoring system may be useful in assessing the cost-effectiveness of their care.

Journal Article↗

Genetic variation in Fusarium section Liseola from no-till maize in Argentina.

Strains of Fusarium species belonging to section Liseola cause stalk and ear rot of maize and produce important mycotoxins, such as fumonisins. We isolated two species, Fusarium verticillioides (Gibberella fujikuroi mating population A) and Fusarium proliferatum (G. fujikuroi mating population D) from maize cultivated under no-till conditions at five locations in the Córdoba province of Argentina. We determined the effective population number for mating population A (N(e)) and found that the N(e) for mating type was 89% of the count (total population) and that the N(e) for male or hermaphrodite status was 36%. Thus, the number of strains that can function as the female parent limits N(e), and sexual reproduction needs to occur only once every 54 to 220 asexual generations to maintain this level of sexual fertility. Our results indicate that the fungal populations isolated from no-till maize are similar to those recovered from maize managed with conventional tillage. We placed 36 strains from mating population A into 28 vegetative compatibility groups (VCGs). Of the 13 strains belonging to five multimember VCGs, only 2 isolates belonging to one VCG were clones based on amplified fragment length polymorphism (AFLP) fingerprints. Members of the other four multimember VCGs had an average similarity index of 0.89, and members of one VCG were no more closely related to other members of the same VCG than they were to other members of the population as a whole. This finding suggests that the common assumption that strains in the same VCG are either clonal or very closely related needs to be examined in more detail. The variability observed with AFLPs and VCGs suggests that sexual reproduction may occur more frequently than estimated by N(e).

Argentina↗

Comparison of systemic cytokine levels in patients with acute respiratory distress syndrome, severe pneumonia, and controls.

BACKGROUND: The inflammatory response has been widely investigated in patients with acute respiratory distress syndrome (ARDS) and pneumonia. Studies investigating the diagnostic values of serum cytokine levels have yielded conflicting results and only little information is available for the differential diagnosis between ARDS and pneumonia. METHODS: Clinical and physiological data, serum concentrations of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6, and quantitative cultures of lower respiratory tract specimens were obtained from 46 patients with ARDS and 20 with severe pneumonia within 24 hours of the onset of the disease and from 10 control subjects with no inflammatory lung disease. Cytokine concentrations were compared between groups and determinants in addition to the diagnosis were tested. RESULTS: Serum TNF-alpha levels were significantly higher in ARDS patients (67 (57) pg/ml) than in patients with severe pneumonia (35 (20) pg/ml; p = 0.031) or controls (17 (8) pg/ml; p = 0.007). For IL-1beta and IL-6 the observed differences were not statistically significant between patients with ARDS (IL-1beta: 34 (65) pg/ml; IL-6: 712 (1058) pg/ml), those with severe pneumonia (IL-1beta: 3 (4) pg/ml, p = 0.071; IL-6: 834 (1165) pg/ml, p = 1.0), and controls (IL-1beta: 6 (11) pg/ml, p = 0.359; IL-6: 94 (110) pg/ml, p = 0.262). TNF-alpha (standardised coefficient beta = 0.410, p<0.001) and IL-1beta (standardised coefficient beta = 0.311, p = 0.006) were most strongly associated with the degree of lung injury, even when the diagnostic group was included in the statistical model. CONCLUSIONS: Serum TNF-alpha levels were higher in patients with ARDS than in those with severe pneumonia or in control subjects. Multivariate results suggest that the levels of systemic TNF-alpha and IL-1beta reflect the severity of the lung injury rather than the diagnosis.

Biomarkers↗

Treatment of severe nosocomial pneumonia: a prospective randomised comparison of intravenous ciprofloxacin with imipenem/cilastatin.

BACKGROUND: A prospective multicentre study was undertaken to compare the efficacy of intravenous ciprofloxacin or imipenem in the treatment of severe nosocomial pneumonia requiring mechanical ventilation. METHODS: Patients with a clinical suspicion of pneumonia were randomised to receive either ciprofloxacin (800-1200 mg/day) or imipenem (2-4 g/day) in doses adjusted for renal function and specimens of the lower respiratory tract were taken. Patients were included in the study when specimens showed significant growth for potentially pathogenic microorganisms in quantitative bacterial cultures (n = 75, ciprofloxacin 41/75 (55%); imipenem 34/75 (45%)). The clinical and bacteriological success rates were the primary and secondary efficacy variables. An intent-to-treat analysis was performed for all randomised patients who received at least one dose of the study medication (n = 149, ciprofloxacin 72/149 (48%), imipenem 77/149 (52%)). RESULTS: The success rates were generally good, but neither the clinical success rates (ciprofloxacin, 29/41 (71%), imipenem, 27/34 (79%); 95% CI -10.8 to 28.1; p = 0.435) nor the bacteriological response rate (ciprofloxacin, 20/41 (49%), imipenem, 17/34 (50%); 95% CI -21.5 to 23.9; p = 1.0) were significantly different between the study arms. Pseudomonas aeruginosa was recovered in 26/75 patients (35%) and clinical (ciprofloxacin, 10/14 (71%), imipenem, 8/12 (67%); 95% CI -40.4 to 30.9; p = 1.0) and bacteriological response rates (ciprofloxacin, 7/14 (50%), imipenem, 3/12 (25%), 95% CI -60.9 to 10.9, p = 0.247) were not significantly different in this subgroup of patients. Resistance of Pseudomonas aeruginosa developed in 5/26 cases (19%), 1/14 (7%) to ciprofloxacin and 4/12 (33%) to imipenem (p = 0.147), and the mortality was 12/75 (16%) with no difference between treatment groups (ciprofloxacin, 8/41(24%), imipenem 4/34 (17%); p = 0.362). The clinical response was evaluable in 109/149 patients (73%) in the intent-to-treat analysis and was successful in 74/109 patients (68%). The clinical response rates were also not significantly different in the intent-to-treat analysis (ciprofloxacin, 34/52 (65%), imipenem, 40/57 (70%); 95% CI -12.8 to 22.3; p = 0.746). CONCLUSIONS: Treatment with either ciprofloxacin or imipenem was effective in a selected group of patients with microbiologically confirmed, severe nosocomial pneumonia requiring mechanical ventilation. Although no differences between the study medication could be documented in this trial, smaller differences between treatment arms may have been missed because of sample size limitations.

Adult↗

Sexual dimorphism in diethylstilbestrol-induced prolactin pituitary tumors in F344 rats.

Female F344 rats treated chronically with diethylstilbestrol (DES) develop prolactin (PRL)-producing pituitary tumors. These tumors are larger in female than in male rats. To investigate gender differences in DES-induced pituitary tumor formation, we employed female and male rats and neonatally androgenized females, which received 100 microg of testosterone propionate (TP) after birth. At 3 months of age, all rats were deprived of their gonads and divided into control and DES-treated groups. Forty days after beginning treatment, control pituitary weight and serum PRL were similar in gonadectomized males (GDX), ovariectomized females (OVX) and androgenized-ovariectomized females (OVX + TP), but weight of DES-induced tumors was 2.5-fold higher and serum PRL 5.6-fold higher in OVX + DES than in GDX + DES or OXV + TP + DES (p<0.001). At the pituitary level, nuclear estrogen receptors (NE(2)R) amounted to >100 fmol/mg DNA in all rats receiving DES. However, NE(2)R were lower in OVX + DES (101.3+/-9.0 fmol/mg DNA) than in GDX + DES (174.6 +/-16.8; p<0.05) and in OXV + DES + TP (150.3+/-27.7; p<0.05). A similar profile was found for cytosolic progestin receptors. Using electron microscopy (EM), hyperplasia/hypertrophy of lactotropes was found in all DES-stimulated pituitaries. However, tumors of OVX + DES rats were enriched in hyperstimulated typical lactotropes, i.e., cells with high rate of hormonal synthesis, processing and secretion. Instead, tumors from GDX + DES and OVX + TP + DES rats were a mixture of typical and atypical lactotropes, i.e. a cell subpopulation with refractory secretory response and a few gonadotropes. In agreement with these data, immunoreactive pituitary PRL was lower in OVX + DES than in OVX + TP + DES and GDX + DES groups. Thus, differences in the sensitivity to DES, serum and tumor PRL, NE(2)R and progestin receptors between estrogenized female rats on one side and male and TP-androgenized females on the other, may by due in part to heterogeneity of cell populations. Our data further suggest that neonatal hypothalamic exposure to androgens, as in normal males or androgenized females with masculinization of hypothalamic centers, may condition the response to DES stimulation later in life.

Animals↗

Pulmonary gas exchange response to oxygen breathing in acute lung injury.

The mechanisms and time course of the pulmonary gas exchange response to 100% O(2) breathing in acute respiratory failure needing mechanical ventilation were studied in eight patients with acute lung injury (ALI) (48 +/- 18 yr [mean +/- SD]) and in four patients (66 +/- 2 yr) with chronic obstructive pulmonary disease (COPD). We postulated that, in patients with ALI while breathing 100% O(2), the primary mechanism of hypoxemia, i.e., increased intrapulmonary shunt, would further worsen (increase) as a result of reabsorption atelectasis. Respiratory and inert gases, and systemic and pulmonary hemodynamics were measured at maintenance fraction of inspired oxygen (FI(O(2))-m), at 30 and 60 min while breathing 100% O(2), and then at 30 min of resuming FI(O(2))-m. During 100% O(2) breathing, in patients with ALI, Pa(O(2)) (by 207 and 204 mm Hg; p < 0.01 each), Pa(CO(2)) (by 4 mm Hg each) (p < 0.05 each), and intrapulmonary shunt (from 16 +/- 10% to 22 +/- 11% and 23 +/- 11%) (p < 0.05 each) increased respectively. By contrast, in patients with COPD, Pa(O(2)) (by 387 and 393 mm Hg; p < 0.001 each), Pa(CO(2)) (by 4 and 5 mm Hg) and the dispersion of pulmonary blood flow (log SDQ) (from 1.33 +/- 0.10 to 1.60 +/- 0.20 and 1.80 +/- 0.30 [p < 0.05]) increased, respectively. In patients with ALI, the breathing of 100% O(2) deteriorates intrapulmonary shunt owing to collapse of unstable alveolar units with very low ventilation-perfusion (V A/Q) ratios, as opposed to patients with COPD, in whom only the dispersion of the blood flow distribution is disturbed, suggesting release of hypoxic pulmonary vasoconstriction.

Aged↗

Capnometric recirculation gas tonometry and weaning from mechanical ventilation.

The aim of this study was to describe changes in regional intramucosal PCO(2) (Pr(CO(2)) measured with capnometric recirculation gas tonometry [CRGT]) in patients with acute respiratory failure, who proceed from mechanical ventilation to weaning. In addition, we compared the predictive power for the weaning outcome of CRGT measurements obtained during mechanical ventilation to the frequency/ tidal volume (f/VT) ratio. A total of 24 patients (31 weaning trials) were included in the study, but four of the 24 patients (17%) were excluded because of extubation failure. Of the remaining 27 weaning trials in 20 patients, 12 (44%) were unsuccessful. Changes observed in patients with weaning failure (increase in Pr(CO(2)) from 60.4 +/- 15.0 mm Hg in mechanical ventilation to 67.4 +/- 21.0 mm Hg, in weaning) were significantly different (p = 0.046) from those observed in patients with weaning success (fall in Pr(CO(2)) from 61.5 +/- 15.0 mm Hg in mechanical ventilation to 56.3 +/- 16.7 mm Hg in weaning). However, absolute values of Pr(CO(2)) were not significantly different between patients with weaning success and failure, neither during mechanical ventilation (success, 61.5 +/- 15.0 versus failure, 60.4 +/- 15.0 mm Hg, p = 0.848) nor during weaning (success, 56.3 +/- 16.7 versus failure, 67.4 +/- 21.0 mm Hg, p = 0.135). The best single predictor for weaning outcome was the f/VT ratio measured early during weaning (area under the curve: 0.844 +/- 0.081; adjusted odds ratio for threshold value </= 105: 42.0, 95% CI 3.8 to 469.1, p = 0.002). CRGT could confirm a significant increase in Pr(CO(2)) during weaning in patients who finally failed the weaning trial. However, differences between patients with weaning success and failure were small and CRGT did not replace or improve the predictive power of the f/VT ratio for weaning outcome.

Acute Disease↗

Treatment of gram-positive nosocomial pneumonia. Prospective randomized comparison of quinupristin/dalfopristin versus vancomycin. Nosocomial Pneumonia Group.

Nosocomial pneumonia is a frequent complication in hospitalized patients. Gram-positive pathogens, particularly Staphylococcus aureus, are responsible for the increasing frequency of nosocomial pneumonia. To evaluate the efficacy and safety of intravenous quinupristin/dalfopristin (Synercid) in the treatment of nosocomial pneumonia caused by gram-positive pathogens we conducted a prospective, randomized, open-label, international, multicenter, comparative clinical trial. Two hundred ninety-eight patients with nosocomial pneumonia were enrolled in 74 active centers in five countries: a subgroup of 171 (87 quinupristin/dalfopristin-treated and 84 vancomycin-treated patients) were evaluable for the major efficacy end points. One hundred fifty received 7.5 mg/kg of quinupristin/dalfopristin every 8 h; 148 patients received 1 g of vancomycin every 12 h. Aztreonam at a dose of 2 g every 8 h could be administered in both groups for coverage of gram-negative organisms, and tobramycin was added for coverage against Pseudomonas aeruginosa. The primary efficacy end point was the clinical response between the seventh and the thirteenth day after the end of treatment in clinically evaluable patients with documented causative pathogen(s) at baseline (bacteriologically evaluable population). Therapy was clinically successful (cure or improvement) in 49 (56.3%) of patients receiving quinupristin/dalfopristin and 49 (58.3%) patients receiving vancomycin (difference, -2.0% [95% CI, -16.8% to 12.8%]) in the bacteriologically evaluable population. Equivalent clinical success rates were also observed in the all-treated population (n = 298), and in the bacteriologically evaluable patients intubated in baseline (39/72 [54%] compared with 36/67 [54%]). The by-pathogen bacteriologic response was similar in both treatment groups, with equivalent clinical success rates for Streptococcus pneumoniae, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus. Adverse events (venous and nonvenous) were equally distributed between groups; 15.3% of quinupristin/dalfopristin patients and 9.5% of vancomycin patients discontinued therapy because of an adverse clinical event. In this study quinupristin/dalfopristin was shown to be equivalent to vancomycin in the treatment of nosocomial pneumonia caused by gram-positive pathogens. Quinupristin/dalfopristin merits further evaluation for the treatment of nosocomial pneumonia caused by methicillin-resistant S. aureus.

Adult↗

Antimicrobial treatment failures in patients with community-acquired pneumonia: causes and prognostic implications.

The aim of the study was to determine the causes and prognostic implications of antimicrobial treatment failures in patients with nonresponding and progressive life-threatening, community-acquired pneumonia. Forty-nine patients hospitalized with a presumptive diagnosis of community-acquired pneumonia during a 16-mo period, failure to respond to antimicrobial treatment, and documented repeated microbial investigation >/= 72 h after initiation of in-hospital antimicrobial treatment were recorded. A definite etiology of treatment failure could be established in 32 of 49 (65%) patients, and nine additional patients (18%) had a probable etiology. Treatment failures were mainly infectious in origin and included primary, persistent, and nosocomial infections (n = 10 [19%], 13 [24%], and 11 [20%] of causes, respectively). Definite but not probable persistent infections were mostly due to microbial resistance to the administered initial empiric antimicrobial treatment. Nosocomial infections were particularly frequent in patients with progressive pneumonia. Definite persistent infections and nosocomial infections had the highest associated mortality rates (75 and 88%, respectively). Nosocomial pneumonia was the only cause of treatment failure independently associated with death in multivariate analysis (RR, 16.7; 95% CI, 1.4 to 194.9; p = 0.03). We conclude that the detection of microbial resistance and the diagnosis of nosocomial pneumonia are the two major challenges in hospitalized patients with community-acquired pneumonia who do not respond to initial antimicrobial treatment. In order to establish these potentially life-threatening etiologies, a regular microbial reinvestigation seems mandatory for all patients presenting with antimicrobial treatment failures.

Community-Acquired Infections↗

Noninvasive versus invasive microbial investigation in ventilator-associated pneumonia: evaluation of outcome.

Noninvasive and invasive diagnostic techniques have been shown to achieve comparable performances in the evaluation of suspected ventilator-associated pneumonia (VAP). We studied the impact of both approaches on outcome in a prospective, open, and randomized study in three intensive care units (ICUs) of a 1,000-bed tertiary care university hospital. Patients with suspected VAP were randomly assigned to noninvasive (Group 1) versus invasive (Group 2) investigation (tracheobronchial aspirates [TBAS] versus bronchoscopically retrieved protected specimen brush [PSB] and bronchoalveolar lavage [BAL]. Samples were cultured quantitatively, and BAL fluid (BALF) was examined for intracellular organisms (ICO) additionally. Initial empiric antimicrobial treatment was administered following the guidelines of the American Thoracic Society (ATS) and adjusted according to culture results (and ICO counts in Group 2). Outcome variables included length of ICU stay and mechanical ventilation as well as mortality. Overall, 76 patients (39 noninvasive, 37 invasive) were investigated. VAP was microbiologically confirmed in 23 of 39 (59%) and 23 of 37 (62%) (p = 0.78). There were no differences with regard to the frequencies of community-acquired and potentially drug-resistant microorganisms (PDRM). Antimicrobial treatment was changed in seven patients (18%) of Group 1 and 10 patients (27%) of Group 2 because of etiologic findings (including five of 17 with ICO = 2% (p = not significant [NS]). Length of ICU stay and mechanical ventilation were also not significantly different in both groups. Crude 30-d mortality was 31 of 76 (41%), and 18 of 39 (46%) in Group 1 and 14 of 37 (38%) in Group 2 (p = 0.46). Adjusted mortality was 16% versus 11% (p = 0.53), and mortality of microbiologically confirmed pneumonia 10 of 23 (44%) in both groups (p = 1.0). We conclude that the outcome of VAP was not influenced by the techniques used for microbial investigation.

Aged↗