Curcumin attenuates staphylococcus aureus-induced acute lung injury.

INTRODUCTION: Curcumin has remarkable anti-inflammatory and antioxidant properties. However, its effects on bacterium-induced acute lung injury (ALI) are not fully understood. OBJECTIVE: To investigate the protective effects of curcumin on a mouse model of S. aureus-induced ALI. METHODS: Mice were pretreated with intraperitoneal injection of curcumin or vehicle 2 h before Staphylococcus aureus instillation. The survival rate and bacterial burden after infection were recorded. Mice were sacrificed for the analyses of severity of pneumonia, integrity of lung barrier, disorder of coagulation cascades and extent of inflammation 12 h postinfection. The production of proinflammatory cytokines and chemokines in the lung and bronchoalveolar lavage fluid was detected. RESULTS: Pretreatment with curcumin markedly attenuated S. aureus-induced pneumonia, barrier disruption, lung edema and vascular leakage. Activation of plasminogen activator inhibitor-1 and infiltration of neutrophils were reduced by curcumin, together with lower levels of proinflammatory cytokines and chemokines. CONCLUSION: Curcumin can alleviate S. aureus-induced ALI through multiple pathways.

Selective V(1a) agonism attenuates vascular dysfunction and fluid accumulation in ovine severe sepsis.

Vasopressin analogs are used as a supplement to norepinephrine in septic shock. The isolated effects of vasopressin agonists on sepsis-induced vascular dysfunction, however, remain controversial. Because V(2)-receptor stimulation induces vasodilation and procoagulant effects, a higher V(1a)- versus V(2)-receptor selectivity might be advantageous. We therefore hypothesized that a sole, titrated infusion of the selective V(1a)-agonist Phe(2)-Orn(8)-Vasotocin (POV) is more effective than the mixed V(1a)-/V(2)-agonist AVP for the treatment of vascular and cardiopulmonary dysfunction in methicillin resistant staphylococcus aureus pneumonia-induced, ovine sepsis. After the onset of hemodynamic instability, awake, chronically instrumented, mechanically ventilated, and fluid resuscitated sheep were randomly assigned to receive continuous infusions of either POV, AVP, or saline solution (control; each n = 6). AVP and POV were titrated to maintain mean arterial pressure above baseline - 10 mmHg. When compared with that of control animals, AVP and POV reduced neutrophil migration (myeloperoxidase activity, alveolar neutrophils) and plasma levels of nitric oxide, resulting in higher mean arterial pressures and a reduced vascular leakage (net fluid balance, chest and abdominal fluid, pulmonary bloodless wet-to-dry-weight ratio, alveolar and septal edema). Notably, POV stabilized hemodynamics at lower doses than AVP. In addition, POV, but not AVP, reduced myocardial and pulmonary tissue concentrations of 3-nitrotyrosine, VEGF, and angiopoietin-2, thereby leading to an abolishment of cumulative fluid accumulation (POV, 9 ± 15 ml/kg vs. AVP, 110 ± 13 ml/kg vs. control, 213 ± 16 ml/kg; P < 0.001 each) and an attenuated cardiopulmonary dysfunction (left ventricular stroke work index, PaO(2)-to-FiO(2) ratio) versus control animals. Highly selective V(1a)-agonism appears to be superior to unselective vasopressin analogs for the treatment of sepsis-induced vascular dysfunction.

Prompt and successful toxin-targeting treatment of three patients with necrotizing pneumonia due to Staphylococcus aureus strains carrying the Panton-Valentine leukocidin genes.

Three patients with extensive necrotizing pneumonia due to Panton-Valentine leukocidin-positive Staphylococcus aureus strains and with aggravating factors (leukopenia count of less than 3x10(9)/liter in all three cases and hemoptysis in two cases) were successfully treated with toxin-suppressing agents introduced rapidly after hospital admission.

Efficacy of quinupristin-dalfopristin against methicillin-resistant Staphylococcus aureus and vancomycin-insensitive S. aureus in a model of hematogenous pulmonary infection.

BACKGROUND: Quinupristin-dalfopristin (Q-D) is a mixture of quinupristin and dalfopristin, which are semisynthetic antibiotics of streptogramin groups B and A, respectively. METHODS: We compared the effect of Q-D to that of vancomycin (VCM) in murine models of hematogenous pulmonary infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and VCM-insensitive S. aureus (VISA). RESULTS: Treatment with Q-D resulted in a significant decrease in the number of viable bacteria in the lungs of mice in an MRSA infection model [Q-D 100 mg/kg, Q-D 10 mg/kg, VCM and control (mean +/- SEM): 2.99 +/- 0.44, 6.38 +/- 0.32, 5.75 +/- 0.43 and 8.40 +/- 0.14 log10 CFU/lung, respectively]. Compared with VCM, high-dose Q-D significantly reduced the number of bacteria detected in the VISA hematogenous infection model [Q-D 100 mg/kg, Q-D 10 mg/kg, VCM and control (mean +/- SEM): 5.17 +/- 0.52, 7.03 +/- 0.11, 7.10 +/- 0.49 and 7.18 +/- 0.36 log10 CFU/lung, respectively]. Histopathological examination confirmed the effect of Q-D. CONCLUSION: Our results suggest that Q-D is potent and effective in the treatment of MRSA and VISA hematogenous pulmonary infections.

Ventilator-associated pneumonia by Staphylococcus aureus. Comparison of methicillin-resistant and methicillin-sensitive episodes.

All episodes of ventilator-associated pneumonia (VAP) caused by Staphylococcus aureus were prospectively analyzed for a 30-mo period. Methicillin-sensitive S. aureus (MSSA) was isolated in 38 episodes and methicillin-resistant S. aureus (MRSA) in 11 others. The two groups were similar regarding sex, severity of underlying diseases, prior surgery, and presence of renal failure, diabetes, cardiopathy, and coma. MRSA-infected persons were more likely to have received steroids before developing infection (relative risk [RR] = 3.45, 95% confidence interval [CI] = 1.38-8.59), to have been ventilated > 6 d (RR = 2.03, 95% CI = 1.36-3.03), to have been older than 25 yr (RR = 1.50, 95% CI = 1.09-2.06), and to have had preceding chronic obstructive pulmonary disease (RR = 2.76, 95% CI = 0.89-8.56) than MSSA-infected patients. MSSA-infected persons were more likely than MRSA-infected patients to have cranioencephalic trauma (RR = 1.94, 95% CI = 1.22-3.09). All patients with MRSA VAP had previously received antibiotics, compared with only 21.1% of those with MSSA infection (p < 0.000001). The incidence of empyema was similar in both groups; nevertheless, the presence of bacteremia and septic shock was more frequent in the MRSA group. Finally, mortality directly related to pneumonia was significantly higher among patients with MRSA episodes (RR = 20.72, 95% CI = 2.78-154.35). This analysis was repeated for monomicrobial episodes, and the difference remained statistically significant. We conclude that MRSA and MSSA strains infect patients with different demographic profiles; previous antibiotic therapy is the most important risk factor for developing MRSA infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Generalized seborrhoeic dermatitis. Clinical and therapeutic data of 25 patients.

Twenty-five infants with generalized seborrhoeic dermatitis have been studied with reference to the provision of optimum treatment. Leucocyte counts and chest x-ray examination are recommended in every case. Irrespective of clinical findings, antibiotics should be given to patients with overt bacterial infection and those with leucocytosis, shift to the left, and toxic granulation. One group of infants was treated with vitamin B complex plus biotin given slowly intravenously over 24 hours; a second group was given only biotin intravenously over 2-3 hours; and a third group only biotin over 1-2 minutes. A fourth group was treated with both biotin and antibiotics for confirmed or suspected superimposed bacterial infection. The results were excellent in all groups. Skin lesions improved within 4-8 days and cleared completely within 15-30 days. Intravenous administration of biotin is recommended as less painful and less dangerous than multiple intramuscular injections.