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Visceral organ abscesses in melioidosis: sonographic findings.

PURPOSE: We describe the sonographic appearances of extrapulmonary visceral organ abscesses in melioidosis and examine the role of sonography in early detection and follow-up of this elusive disease. METHODS: The sonograms and records of 80 patients with melioidosis were retrospectively reviewed. The number, size, sonographic appearances, and distribution of abscesses in the abdominal visceral organs were analyzed. RESULTS: The most common suspected diagnoses upon hospital admission were septicemia and pyrexia of unknown origin (39%). Abdominal visceral organ abscess was suspected in only 28% of patients. Fifty-seven patients (71%) had single organ involvement, and 23 (29%) had multiple organ involvement. There were lesions in the spleen in 59 patients (74%), liver in 37 (46%), and kidney in 10 (12%). Multiple abscesses were much more common than a solitary abscess in each organ and were demonstrated in 83%, 68%, and 75% of patients with spleen, liver, and kidney involvement, respectively. The sonographic findings of multiple small abscesses with a "target-like" appearance and larger multiloculated abscesses were common in every organ. CONCLUSIONS: The findings of multiple small, discrete abscesses in visceral organs, particularly the spleen, should raise the suspicion of this disease. In endemic areas, screening sonography should be done in every patient presenting with septicemia or fever of unknown origin.

Abscess↗

Construction of a specific DNA probe for diagnosis of melioidosis and use as an epidemiological marker of Pseudomonas pseudomallei.

Pseudomonas pseudomallei is a causative agent of melioidosis. The disease manifestations range from fulminant sepsis to asymptomatic seroconversion. In septicemic cases, a mortality rate of 80-90% is reported. Rapid and specific diagnosis has become important to the clinical microbiology laboratory. We have developed a P. pseudomallei-specific DNA probe. The cloned fragment, herein designated pKKU-S23L, contained 1.5 kb of P. pseudomallei chromosomal DNA. A radioactively labelled pKKU-S23L insert could detect 1.5 ng of its genomic DNA or 40,000 P. pseudomallei cells. The probe was highly specific for P. pseudomallei DNA and did not cross-hybridize with DNAs prepared from other related bacteria. Using pKKU-S23L as a probe in total cellular DNA digestions and Southern blot hybridization, we were able to classify 60 P. pseudomallei clinical isolates obtained from individual melioidosis patients into eight categories. Therefore, this probe has a potential not only for use in development of specific detection of bacterial DNA in clinical specimens but also for application in epidemiological studies of P. pseudomallei.

Blotting, Southern↗

Melioidosis--rare or overlooked?

The word melioidosis conjures images of a rare, exotic disease meant only for large textbooks of pediatrics, to be read only to be forgotten or even to be ignored completely. The following two cases of melioidosis from India will surely serve as an eye opener.

Ceftazidime↗

Highly resistant Burkholderia pseudomallei small colony variants isolated in vitro and in experimental melioidosis.

Burkhloderia pseudomallei is the causative agent of melioidosis, a disease in which treatment failures and relapses are common. This study reports on slow growing B. pseudomallei 'small colony variants' (SCVs), isolated either in vitro after exposure to ceftazidime, ciprofloxacin or gentamicin or from the spleen and liver in a mouse model of melioidosis after treatment with ceftazidime. Interestingly, SCVs isolated by either method or antimicrobial agent showed a significant increase in the minimal inhibitory concentrations of various unrelated classes of antimicrobial agents. B. pseudomallei SCVs did not differ from their parental strains in standard biochemical profiles, nor by pulsed field gel electrophoresis or electron microscopy. Although the SCV phenotype was stable throughout numerous passages on antibiotic-free solid media, revertants with the parental colony morphology and, most importantly, with the parental susceptibility pattern occurred. These revertants led to rapid overgrowth of SCVs in liquid media without added antibiotics. Future studies will have to determine the clinical relevance of B. pseudomallei SCVs especially in treatment failure and relapse of infection.

Animals↗

Granulocyte colony-stimulating factor and an in vitro whole blood model of melioidosis.

The study reported here was conducted in order to explore the mechanism of action of granulocyte colony-stimulating factor (G-CSF) in the treatment of Burkholderia pseudomallei infections (otherwise known as melioidosis). Use of G-CSF as an adjunct to antibiotics has been associated with decreasing mortality among patients with melioidosis in the tropical region of the Northern Territory of Australia. However, using an in vitro whole blood assay, no significant difference was detected in the bactericidal activity of samples obtained from dialysis patients, patients with type 2 diabetes mellitus and healthy controls, and there was no improvement following coincubation with G-CSF.

Australia↗

A case of imported melioidosis presenting as prostatitis.

We report a case of melioidosis in a previously healthy Belgian man. He presented with septicemia and prostatic abscesses 1 week after a trip to Vietnam. Burkholderia pseudomallei was isolated from multiple hemocultures. He was treated successfully with intravenous ceftazidime and trimethoprim-sulfamethoxazole, followed by a per-oral maintenance therapy of amoxicillin-clavulanate with supplementary amoxicillin. There was no need for surgical drainage. This is the second reported case of melioidosis in Belgium.

Abscess↗

Melioidosis: a reminder.

Recrudescent pulmonary melioidosis developed in two patients 12 and 16 years after their last travels to an endemic area. In one, a clinically silent prostatic abscess may have been the focus; and in both, the diagnosis was difficult to make even when the laboratory was notified of the possibility of infection with Pseudomonas pseudomallei. Recrudescent melioidosis should be considered in febrile patients who have been in endemic areas regardless of the interval from last exposure to the development of disease.

Humans↗

Melioidosis: a serological survey in a tuberculosis sanatorium in Hong Kong.

A serological survey of 275 Chinese patients with underlying pulmonary diseases in a tuberculosis sanatorium in Hong Kong showed that 39 (14%) had haemagglutinating antibody (HA) against Pseudomonas pseudomallei in a titre of 1: 80 or above. Only 9 of these 39 patients had travelled to endemic areas, suggesting that at least 30 patients (11%) had been exposed to Ps. pseudomallei locally. Females are affected as often as males, and the seropositive rate is the same whether patients are immunosuppressed or not. Because subclinical melioidosis is prevalent and HA may persist for a long time, even at a high titre, after infection, determination of HA alone cannot differentiate between active melioidosis and its masquerade--active tuberculosis.

Adolescent↗

[Melioidosis].

Melioidosis is an emerging zoonosis, due to Burkholderia pseudomallei, which is a highly invasive, resistant, and resilient soil bacteria, transmitted by cutaneous or airborne route, and is a potential weapon for bioterrorism. Although the agent has been identified all over the world, the human disease is endemic only in SE Asia and Northern Australia, and gained recent interest after the December 2004 tsunami. Human infection can be a very severe systemic disease (mortality 20 to 80%), with protean expression, but the lung is the most affected organ (50%). Pathophysiology remains unclear. Diabetes mellitus is a major risk factor, and is present in half the Asian patients with melioidosis. Recommended antibiotic regimens are expensive, and in severe disease should be prolonged to 20 weeks to reduce the risk of relapse. Prospects for prevention are limited, and no vaccine is available yet.

Australia↗

Genome fingerprinting by pulsed-field gel electrophoresis of isolates of Burkholderia pseudomallei from patients with melioidosis in Thailand.

A total of 95 isolates of Burkholderia pseudomallei from 53 sporadic cases in Thailand were examined by pulsed-field gel electrophoresis. Digestion of genomic DNA of all isolates by NcoI generated a macrorestriction pattern similar to that of B. pseudomallei which cannot assimilate L-arabinose. Analysis using restriction enzymes SpeI and AvrII demonstrated greater sensitivity than NcoI digestion in the differentiation of B. pseudomallei and could be used for epidemiological groupings. Four cluster groups were evident among 37 isolates tested and the majority of isolates within each cluster displayed more than 65% similarity. Furthermore, multiple isolates from 18 and 35 patients with single and recurrent episodes of melioidosis, respectively, were examined. All patients with a single episode yielded genetically identical isolates and four of 35 patients with recurrent episodes were infected with strains of different genotypic patterns from the primary isolate(s). Hence, most repeated episodes of infection in melioidosis are as a result of the original infecting strains.

Bacterial Typing Techniques↗

Pathogenesis of and immunity to melioidosis.

While Burkholderia pseudomallei, the causative agent of melioidosis, is becoming increasingly recognized as a significant cause of morbidity and mortality in regions to which it is endemic, no licensed vaccine preparation currently exists for immunization against the disease. Therefore, one of the primary goals of our research has been to identify and characterize antigens expressed by B. pseudomallei isolates for the intended purpose of developing a vaccine construct that can be used to actively immunize specific high risk populations against the disease. By utilizing a combination of biochemical, immunological and molecular approaches, our studies now indicate that some of the most promising candidates for this task include flagellin proteins and the endotoxin derived O-polysaccharide (PS) antigens expressed by the organism. In this review, we have attempted to summarize the current status of B. pseudomallei research while endeavoring to provide a rationale for our approach towards the development of a melioidosis vaccine.

Antigens, Bacterial↗

Comparison of three PCR primer sets for diagnosis of septicemic melioidosis.

Several sets of PCR primers have recently been developed for detection of Burkholderia pseudomallei. In this report, the performance of 16S rRNA gene primers (16S), rRNA spacer gene primers (spacer), and 'LPS' primers (LPS) were compared. All primer sets were tested by PCR amplification of the same DNA samples extracted from blood specimens of 46 patients from northeastern Thailand, of which 29 had melioidosis based on blood culture as a gold standard. The sensitivities were 41, 35.7, and 31% while the specificities were 47, 59, and 100% for the 16S, spacer, and LPS primers, respectively. The positive predictive values were 60, 59, and 100%, while negative predictive values were 35, 34, and 46%, for these primers. The low sensitivity of PCR was suspected to be because of small numbers of bacteria in the samples. In addition, one primer set could not detect all B. pseudomallei strains. To make PCR for melioidosis more practical, bacterial concentration steps must be added. Lastly, mixed infection of patients in endemic areas may be the cause of controversial false positive PCR results, and should be further investigated.

Bacteremia↗

Melioidosis in childhood.

Two cases of childhood melioidosis in conjunction with five from the literature are presented. Although most reported cases come from Southeast Asia, importation into the United States by travelers and military personnel has occurred. The course of the disease may be acute or chronic; the onset is generally with fever and pneumonia. Melioidosis should be considered in any patient with pneumonia who has returned recently from an endemic area.

Abscess↗

Chlorination and pH of drinking water do not correlate with rates of melioidosis in the Northern Territory, Australia.

Prompted by 2 outbreaks of melioidosis with fatalities linked to culture-positive drinking water, we theorized that there may be a correlation between low drinking water pH or lack of chlorination and the rate of melioidosis in rural communities in tropical Australia. However, following adjustment for rainfall, such associations were not apparent in a multivariate regression model.

Chlorine Compounds↗

Oral fluoroquinolones for maintenance treatment of melioidosis.

Ciprofloxacin (20 mg/kg/d) or ofloxacin (12 mg/kg/d) given for a median of 15 weeks (range 12-40) were used for maintenance treatment of 57 adult patients with melioidosis. The median duration of follow-up in the 45 patients who complied with treatment and were followed for at least 6 months was 28 months (range 6-65). Fluoroquinolone treatment was well tolerated. There were 13 treatment failures (5 failures to respond, 8 relapses), a failure rate of 29% (95% confidence interval 17-43%). The median time to treatment failure was 7 months (range 2-26). These results are inferior to those with courses lasting 20 weeks of amoxycillin/clavulanic acid or the combination of chloramphenicol, doxycycline and trimethoprim/sulphamethoxazole, and suggest that the fluoroquinolones should be reserved as third line agents, and not used for the maintenance treatment of melioidosis unless there is resistance to, or intolerance of, the other available antimicrobial compounds.

Adolescent↗

Fatal melioidosis in a tourist returning from Thailand.

Severe infections with Pseudomonas pseudomallei, the causative agent of melioidosis, is a common cause of community acquired septicaemia in South East Asia and parts of Northern Australia, but infection in travellers returning to the United Kingdom is extremely rare. We describe the case of a tourist who acquired melioidosis in Thailand. Despite intensive intravenous therapy with antibiotics to which the organism was sensitive, the patient's infection proved fatal. Ps. pseudomallei was isolated from blood cultures at a late stage in his illness by use of a commercial blood culture system that included an antibiotic removal device (Bac/TAlert, Organon-Technica).

Anti-Bacterial Agents↗

Melioidosis.

Melioidosis is an infection with the gram-negative bacillus Burkholdria pseudomallei, previous known as Pseudomonas pseudomallei. We present a case report of a man with Non-Hodgkin's Lymphoma, who after visiting Indonesia presented himself with a urosepsis, with positive cultures to B. pseudomallei. Melioidosis is endemic in areas of southeast Asia and the northern part of Australia. Infection with the B. pseudomallei has a high mortality rate. Diagnosis can be made on the basis of cultures, the bacteria grow on standard media. Treatment should be based up on sensitivity studies. The optimum duration of therapy and choice of antibiotics remain to be determined. Due to the increase in travel, the infection will be seen more frequently in other parts of the world.

Anti-Bacterial Agents↗

Antibiotic susceptibility of Burkholderia pseudomallei from tropical northern Australia and implications for therapy of melioidosis.

From a prospective melioidosis study commencing in 1989 at Royal Darwin Hospital, 170 initial isolates of Burkholderia pseudomallei were available for susceptibility testing. Of these 163 (96%) were susceptible to meropenem/imipenem, ceftazidime, trimethoprim-sulphamethoxazole (SMX/TMP) and doxycycline. Seven (4%) showed primary resistance; three had low-level resistance to SMX/TMP, one to ceftriaxone and amoxycillin/clavulanate (AMOX/CA) and three to doxycycline. Of 167 patients who survived their initial presentation, seven (4%) had culture positive infections which persisted for greater than 3 months after start of therapy. All ultimately cleared carriage of B. pseudomallei though three required changing to SMX/TMP after development of doxycycline resistance. Nineteen (11%) of the initial survivors clinically relapsed and 17 of these had repeat isolates available for testing. Four of these had acquired resistance: one to doxycycline, one to AMOX/CA and ceftazidime, one to SMX/TMP and one to both SMX/TMP and doxycycline. Molecular typing using randomly amplified polymorphic DNA and pulsed-field gel electrophoresis showed all but one relapse isolate to be the same as the original strain. These data are similar to published data from Thailand. As melioidosis has a high mortality (21% in this series) these results emphasize the need for prolonged eradication therapy and regular clinical and microbiological monitoring so that the emergence of resistance can be detected early and appropriate treatment modifications made.

Amoxicillin-Potassium Clavulanate Combination↗