Burkholderia pseudomallei Endophthalmitis

Abstract

Melioidosis is an infectious disease caused by Burkholderia pseudomallei, a gram-negative bacillus. We report a case of endogenous endophthalmitis caused by B. pseudomallei that was treated with systemic and intravitreal ceftazidime. Finally, the patient achieved a final visual acuity of 20/60 without complication.

CASE REPORT

A 51-year-old Taiwanese male had a medical history of diabetes mellitus without regular medical control for 2 years and old pulmonary tuberculosis with complete treatment in 2005. He had complained of intermittent fever and chills for 1 month without certain identification of an infectious or tumor source. Due to persistent fever and chills, he was referred to the emergency department of Chang Gung Memorial Hospital, Taoyuan, Taiwan. There was no history of travel or a significant skin abrasion wound. He had no productive cough, tachypnea, or hemoptysis. He suffered from dysuria and bilateral leg pitting edema; in addition, urine analysis revealed white blood cells and bacteria.

The results of the laboratory testing showed a white blood cell count of 13 × 10³/μl (89% neutrophils), a red blood cell count of 2.82 × 10⁶/μl, a platelet count of 197 × 10³/μl, a hematocrit of 21.9%, a hemoglobin concentration of 7.1 g/dl, an aspartate aminotransferase concentration of 36 U/liter, an alanine aminotransferase concentration of 11 U/liter, an alkaline phosphatase concentration of 296 U/liter, a creatinine concentration of 1.5 mg/dl, a sodium level of 132 meq/liter, a potassium level of 3.7 meq/liter, a glucose concentration of 373 mg/dl, and a hemoglobin A_1c percentage of 9.9%.

Due to inactive, old pulmonary tuberculosis, chest roentgenograms demonstrated a coarse reticular density without infiltration on the right upper lung. The results of an abdominal echography and computed tomography of the brain were normal. Urinary tract infection was diagnosed, and the patient was treated initially with intravenous antibiotics, including cefazolin (2 g/day) and gentamicin (120 mg/day).

On day 3, blood and urine cultures revealed the organism Burkholderia pseudomallei; in addition, the sputum culture was negative. The organism was a motile and oxidase-positive bacillus that produced wrinkled, creamy white colonies. Other conventional biochemical tests revealed acid reactions of glucose, maltose, lactose, and mannitol. Moreover, the isolate was identified as B. pseudomallei on the basis of biochemical testing (ID 32 GN; bioMerieux, Marcy l'Etoile, France). Antibiotic susceptibility testing was performed by broth macrodilution methods. The isolate was susceptible to the following antibiotics: ceftazidime (MIC, 2 μg/ml), imipenem (MIC, 2 μg/ml), piperacillin (MIC, 2 μg/ml), ceftizoxime (MIC, 2 μg/ml), ciprofloxacin (MIC, 2 μg/ml), and trimethoprim-sulfamethoxazole (MIC, 2 μg/ml). It was resistant or intermediate to other antibiotics tested: ampicillin (MIC, ≥16 μg/ml [resistant]), amikacin (MIC, ≥32 μg/ml [resistant]), cephalothin (MIC, ≥32 μg/ml), gentamicin (MIC, ≥16 μg/ml [resistant]), cefamandole (MIC, ≥32 μg/ml [resistant]), and cefepime (MIC, 16 μg/ml [intermediate]). According to the laboratory data, the patient was treated with intravenous ceftazidime (3 g/day) and oral sulfamethoxazole-trimethoprim (800 mg/160 mg, twice a day).

On day 13, the patient complained that he had had progressively blurry vision in the right eye for 4 days. However, the patient's systemic condition was stable, and he was without persistent fever or chills. His visual acuity was 20/100 in the left eye, and he could count fingers with his right eye. Ocular history did not reveal diabetic retinopathy, and ocular trauma and operation history were not reported. On examination, the anterior segment demonstrated fine keratic precipitates, fibrin over the pupillary margin, posterior synechia at the 2 o'clock position, and a 1-mm hypopyon. Fundus examination revealed grade III opacity with yellowish infiltration (subretinal hypopyon) at the superior midperipheral area of the choroid. The macula and posterior pole did not show significant vasculitis or infiltration. Intravitreal injections of vancomycin (1 mg/0.1 ml) and ceftazidime (2.25 mg/0.1 ml) were performed immediately. Topical vancomycin (25 mg/ml, hourly), ceftazidime (50 mg/ml, hourly), and 1% prednisolone acetate (four times per day) were used to treat the right eye. The inflammation of the anterior segment subsided after 3 days of the intravitreal antibiotic therapy; however, the vitreous culture tested negative. On day 33, the inflammation of the vitreous and anterior chambers decreased, and the patient's visual acuity recovered to 20/400 in the right eye. After 4 weeks of intravenous ceftazidime and 3 months of oral sulfamethoxazole-trimethoprim, the infection of B. pseudomallei was completely eradicated. Three months later, the final visual acuity was 20/60 in the right eye. The anterior segment demonstrated no reaction, except residual posterior synechia. Fundus examination showed choroidal scarring with subretinal fibrosis over the area of the choroid that was previously infiltrated.

Discussion.

Melioidosis is an infectious disease caused by the bacterium Burkholderia pseudomallei. It is clinically and pathologically similar to glanders disease, caused by Burkholderia mallei. B. pseudomallei has a specific ecological niche, existing in soil and stagnant water in an area between the latitudes 20°N and 20°S of the equator, primarily in Thailand, Vietnam, and parts of northern Australia (2). Recent reports confirm that it is endemic in China, Taiwan, and Laos, but the true incidence in most countries is unknown (4, 9). The bacteria causing melioidosis are found in contaminated water and soil. Infection is acquired by inhalation of dust, ingestion of contaminated water, contact with contaminated soil, especially through skin abrasions, and, for military troops, contamination of war wounds. Person-to-person transmission may also occur. Most infections are asymptomatic or present as a self-limited, short-term, flu-like illness and can be diagnosed only by serology (1). The incubation period (the time between exposure and the appearance of clinical symptoms) is not clearly defined but may range from 2 days to many years.

Definitive diagnosis of melioidosis, which has been called “the great mimicker,” depends on the isolation and identification of B. pseudomallei from clinical specimens. Three forms of melioidosis have been described: (i) acute disease, presenting as septicemia with metastatic lesions; (ii) subacute disease, presenting as a tuberculosis-like pneumonia with cellulitis and lymphangitis; and (iii) chronic disease, presenting as a localized chronic cellulitis. Diabetes mellitus has been shown to be a risk factor for the development of bacteremic melioidosis (8). Recrudescence of melioidosis from its latency may be triggered by decreased immunocompetence. The major risk factors of diabetes mellitus and pulmonary tuberculosis may also explain why our patient had acute melioidosis.

Ocular melioidosis, including endophthalmitis and corneal ulcers, is rarely described in the literature (7, 10). Early diagnosis and treatment of endophthalmitis caused by B. pseudomallei may prevent loss of vision and evisceration of the eyes. Even if systemic ceftazidime and trimethoprim-sulfamethoxazole were used to treat this patient, the occurrence of endogenous endophthalmitis caused by B. pseudomallei would still be unpreventable. Intravitreal ceftazidime at an appropriate dosage may be necessary for cases of B. pseudomallei endophthalmitis. Unlike the subject of a previous report who had a poor visual outcome (10), this patient achieved a favorable final visual acuity of 20/60.

The mortality rate is 95% for B. pseudomallei endophthalmitis patients with acute disease who are not treated; therefore, treatment should be initiated early in the course of the disease. B. pseudomallei is intrinsically resistant to many antibiotics, including the penicillins, narrow- and expanded-spectrum cephalosporins, macrolides, and the aminoglycosides (3).

B. pseudomallei is generally susceptible to trimethoprim-sulfamethoxazole, broad-spectrum cephalosporins, and carbapenems (9). Ceftazidime has been the treatment of choice for severe melioidosis, but response to high-dose parenteral treatment is slow (9). Carbapenem antibiotics have been shown to be highly active against B. pseudomallei in vitro, and in one study, imipenem alone was shown to be an effective treatment for acute severe melioidosis, resulting in fewer treatment failures than with ceftazidime (5, 6). In one study, the use of a combination therapy of cefoperazone-sulbactam plus trimethoprim-sulfamethoxazole appeared to be as efficacious for the treatment of severe melioidosis as ceftazidime plus trimethoprim-sulfamethoxazole (3).

For acute or chronic infections, parenteral administration of imipenem or ceftazidime for 2 to 4 weeks followed by oral therapy with amoxicillin-clavulanate or a combination of doxycycline and trimethoprim-sulfamethoxazole for 3 to 6 months is recommended. Given the possible fulminant course and high mortality rate, ophthalmologists should be alert to the occurrence of endogenous endophthalmitis caused by melioidosis. Intravitreal ceftazidime or carbapenem may prove efficacious for the treatment of endophthalmitis caused by B. pseudomallei.