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Fatal bacteremic melioidosis in patients with prolonged neutropenia
Diagnostic Microbiology and Infectious Disease 84 (2016) 258–260
Contents lists available at ScienceDirect
Diagnostic Microbiology and Infectious Disease journal homepage: www.elsevier.com/locate/diagmicrobio
Fatal bacteremic melioidosis in patients with prolonged neutropenia Siddharth Sridhar a, Jade L.L. Teng a, Susanna K.P. Lau a,b,c,d, Patrick C.Y. Woo a,b,c,d,⁎ a
Department of Microbiology, The University of Hong Kong, Hong Kong Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong c Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong d State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong b
a r t i c l e
i n f o
Article history: Received 5 October 2015 Received in revised form 5 November 2015 Accepted 6 November 2015 Available online 10 November 2015
a b s t r a c t Melioidosis, an infection with an expanding geographic range, is extremely rare in neutropenic patients. We report bacteremic melioidosis (ST-70 and ST-660) in 2 patients with prolonged neutropenia, who succumbed despite appropriate antibiotics. Clinicians should be aware of this emerging infection in neutropenic patients residing in or returning from endemic areas. © 2016 Elsevier Inc. All rights reserved.
Keywords: Burkholderia pseudomallei Melioidosis Prolonged neutropenia Bacteremia
Melioidosis, caused by the highly pathogenic Gram-negative bacterium, Burkholderia pseudomallei, is endemic to Southeast Asia and Australia. Risk factors for melioidosis include diabetes mellitus, kidney disease, thalassemia, and chronic lung disease (Suputtamongkol et al., 1999). In addition, there is compelling experimental evidence to suggest that neutrophils play a crucial role in the immune response to melioidosis by direct bacterial killing and proinflammatory cytokine release (Easton et al., 2007). In view of this, neutropenic individuals are theoretically at risk for severe melioidosis. Surprisingly, the medical literature contains very few accounts of melioidosis in neutropenic patients (Lin et al., 1980; Mukhopadhyay et al., 2010; Rossi et al., 2013) (Table 1). Recently, we identified 2 cases of bacteremic melioidosis affecting neutropenic adults in Queen Mary Hospital, a tertiary referral center offering hematological oncology services in Hong Kong, which is located in Southern China—a melioidosis-endemic area (Chen et al., 2015). Despite timely initiation of in vitro effective antibiotics and an initial improvement in condition, both patients died. These cases offer valuable insight into the importance of prolonged neutropenia as a distinct risk factor for bacteremic melioidosis. In case 1, a 55-year-old man with acute myeloid leukemia developed pancytopenia with prolonged neutropenia of less than 1 × 109/L (normal range: 2.01–7.42 × 10 9/L) after induction chemotherapy. Bone marrow examination showed markedly hypoplastic marrow. He was treated with supportive blood transfusions, iron chelation, and regular recombinant granulocyte-colony stimulating factor (G-CSF). No further chemotherapy was given. ⁎ Corresponding author. Tel.: +852-22554892; fax: +852-28551241. E-mail address: [email protected] (P.C.Y. Woo). http://dx.doi.org/10.1016/j.diagmicrobio.2015.11.004 0732-8893/© 2016 Elsevier Inc. All rights reserved.
Three years later, he presented with fever without localizing symptoms or signs. Cell counts on admission showed a neutrophil count of 0.47 × 109/L, which was slightly lower than his baseline (~0.9 × 109/L). Hemoglobin was 8.7 g/dL (normal range: 13.3–17.1 g/dL), and platelet count was 27 × 109/L (normal range: 162–341 × 109/L). Chest radiograph on admission did not show any consolidation. He was empirically started on intravenous meropenem at 500 mg every 8 hours after a blood culture was obtained. The blood culture yielded an isolate of B. pseudomallei, which was sensitive to imipenem and ceftazidime by disk diffusion testing. Multilocus sequence typing (MLST) showed that the isolate belonged to sequence type (ST) 70 (http://bpseudomallei.mlst.net/). He was switched to intravenous ceftazidime at 2 g every 8 hours and was given regular adjunctive G-CSF, but the neutrophil response was poor and levels were consistently below 0.75 × 109/L. He initially defervesced, and blood cultures were rendered negative. However, after 7 days of treatment, he developed worsening right lung middle and lower lobe consolidation requiring intubation and intensive care support (Fig. 1). His condition deteriorated, and he succumbed 10 days after admission. In case 2, a 57-year-old man suffered from advanced follicular lymphoma that was refractory to first and second-line chemotherapy. He had documented bone marrow involvement with persistently low neutrophil counts. He presented with generalized malaise and epistaxis. Cell counts on admission showed neutrophil count of 0.52 × 109/L and platelet count of 5 × 10 9/L (normal range: 162–341 × 10 9/L). Lymphocyte counts were within normal range. Two days after admission, he developed high fever and right knee swelling. The neutrophil count dropped further to 0.27 × 10 9/L. Ultrasonographic examination of the swollen knee showed evidence of infrapatellar bursitis. Tapping of the bursal fluid could not be carried out due to severe thrombocytopenia.
S. Sridhar et al. / Diagnostic Microbiology and Infectious Disease 84 (2016) 258–260
259
Table 1 Characteristics of neutropenic patients with melioidosis described in the literature. References
Year of reporting
Age (y)/sex
Country
Underlying condition
Site(s) of involvement
Outcome
Lin et al. (1980) Mukhopadhyay et al. (2010) Mukhopadhyay et al. (2010) Rossi et al. (2013) Present case 1 Present case 2
1980 2010 2010 2013 2015 2015
13/male 46/female 35/male 48/male 55/male 57/male
Malaysia India India France ex. Thailand Hong Kong Hong Kong
Acute lymphoblastic leukemia on chemotherapy Ovarian carcinoma on chemotherapy Gastric carcinoma on chemotherapy Hairy cell leukemia Acute myeloid leukemia, postchemotherapy Follicular lymphoma
Skin, bloodstream Bloodstream Lung Liver abscess Blood Blood
Death Death Recovered Recovered Death Death
The patient was empirically given intravenous meropenem 500 mg every 6 hours. G-CSF was not given due to active hematological malignancy in the bone marrow. Blood culture obtained at fever onset yielded B. pseudomallei. MLST showed that the isolate belonged to ST-660. Repeated blood culture taken after 1 week of meropenem still yielded B. pseudomallei, and the isolate remained sensitive to imipenem by disk diffusion testing. In view of treatment failure with meropenem, the antibiotic was switched to intravenous ceftazidime at 2 g every 12 hours. Although subsequent blood cultures were rendered negative, the patient developed new-onset consolidative changes over both lung fields. Due to underlying terminal malignancy, further invasive investigations were not pursued. The patient succumbed 25 days after admission. Both our patients had prolonged neutropenia prior to admission without other risk factors for melioidosis. The 2 B. pseudomallei isolates recovered in the present study belonged to ST-70 and ST-660, respectively. ST70 has been extensively reported in patients with invasive diseases and various environmental sources in Hong Kong and Thailand (Godoy et al., 2003; Vesaratchavest et al., 2006), whereas ST-660 has only been found in rainwater in Hong Kong. With the expanding geographic range of melioidosis, more immunocompromised patients may be at risk for neutropenic melioidosis. Both patients deteriorated with pulmonary involvement despite initially responding to appropriate antibiotic therapy. It is notable that both neutropenic patients with bacteremic melioidosis reported previously in the literature also succumbed (Lin et al., 1980; Mukhopadhyay et al., 2010), highlighting the severe outcomes of this condition in the neutropenic population. These cases cumulatively illustrate the difficulty in controlling melioidosis without reconstitution of an effective immune response. A small randomized controlled trial of G-CSF therapy in patients with melioidosis showed no improvement in overall
A
outcome; however, there was evidence of longer survival (Cheng et al., 2007). However, this trial excluded neutropenic patients during recruitment. G-CSF needs to be considered in the management of melioidotic neutropenic patients due to the high mortality despite appropriate antibiotic use. Melioidosis in neutropenic patients is likely to be underdiagnosed. Cultures remain the “gold standard” for the diagnosis of melioidosis; however, the sensitivity of culture-based diagnosis is poor. Culturing B. pseudomallei from nonsterile samples requires selective media, which relies on the clinician to alert the laboratory on the possibility of melioidosis (Lau et al., 2015; Limmathurotsakul et al., 2010). This problem is compounded in neutropenic patients who are often empirically given carbapenems before adequate microbiological specimens can be obtained, further compromising the sensitivity of cultures. Even with successful culture, identification of the isolate by matrixassisted laser desorption ionization–time of flight mass spectrometry requires that adequate reference spectra for B. pseudomallei and closely related species such as Burkholderia thailandensis are included in the database (Lau et al., 2012). As for serological diagnosis, melioidosis antibody seronegativity during bacteremia is well described even among immunocompetent individuals (Harris et al., 2009). Both the patients presented in this report were seronegative using an in-house lipopolysaccharide-based enzyme immunoassay. Clinicians must be aware of the possibility of melioidosis when treating patients with febrile neutropenia residing in or returning from endemic areas, particularly in patients who have prolonged low neutrophil counts before the onset of fever. Timely diagnosis and treatment with appropriate antibiotics and G-CSF may prolong survival; however, new management algorithms to improve outcomes are required in neutropenic patients with bacteremic melioidosis.
B
Fig. 1. Development of right lung consolidation despite appropriate antimicrobial therapy for melioidosis in case 1. (A) Baseline chest radiograph. (B) Chest radiograph after 7 days of ceftazidime treatment.
260
S. Sridhar et al. / Diagnostic Microbiology and Infectious Disease 84 (2016) 258–260
Funding information This work is partly supported by the Strategic Research Theme Fund, The University of Hong Kong, Hong Kong, and Croucher Senior Medical Research Fellowship, Croucher Foundation, Hong Kong. Conflict of interests We declare no conflicts of interest. Acknowledgments We thank Dr Philip Yeung and Justin Jia for facilitation of the study. References Chen H, Xia L, Zhu X, Li W, Du X, Wu D, et al. Burkholderia pseudomallei sequence type 562 in China and Australia. Emerg Infect Dis 2015;21:166–8. Cheng AC, Limmathurotsakul D, Chierakul W, Getchalarat N, Wuthiekanun V, Stephens DP, et al. A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand. Clin Infect Dis 2007;45:308–14. Easton A, Haque A, Chu K, Lukaszewski R, Bancroft GJ. A critical role for neutrophils in resistance to experimental infection with Burkholderia pseudomallei. J Infect Dis 2007; 195:99–107.
Godoy D, Randle G, Simpson AJ, Aanensen DM, Pitt TL, Kinoshita R, et al. Multilocus sequence typing and evolutionary relationships among the causative agents of melioidosis and glanders, Burkholderia pseudomallei and Burkholderia mallei. J Clin Microbiol 2003;41:2068–79. Harris PN, Ketheesan N, Owens L, Norton RE. Clinical features that affect indirecthemagglutination-assay responses to Burkholderia pseudomallei. Clin Vaccine Immunol 2009;16:924–30. Lau SK, Tang BS, Curreem SO, Chan TM, Martelli P, Tse CW, et al. Matrix-assisted laser desorption ionization-time of flight mass spectrometry for rapid identification of Burkholderia pseudomallei: importance of expanding databases with pathogens endemic to different localities. J Clin Microbiol 2012;50:3142–3. Lau SK, Sridhar S, Ho CC, Chow WN, Lee KC, Lam CW, et al. Laboratory diagnosis of melioidosis: past, present and future. Exp Biol Med 2015;240:742–51. Limmathurotsakul D, Jamsen K, Arayawichanont A, Simpson JA, White LJ, Lee SJ, et al. Defining the true sensitivity of culture for the diagnosis of melioidosis using Bayesian latent class models. PLoS One 2010;5:e12485. http://dx.doi.org/10.1371/journal.pone.0012485. Lin HP, Puthucheary SD, Sinniah D. Acute septicemic melioidosis occurring in a child with acute lymphoblastic leukemia. Clin Pediatr (Phila) 1980;19:697–9. Mukhopadhyay C, Chawla K, Vandana KE, Krishna S, Saravu K. Pulmonary melioidosis in febrile neutropenia: the rare and deadly duet. Trop Doct 2010;40:165–6. Rossi B, Epelboin L, Jauréguiberry S, Lecso M, Roos-Weil D, Gabarre J, et al. Melioidosis and hairy cell leukemia in 2 travelers returning from Thailand. Emerg Infect Dis 2013;19: 503–5. Suputtamongkol Y, Chaowagul W, Chetchotisakd P, Lertpatanasuwun N, Intaranongpal S, Ruchutrakool T, et al. Risk factors for melioidosis and bacteremic melioidosis. Clin Infect Dis 1999;29:408–13. Vesaratchavest M, Tumapa S, Day NP, Wuthiekanun V, Chierakul W, Holden MT, et al. Nonrandom distribution of Burkholderia pseudomallei clones in relation to geographical location and virulence. J Clin Microbiol 2006;44:2553–7.
Contents lists available at ScienceDirect
Diagnostic Microbiology and Infectious Disease journal homepage: www.elsevier.com/locate/diagmicrobio
Fatal bacteremic melioidosis in patients with prolonged neutropenia Siddharth Sridhar a, Jade L.L. Teng a, Susanna K.P. Lau a,b,c,d, Patrick C.Y. Woo a,b,c,d,⁎ a
Department of Microbiology, The University of Hong Kong, Hong Kong Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong c Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong d State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong b
a r t i c l e
i n f o
Article history: Received 5 October 2015 Received in revised form 5 November 2015 Accepted 6 November 2015 Available online 10 November 2015
a b s t r a c t Melioidosis, an infection with an expanding geographic range, is extremely rare in neutropenic patients. We report bacteremic melioidosis (ST-70 and ST-660) in 2 patients with prolonged neutropenia, who succumbed despite appropriate antibiotics. Clinicians should be aware of this emerging infection in neutropenic patients residing in or returning from endemic areas. © 2016 Elsevier Inc. All rights reserved.
Keywords: Burkholderia pseudomallei Melioidosis Prolonged neutropenia Bacteremia
Melioidosis, caused by the highly pathogenic Gram-negative bacterium, Burkholderia pseudomallei, is endemic to Southeast Asia and Australia. Risk factors for melioidosis include diabetes mellitus, kidney disease, thalassemia, and chronic lung disease (Suputtamongkol et al., 1999). In addition, there is compelling experimental evidence to suggest that neutrophils play a crucial role in the immune response to melioidosis by direct bacterial killing and proinflammatory cytokine release (Easton et al., 2007). In view of this, neutropenic individuals are theoretically at risk for severe melioidosis. Surprisingly, the medical literature contains very few accounts of melioidosis in neutropenic patients (Lin et al., 1980; Mukhopadhyay et al., 2010; Rossi et al., 2013) (Table 1). Recently, we identified 2 cases of bacteremic melioidosis affecting neutropenic adults in Queen Mary Hospital, a tertiary referral center offering hematological oncology services in Hong Kong, which is located in Southern China—a melioidosis-endemic area (Chen et al., 2015). Despite timely initiation of in vitro effective antibiotics and an initial improvement in condition, both patients died. These cases offer valuable insight into the importance of prolonged neutropenia as a distinct risk factor for bacteremic melioidosis. In case 1, a 55-year-old man with acute myeloid leukemia developed pancytopenia with prolonged neutropenia of less than 1 × 109/L (normal range: 2.01–7.42 × 10 9/L) after induction chemotherapy. Bone marrow examination showed markedly hypoplastic marrow. He was treated with supportive blood transfusions, iron chelation, and regular recombinant granulocyte-colony stimulating factor (G-CSF). No further chemotherapy was given. ⁎ Corresponding author. Tel.: +852-22554892; fax: +852-28551241. E-mail address: [email protected] (P.C.Y. Woo). http://dx.doi.org/10.1016/j.diagmicrobio.2015.11.004 0732-8893/© 2016 Elsevier Inc. All rights reserved.
Three years later, he presented with fever without localizing symptoms or signs. Cell counts on admission showed a neutrophil count of 0.47 × 109/L, which was slightly lower than his baseline (~0.9 × 109/L). Hemoglobin was 8.7 g/dL (normal range: 13.3–17.1 g/dL), and platelet count was 27 × 109/L (normal range: 162–341 × 109/L). Chest radiograph on admission did not show any consolidation. He was empirically started on intravenous meropenem at 500 mg every 8 hours after a blood culture was obtained. The blood culture yielded an isolate of B. pseudomallei, which was sensitive to imipenem and ceftazidime by disk diffusion testing. Multilocus sequence typing (MLST) showed that the isolate belonged to sequence type (ST) 70 (http://bpseudomallei.mlst.net/). He was switched to intravenous ceftazidime at 2 g every 8 hours and was given regular adjunctive G-CSF, but the neutrophil response was poor and levels were consistently below 0.75 × 109/L. He initially defervesced, and blood cultures were rendered negative. However, after 7 days of treatment, he developed worsening right lung middle and lower lobe consolidation requiring intubation and intensive care support (Fig. 1). His condition deteriorated, and he succumbed 10 days after admission. In case 2, a 57-year-old man suffered from advanced follicular lymphoma that was refractory to first and second-line chemotherapy. He had documented bone marrow involvement with persistently low neutrophil counts. He presented with generalized malaise and epistaxis. Cell counts on admission showed neutrophil count of 0.52 × 109/L and platelet count of 5 × 10 9/L (normal range: 162–341 × 10 9/L). Lymphocyte counts were within normal range. Two days after admission, he developed high fever and right knee swelling. The neutrophil count dropped further to 0.27 × 10 9/L. Ultrasonographic examination of the swollen knee showed evidence of infrapatellar bursitis. Tapping of the bursal fluid could not be carried out due to severe thrombocytopenia.
S. Sridhar et al. / Diagnostic Microbiology and Infectious Disease 84 (2016) 258–260
259
Table 1 Characteristics of neutropenic patients with melioidosis described in the literature. References
Year of reporting
Age (y)/sex
Country
Underlying condition
Site(s) of involvement
Outcome
Lin et al. (1980) Mukhopadhyay et al. (2010) Mukhopadhyay et al. (2010) Rossi et al. (2013) Present case 1 Present case 2
1980 2010 2010 2013 2015 2015
13/male 46/female 35/male 48/male 55/male 57/male
Malaysia India India France ex. Thailand Hong Kong Hong Kong
Acute lymphoblastic leukemia on chemotherapy Ovarian carcinoma on chemotherapy Gastric carcinoma on chemotherapy Hairy cell leukemia Acute myeloid leukemia, postchemotherapy Follicular lymphoma
Skin, bloodstream Bloodstream Lung Liver abscess Blood Blood
Death Death Recovered Recovered Death Death
The patient was empirically given intravenous meropenem 500 mg every 6 hours. G-CSF was not given due to active hematological malignancy in the bone marrow. Blood culture obtained at fever onset yielded B. pseudomallei. MLST showed that the isolate belonged to ST-660. Repeated blood culture taken after 1 week of meropenem still yielded B. pseudomallei, and the isolate remained sensitive to imipenem by disk diffusion testing. In view of treatment failure with meropenem, the antibiotic was switched to intravenous ceftazidime at 2 g every 12 hours. Although subsequent blood cultures were rendered negative, the patient developed new-onset consolidative changes over both lung fields. Due to underlying terminal malignancy, further invasive investigations were not pursued. The patient succumbed 25 days after admission. Both our patients had prolonged neutropenia prior to admission without other risk factors for melioidosis. The 2 B. pseudomallei isolates recovered in the present study belonged to ST-70 and ST-660, respectively. ST70 has been extensively reported in patients with invasive diseases and various environmental sources in Hong Kong and Thailand (Godoy et al., 2003; Vesaratchavest et al., 2006), whereas ST-660 has only been found in rainwater in Hong Kong. With the expanding geographic range of melioidosis, more immunocompromised patients may be at risk for neutropenic melioidosis. Both patients deteriorated with pulmonary involvement despite initially responding to appropriate antibiotic therapy. It is notable that both neutropenic patients with bacteremic melioidosis reported previously in the literature also succumbed (Lin et al., 1980; Mukhopadhyay et al., 2010), highlighting the severe outcomes of this condition in the neutropenic population. These cases cumulatively illustrate the difficulty in controlling melioidosis without reconstitution of an effective immune response. A small randomized controlled trial of G-CSF therapy in patients with melioidosis showed no improvement in overall
A
outcome; however, there was evidence of longer survival (Cheng et al., 2007). However, this trial excluded neutropenic patients during recruitment. G-CSF needs to be considered in the management of melioidotic neutropenic patients due to the high mortality despite appropriate antibiotic use. Melioidosis in neutropenic patients is likely to be underdiagnosed. Cultures remain the “gold standard” for the diagnosis of melioidosis; however, the sensitivity of culture-based diagnosis is poor. Culturing B. pseudomallei from nonsterile samples requires selective media, which relies on the clinician to alert the laboratory on the possibility of melioidosis (Lau et al., 2015; Limmathurotsakul et al., 2010). This problem is compounded in neutropenic patients who are often empirically given carbapenems before adequate microbiological specimens can be obtained, further compromising the sensitivity of cultures. Even with successful culture, identification of the isolate by matrixassisted laser desorption ionization–time of flight mass spectrometry requires that adequate reference spectra for B. pseudomallei and closely related species such as Burkholderia thailandensis are included in the database (Lau et al., 2012). As for serological diagnosis, melioidosis antibody seronegativity during bacteremia is well described even among immunocompetent individuals (Harris et al., 2009). Both the patients presented in this report were seronegative using an in-house lipopolysaccharide-based enzyme immunoassay. Clinicians must be aware of the possibility of melioidosis when treating patients with febrile neutropenia residing in or returning from endemic areas, particularly in patients who have prolonged low neutrophil counts before the onset of fever. Timely diagnosis and treatment with appropriate antibiotics and G-CSF may prolong survival; however, new management algorithms to improve outcomes are required in neutropenic patients with bacteremic melioidosis.
B
Fig. 1. Development of right lung consolidation despite appropriate antimicrobial therapy for melioidosis in case 1. (A) Baseline chest radiograph. (B) Chest radiograph after 7 days of ceftazidime treatment.
260
S. Sridhar et al. / Diagnostic Microbiology and Infectious Disease 84 (2016) 258–260
Funding information This work is partly supported by the Strategic Research Theme Fund, The University of Hong Kong, Hong Kong, and Croucher Senior Medical Research Fellowship, Croucher Foundation, Hong Kong. Conflict of interests We declare no conflicts of interest. Acknowledgments We thank Dr Philip Yeung and Justin Jia for facilitation of the study. References Chen H, Xia L, Zhu X, Li W, Du X, Wu D, et al. Burkholderia pseudomallei sequence type 562 in China and Australia. Emerg Infect Dis 2015;21:166–8. Cheng AC, Limmathurotsakul D, Chierakul W, Getchalarat N, Wuthiekanun V, Stephens DP, et al. A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand. Clin Infect Dis 2007;45:308–14. Easton A, Haque A, Chu K, Lukaszewski R, Bancroft GJ. A critical role for neutrophils in resistance to experimental infection with Burkholderia pseudomallei. J Infect Dis 2007; 195:99–107.
Godoy D, Randle G, Simpson AJ, Aanensen DM, Pitt TL, Kinoshita R, et al. Multilocus sequence typing and evolutionary relationships among the causative agents of melioidosis and glanders, Burkholderia pseudomallei and Burkholderia mallei. J Clin Microbiol 2003;41:2068–79. Harris PN, Ketheesan N, Owens L, Norton RE. Clinical features that affect indirecthemagglutination-assay responses to Burkholderia pseudomallei. Clin Vaccine Immunol 2009;16:924–30. Lau SK, Tang BS, Curreem SO, Chan TM, Martelli P, Tse CW, et al. Matrix-assisted laser desorption ionization-time of flight mass spectrometry for rapid identification of Burkholderia pseudomallei: importance of expanding databases with pathogens endemic to different localities. J Clin Microbiol 2012;50:3142–3. Lau SK, Sridhar S, Ho CC, Chow WN, Lee KC, Lam CW, et al. Laboratory diagnosis of melioidosis: past, present and future. Exp Biol Med 2015;240:742–51. Limmathurotsakul D, Jamsen K, Arayawichanont A, Simpson JA, White LJ, Lee SJ, et al. Defining the true sensitivity of culture for the diagnosis of melioidosis using Bayesian latent class models. PLoS One 2010;5:e12485. http://dx.doi.org/10.1371/journal.pone.0012485. Lin HP, Puthucheary SD, Sinniah D. Acute septicemic melioidosis occurring in a child with acute lymphoblastic leukemia. Clin Pediatr (Phila) 1980;19:697–9. Mukhopadhyay C, Chawla K, Vandana KE, Krishna S, Saravu K. Pulmonary melioidosis in febrile neutropenia: the rare and deadly duet. Trop Doct 2010;40:165–6. Rossi B, Epelboin L, Jauréguiberry S, Lecso M, Roos-Weil D, Gabarre J, et al. Melioidosis and hairy cell leukemia in 2 travelers returning from Thailand. Emerg Infect Dis 2013;19: 503–5. Suputtamongkol Y, Chaowagul W, Chetchotisakd P, Lertpatanasuwun N, Intaranongpal S, Ruchutrakool T, et al. Risk factors for melioidosis and bacteremic melioidosis. Clin Infect Dis 1999;29:408–13. Vesaratchavest M, Tumapa S, Day NP, Wuthiekanun V, Chierakul W, Holden MT, et al. Nonrandom distribution of Burkholderia pseudomallei clones in relation to geographical location and virulence. J Clin Microbiol 2006;44:2553–7.