The Journal of Bone & Joint Surgery

The Journal of Bone & Joint Surgery, Volume 85, Issue 6

Scientific Article | June 01, 2003

Melioidotic Septic Arthritis and Its Risk Factors

Weerachai Kosuwon, MD; Twatchai Taimglang, MD; Winia Sirichativapee, MD; Polasak Jeeravipoolvarn, MD

Investigation performed at the Department of Orthopedics, Khon Kaen University, Khon Kaen, Thailand

Weerachai Kosuwon, MD
Twatchai Taimglang, MD
Winia Sirichativapee, MD
Polasak Jeeravipoolvarn, MD
Department of Orthopedics, Khon Kaen University, Khon Kaen 40002, Thailand. E-mail address for W. Kosuwon: weera_ko@kku.ac.th

The authors did not receive grants or outside funding in support of their research or preparation of this manuscript. They did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

J Bone Joint Surg Am, 2003 Jun 01;85(6):1058-1061

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Abstract

Background: Melioidotic septic arthritis is an infection caused by the gram-negative bacillus Burkholderia pseudomallei . It is commonly found in Northeast Thailand. The goal of our study was to identify specific characteristics of patients with melioidotic septic arthritis by comparing them with patients with non-melioidotic septic arthritis and to describe the results of treatment of melioidotic septic arthritis.

Methods: We conducted a retrospective study of seventy-seven patients with septic arthritis who were treated in our hospital over a period of four years. Twenty-five of the patients had melioidotic septic arthritis, and fifty-two had non-melioidotic septic arthritis. Univariate and multivariate analyses were conducted to identify the risk factors for melioidotic septic arthritis, and the clinical course of the twenty-five patients with melioidotic septic arthritis was followed until the infection resolved.

Results: Patients with melioidotic septic arthritis differed significantly (p = 0.002 ) from those with non-melioidotic septic arthritis with regard to the frequency of diabetes mellitus and of involvement of an upper-extremity joint. The odds ratio that melioidosis was the cause of the infection was 15.7 (95% confidence interval, 4.5 to 55.6) in a patient with diabetes mellitus and 4.51 (95% confidence interval, 1.04 to 19.65) in a patient with involvement of an upper-extremity joint. Twenty-two of the twenty-five patients with melioidotic septic arthritis responded to treatment, which consisted of six months of antibiotic therapy combined with needle aspiration, as well as surgical drainage of the affected joint when necessary (sixteen patients).

Conclusions: A diagnosis of melioidotic septic arthritis should be considered when septic arthritis is seen in an individual who is indigenous to or has recently visited Southeast Asia. The infection is more likely to be melioidotic septic arthritis if it involves an upper-extremity joint and if the patient has diabetes mellitus.

Level of Evidence: Prognostic study, Level II-1 (retrospective study). See Instructions to Authors for a complete description of levels of evidence.

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Introduction

Melioidosis is an infectious disease caused by the gram-negative bacterium Pseudomonas pseudomallei or Burkholderia pseudomallei . This disease was reported in 1912 by Whitmore and Krishnaswami ^l and subsequently by many others ^2-15 . During the conflict in Vietnam, melioidosis became an important problem in American military medicine, as many American soldiers became infected ¹¹ . The organism exists in the soil and water of Southeast Asia, tropical Australia ^7-16 , and Central America ¹⁷ . All human infections in North America and Europe can be traced to Southeast Asia, either directly or indirectly (laboratory-acquired infections or sexual transmission) ^18,19 . In Thailand, the disease commonly occurs in the Northeast region ^12,13 . It has several clinical presentations, including pulmonary infection, splenic abscess, lymphadenitis, pericarditis, septic arthritis, multiple-organ involvement, or septicemia and death ²⁰ . Melioidosis can present in a manner similar to tuberculosis ^6,20 .

One of us (W.K.) and Mahakkanukrauh et al. reported that the risk factors for musculoskeletal melioidosis were diabetes, which they found in five of ten cases, and thalassemia ² ; however, the risk factors specifically for melioidotic septic arthritis have not been reported, to our knowledge. The goal of our study was to determine such risk factors as well as the clinical features of and clinical diagnostic tests for melioidotic septic arthritis. This information should be useful to orthopaedic surgeons in countries other than our own, especially those who see patients who have returned from Southeast Asia or Australia.

Materials and Methods

Between January 1997 and September 2000, 104 patients were diagnosed with septic arthritis at Srinagarind University Hospital, Khon Kaen, Thailand, with use of the International Classification of Diseases, Ninth and Tenth Revisions (codes 7110 and M0095, respectively). The signs and symptoms leading to the diagnosis were fever with joint pain and swelling. Positive laboratory studies included a synovial white blood-cell count of >50,000 cells/mm ³ (50 × 10 ⁹ /L), a positive gram stain and culture of synovial fluid and/or blood, and serum titers of indirect hemagglutination antibodies for Burkholderia pseudomallei . Twenty-seven patients were excluded from the study on the basis of a negative culture of synovial fluid, leaving seventy-seven, who made up the study population. Twenty-five patients were diagnosed with melioidotic septic arthritis on the basis of a gram stain or a culture that was positive for Burkholderia pseudomallei and/or an indirect hemagglutination antibodies titer of >1:80 or a fourfold rise in the titer. Fifty-two patients were diagnosed as having non-melioidotic septic arthritis on the basis of a gram stain or a culture that was positive for other organisms and/or histological sections positive for tuberculosis. The signs and symptoms, the joints that were involved, the patient's occupation, the duration of symptoms, and any concurrent diseases were recorded (see Appendix). All patients were treated with needle aspirations and antibiotics and, when necessary, with arthrotomy with irrigation and débridement (sixteen patients). The range of motion of the affected joints was recorded at the time of follow-up.

To compare the group with melioidotic septic arthritis and that with non-melioidotic septic arthritis, a univariate analysis was performed with use of the two-sample Student t test for continuous variables and the Fisher exact test for categorical variables. Stepwise multiple logistic regression with backward selection was used to identify independent clinical predictors with the same group comparisons used in the univariate analysis. Variables with a p value of <0.20 in the univariate analysis were chosen as candidates for the multivariate model, and significance was determined with use of the likelihood ratio chi-square test. Statistical analyses were carried out with SPSS software (version 8.0; SPSS, Chicago, Illinois).

Results

Thirteen men and twelve women had melioidotic septic arthritis, and thirty-two men and twenty women had non-melioidotic septic arthritis. The mean age (and standard deviation) was 53.7 ± 12.2 years in the group with melioidotic septic arthritis and 47.2 ± 17.7 years in the group with non-melioidotic septic arthritis; the mean duration of symptoms was 15.8 ± 13.1 and 8.8 ± 9.3 days, respectively. Eighteen of the patients with melioidotic septic arthritis and thirty of those with non-melioidotic septic arthritis were farmers. Eleven (44%) of the patients with melioidotic septic arthritis and five (10%) of those with non-melioidotic septic arthritis had involvement of an upper-extremity joint, so the odds ratio that an infection in an upper-extremity joint was caused by melioidosis was 2.99 (95% confidence interval, 1.70 to 5.28; p = 0.002 ). Twenty-two patients (88%) with melioidotic septic arthritis and twenty-one patients (40%) with non-melioidotic septic arthritis had a concurrent disease (p < 0.0001). The odds of a patient having melioidotic septic arthritis was 5.79 times greater when he or she had concurrent diabetes, chronic renal failure, or systemic lupus erythematosus than when he or she did not. However, when only patients with diabetes mellitus (eighteen of the twenty-five with melioidotic septic arthritis and six of the fifty-two with non-melioidotic septic arthritis) were considered, the odds ratio for being infected by Burkholderia pseudomallei rather than another organism was 5.68.

Results of the stepwise logistic regression analysis confirmed only two independent variables as risk factors for melioidotic septic arthritis: diabetes mellitus and involvement of an upper-extremity joint. The logistic regression formula was: MSA = e ^{(0.0136 - 2.76 × DM - 1.51 × UE)} , where MSA = melioidotic septic arthritis, DM = diabetes mellitus, and UE = upper extremity. In this analysis, the true odds of a patient having melioidotic septic arthritis were 15.7 times greater, with a 95% confidence interval of 4.5 to 55.6, if the patient had diabetes mellitus than if he or she did not. The upper-extremity joints were 4.5 times more likely to be infected with Burkholderia pseudomallei than were the lower-extremity joints, with a 95% confidence interval of 1.04 to 19.65.

Of the sixteen patients who underwent arthrotomy for drainage, three needed more than one arthrotomy before the infection resolved. Nine patients were treated with aspiration and antibiotics alone. Double antibiotic therapy (doxycycline and cotrimoxazole) or triple antibiotic therapy (doxycycline, cotrimoxazole, and ceftazidime) was given to all patients for six months to prevent a recurrence of the infection. The patients were followed monthly until the clinical examination, radiographs of the affected joint, and erythrocyte sedimentation rate showed that the infection had resolved. The median duration of follow-up was nine months (range, five to twenty-five months). No patient died during the study period. Three had recurrence of the infection after eight months of follow-up and were managed with débridement and triple antibiotic therapy with doxycycline, cotrimoxazole, and ceftazidime. The outcome was a fibrous ankylosis of the joint in all three.

Discussion

We believe that our study is the first to identify the risk factors for the development of melioidotic septic arthritis rather than another type of septic arthritis. Burkholderia pseudomallei is a common cause of opportunistic infections in certain areas of the world. Individuals particularly susceptible to the infection include those with diabetes mellitus or renal disease ^21-25 . In our study, diabetes mellitus was identified as a definite risk factor, with an odds ratio of almost 16.

The upper-extremity joints, especially the shoulder, were the most commonly affected joints in our study. This finding has not been mentioned elsewhere, to our knowledge, and we cannot explain it. In our study, most of the patients with melioidotic septic arthritis had had a longer duration of symptoms than those with non-melioidotic septic arthritis. The organism is a facultative intracellular pathogen, and the incubation period has not been well defined (range, two days to twenty-six years ^26,27 ); hence, the potential exists for a prolonged latency period before a diagnosis is made.

Clinically, melioidotic septic arthritis can mimic acute or chronic forms of other infections or rheumatic disorders ² . Histological examination of gram-stained synovial fluid or pus may be the quickest way to make a diagnosis, although such identification is infrequent and bacteriological studies are the mainstay of diagnosis. A culture of synovial fluid or pus from the affected joint was positive in twenty-two (88%) of our twenty-five cases, whereas blood cultures were positive in only twelve (48%). This finding, however, does not represent the true clinical setting because we studied only cases of melioidotic septic arthritis with a positive synovial or blood culture. Therefore, our study included a relatively high percentage of positive blood cultures even though blood cultures are rarely positive with the localized form of melioidosis ² .

Determination of the titer of indirect hemagglutination antibodies against Burkholderia pseudomallei was used as a diagnostic test in our study. The cutoff value for a positive titer was set at 1:80, with 64.7% sensitivity, 93.6% specificity, 83.45% accuracy, a 35.3% false-negative rate, and a 6.4% false-positive rate. Although the sensitivity of this test was not high, the false-positive rate was low. Therefore, we had a minimal chance of missing the diagnosis of melioidosis. Moreover, only two cases were diagnosed solely on the basis of the indirect hemagglutination antibodies titer. Today, there are newer laboratory tests for the diagnosis of melioidosis; the most sensitive and specific, although expensive, is the enzyme-linked immunosorbent assay ²⁸ .

It has been reported that there is no correlation between the antibody level, as measured by indirect hemagglutination antibodies levels, and the severity, prognosis, or clinical form of the disease, but a rising titer may indicate a recurrence of disease activity ²⁹ . Therefore, we used not only clinical evaluation and the erythrocyte sedimentation rate but also indirect hemagglutination antibodies titers to follow our patients. Recent studies have indicated that early detection of bacteria (within twenty-four hours after infection) and the amount of bacteria circulating in the blood are related to the clinical outcome ^30,31 .

In 2000, most strains of Burkholderia pseudomallei in our hospital were 100% sensitive to doxycycline, cotrimoxazole, and ceftazidime. Aspiration and sometimes surgical drainage, together with a combination of drugs to which the organism was sensitive, were effective for the treatment of melioidotic septic arthritis in our patients and resulted in a low rate of recurrence.

Appendix

A table showing demographic and clinical data on all patients in this study is available with the electronic versions of this article, on our web site at www.jbjs.org (go to the article citation and click on "Supplementary Material") and on our quarterly CD-ROM (call our subscription department, at 781-449-9780, to order the CD-ROM).

Note: The authors thank Mr. Bryan Roderick Hamman and Mrs. Janice Loewen-Hamman for assistance with the English-language presentation of the manuscript.

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Topics

bacterial arthritis ; burkholderia pseudomallei ; melioidosis ; infection

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Weerachai Kosuwon, Twatchai Taimglang, Winia Sirichativapee, Polasak Jeeravipoolvarn; Melioidotic Septic Arthritis and Its Risk Factors. The Journal of Bone & Joint Surgery. 2003 Jun;85(6):1058-1061.

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