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D Musher

Publications and source records attributed to D Musher.

8 recordsLinked to original sources

Levels of rifampin and ciprofloxacin in nasal secretions: correlation with MIC90 and eradication of nasopharyngeal carriage of bacteria.

To predict the efficacy of antibiotics in eliminating nasopharyngeal carriage of organisms such as Neisseria meningitidis, Haemophilus influenzae, and methicillin-resistant Staphylococcus aureus (MRSA), a novel approach for measuring drug concentrations in nasal secretions was developed. Five healthy individuals received four doses of rifampin and then, at a later date, ciprofloxacin. At 2, 5, and 8 h after the last dose, serum, saliva, and cold-stimulated nasal secretion samples were collected, and drug levels were analyzed by high-performance liquid chromatography. Nasopharyngeal levels of rifampin reached but did not substantially exceed 90% of the minimal inhibitory concentration (MIC90) for H. influenzae, exceeded the MIC90 for N. meningitidis, and were well above that for MRSA. Ciprofloxacin levels in nasal secretions far exceeded the MIC90 for meningococci and Haemophilus organisms but were below that for MRSA. These findings are consistent with the clinical studies showing that rifampin eliminates, in most instances, the nasal carriage of N. meningitidis and to a lesser extent H. influenzae. A single dose of ciprofloxacin has been shown to eradicate meningococci, yet a long course of treatment with this drug is not adequate for MRSA. On the basis of these results, clinical trials with ciprofloxacin to eliminate nasopharyngeal carriage of H. influenzae appear to be warranted.

Carrier State

Syphilis.

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HIV Infections

Cephalosporin penetration into soft tissue of paralyzed limbs.

Poor penetration of antibiotics into paralyzed tissue may contribute to the difficulty of curing soft tissue infections in paralyzed limbs. A novel model of spinal cord hemisection was used to induce paralysis of one hind leg in mice. Five, 10, or 20 days after induction of paralysis, six groups of 10 mice were injected intravenously with a single dose or with four sequential doses of cefepime, a new broad-spectrum cephalosporin, and then sacrificed. High-performance liquid chromatography was used to compare cefepime levels in soft tissue homogenates of paralyzed and normal hind legs; no significant differences were found in any group. Factors other than antibiotic delivery may be responsible for difficulty in curing infections in paralyzed soft tissue.

Animals

Effect macrophage activation on infection with Treponema pallidum.

Infection of rabbits with Treponema pallidum induces nonspecific acquired cellular resistance (ACR) to Listeria monocytogenes. This resistance can be adoptively transferred using thymus-dependent lymphocytes. Since infections that induce ACR are usually brought under control by cellular mechanisms, we sought to determine whether induction of ACR in rabbits stimulates resistance to challenge with T. pallidum. When BCG-infected rabbits which suppressed the growth of Listeria were challenged intravenously with T. pallidum, lesions appeared at the same time and progressed in a fashion similar to that in non-BCG-infected controls. There was a tendency for syphilitic lesions to disseminate more widely in BCG-infected animals and for the lesions to necrose more rapidly in controls. T. pallidum may resist phagocytosis by macrophages, as has been suggested previously, or macrophages may fail to be activated locally in the dermis. Although syphilitic infeciton appears to stimulate ACR, activation of the macrophages may not contribute significantly to the ability of the host to suppress T. pallidum.

Animals

Induction of acquired cellular resistance following transfer of thymus-dependent lymphocytes from syphilitic rabbits.

Syphilitic rabbits have previously been shown to resist challenge with Listeria monocytogenes. Thirty days after rabbits were infected with Treponema pallidum, transfer of 4 to 6 times 10-8 viable spleen cells along with T. pallidum conferred resistance to Listeria on normal recipients. Treatment of the spleen cells with anti-thymus serum and complement inhibited or abolished their ability to transfer resistance to Listeria. These results support the hypothesis that the ability of syphilitic rabbits to suppress the growth of Listeria reflects stimulation of cell-mediated immunity during active infection with T. pallidum.

Animals