Yeast central nervous system infection in a critically ill patient: a case report.

Introduction: Invasive fungal infections are alarmingly common in intensive care unit patients; invasive fungal infections are associated with increased morbidity and mortality. Risk factors are the increased use of indwelling central venous catheters, the use of broad spectrum antibiotics, parenteral nutrition, renal replacement therapy and immunosuppression. Diagnosis of these infections might be complicated, requiring tissue cultures.

Early administration of hydrocortisone replacement after the advent of septic shock: impact on survival and immune response*.

Objectives: To investigate the impact of early initiation of hydrocortisone therapy on the clinical course of septic shock and on cytokine release.

Design: Prospective study in patients with septic shock treated with low doses of hydrocortisone.

Setting: ICUs and general wards.

Intravenous paracetamol as an antipyretic and analgesic medication: the significance of drug metabolism.

One prospective, open-label, non-randomized study was conducted in 100 patients to define the antipyretic and analgesic effect of a new intravenous formulation of 1 g of paracetamol; 71 received paracetamol for the management of fever and 29 received paracetamol for pain relief after abdominal surgery or for neoplastic pain. Serial follow-up measurements of core temperature and of pain intensity were done for 6 h. Additional rescue medications were recorded for 5 days.

Comparative efficacy of tigecycline VERSUS vancomycin in an experimental model of soft tissue infection by methicillin-resistant Staphylococcus aureus producing Panton-Valentine leukocidin.

Methicillin-resistant Staphylococcus aureus (MRSA) producing Panton-Valentine leukocidin (PVL) is highly virulent. This study aimed to compare the efficacy of tigecycline versus vancomycin in experimental thigh abscess by a PVL-producing MRSA isolate. One hundred and ninety-six Wistar rats were divided into five groups: group A, controls; groups B and C, administered vancomycin starting 1 and 6 h after bacterial challenge respectively; groups D and E, administered tigecycline starting 1 and 6 h after bacterial challenge respectively.

Effect of clarithromycin in patients with suspected Gram-negative sepsis: results of a randomized controlled trial.

Background: A previous randomized study showed that clarithromycin decreases the risk of death due to ventilator-associated pneumonia and shortens the time until infection resolution. The efficacy of clarithromycin was tested in a larger population with sepsis.

Methods: Six hundred patients with systemic inflammatory response syndrome due to acute pyelonephritis, acute intra-abdominal infections or primary Gram-negative bacteraemia were enrolled in a double-blind, randomized, multicentre trial.

How to select an antifungal agent in critically ill patients.

Fungal infections are common in critically ill patients and are associated with increased morbidity and mortality. Candida spp are the most commonly isolated fungal pathogens. The last 2 decades have seen an increased incidence of fungal infections in critical illness and the emergence of new pathogenic fungal species and also the development of more effective (better bioavailability) and safer (less toxicity, fewer drug interactions) drugs.

An algorithm for the management of Staphylococcus aureus carriage within patients with recurrent staphylococcal skin infections.

Recurrent skin infections of staphylococcal origin raise the question of probable skin colonization by Staphylococcus aureus and the need for eradication. Available evidence does not exist for such settings. A management algorithm was developed by a group of experts that was implemented prospectively in 125 patients admitted for recurrent staphylococcal skin infections.

The functional role of natural killer cells early in clinical sepsis.

Although much information is available for the function of circulating monocytes when signs of sepsis are apparent, little is known for natural killer (NK) cells. NK cells were isolated from 10 healthy controls and from 103 patients with sepsis within the first 24 h from diagnosis. NK cells were stimulated with lipopolysaccharide for cytokine production.

Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor.

Introduction: Early risk assessment is the mainstay of management of patients with sepsis. APACHE II is the gold standard prognostic stratification system. A prediction rule that aimed to improve prognostication by APACHE II with the application of serum suPAR (soluble urokinase plasminogen activator receptor) is developed.

Genetic polymorphisms within tumor necrosis factor gene promoter region: a role for susceptibility to ventilator-associated pneumonia.

Debatable findings exist among various studies regarding the impact of single nucleotide polymorphisms (SNPs) within the promoter region of the tumor necrosis factor (TNF) gene for susceptibility to infections. Their impact was investigated in a cohort of mechanically ventilated patients who developed ventilator-associated pneumonia (VAP). Two-hundred and thirteen mechanically ventilated patients who developed VAP were enrolled.

Effect of clarithromycin in inflammatory markers of patients with ventilator-associated pneumonia and sepsis caused by Gram-negative bacteria: results from a randomized clinical study.

One recent, double-blind, randomized clinical trial with 200 patients showed that clarithromycin administered intravenously for 3 days in patients with ventilator-associated pneumonia (VAP) accelerated the resolution of pneumonia and decreased the risk of death from septic shock and multiple organ dysfunctions (MODS). The present study focused on the effect of clarithromycin on markers of inflammation in these patients. Blood was drawn immediately before the administration of the allocated treatment and on six consecutive days after the start of treatment.

Role of tumor necrosis factor gene single nucleotide polymorphisms in the natural course of 2009 influenza A H1N1 virus infection.

Objectives: To identify the role of single nucleotide polymorphisms (SNPs) of the tumor necrosis factor (TNF) gene in the natural course of 2009 influenza A H1N1 virus infection.

Methods: Genomic DNA was isolated from 109 patients with an H1N1 infection and from 108 healthy volunteers. SNPs of the TNF gene were assessed after electrophoresis of the digested PCR products by restriction enzymes.

Detrimental effect of apoptosis of lymphocytes at an early time point of experimental abdominal sepsis.

Background: Apoptosis of lymphocytes is considered a late sequelum in the sepsis cascade. The role of apoptosis of lymphocytes as a driver of final outcome was investigated.

Methods: Abdominal sepsis was induced after cecal ligation and puncture (CLP) in 31 rabbits.

Soluble urokinase plasminogen activator receptor (suPAR) for assessment of disease severity in ventilator-associated pneumonia and sepsis.

Urokinase plasminogen activator (uPAR) is a receptor mainly expressed on peripheral blood mononuclear cells and neutrophils. The role of its soluble form, namely suPAR, as a predictor of sepsis outcome in a homogenous cohort of 180 septic patients, was investigated. Blood from 180 patients with ventilator-associated pneumonia (VAP) and sepsis was collected for seven consecutive days.

Inhibition of caspase-1 activation in Gram-negative sepsis and experimental endotoxemia.

Introduction: Down-regulation of ex-vivo cytokine production is a specific feature in patients with sepsis. Cytokine downregulation was studied focusing on caspase-1 activation and conversion of pro-interleukin-1β into interleukin-1β (IL-1β).

Methods: Peripheral blood mononuclear cells were isolated from a) 92 patients with sepsis mainly of Gram-negative etiology; b) 34 healthy volunteers; and c) 5 healthy individuals enrolled in an experimental endotoxemia study.

Immunomodulation in sepsis: state of the art and future perspective.

Despite advances in supportive care of critically ill patients, sepsis remains an important cause of death worldwide. More than 750,000 individuals develop severe sepsis in North America annually, with a mortality rate varying between 35 and 50%. Over recent years, numerous efforts have been committed to understanding the pathophysiology of septic syndrome, as well as attempts to intervene in the inflammatory cascade with the aim of altering the outcome of the syndrome and to improve survival.

Early alterations of the innate and adaptive immune statuses in sepsis according to the type of underlying infection.

Introduction: Although major changes of the immune system have been described in sepsis, it has never been studied whether these may differ in relation to the type of underlying infection or not. This was studied for the first time.

Methods: The statuses of the innate and adaptive immune systems were prospectively compared in 505 patients.

Effect of the novel influenza A (H1N1) virus in the human immune system.

Background: The pandemic by the novel H1N1 virus has created the need to study any probable effects of that infection in the immune system of the host.

Methodology/principal Findings: Blood was sampled within the first two days of the presentation of signs of infection from 10 healthy volunteers; from 18 cases of flu-like syndrome; and from 31 cases of infection by H1N1 confirmed by reverse RT-PCR. Absolute counts of subtypes of monocytes and of lymphocytes were determined after staining with monoclonal antibodies and analysis by flow cytometry.

Effect of clarithromycin in patients with sepsis and ventilator-associated pneumonia.

Background: Because clarithromycin provided beneficiary nonantibiotic effects in experimental studies, its efficacy was tested in patients with sepsis and ventilator-associated pneumonia (VAP).

Methods: Two hundred patients with sepsis and VAP were enrolled in a double-blind, randomized, multicenter trial from June 2004 until November 2005. Clarithromycin (1 g) was administered intravenously once daily for 3 consecutive days in 100 patients; another 100 patients were treated with placebo.

The importance of fever as a predictive symptom for the potency of host's monocytes to release pro- and anti-inflammatory mediators.

Objective: To clarify whether time lapsing from advent of fever as a first sign of sepsis may be indicative of the potency of monocytes for the release of pro- and anti-inflammatory mediators.

Methods: Monocytes were isolated from blood of 51 septic patients and 9 healthy donors. Monocytes were incubated in the absence and presence of patients' serum and concentrations of tumour necrosis factor-alpha (TNF alpha), interleukin (IL)-6, IL-10, and malondialdehyde (MDA) were estimated in supernatants.

The impact of multidrug resistance on the pathogenicity of Escherichia coli: an experimental study.

Based on the controversial findings of clinical studies regarding the influence of multidrug resistance on mortality, 10 susceptible and 10 multidrug-resistant (MDR) and extended-spectrum beta-lactamase-producing isolates of Escherichia coli were applied to stimulate monocytes isolated from healthy donors. Immune mediators were estimated in supernatants. Four susceptible isolates (Group A) and four MDR isolates (Group B) were used to initiate acute pyelonephritis in 48 rabbits following inoculation of the pathogen into the right renal pelvis.

Early changes of CD4-positive lymphocytes and NK cells in patients with severe Gram-negative sepsis.

Introduction: Our aim was to define early changes of lymphocytes and of NK cells in severe sepsis and to correlate them with serum levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1).

Methods: Blood was sampled from 49 patients with proven highly suspected infection by Gram-negative pathogens, within 12 hours of the advent of severe sepsis, and was also sampled from six healthy volunteers. White blood cells were targeted with monoclonal antibodies and were analyzed by flow cytometry.

Multidrug resistance to antimicrobials as a predominant factor influencing patient survival.

The impact of multidrug resistance to antimicrobials was assessed in a cohort of 243 patients with microbiologically documented infections by a variety of susceptible and multidrug-resistant (MDR) species. Multidrug resistance was defined as resistance to more than two antimicrobial agents of different chemical structure. Cox regression analysis was performed to define differences and the significance of any predisposing factors.

Clarithromycin is an effective immunomodulator in experimental pyelonephritis caused by pan-resistant Klebsiella pneumoniae.

Objectives: To apply clarithromycin as an immunomodulatory treatment in experimental infection caused by pan-resistant Klebsiella pneumoniae.

Methods: Acute pyelonephritis was induced in 80 rabbits after inoculation of the test isolate in the renal pelvis. Rabbits were divided into eight groups, with 10 animals in each group.