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Melioidosis
The Netherlands Journal of Medicine 54 (1999) 76–79
Brief report
Melioidosis A. Beeker*, K.D. Van de Stadt, K. Bakker ¨ 2, 2102 CW Heemstede, The Netherlands Department of Internal Medicine, Spaarne Ziekenhuis Heemstede, Handellaan Received 12 May 1998; received in revised form 8 September 1998; accepted 13 October 1998
Abstract 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. 1999 Published by Elsevier Science B.V. All rights reserved. Keywords: Melioidosis; Burkholdria pseudomallei; Pseudomonas pseudomallei
Introduction Melioidosis is an infection with the gram-negative aerobe bacillus Burkholdria pseudomallei, previously known as Pseudomonas pseudomallei. It is a tropical infection which is endemic in parts of southeast Asia and northern Australia. It can cause symptomatic infections sometimes followed by overwhelming sepsis. Symptomatic infections cause serious morbidity and mortality. Infection usually occurs by the respiratory or cutaneous route.
Case A 48-year-old man, who was treated in the past for a Non-Hodgkin’s Lymphoma, presented himself *Corresponding author. Tel.: 1 31-23-5141516.
at the hospital with high fever a few weeks after returning from a holiday in Indonesia. He also experienced rigor and a painful micturition. On physical examination we saw a man who was seriously ill. Vitals: BP: 130 over 90, pulse: 95 regular and a temperature of 39.28C. Palpation of the abdomen was painful in the right kidney region. There were no other physical abnormalities. Laboratory findings: ESR 100mm, leukocyte count 8.9 3 10 9 / l, with a normal differentiation. The C-reactive protein was 127 mg / l. A urine examination showed bacteria, leukocytes and protein. A diagnosis of urosepsis was made and treatment with parenteral ciprofloxacin was started. When the blood and urine cultures became positive for Burkholdria pseudomallei treatment was changed into ceftazidime 3 3 2 gram for six weeks i.v. followed by amoxycillin / clavulanate 4 3 1000 / 200 mg orally for six months. Within a few days the patient was feeling better, and
0300-2977 / 99 / $ – see front matter 1999 Published by Elsevier Science B.V. All rights reserved. PII: S0300-2977( 98 )00129-6
A. Beeker et al. / The Netherlands Journal of Medicine 54 (1999) 76 – 79
after six weeks of antibiotic treatment he could be discharged. After a few months the patient experienced a severe relapse of his Non-Hodgkin’s Lymphoma. The decision was made to treat the patient with chemotherapy. During every course of his chemotherapeutic therapy he also received i.v. ceftazidime and oral amoxicillin / clavulanate to prevent a relapse of his melioidosis. The patient is symptom-free for over two years now.
77
experiences headache, myalgia, anorexia and high fevers, followed by rigors, chest pain, cough that may be productive or even haemoptosis. An acute localised supportive infection of the skin usually presents itself as an nodule with an area of lymphangitis and lymphadenopathy. Other common forms of infection include urinary tract infections and arthritis [1,3]. More rare manifestations include central nervous system infections and osteomyelitis [1,3].
Septicaemic infection Clinical manifestations Infection with B. pseudomallei can present itself in many ways, mimicking other infectious diseases. Therefore it is sometimes named ‘the great imitator of every infectious disease.’ More concrete, infection with B. pseudomallei can be divided in four categories: asymptomatic infection, localised infection, septicaemia and chronic infection. Cases of symptomatic infection are from all over the world, but the majority of cases are reported from southeast Asia where melioidosis is endemic.
Septicaemia caused by B. pseudomallei often has a rapidly fatal course. In one study in Thailand melioidosis accounted for 19% of admissions and 40% of deaths from community-acquired septicaemia [5]. Mortality rates as high as 90% have been reported [3]. The mortality rates have declined in recent years because of newer more effective antibiotics like ceftazidime [6–8]. Symptoms differ accordingly to the primary site of infection. Patients with the septicaemic form of melioidosis often are compromised hosts. Underlying diseases include diabetes mellitus, AIDS, renal failure and malignancies [1,3,9].
Asymptomatic infections Chronic infection This is probably the most common form of infection [1,2]. Serological studies in children from northeast Thailand revealed a seroconversion rate for B. pseudomallei antibodies of 24% per year, to a plateau of 80% seroprevalence in those 4 years of age, without having experienced an symptomatic infection [2]. One has to realise that an asymptomatic infection can become symptomatic even after a latency period of up to many years [1,3].
Chronic melioidosis in most cases causes abscesses which develop in infected tissues [1,3,10]. Secondary abscesses can develop in almost any organ: lung, liver, bone, and even in the brain. Symptoms vary according to the site of infection. It is important to realise that these patients can be afebrile.
Diagnosis Symptomatic localised infections The localised infection with B. pseudomallei can be seen in every organ system but most cases are presented as acute pulmonary infections [1,3,4]. The infection can range from a mild bronchitis to a necrotising pneumonia. The pneumonia more frequently involves the upper lobes. The patient usually
As the bacteria can be cultured easily on standard agar media, it is not difficult to diagnose this infectious disease [1,3]. Other diagnostic tools include an enzyme-linked immunosorbent assay (ELISA) for B. pseudomallei [1], an indirect haemagglutination assay (IHA) [1,2], a latex agglutination test [11] and a enzyme immunoassay detection of urinary B. pseudomallei antigen [12]. All
78
A. Beeker et al. / The Netherlands Journal of Medicine 54 (1999) 76 – 79
of the tests as mentioned can be helpful in making the diagnosis of melioidosis in patients, in case bacterial cultures are negative. One of the practical problems is that not all of these tests are available in all countries. Another problem is that positive serological tests prove infection but cannot distinguish between active and latent disease [1]. Therefore bacterial cultures still are the hallmark for the diagnosis of melioidosis. Due to the increasing mobility of the world population, it is important to consider melioidosis in every differential diagnosis of a patient with febrile illness who has traveled to southeast Asia and the northern part of Australia, especially those patients who present themselves with pulmonary infection, septicaemia or being compromised host.
Treatment B. pseudomallei infections are difficult to treat and to eradicate [1,3]. The bacteria is resistant to several antibiotics, as benzylpenicillin G, erythromycin, streptomycin and ciprofloxacin [3,13–15]. Treatment should therefore be based upon sensitivity studies [14,15]. MIC studies showed that imipenem, piperacillin, amoxicillin / clavulanate and ceftazidime are the most effective antibiotics [14]. To evaluate the management of melioidosis repetitive cultures, C-reactive protein and the temperature of the patient are the best parameters [16,17]. Even after successful treatment of melioidosis there is still a serious risk of relapse of the infection [16].
Septicaemic infection Although there is some in vitro evidence that newer carbapenem antibiotics perform better, i.v. ceftazidime is the drug of choice in the treatment of severe melioidosis [1,3,6–8,13–15]. Treatment for severe melioidosis should consist of i.v. antibiotics for up to 6 weeks followed by oral maintenance treatment for up to 6 months [6,7]. Oral maintenance treatment can consist of the combination of doxycycline and trimethoprim / sulfamethoxazole, but monotherapy with amoxicillin / clavulanate seems also to be effective [7].
Localised infections For localised infections treatment should consist of oral antibiotics for at least 2 months. When the infection consists of an extrapulmonary supportive lesion, treatment should be continued much longer [1,3].
Conclusion Melioidosis, an infection with the Burkholdria pseudomallei, is endemic in some parts of the world. The infection can present itself in many different ways. Due to the growing mobility of the world population, infections are likely to be seen in other then the endemic areas alone. People with underlying disease are especially at risk. In the case we presented we considered the patient to be immunocompromised because of his Non-Hodgkin’s Lymphoma. This fact, and his visit to an endemic area, made us aware of the possibility of melioidosis and the diagnosis was quickly made. The process of diagnosing is relatively easy as the bacteria grow on standard media. Treatment should be based on resistance patterns. A combination of i.v. antibiotics for at least 2 to 6 weeks followed by oral maintenance therapy for up to 6 months is the regimen of choice for the treatment of serious infections. The optimum duration of therapy and choice of antibiotics remain to be determined. About one out of four patients experiences a relapse of the infection. To prevent a relapse of the melioidosis we have chosen to treat our patient during chemotherapeutic treatment for his Non-Hodgkin’s Lymphoma with i.v. ceftazidime and oral amoxicillin / clavalunate.
References [1] Leelarasamee A, Bovornkitti S. Melioidosis: review and update. Rev Infect Dis 1989;11:413–25. [2] Kanaphun P, Thirawattanasuk N, Suputtamongkol Y, et al. Serology and carriage of Pseudomonas pseudomallei: A prospective study in 1000 hospitalized children in northeast Thailand. J Infect Dis 1993;167:230–3. [3] Sanford J.P. Pseudomonas species. In: Mandell G.I., Douglas R.G., Jr., Bennet J.E., editors. Principles and Practice of
A. Beeker et al. / The Netherlands Journal of Medicine 54 (1999) 76 – 79
[4] [5]
[6]
[7]
[8]
[9]
[10] [11]
Infectious Diseases, 4th ed. New York: John Wiley and Sons, 1995:2003–2008. Everett DE, Nelson RA. Pulmonary melioidosis. Am Rev Resp Dis 1975;112:331–40. Chaowagul W, White NJ, Dance DAB. Melioidosis: a major cause of community-acquired septicemia in north-eastern Thailand. J Infect Dis 1989;159:890–9. White N.J., Chaowagul W., Wuthiekanun V., Dance D.A.B, .Wattanagoon Y., Pitakwatchara N. Halving of mortality of severe melioidosis by ceftazidime. The Lancet 1989:697– 701. Suputtamongkol Y, Rajchanuwong A, Chaowagul W, et al. Ceftazidime vs. amoxicillin / clavulanate in the treatment of severe melioidosis. Clin Infect Dis 1994;19:846–53. Sauerwein RW, Lammers JW, Horrevoets AM. Ceftazidime monotherapy for pulmonary melioidosis in a traveller returning from Thailand. Chest 1992;101:555–7. Tamphaichitra D. Tropical disease in the immunocompromised host: Melioidosis and pythosis. Rev Infect Dis 1989;11:s1629–43. Wong KT, Puthucheary SD, Vadivelu J. The histopathology of human melioidosis. Histopathology 1995;26:51–5. Smith MD, Wuthiekanun V, Walsh AL, Pitt TL. Latex
[12]
[13]
[14]
[15]
[16]
[17]
79
agglutination test for identification of Pseudomonas pseudo¨ J Clin Path 1993;46:374–5. malleı. Desakorn V, Smith MD, Wuthiekanun V, et al. Detection of Pseudomonas pseudomalleı¨ antigen in urine for the diagnosis of melioidosis. Am J Trop Med Hyg 1994;51:627–33. Dance D.A.B., Wuthiekanun V., White N.J., Chaowagul W. Antibiotic resistance in Pseudomonas pseudomalleı¨ (Letter). The Lancet 1988:994–995. Dance DAB, Wuthiekanun V, Chaowagul W, White NJ. The ¨ antimicrobial susceptibility of Pseudomonas pseudomalleı. Emergence of resistance in vitro and during treatment. J Antimicrob Chemother 1989;24:295–309. Smith M.D., Wuthiekanun V., Walsh A.L., White N.J. Susceptibility of Pseudomonas pseudomalleı¨ to some newer blactam antibiotics and antibiotic combinations using time-kill studies. Chowagul W, Suputtamongkol Y, Dance DAB, Rajchanuvong A, Pattara-arechachai J, White NJ. Relapse in melioidosis: Incidence and risk factors. J Infect Dis 1993;168:1181–5. Ashdown LR. Serial serum c-reactive protein levels as an aid to the management of melioidosis. Am J Trop Med Hyg 1992;46:151–7.
Brief report
Melioidosis A. Beeker*, K.D. Van de Stadt, K. Bakker ¨ 2, 2102 CW Heemstede, The Netherlands Department of Internal Medicine, Spaarne Ziekenhuis Heemstede, Handellaan Received 12 May 1998; received in revised form 8 September 1998; accepted 13 October 1998
Abstract 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. 1999 Published by Elsevier Science B.V. All rights reserved. Keywords: Melioidosis; Burkholdria pseudomallei; Pseudomonas pseudomallei
Introduction Melioidosis is an infection with the gram-negative aerobe bacillus Burkholdria pseudomallei, previously known as Pseudomonas pseudomallei. It is a tropical infection which is endemic in parts of southeast Asia and northern Australia. It can cause symptomatic infections sometimes followed by overwhelming sepsis. Symptomatic infections cause serious morbidity and mortality. Infection usually occurs by the respiratory or cutaneous route.
Case A 48-year-old man, who was treated in the past for a Non-Hodgkin’s Lymphoma, presented himself *Corresponding author. Tel.: 1 31-23-5141516.
at the hospital with high fever a few weeks after returning from a holiday in Indonesia. He also experienced rigor and a painful micturition. On physical examination we saw a man who was seriously ill. Vitals: BP: 130 over 90, pulse: 95 regular and a temperature of 39.28C. Palpation of the abdomen was painful in the right kidney region. There were no other physical abnormalities. Laboratory findings: ESR 100mm, leukocyte count 8.9 3 10 9 / l, with a normal differentiation. The C-reactive protein was 127 mg / l. A urine examination showed bacteria, leukocytes and protein. A diagnosis of urosepsis was made and treatment with parenteral ciprofloxacin was started. When the blood and urine cultures became positive for Burkholdria pseudomallei treatment was changed into ceftazidime 3 3 2 gram for six weeks i.v. followed by amoxycillin / clavulanate 4 3 1000 / 200 mg orally for six months. Within a few days the patient was feeling better, and
0300-2977 / 99 / $ – see front matter 1999 Published by Elsevier Science B.V. All rights reserved. PII: S0300-2977( 98 )00129-6
A. Beeker et al. / The Netherlands Journal of Medicine 54 (1999) 76 – 79
after six weeks of antibiotic treatment he could be discharged. After a few months the patient experienced a severe relapse of his Non-Hodgkin’s Lymphoma. The decision was made to treat the patient with chemotherapy. During every course of his chemotherapeutic therapy he also received i.v. ceftazidime and oral amoxicillin / clavulanate to prevent a relapse of his melioidosis. The patient is symptom-free for over two years now.
77
experiences headache, myalgia, anorexia and high fevers, followed by rigors, chest pain, cough that may be productive or even haemoptosis. An acute localised supportive infection of the skin usually presents itself as an nodule with an area of lymphangitis and lymphadenopathy. Other common forms of infection include urinary tract infections and arthritis [1,3]. More rare manifestations include central nervous system infections and osteomyelitis [1,3].
Septicaemic infection Clinical manifestations Infection with B. pseudomallei can present itself in many ways, mimicking other infectious diseases. Therefore it is sometimes named ‘the great imitator of every infectious disease.’ More concrete, infection with B. pseudomallei can be divided in four categories: asymptomatic infection, localised infection, septicaemia and chronic infection. Cases of symptomatic infection are from all over the world, but the majority of cases are reported from southeast Asia where melioidosis is endemic.
Septicaemia caused by B. pseudomallei often has a rapidly fatal course. In one study in Thailand melioidosis accounted for 19% of admissions and 40% of deaths from community-acquired septicaemia [5]. Mortality rates as high as 90% have been reported [3]. The mortality rates have declined in recent years because of newer more effective antibiotics like ceftazidime [6–8]. Symptoms differ accordingly to the primary site of infection. Patients with the septicaemic form of melioidosis often are compromised hosts. Underlying diseases include diabetes mellitus, AIDS, renal failure and malignancies [1,3,9].
Asymptomatic infections Chronic infection This is probably the most common form of infection [1,2]. Serological studies in children from northeast Thailand revealed a seroconversion rate for B. pseudomallei antibodies of 24% per year, to a plateau of 80% seroprevalence in those 4 years of age, without having experienced an symptomatic infection [2]. One has to realise that an asymptomatic infection can become symptomatic even after a latency period of up to many years [1,3].
Chronic melioidosis in most cases causes abscesses which develop in infected tissues [1,3,10]. Secondary abscesses can develop in almost any organ: lung, liver, bone, and even in the brain. Symptoms vary according to the site of infection. It is important to realise that these patients can be afebrile.
Diagnosis Symptomatic localised infections The localised infection with B. pseudomallei can be seen in every organ system but most cases are presented as acute pulmonary infections [1,3,4]. The infection can range from a mild bronchitis to a necrotising pneumonia. The pneumonia more frequently involves the upper lobes. The patient usually
As the bacteria can be cultured easily on standard agar media, it is not difficult to diagnose this infectious disease [1,3]. Other diagnostic tools include an enzyme-linked immunosorbent assay (ELISA) for B. pseudomallei [1], an indirect haemagglutination assay (IHA) [1,2], a latex agglutination test [11] and a enzyme immunoassay detection of urinary B. pseudomallei antigen [12]. All
78
A. Beeker et al. / The Netherlands Journal of Medicine 54 (1999) 76 – 79
of the tests as mentioned can be helpful in making the diagnosis of melioidosis in patients, in case bacterial cultures are negative. One of the practical problems is that not all of these tests are available in all countries. Another problem is that positive serological tests prove infection but cannot distinguish between active and latent disease [1]. Therefore bacterial cultures still are the hallmark for the diagnosis of melioidosis. Due to the increasing mobility of the world population, it is important to consider melioidosis in every differential diagnosis of a patient with febrile illness who has traveled to southeast Asia and the northern part of Australia, especially those patients who present themselves with pulmonary infection, septicaemia or being compromised host.
Treatment B. pseudomallei infections are difficult to treat and to eradicate [1,3]. The bacteria is resistant to several antibiotics, as benzylpenicillin G, erythromycin, streptomycin and ciprofloxacin [3,13–15]. Treatment should therefore be based upon sensitivity studies [14,15]. MIC studies showed that imipenem, piperacillin, amoxicillin / clavulanate and ceftazidime are the most effective antibiotics [14]. To evaluate the management of melioidosis repetitive cultures, C-reactive protein and the temperature of the patient are the best parameters [16,17]. Even after successful treatment of melioidosis there is still a serious risk of relapse of the infection [16].
Septicaemic infection Although there is some in vitro evidence that newer carbapenem antibiotics perform better, i.v. ceftazidime is the drug of choice in the treatment of severe melioidosis [1,3,6–8,13–15]. Treatment for severe melioidosis should consist of i.v. antibiotics for up to 6 weeks followed by oral maintenance treatment for up to 6 months [6,7]. Oral maintenance treatment can consist of the combination of doxycycline and trimethoprim / sulfamethoxazole, but monotherapy with amoxicillin / clavulanate seems also to be effective [7].
Localised infections For localised infections treatment should consist of oral antibiotics for at least 2 months. When the infection consists of an extrapulmonary supportive lesion, treatment should be continued much longer [1,3].
Conclusion Melioidosis, an infection with the Burkholdria pseudomallei, is endemic in some parts of the world. The infection can present itself in many different ways. Due to the growing mobility of the world population, infections are likely to be seen in other then the endemic areas alone. People with underlying disease are especially at risk. In the case we presented we considered the patient to be immunocompromised because of his Non-Hodgkin’s Lymphoma. This fact, and his visit to an endemic area, made us aware of the possibility of melioidosis and the diagnosis was quickly made. The process of diagnosing is relatively easy as the bacteria grow on standard media. Treatment should be based on resistance patterns. A combination of i.v. antibiotics for at least 2 to 6 weeks followed by oral maintenance therapy for up to 6 months is the regimen of choice for the treatment of serious infections. The optimum duration of therapy and choice of antibiotics remain to be determined. About one out of four patients experiences a relapse of the infection. To prevent a relapse of the melioidosis we have chosen to treat our patient during chemotherapeutic treatment for his Non-Hodgkin’s Lymphoma with i.v. ceftazidime and oral amoxicillin / clavalunate.
References [1] Leelarasamee A, Bovornkitti S. Melioidosis: review and update. Rev Infect Dis 1989;11:413–25. [2] Kanaphun P, Thirawattanasuk N, Suputtamongkol Y, et al. Serology and carriage of Pseudomonas pseudomallei: A prospective study in 1000 hospitalized children in northeast Thailand. J Infect Dis 1993;167:230–3. [3] Sanford J.P. Pseudomonas species. In: Mandell G.I., Douglas R.G., Jr., Bennet J.E., editors. Principles and Practice of
A. Beeker et al. / The Netherlands Journal of Medicine 54 (1999) 76 – 79
[4] [5]
[6]
[7]
[8]
[9]
[10] [11]
Infectious Diseases, 4th ed. New York: John Wiley and Sons, 1995:2003–2008. Everett DE, Nelson RA. Pulmonary melioidosis. Am Rev Resp Dis 1975;112:331–40. Chaowagul W, White NJ, Dance DAB. Melioidosis: a major cause of community-acquired septicemia in north-eastern Thailand. J Infect Dis 1989;159:890–9. White N.J., Chaowagul W., Wuthiekanun V., Dance D.A.B, .Wattanagoon Y., Pitakwatchara N. Halving of mortality of severe melioidosis by ceftazidime. The Lancet 1989:697– 701. Suputtamongkol Y, Rajchanuwong A, Chaowagul W, et al. Ceftazidime vs. amoxicillin / clavulanate in the treatment of severe melioidosis. Clin Infect Dis 1994;19:846–53. Sauerwein RW, Lammers JW, Horrevoets AM. Ceftazidime monotherapy for pulmonary melioidosis in a traveller returning from Thailand. Chest 1992;101:555–7. Tamphaichitra D. Tropical disease in the immunocompromised host: Melioidosis and pythosis. Rev Infect Dis 1989;11:s1629–43. Wong KT, Puthucheary SD, Vadivelu J. The histopathology of human melioidosis. Histopathology 1995;26:51–5. Smith MD, Wuthiekanun V, Walsh AL, Pitt TL. Latex
[12]
[13]
[14]
[15]
[16]
[17]
79
agglutination test for identification of Pseudomonas pseudo¨ J Clin Path 1993;46:374–5. malleı. Desakorn V, Smith MD, Wuthiekanun V, et al. Detection of Pseudomonas pseudomalleı¨ antigen in urine for the diagnosis of melioidosis. Am J Trop Med Hyg 1994;51:627–33. Dance D.A.B., Wuthiekanun V., White N.J., Chaowagul W. Antibiotic resistance in Pseudomonas pseudomalleı¨ (Letter). The Lancet 1988:994–995. Dance DAB, Wuthiekanun V, Chaowagul W, White NJ. The ¨ antimicrobial susceptibility of Pseudomonas pseudomalleı. Emergence of resistance in vitro and during treatment. J Antimicrob Chemother 1989;24:295–309. Smith M.D., Wuthiekanun V., Walsh A.L., White N.J. Susceptibility of Pseudomonas pseudomalleı¨ to some newer blactam antibiotics and antibiotic combinations using time-kill studies. Chowagul W, Suputtamongkol Y, Dance DAB, Rajchanuvong A, Pattara-arechachai J, White NJ. Relapse in melioidosis: Incidence and risk factors. J Infect Dis 1993;168:1181–5. Ashdown LR. Serial serum c-reactive protein levels as an aid to the management of melioidosis. Am J Trop Med Hyg 1992;46:151–7.