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Biomedical subjects

D A Dance

Publications and source records attributed to D A Dance.

At least 55 records · Page 3Linked to original sources
PubMed1992

Tumor necrosis factor in septicemic melioidosis.

Plasma concentrations of the cytokine tumor necrosis factor (TNF) were measured serially in 91 patients suspected of having septicemic melioidosis. This was confirmed in 55. TNF was detectable in admission plasma (TNF0) in 3 of 15 survivors of septicemic melioidosis and 21 of 26 fatal cases (P less than .001). The median (range) TNF0 concentration in melioidosis patients who died was 96 (1-4774) pg/ml, and the median time to death was 25 (5-672) h. TNF0 was inversely correlated with the lowest mean arterial pressure in the succeeding 12 h (Spearman's rank correlation coefficient = .67, 2P less than .001). Three patterns of TNF plasma concentrations were evident: relatively constant values between 100 and 500 pg/ml (n = 7), high admission concentrations (greater than 1000 pg/ml) associated with early death (n = 4), and an apparent pulse release after treatment, with peak values greater than 1000 pg/ml, which then declined with a mean (SD) apparent half-time of 131 (50) min (n = 8). Further studies are necessary to determine whether TNF contributes to lethality in melioidosis.

Adolescent↗
PubMed1991

Immune cell activation in melioidosis: increased serum levels of interferon-gamma and soluble interleukin-2 receptors without change in soluble CD8 protein.

To evaluate immune cell activation in patients with melioidosis, serum samples were assayed for interferon-gamma (IFN-gamma), soluble interleukin-2 receptors (sIL-2R), and soluble CD8 protein (sCD8). Forty patients with sepsis (23 fatal cases, 17 survivors) and 13 with localized disease were studied during acute illness; 12 additional patients were studied after discharge while on maintenance antimicrobial therapy. Serum concentrations of IFN-gamma and sIL-2R were greatly elevated, but sCD8 concentrations were not. These levels increased with disease severity and were associated with fatal outcomes. Macrophage activation by high concentrations of the cytokine IFN-gamma may contribute to pathophysiology and death in septicemic patients. Both IFN-gamma and sIL-2R seem to be predictive of outcome in patients with severe melioidosis and may prove useful in detection of relapse.

Adolescent↗
PubMed1991

Pseudomonas pseudomallei resistance to beta-lactam antibiotics due to alterations in the chromosomally encoded beta-lactamase.

Pseudomonas pseudomallei, the causative agent of melioidosis, is generally susceptible to some of the newer extended-spectrum cephalosporins or to combinations of a beta-lactam and clavulanic acid, a beta-lactamase inhibitor. Resistance to these agents may, however, emerge during treatment. We report on alterations in the chromosomal beta-lactamase associated with the development of resistance. Three resistance patterns resulted from three different mechanisms in the strains investigated. Derepression of the chromosomal enzyme resulted in a general increase in the MICs of all of the beta-lactams tested. The second mechanism observed was an insensitivity to inhibition of the beta-lactamase by clavulanic acid. In this case, the level of susceptibility to beta-lactams as independent entities remained unchanged. The final "resistance" pattern occurred in a patient treated with ceftazidime and resulted in a beta-lactamase that was capable of hydrolyzing this antibiotic at detectable levels, but with reduced efficacy against other beta-lactams. The net result was a strain that was generally susceptible to all of the beta-lactams tested except ceftazidime. In all cases, the level of susceptibility to antibiotics other than beta-lactams remained unchanged. Such variability found within one genus over a relatively short time course suggests that treatment of infections caused by this organism should be carefully monitored to detect susceptibility alterations to the chosen therapy.

Anti-Bacterial Agents↗
PubMed1991

Melioidosis: the tip of the iceberg?

For nearly 80 years clinical melioidosis has been considered a rare disease. This bacterial infection is caused by Pseudomonas pseudomallei, a saprophyte found in soil and surface water of endemic areas. Consequently, those who have most contact with soil, the rural poor, are likely to be at greatest risk of infection. Since the diversity of clinical manifestations necessitates the isolation and identification of the causative organism for a definitive diagnosis of melioidosis and the population at greatest risk within endemic areas rarely have access to an appropriate level of health care, the disease has probably been underrecognized. Melioidosis is now known to be an important cause of human morbidity and mortality in Thailand, and this may be true throughout Southeast Asia, which is usually regarded as the main endemic area for the disease. In Australia, melioidosis causes a smaller number of human infections, while disease among livestock has important economic and possible public health implications. Sporadic reports of the infection indicate its presence in several other tropical regions: in the Indian subcontinent, Africa, and Central and South America. Clinical melioidosis may be highly prevalent in these areas, but underdiagnosed as a result of a lack of awareness of the clinical and microbiological features of the disease, or simply because of a lack of health care facilities. Furthermore, during the last two decades the importation and transmission of melioidosis within nontropical zones have been documented. The causative organism is not difficult to grow, and modern antibiotics have improved disease prognosis. Further studies are needed to determine the true worldwide distribution and prevalence of melioidosis so that improved therapeutic and preventive measures can be developed and applied.

Global Health↗
PubMed1990

The use of selective media for the isolation of Pseudomonas pseudomallei in clinical practice.

Ashdown's selective-differential agar medium, with or without preenrichment in selective broth, was evaluated for the isolation of Pseudomonas pseudomallei from 1972 clinical specimens obtained from 643 subjects in Northeast Thailand; 226 patients proved to have meliodosis. The use of Ashdown's medium significantly increased the frequency of recovery of P. pseudomallei from sites or specimens with an extensive normal flora (throat, rectum, wounds and sputum) as compared to the recovery on blood and MacConkey agars (p less than 0.01). The isolation frequency from throat, rectal and wound swabs was further increased by the use of the broth pre-enrichment. The colonial morphology of P. pseudomallei on Ashdown's medium was sufficiently characteristic to allow presumptive identification. With the use of these selective media it was possible to culture P. pseudomallei from throat swabs taken from 87% of the patients from whom the organism could also be isolated from corresponding tracheal aspirates or sputum specimens. P. pseudomallei was isolated from rectal swabs taken from 51 patients, the first time that faecal excretion of the organism has been demonstrated in man. The diagnosis of melioidosis would not have been confirmed bacteriologically in eight patients (3.5%) without the use of the selective media. It is suggested that, in areas endemic for melioidosis, all sputum specimens should be cultured on selective media, such as Ashdown's. For the investigation of clinically suspected cases of melioidosis, and for follow-up during treatment of the disease, the use of broth pre-enrichment is recommended for specimens obtained from sites with an extensive normal flora.

Bacteriological Techniques↗
PubMed1989

Halving of mortality of severe melioidosis by ceftazidime.

An open randomised trial was conducted to compare ceftazidime (120 mg/kg/day) with "conventional therapy" (chloramphenicol 100 mg/kg/day, doxycycline 4 mg/kg/day, trimethoprim 10 mg/kg/day, and sulphamethoxazole 50 mg/kg/day) in the treatment of severe melioidosis. A paired restricted sequential trial designed to detect a reduction in mortality from 80 to 40% in culture-positive patients surviving greater than 48 hours was stopped after 22 months. Of the 161 patients entered into the study, 65 had bacteriologically confirmed melioidosis and 54 of these were septicaemic. Ceftazidime treatment was associated with a 50% (95% CI 19-81%) lower overall mortality than conventional treatment (74% vs 37%; p = 0.009) and should now become the treatment of choice for severe melioidosis.

Actuarial Analysis↗
PubMed1989

Acute suppurative parotitis caused by Pseudomonas pseudomallei in children.

During a prospective clinical study of melioidosis in northeast Thailand, suppurative parotitis was observed as a characteristic presentation in children. Parotitis constituted 6.3% of all culture-positive melioidosis and 38% of melioidosis in children. Nine cases are described. None had apparent predisposition to infection, although two patients developed rising mumps virus antibody titers, suggesting a possible relation between these conditions. Complications included abscess formation (nine), spontaneous rupture into the auditory canal (five), facial nerve palsy (two), and septicemia and osteomyelitis with septic arthritis (one each). All children initially responded to surgical drainage and appropriate antibiotic therapy. Pseudomonas pseudomallei parotitis should be considered in children from endemic areas with fever and facial swelling. It has a good prognosis with appropriate treatment. It may also prove to be a sensitive clinical indicator of the presence of melioidosis within a particular geographic area.

Abscess↗
PubMed1989

Melioidosis: a major cause of community-acquired septicemia in northeastern Thailand.

In a prospective study of all patients with Pseudomonas pseudomallei infections admitted to a large provincial hospital in northeastern Thailand, 63 cases of septicemic melioidosis and 206 patients with other community-acquired septicemias were documented during a 1-y period. Apart from P. pseudomallei, the spectrum of bacteria isolated from blood cultures and the overall mortality (32%) were similar to those previously reported elsewhere. Death from septicemia was associated with failure to develop a leukocytosis or pyrexia over 38 degrees C, azotemia, hypoglycemia, and jaundice. Septicemic melioidosis presented mainly in the rainy season, occurred predominantly in rice farmers or their families, and was significantly associated with preexisting diabetes mellitus or renal failure (P = .03). Blood-borne pneumonia and visceral abscesses were common and the mortality was high (68%; P less than .001). The response to appropriate treatment was slow (median fever clearance time 5.5 d) and the median duration of hospital stay was 4 w. Septicemic melioidosis is a major cause of morbidity and mortality in northeast Thailand.

Diabetes Complications↗
PubMed1989

The antimicrobial susceptibility of Pseudomonas pseudomallei. Emergence of resistance in vitro and during treatment.

We have measured the in-vitro activity of 27 antimicrobials against 211 clinical and ten reference strains of Pseudomonas pseudomallei. Imipenem was the most active antibiotic tested, followed by piperacillin, doxycycline, amoxycillin/clavulanic acid, cefixime, cefetamet, azlocillin and ceftazidime, all of which had MICs of less than or equal to 2 mg/l for the majority of strains. The measured MICs were dependent on the media and inocula used, to an extent which varied with the antibiotic class under test; MICs of ureidopenicillins were particularly inoculum-dependent. The beta-lactams and ciprofloxacin were bactericidal, whereas the agents conventionally used to treat melioidosis (doxycycline, chloramphenicol, sulphamethoxazole and trimethoprim) had bacteriostatic activity only. Strains highly resistant to chloramphenicol (MIC greater than or equal to 256 mg/l) emerged during treatment in 7.1% of patients. These strains were fully virulent, and frequently showed cross-resistance to tetracyclines, sulphamethoxazole, trimethoprim and ciprofloxacin, with paradoxical increased susceptibility to beta-lactams and aminoglycosides. Similar resistance patterns were seen in mutants generated in vitro and two reference strains. One strain with isolated ceftazidime resistance, reversible by clavulanic acid, emerged during treatment. Several of the new beta-lactam antibiotics are of potential value in the therapy of P. pseudomallei infections. Patients should be carefully monitored for the emergence of antibiotic-resistant strains during treatment of melioidosis.

Anti-Bacterial Agents↗
PubMed1989

Interactions in vitro between agents used to treat melioidosis.

Combinations of antimicrobial agents are usually recommended for the treatment of melioidosis. In Thailand, the conventional treatment regimen for Pseudomonas pseudomallei infections is a combination of chloramphenicol, doxycycline and cotrimoxazole. We have consistently observed antagonism between these agents during routine disc susceptibility testing. Interactions between these antimicrobials were studied further by a chequerboard microdilution method, using five clinical isolates of P. pseudomallei. Both trimethoprim and sulphamethoxazole antagonised the bacteriostatic activity of chloramphenicol and doxycycline. The combination of trimethoprim and sulphamethoxazole was synergistic, but not bactericidal. Bacteriostatic drugs antagonised the bactericidal activity of ceftazidime, which is undergoing clinical trials in severe melioidosis. These findings may be of therapeutic relevance.

Anti-Bacterial Agents↗
PubMed1989

Identification of Pseudomonas pseudomallei in clinical practice: use of simple screening tests and API 20NE.

The API 20NE kit and a simple screening system involving Gram's stain, the oxidase reaction, colistin and gentamicin resistance, and colonial characteristics on a differential agar medium, were used to test 400 strains of Pseudomonas pseudomallei. The API kit identified 390 (97.5%) strains correctly on first testing and all but one of the remainder on second testing. Only one strain was initially misidentified (as Ps cepacia). The screening system was 100% accurate in identifying Ps pseudomallei. In non-endemic areas the API 20NE kit may be used to identify sporadic imported strains of Ps pseudomallei. Such kits may also help to delineate the geographical distribution of melioidosis. In endemic areas the screening tests described offer a cheap, simple, and accurate means of presumptively identifying Ps pseudomallei from clinical specimens.

Bacteriological Techniques↗
PubMed1989

Rapid detection of Haemophilus ducreyi in clinical and experimental infections using monoclonal antibody: a preliminary evaluation.

A monoclonal antibody raised against Haemophilus ducreyi was tested for its sensitivity and specificity as an immunofluorescence (IF) reagent using simulated vaginal smears containing H. ducreyi, smears taken from skin lesions of mice infected with H. ducreyi and patients from South Africa, Thailand and Malaysia with clinically diagnosed chancroid. The IF test was more sensitive than culture or Gram staining in the simulated smears, theoretically detecting less than 4 organisms/sample. It detected H. ducreyi in 95% of the animal lesions compared with 14% detected by culture. Immunofluorescence testing identified over 90% of culture-positive cases of chancroid but also detected organisms in some culture-negative cases where clinical evidence for the diagnosis was strong. These results suggest that this antibody may provide a simple, rapid and sensitive means of detecting H. ducreyi in cases of chancroid.

Animals↗