The diagnosis and management of prosthetic joint infections.

A host of technical and operative improvements have seen the rates of infection associated with joint replacement reach historic lows. However, the increasing number of operations being performed means that the absolute number of such infections remains significant. Diagnosis may be challenging and delaying appropriate treatment can lead to reduced joint function and the need for more complex, perhaps multiple, procedures. Individual centres tend to see small numbers of such cases, and in the absence of large clinical trials management varies. Early diagnosis, selection of an appropriate surgical strategy, accurate identification of the responsible microorganisms and construction of an appropriate antibiotic regimen are essential elements of any management strategy. Such packages of care are best delivered by a multidisciplinary team composed of orthopaedic and plastic surgeons, microbiologists, infectious disease physicians, specialist nurses, physiotherapists and occupational therapists. Each treatment plan must be developed in consultation with the patient, taking into account their aims and realistic goals. This review provides an overview of current understanding regarding diagnosis and treatment of prosthetic joint infections and suggests a treatment algorithm.

The microbiology of chronic osteomyelitis: prevalence of resistance to common empirical anti-microbial regimens.

OBJECTIVES: This study describes the microbiological spectrum of chronic osteomyelitis and so guides the choice of empirical antibiotics for this condition. METHODS: We performed a prospective review of a 166 prospective patient series of chronic osteomyelitis from Oxford, UK in which a standardised surgical sampling protocol was used. RESULTS: Staphylococcus aureus was most commonly isolated (32%) amongst a wide range of organisms including gram negative bacilli, anaerobes and coagulase negative staphylococci. Low grade pathogens were not confined to patients with a history of metalwork, a high proportion of cases were polymicrobial (29%) and culture negative cases were common (28%). No clear predictors of causative organism could be established. Many isolates were found to be resistant to commonly used empirical anti-microbial regimens. CONCLUSIONS: The wide range of causative organisms and degree of resistance to commonly used anti-microbials supports the importance of extensive intra-operative sampling and provides important information to guide clinicians' choice of empirical antibiotics.

Two-stage revision for prosthetic joint infection: predictors of outcome and the role of reimplantation microbiology.

OBJECTIVES: We describe rates of success for two-stage revision of prosthetic joint infection (PJI), including data on reimplantation microbiology. METHODS: We retrospectively collected data from all the cases of PJI that were managed with two-stage revision over a 4 year period. Patients were managed with an antibiotic-free period before reimplantation, in order to confirm, clinically and microbiologically, that infection was successfully treated. RESULTS: One hundred and fifty-two cases were identified. The overall success rate (i.e. retention of the prosthesis over 5.75 years of follow-up) was 83%, but was 89% for first revisions and 73% for re-revisions [hazard ratio = 2.9, 95% confidence interval (CI) 1.2-7.4, P = 0.023]. Reimplantation microbiology was frequently positive (14%), but did not predict outcome (hazard ratio = 1.3, 95% CI 0.4-3.7, P = 0.6). Furthermore, most unplanned debridements following the first stage were carried out before antibiotics were stopped (25 versus 2 debridements). CONCLUSIONS: We did not identify evidence supporting the use of an antibiotic-free period before reimplantation and routine reimplantation microbiology. Re-revision was associated with a significantly worse outcome.

Pharmacotherapy of diabetic foot osteomyelitis.

Diabetic foot osteomyelitis (DFO) complicates about 20% of diabetic foot infections (DFIs) and increases the risk of lower extremity amputation. This contentious infection is important to discuss, given the frequency with which diabetes mellitus and its complications occur and the devastating consequences of amputation. The diagnosis and management of DFO is complicated by the diverse presentations, delayed recognition, poorly defined diagnostic criteria, and lack of validated treatment regimens. Major issues of concern include when to undertake bone resection surgery and which antimicrobial agents to use, by what route, and for how long. Patients in whom DFO is suspected are best cared for by a multidisciplinary team, including infectious disease physicians or clinical microbiologists, orthopaedic, plastic and vascular surgeons, diabetologists, primary care physicians, podiatrists and specialist (especially tissue viability) nurses. Such multidisciplinary teams have repeatedly been shown to improve disease outcomes. We herein analyse the limited, and recently published, literature on the pharmacotherapy of DFO and put it into the broader context of management of DFI and osteomyelitis.

One hundred and twelve infected arthroplasties treated with 'DAIR' (debridement, antibiotics and implant retention): antibiotic duration and outcome.

OBJECTIVES: We describe treatment failure rates by antibiotic duration for prosthetic joint infection (PJI) managed with debridement, antibiotics and implant retention (DAIR). METHODS: We retrospectively collected data from all the cases of PJI that were managed with DAIR over a 5 year period. Surgical debridement, microbiological sampling, early intravenous antibiotics and prolonged oral follow-on antibiotics were used. RESULTS: One hundred and twelve cases of PJI were identified. Twenty infections (18%) recurred during a mean follow-up of 2.3 years. The mean duration of antibiotic use was 1.5 years. Failure was more common after arthroscopic debridement, for previously revised joints and for Staphylococcus aureus infection. There were 12 failures after stopping antibiotics and 8 while on antibiotics [hazard ratio (HR) = 4.3, 95% confidence interval (CI) 1.4-12.8, P = 0.01]. However, during the first 3 months of follow-up, there were eight failures after stopping antibiotics and two while on antibiotics (HR = 7.0, 95% CI 1.5-33, P = 0.015). The duration of antibiotic therapy prior to stopping did not predict outcome. CONCLUSIONS: PJI may be managed by DAIR. The risk of failure with this strategy rises after stopping oral antibiotics, but lengthening antibiotic therapy may simply postpone, rather than prevent, failure.

Pristinamycin as adjunctive therapy in the management of Gram-positive multi-drug resistant organism (MDRO) osteoarticular infection.

OBJECTIVE: Osteoarticular infection often requires prolonged antibiotic therapy as an adjunct to surgery. We report our experience using pristinamycin, an oral streptogramin, when conventional antibiotics were poorly tolerated or inappropriate because of multi-drug resistant organisms (MDROs). METHODS: We retrospectively identified, from pharmacy records, all patients prescribed pristinamycin between 1/1/2004 and 31/12/2006. We collected clinical and microbiological data. RESULTS: Twenty-one patients were identified (13 male and eight female patients, age range 18-83 years). Sixteen patients (76%) had infection due to MDROs and five (24%) were intolerant of conventional antibiotics. Ten patients received other concurrent oral antibiotics. Eleven of 21 (52%) patients remained free of recurrent infection off antibiotics at a mean follow up duration of 13 months, (range 4-25 months). Suppression of infection while still on therapy was achieved in a further four patients (19%) with a mean follow up of 11.5 months (range 5-15 months). Six patients (29%) failed therapy, all requiring a further surgical procedure. CONCLUSION: Oral pristinamycin was a well tolerated and useful adjunctive treatment in this group with complex orthopaedic infection. Pristinamycin can be considered in patients with osteoarticular infection due to Gram-positive organisms when antibiotic multi-resistance or intolerance makes conventional therapies impossible. SUMMARY: We report our experiences of using pristinamycin in the management of 21 patients with Gram-positive MDRO osteoarticular infection or who were unable to tolerate more conventional regimens. Our results show that pristinamycin is well tolerated with outcomes comparable to those of other agents described in the literature on osteoarticular infection.

Guiding empirical antibiotic therapy in orthopaedics: The microbiology of prosthetic joint infection managed by debridement, irrigation and prosthesis retention.

OBJECTIVES: This study describes the microbiological spectrum of prosthetic joint infection (PJI) managed by debridement, washout and retention and so guides the choice of empirical antibiotics within this patient group. METHODS: We performed a retrospective review of all patients admitted to our specialist tertiary unit for PJI who were managed with debridement and irrigation or arthroscopic washout of infected prosthetic joints between 1st January 1998 and 30th April 2003. Clinical and microbiological data sets were analysed using the Access database. RESULTS: One hundred and twelve patients met the criteria for inclusion. 69% received their surgical intervention in the first three months after implantation ('early') and 21% after 12 months. Overall the most frequently isolated organisms were coagulase negative staphylococci (47% patients) and methicillin-sensitive Staphylococcus aureus (MSSA, 44% patients). 8% grew methicillin-resistant Staphylococcus aureus (MRSA) and 7% grew anaerobes. Most Gram-negative isolates were resistant to cefuroxime; all were sensitive to meropenem. Eighty-six percent of polymicrobial cultures occurred in early infections when 47% of patients grew more than one organism. MSSA was the most frequently isolated organism at all time points. CONCLUSIONS: Most infections involved staphylococci. MRSA was infrequently isolated. Most polymicrobial infections occurred in early infection. A high rate of resistance to cephalosporins among Gram-negative organisms justifies the use of a broader agent such as a carbapenem in the early empirical antibiotic regime for PJI.

Internal fixation for osteomyelitis of cervical spine: the issue of persistence of culture positive infection around the implants.

BACKGROUND: We describe the management of osteomyelitis of the cervical spine, utilizing internal fixation with subsequent removal and culture of the implants. Four out of five patients had evidence of bacterial colonisation in close proximity to the internal fixation device. METHODS: Five consecutive patients (all female, ranging in age from 50 to 74 yrs) presenting with unstable cervical osteomyelitis were treated by surgical decompression, primary internal fixation followed by three months of intravenous antibiotics. The internal fixation was removed in 4 out of 5 cases within a year of stopping the intravenous regime. The remaining patient was deemed medically unfit for further operation. Multiple specimens from the screw sites were taken at the time of metal removal. A final course of oral antibiotics was prescribed based on the results of these specimens. FINDINGS: Four patients, who had removal of the implants, had positive cultures growing different bacteria from the primary infection, at the time of removal of the implant. None of the patients developed instability after removal of the implant. INTERPRETATION: Asymptomatic bacterial colonisation of a metallic implant has profound management implications. We recommend long-term oral antibiotic regimes after insertion of internal fixation devices in the face of infection and eventual removal of these implants and microbiological re-sampling.

Randomised controlled trial and economic evaluation of podophyllotoxin solution, podophyllotoxin cream, and podophyllin in the treatment of genital warts.

OBJECTIVES: To evaluate the efficacy and cost effectiveness of self applied podophyllotoxin 0.5% solution and podophyllotoxin 0.15% cream, compared to clinic applied 25% podophyllin in the treatment of genital warts over 4 weeks. METHODS: We conducted a randomised controlled trial in 358 immunocompetent men and women with genital warts of 3 months' duration or less. RESULTS: In the principal analysis both podophyllotoxin solution (OR 2.93, 95% CI 1.56 to 5.50) and podophyllotoxin cream (OR 1.97, 95% CI 1.04 to 3.70) were associated with significantly increased odds of remission of all warts compared to podophyllin. We performed two further analyses. When subjects defaulting from follow up were assumed to have been cured odds of remission of all warts were also significantly increased both for podophyllotoxin solution (OR 3.04, 95% CI 1.68 to 5.49) and for podophyllotoxin cream (OR 2.46, 95% CI 1.38 to 4.40). When subjects defaulting from follow up were assumed not to have been cured odds of remission of all warts were significantly increased for podophyllotoxin solution (OR 1.92, 95% CI 1.13 to 3.27), but not for podophyllotoxin cream (OR 1.17, 95% CI 0.69 to 2.00). Local side effects were seen in 24% of subjects, and recurrence of warts within 12 weeks of study entry in 43% of all initially cleared subjects, without statistically significant differences between the treatment groups. Direct, indirect, and total costs were similar across the three treatment groups. Podophyllotoxin solution was the most cost effective treatment, followed by podophyllotoxin cream, with podophyllin treatment being the least cost effective. CONCLUSIONS: Self treatment of anogenital warts with podophyllotoxin showed greater efficacy and cost effectiveness than clinic based treatment with podophyllin.

Cutaneous tuberculosis of the penis and sexual transmission of tuberculosis confirmed by molecular typing.

A case of culture-positive primary cutaneous Mycobacterium tuberculosis infection of the penis was diagnosed in a male patient; 1 year later, endometrial tuberculosis was diagnosed in the patient's wife. These organisms were confirmed to be indistinguishable by use of molecular techniques.

Lichen sclerosus in adult men: a study of HLA associations and susceptibility to autoimmune disease.

Lichen sclerosus is a skin disorder of unknown prevalence affecting both men and women, and several studies have established HLA associations in women with this disease. Autoimmune disease associations in the form of a personal and/or family history of autoimmune disease have also been shown to be related to lichen sclerosus. In this study, we examined 58 men (mean age 38 years) with lichen sclerosus, 39 of whom had histologically proven disease. HLA tissue typing by phototyping was performed on these patients and contrasted with that of 602 control subjects. There was no difference in antigen frequencies of the HLA class I loci. The patient group was found to have an increased frequency of several HLA antigens of the class II loci: DR11, 13 of 58 (22%) patients vs. 75 of 602 (13%) control subjects (P = 0.05); DR12, five of 58 (9%) patients vs. 16 of 602 (3%) control subjects (P = 0.04); DQ7, 26 of 58 (45%) patients vs. 189 of 602 (31%) control subjects (P = 0.05). There were few autoimmune disease associations: two of 58 (3%) patients had a personal history of a different autoimmune disease, two patients were found to have abnormal thyroid function and six of 58 (10%) had a first-degree relative with an autoimmune disease. There was no difference in the frequency of the autoimmune haplotype HLA A1, B8, DR3/17, DQ2 compared with the control population. HLA DQ7 has now been shown to occur more frequently in both male and female patients with lichen sclerosus, which may reflect the immunopathogenesis of the disease. Autoimmune disease associations, however, are less common in men with lichen sclerosus.