SP15-2 The elimination of Group C meningococcal disease in the UK: the continuing story

SP15-2 The elimination of Group C meningococcal disease in the UK: the continuing story

Keynote sessions and Symposia / International Journal of Antimicrobial Agents 42S2 (2013) S1–S40 to invasive disease and rheumatic heart disease and ...

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Keynote sessions and Symposia / International Journal of Antimicrobial Agents 42S2 (2013) S1–S40

to invasive disease and rheumatic heart disease and mainly amongst the young and elderly populations. Population-based studies have described the epidemiology and clinical features of GAS diseases ranging from classic sore throat to severe life-threatening infections, such as septicaemia, streptococcal toxic shock syndrome (STSS) and necrotising fasciitis. GAS epidemiology varies with time and is dependent upon geographic location and socio-economic conditions. Timely monitoring of incidence, mortality and microbiological characteristics is essential to identify changes in disease patterns and emergence of hypervirulent strains, providing opportunities for alerts to be cascaded to frontline medical staff to facilitate early diagnosis, prompt initiation of life-saving therapy and inform the development of guidelines for control and management. The organism possesses numerous cell surface proteins that play a key role in host–bacteria relationships such as virulence and or adherence and form the basis of the GAS typing scheme. These proteins also represent choice candidates for vaccine developments. M-protein is a surface protein encoded by the emm gene which acts as a major virulence factor. Emm -typing is the molecular gold standard and there are currently more than 200 emm types described worldwide. More recently the application of novel comparative genomics has contributed towards our knowledge of the mechanisms underlying GAS pathogenesis. The information gained from current whole genome sequencing studies could translate into improved diagnostics; identification of novel molecular markers and potential predictors for the iGAS disease process and new targets for therapeutic drugs and vaccines. SP14-2 Clinical implications and microbiological characteristics of bacteremia caused by Streptococcus bovis group L. Teng1 *, P. Hsueh2,3 , W. Sheng3 , Y. Chuang3 . 1 Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taiwan , 2 Department of Laboratory Medicine, National Taiwan University Hospital, Taiwan, 3 Department od Internal Medicine, National Taiwan University Hospital, Taiwan E-mail address : [email protected] The Streptococcus bovis group is a large bacterial complex that includes various species and subspecies. Based on biochemical characteristics, S. bovis is divided into biotypes I, II/1, and II/2. The association of S. bovis biotypes with types of clinical infection and underlying malignancies has been reported by many studies. The recent taxonomy provides new tools to better understand the clinical significance and its etiological role. We have previously found that the majority of isolates causing primary bacteremia, hepatobiliary infections, and primary bacterial peritonitis were biotype II, while most isolates associated with infective endocarditis were biotype I. By using new taxonomy based on 16S rRNA gene sequencing and PCR-RFLP of groESL genes, we recently found that S. gallolyticus ssp. pasteurianus is more likely associated with malignancies of digestive tract. Antimicrobial susceptibility revealed penicillin retains good activity, while reduced activities were found in clindamycin and macrolides. Since we have previously found that many erythromycinresistant S. gallolyticus ssp. pasteurianus strains were inducible and harbored erm(T) gene which is flanked by IS1216V, further monitoring of resistance genes is also needed. SP14-3 Streptococcus pneumoniae : focus on antimcirobial resistance R.S. Kozlov1 *, L.V. Kozlova2 . 1 Institute of Antimicrobial Chemotherapy, Smolensk State Medical Academy, Smolensk, Russian Federation , 2 OGBUZ ‘Childrens Clinical Hospital’, Smolensk, Russian Federation E-mail address : [email protected] This presentation provides an update on the current state of antimicrobial resistance of community-acquired pathogens of respiratory tract infections in Russia, compared with those in other European countries with a particular focus on invasive isolates. Results are based on the results of multicentre studies organized under the auspices of the Institute of Antimicrobial Chemotherapy (IAC) of the Smolensk State Medical Academy (SSMA) and the

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Scientific Center for Monitoring of Antibiotic Resistance (CMAR). For all studies, CLSI/NCCLS methodology was used. A total of 2419 Streptococcus pneumoniae isolates from 23 cities of Central, NorthWestern, Southern, Privolgsk, Ural, Siberian and Far-Eastern regions of Russia were studied from 1999 to 2009. Beta-lactams retained high in vitro activity against S. pneumoniae : non-susceptibility to penicillin, amoxicillin, amoxicillin/clavulanate and ceftriaxone/cefotaxime was 9.7%, 0.1%, 0% and 1.8% between 1999 and 2003, and 11.2%, 0.4%, 0.4% and 1.0% between 2006 and 2009, respectively. Resistance to macrolides varied from 2.0% to 8.2% between 1999 and 2003, and from 6.3% to 7.3% between 2007 and 2009. The proportion of clindamycin-resistant isolates in the above-mentioned periods was 2.9% and 4.3% respectively. Susceptibility to chloramphenicol varied from 92.3% to 92.9%. Non-susceptibility to tetracycline was high between 1999 and 2009 (27.3 to 24.6%). Resistance to co-trimoxazole increased from 31.7% in 1999–2003 to 39.0% between 2007 and 2009 (p < 0.05). Vancomycin and respiratory fluoroquinolones retained high activity against S. pneumoniae . The proportion of multi-resistant S. pneumoniae was 11.8% between 1999 and 2003 and 14.5% between 2007 and 2009. A study of nasopharyngeal pneumococci in 4135 children younger than 7 years, from 91 organized communities, in 19 cities of European and Asian Russia, showed higher resistance in such strains compared with clinical isolates, with orphanages being ‘hot spots’ of resistance. These data suggest that orphanages could be reservoirs for the development and further spread of resistant isolates. This hypothesis should be confirmed in further studies potentially involving longterm care facilities. At the same time, substantial differences exist between the different countries and even within countries, thus dictating the need for regional surveillance studies. Striking differences in prevalence of resistance in pneumococci are very obvious in Europe. Certain countries, like Greece, Spain, Hungary, Slovakia and France reporting extremely high penicillin-non-susceptibility and erythromycin-resistance (60%/52%, 36%/34%, 60%/43%, 52%/33% and 46.7%/56%), are traditionally considered to be ‘hot spots’ of resistance. At the same time, others, e.g. UK, the Netherlands, Germany, Russia, reported low incidences (5.0%/10.4%, 2%/8%, 0%/13.7%, 6%/6%). Symposium 15. New developments in the global fight against meningococcal disease SP15-2 The elimination of Group C meningococcal disease in the UK: the continuing story D.M. Salisbury *. Director of Immunisation, Department of Health, London, UK E-mail address : [email protected] Anticipating a rise in Group C meningococcal disease in the UK, the Department of Health initiated a public private partnership with three vaccine manufacturers to develop a conjugate meningococcal group C vaccine. The time from start of the collaboration to launch of a national campaign, including clinical trials and licensing, was less than five years. Starting in November 1999, vaccine was offered to all children from 2 months of age to 18 years over a one-year period. High coverage was achieved. The vaccine was then offered to those up to 25 years. The impact was the achievement of the elimination of group C meningococcal disease. Despite no recurrence of disease, successive studies have demonstrated the rapid decline of antibodies in vaccinated children with the most rapid declines in those vaccinated at the youngest ages. A combined Hib/MenC conjugate vaccine was then developed specifically for the UK, and given at 13 months of age. The original schedule of three infant doses was progressively reduced to two doses and is about to be reduced again to a single dose. Evidence that is more recent confirms that the children who were the first to be vaccinated at the start of the programme now have very low levels of antibodies and they are now adolescents/teenagers. However, there continue to be no cases of group C meningococcal disease. In order to prevent any future cases, the infant dose that is presently being removed from the schedule (as above) will be reinstated as an adolescents’ dose to be given at 13 or 14 years.

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Keynote sessions and Symposia / International Journal of Antimicrobial Agents 42S2 (2013) S1–S40

The UK experience has shown that rapid development of new vaccines can be achieved through public private partnership, that the implementation of group C vaccines on a broad campaign basis not only protected vaccines but also interrupted transmission amongst those not vaccinated, that once transmission has been interrupted, the schedule can be reduced but that re-emergence of meningococcal disease in older individuals needs to be anticipated and prevented. Friday, 7th June 2013

Symposium 16. Current topics in antimicrobial stewardship SP16-1 The role of diagnostics in antibiotic stewardship H. Wertheim *. Oxford University Clinical Research Unit, National Hospital of Tropical Diseases, Oxford, UK E-mail address : [email protected] With microbiological laboratories we can know what bacteria are causing infections and the antibiotic susceptibilities. Traditional microbiology takes time: results often take 2–3 days before they can be reported. Recent developments have reduced reporting time: (1) PCR based tests, (2) point-of-care (POC) tests with either nucleic acid or antigen as target, and (3) MALDI-TOF mass spectrometry. These tests are supplementary to traditional culture-based methods. The disadvantage of PCR-based and POC tests is that they only detect the pathogens for which the test is designed. PCR-based tests developed for specimens to detect resistance have mainly focused on MRSA and VRE, for screening patients as part of infection control efforts. Furthermore, these tests still require laboratories to first culture the bacterium after which specific resistance targets (e.g. extended spectrum beta-lactamase) can be sought. As the mechanisms for antibiotic resistance are very diverse and evolving continuously, particularly for Gram-negative rods it is currently not possible to capture this in a POC or PCR-based test, and we continue to rely on phenotypic culture-based testing. Phenotypic testing also allows that new resistance profiles can be detected. As full genome sequencing is becoming cheaper and faster, this may change in the foreseeable future. There are tests available that make use of next generation sequencing techniques and test for multiple organisms and resistance genes. It is expected that affordable and rapid full genome sequencing can provide useful information regarding resistance and transmission in the near future. In the area of traditional microbiology and phenotypic testing, important advancements are being made. Microbiology laboratories in developed nations are becoming more automated with inoculation and incubation systems, and visualization techniques that can detect early growth. Combined with MALDI-TOF, these systems will result in rapid and reliable detection and identification of bacterial infections. MALDI-TOF techniques are not yet suitable to provide susceptibility results for routine tests, but developments in this area are ongoing. Studies have shown that rapid testing and decreasing time to reporting does reduce antibiotic use and optimizes antibiotic treatment earlier. However, these advances have not yet been shown to convincingly reduce mortality, but can reduce hospital stay and costs. Diagnostics that help to reduce antibiotic use or narrow the spectrum should be promoted. Even if these may not have a direct benefit on clinical outcome, reducing antibiotic pressure can aid in slowing down resistance spread. Good long-term studies are needed to assess whether rapid testing, besides reduce antibiotic use, actually has an impact on antibiotic resistance levels. Reducing antibiotic resistance and its transmission should become a primary endpoint in studies, besides clinical endpoints like hospital stay or mortality.

SP16-2 Problems with standard treatment guidelines in low-resource settings E.R. Vlieghe *. Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium E-mail address : [email protected] Antibiotic stewardship refers to a set of activities and policies to improve the rational use of antibiotics. Essential (minimum) elements of an antibiotic policy include a stable and restrictive list of antibiotics in use, standard treatment guidelines, audit and feedback of prescriptions, surveillance of bacterial resistance and antibiotic use and education at all levels. However essential in steering the use of antibiotics, standard treatment guidelines (STG) are not always fulfilling their role. Guidelines may be international, regional, national or local of nature. International guidelines are often written by authors from resourcerich settings, where clinical realities are very different from those in (tropical) low-resource settings. National guidelines are often outdated and/or not disseminated to the genuine prescribers, who in turn may use a combination of outdated textbooks, international, but locally irrelevant guidelines or just the habits of their teachers. In addition, the necessary underlying local evidence is largely lacking due to limited diagnostic laboratory capacity, in particular bacterial cultures. There is need for concentrated efforts at the national levels to invest in the revision of their STG into clear, simple, updated, locally relevant and accessible documents. A particular, also ethical challenge will be the resistance thresholds warranting the switch to a broader spectrum antibiotic. SP16-3 Successful antimicrobial stewardship in low to middle income countries – Can it happen? S. Mehtar *. Unit for Infection Prevention and Control, Div Comm Health, FMHS, Stellenbosch Uni, Cape Town, Western Cape, South Africa E-mail address : [email protected] Antimicrobial stewardship is not a new concept – in Europe it has been around since the 1980’s, driven by the cost of treating infection, increasing antimicrobial resistance and drying up of new antimicrobial agents in the pipeline. In High Income (HI) countries a concerted effort by the clinicians, microbiologists, infection control practitioners and pharmacists helped to bring down the misuse of antimicrobials – each one of these professionals contributing equally to the process. The infrastructure in most healthcare facilities in HI countries supports good infection prevention and control (IPC) practices such as heat disinfection of bedpans and urinals, standardised decontamination of medical devices, provision for hand hygiene and providing a dry and clean environment. When and where multiply drug resistant (MDR) bacteria emerged, it was usually due to a breakdown in IPC practices and could be rectified. Microbiological laboratory support is vital to ensure good antimicrobial stewardship (AMS). In low to middle income (LMI) countries particularly in Africa, several factors pose a challenge to establish AMS in the conventional manner as seen in HI countries. The challenges are a lack of skilled specialist staff, laboratory support, pharmacy support, and trained IPC practitioners. The clinical area infrastructure is inadequate and often there is a lack of coherent education and training. ICAN proposes the development of simple methods to start AMS. The application of clinical skills is paramount – differentiating between colonisation and infection is essential. While some surveillance of local pathogens is necessary, this may not always be possible so a point prevalence survey might serve a similar purpose. To improve the IPC practices will require training which is possible via short courses, constant ward rounds and discussion. The infrastructure may not exist but emphasis on hand hygiene, adequate decontamination of bedpans and urinals and early discharge from healthcare facilities could help. The control of antimicrobials in community and general practice is less likely to occur but can be dealt with via other conduits through the national departments. Finally, organisations such as ICAN