Am. J. Trop. Med. Hyg., 84(6), 2011, pp. 858–861 doi:10.4269/ajtmh.2011.10-0618 Copyright © 2011 by The American Society of Tropical Medicine and Hygiene Short Report: Repeat Blood Culture Positive for B. pseudomallei Indicates an Increased Risk of Death from Melioidosis Direk Limmathurotsakul,* Vanaporn Wuthiekanun, Gumphol Wongsuvan, Sukanya Pangmee, Premjit Amornchai, Prapit Teparrakkul, Nittaya Teerawattanasook, Nicholas P. J. Day, and Sharon J. Peacock Department of Tropical Hygiene, Department of Microbiology and Immunology and Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Medicine and Department of Clinical Pathology, Sappasithiprasong Hospital, Ubon Ratchathani, Thailand; Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom; Department of Medicine, Cambridge University, Addenbrooke’s Hospital, Cambridge, United Kingdom Abstract. Melioidosis, a bacterial infection caused by Burkholderia pseudomallei, is notoriously difficult to cure despite appropriate antimicrobial therapy and has a mortality rate of up to 40%. We demonstrate that a blood culture positive for B. pseudomallei taken at the end of the first and/or second week after hospitalization for melioidosis is a strong prog- nostic factor for death (adjusted odds ratio = 4.2, 95% confidence interval = 2.1–8.7, P < 0.001 and adjusted odds ratio = 2.6, 95% confidence interval = 1.1–6.0, P = 0.03, respectively). However, repeat cultures of respiratory secretions, urine, throat swabs, or pus/surface swabs provide no prognostic information. This finding highlights the need for follow-up blood cultures in patients with melioidosis. Melioidosis is a community-acquired infectious disease caused by the Gram-negative bacillus Burkholderia pseudo- mallei.1 This organism is present in the environment in areas where melioidosis is endemic, and infection is acquired through skin inoculation, inhalation or ingestion. Melioidosis is the most common cause of community-acquired bacteremic pneumonia in northern Australia2 and the third most frequent cause of death from infection diseases in northeastern Thailand (after human immunodeficiency virus/acquired immunodefi- ciency syndrome and tuberculosis).1 Common manifestations include pneumonia, hepatosplenic abscesses, septic arthritis, parotid and prostatic abscesses, and urinary tract infection. Persons with suspected melioidosis require hospital admission cultures of blood, respiratory secretions, urine, throat swab, pus if abscesses are identified and accessible, and swabs from any skin lesions. Burkholderia pseudomallei is not part of the normal human flora, and isolation of this organism from any specimen is diagnostic for melioidosis. Death occurs in 40% of patients with melioidosis in our setting.1 Several factors have been identified that are associ- ated with a higher risk of death, including older age, pneumo- nia, markers of organ dysfunction, positive blood culture, and high quantitative count of B. pseudomallei in blood or urine.3,4 Follow-up cultures are easy to perform and relatively inex- pensive, but there is limited information on the significance of positive B. pseudomallei cultures over time and whether these provide additional prognostic information. We evaluated the hypothesis that follow-up qualitative and/or quantitative cul- ture can be used to predict survival outcome in patients with melioidosis. The patients described here were consecutive individuals presenting to Sappasithiprasong Hospital between January 1, 1997 and December 31, 2006 with culture-confirmed melioido- sis who were identified as part of on-going surveillance associ- ated with clinical trials. The hospital diagnostic laboratory was contacted daily to identify patients with one or more cultures *Address correspondence to Direk Limmathurotsakul, Mahidol- Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithee Road, Bangkok, 10400 Thailand. E-mail: direk@tropmedres.ac 858 positive for B. pseudomallei. Rounds of the medical and inten- sive care wards were conducted daily to identify additional cases. Any patient not already known to us who we suspected of having melioidosis on the basis of admission clinical fea- tures had samples obtained for culture, including blood, respi- ratory secretions (sputum, or tracheal aspirate if intubated), urine, throat swab, pus, and surface swabs from skin lesions. Microbiologic specimens were processed as described pre- viously.5 All patients with microbiologically confirmed melioi- dosis were subsequently visited daily to obtain information on history, examination findings, and outcome (defined as survival to discharge or in-hospital death). Repeat blood cul- ture was performed at the end of the first and second weeks after diagnosis in patients who were failing to improve despite parenteral antimicrobial therapy. In addition, other specimen types that were positive for B. pseudomallei at admission were obtained every week until negative results were obtained, and patients in whom new signs and symptoms developed and were suspected of new organ involvement had a repeat screening of relevant clinical specimens. For purposes of analysis, clinical specimens obtained within the first three days were grouped as admission samples, those obtained during days 4–10 as first follow-up samples, and those obtained after day 10 as second follow-up samples. A few rela- tives took moribund patients home to die and these patients were assumed to have died. Ethical approval for all clinical trials was obtained from the Ethical and Scientific Review Subcommittee of Thai Ministry of Public Health.6–9 Quantitative culture of blood, urine, spu- tum, and pus was performed in adult patients (> 18 years of age) during 2004–2006 as described.10 Simple and multivariable logistic regression analysis was used to examine the association between culture result and outcome. Sex, age, history of diabetes, pneumonia, hypoten- sion, and duration of in-hospital intravenous antimicrobial treatment received were included in the multivariable analy- sis. Drugs used were amoxicillin/clavulanate, ceftazidime, and carbapenems. Fisher’s exact test and the Mann-Whitney test were used to compare categorical variables and continuous variable between groups, respectively. There were 2,243 patients admitted to Sappasithipra- song Hospital during 1997–2006 with their first episode of