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Septic Arthritis in Patients with Human Immunodeficiency Virus

Zalavras, Charalampos G, MD; Dellamaggiora, Ryan, MD; Patzakis, Michael J, MD; Bava, Eric, MD; Holtom, Paul D, MD

Section Editor(s): Garvin, Kevin MD, Guest Editor

Clinical Orthopaedics and Related Research®: October 2006 - Volume 451 - Issue - p 46-49
doi: 10.1097/01.blo.0000229305.97888.17
SECTION I: SYMPOSIUM I: Papers Presented at the 2005 Meeting of the Musculoskeletal Infection Society
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The literature contains few descriptions of the infective organisms and diagnostic issues associated with musculoskeletal infections in patients with HIV. We retrospectively reviewed 19 patients with HIV treated at our musculoskeletal infection ward for septic arthritis. The mean CD4 count was 154/mm3 (range, 7-482/mm3), and 11 patients had a CD4 count < 200/mm3 and were diagnosed with AIDS. The most common pathogen (six patients) was oxacillin-resistant Staphylococcus aureus. Mycobacterial infections occurred in three patients but no fungal pathogens were identified. Septic arthritis was monoarticular in 14 patients and involved the knee in eight patients, the hip in three patients, and the wrist in three patients. Five patients presented with polyarticular septic arthritis. All mycobacterial infections and four of the five polyarticular infections occurred in patients with a CD4 count < 200/mm3. Patients with CD4 count < 200/mm3 had a lower joint fluid WBC count compared to patients with a CD4 count > 200/mm3 (40,500 vs 69,000/mm3). Oxacillin-resistant Staphylococcus aureus was the most common pathogen. A high index of suspicion for Mycobacterium. tuberculosis arthritis and polyarticular septic arthritis is necessary in patients with HIV and a CD4 count < 200/mm3.

Level of Evidence: Level IV, diagnostic study. See Guidelines for Authors for a complete description of Levels of Evidence.

From the Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, and the University of Southern California Medical Center, Los Angeles, CA.

Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

Each author certifies that his or her institution has approved or waived approval for the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

Correspondence to: Charalampos G. Zalavras, MD, LAC + USC Medical Center, 1200 N. State Street, GNH 3900, Los Angeles, CA 90033. Phone: 323-226-7346; Fax: 323-226-4501; E-mail: zalavras@usc.edu.

Musculoskeletal conditions such as Reiter's syndrome, psoriatic arthritis, human immunodeficiency (HIV)-associated arthritis, painful articular syndrome, acute symmetric polyarthritis, hypertrophic osteoarthropathy, and osteonecrosis have been reported in 11% to 72% of patients with HIV.1,2,20,22 Despite the immunosuppressive effect of HIV however, musculoskeletal infections occur only in 0.3% to 3.6% of patients with HIV and do not occur more frequently compared with nonimmunocompromised patients.10,22,30,31

The literature on septic arthritis in patients with HIV is limited to case reports and small series. Some authors have reported opportunistic pathogens as the infecting agents, which were attributed to the immunosuppressive effect of HIV.3,4,6-9,11-16,18,21,24-29,32 Other investigators did not encounter septic arthritis from such organisms,20,31 or identified opportunistic pathogens in only a few patients, whereas septic arthritis was caused by staphylococcal or streptococcal species in most patients.10,22,30 Overall, infections with opportunistic organisms range from 0%20,31 to 51% of patients,30 and staphylococcal infections range from 31%30 to 59%.22

The range of infective organisms of septic arthritis in patients with HIV remains unclear, although the few case reports suggest considerable variability. Additional information may assist in the selection of empiric antibiotic therapy for the management of these uncommon infections. Moreover, the existing literature has not evaluated whether the CD4 count has an effect on the clinical and laboratory characteristics of septic arthritis.

The primary purpose of our study was to determine whether opportunistic pathogens are common pathogens causing septic arthritis in a large cohort of patients with HIV. We also evaluated the location and number of involved joints and the effect of the CD4 count on the clinical and laboratory characteristics of septic arthritis.

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MATERIALS AND METHODS

We retrospectively reviewed 19 consecutive patients with HIV who had septic arthritis of the upper or lower extremity treated at our musculoskeletal infection ward from 1993 to 2004. The inclusion criteria were: (1) patients with HIV diagnosed with enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot, (2) septic arthritis diagnosed by positive cultures of joint fluid (we routinely send specimens for aerobic, anaerobic, fungal, and mycobacterial cultures) and/or clinical and laboratory findings consistent with septic arthritis (pain, limited motion, effusion of the involved joint, and aspiration of purulent material), and (3) adults (≥ 18 years). Patients with a history of trauma and/or surgery of the involved joint were excluded. All 19 patients were male with a mean age of 42 years (range, 25-56 years). Risk factors for HIV were identified in 12 patients and included intravenous drug abuse in six patients and homosexuality in six patients. Sixteen patients knew they had HIV for a mean period of 4.8 years (range, 2 months to 11 years) before presentation. Four these patients were taking medications for HIV at that time. Three patients who had risk factors for HIV were diagnosed with HIV during their admission for the management of a septic joint. Our study was performed after institutional review board approval.

Patients' mean CD4 count was 154/mm3 (range, 7-482/mm3). Eleven patients had a CD4 count < 200/mm3 and met the diagnostic criteria for AIDS, which included a CD4 count < 200/mm3 or presence of a clinical condition included in the 1993 AIDS surveillance case definition by the Center for Disease Control.5

From the patients' charts we extracted clinical data (number and location of involved joints), laboratory data (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], peripheral blood white blood cell count [WBC], CD4 count, joint aspirate WBC count, and differential), and culture results.

In order to assess the potential effect of the CD4 count on the clinical and laboratory findings of septic arthritis comparisons were performed between two groups of patients with a CD4 count greater or smaller than 200/mm3. Proportions were compared with the Fisher's exact test and continuous variables with the Mann-Whitney U test. All tests were two-tailed and significance was set at < 0.05.

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RESULTS

Mycobacterium tuberculosis infections were present in three of 19 patients, whereas no atypical mycobacterial or fungal pathogens were identified. Staphylococcus aureus was present in seven patients. The organism was oxacillin-resistant in six of these seven patients. Streptococcal species were present in six patients, coagulase-negative staphylococcus in two patients, enterococcus in one, and Neisseria gonorrhea in one. The infection was monomicrobial in 18 patients and polymicrobial in one patient.

Septic arthritis was monoarticular in 14 patients and involved the knee in eight, the hip in three, and the wrist in three. Five patients presented with septic arthritis of multiple joints and the knee was involved in four of these patients. The knee was involved in 12 of the 19 patients. All patients complained of pain and limited range of motion of the affected joint(s). Eighteen of 19 patients were febrile with a mean temperature of 102.4°F (range, 100.2-104.3°F). Three patients were in septic shock upon presentation. One patient with a septic hip, who had a CD4 count of 101/mm3, renal failure and hyperkalemia, refused any intervention and died 4 days later. The other two patients in septic shock (with CD4 counts of 88/mm3 and 287/mm3) were treated surgically on the day of admission, had an uneventful postoperative course and were discharged home. Excluding the patient who died and two patients who were transferred to other facilities, the clinical response of the remaining 16 patients to treatment was characterized by persistence of symptoms in three patients during their hospitalization. Adjacent osteomyelitis was present in the distal femur and proximal tibia of two patients with septic knee arthritis and in the femoral head of one patient with septic hip arthritis. These three patients underwent a repeat débridement and drainage procedure.

Analysis of the groups of patients with a CD4 count greater or smaller than 200/mm3 demonstrated all three mycobacterial infections and four of the five polyarticular infections occurred in patients with a CD4 count < 200/mm3. Patients with CD4 count < 200/mm3 had a lower (p = 0.04) joint fluid WBC count compared to patients with a CD4 count > 200/mm3 (40,500 vs 69,000/mm3, respectively). Patients with CD4 count < 200/mm3 tended to have a lower (p = 0.09) peripheral blood WBC count (5700 vs 11700/mm3, respectively).

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DISCUSSION

Musculoskeletal infections are not common in patients with HIV, and the estimated prevalence of septic arthritis or osteomyelitis ranges from 0.3% to 3.6% in the literature.10,22,30,31 The literature on septic arthritis in patients with HIV is limited to case reports and small series of patients.3,4,6-9,11-16,18,21,24-29,32 The microbiology of septic arthritis in patients with HIV remains unclear. In the current study Staphylococcus aureus was the most common pathogen present in 7 of 19 patients, whereas Myco-bacterium tuberculosis was present in three patients. No atypical mycobacterial or fungal infections were identified.

We note several limitations to our retrospective review. While our patient numbers are small, this is a relatively large series of patients with HIV and septic arthritis considering the rare occurrence of musculoskeletal infections in this patient population.1,10,30,31 A prospective comparison of patients with and without HIV treated for septic arthritis would be useful to determine the role of HIV in the clinical presentation and microbiology of septic arthritis. We do not report the outcomes for these infections. The diagnosis of HIV may have been missed in some patients because testing requires consent and is not routinely performed. The incidence of septic arthritis in patients with HIV is not reported because we did not follow such a cohort over the period of the study.

In 1985, Lipstein-Kresch et al13 reported septic arthritis from Sporothrix schenkii in a patient with AIDS. Since then, several authors have described septic arthritis from opportunistic pathogens such as atypical mycobacteria and fungi.3,6-8,12,15,18,21,25-28,32 Mycobacterial species resulting in septic arthritis in patients with HIV include Myco-bacterium avium,3,6,27,32 Mycobacterium kansasii,8 and Mycobacterium haemophilum.12,15,26 Candida albicans,7,18,28 Cunninghamella bertholletiae,21 and Cryptococcus neoformans25 are some of the fungal pathogens associated with septic arthritis in patients with HIV. Septic arthritis from Nocardia asteroides,24 Helicobacter species,4,11 Salmonella,9,14,29 and Staphylococcus cohnii16 has been reported. In these patients, the presence of opportunistic pathogens may be attributed to the well-established immunosuppressive effect of HIV.23

In some small series of patients with HIV and septic arthritis, opportunistic organisms were not present20,31 or were responsible for a small proportion of infections.10,22,30 In a series of 17 patients, 10 of whom had septic arthritis of extremity joints, Munoz Fernandez et al22 reported Staphylococcus aureus was present in 59% or patients and Candida albicans was present in 24% of patients. Hughes et al10 reported Staphylococcus aureus was present in three of seven patients, whereas Histoplasma capsulatum was present in one patient (14%). Vassilopoulos et al30 described 10 patients with septic arthritis and identified Streptococcus pneumoniae in 40% of patients and fungal pathogens in 20% of patients. However, a literature review of 99 published cases of septic arthritis in patients with HIV identified opportunistic pathogens in 51% of patients, whereas Staphylococcus aureus and streptococcal species were present in 31% and 8% of septic joints, respectively.30 Therefore, the role of opportunistic organisms in the pathogenesis of septic arthritis in patients with HIV is controversial.

In our series, Staphylococcus aureus and streptococcal species were the most common pathogens, present in 7 and 6 patients, respectively. Despite their immunocompromised status, and in contrast to previous studies,10,30 patients with HIV did not develop septic arthritis from fungi or atypical mycobacteria. However, three patients had septic arthritis from Mycobacterium tuberculosis, which is more than reported in other studies10,30 A literature review of 99 patients with HIV and septic arthritis reported Mycobacterium tuberculosis in only 1% of patients.30 The variability among study results may be attributed to different degrees of immunosuppression among patient cohorts, variability in the culture techniques among laboratories, and the inherent flaws of retrospective studies.

The microbiological data we report have important clinical implications. Because the predominant pathogen is Staphylococcus aureus it should always be covered with initial empiric antibiotic therapy based on the antibiogram of the treating institution. The increased proportion of ORSA (6 of 19 patients) in our series is consistent with recent studies reporting the emergence of ORSA as a pathogen in HIV infected patients.17,19 Colonization of HIV-infected drug users with ORSA was 14% compared to 3% in HIV-uninfected ones,19 and ORSA infections in HIV infected patients increased more than 6-fold in a 4 year period.17 Therefore, the use of vancomycin as empiric antibiotic therapy may be justified. Empiric coverage for opportunistic pathogens does not appear to be justified in patients with HIV.

Based on the literature a high index of suspicion for opportunistic pathogens, including mycobacterial and fungal pathogens, is necessary for patients with HIV, especially if the CD4 count is < 200/mm3. In the current study, three of 11 patients with a CD4 count < 200/mm3 had Mycobacterium tuberculosis infections. Joint fluid obtained from joint aspiration or surgical drainage should be evaluated by specialized stains and culture techniques to make the diagnosis of tuberculous arthritis. In addition, pathologic examination of a synovial specimen may be helpful in expediting the diagnosis of these infections. Polyarticular septic arthritis should also be suspected in patients with HIV, especially if they present with a CD4 count < 200/mm3. Symptoms from more than one joint should be thoroughly evaluated with a high index of suspicion for septic arthritis to promptly diagnose and treat the multiple infectious processes.

Oxacillin resistant Staphylococcus aureus is the most common pathogen found in these patients and should be covered by empiric antibiotic therapy. Opportunistic pathogens are not common pathogens in patients with HIV and septic arthritis. However, a high index of suspicion for mycobacterial and fungal septic arthritis and for septic arthritis of multiple joints is necessary in patients with HIV if the CD4 count is < 200/mm3.

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