Bacteriophage Application for Difficult-to-treat Musculoskeletal Infections: Development of a Standardized Multidisciplinary Treatment Protocol.

Bacteriophage therapy has recently attracted increased interest, particularly in difficult-to-treat infections. Although it is not a novel concept, standardized treatment guidelines are currently lacking. We present the first steps towards the establishment of a "multidisciplinary phage task force" (MPTF) and a standardized treatment pathway, based on our experience of four patients with severe musculoskeletal infections. After review of their medical history and current clinical status, a multidisciplinary team found four patients with musculoskeletal infections eligible for bacteriophage therapy within the scope of Article 37 of the Declaration of Helsinki. Treatment protocols were set up in collaboration with phage scientists and specialists. Based on the isolated pathogens, phage cocktails were selected and applied intraoperatively. A draining system allowed postoperative administration for a maximum of 10 days, 3 times per day. All patients received concomitant antibiotics and their clinical status was followed daily during phage therapy. No severe side-effects related to the phage application protocol were noted. After a single course of phage therapy with concomitant antibiotics, no recurrence of infection with the causative strains occurred, with follow-up periods ranging from 8 to 16 months. This study presents the successful outcome of bacteriophage therapy using a standardized treatment pathway for patients with severe musculoskeletal infection. A multidisciplinary team approach in the form of an MPTF is paramount in this process.

Rheumatic and musculoskeletal features of Whipple disease: a report of 29 cases.

OBJECTIVE: Whipple disease is a rare infection caused by Tropheryma whipplei. Although patients commonly complain of osteoarticular involvement, musculoskeletal manifestations have been poorly described. We report cases of Whipple disease with rheumatic symptoms and describe their clinical presentation, modes of diagnosis, and outcomes. METHODS: This retrospective multicenter study included patients with Whipple disease diagnosed and referenced between 1977 and 2011 in 10 rheumatology centers in France and Italy. RESULTS: Twenty-nine patients were included. The median age was 55 years. The median time to diagnosis from first symptoms was 5 years. Polyarthritis was the most frequent presentation (20/29), and was most often chronic, intermittent (19/29), seronegative (22/23), and nonerosive (22/29). In all cases, the symptoms had led to incorrect diagnosis of inflammatory rheumatic disease and immunosuppressants, including biotherapy, were prescribed in most cases (24/29) without success. The diagnosis of Whipple disease was made by histological analysis, molecular biology tests, or both in 21%, 36%, and 43% of the cases, respectively. Duodenal biopsies were performed in most cases (86%). Synovial biopsies were performed in 18% of cases, but all contributed to diagnosis. The clinical outcomes after antibiotic therapy were good for all patients. CONCLUSION: Polyarthritis is the main feature observed in cases of Whipple disease; it is seronegative and associated with general and gastrointestinal symptoms. The molecular analysis of duodenal tissue and/or other tissues remains the method of choice to confirm the diagnosis. Reducing the time to diagnosis is important because severe late systemic and fatal forms of the disease may occur.

Musculoskeletal features of Lyme disease: understanding the pathogenesis of clinical findings helps make appropriate therapeutic choices.

Patients with Lyme disease, that is, active infection with Borrelia burgdorferi, experience many types of musculoskeletal complaints, with different explanatory mechanisms. Appropriate therapy depends on understanding the underlying cause of the complaint and addressing that specific root cause. In the case of active infection the dosage, duration, drug, and method of administration of antibiotics should be determined by the state of the infection and history of prior therapy, according to the established and validated recommendations of the Infectious Disease Society of America. Many patients have musculoskeletal complaints not attributable to active infection; some patients have residual complaints following a documented infection that has been adequately treated with antibiotics previously, and others never had true B. burgdorferi infection in the first place. For such patients, antibiotics are not warranted and in fact may be physically and emotionally harmful. Complaints following an episode of Lyme disease are not necessarily due to ongoing infection, especially adequately treated. Consideration of other diagnoses may suggest use of other effective modalities, including physical therapy and emotional support. Appropriate ordering and interpretation of the various validated seroconfirmatory tests available to study B. burgdorferi infection are critical, as these tests are often misapplied and misconstrued in pursuit of strategies aimed at eliminating patients' suffering. Although seronegative Lyme disease has been reported, seronegativity in a reputable laboratory makes the likelihood of Lyme arthritis very low. On the other hand, a positive result from certain unvalidated laboratories or novel assays proves nothing and should not be viewed as substantiating the diagnosis.

Melioidosis: a review of orthopedic manifestations, clinical features, diagnosis and management.

Melioidosis is an infectious disease caused by gram-negative soil-dwelling bacillus Burkholderia pseudomallei. Musculoskeletal melioidosis mimics other infections both clinically and radiologically. An extensive literature review has been performed over musculoskeletal melioidosis through various search engines such as Pubmed, Embase, Medscape, Altavista and Google. Diagnosis requires a high index of clinical suspicion and is dependent on microbiological confirmation. Prompt treatment with long-term combination antibiotics in high dosages and surgical drainage of abscesses improves survival.

Suction drainage culture as a guide to effectively treat musculoskeletal infection.

Following surgery for musculoskeletal infection, a positive suction drainage culture (SDC) is consistent with persistent sepsis. Our objective was to determine the effect of a negative SDC obtained in subsequent operations on the outcome of a musculoskeletal infection. 99 patients were prospectively enrolled, all treated surgically for musculoskeletal infection utilizing suction drainage and appropriate antimicrobial therapy. Surgery consisted of irrigation, debridement, and prosthetic exchange or implant removal. SDC was considered negative if all bottles resulted in negative cultures. Following SDC results, patients were placed into 1 of 2 treatment groups: 1) Negative SDC, and no new operation; or 2) Positive SDC, and new operation(s) until SDC was negative. Antibiotic therapy ranged from 6-12 weeks (osteomyelitis) to 10-21 d (soft tissue). Both groups were similar with regard to baseline characteristics. Cure was obtained in 91.8% of patients (56/61) in group 1 and 91.6% of patients (22/24) in group 2. Similar results were obtained in patients with an infection in the presence of an implant. In conclusion, a negative SDC following surgery for a musculoskeletal infection is a strong indication of eventual outcome.