Infections caused by drug-resistant pathogens are on the rise. Daptomycin, a cyclic lipopeptide with activity against most Gram-positive pathogens, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus, is a newly US-FDA approved antimicrobial for complicated skin and skin structure infections (cSSSI). Daptomycin has a unique mechanism of action that results in destruction of the membrane potential. The rapid bactericidal activity of daptomycin makes it an attractive antibiotic for serious Gram-positive infections.

These data suggest that the neutrophils of newborns are selectively deficient in BPI, a central effector of antibacterial activity against gram-negative bacteria. BPI deficiency correlates with decreased antibacterial activity of newborn neutrophil extracts against serum-resistant E coli and could contribute to the increased incidence of gram-negative sepsis among newborns relative to healthy adults.neonatal sepsis, gram-negative bacteria, endotoxin, neutrophil, polymorphonuclear leukocyte, innate immunity, bactericidal/permeability-increasing protein, defensin, myeloperoxidase.

Clostridium difficile was shown to produce a toxin which could be biochemically separated from the previously described cytotoxin of the same organism. The two proteins differ in biological activity and physical properties. Antiserum prepared to the second toxin does not neutralize the biological activity of the cytotoxin, and immunological cross-reactivity could not be demonstrated. However, some relationship may exist between the two toxins, since the newly described toxin degrades on polyacrylamide electrophoresis into two molecules, one of which appears to migrate with the band of purified cytotoxin. We suggest that this newly described toxin be designated toxin A until its primary biological activity and physical relationship to cytotoxin is determined. This toxin is active in biological assays of enteric disease and may play an important role in C. difficile-induced colitis. Previous observations in several laboratories implicate Clostridium difficile as the etiological agent of pseudomembranous colitis, a serious disease which is usually a complication of antimicrobial therapy. This conclusion is supported by studies showing that stools from patients with pseudomembranous colitis contain a cytotoxin which is neutralized by clostridial antitoxins, that cultures of specimens yield C. difficile, and that these isolates produce a similar or identical cytotoxin in vitro (2, 3, 6, 12-14, 18, 19, 22). Also, intracecal injection of cell-free supernatant of stool or broth culture of C. difficile produces lesions similar to those of pseudomembranous colitis in experimental animals (2, 4). Recent studies from several groups indicate that stools from 90 to 95% of patients with pseudomembranous colitis have both the cytotoxin and C. difficile (2, 12, 16). These observations have provided the impetus for several groups to purify, characterize, and study the mechanism of action of C. difficile cytotoxin (1, 15, 23, 26). In this report, we present evidence that C. difficile produces another toxin which elicits positive responses in biological assays of enteric disease. Our findings suggest that this second toxin may play an important role in the clinical symptoms and pathological changes ascribed to C. difficile. MATERIALS AND METHODS Culture preparation. For toxin purification, C.

Daptomycin is not effective for the treatment of CAP, including infections caused by Streptococcus pneumoniae and Staphylococcus aureus. The observation that as little as 24 h of prior effective therapy may impact clinical outcome suggests that trials to evaluate CAP treatment may need to exclude patients who have received any potentially effective therapy before enrollment.