Fatal Melioidosis in Goats in Bangkok,Thailand

Bangkok, Thailand, is a city considered to be at low risk for melioidosis. We describe 10 goats that died of melioidosis in Bangkok. Half of them were born and reared in the city. Multilocus sequence typing ruled out an outbreak. This finding challenges the assumption that melioidosis is rarely acquired in central Thailand.Melioidosis, an often fatal infectious disease for humans and animals, is caused by the Gram-negative bacillus and biothreat select agent Burkholderia pseudomallei.¹ This organism is present in soil and water in melioidosis-endemic regions of the world, including much of Asia, northern Australia, regions of South America, some countries in Africa, and various Pacific and Indian Ocean islands.¹ Most infections in humans and animals occur after skin inoculation, inhalation, or ingestion of the organism from the environment. A wide range of animal species are susceptible to melioidosis, including sheep, goats, swine, horses, cats, dogs, and non-human primates.²We recently described the first report of culture-confirmed melioidosis in animals in Thailand, in which goats were the most frequently affected species.³ The regions where animal melioidosis were reported mapped to those areas where melioidosis is endemic in humans, including northeastern, eastern, southern, and western Thailand. To our knowledge, animal melioidosis has not been reported from central Thailand, and melioidosis is not considered to be endemic in humans in this area.^1,4 Here, we describe 10 goats that died of melioidosis in Bangkok in central Thailand.Study animals underwent necropsy as part of a routine service at the Veterinary Diagnostic Center, Mahanakorn University of Technology, Nong Chok District, Bangkok, Thailand. Organs with gross pathologic lesions were cultured on bovine blood agar and MacConkey agar. Presumptive B. pseudomallei colonies were confirmed by using conventional biochemical tests, multiplex polymerase chain reaction,⁵ and latex agglutination tests.⁶ A total of 72 goats and 367 other animals were necropsied during 2006–2012. Ten goats (14%) had at least one specimen that was culture positive for B. pseudomallei, and all other animals were culture negative for this species.The ten goats were from six different farms (range = 1–4 goats/farm) located in two districts in Bangkok (Nong Chok and Khlong Sam Wa). The median age of affected goats was three years (range = 2–4 years), and nine (90%) were female. Common symptoms before death were pneumonia (n = 9), weakness (n = 4), anorexia (n = 2), neurologic symptoms (n = 2), and mastitis (n = 2). All cases had more than one organ involved, and multiple abscesses in the lung, liver, and spleen were common (

Repeat blood culture positive for B. pseudomallei indicates an increased risk of death from melioidosis

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 prognostic 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.     

Antimicrobial resistance to ceftazidime involving loss of penicillin-binding protein 3 in Burkholderia pseudomallei

Known mechanisms of resistance to β-lactam antibiotics include β-lactamase expression, altered drug target, decreased bacterial permeability, and increased drug efflux. Here, we describe a unique mechanism of β-lactam resistance in the biothreat organism Burkholderia pseudomallei (the cause of melioidosis), associated with treatment failure during prolonged ceftazidime therapy of natural infection. Detailed comparisons of the initial ceftazidime-susceptible infecting isolate and subsequent ceftazidime-resistant variants from six patients led us to identify a common, large-scale genomic loss involving a minimum of 49 genes in all six resistant strains. Mutational analysis of wild-type B. pseudomallei demonstrated that ceftazidime resistance was due to deletion of a gene encoding a penicillin-binding protein 3 (BPSS1219) present within the region of genomic loss. The clinical ceftazidime-resistant variants failed to grow using commonly used laboratory culture media, including commercial blood cultures, rendering the variants almost undetectable in the diagnostic laboratory. Melioidosis is notoriously difficult to cure and clinical treatment failure is common in patients treated with ceftazidime, the drug of first choice across most of Southeast Asia where the majority of cases are reported. The mechanism described here represents an explanation for ceftazidime treatment failure, and may be a frequent but undetected resistance event.