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Biomedical subjects

D C Shanson

Publications and source records attributed to D C Shanson.

At least 19 recordsLinked to original sources

Susceptibility of Cryptococcus neoformans by the NCCLS microdilution and Etest methods using five defined media.

The susceptibility of 12 isolates of Cryptococcus neoformans to amphotericin B, 5-fluorocytosine, fluconazole, itraconazole and ketoconazole was tested using the NCCLS and Etest methods with yeast nitrogen base (YNB) pH 5.6 and pH 7.0, RPMI MOPS pH 7.0 with and without added glucose (2%) and RPMI buffered with phosphate buffer to pH 7.0. Some isolates yielded poor growth in RPMI MOPS after 72 h. Tests indicated that YNB pH 5.6 was the best medium for 5-fluorocytosine but was unsuitable for ketoconazole. In conclusion, YNB pH 7.0 or RPMI MOPS with 2% glucose can be used with either method.

Amphotericin B↗

An outbreak of methicillin-resistant staphylococcus aureus (MRSA) in a dermatology day-care unit.

We describe an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in a dermatology day-care unit and the methods used to determine the mechanism of spread and control it. The epidemic strain had a characteristic sensitivity pattern and was typeable with phages 29, 80, 95, 47, 54 and 77, which was of considerable value in interpreting the epidemiological data. The method of spread was studied by examination of the medical and nursing records of patients who had acquired MRSA (to determine which members of staff they had encountered and which other MRSA-positive patients had been present in the department at the same time) and by the microbiological screening of all patients and staff. However, screening of all staff by nasal swabbing failed to identify carriage of the epidemic strain, while extensive swabbing of surfaces on the day-care unit also failed to show any evidence of MRSA in the environment. This suggests that the MRSA was most probably spread from patient to patient via the hands of staff, although there was also the possibility of direct transmission from patient to patient. Nine patients acquired the unique strain of MRSA and once acquired it proved difficult to eradicate, although in the majority, the infection did not appear to be clinically significant. However, in two patients MRSA contributed to a fatal outcome: these were the two most elderly patients and were the only two who were receiving systemic corticosteroids. The outbreak was brought under control with rigorous hygienic measures and the decision to discharge all patients with MRSA from the day-care unit. Repeat screening (swabs of nose, axilla and groin) of all day-care unit and in-patients 11 months after the last MRSA case showed no evidence of any residual MRSA infection in the day-care unit.

Adolescent↗

Comparison of a new insertion element, IS1407, with established molecular markers for the characterization of Mycobacterium celatum.

Genomic analyses of 18 Mycobacterium celatum strains obtained from different patients in three countries (United States, United Kingdom, and France) were performed; the methods used in this study were restriction fragment length polymorphism (RFLP) analysis, pulsed-field gel electrophoresis (PFGE) analysis, and PCR restriction analysis (PRA) of the hsp-65 gene. A new insertion sequence, IS1407 (GenBank accession no. X97307), belonging to the IS256 family, was identified in M. celatum type 1 strains and was characterized by sequencing. When a probe for Mycobacterium xenopi IS1395-like sequences was used, the RFLP analysis of M. celatum type 1 strains revealed that they contained three or four copies of IS1407 in identical genomic positions, while this element was absent in all M. celatum type 2 strains. PFGE performed with three different endonucleases revealed a unique large restriction fragment (LRF) pattern for M. celatum type 1 strains, whereas the LRF patterns obtained for M. celatum type 2 strains were polymorphic. Moreover, PFGE of nondigested genomic DNA revealed extrachromosomal elements in M. celatum type 2. The type strain of M. celatum type 3 could not be differentiated from M. celatum type 1 strains on the basis of the results of the RFLP analysis, the PFGE analysis, and the PRA of IS1407. In this study we confirmed that M. celatum types 1 and 2 represent distinct genomic clusters and that the molecular markers in M. celatum type 2 exhibit greater polymorphism than the molecular markers in M. celatum type 1.

Bacterial Proteins↗

Pilot studies of azithromycin, letrazuril and paromomycin in the treatment of cryptosporidiosis.

Pilot studies of the safety and efficacy of 3 drugs thought to have anticryptosporidial activity were carried out to determine whether any of them are suitable for large-scale clinical trials. Open studies of the use of azithromycin, letrazuril and paromomycin in patients with acquired immunodeficiency syndrome (AIDS) and confirmed cryptosporidial diarrhoea for at least a month. Azithromycin 500 mg daily was ineffective. Letrazuril 150-200 mg daily was associated with an improvement in symptoms in 40% of patients treated and cessation of excretion of cryptosporidial oocysts in the stool in 70%; however biopsies remained positive. Paromomycin therapy was associated with a complete resolution of diarrhoea in 60% of patients treated and some improvement in symptoms in a further 5% but it did not eliminate the infection. None of the drugs had any major toxicities. Dose escalation studies of azithromycin should be performed. Letrazuril should be further investigated for efficacy in double-blind placebo-controlled trials. Paromomycin appears to result in prolonged symptomatic remission of cryptosporidial diarrhoea, but has no effect on cryptosporidial cholangitis.

AIDS-Related Opportunistic Infections↗

A new group (type 3) of Mycobacterium celatum isolated from AIDS patients in the London area.

We describe a new group (type 3) of the recently proposed species Mycobacterium celatum isolated from eight patients with AIDS in London, England. Sequences of genes coding for 16S rRNA (EMBL accession no. Z46664) showed a divergence of 17 bases from M. celatum type 2 reference isolates and a divergence of 7 bases from M. celatum type 1 reference isolates. A reference strain is available (NCTC 12882).

Acquired Immunodeficiency Syndrome↗

Septicaemia in patients with and without AIDS at Westminster Hospital, London.

The types of organism causing septicaemia in patients with AIDS and without AIDS at Westminster Hospital were examined prospectively over a period of 2 years (1990-1991). Altogether 417 episodes of septicaemia were diagnosed, 148 (35%) of which were in patients with AIDS. Of septicaemias in patients with AIDS, 53 (36%) were caused by mycobacteria. Non-mycobacterial septicaemias were associated with IV access devices in 58 (61%) of patients with AIDS and in 50 (19%) of those without AIDS. Gram-negative organisms were responsible for septicaemia associated with IV access devices in 16 (28%) of 58 patients with AIDS and in 8 (16%) of 50 patients without AIDS. Non-typhoidal Salmonella species or Shigella species caused 13 (31%) of 42 episodes of septicaemia caused by Gram-negative organisms in patients with AIDS. These findings have influenced the strategy for empirical therapy of septicaemia in patients with AIDS at Westminster Hospital.

Acquired Immunodeficiency Syndrome↗

Evaluation of a commercial chemiluminescent gene probe system 'AccuProbe' for the rapid differentiation of mycobacteria, including 'MAIC X', isolated from blood and other sites, from patients with AIDS.

Optimal therapy of mycobacterial infections in acquired immunodeficiency syndrome (AIDS) is difficult to achieve because of the time needed for a conventional culture to differentiate between Mycobacterium avium-intracellulare complex (MAIC) and Mycobacterium tuberculosis complex (MTBC). The recent commercial availability of gene probing techniques has introduced the potential for more rapid differentiation. We have evaluated the suitability of this technique. The specificity of the chemiluminescent gene probe system 'AccuProbe' was determined for differentiating mycobacterial isolates from 114 AIDS patients. 'AccuProbe' was 100% specific for MTBC isolates (21 of 21 isolates). Using two separate probes to MAIC and 'M. avium-intracellulare complex subtype X' (MAIC-X), 'AccuProbe' was 96% specific (87 of 91 isolates) with 5% of isolates belonging to the MAIC-X group. There were no cross-reactions between any of the probes. Using a modification of the manufacturer's protocol, 'AccuProbe' was used in a 6-month trial for the rapid differentiation of mycobacteria grown from 'Bactec' blood culture. Fifty-seven isolates (31 patients) from 805 Bactec 13A blood cultures (510 patients) were investigated. Ninety-nine per cent of isolates were able to be identified after a mean incubation period of 2.1 weeks (SD 1.2 weeks). Ninety-three per cent of isolates were reported with a presumptive identification the same day and 99% by the day after the culture flagged positive.

Acquired Immunodeficiency Syndrome↗

The in-vitro bactericidal activities of combinations of antimicrobial agents against clinical isolates of Mycobacterium avium-intracellulare.

The in-vitro activities of five antimicrobial agents (rifabutin, clarithromycin, ethambutol, ciprofloxacin and amikacin), alone and in combination, were evaluated against 21 strains of Mycobacterium avium-intracellulare isolated from patients with AIDS. The combined activities of these agents were studied on solid medium by a full chequerboard method. Synergy was demonstrated most frequently (28-71% of isolates) with those combinations that included ethambutol. In killing curve experiments where double and triple combinations of agents were tested against two of the strains, 99% kill was achieved in seven days at concentrations well below those that are attainable in serum. However, an additive rather than a synergic effect was seen in most instances. Although ciprofloxacin alone had the greatest bactericidal activity against these two strains, its activity was antagonized in the presence of rifabutin; this antagonism became inapparent when a third agent was added. Demonstration of bactericidal activity in broth culture may be more relevant than the results of susceptibility testing on solid medium when choosing antimicrobial therapy for patients with this infection.

Anti-Bacterial Agents↗