Melioidosis presenting as sepsis syndrome: a case report

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International Journal of Infectious Diseases 15 (2011) e217–e218

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International Journal of Infectious Diseases journal homepage: www.elsevier.com/locate/ijid

Case Report

Melioidosis presenting as sepsis syndrome: a case report§ Maria Carolyn Redondo a,*, Maria Go´mez b, Maria Eugenia Landaeta a, H. Rı´os c, Rosa Khalil c, Rafael Napoleo´n Guevara a, Sandra Palavecino c, Manuel Figuera a, Jocays Caldera a, R. Rivera c, ˜ ez a Alberto Calvo d, Juana Vitelli e, Mariana Moro´n b, Maria Josefina Nun a

Infectious Diseases Service, Hospital Universitario de Caracas, Caracas, Venezuela Bacteriology Section, Tropical Medicine Institute, Universidad Central de Venezuela, Caracas, Venezuela c Internal Medicine Service, Hospital Universitario de Caracas, Caracas, Venezuela d Bacteriology Laboratory, Policlı´nica Metropolitana, Caracas, Venezuela e Experimental Biology institute, Universidad Central de Venezuela, Caracas, Venezuela b

A R T I C L E I N F O

S U M M A R Y

Article history: Received 28 July 2010 Received in revised form 19 November 2010 Accepted 25 November 2010

Melioidosis is an important disease in Asia and Australia. It is very rare in Venezuela. We describe the case of a 50-year-old diabetic patient with several episodes of right tibial osteomyelitis, left shoulder arthritis, sternal osteomyelitis, right parietal osteomyelitis, and subperiosteal abscess, followed by septic arthritis of the right knee. In all cases Gram stain smear showed Gram-negative bacilli. Culture yielded Burkholderia pseudomallei, susceptible to third- and fourth-generation cephalosporins, ciprofloxacin and aztreonam, and resistant to aminoglycosides. He developed sepsis syndrome. Blood cultures and culture of abscess and joint fluids also revealed B. pseudomallei. The patient was treated with ceftazidime and ciprofloxacin, then cefepime and trimethoprim–sulfamethoxazole. He was discharged with suppressive therapy consisting of oral doxycycline and trimethoprim–sulfamethoxazole, and follow-up has continued to date. At this time he remains asymptomatic. Melioidosis is an extremely rare disease in our country. To our knowledge, this is only the second case reported in Venezuela. ß 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Corresponding Editor: William Cameron, Ottawa, Canada Keywords: Melioidosis Sepsis syndrome Burkholderia pseudomallei

1. Introduction Melioidosis is a disease of public health importance in Southeast Asia and northern Australia, which has the potential for epidemic spread to areas where it is not endemic.1 The three main modes of acquisition of this agent are inhalation, ingestion, and inoculation. Other unusual modes of transmission described in case reports include person-to-person, sexual, perinatal, vertical, and nosocomial.1 Melioidosis is a fascinating infection in terms of its pathogenesis. The outcome of the host–pathogen interaction ranges from asymptomatic seroconversion to rapidly fatal, overwhelming sepsis. Between these extremes the infection may run a chronic or relapsing course, or may remain latent for long periods of time before declaring itself. It has been proposed as a model of Gramnegative sepsis, but the organism differs from other Gram-negative

bacteria in its ability to survive intracellularly. The potential severity of acute melioidosis indicates that it has potent virulence factors, and the most important are the polysaccharide capsule and lipopolysaccharide. They mediate resistance to complementmediated killing.1 Several studies have reported risk factors for this disease, and they are well known.1,2 Clinical presentations include the bacteremic form, with or without septic shock, and the nonbacteremic form, including pneumonia, genitourinary and soft tissue infections, osteomyelitis, and others.1–3 Treatment in the intensive care unit with third- or fourth-generation cephalosporins and carbapenems, followed by eradication therapy with trimethoprim–sulfamethoxazole with or without tetracyclines is associated with decreased mortality.1 We report a case of melioidosis presenting as sepsis syndrome occurring in Caracas, Venezuela. 2. Case report

§ This case was presented as a poster (No. 58.026) at the 11th International Congress on Infectious Diseases, Cancun, Mexico, March 4–7, 2004. * Corresponding author. Current address: PO Box 66866, Plaza Las Ame´ricas, El Cafetal, Caracas, 01061 Venezuela. Fax: +58 212 6626091. E-mail address: [email protected] (M.C. Redondo).

We report the case of a 50-year-old diabetic patient from Maracay (50 miles from Caracas), who was an electricity worker in the rice plantations. His prior history consisted of non-insulindependent diabetes with irregular treatment and right tibial

1201-9712/$36.00 – see front matter ß 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijid.2010.11.009

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M.C. Redondo et al. / International Journal of Infectious Diseases 15 (2011) e217–e218

osteomyelitis over the previous 5 years, with isolation of Pseudomonas sp, treated with multiple antibiotics, which he completed for 3 months. In 1999 he developed arthritis in the left shoulder and underwent surgery. Joint surgical debridement was performed, with no culture. Actinomycosis was suspected and the patient was treated with high-dose penicillin. In September 2000, he was admitted with sternal osteomyelitis, presenting secretion of yellow pus in the sternal area. His erythrocyte sedimentation rate was 70 mm/h. Liver enzymes were: total bilirubin 6.6 mg/dl, with direct bilirubin 5.6 mg/dl, alanine aminotransferase 105 mg/dl, and aspartate aminotransferase 80 mg/dl. A Gram stain smear showed Gram-negative bacilli. Culture yielded Burkholderia pseudomallei, susceptible only to thirdand fourth-generation cephalosporins, ciprofloxacin and aztreonam, and resistant to aminoglycosides. He was started on therapy with intravenous (IV) ceftazidime and ciprofloxacin for 3 weeks. He was discharged on 6-week therapy with IV cefepime plus oral ciprofloxacin. Follow-up continued until September 2002, when he was admitted with right parietal osteomyelitis and subperiosteal abscess, followed by septic arthritis of the right knee. He developed sepsis syndrome with pale skin, tachycardia, tachypnea, hypoxemia, mental status alterations, and gastrointestinal bleeding. He underwent surgery for drainage of the abscess and debridement of the osteomyelitis and septic arthritis. Blood cultures and culture of abscess and joint fluids revealed B. pseudomallei, susceptible to cefepime, ceftazidime and imipenem, and resistant to aminoglycosides and ciprofloxacin. He was started on IV cefepime and IV trimethoprim–sulfamethoxazole. Suppressive therapy consisting of oral doxycycline (100 mg every 12 h) and trimethoprim–sulfamethoxazole (1 double strength tablet every 12 h) was given for 1 year. At this time he remains asymptomatic. 3. Discussion Melioidosis is endemic in Southeast Asia and northern Australia. In parts of northeastern Thailand, it is the most common cause of severe community-acquired sepsis.1 The first reported case in the northern territory of Australia occurred in 1960 and melioidosis is now recognized as the most common cause of fatal community–acquired bacteremic pneumonia.1 In several published series, pneumonia is the most frequent presentation of melioidosis and is involved in approximately half of all cases.1–3 In Venezuela, only one case has been reported, although it was never published. In 1995 Marin et al. described a case of necrotizing pneumonia diagnosed by bronchoscopy, in which culture yielded B. pseudomallei.4 In our report, co-morbidity, occupation and age were most relevant. The patient was a diabetic 50-year-old man, who had been an electrician in a rice plantation for several years. B. pseudomallei is visualized as a slender Gram-negative bacillus with rounded ends and bipolar staining, and is vacuolated; it is often described as having a safety-pin appearance. It is oxidasepositive, and on culture, the organisms demonstrate different colony morphology.1 In this case, on Gram stain the pathogen was observed as scarce Gram-variable bacilli. Culture in blood agar yielded a small, dry, earth-smelling colony.

Isolation of B. pseudomallei from the body fluids of patients remains the gold standard in the diagnosis and requires the use of selective media for non-sterile specimens. Gram stain and other histopathological stains are not specific for the organism. Skin and soft tissue infection is a common manifestation of melioidosis, and may result from hematogenous spread and can be the source of systemic infection. Presentation may be of rapid progression, similar to necrotizing fasciitis. Bone and joint infections are uncommon (4–12%) and may be difficult to diagnose, and systemic manifestations are prominent. Surgical drainage and long courses of antibiotics are required.1–5 In our case, the patient developed sepsis syndrome, which started as osteomyelitis and septic arthritis. Currie et al. reported seven cases of septic shock with high mortality (100%).2 Regarding other non-bacteremic forms, they reported five cases of osteomyelitis and septic arthritis with no mortality (0%). In published series from Thailand and Australia, other frequent presentations have been suppurative parotitis, prostatic abscesses, urinary infection and encephalomyelitis syndrome.3,5 Several randomized, controlled trials have examined intensive phase interventions in severe melioidosis and are the basis of ceftazidime-based regimens.1,5 Ceftazidime has been shown to be of benefit in the treatment of this disease in a sequential open-label randomized trial of ceftazidime against chloramphenicol–doxycycline–trimethoprim–sulfamethoxazole (known as conventional therapy) in severe disease, at least for 6 months.1 Other trials have used amoxicillin–clavulanate and imipenem, granulocyte colonystimulating factor (G-CSF) and activated protein C in severe cases of sepsis.1 For maintenance therapy, amoxicillin–clavulanate vs. chloramphenicol, doxycycline, trimethoprim–sulfamethoxazole and ciprofloxacin have been recommended, with a duration of 12–20 weeks.1 To our knowledge, this is one of very few cases reported in South America, raising the alarm for a suspicion of melioidosis in the differential diagnosis of sepsis in this area and among travelers coming from this area. Melioidosis is an extremely rare disease in our country; this is only the second case reported in Venezuela. Physicians should be aware of the disease and suspect it in patients coming from rice plantations. Conflict of interest: No conflict of interest to declare.

References 1. Cheng AC, Currie BJ. Melioidosis: epidemiology, pathophysiology and management. Clin Microbiol Rev 2005;18:383–416. 2. Currie BJ, Fisher DA, Howard DM, Burrow JN, Lo D, Selva-Nayagam S, et al. Endemic melioidosis in tropical northern Australia: a 10-year prospective study and review of the literature. Clin Infect Dis 2000;31:981–6. 3. Dance D. Melioidosis. Curr Opin Infect Dis 2002;15:127–32. 4. Marin M, Marty F, Cortesia M, Herrera L, Vainrub B. Melioidosis pulmonar adquirida en Venezuela. Poster presentation at the IX Jornadas Nacionales de Infectologı´a ‘‘Dr. Juan Guido Tata´ Cumana’’, San Cristo´bal, Venezuela, November 22–24, 1995. 5. Douglas MW, Lum G, Roy J, Fisher DA, Anstey NM, Currie BJ. Epidemiology of community-acquired and nosocomial bloodstream infections in tropical Australia: a 12-month prospective study. Trop Med Int Health 2004;9:795–804.

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