Characterization of a fish antimicrobial peptide: gene expression, subcellular localization, and spectrum of activity.

Antimicrobial peptides are proposed to act as the first line of mucosal host defense by exerting broad-spectrum microbicidal activity against pathogenic microbes. Pleurocidin, a new 25-residue linear antimicrobial peptide, was recently isolated from the skin secretions of winter flounder (Pleuronectes americanus). The present study identifies the cDNA and gene encoding pleurocidin. The pleurocidin gene comprises four exons. Its upstream region demonstrates consensus binding sequences for transcription factors found in host defense genes in mammals, including sequences identical to the NF-IL6 and alpha and gamma interferon response elements. Pleurocidin is predicted to exist as a 68-residue prepropeptide that undergoes proteolytic cleavage of its amino-terminal signal and carboxy-terminal anionic propiece to form the active, mature peptide. Transmission electron microscopy localized pleurocidin to the mucin granules of skin and intestinal goblet cells. Significant synergy was shown to occur between pleurocidin and D-cycloserine targeting Mycobacterium smegmatis. Pleurocidin was functionally active at physiologic concentrations of magnesium and calcium; however, high concentrations of these divalent cations ablated pleurocidin's activity against a standard test strain, Escherichia coli D31. Pleurocidin was tested against bacterial and fungal clinical isolates and showed broad-spectrum antimicrobial activity. Together, these data support the hypothesis that pleurocidin participates in innate mucosal immunity, and it may prove to be a beneficial therapeutic agent.

Minocycline and ethylenediaminetetraacetate for the prevention of recurrent vascular catheter infections.

Three patients with recurrent vascular catheter-related bacteremia were successfully treated by allowing a solution of minocycline and ethylenediaminetetraacetate (EDTA) to dwell in the lumen of the indwelling catheter or by coating polyurethane catheters with minocycline/EDTA and flushing the lumen daily with the same solution. In vitro and in vivo experiments showed that minocycline/EDTA may have broad-spectrum antimicrobial activity, may have optimal anticoagulant activity, and may be highly efficacious in preventing catheter colonization.

Antibiotic prophylaxis for urodynamic testing in patients with spinal cord injury: a preliminary study.

This study was performed in order to: (i) determine the incidence of symptomatic urinary tract infection (UTI) in patients with spinal cord injury after urodynamic testing; (ii) evaluate the role of antibiotic prophylaxis for such a procedure; and (iii) investigate whether pre-existing bacteriuria predisposes to the development of symptomatic UTI after urodynamic testing. Forty patients were prospectively randomized in a double-blind fashion to receive a 3-day oral course of either ciprofloxacin (18 patients) or placebo (22 patients), beginning 2 days prior to the urodynamic procedure. None of 18 (0%) patients who received ciprofloxacin developed symptomatic UTI within 5 days after the procedure compared with three of 22 (14%) subjects randomized to the placebo group; the protective efficacy of antibiotic prophylaxis, however, did not attain statistical significance (P = 0.24). None of the three bacterial isolates that were responsible for symptomatic infection were grown in corresponding urine cultures prior to the procedure. These findings may serve as a pilot for a larger study.

Eradication of colonization by methicillin-resistant Staphylococcus aureus by using oral minocycline-rifampin and topical mupirocin.

In an attempt to control the spread of methicillin-resistant Staphylococcus aureus (MRSA) within a spinal cord injury unit, we investigated the mode of transmission and implemented a multidisciplinary approach for control that consisted of grouping of patients into cohorts, contact isolation, and antibiotics. Surveillance cultures of patients and nose and hand cultures of medical personnel were performed. Of 11 colonized patients, 6 had MRSA isolates that shared a similar plasmid profile and antibiogram, raising the possibility of interpatient spread of the organism. Medical personnel had no evident role in transmitting MRSA. All patients' pretherapy MRSA isolates were susceptible to minocycline and, except for one, to rifampin. Time-kill studies showed an indifferent interaction of these two antibiotics. Ten colonized patients received a 2-week oral course of 100 mg of minocycline twice daily and 600 mg of rifampin once daily, while the 11th patient was treated for only 1 week. Patients with colonization of the nares also had twice daily nasal application of 2% mupirocin for 5 days. Colonization with MRSA cleared in 10 of 11 patients (91%) and 20 of 21 sites (95%). When the individual circumstances of a medical facility justify eradication of MRSA colonization, a multidisciplinary approach that includes antibiotic therapy with oral minocycline and rifampin, along with topical mupirocin for those with nasal carriage, may be successful.