Ampicillin/sulbactam compared with polymyxins for the treatment of infections caused by carbapenem-resistant Acinetobacter spp.

Background: There has been an increase in worldwide infections caused by carbapenem-resistant Acinetobacter. This poses a therapeutic challenge as few treatment options are available. Objectives: The aim of this study was to evaluate the efficacy and safety of polymyxins and ampicillin/sulbactam for treating infections caused by carbapenem-resistant Acinetobacter spp. and to evaluate prognostic factors. Methods: This was a retrospective review of patients from two teaching hospitals who had nosocomial infections caused by carbapenem-resistant Acinetobacter spp. from 1996 to 2004. Diagnosis of infection was based on CDC criteria plus the isolation of Acinetobacter from a usually sterile site or from bronchoalveolar lavage. Urinary tract infections were not included. Data on demographic and clinical features and treatment were collected from medical records. Prognostic factors associated with two outcomes (mortality during treatment and in-hospital mortality) were evaluated. Results: Eighty-two patients received polymyxins and 85 were treated with ampicillin/sulbactam. Multiple logistic regression analysis revealed that independent predictors of mortality during treatment were treatment with polymyxins, higher Acute Physiological and Chronic Health Evaluation II (APACHE II) score, septic shock, delay in starting treatment and renal failure. On multivariate analysis, prognostic factors for in-hospital mortality were older age, septic shock and higher APACHE II score. Conclusions: This is the first study comparing current therapeutic options for infections due to carbapenem-resistant Acinetobacter. The most important finding of the present study is that ampicillin/sulbactam appears to be more efficacious than polymyxins, which was an independent factor associated with mortality during treatment.

Impact of antimicrobial resistance on the treatment and outcome of patients with sepsis

Antimicrobial therapy is one of the main stones of sepsis therapy. A recent study of septic shock patients showed that each hour of delay in antimicrobial administration during the ensuing 6 h after the onset of hypotension was associated with a decrease in survival rates. However, many questions regarding the impact of infection caused by antimicrobial-resistant pathogens on the mortality of patients with sepsis still need to be clarified. There is a lack of fair studies in the literature. Most studies have had inadequate sample size, inadequate adjustment for predictors of adverse outcomes, and inadequate definition of appropriate antibiotic therapy. Despite the fact that appropriate therapy is essential to treat sepsis, it seems that severity of underlying diseases and comorbidities are more important than resistance, although the studies were not well designed to examine the real impact of resistance on outcome. Finally, new technologies such as microarray that can identify different microorganisms, genes of resistance, and virulence in a few hours might have a great impact on the treatment of sepsis due to antimicrobial-resistant pathogens in the future.

Cor pulmonale in a patient with Brown-Vialetto-Van Laere syndrome: A case report

Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare neurological disease characterized by sensorineural hearing loss and multiple cranial nerve palsies, usually involving the VIIth and IXth to XIIth cranial nerves. We describe the clinical and pathological features of a 33-year-old woman with BVVLS. The patient developed progressive exertional dyspnea, with clinical and laboratory findings of right-sided heart failure and pulmonary hypertension. She developed status epilepticus in the setting of cardiac deterioration and respiratory infection, and died of cardiogenic and septic shock. Autopsy disclosed bilateral neuronal loss and gliosis in the inferior colliculi, locus coeruleus and facial and vestibular nuclei. Cor pulmonale is a complication of hypoventilation-induced hypoxia and hypercapnia and had not yet been reported in BVVLS. (C) 2010 Elsevier B.V. All rights reserved.

Early short-term versus prolonged low-dose methylprednisolone therapy in acute lung injury

The present study compared the effects of early short-term with prolonged low-dose corticosteroid therapy in acute lung injury (ALI). In total, 120 BALB/c mice were randomly divided into five groups. In the control group, saline was intratracheally (i.t.) instilled. In the ALI group, mice received Escherichia coli lipopolysaccharide (10 mu g i.t.). ALI animals were further randomised into four subgroups to receive saline (0.1 mL i.v.) or methylprednisolone (2 mg center dot kg(-1) i.v.) at 6 h, 24 h or daily (for 7 days, beginning at day 1). At 1, 3 and 8 weeks, in vivo and in vitro lung mechanics and histology (light and electron microscopy), collagen and elastic fibre content, cytokines in bronchoalveolar lavage fluid and the expression of matrix metalloproteinase (MMP)-9 and -2 were measured. In vivo (static elastance and viscoelastic pressure) and in vitro (tissue elastance and resistance) lung mechanics, alveolar collapse, cell infiltration, collagen and elastic fibre content and the expression of MMP-9 and MMP-2 were increased in ALI at 1 week. Methylprednisolone led to a complete resolution of lung mechanics, avoided fibroelastogenesis and the increase in the expression of MMP-9 and MMP-2 independent of steroid treatment design. Thus, early short-term, low-dose methylprednisolone is as effective as prolonged therapy in acute lung injury.

Methylprednisolone improves lung mechanics and reduces the inflammatory response in pulmonary but not in extrapulmonary mild acute lung injury in mice

Objective: Gorticosteroids have been proposed to be effective in modulating the inflammatory response and pulmonary tissue remodeling in acute lung injury (ALI). We hypothesized that steroid treatment might act differently in models of pulmonary (p) or extrapulmonary (exp) ALI with similar mechanical compromise. Design: Prospective, randomized, controlled experimental study. Setting: University research laboratory. Subjects: One hundred twenty-eight BALB/c mice (20-25 g). Interventions: Mice were divided into six groups. In control animals sterile saline solution was intratracheally (0.05 mL, Cp) or intraperitoneally (0.5 mL, Gexp) injected, whereas ALI animals received Escherichia coli lipopolysaccharide intratracheally (10 mu g, ALIp) or intraperitoneally (125 mu g, ALIexp). Six hours after lipopolysaccharide administration, ALIp and ALlexp animals were further randomized into subgroups receiving saline (0.1 mL intravenously) or methylprednisolone (2 mg/kg intravenously, Mp and Mexp, respectively). Measurements and Main Results: At 24 hrs, lung state elastance, resistive and viscoelastic pressures, lung morphometry, and collagen fiber content were similar in both ALI groups. KC, interieukin-6, and transforming growth factor (TGF)-beta levels in bronchoatveolar lavage fluid, as well as tumor necrosis factor (TNF)-alpha, migration inhibitory factor (MIF), interferon (IFN)-gamma, TGF-beta 1 and TGF-beta 2 messenger RNA expression in lung tissue were higher in ALIp than in ALIexp animals. Methylprednisolone attenuated mechanical and morphometric changes, cytokine levels, and TNF-alpha, MIF, IFN gamma, and TGF-beta 2 messenger RNA expression only in ALIp animals, but prevented any changes in collagen fiber content in both ALI groups. Conclusions. Methylprednisolone is effective to inhibit fibrogenesis independent of the etiology of ALI, but its ability to attenuate inflammatory responses and lung mechanical changes varies according to the cause of ALI.

Loxosceles venom-induced cytokine activation, hemolysis, and acute kidney injury

Herein, we describe a confirmed case of Loxosceles spider bite that illustrates the critical complications seen in loxoscelism, including skin necrosis, rhabdomyolysis, hemolysis, coagulopathy, acute kidney failure, and electrolyte disorders. Upon initial assessment, laboratory studies revealed the following: the white blood cell count was 29 400 WBCs/mm(3), hemoglobin was 9.2g/dL, and the platelet count was 218000cells/mm(3). Coagulation studies revealed the following: international normalized ratio, 1.83; activated partial-thromboplastin time, 62s; D-dimer, 600 ng/mL (normal range < 500 ng/mL); free protein S, 37% (normal range = 64-114%); protein C, negative; and antithrombin III, negative. Various serum levels were abnormal: urea, 110mg/dL; creatinine, 3.1 mg/dL; indirect bilirubin, 3.8 mg/dL; creatine kinase, 1631 U/L, lactate dehydrogenase, 6591 U/L; potassium 6.2mmol/L. Urine tests were positive for hemoglobin and bilirubin. In addition, concentrations of interleukin-6 and tumor necrosis factor-alpha were notably elevated in the serum. In conclusion, physicians must be alert to the possibility of loxoscelism when a patient presents with the clinical and laboratory findings described above, especially if the patient resides in an endemic area. Advances in our understanding of multiple pathways and mediators that orchestrate the response to Loxosceles venom might reveal new possibilities for the management of loxoscelism. (C) 2007 Elsevier Ltd. All rights reserved.

Early and late effects of bone marrow-derived mononuclear cell therapy on lung and distal organs in experimental sepsis

We tested the hypothesis that bone marrow-derived mononuclear cells (BMDMCs) at an early phase of cecal ligation and puncture (CLP)-induced sepsis may have lasting effects on: (1) lung mechanics and histology, (2) the structural remodelling of lung parenchyma, (3) lung, kidney, and liver cell apoptosis, and (4) pro- and anti-inflammatory cytokines and growth factors. At day 1, BMDMC significantly reduced mortality, as well as caspase-3, interleukin (IL)-6 and IL-1 beta vascular endothelial growth factor, platelet-derived growth factor, hepatocyte growth factor, and transforming growth factor-beta, but increased IL-10 mRNA expression in lung tissue in septic mice contributing to endothelium and epithelium alveolar repair and improvement of lung mechanics. BMDMC also prevented the increase of apoptotic cells in lung, liver, and kidney. At day 7, these early functional and morphological effects were preserved or further improved. In conclusion, in the present model of sepsis, the beneficial effects of early administration of BMDMCs on lung and distal organs were preserved, possibly by paracrine mechanisms. (C) 2011 Elsevier B.V. All rights reserved.

Hantavirus infection associated to a staphylococcal sepsis. Report of one case

We report a previously healthy 36-year-old male who developed a pulmonary syndrome caused by Hantavirus infection He was admitted to an intensive care unit in shock awl respiratory failure and died four hours after admission. Blood cultures were positive for Staphylococcus aureus This patient could be an index case that shows, for the first time, an association of Hantavirus Pulmonary Syndrome with Staphylococcus nitwits infection similar to what happens with other viruses (Rev Med Chile 2010, 138: 338-340).

HEMODYNAMIC AND PERFUSION END POINTS FOR VOLEMIC RESUSCITATION IN SEPSIS

Sepsis is the systemic inflammatory response syndrome secondary to a local infection, and severe sepsis and septic shock are the more devastating scenarios of this disease. In the last decade, considerable achievements were obtained in sepsis knowledge, and an international campaign was developed to improve the treatment of this condition. However, sepsis is still one of the most important causes of death in intensive care units. The early stages of sepsis are characterized by a variety of hemodynamic derangements that induce a systemic imbalance between tissue oxygen supply and demand, leading to global tissue hypoxia. This dysfunction, which may occur in patients presenting normal vital signs, can be accompanied by a significant increase in both morbidity and mortality. The early identification of high-risk sepsis patients through tissue perfusion markers such as lactate and venous oxygen saturation is crucial for prompt initiation of therapeutic support, which includes early goal-directed therapy as necessary. The purpose of this article was to review the most commonly used hemodynamic and perfusion parameters for hemodynamic optimization in sepsis, emphasizing the physiological background for their use and the studies that demonstrated their effectiveness as goals of volemic resuscitation.

Generalized Pustular Psoriasis in Childhood

Generalized pustular psoriasis is a rare form of psoriasis consisting of a generalized eruption of sudden onset with erythema and sterile pustules. In children, generalized pustular psoriasis is even more uncommon and may present as a severe and potentially life-threatening disorder. In this study, we present demographics, clinical aspects, treatment response, and follow-up of seven children with generalized pustular psoriasis. Retrospective study reviewing the records of seven children with generalized pustular psoriasis including age, gender, age of onset, presence of scalp and nail involvement, family history, concomitant diseases, precipitating factors, treatment modalities, and outcome. Age of first symptoms ranged from 1 month to 11 years. All patients received systemic retinoids at one time of the follow-up period. Other treatment modalities included immunosuppressive drugs, biologics, phototherapy, and sulfasalazine. Two patients presented with severe constitutional illness, secondary infection and septic shock, including one fatal outcome. All further cases have remained free of recurrences for a mean period of up to 3 years. In our study, generalized pustular psoriasis presented a wide clinical spectrum in children ranging from mild, asymptomatic outbreaks to more severe, life-threatening episodes. One fatality was observed. Children generally responded well to systemic retinoids. Further studies and long-term follow-up periods are needed to define potential trigger factors, efficacy and safety of different treatment modalities in children with generalized pustular psoriasis.

Fluid Replacement With Hypertonic or Isotonic Solutions Guided by Mixed Venous Oxygen Saturation in Experimental Hypodynamic Sepsis

Background: Splanchnic perfusion is prone to early injury and persists despite normalization of global hemodynamic variables in sepsis. Volume replacement guided by oxygen derived variables has been recommended in the management of septic patients. Our hypothesis was that a hypertonic isoneotic solution Would improve the benefits of crystalloids replacement guided by mixed venous oxygen saturation. Methods: Seventeen anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live E. coli in 30 minutes. They were then randomized into three groups: control group (n = 3) bacterial infusion without treatment; normal saline (n = 7), initial fluid replacement with 32 mL/kg of normal saline during 20 minutes; hypertonic solution (n = 7), initial fluid replacement with 4 mL/kg of hypertonic solution during 5 minutes. After 30 and 60 Minutes, additional boluses of normal saline were administered when mixed venous oxygen saturation remained below 70%. Mean arterial pressure, cardiac output; regional blood flows, systemic and regional oxygen-derived variables, and lactate levels were assessed. Animals were observed for 90 minutes and then killed. Hystopathological analysis including apoptosis detection using terminal deoxynucleotidil transferase mediated dUTP-biotin nick end labeling was performed. Results: A hypodynamic septic shock was observed after bacterial infusion. Both the fluid-treated groups presented similar transient benefits in systemic and regional variables. A greater degree of gut epithelial cells apoptosis was observed in normal saline-treated animals. Conclusions: Although normalization of mixed venous oxygen saturation was not associated with restoration of markers of splanchnic or other systemic perfusion variables, the initial fluid savings with hypertonic saline and its latter effect on gut apoptosis may be of interest in sepsis management.

One-Stage Revision of Infected Total Hip Arthroplasty with Bone Graft

There are many different opinions in the literature regarding the best procedure for revision of infected hip arthroplasty and hence in achieving long-term stabilization of a new implant. Thirty-two patients with 32 loose and infected total hip arthroplasties underwent revision with a bone graft in a 1-stage procedure. The bone graft was used in the acetabulum and femure in 25 patients, in the acetabulum alone in 4 patients and in the femur alone in 3 patients. A metal mesh was necessary in 15 patients to contain the morselized bone graft. At the time of surgical revision, 9 patients had a draining sinus, 6 had a closed sinus, and 17 had never had sinuses in the surgical wound. Antibiotic therapy was administered intravenously and orally for 6 months. Mean follow-up was 103 months (range, 63-183 months), and infection recurred in 2 (6.2%) cases. Further studies are necessary, and continuation of this method is justified.

EFFECTS OF A POTENT PEROXYNITRITE DECOMPOSITION CATALYST IN MURINE MODELS OF ENDOTOXEMIA AND SEPSIS

Excessive free-radical production due to various bacterial components released during bacterial infection has been linked to cell death and tissue injury. Peroxynitrite is a highly reactive oxidant produced by the combination of nitric oxide (NO) and superoxide anion, which has been implicated in cell death and tissue injury in various forms of critical illness. Pharmacological decomposition of peroxynitrite may represent a potential therapeutic approach in diseases associated with the overproduction of NO and superoxide. In the present study, we tested the effect of a potent peroxynitrite decomposition catalyst in murine models of endotoxemia and sepsis. Mice were injected i.p. with LPS 40 mg/kg with or without FP15 [Fe(III) tetrakis-2-(N-triethylene glycol monomethyl ether) pyridyl porphyrin] (0.1, 0.3, 1, 3, or 10 mg/kg per hour). Mice were killed 12 h later, followed by the harvesting of samples from the lung, liver, and gut for malondialdehyde and myeloperoxidase measurements. In other subsets of animals, blood samples were obtained by cardiac puncture at 1.5, 4, and 8 h after LPS administration for cytokine (TNF-alpha, IL-1 beta, and IL-10), nitrite/nitrate, alanine aminotransferase, and blood urea nitrogen measurements. Endotoxemic animals showed an increase in survival from 25% to 80% at the FP15 doses of 0.3 and 1 mg/kg per hour. The same dose of FP15 had no effect on plasma levels of nitrite/nitrate. There was a reduction in liver and lung malondialdehyde in the endotoxemic animals pretreated with FP15, as well as in hepatic myeloperoxidase and biochemical markers of liver and kidney damage (alanine aminotransferase and blood urea nitrogen). In a bacterial model of sepsis induced by cecal ligation and puncture, FP15 treatment (0.3 mg/kg per day) significantly protected against mortality. The current data support the view that peroxynitrite is a critical factor mediating liver, gut, and lung injury in endotoxemia and septic shock: its pharmacological neutralization may be of therapeutic benefit.

Surviving sepsis campaign in Brazil

Severe sepsis and septic shock have long been a challenge in intensive care because of their common occurrence, high associated costs of care, and significant mortality. The Surviving Sepsis Campaign (SSC) was developed in an attempt to address clinical inertia in the adoption of evidence-based strategies. The campaign relies on worldwide support from professional societies and has gained consensus on the management of patients with severe sepsis. The guidelines have subsequently been deployed into two bundles, with each bundle component sharing a common relationship in time. The widespread adoption of such evidence-based practice in clinical care has been disappointingly slow despite the quantifiable benefits regarding mortality. In Brazil, a country of continental dimensions with a heterogeneous population and unequal access to health services, this reality is no different. From 2004 to 2007, four prospective studies were published describing the country`s reality. In the multicenter Promoting Global Research Excellence in Severe Sepsis (PROGRESS) Study, the in-hospital mortality rate was higher in Brazil when compared with other countries: 56% against 30% in developed countries and 45% in other developing countries. During these 2.5 years of the campaign in Brazil, 43 hospitals have been receiving the necessary training to put in practice the recommended measures in all Brazilian regions, except for the North. The idea of the campaign is based on a 25% reduction in the relative risk of death from severe sepsis and septic shock within 5 years in the SSC-participating Brazilian hospitals. Ideally, the mortality rate should come to a 41.2% level subject to the 2009 deadline. This article aims to describe the actual scenario of the SSC implementation in Brazilian institutions and to report on some initiatives that have been used to overcome barriers.

A NEW ADJUSTABLE PINCH DESIGNED FOR PRODUCING CRUSH NERVE INJURIES IN THE SCIATIC NERVE OF RATS

Objective: A new adjustable pinch has been developed for producing a crush injury, with a previously known load of 5 kg, on a 5 mm-long segment of the nerve. Methods: Stainless steel was the material selected for building the pinch due its durability and possibility of sterilization with anti-septic substances, which are often corrosive. The crushing load of the pinch is adjustable by increasing or decreasing the tension of the spring by means of a screw used for calibration, which is performed by a load cell. Result: This pinch has been used in a few experimental investigations and was shown to be as efficient as both the universal testing machine and the dead weight machine, previously used. Conclusion: The developed pinch has the advantages of being portable and user-friendly. In addition, the pinch is cheap and allows for the standardization of the applied load.