18 research outputs found
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. Main outcomes were resolution of VAP, duration of mechanical ventilation, and sepsis-related mortality within 28 days. Results. The groups were well matched with regard to demographic characteristics, disease severity, pathogens, and adequacy of the administered antimicrobials. Analysis comprising 141 patients who survived revealed that the median time for resolution of VAP was 15.5 days and 10.0 days among placebo- and clarithromycin-treated patients, respectively (P=.011); median times for weaning from mechanical ventilation were 22.5 days and 16.0 days, respectively (P=.049). Analysis comprising all enrolled patients showed a more rapid decrease of the clinical pulmonary infection score and a delay for advent of multiple organ dysfunction in clarithromycin-treated patients, compared with those of placebo-treated patients (P=.047). Among the 45 patients who died of sepsis, time to death was significantly prolonged in clarithromycin-treated compared with placebo-treated patients (P=.004). Serious adverse events were observed in 0% and 3% of placebo- and clarithromycin-treated patients, respectively (P=.25). Conclusions. Clarithromycin accelerated the resolution of VAP and weaning from mechanical ventilation in surviving patients and delayed death in those who died of sepsis. The mortality rate at day 28 was not altered. Results are encouraging and render new perspectives on the management of sepsis and VA
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. Peripheral blood mononuclear cells (PBMCs) were isolated from patients and stimulated with various bacterial stimuli. Concentrations of tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-18, interferon (FN)-alpha and of IFN-gamma were estimated in supernatants by an enzyme immunoassay. Infection by H1N1 was accompanied by an increase of monocytes. PBMCs of patients evoked strong cytokine production after stimulation with most of bacterial stimuli. Defective cytokine responses were shown in response to stimulation with phytohemagglutin and with heat-killed Streptococcus pneumoniae. Adaptive immune responses of H1N1-infected patients were characterized by decreases of CD4-lymphocytes and of B-lymphocytes and by increase of T-regulatory lymphocytes (Tregs). CONCLUSIONS/SIGNIFICANCE: Infection by the H1N1 virus is accompanied by a characteristic impairment of the innate immune responses characterized by defective cytokine responses to S.pneumoniae. Alterations of the adaptive immune responses are predominated by increase of Tregs. These findings signify a predisposition for pneumococcal infections after infection by H1N1 influenza
Clarithromycin is an effective immunomodulator when administered late in experimental pyelonephritis by multidrug-resistant Pseudomonas aeruginosa
BACKGROUND: To apply clarithromycin as an immunomodulatory treatment in experimental urosepsis by multidrug-resistant Pseudomonas aeruginosa. METHODS: Acute pyelonephritis was induced in 40 rabbits after inoculation of the test isolate in the renal pelvis. Therapy was administered upon signs of sepsis in four groups: A, controls; B, intravenous clarithromycin; C, amikacin; and D, both agents. Survival and vital signs were recorded; blood was sampled for culture and estimation of pro-inflammatory mediators; monocytes were isolated for determination of apoptotic rate and ex vivo TNFα secretion. Quantitative cultures and biopsies of organs were performed after death. RESULTS: Increased rectal temperature and oxygen saturation were found in groups B and D compared to A and C. Mean survival of groups A, B, C and D was 2.65, 7.15, 4.25 and 8.70 days respectively. No differences were noted between groups concerning bacterial load in blood and tissues and serum endotoxins. Serum MDA and total caspase-3 activity of monocytes of group D decreased following treatment compared to other groups. Negative correlation was detected between cytoplasmic caspase-3 and ex vivo secretion of TNFα of blood monocytes of group A; similar correlation was not found for any other group. Pathology scores of liver and lung of group B were lower than group A. CONCLUSION: Clarithromycin administered late in experimental urosepsis by multidrug-resistant P. aeruginosa prolonged survival and ameliorated clinical findings. Its effect is probably attributed to immunomodulatory intervention on blood monocytes
Role of soluble triggering receptor expressed on myelold cells in inflammatory bowel disease
AIM: To investigate the probable role of soluble triggering receptor
expressed on myeloid cells-1 (sTREM-1) in the pathogenesis of
inflammatory bowel disease (IBD).
METHODS: Fifty-eight patients were enrolled; nineteen healthy volunteers
served as controls; 8 patients were diagnosed with Crohn’s disease, and
31 with ulcerative colitis. Clinical and endoscopic activity indexes of
patients with Crohn’s disease and ulcerative colitis respectively were
estimated. Upon admission blood was sampled; sTREM-1 and TNF alpha were
measured by an immunoassay and malondialdehyde (MDA) by the
thiobarbitourate assay, after passage through an HPLC system.
RESULTS: Median SE of TNFa of controls, patients with Crohn’s disease
and patients with ulcerative colitis were 6.02 +/- 3.94, 7.98 +/- 5.08
(P = NS vs controls), and 8.45 +/- 4.15 ng/L (P = 0.018 vs controls)
respectively. Respective values of sTREM-1 were 53.31 +/- 32.93, 735.10
+/- 197.17 (P = 0.008 vs controls) and 435.82 +/- 279.71 ng/L (P = 0.049
vs controls). sTREM-1 was positively correlated with Crohn’s disease
activity index and clinical and endoscopic activity indexes of
ulcerative colitis (P = 0.002, 0.001 and 0.009, respectively). sTREM-1
of patients with ulcerative colitis was positively correlated with TNF
alpha (P = 0.001).
CONCLUSION: sTREM-1 seems to behave as a novel mediator in IBD in
correlation with the degree of the :inflammatory reaction of the
intestinal mucosa. 2006 The WIG Press. All rights reserved
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.
Results: The frequency of the -238 A allele was significantly greater
among patients than among controls. Viral pneumonia developed in 20 of
96 non-carriers of at least one -238 A allele (20.8%) and in seven of
13 carriers of at least one -238 A allele (53.8%, p = 0.016). Logistic
regression analysis showed that the most important factors associated
with the development of pneumonia were the presence of an underlying
disease (p = 0.021, odds ratio (OR) 3.08) and the carriage of at least
one -238 A allele (p = 0.041, OR 3.74). Gene transcripts of the TNF gene
were greater among non-carriers of the -238 A allele than among carriers
of the -238 A allele.
Conclusions: The -238 A SNP allele of the TNF gene imposes on the course
of 2009 H1N1 virus infection and is an independent risk factor for
pneumonia. (C) 2012 International Society for Infectious Diseases.
Published by Elsevier Ltd. All rights reserved
Oleuropein: A novel immunomodulator conferring prolonged survival in experimental sepsis by Pseudomonas aeruginosa
Oleuropein, a novel immunomodulator derived from olive tree, was
assessed in vitro and in experimental sepsis by Pseudomonas aeruginosa.
After addition in monocyte and neutrophil cultures, malondialdehyde,
TNF-alpha, IL-6, and bacterial counts were estimated in supernatants.
Acute pyelonephritis was induced in 70 rabbits after inoculation of
pathogen in the renal pelvis. Intravenous therapy was administered in
four groups postchallenge by one multidrug-resistant isolate (A,
controls; B, oleuropein; C, amikacin; D, both agents) and in three
groups postchallenge by one susceptible isolate (E, controls; F,
oleuropein; G, amikacin). Survival was recorded; bacterial growth in
blood and organs was counted; endotoxins (LPS), malondialdehyde, total
antioxidant status, and TNF-alpha in serum were estimated. TNF-alpha and
IL-6 of cell supernatants were not increased compared with controls when
triggered by LPS and P. aeruginosa. Counts of multidrug-resistant P.
aeruginosa were decreased in monocyte supernatants. Median survival of
groups A, B, C, D, E, F, and G were 3.00, 6.00, 2.00, 10.00, 1.00, 5.00,
and 1.00 days, respectively. Bacteria in blood were lower at 48 h in
groups B and D compared with A and in groups F and G compared with E.
Total antioxidant status decreased steadily overtime in groups A, C, D,
and G, but not in groups B and F. TNF-alpha of groups B, C, and D was
lower than A at 48 h. Tissue bacteria decreased in group F compared with
E. Oleuropein prolonged survival in experimental sepsis probably by
promoting phagocytosis or inhibiting biosynthesis of proinflammatory
cytokines
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. Main outcomes were resolution of VAP, duration of
mechanical ventilation, and sepsis-related mortality within 28 days.
Results. The groups were well matched with regard to demographic
characteristics, disease severity, pathogens, and adequacy of the
administered antimicrobials. Analysis comprising 141 patients who
survived revealed that the median time for resolution of VAP was 15.5
days and 10.0 days among placebo-and clarithromycin-treated patients,
respectively (P = .011); median times for weaning from mechanical
ventilation were 22.5 days and 16.0 days, respectively (P = .049).
Analysis comprising all enrolled patients showed a more rapid decrease
of the clinical pulmonary infection score and a delay for advent of
multiple organ dysfunction in clarithromycin-treated patients, compared
with those of placebo-treated patients (P = .047). Among the 45 patients
who died of sepsis, time to death was significantly prolonged in
clarithromycin-treated compared with placebo-treated patients (P =
.004). Serious adverse events were observed in 0% and 3% of
placebo-and clarithromycin-treated patients, respectively (P = .25).
Conclusions. Clarithromycin accelerated the resolution of VAP and
weaning from mechanical ventilation in surviving patients and delayed
death in those who died of sepsis. The mortality rate at day 28 was not
altered. Results are encouraging and render new perspectives on the
management of sepsis and VAP