EH 6/2014

Y O U R S T E R I L E S I N G L E - U S E S O L U T I O N W I T H O U T C O M P R O M I S E Onceused. Workﬂowimproves. t +44 (0)1792 797910 e info@dtrmedical.com w www.dtrmedical.com ® Proliferation Adhesion Mature Biofilm Dispersal EUROPEAN HOSPITAL Vol 23 Issue 6/14 10 INFECTION CONTROL Early diagnosis and treatment for joint implant contamination Improving contamination management Periprosthetic infections: a new disease Implant and tissue infections Early diagnosis and effective therapy of periprosthetic joint infections (PJI) remain a challenge for many physicians due to the complexity and heterogeneity of clinical symptoms. As individual solutions are needed, opportunities to discuss and exchange ideas are welcome, as clearly shown during the satellite symposium on the diagnosis and treatment of periprosthetic knee infections held at this year’s German Congress for Orthopaedics and Trauma Surgery (DKOU) Periprosthetic infections must be taken seriously – The two-year infec- tion rate for knee replacements is currently five percent, according to arthroplasty expert Professor Rudolf Ascherl, from the Hospital Medical Centre Stiftland Tirschenreuth, joint speaker with Professor Andrej Trampuz, from Berlin’s Charité Medical University. Due to demographic develop- ments, an increase in infection rates is anticipated; indeed the absolute number of periprosthetic knee infec- tions is already rising. Therefore, says Ascherl, periprosthetic infec- tions should be considered a new disease, which, to a certain extent, is unavoidable and requires specific diagnostic and therapy concepts. In addition, a stronger focus on periprosthetic infections is expedi- ent for financial reasons since infec- tion treatment is expensive, and the later the diagnosis is made, the higher the costs. The 21-days rule – If an acute infection is diagnosed early, the movable parts of the prosthesis can often be preserved while late detec- tion usually means the entire pros- thesis has to be replaced. Day 21 of the infection, Trampuz explains, is the cut-off day: by now the local biofilm produced by the patho- gens is too stable for the patient’s immune system, or antibiotics, to be effective. Even more importantly, individual bacteria leave the biofilm to colo- Report: Ludger Weß Prosthetic joint infections (PJI) are the most frequent complication in orthopaedic implant patients and may occur any time: weeks, months, or even years after an implantation. The disease is debilitating and can develop into a life-threatening condi- tion if not treated properly. Treatment requires the exact diagnosis of the pathogens involved and the antibiotic resistances they harbour. Based on this information, doctors can select an antibiotic and chose from a vari- ety of treatment procedures, usually a combination of systemic treatment, local delivery by e.g. an antibiotic- releasing bone cement, and surgical procedures. Nevertheless, the failure rate is between 10 and 20 percent. Diagnosis is difficult and can take up to 14 days. One reason is the for- mation of biofilms on the implant’s surface. These biofilms are difficult to remove and cannot be dissolved eas- ily. Moreover, bacteria in biofilms live in a dormant state and therefore are often not detectable with conventional microbiology culture techniques. To improve management of these infections, German molecular diag- nostics company Curetis AG has developed a highly multiplexed, PCR- based lab-in-a-cartridge to enable a fast, and automated, reliable diagnosis of pathogens plus resistance genes. The disposable Unyvero i60 cartridge is covering up to 114 analytes, includ- ing pathogens that are hard to grow in culture, such as anaerobes, and many resistance markers. It needs only a few minutes of operating time and provides results in about five hours. ‘The i60 cartridge adds to our Unyvero Solution, consisting of a sample lysator, analyser, cockpit and cartridges for various indications,’ explains Dr Oliver Schacht, CEO of Curetis AG. ‘Our Unyvero L4 Lysator is powerful enough to process bio- films and the i60 cartridge’s PCR- based technology can handle and analyse small amounts of bacteria and fungi present in the sample, regard- less of whether they are dormant or dividing. We just need the DNA.’ The cartridge also covers other indi- cations, e.g. diabetic foot, surgical site, deep skin and tissue infections as well as cardiac and catheter-related infec- tions. The i60 cartridge was launched in May 2014 after thorough testing in a CE performance evaluation study comprising about 800 native analytical and clinical samples such as swabs, synovial and sonication fluids, tissue and catheter tips. ‘Among others, our cartridge detect- ed several key pathogens with sensi- tivities in the range between 75 to 100 percent at an overall panel sensitivity of 67 percent and panel specificity of 97.8 percent for the 81 analytes that have been successfully validated so far,’ Schacht added. ‘We also identified about 150 clinically important pathogens not found by standard microbiology cul- ture. In particular, in every second sonication fluid and every third syno- vial fluid sample, i60 detected patho- gens missed by microbiology culture.’ The cartridge is now in clinical evaluations in more than 20 hospi- tals across Europe and is also being evaluated in the investigator-initiated European Prosthetic Joint Infection Cohort Study (EPJIC). The EPJIC start- ed in autumn 2014 and will enrol up to 5,000 PJI patients from up to 100 study centres across Europe. As part of the study, 500 patient samples will be measured by the Unyvero i60 ITI multiplex PCR cartridge system to identify pathogens involved in pros- thetic joint infection. ‘Adding rapid molecular testing to today’s standard of care bears great improvement potential for patients, as well as hospitals and their health economics,’ said Dr Andrej nise the interface of the prosthesis and the bone, thus causing a fistula or osteomyelitis around the implant. At that point, Trampuz underlines, full revision surgery becomes nec- essary. Low-grade infection – How to deal with culture-negative infec- tions: Diagnosing a periprosthetic infection is complicated because it can develop a multitude of symp- toms. The diagnosis of a chronic or so-called low-grade infection is particularly difficult because they are often detected months, or even years, after the surgery. Slow-growing bacteria, such as Staphylococcus epidermidis or Propionibacterium acnes, which tend to fall through the microbiol- ogy grid, frequently cause them. Both professors recommended a joint punction with microbiological analysis of the synovial fluid and white blood cell count (concen- tration in periprosthetic infections >2000/ μl leukocytes or >65 % granulocytes) to confirm the infec- tion. ‘When microbiology and cytol- ogy tests are performed at the same time, the results have a sensitivity of 98 percent and a specificity of 99 percent; thus even ‘low-low-low- grade’ infections can be diagnosed,’ Trampuz points out. However, there is one drawback: the cell count only provides diagnostically rele- vant information two months after the surgery. Antibiotic therapy – Trampuz underlines that detection of the pathogen is crucial. Particularly when a low-grade infection is sus- pected, to be able to detect the bac- terium the patient must be off anti- biotics for 14 days before sampling. As soon as the culprit has been identified a pathogen-specific anti- biotic therapy can be initiated. For two-stage exchanges, both experts strongly recommended an initial local antibiotic therapy, e.g. with a revision cement loaded with antibiot- ics or collagen sponges, followed by systemic antibiotic therapy. ‘Usually we do everything possible in terms of locally applied antibiotics, but then we go for a systemic anti- biotic therapy,’ Trampuz explains. In the case study he presented at the symposium, the patient with MRSA underwent temporary arthro- desis using revision cement loaded with gentamicin and vancomycin. Following the prosthesis replace- ment, 14 days later, and a resistance test, she received levofloxacin and rifampicin orally. However, without extensive debridement, neither the best local nor the best systemic antibiotic ther- apy will be effective. Surgeons and infectious disease specialists have to cooperate to ensure the success of any periprosthetic infection therapy. Individualised therapy – Success shows the way ahead. ‘There isn’t one single therapy concept that you can apply across the board, Ascherl said when summarising the tuto- rial. ‘Rather, you have to develop your own concept that has proven to be reliable and successful.’ This is where the symposium organ- iser Heraeus Medical provides sup- port. The company, together with Swiss orthopaedics (SO) and the Swiss Society for Infectious Diseases (SGInf), has published the compen- dium ‘Infections of the musculoskel- etal system’. Additionally, the educational app for iPad ‘Essentials in Diagnostics of Periprosthetic Joint Infection (PJI)’ from Heraeus Medical provides practical orientation based on case studies. * The educational app can be downloaded free of charge from the App Store. The book ‘Infections of the musculoskeletal system’ can be ordered free of charge in German (2013) or English (2014) at www.heraeus-medical.com Prof. Andrej Trampuz, Section Infectious Diseases and Septic Surgery and Centre for Musculoskeletal Surgery at Berlin’s Charité Medical University Prof. Rudolf Ascherl, Clinic for Special Surgery and Arthroplasty at the Hospital Medical Centre Stiftland Tirschenreuth The biofilm is an efficient strategy for microorganisms to survive and proliferate even in adverse circumstances. Formation and maturation: After adhesion the microorganisms proliferate on the surface – for example of an implant – and form a multi-layered 3-D structure that develops into a stable cell matrix. Due to their slow growth, bacteria in the biofilm are up to 1,000 times more resistant to antibiotics than unattached bacteria. Over time individual microorganisms leave the biofilm and transform into planktonic bacteria, which are metabolically active again and proliferate quickly. The Unyvero i60 ITI multiplex PCR cartridge system is able to identify pathogens involved in prosthetic joint infection. t +44 (0)1792797910 e info@dtrmedical.com w www.dtrmedical.com

EH 6/2014

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