The synthesis of 11 peptides, ranging in composition from 9 to 17 amino acid residues, by solid-phase methodology was accomplished with the purpose of studying how the amphiphilic and hydrophobic character, the size of the molecule, and the charge distribution modulate the antibacterial activity. It was found that peptides composed of 16 and 17 amino acid residues, with high hydrophobic (mainly due to Trp or Phe) and hydrophilic (due to Lys) character distributed along opposite amphiphilic faces, showed considerable antibacterial activity against clinically isolated bacteria together with Gram positive and Gram negative ATCC bacterial strains. However, the hemolytic capacity of the peptides was also significant. Decreasing the hydrophobic character of the molecule by replacing Trp or Phe with Leu residues while maintaining the basic contribution of Lys drastically reduced the hemolytic activity and only slightly decreased the bioactivity. Peptides composed of 9-10 amino acid residues with high hydrophobic and basic nature possess antibacterial activity but, in general, are less active than the larger counterpart peptides. By replacing all Trp residues of a short peptide by Leu residues, the activity was considerably reduced. Circular dichroism studies and antibacterial assays showed that shorter peptides with very low helical content, and thus deprived of amphiphilic character, still have appreciable bioactivity. This observation, coupled with the fact that due to their small size they cannot span the bacterial outer lipid bilayer, may suggest different mechanisms of action for long-chain vis-a-vis short-chain peptides.
The medical records of 25 patients with nosocomial meningitis due to Acinetobacter baumannii were retrospectively reviewed. Most cases occurred in the neurosurgical intensive care unit over a 5-year period, with an increased rate during summer. The majority of infections were associated with indwelling ventriculostomy tubes or CSF fistulae in patients receiving antimicrobial therapy. Repeated environmental cultures failed to reveal a source of the microorganism, and control measures had no apparent effect on the outbreak. However, no further cases appeared following a sharply reduced total intake of antibiotics in the neurosurgical department. Forty-one cases of acinetobacter meningitis, secondary to invasive procedures, were found in the English-language literature and were compared with the cases presented. To our knowledge, our series is the largest of acinetobacter meningitis reported hitherto. Although not one of the most common pathogens in hospitals, Acinetobacter constitutes an increasing threat for patients, especially those receiving antimicrobial therapy in intensive care units who are being maintained by various life-support systems.
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