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Abstract

  1. Top of page
  2. Abstract
  3. Case Report 1
  4. Case Report 2
  5. Discussion
  6. Acknowledgments
  7. Declaration of Interests
  8. References

Infections caused by Burkholderia pseudomallei are rare in nonendemic areas, such as Scandinavia. We report the first two cases of melioidosis in Norway presenting with bacteraemia and splenic and prostatic abscesses, respectively.


Case Report 1

  1. Top of page
  2. Abstract
  3. Case Report 1
  4. Case Report 2
  5. Discussion
  6. Acknowledgments
  7. Declaration of Interests
  8. References

A 38-year-old man, originally from Sri Lanka, but living in Norway since 2005, was admitted to the local hospital with septicemia during spring 2007 after a history of fever, vomiting, and abdominal pain, starting a few days before admission. He suffered from diabetes mellitus type 2, but was otherwise healthy. In the previous years he had complained of intermittent abdominal pain, but both an ultrasound and X-ray performed the previous year were normal. He did not return to Sri Lanka or visit other tropical areas in the period of 2005 to 2007. At admission his blood samples showed white blood cell count (WBC) of 10.7 × 109 L−1 and the C-reactive protein (CRP) level was 100 mg/L. Abdominal computed tomography (CT) scan demonstrated a splenic abscess (Figure 1A), and he was transferred to the regional hospital for further treatment. The abscess was drained, and treatment with antibiotics was started. A fistula between the spleen and colon was eventually diagnosed, and a splenectomy was performed. Histological examination of biopsies from colon and spleen demonstrated subacute inflammation, fibrosis, and necrosis. One week after surgery he developed a subphrenic abscess that was drained successfully.

image

Figure 1. Abdominal computed tomography (CT) scan demonstrates a splenic abscess in case report 1 (A) and a prostatic abscess in case report 2 (B).

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Five days after admission there was growth in blood culture of a nonfermentative, oxidase-positive, gram-negative rod with bipolar staining. The bacteria grew on blood and lactose agar. After some days of culture, the colonies appeared large and dry with a typical wrinkled surface. The bacteria isolated from blood were identified as Burkholderia pseudomallei by the Vitek 2 system with 96.4% probability. Sequencing of the 16S rRNA gene demonstrated DNA sequences identical to sequences of B pseudomallei in GenBank. Later, the bacteria were isolated from both the splenic and the subphrenic abscesses. The commercial biochemical test API 20 NE (BioMérieux, Marcy l’Etoile, France) supported the identification. The rod grew at 42°C, which is in contrast to the characteristics of Burkholderia mallei. The minimum inhibitory concentration (MIC) values obtained from the E-tests (AB Biodisk, BioMérieux) performed on the isolates are summarized in Table 1.

Table 1.  Sensitivity patterns for the Burkholderia pseudomallei blood isolates
AntibioticsPatient 1Patient 2
MIC (mg/mL)*InterpretationMIC (mg/mL)*Interpretation
  1. MIC = minimum inhibitory concentration; NT = not tested; R = resistant; S = susceptible; TMP-SMX = trimethoprim sulfamethoxazole.

  2. *EUCASTs clinical breaking points for Pseudomonas sp. are used.

  3. Trimethoprim sulfamethoxazole.

  4. Performed on splenic isolates.

  5. §No existing breaking point.

  6. Piperacillin-tazobactam.

Meropenem1.5S1.5S
TMP-SMX0.38§3§
Pip/tazo0.75S0.75S
Gentamycin64R96R
Colistin>1,024R>256R
Ciprofloxacin6R3R
Ceftazidime3S2S
Cefotaxime16§NT 
Tetracycline1.5§3§
Aztreonam128R32R

The patient was treated with antibiotics intravenously for a total of 6 weeks. At the admission to hospital he initially received cefuroxime and metronidazole, but because of lack of clinical response this was changed to meropenem after a few days. For the last couple of weeks of the treatment he received piperacillin-tazobactam according to susceptibility data, available before the bacteria were identified. Although piperacillin-tazobactam appears to be effective in vitro, there is little clinical experience on which to recommend their use.1 However, the clinical condition of the patient improved during this period, so there is reason to believe that also in vivo susceptibility existed for this antibiotic. He was thereafter transferred back to his local hospital and received eradication therapy with trimethoprim-sulfamethoxazole (TMP-SMX) and doxycycline for a total of 20 weeks with gradual improvement of his clinical condition.

Case Report 2

  1. Top of page
  2. Abstract
  3. Case Report 1
  4. Case Report 2
  5. Discussion
  6. Acknowledgments
  7. Declaration of Interests
  8. References

A 58-year-old male with chronic lung disease, benign prostate hyperplasia, psoriatic arthritis, and excessive alcohol use returned home with his Thai wife after a 3-week stay in her home village in the southeast part of Thailand in July 2009. When returning, he had diarrhea, fever, dry cough, symptoms of urinary tract infection (UTI), and a skin abscess on his buttock that had ruptured spontaneously. At the outpatient clinic he was diagnosed with possibly pneumonia and UTI, and he was treated with oral amoxicillin. When his condition deteriorated he was admitted to the local hospital and received cefotaxime and eventually ciprofloxacin. The patient then developed kidney failure and was transferred to the regional hospital. At admission, he had fever, ataxia, and urine retention, and was mentally disorientated. His blood samples showed hemoglobin 7.8 g/mL, platelets 64 × 109 L−1, WBC 9.9 × 109 L−1, creatinine 379 umol/L, and CRP 218 mg/L. Hemolytic uremic syndrome/thrombotic thrombocytopenic purpura was excluded. A CT scan demonstrated normal abdominal parenchymal organs, muscles, and skeleton. In the lungs there were minor parenchymal infiltrates and some pleural fluid. The prostate was significantly enlarged and revealed several prostatic abscesses (Figure 1B) that were drained through the urethra. Cerebral CT and magnetic resonance imaging (MRI) scans were normal.

In the blood culture taken at the local hospital, a gram-negative nonfermentative rod grew after 24 hours of aerobic incubation and the next day the rod grew on blood (sheep) and lactose agars (incubated at 35°C with 5% CO2). The same bacteria were found in the urine. Pseudomonas sp. was suspected because the bacteria were nonfermentative, motile, and oxidase positive. However, subculture on Burkholderia medium [oxidative-fermentative polymyxin B-bacitracin-lactose agar (OFPBL)] revealed growth consistent with Burkholderia sp. Identification performed with API 20 NE did not give conclusive results (probability of B pseudomallei 51%, Pseudomonas fluorescens 39%, and Burkholderia cepacia 11%). 16S rRNA gene sequencing identified the rod as Burkholderia sp., most likely B pseudomallei or B mallei. The rod was aminoglycoside resistant and motile; therefore, B pseudomallei was concluded. The identity was later confirmed with specific real-time PCR at the Norwegian Institute of Public Health.2 The MIC values obtained from the E-tests (AB Biodisk, BioMérieux) performed on the blood isolate are summarized in Table 1.

When B pseudomallei was suspected, the patient was treated with meropenem for 14 days and his clinical condition improved. Thereafter he received eradication therapy with doxycycline and TMP-SMX for 20 weeks. No relapse of his illness had occurred 1 year after therapy. Further investigation of his renal function showed chronic renal failure with anemia because of unrecognized hypertension.

Discussion

  1. Top of page
  2. Abstract
  3. Case Report 1
  4. Case Report 2
  5. Discussion
  6. Acknowledgments
  7. Declaration of Interests
  8. References

Melioidosis is an infectious disease caused by the bacteria B pseudomallei,3,4 a strict aerobic, nonspore-forming, gram-negative rod. It is an environmental organism found in water and soil, primarily in tropical and subtropical areas, and the infection is endemic in certain areas of southeast Asia, northern Australia, and China.5,6 The mode of acquisition is by inhalation, inoculation, or ingestion. In high-endemic countries melioidosis is the most common cause of pneumonia with septicemia during the rainy season.3Burkholderia pseudomallei is also a potential agent for biological terrorism.

The two patients presented are to our knowledge the first Norwegian melioidosis cases ever reported. Outside the endemic areas, melioidosis is usually diagnosed in returning tourists or in people originating from these regions. Various clinical presentations of melioidosis have been reported in surviving Swedish and Finnish tourists after the tsunami in 2004,7,8 and in a recent publication five cases from Denmark were presented.9 Still, the risk of contracting infection with B pseudomallei is low among tourists and melioidosis is a rare disease in Scandinavia. Thus, the awareness of melioidosis is limited among the clinicians.

Melioidosis is a clinically diverse disease, with a wide range of manifestations and severities, varying from potentially fatal bacteraemia to subacute or chronic infections that can be localized or disseminated involving any organ.3 In a study from the Northern Territory in Australia, the mortality rate was 4% in the cases without bacteraemia, compared to 37% in the cases with bacteraemia.10 Abscesses in abdominal organs are well recognized, especially in the kidney, spleen, and prostate, as in our patients. Antibiotics most often resolve the infection, but prostatic abscesses may require drainage because treatment failures have developed when this was not performed.6 Splenic abscesses are generally uncommon, but in a recent study from Singapore, the most common etiological agent was B pseudomallei.11Burkholderia pseudomallei can be reactivated from latent disease long after exposure, resembling infections with Mycobacterium tuberculosis both clinically and histologically.3 Patient 1 did not return to Sri Lanka or visit other tropical areas in the period of 2005 to 2007. Thus, this might be a case of reactivation of latent melioidosis or progression of subclinical infection because the patient suffered from abdominal pain at regular intervals throughout this time period.

Risk factors for developing severe melioidosis are diabetes, excessive alcohol consumption, chronic lung disease, and chronic renal disease.3,12 It seems that patients with cystic fibrosis are at special risk of airway colonization and pulmonary infections,13 and they should be warned about the risk of traveling to melioidosis endemic regions. Still, as much as one third of the cases of melioidosis have no predisposing risk factors.4 Healthy individuals may develop fulminant melioidosis, but severe disease and fatalities are uncommon in patients without risk factors.14 Patient 2 with prostatic abscesses had several risk factors that also increased his risk of severe illness. Patient 1 was also predisposed for contracting melioidosis, due to diabetes, but was otherwise healthy.

To avoid possible delay in identification and risk of laboratory-acquired infections, clinical awareness and travel history must be communicated to the laboratory. Personnel are at special risk for exposure of B pseudomallei before the identity is recognized and precautions have been taken. Two cases of laboratory-acquired melioidosis have been described.15 Thus, to avoid infecting personnel, as soon as B pseudomallei is suspected, the isolate should be handled within Biosafety Level 3 facilities.

Culture of B pseudomallei from any clinical specimen remains the diagnostic gold standard. The bacteria grow on most routine laboratory agars within standard incubation time. However, it has been reported that cultures may be negative, and diagnosis in endemic regions is commonly based on clinical presentation.14 To identify the bacteria, conventional tests (ie, motility and oxidase), growth, and resistance pattern are crucial because manual and automated systems, as API 20 NE and Vitek 2, may fail to reliably identify B pseudomallei.16–18 The new Vitek 2 GN card performs better than earlier versions, but the sensitivity differs when taken from different agars.16 The diagnostic sensitivity of API 20 NE varies in different studies from 37% to 98%.17–19 A possible reason could be that the interpretation of assimilation tests can be difficult to read.19 It is known that Burkholderia thailandensis can be misidentified as B pseudomallei in these biochemical tests.17–19 However, this species is usually not pathogenic and rarely presents in clinical specimens. Further, studies have shown that gas–liquid chromatography analysis of bacterial fatty acid methyl esters (GLC-FAME) identifies 98% of the B pseudomallei isolates.17 Some centers have also developed in-house agglutination tests that show high sensitivity.17 Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is a relatively new and rapid method for identification of bacteria, but at present the method is not reliable in the identification of B pseudomallei.20 Finally, 16S rRNA gene sequencing21 or specific PCR2,17 will identify the bacteria to species level. The availability of these different diagnostic tests may however vary in different laboratories. An overview of the known sensitivities and specificities of the various tests for the diagnosis of B pseudomallei is shown in Table 2.

Table 2.  The sensitivities and specificities of various diagnostic methods for identification of Burkholderia pseudomallei
MethodSensitivity %Specificity %CommentMTTP
  1. MTTP = minimum time to positive.

  2. *The specificity is not given.

API 20 NE17,1937–9892Inter-study variations2.5 d
Vitek 11899*Probable ID2 d
Vitek 216,1819–81*Probable ID2 d
Monoclonal antibody agglutination test17,1994–9983Probable/confirmatory ID5 min
Specific PCR17100100Definite ID1 d
16 rRNA gene sequencing21100100Definite ID2 d

In our patients, although they were treated with adequate antibiotics, the final diagnosis was delayed. Thus, these case reports highlight the clinical and diagnostic challenges and the need of awareness among clinicians and laboratory personnel of the possibility of melioidosis in returning travelers or in patients with origin from endemic regions.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Case Report 1
  4. Case Report 2
  5. Discussion
  6. Acknowledgments
  7. Declaration of Interests
  8. References

The authors thank Per Sandven, Norwegian Institute of Public Health, Oslo, for the real-time PCR identification, Tom Øystein Jonassen at the Department of Microbiology, Oslo University Hospital, Oslo, for the DNA sequencing, and Haima Mylvaganam, Department of Microbiology, Haukeland University Hospital, Bergen, for valuable diagnostic advice.

Declaration of Interests

  1. Top of page
  2. Abstract
  3. Case Report 1
  4. Case Report 2
  5. Discussion
  6. Acknowledgments
  7. Declaration of Interests
  8. References

The authors state that they have no conflict of interest to declare.

References

  1. Top of page
  2. Abstract
  3. Case Report 1
  4. Case Report 2
  5. Discussion
  6. Acknowledgments
  7. Declaration of Interests
  8. References
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