A prospective population-based study was carried out to determine predictive factors associated with penicillin-resistant pneumococcal invasive disease. A total of 374 patients (250 males and 124 females; mean age, 50.3 +/- 27 years) with invasive pneumococcal infection were admitted to one of the five hospitals in El Vallés County (an industrial area with 800,000 inhabitants in the province of Barcelona, Spain) over a period of 5 years. Of the 374 episodes, 21 (5.6%) were due to highly penicillin-resistant pneumococci and 67 (17.9%) to intermediately penicillin-resistant pneumococci. Multivariate analysis showed a statistically significant association between infection with intermediately penicillin-resistant pneumococci and an age of 0-4 years (odds ratio [OR] = 5.3; 95% confidence interval [CI] = 2.2-12.6), the presence of an immunosuppressive underlying disease (OR = 3.0; 95% CI = 1.5-6.0), and the previous use of beta-lactam antibiotics (OR = 2.1; 95% CI = 1.0-4.5). Infection with highly penicillin-resistant pneumococci was associated only with the previous use of beta-lactam antibiotics (OR = 5.9; 95% 95% CI = 2.2-15.8). Highly resistant strains were of serotypes 6, 9, 14, 15, 19, and 23, of which all but serotypes 9 and 15 are included in the newly formulated conjugated vaccine.
The role of tumor necrosis factor alpha (TNF) in the toxic and lethal effects of the endotoxemia associated with septic shock is well known. This study was designed to establish whether natural somatostatin (SS-14) is capable of modifying the production of TNF in a model of septic shock induced in the rat by bacterial lipopolysaccharide (LPS), and its theoretical relationship to prostaglandin E2 (PGE2). An experimental study was carried out in 80 Wistar rats subjected to intravenous LPS injection. Perfusion of SS-14 at 2 micrograms/h or continuous isotonic saline (IS) at 0.1 ml/h started 30 min prior to LPS injection and continued until 90 min after. All the animals were primed 15 days earlier with on intraperitoneal dose of BCG (2.2 x 10(7) CFU). ELISA assays were used to measure TNF levels after 90 min of perfusion and those of PGE2 at 30 and 90 min. The effects of two different doses of LPS (0.5 mg/kg of body weight and 5 mg/kg bw) were compared. SS-14 administration was associated with a decrease in TNF levels (1130.0 +/- 272.4 vs 4720.0 +/- 1278.1 pg/ml, P = 0.013), and an increase in serum PGE2 basally (255.7 +/- 94.2 vs 62.0 +/- 10.6 pg/ml, P = 0.04) and after 90 min of perfusion (1872.7 +/- 1250.6 vs 1009.7 +/- 612.0 pg/ml, P = NS), there being a statistically significant correlation between the basal PGE2 levels and these TNF after 90 min when compared using a regression model (r = -0.88, P = 0.04 for the 0.5 mg/kg dose; r = -0.47, P = 0.07 for 5 mg/kg). At 90 min, the level of TNF also depended on the PGE2 values (r = 0.84, P = 0.07 for 0.5 mg/kg; r = 0.55, P = 0.03 for 5 mg/kg). Multiple regression permitted TNF levels to be estimated on the basis of basal and 90 min PGE2 levels (P = 0.03). Pretreatment with SS-14 led to a significant reduction of TNF and an increase of PGE2, there being an apparent correlation between the two.
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