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الانزيمات
Burkholderia pseudomallei and Burkholderia mallei
المؤلف:
Stefan Riedel, Jeffery A. Hobden, Steve Miller, Stephen A. Morse, Timothy A. Mietzner, Barbara Detrick, Thomas G. Mitchell, Judy A. Sakanari, Peter Hotez, Rojelio Mejia
المصدر:
Jawetz, Melnick, & Adelberg’s Medical Microbiology
الجزء والصفحة:
28e , p256-257
2025-09-03
66
Burkholderia pseudomallei is a small, motile, oxidase-positive, aerobic Gram-negative bacillus, which is also indole-negative and resistant to colistin and gentamicin. It grows on standard bacteriologic media (eg, sheep blood agar), forming colonies that are initially (24–48 hours) mucoid and smooth/creamy, but upon further length of incubation change in appearance to rough and wrinkled and in color from cream to orange. The organism grows at 42°C and oxidizes glucose, lactose, and a variety of other carbohydrates. B. pseudomallei is the cause of melioidosis (also called Whitmore’s disease) that occurs predominantly in Southeast Asia and Northern Australia. In these regions of endemicity, infection is typically seasonal, with highest rates of occurrence during the monsoon wet season. The organism is a natural saprophyte that has been cultured from soil, fresh water, rice paddies, and vegetable produce. Human infection probably originates from these sources by ingestion or inhalation of contaminated dust or water, and by contact with contaminated soil via skin abrasions. Epizootic B. pseudomallei infection occurs in sheep, goats, swine, horses, and other animals, although animals do not appear to be a primary reservoir for the organism. Because the organism has been used as an agent of biowarfare/bio terrorism by some countries in the past, B. pseudomallei is currently classified as a Category B agent of bioterrorism by the U.S. Centers for Disease Control and Prevention (CDC); if weaponized, the bacterium would be moderately easy to disseminate (eg, aerosolization), resulting in moderate to severe morbidity, and high mortality if untreated. However, mortality is likely much lower (fewer than 2 out of 10 people according to the CDC’s information), if timely and appropriate antibiotic treatment is administered.
Melioidosis may manifest itself as acute, subacute, or chronic infection. The incubation period can be as short as 2–3 days, but latent periods of months to years also occur. A localized suppurative infection can occur at the inoculation site where there is a break in the skin. This localized infection may lead to the acute septicemic form of infection with involvement of many organs. The signs and symptoms depend upon the major sites of involvement. The most common form of melioidosis is pulmonary infection, which may be a primary pneumonitis (B. pseudomallei transmitted through the upper airway or nasopharynx) or subsequent to a localized suppurative infection and bacteremia. The patient may have fever and leukocytosis with consolidation of the upper lobes. Subsequently, the patient may become afebrile, while upper lobe cavities develop, yielding an appearance similar to that of tuberculosis on chest films. Some patients develop chronic suppurative infection with abscesses in skin, brain, lung, myocardium, liver, bone, and other sites. Patients with chronic suppurative infections may be afebrile and have indolent disease. Latent infection is sometimes reactivated as a result of immunosuppression.
The diagnosis of melioidosis should be considered for a patient from an endemic area who has fulminant upper lobe pulmonary or unexplained systemic disease. A Gram-stain of an appropriate specimen will show small Gram-negative bacilli; bipolar staining (safety pin appearance) is seen with Wright’s stain or methylene blue stain. A positive culture result is diagnostic. A positive serologic test result is diagnostically helpful and constitutes evidence of past infection.
Melioidosis has a high mortality rate if untreated. Surgical drainage of localized infection may be necessary. B. pseudomallei is intrinsically resistant to penicillin, ampicillin, first- and second-generation cephalosporins, gentamicin and tobramycin, and macrolides. B. pseudomallei is generally susceptible to ceftazidime, imipenem, meropenem, and amoxicillin–clavulanic acid, ceftriaxone, cefotaxime, and trimethoprim–sulfamethoxazole (TMP SMX); however, antimicrobial susceptibility testing should be performed to determine actual susceptibility patterns for a specific strain or organism. Resistance to TMP-SMX has been reported in B. pseudomallei, and depends on the geo graphic region where the organisms is endemic (rates vary between 2% and 16%). Depending on the clinical setting, the initial antimicrobial therapy should be for a minimum of 10–14 days with ceftazidime, imipenem, or meropenem; TMP-SMX can be considered in patients with severe allergy to β-lactam antimicrobials. Eradication therapy with TMP-SMX or doxycycline should follow the intensive initial therapy and be continued for a minimum of 3 months. Recurrent disease because of failure of organism eradication can occur for several reasons, including resistance to TMP-SMX or any other of the other antibiotics of choice; however, the most important cause is likely noncompliance with the long-term eradication therapy.
Burkholderia mallei is the cause of glanders, a highly communicable disease, typically affecting livestock (eg, horses). Although rare, it can be transmitted to humans. Since the 1940s, no case of glanders in animals has been reported in the United States; the last human case in the United States was reported in 1934. Along with anthrax, B. mallei was used as an agent of biowarfare during World War I; therefore, like B. pseudomallei, it is also currently classified as a Category B agent of bioterrorism by the CDC. The organism is a small Gram-negative, oxidase-positive, aerobic bacillus. Unlike B. pseudomallei, B. mallei is nonmotile and does not persist in the environment. The organism can be isolated from blood, sputum, urine, or skin lesions. Human glanders can be acute or chronic; after inhalation of the organism, an acute febrile illness can occur, with ulcerative necrosis of the upper airways, potentially leading to bronchopneumonia, followed by septicemia and dissemination to other internal organs. Percutaneous exposure causes local suppurative skin lesions with associated regional lymphadenopathy. Recommended treatment for glanders is the same as for melioidosis. With animal quarantine and other control measures, equine glanders has been eradicated in most countries, worldwide, and human cases are exceedingly rare.
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