Correspondence *Wilford Hall Medical Center, Urology, 8423 Feather Trail, Helotes, TX 78023, USA

Email jorge.arzola@lackland.af.mil

The case

A 67-year-old Hispanic male presented to the emergency room complaining of worsening fevers, chills, and malaise over a 2-week period. He reported a 2-year history of stable lower urinary tract symptoms, including nocturia and urinary frequency every 3 h. The patient's medical history included diet-controlled diabetes mellitus, benign prostatic hyperplasia, and a remote history of gonococcal urethritis. His surgical history was unremarkable and he was taking no outpatient medications. He drank alcohol excessively until 13 years ago, but reported no recent alcohol consumption. The patient resides for half the year in rural Indonesia, where he was a first-hand witness to the December 2004 tsunami, which claimed over 186,000 lives in Asia. He specifically reported having gone beachcombing for several weeks following the tsunami, looking for items of value. During this period he stood in stagnant water and walked through debris. His symptoms began approximately 6 weeks after the catastrophic event, on his return to San Antonio, TX, where he resides for the other 6 months of the year.

On admission, he was febrile, with a temperature of 39 °C, and mildly tachycardic. He was hemodynamically stable, but in obvious discomfort. On physical examination, he had a tender, but nonfluctuant, 40 g prostate gland, but no other physical abnormalities. Initial laboratory work-up revealed an elevated leukocyte count of 20 10³ with a left shift. Blood and urine cultures were sent from the emergency room. His urine analysis revealed 15–19 red blood cells per high-power field, 20–29 leukocytes per high-power field, positive bacteria with negative nitrates and leukocyte esterase, and few hyaline casts. A chest X-ray was unremarkable, but a CT scan of the abdomen and pelvis revealed an enlarged, heterogeneous prostate, with small, nonenhancing fluid collections (Figure 1).

Figure 1 CT scan revealing the patient's enlarged, heterogenous prostate with nonenhancing fluid collections.

 

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The patient was admitted with a diagnosis of systemic inflammatory response syndrome and acute bacterial prostatitis, with concern for gram-negative sepsis. He was treated with standard doses of vancomycin hydrochloride (1 g intravenously every 12 h) and piperacillin plus tazobactam (3.375 g intravenously every 6 h), intravenous fluids, antipyretics, analgesics, and bed rest.

The patient failed to improve and remained febrile despite broad-spectrum antibiotic coverage. Although the urine cultures revealed no growth, the blood culture grew gram-negative rods, subsequently identified as Burkholderia pseudomallei. On the basis of susceptibility-test results, the antibiotic regimen was changed to intravenous imipenim-cilastatin 1 g every 8 h.

Despite these interventions, the patient's fever persisted. An ¹⁸F-fluorodeoxyglucose PET scan was ordered to elucidate any other nidus of infection. Using the ¹⁸F-fluorodeoxyglucose tracer, PET can determine the presence of abnormal glucose metabolism in malignant and inflammatory cells. This scan was only positive for increased uptake within the prostate gland (Figure 2). We elected to further evaluate the prostate with a transperineal ultrasound and discovered the presence of a small hypoechoic region in the left base of the prostate, which correlated with the fluid collection seen on the CT scan performed at admission. An ultrasound-guided fine needle aspiration of this fluid collection was performed, draining a small volume of purulent material, which grew B. pseudomallei bacteria. After the procedure, the patient's condition improved and he was discharged with a peripherally inserted central catheter to complete a 2-week course of imipenem-cilastin, followed by oral trimethoprim plus sulfamethoxazole for eradication therapy. As the result of the patient's intractable nausea when taking trimethoprim plus sulfamethoxazole, he was switched to co-amoxiclav 875 mg twice daily and doxycycline 100 mg twice daily for 3 months. The patient was asymptomatic at 3 months' follow-up.

Figure 2 ¹⁸F-fluorodeoxyglucose PET scan showing the patient's increased prostatic uptake, which signals residual infection and a possible abscess.

 

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Discussion of diagnosis

B. pseudomallei is a highly virulent, facultative, intracellular gram-negative bacterium, found in soil and fresh water as a natural saprophyte.¹ Endemic areas include southeast Asia, northern Australia, southern Asia and China, making B. pseudomallei a common pathogen found in people of all nationalities who have been in these areas. Recent cases have also been reported in the western hemisphere, including Puerto Rico and Brazil.² It is acquired via exposure to wet season soils or contaminated water. Infection occurs via respiratory exposure, or via cutaneous infection through broken skin. Authors have reported several patients with melioidosis following the tsunami of December 2004. One author in Bangkok, Thailand, reported a patient with lung abscess and a patient with pneumonia and septic melioidosis,³ while another reported four cases of pneumonia due to B. pseudomallei in Banda Aceh, Indonesia.⁴ Of these four patients, none had any identified risk factors for melioidosis other than the tsunami. Melioidosis occurred in six tsunami survivors in Phangnga, in southern Thailand, with pulmonary disease in all six cases and bacteremia in three.⁵ Of the six, three had diabetes mellitus and the other three had no known risk factors. No cases of septicemic melioidosis with prostatic abscess following the tsunami have yet been reported. In this patient's case, he could have come into contact with the bacterium through contaminated water or by collecting contaminated objects from the beach in the weeks following the tsunami.

Risk factors for melioidosis include diabetes mellitus, immunosuppression, kidney disease, thalassemia, and occupational exposure to contaminated soil or water. In particular, diabetic patients, such as the patient presented in this case report, are at risk of bacteremic complications of melioidosis. The highest-risk group includes individuals with both diabetes mellitus and occupational exposure, such as diabetic rice farmers in southeast Asia.⁶ Despite its impact on cell-mediated immunity, HIV infection does not seem to be a risk factor for melioidosis.⁷

There are four clinical types of melioidosis: localized, pulmonary, septic, and chronic forms. In the localized form, the bacterium enters the skin through a laceration or abrasion, and a local infection with ulceration develops. The pulmonary form is aerosolized and the bacterium enters the respiratory tract via inhalation or hematogenous spread. Intense rain has been directly correlated with increasing rates of the pulmonary form, which can lead to pneumonia and death from melioidosis.⁸ Pulmonary melioidosis might present as an acute pneumonia, or, less often, can mimic pulmonary tuberculosis as a chronic illness with hemoptysis, weight loss, and cavitations (seen on chest radiograph). In the septic form, the bacteria disseminate in the bloodstream and are capable of seeding multiple organs. The chronic form involves multiple abscesses, which can affect any organ including the liver, spleen, skin, muscles, and, as illustrated in this case, the prostate gland. Complications of acute or chronic disease may include deep abscesses, septic arthritis, osteomyelitis, and encephalomyelitis.

Melioidosis covers the wide spectrum of clinical presentations that can occur with B. pseudomallei infections. Most otherwise healthy patients remain asymptomatic or present with pneumonia. There are four stages of infection: incubation, acute, chronic, and latent stages. The incubation stage typically lasts 1–21 days, and is usually an asymptomatic stage. The acute disease stage is the most common and usually lasts less than 2 months. Chronic disease is rare and is defined by symptoms that last longer than 2 months. Latent infection with reactivation is reported in less than 3% of cases, but can occur as long as 19–29 years after the initial presentation.^{9, 10} Concerns about the potential for reactivated melioidosis in Vietnam War veterans gave rise to the phrase 'the Vietnam time bomb'.

Prostatic involvement in melioidosis is common. In a series of melioidosis cases in northern Australia, prostatic abscesses occurred in 18% of male patients. In this series, four of the five patients with genitourinary infection and septic shock died of the disease. All patients with genitourinary infection without septic shock survived.¹¹

The diagnosis of melioidosis requires isolation of the B. pseudomallei organism from clinical specimens, including blood, sputum, and abscess fluid. The organism is an oxidase-positive, gram-negative bacillus (Figure 3). Mature colonies often demonstrate a wrinkled appearance (Figure 4). B. pseudomallei is readily cultured and identified using conventional automated microbiology laboratory methods, but certain commercial systems are more likely than others to identify it correctly.¹² As clinical laboratories in nonendemic areas are more likely to misidentify B. pseudomallei, clinicians should notify the laboratory if melioidosis is suspected.

Figure 3 Sputum gram stain from a patient with pulmonary melioidosis.

Gram-negative bacilli are Burkholderia pseudomallei. Photo courtesy of Dr Gary Lum, Northern Territory Government Pathology Service, Australia.

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Figure 4 Burkholderia pseudomallei colonies on MacConkey agar.

Mature colonies frequently demonstrate the wrinkled appearance seen here. Photo courtesy of Dr Gary Lum, Northern Territory Government Pathology Service, Australia.

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Treatment and management

Antimicrobial therapy for melioidosis includes an initial intensive phase followed by a prolonged eradication phase to prevent relapse. B. pseudomallei is intrinsically resistant to the conventional antibiotic regimen employed by most urologists, including ampicillin and gentamicin. It is also resistant to other older penicillins and first and second generation cephalosporins.

The intensive phase should consist of a 2-week course of either intravenous ceftazidime 2 g every 6 h or intravenous imipenem plus cilastatin 1 g every 8 h. These two agents are equivalent in terms of patient mortality, but imipenem plus cilastatin produces fewer treatment failures.¹³ A recent analysis showed no benefit in terms of mortality of the addition of trimethoprim plus sulfamethoxazole to the intensive phase of therapy.¹⁴ Patients who have extensive pulmonary disease, undrained deep abscesses, osteomyelitis, or neurologic melioidosis might require longer, intensive antibiotic courses.

To prevent relapse, an additional eradication regimen of double-strength trimethoprim plus sulfamethoxazole twice daily for a minimum of 3 months should follow. Co-amoxiclav, doxycycline, and fluoroquinolones are second-line alternatives for patients who cannot tolerate sulfa medications, but relapse has been demonstrated to be more common in patients who do not take sulfa drugs.¹⁵ Abscesses require aspiration or surgical drainage, and, if large enough and located in the prostate, a transurethral resection (unroofing) of the abscess should be considered.

Untreated septicemia can be fatal. Before the advent of third-generation cephalosporins, the death rate for septic disease was 95%.¹ Today, the mortality rate is still greater than 50% for septic disease and 20% for localized disease, despite treatment. Overall mortality can be as high as 40%.³ It should, therefore, be no surprise that B. pseudomallei is listed by the US Army Medical Research Institute of Infectious Diseases at Fort Detrick, MD, as a possible weapon of bioterrorism.²

Conclusion

Melioidosis is an often fatal disease caused by the gram-negative bacterium B. pseudomallei. Although rare in the US, an increasing number of cases have been reported among tourists returning from endemic areas.¹ It can form abscesses in any organ tissue, including the prostate. This Case Study should alert the practicing urologist to this rare, yet potentially life threatening, cause of prostatitis and prostatic abscesses.

Acknowledgments

The authors would like to thank Dr Gary Lum of the Northern Territory Government Pathology Service, Australia for the photographs, and Dr Clinton Murray of the Infectious Disease Service, Brooke Army Medical Center for his assistance with the manuscript.

The views expressed herein are those of the authors and do not reflect the official policy or position of the Department of the Army, the Department of Defense, or the US government. The authors are employees of the US government, and this article was written as part of their official duties; therefore, no copyright is claimed.

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Subject areas under which this article appears: Infections, inflammation and prostatitis