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To examine risk factors for early-onset ventilator-associated pneumonia (EOP) in patients requiring mechanical ventilation (MV), we performed a prospective cohort study that included 747 patients. Pneumonia was defined as a positive result for a protected quantitative distal sample. EOP was defined as pneumonia that occurred from day 3 to day 7 of MV. Eighty patients (10.7%) experienced EOP. Independent predictors of EOP were male sex (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.18-3.63), actual Glasgow Coma Scale value of 6-13 (OR, 1.95; 95% CI, 1.2-3.18), high Logistic Organ Dysfunction score at day 2 (OR, 1.12 per point; 95% CI, 1.02-1.23), unplanned extubation (OR, 3.19; 95% CI, 1.28-7.92), and sucralfate use (OR, 1.81; 95% CI, 1.01-3.26). Protection occurred with use of aminoglycosides (OR, 0.36; 95% CI, 0.17-0.76), β-lactams and/ or β-lactamase inhibitors (OR, 0.47; 95% CI, 0.28-0.83), or third-generation cephalosporins (OR, 0.33; 95% CI, 0.16-0.74). Sucralfate use and unplanned extubation are independent risk factors for EOP. Use of aminoglycosides, β-lactams/β-lactamase inhibitors, or third-generation cephalosporins protects against EOP. [ABSTRACT FROM AUTHOR]

The role of HCV RNA levels and host factors in the severity of liver injury was studied. Enrolled were 298 consecutive liver biopsy-proven chronic hepatitis (CH) C patients (179 men; median age: 52 years, range 19-68; CH, 198; cirrhosis, 100) and 18 chronic hepatitis C with normal ALT. HCV genotypes were: 1a, 4.3%; 1b, 53%; 2a/c, 28%; 3a, 7%; 4, 1.3%, and mixed 6.4%. Serum HCV RNA levels were similar for all genotypes (median: 2.8 x 10(6) eq/ml; range <0.2-69). In patients with chronic hepatitis without cirrhosis, the serum HCV RNA levels reflected the grade of liver necroinflammatory activity (R = 0.45; P < 0.001) and the stage of fibrosis (R = 0.51; P < 0.001), regardless of age, gender, HCV genotype, hepatic steatosis, and hepatic iron overload. Patients with high serum HCV RNA levels (> or =3 x 10(6) eq/ml) had higher ALT values (P < 0.002) than those with lower HCV RNA levels. Patients with normal ALT showed low HCV RNA levels (median: 0.82 x 10(6) eq/ml) and histological features of minimal or mild chronic hepatitis. Cirrhotic patients showed significantly lower levels of viremia than those with chronic hepatitis with a similar HAI. The data of a subgroup of 62 patients with an established time of infection showed that for a similar duration of disease, patients with serum HCV RNA levels > or =3 x 10(6) eq/ml had a significantly higher fibrosis score than those with lower levels. HAI and fibrosis score were significantly higher in patients with HCV RNA levels > or =3 x 10(6) eq/ml and grade 3-4 steatosis than those with lower HCV RNA levels and steatosis grades. The data indicate that the liver damage is correlated with the HCV RNA levels and that a high viral load acts together with steatosis in accelerating the progression of liver injury. [ABSTRACT FROM AUTHOR]

The intracellular activity of streptomycin, gentamicin, and netilmicin on Escherichia coli phagocytosed by murine peritoneal macrophages was studied using a sensitive and standardized method. Intracellular activity of streptomycin and gentamicin at therapeutic concentrations was seen after 1 h of incubation of antibiotics with macrophages containing phagocytosed bacteria, whilst for netilmicin a significant intracellular activity was observed only after 3 h exposure. The activity of these antibiotics against intraphagocytic bacteria was significantly lower than that observed against extracellular bacteria. Sub-inhibitory concentrations of streptomycin were active against intracellular E. coli. Streptomycin was also active for a phagocytosed streptomycin-resistant strain of E. coli, but this activity was eliminated when the O2-dependent killing mechanisms of macrophages were inhibited by sodium fluoride. The data demonstrate that aminoglycosides may exert a dose-dependent intraphagocytic activity against E. coli that correlates with the time of incubation of the antibiotics with infected macrophages. Streptomycin appears to be the most effective agent followed by gentamicin and the least active was netilmicin. In the case of streptomycin, the intraphagocytic activity seems to be due, at least in part, to the stimulation of O2-dependent cellular microbactericidal mechanisms. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate whether pre-exposure of bacteria to a subinhibitory concentration (sub-MIC) of loracarbef (LY 163892) or daptomycin (LY 146032) could modify bacterial susceptibility to serum bactericidal activity and to phagocytosis and killing by murine peritoneal macrophages and by human polymorphonuclear leucocytes. Escherichia coli, Haemophilus influenzae type b and Staphylococcus aureus grown in the presence of one quarter the MIC of loracarbef, and S. aureus exposed to one quarter the MIC of daptomycin were phagocytosed and killed in numbers significantly higher than non-exposed bacteria. Pre-exposure to loracarbef resulted in increased susceptibility of E. coli and H. influenzae type b to the bactericidal activity of antiserum, but exposure to loracarbef or daptomycin did not modify serum sensitivity of S. aureus. Loracarbef treatment and antiserum enhanced phagocytosis and killing of E. coli and H. influenzae type b to a greater extent than either antibiotic treatment or antiserum alone. These data indicate that loracarbef and daptomycin at sub-MIC enhance the susceptibility of bacterial pathogens to cellular and host defence mechanisms. [ABSTRACT FROM AUTHOR]

The intracellular activity of cefamandole and aztreonam against phagocytosed Escherichia coli and cefamandole against phagocytosed Staphylococcus aureus was studied using a sensitive and standardized method of murine peritoneal macrophages. Cefamandole and aztreonam exerted an intracellular antibacterial activity against E. coli which was greater than their extracellular one. With concentrations of both antibiotics up to 16 x MBC a dose-dependent decrease of the initial number of intracellular E. coli which ranged from 32% to 90% was observed. However, similar antibiotic concentrations above the MBC affected the viability of extracellular E. coli by only 20% to 30%. The intracellular antibacterial activity of both antibiotics against E. coli was further enhanced by immune serum. Cefamandole at 4 x the MBC did not affect the survival of intracellular S. aureus, but killed 41% of extracellular bacteria by 1 h and 99% after 3 h. The intracellular activity of both antibiotics against E. coli was also maintained in NaF-pulsed macrophages which have an impaired oxidative metabolism. The data suggest that both cefamandole and aztreonam possess an intracellular antibacterial activity against E. coli that seems at least in part due to a positive cooperation of antibiotics with the O2-independent microbicidal system of macrophages. [ABSTRACT FROM AUTHOR]

Described here is the first definite case of endocarditis due to Moraxella phenylpyruvica, which occurred in a 50-year-old male with a bicuspid aortic valve. The diagnosis was delayed because of the confounding positivity of the Widal and Wright tests. The patient was cured with surgical valve replacement and antibiotic treatment. [ABSTRACT FROM AUTHOR]