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ABSTRACT: Evidence from a recent randomized study of our group suggests that intravenous clarithromycin resulted in earlier resolution of ventilator-associated pneumonia. The need to understand the mechanism of action of clarithromycin guided to the study of a model of experimental empyema by multidrug-resistant Pseudomonas aeruginosa in 40 rabbits. Animals were randomized into controls (group A); treatment with clarithromycin (group B); treatment with piperacillin/tazobactam (group C); and treatment with both agents (group D). Pleural fluid was collected at regular time intervals for quantitative culture, estimation of cell apoptosis and of concentrations of tumour necrosis factor-alpha (TNFα). After 7 days, animals were euthanized for estimation of tissue growth. Bacterial growth in the pleural fluid of group D was significantly decreased compared with the other groups on day 5. Lung growth of group D was lower than group A. That was also the case of cytokine stimulation by pleural fluid samples on U937 monocytes. It is concluded that administration of clarithromycin enhanced the antimicrobial efficacy of piperacillin/tazobactam and decreased bacterial growth in the pleural fluid and in tissues. It also attenuated the pro-inflammatory phenomena induced by the β-lactam.
Apmis 05/2013; · 1.99 Impact Factor
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ABSTRACT: We evaluated the efficacy of tigecycline in a rabbit model of experimental endocarditis caused by a linezolid resistant, clinical strain of Enterococcus faecium. Tigecycline-treated animals had a 2.8 log10 cfu/g reduction in microbial counts in excised vegetations compared with controls. Addition of gentamicin caused a further arithmetical reduction in colony counts. Therapeutic effect was sustained five days after completion of treatment, as shown by relapse studies performed in treatment groups.
Antimicrobial Agents and Chemotherapy 04/2013; · 4.84 Impact Factor
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ABSTRACT: Introduction Recent evidence suggests a link between excess lipid peroxidation and specific organ failures in sepsis. No study has ever been performed in sepsis by multidrug-resistant (MDR) Gram-negative bacteria. Methods Lethal sepsis was induced in rats by the intraperitoneal injection of one MDR isolate of Pseudomonas aeruginosa. Produced malondialdehyde (MDA) was measured in tissues five hours after bacterial challenge with the thiobarbiturate assay followed by HPLC analysis. Results were compared with those coming from a cohort of patients with ventilator-associated pneumonia (VAP) and sepsis by MDR Gram-negative bacteria. More precisely, serum MDA was measured on seven consecutive days and it was correlated with clinical characteristics. Results MDA of septic rats was greater in the liver, spleen and aortic wall and it was lower in the right kidney compared to sham-operated animals. Findings were confirmed by the studied cohort. Circulating MDA was greater in patients with hepatic dysfunction and acute respiratory distress syndrome (ARDS) compared with patients without any organ failures. The opposite was found for patients with acute renal dysfunction. No differences were found between patients with ARDS without or with cardiovascular (CV) failure and patients without any organ failure. Serial measurements of MDA in serum of patients indicated that levels of MDA were greater in survivors from hepatic dysfunction and ARDS and lower in survivors from acute renal dysfunction. Conclusions Animal findings and results of human sepsis are complementary and they suggest for a compartmentalization of lipid peroxidation in systemic infections by MDR Gram-negative bacteria.
Critical care (London, England) 01/2013; 17(1):R6. · 4.61 Impact Factor
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ABSTRACT: The present study focused on the impact of methicillin resistance of Staphylococcus aureus on cytokine production by monocytes. Cytokine stimulation was studied by 20 heat-killed isolates, 10 methicillin-susceptible Staphylococcus aureus (MSSA) and 10 methicillin-resistant Staphylococcus aureus (MRSA). Bacterial endocarditis was induced in 27 male rabbits by challenge with 1 MSSA isolate and 1 MRSA isolate. Blood was sampled for estimation of tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA) and stimulation of monocytes. MSSA induced greater stimulation of TNF-α than MRSA, as shown after addition of a Toll-like receptor-4 (TLR4) antagonist. Survival of rabbits challenged by MRSA was prolonged compared to those challenged by MSSA. Serum MDA was greater after MSSA stimulation. Serum of animals challenged by MRSA stimulated greater release of interleukin (IL)-8 and IL-10 compared with MSSA: the opposite was observed for TNF-α. It is concluded that MSSA and MRSA induce a different pattern of TNF-α stimulation through a TLR4-independent mechanism, leading to shorter survival in experimental endocarditis.
Journal of Infection and Chemotherapy 10/2012; · 1.80 Impact Factor
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Ira-Maria Tzepi,
Evangelos J Giamarellos-Bourboulis,
Dionyssia-Pinelopi Carrer, Thomas Tsaganos,
Ralf A Claus,
Ilia Vaki,
Aimilia Pelekanou,
Antigone Kotsaki,
Vassiliki Tziortzioti,
Stavros Topouzis,
Michael Bauer,
Andreas Papapetropoulos
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ABSTRACT: Levels of circulating angiopoietin-2 (Ang-2) increase in sepsis, raising the possibility that Ang-2 acts as a modulator in the sepsis cascade. To investigate this, experimental sepsis was induced in male C57BL6 mice by a multidrug-resistant isolate of Pseudomonas aeruginosa; survival was determined along with neutrophil tissue infiltration and release of proinflammatory cytokines. Survival was significantly increased either by pretreatment with recombinant Ang-2 2 h before or treatment with recombinant Ang-2 30 min after bacterial challenge. Likewise, Ang-2 pretreatment protected against sepsis-related death elicited by Escherichia coli; however, Ang-2 failed to provide protection in lipopolysaccharide (LPS)-challenged mice. The survival advantage of Ang-2 in response to P. aeruginosa challenge was lost in tumor necrosis factor (TNF)-deficient mice or neutropenic mice. Infiltration of the liver by neutrophils was elevated in the Ang-2 group compared with saline-treated animals. Serum TNF-α levels were reduced by Ang-2, whereas those of interleukin (IL)-6 and IL-10 remained unchanged. This was accompanied by lower release of TNF-α by stimulated splenocytes. When applied to U937 cells in vitro, heat-killed P. aeruginosa induced the secretion of IL-6 and TNF-α; low levels of exogenous TNF-α synergized with P. aeruginosa. This synergistic effect was abolished after the addition of Ang-2. These results put in evidence a striking protective role of Ang-2 in experimental sepsis evoked by a multidrug-resistant isolate of P. aeruginosa attributed to modulation of TNF-α production and changes in neutrophil migration. The protective role of Ang-2 is shown when whole microorganisms are used and not LPS, suggesting complex interactions with the host immune response.
Journal of Pharmacology and Experimental Therapeutics 08/2012; 343(2):278-87. · 3.83 Impact Factor
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Aikaterini Spyridaki,
Maria Raftogiannis,
Anastasia Antonopoulou, Thomas Tsaganos,
Christina Routsi,
Fotini Baziaka,
Vassiliki Karagianni,
Maria Mouktaroudi,
Pantelis Koutoukas,
Aimilia Pelekanou,
Anastasia Kotanidou,
Stylianos E Orfanos,
Jos W M van der Meer,
Mihai G Netea,
Evangelos J Giamarellos-Bourboulis
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ABSTRACT: 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. The concentrations of circulating markers were measured. Monocytes and neutrophils were isolated for immunophenotyping analysis and for cytokine stimulation. The ratio of serum interleukin-10 (IL-10) to serum tumor necrosis factor alpha (TNF-α) was decreased in the clarithromycin group compared with the results in the placebo group. Apoptosis of monocytes was significantly increased on day 4 in the clarithromycin group compared with the rate of apoptosis in the placebo group. On the same day, the expression of CD86 was increased and the ratio of soluble CD40 ligand (sCD40L) to CD86 in serum was unchanged. The release of TNF-α, IL-6, and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) by circulating monocytes after stimulation was greater in the clarithromycin group than in the placebo group. The expression of TREM-1 on monocytes was also increased in the former group. These effects were pronounced in patients with septic shock and MODS. These results suggest that the administration of clarithromycin restored the balance between proinflammatory versus anti-inflammatory mediators in patients with sepsis; this was accompanied by more efficient antigen presentation and increased apoptosis. These effects render new perspectives for the immunotherapy of sepsis.
Antimicrobial Agents and Chemotherapy 05/2012; 56(7):3819-25. · 4.84 Impact Factor
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Anastasia Antonopoulou,
Fotini Baziaka, Thomas Tsaganos,
Maria Raftogiannis,
Pantelis Koutoukas,
Aikaterini Spyridaki,
Maria Mouktaroudi,
Antigone Kotsaki,
Athina Savva,
Marianna Georgitsi,
Evangelos J Giamarellos-Bourboulis
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ABSTRACT: 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.
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.
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.
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.
International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 03/2012; 16(3):e204-8. · 2.17 Impact Factor
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ABSTRACT: Severe trauma induces systemic inflammatory response syndrome (SIRS) through the release of proinflammatory mediators. Angiopoietin-2 (Ang-2) is over-produced in sepsis and leads to dysfunction of endothelial cells and subsequent multiple organ dysfunction. In order to define the role of Ang-2 in lethal injury, 45 rabbits were studied; eight were administered anesthesia; 11 were sham-operated and 26 were subject to femoral injury. Concentrations of Ang-2, malondialdehyde (MDA), tumor necrosis factor-alpha (TNFα) and endotoxins (LPS) were determined in serum and of Ang-2 in tissues; vital signs and overall survival were recorded. Bacterial growth was quantitatively assessed in liver, spleen and lung of animal that died. Survival of injured animals was shorter than sham operated ones. Serum concentrations of Ang-2 at 4 h was greater among animals where death supervened early, i.e. within 48 h after injury than among rabbits that died later. That was also the case for systolic, diastolic and mean arterial pressures. Serum MDA and TNFα and tissue bacterial growth did not differ between rabbits that died early and rabbits that died late. Serum LPS remained below the limit of detection. These results suggest that circulating Ang-2 participates in the pathogenesis of SIRS after injury connected with early haemodynamic instability.
Cytokine 12/2011; 56(3):817-22. · 3.02 Impact Factor
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ABSTRACT: Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) participates in the inflammatory process.
To describe changes of sTREM-1 in the serum after hemiarthroplasty (HA) and total hip arthroplasty (THA).
Serial blood samples were drawn from 122 patients with hip fracture. Interleukin-6 (IL-6), sTREM-1, and C-reactive protein (CRP) were measured. Results: IL-6 and CRP were similarly increased after both HA and THA. sTREM-1 was increased early in HA and late after THA. The only parameter that was higher among patients who developed systemic inflammatory response syndrome was IL-6.
Kinetics of sTREM-1 differs among patients undergoing HA of the hip and those undergoing THA.
Biomarkers 09/2011; 16(7):600-4. · 2.21 Impact Factor
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Athina Savva,
Maria Raftogiannis,
Fotini Baziaka,
Christina Routsi,
Anastasia Antonopoulou,
Pantelis Koutoukas, Thomas Tsaganos,
Anastasia Kotanidou,
Efterpi Apostolidou,
Evangelos J Giamarellos-Bourboulis,
George Dimopoulos
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ABSTRACT: 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. suPAR and PCT were measured in serum by an enzyme immunoassay and an immuno-time-resolved amplified cryptate assay respectively. Neutrophils and monocytes were isolated on day 1 and incubated. suPAR levels greater than 10.5 ng/ml had 80% specificity and 77.6% positive predictive value to discriminate between severe sepsis and sepsis. suPAR levels greater than 12.9 ng/ml had 80% specificity and 76.1% positive predictive value for prognosis of unfavorable outcome. suPAR levels were significantly lower among survivors than among non-survivors over follow-up. Step-wise Cox regression analysis found suPAR as an independent factor related with unfavorable outcome (p: 0.026). Concentrations of suPAR in supernatants of neutrophils of patients with sepsis were greater compared to controls. It is concluded that suPAR is a reliable marker of sepsis severity and a strong independent predictor of unfavorable outcome in VAP and sepsis. Neutrophils are involved in release.
The Journal of infection 08/2011; 63(5):344-50. · 4.13 Impact Factor
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ABSTRACT: Pseudomonas aeruginosa is a cause of infections of the lower respiratory tract among patients with chronic lung disorders. It is questionable whether virulence of this species may be influenced by multidrug resistance (MDR).
To define the impact of MDR in experimental lung infection.
Experimental empyema was induced in rabbits by MDR (group A, n = 16) and by susceptible isolates (group B, n = 10). Pleural fluid was sampled for quantitative culture and estimation of cell apoptosis and of tumor necrosis factor-alpha (TNFα) and malondialdehyde (MDA). Survival was recorded. Cytokine production was stimulated in U937 monocytes by samples of pleural fluid. Whole blood of rabbits was incubated with the isolates; induction of apoptosis was assessed.
Survival of group A was prolonged compared to group B. This was accompanied by lower bacterial counts of the inoculated pathogens in pleural fluid and in the lungs of group A compared with group B. Early apoptosis of neutrophils of pleural fluid of group A was lower compared with group B. Pleural fluid concentrations of TNFα and MDA did not differ between the groups. Cytokine production by U937 monocytes after stimulation with pleural fluid was greater in group B than in group A. The susceptible isolate induced apoptosis of neutrophils in vitro at a greater rate than the MDR isolate.
Experimental empyema by susceptible P. aeruginosa is accompanied by greater mortality compared with MDR P. aeruginosa. This phenomenon may be attributed to the different growth pattern of the pathogens or to their interaction with the innate immune system.
Respiration 01/2011; 82(1):46-53. · 2.26 Impact Factor
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ABSTRACT: Although metallo-β-lactamases (MBLs) hydrolyse most β-lactams, including carbapenems, MBL-producing Enterobacteriaceae very often remain susceptible to carbapenems in vitro. We studied the in vivo efficacy of imipenem, meropenem, ertapenem and aztreonam against a carbapenem-susceptible MBL-producing clinical Escherichia coli strain in a rabbit intra-abdominal abscess model.
Rabbits were inoculated intraperitoneally with 10(8) cfu/mL of VIM-1-positive E. coli and were assigned to receive no treatment (controls) or intravenous imipenem/cilastatin (imipenem) 70 mg/kg/12 h or meropenem 125 mg/kg/12 h or ertapenem 60 mg/kg/12 h or aztreonam 70 mg/kg/12 h. Dosing regimens were chosen on the basis of preliminary pharmacokinetic studies so that T(>MIC) was achieved for ≥50% of the dosing interval for all tested antibiotics. A total of eight doses were administered before sacrifice and the abscesses were harvested and quantitatively cultured.
MICs of imipenem, meropenem, ertapenem and aztreonam for the infecting isolate were 1, ≤0.25, 1.5 and ≤0.25 mg/L, respectively. The log(10) cfu/g (mean ± SD) viable counts in pus were as follows: controls (n = 16), 8.71 ± 1.34 (P < 0.001 versus all other groups); imipenem (n = 15), 4.89 ± 2.42; meropenem (n = 15), 4.24 ± 2.44; ertapenem (n = 16), 3.17 ± 1.85 (P = 0.022 versus imipenem); and aztreonam (n = 15), 3.62 ± 3.05. Mortality among treated rabbits was significantly reduced compared with controls. Four animals in the aztreonam group (26.7%) had culture-negative pus and no mortality was noted among aztreonam-treated animals.
In the rabbit experimental model, carbapenems were shown to be effective in the treatment of intra-abdominal infection due to an extended-spectrum β-lactamase-negative carbapenem-susceptible VIM-1-producing clinical E. coli strain, but treatment with aztreonam resulted in a more favourable outcome overall.
Journal of Antimicrobial Chemotherapy 12/2010; 66(3):611-7. · 5.07 Impact Factor
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ABSTRACT: In an attempt to define the efficacy of intravenously administered n-3 polyunsaturated fatty acids (PUFAs) in an animal model of lethal trauma following femur fracture, an intravenous solution of eicosapentanoic acid (EPA) - one n-3 PUFA - was administered in 25 rabbits; 13 were controls and 12 were treated with EPA 30 min after fracture. Vital signs were recorded and serum concentrations of tumor necrosis factor-alpha (TNFalpha) and respiratory burst of neutrophils were assessed. Survival of controls was 7.7% and of animals treated with EPA 50% (log-rank: 5.162; p: 0.023). Vital signs of both groups did not differ. Oxidative burst of neutrophils was greater among EPA-treated animals compared with controls at 48 h (p: 0.010). Serum levels of TNFalpha of the former group were decreased compared with the latter at 48 h (p: 0.019). Bacterial growth of enterobacteriaceae from liver and spleen after death or euthanasia was lower among EPA-treated rabbits than controls. These results suggest that EPA possesses considerable immunomodulatory activities improving survival in a model of lethal trauma. Restoration of oxidative burst conferring efficient phagocytosis of evading bacteria seems the most probable mechanism of action.
Prostaglandins Leukotrienes and Essential Fatty Acids 08/2010; 83(2):69-74. · 3.37 Impact Factor
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Charalambos Gogos,
Antigone Kotsaki,
Aimilia Pelekanou,
George Giannikopoulos,
Ilia Vaki,
Panagiota Maravitsa,
Stephanos Adamis,
Zoi Alexiou,
George Andrianopoulos,
Anastasia Antonopoulou, [......],
Aikaterini Spyridaki,
Ioannis Strouvalis, Thomas Tsaganos,
George Zografos,
Konstantinos Mandragos,
Phylis Klouva-Molyvdas,
Nina Maggina,
Helen Giamarellou,
Apostolos Armaganidis,
Evangelos J Giamarellos-Bourboulis
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ABSTRACT: 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.
The statuses of the innate and adaptive immune systems were prospectively compared in 505 patients. Whole blood was sampled within less than 24 hours of advent of sepsis; white blood cells were stained with monoclonal antibodies and analyzed though a flow cytometer.
Expression of HLA-DR was significantly decreased among patients with severe sepsis/shock due to acute pyelonephritis and intraabdominal infections compared with sepsis. The rate of apoptosis of natural killer (NK) cells differed significantly among patients with severe sepsis/shock due to ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) compared with sepsis. The rate of apoptosis of NKT cells differed significantly among patients with severe sepsis/shock due to acute pyelonephritis, primary bacteremia and VAP/HAP compared with sepsis. Regarding adaptive immunity, absolute counts of CD4-lymphocytes were significantly decreased among patients with severe sepsis/shock due to community-acquired pneumonia (CAP) and intraabdominal infections compared with sepsis. Absolute counts of B-lymphocytes were significantly decreased among patients with severe sepsis/shock due to CAP compared with sepsis.
Major differences of the early statuses of the innate and adaptive immune systems exist between sepsis and severe sepsis/shock in relation to the underlying type of infection. These results may have a major impact on therapeutics.
Critical care (London, England) 01/2010; 14(3):R96. · 4.61 Impact Factor
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ABSTRACT: A synthetic crystallic semihydrate form of calcium sulfate, Stimulan, was evaluated as a biodegradable carrier for the daily in vitro elution of daptomycin. Daptomycin and Stimulan were admixed at a ratio of 95:5. Elution lasted for 28 days. Eluted concentrations peaked on days 1 and 11, when the mean values were 1,320.1 and 949.2 microg/ml, respectively. The lowest eluted concentration was detected on day 28. These results support the application of the system described in experimental models of osteomyelitis.
Antimicrobial Agents and Chemotherapy 05/2009; 53(7):3106-7. · 4.84 Impact Factor
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ABSTRACT: Mechanical ventilation and administration of a high oxygen concentration are simultaneously used in the management of respiratory failure. We conducted this study to evaluate the effect of a high inspired oxygen concentration on ventilator-induced lung injury.
Forty sets of isolated/perfused rabbit lungs were randomized for 60 min of pressure-control ventilation at a plateau inspiratory pressure of 25 or 15 cm H(2)O and positive end-expiratory pressure of 3 cm H(2)O while receiving 100% or 21% O(2). The temperature, pH, and partial pressure of CO(2) in the perfusate were maintained the same in all groups (n = 10 for each group). The outcome measures used to assess lung injury included: the change in weight gain and ultrafiltration coefficient, the frequency of vascular failure, the histological lesions and the concentration of tumor necrosis factor-alpha and malondialdehyde in the bronchoalveolar lavage fluid.
The two groups ventilated at the higher inspiratory pressure/tidal volume experienced greater weight gain and increases in the ultrafiltration coefficient, more frequently suffered vascular failure, and presented higher composite scores of histological damage than the two groups ventilated at the lower inspiratory pressure/tidal volume. Hyperoxia was not found to further increase any of the monitored markers of lung injury. No difference was noticed among the four experimental groups in the alveolar lavage fluid levels of tumor necrosis factor-alpha or malondialdehyde.
These findings suggest that short-term administration of a high oxygen concentration is not a major determinant of ventilator-induced lung injury in this experimental model.
Anesthesia and analgesia 03/2009; 108(2):556-64. · 3.08 Impact Factor
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ABSTRACT: The characteristics of cancellous bone allografts as carriers of moxifloxacin are described. Particles of cancellous bone were compressed into a wire-mesh cylinder and impregnated into a solution of moxifloxacin for different time periods. Five replicas were impregnated for 1 h; another five for 24 h; and another five for 48 h. Impregnated allografts were then transferred into vials containing 5 ml of Mueller-Hinton broth and incubated at 37 degrees C. Broth was replaced daily. Concentrations of moxifloxacin in broth were determined after analysis by an high performance liquid chromatography system. Moxifloxacin was eluted at very high concentrations within the first days. Concentrations remained above 100 microg/ml until day 8 and above 40 microg/ml until day 20. It is concluded that cancellous bone allografts may allow the adequate in vitro elution of moxifloxacin. The latter results support their application in experimental models of osteomyelitis.
Journal of Biomedical Materials Research Part A 02/2009; 92(1):52-5. · 2.63 Impact Factor
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ABSTRACT: The objectives of this study were to assess the efficacy of a synthetic semihydrate form of calcium sulphate (Stimulan) in experimental bone infection caused by methicillin-resistant Staphylococcus aureus (MRSA). Osteomyelitis was induced after inoculation of the test pathogen in the left tibia of 72 New Zealand rabbits assigned to the following groups: 18 control rabbits (Group A); 18 rabbits with Stimulan implanted (Group B); and 36 rabbits with moxifloxacin-impregnated Stimulan implanted (Group C). Rabbits were sacrificed at weekly intervals and cancellous bone was harvested for histopathology and for estimation of bacterial growth and concentrations of moxifloxacin. Bacterial growth from cancellous bone of Group C was significantly lower than the respective growth of Groups A and B on all days of sacrifice. The main histological finding of animals in all three groups was a moderate to intense inflammatory reaction accompanied by fibrosis. The degree of fibrosis was higher in Group C compared with both other groups. Infiltration by giant cells was also observed, which was greater in Group C on Day 42. Antibiotic levels in bone were higher for bone samples closer to the site of implantation. In conclusion, Stimulan admixed with 10% moxifloxacin was very effective in achieving complete eradication of the causative pathogen in experimental osteomyelitis caused by MRSA.
International journal of antimicrobial agents 01/2009; 33(4):354-9. · 3.03 Impact Factor
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Evangelos J Giamarellos-Bourboulis,
Maria Raftogiannis,
Anastasia Antonopoulou,
Fotini Baziaka,
Pantelis Koutoukas,
Athina Savva,
Theodora Kanni,
Marianna Georgitsi,
Aikaterini Pistiki, Thomas Tsaganos, [......],
Efthymia Giannitsioti,
Dimitra Kavatha,
Flora Kontopidou,
Maria Mouktaroudi,
Garyfallia Poulakou,
Vissaria Sakka,
Periklis Panagopoulos,
Antonios Papadopoulos,
Kyriaki Kanellakopoulou,
Helen Giamarellou
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ABSTRACT: 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.
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).
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.
PLoS ONE 01/2009; 4(12):e8393. · 4.09 Impact Factor
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ABSTRACT: To evaluate the ex vivo immunomodulatory properties of moxifloxacin, we applied serum and cerebrospinal fluid (CSF) samples from 50 patients who received a single oral dose of 400 mg. Patients were divided into 5 groups according to time lapsing between sampling and drug intake: group I, 0.5 to 1 h; group II, 1 to 2 h; group III, 2 to 4 h; group IV, 4 to 6 h; and group V, 6 to 8 h. Samples were added to cultures of U937 monocytes stimulated by 10 ng/mL of lipopolysaccharide (LPS) and 1 x 10(5) colony-forming unit (CFU) of 1 heat-killed penicillin-resistant isolate of Streptococcus pneumoniae. Concentrations of cytokines were estimated in supernatants. Concentrations of interleukin (IL)-1beta, IL-10, and IL-12 released after stimulation by LPS were significantly decreased by CSF of groups I, IV, and V. After stimulation by the heat-killed isolate, concentrations of tumor necrosis factor alpha (TNF-alpha), IL-1beta, IL-6, and IL-10 were increased in the presence of CSF of group III; those of IL-12p70 were decreased by CSF of groups I and II. Concentrations of IL-1beta, IL-6, and IL-8 drawn after stimulation by LPS were significantly decreased upon addition of serum from all groups. After stimulation by the heat-killed isolate, concentrations of TNF-alpha were decreased by serum drawn from all patients; IL-1beta was increased after addition of serum of groups I, II, and V. It is concluded that CSF and serum of patients administered moxifloxacin may effectively modulate the production of pro- and anti-inflammatory cytokines by human monocytes. These results render new perspectives for the therapy for meningitis.
Diagnostic microbiology and infectious disease 12/2008; 63(1):62-9. · 2.45 Impact Factor
