JAC Advance Access originally published online on June 26, 2007
Journal of Antimicrobial Chemotherapy 2007 60(3):464-469; doi:10.1093/jac/dkm216
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Meeting report |
Meeting report: Fourth Forum on Respiratory Tract Infections, Sitges, Spain, 8–11 February 2007
1 Replidyne Inc., Milford, CT, USA 2 Coireseileach, Clachan Seil, Argyll PA34 4QZ, Scotland, UK
* Corresponding author. Tel: +44-1852-300312 or +34-966-471513; E-mail: peterball1{at}aol.com
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Abstract |
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Over 420 delegates participated in this, the fourth of a biennial series of scientific meetings, drawing from 30 or more nations and encompassing the specialties of infectious diseases, clinical microbiology, pulmonary and general medicine and Industry inter alia. The 2007 Forum was chaired by Professors Antoni Torres Marti, Giuliana Gialdroni Grassi and Dr Peter Ball and received academic endorsement from the British Society for Antimicrobial Chemotherapy (BSAC), Italian Society for Chemotherapy, Spanish Pulmonology Society, Paul Ehrlich Society and the Société de Pneumologie de Langue Français. The Scientific Programme was scientifically and financially supported by the BSAC and a consortium of pharmaceutical companies. Discussion focused on key contemporary issues in respiratory tract infection (RTI), including the impact of antibiotic resistance on clinical outcomes and the continuing need for antibiotic conservation via evolving guidelines, the challenges of avian influenza, nosocomial RTIs and the emergence of new pathogens, e.g. community-acquired methicillin-resistant Staphylococcus aureus, novel antimicrobial agents, disease definitions (e.g. healthcare-associated pneumonia) and therapeutic assessment criteria, such as patient-reported outcome measures, in improving RTI management. The entire meeting was granted CME recognition (18 sessions) by the European Accreditation Council for continuing medical education.
Keywords: antibiotic resistance/conservation , new antibiotics , disease definitions and management , outcome assessments , avian influenza
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Introduction |
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TopAbstractIntroductionIntroductory symposia--impact of...The BSAC Lecture--Avian...Symposia and plenary sessionsTransparency declarationsDate of next meeting |
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Current status and management of respiratory tract infections (RTIs) require regular review due to the evolution of causative pathogens, recognition of changes in patient populations and development of new assessment criteria for definition of disease, its severity and the (comparative) efficacy of various therapeutic modalities. The Forum on Respiratory Tract Infection provides an informal and interactive background to a curriculum of Plenary Lectures and Symposium presentations by international authorities in the field. This report provides an overview of the data presented at and conclusions from the 2007 meeting.
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Introductory symposia—impact of resistance and challenges in serious infections |
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TopAbstractIntroductionIntroductory symposia--impact of...The BSAC Lecture--Avian...Symposia and plenary sessionsTransparency declarationsDate of next meeting |
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Donald Low (Canada) in the Keynote Lecture reviewed the growing evidence supporting the clinical significance of antibiotic resistance and the need for appropriate use to slow or inhibit this trend. Both hospital- and community-derived data implicate resistance not only in clinical treatment failure in certain patient groups but also in associated increased costs. The best means to counter such effects was to use the ‘best in class’ approach to optimized prescribing of antibiotics, based on the selection of the pharmacodynamically most active agent. Attention was drawn to fallibility in current interpretations of levels of bacterial inhibition by drugs in vitro, which inadequately reflect drug concentrations in vivo and result in substantial proportions of infection being misconstrued as resistant to standard antibiotic therapy. More sensitive measures of failure and use of pharmacodynamic predictors may better assess the true effects of bacterial resistance, and ongoing discussions of the requirement for revision of some current breakpoints were a reflection of this. Alasdair MacGowan (UK) described the pharmacodynamic principles underlying such choices in both RTI and anaerobic infections, and the benefits of optimal bacterial eradication, associated with the best in class approach, were reviewed by Keith Klugman (RSA/USA), who also referred to recent evidence from long-term nursing facilities associating increased fluoroquinolone resistance to the use of less potent, single target fluoroquinolones, such as levofloxacin. He further voiced concerns over collateral damage occurring during macrolide exposure, specifically the selection of linezolid resistance. Importantly, it is now recognized that both ‘high level’ [erm(B)] and ‘low level’ [mef(A)] pneumococcal macrolide resistance is associated with treatment failure once MICs are 1 mg/L or greater.
Mark Wilcox (UK) reviewed approaches to resistance control, including cyclical policies, and also the environmental, infection control and antibiotic usage issues relating to outbreaks of Clostridium difficile-associated diarrhoea (CDAD), including the emerging more virulent and resistant strain. Prevention of transmission remains key to control, but the recent Cochrane analysis (P. Davey et al. CD003543, 2005) had concluded that restriction of cephalosporin and clindamycin use also leads to reduction in CDAD. However, the most significant factor impacting on outbreak modification (environmental hygiene) had been highlighted in Quebec, where a $25 million lavatory refurbishment programme appeared money well spent! In terms of a single factor, infection control may outweigh antibiotic restriction in outbreak management.
Santiago Ewig (Germany) described the changing patient environment, noting differences in the ageing population in respect of activity indices and functional impairment, frequent co-morbidity and potential interactions of antibiotic therapy with concomitant treatment. Drugs with rapid bactericidal activity but also designed to function in this environment were clearly required.
The pharmacodynamically predictable value, including high oral bioavailability and pulmonary penetration, of the respiratory fluoroquinolones in managing community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis and, incidentally, surgical infections, against this background was discussed in detail, highlighting their clinical efficacy and relative safety in terms of a more rapid patient recovery, as well as maintained exacerbation remission in chronic obstructive pulmonary disease (COPD). Aspects highlighted by Michael Niederman (USA) and Antonio Anzueto (USA) included outpatient therapy, convenience of intravenous–oral switch therapy and superiority in clinical trials. Ellie Goldstein (USA) welcomed the recent approval of moxifloxacin in monotherapy of complicated intra-abdominal infections by the American Food and Drugs Administration (FDA), an area of significant unmet medical need since the withdrawal of trovafloxacin some years previously. The attraction of single daily monotherapy and intravenous–oral switch is clear and extension into allied areas, e.g. diverticulitis, pelvic inflammatory disease and post-surgical pelvic infection, was anticipated.
In sessions on the implications of extended fluoroquinolone use in RTI and the challenges of the modern hospital environment, Javier Garau (Spain) and Ron Grossman (Canada) highlighted the appropriate use of these compounds. The widespread indications and medical acceptance of the value of fluoroquinolones should be tempered with recognition that overuse/abuse, notably of the single target agents and especially in the untutored junior staff/emergency room context, was encouraging resistance in pneumococci, selecting for fluoroquinolone-resistant methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum ß-lactamase (ESBL)-producing pathogens and being incriminated in the emergence of highly pathogenic strains of C. difficile. Recent prior use of fluoroquinolones should be considered in terms of contemporary therapy of a possibly quinolone-resistant infection. The value of modern fluoroquinolones, such as moxifloxacin, was unchallenged but the need for conservation and appropriate use was imperative.
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The BSAC Lecture—Avian influenza 2007: residual threat or impending reality |
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TopAbstractIntroductionIntroductory symposia--impact of...The BSAC Lecture--Avian...Symposia and plenary sessionsTransparency declarationsDate of next meeting |
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Karl Nicholson (UK), in the British Society for Antimicrobial Chemotherapy Lecture, discussed the history and future of influenza, particularly the issues surrounding avian influenza and the likelihood of an impending pandemic. The H5 strain of influenza virus has been isolated in more than 50 countries: 38 reporting poultry outbreaks, the financial impact of which has exceeded US$10 billion. Although human impact, since the recognition of transmission to humans (1997), is so far small: 270 cases with 164 deaths, the WHO in December 2006 noted that: "we are closer to a pandemic now than at any time since 1968". Pandemics occur on average at 25 year intervals, but the range of 11–52 years complicates prediction of the next. Influenza has a short incubation and spreads rapidly leading to acute respiratory and systemic illness: an outbreak may become established even prior to recognition of index cases. One of the alarming features of H5 influenza in humans is an apparent increased mortality among young adults, probably due to an induced cytokine storm. This pattern of mortality was observed during the 1918–19 pandemic.
The A/goose/Guandong precursor of recent H5 outbreaks was first isolated in China. In the past, China has usually been the epicentre of pandemics, possibly because of the high population densities of humans, poultry and pigs in this region. The large percentage of the population in southeast Asia who live in rural communities and have close contact with poultry, together with factors including wet markets, agricultural methods and animal movements, create ideal conditions for viral proliferation, dissemination and acquisition. Increased Western tourist influx (Vietnam has seen a 14-fold increase in visitors arriving by air in the last 15 years) potentially enables rapid migration of the virus to new susceptible populations. Additionally, the acquisition and transmission of the virus by migratory birds will accelerate spread.
Anti-influenzal therapy includes the neuraminidase inhibitors (oseltamivir and zanamivir). Randomized controlled trials, cohort studies and modelling studies show that the neuraminidase inhibitors, if given promptly, can reduce the length of illness, viral secretion and complication rates. Unfortunately, resistance of H1N1 and H3N2 subtypes of influenza A to oseltamivir (Tamiflu), which may appear within days of commencing therapy, has developed among approximately one in six Japanese children who received treatment. Resistance of H5 virus has also been reported in patients treated in Vietnam and Egypt, and resistance of H5 strains to amantadine has been observed among some virus clades. Used prophylactically, these agents may lower peak clinical attack rates. Previous pandemics have shown that secondary bacterial complications (mainly pneumonia) have a high morbidity and mortality. Appropriate empirical therapy, active against Streptococcus pneumoniae, S. aureus and Haemophilus influenzae, should be prescribed promptly. In the USA, community-acquired MRSA (CA-MRSA) may also require coverage.
Although human impact is currently slight, Nicholson noted that ‘recurrent outbreaks of H5 virus infection in domestic poultry, together with human cases ... ... suggest that we are currently watching an H5 pandemic in evolution’. The human implications will depend on transmissibility, virulence of the adapted or recombinant strain, effective epidemiological control measures including vaccines and the efficacy of antiviral chemotherapy. Avian control measures have included poultry slaughter, which has not prevented re-emergence of H5 influenza in domestic flocks, poultry vaccination and closure of bird markets. Specific vaccines for humans will almost certainly be unavailable for the first wave of influenza infections and questions surround both the adequacy of supply and efficacy of antiviral agents for the second.
It appeared, from a contemporary perspective (February 2007), that a pandemic was unlikely in the next few months. Fortunately, avian viruses preferentially recognize different host cell receptors (NeuAc 2,3 galactose linkage) to those in man (2,6 linkage) and mutation would be required to convert to human affinity. Acquisition of human characteristics alone (internal protein genes) is probably insufficient for the development of pandemic potential and further adaptation will be necessary for H5 viruses to become highly transmissible. However, their potentially extraordinary virulence makes pandemic preparedness paramount.
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Symposia and plenary sessions |
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Healthcare-associated pneumonia
The recent recognition of a new variant presentation of pneumonia has defined ‘healthcare-associated pneumonia’ (HCAP), which has been the subject of newly proposed guidelines from the American Thoracic Society and the Infectious Diseases Society of America. These reflect increasing ‘out-of-hospital’ care and the role of the different HCAP pathogens in patients who tend to be older, have more risk factors for infection and poor outcome and harbour more resistant pathogens than typical CAP patients.
The definitions and approaches to management of HCAP were discussed by Michael Niederman (USA), Carlos Luna (Argentina) and Jordi Carratala (Spain). Empirical antibiotic therapy should clearly reflect the HCAP scenario and merits a distinct approach, but many such patients are still treated inappropriately, with risk factors, such as prior antibiotic exposure and length of hospitalization, being ignored. Two categories of HCAP are differentiated by the presence of two of three risk factors for multidrug-resistant pathogens: (i) severe pneumonia requiring mechanical ventilation; (ii) prior antibiotics—for more than 3 days in the prior 6 months; and (iii) poor functional status: Activities of Daily Living (ADL) score > 12.5. Proposed guidelines, which remain unvalidated, suggest limited spectrum therapy for patients, in or out of the hospital, who do not have two of three risk factors. It might comprise a respiratory fluoroquinolone alone (e.g. moxifloxacin or high-dose levofloxacin) or a ß-lactam active against resistant S. pneumoniae, plus an additional macrolide—if legionellosis is suspected. Broad-spectrum therapy is recommended for patients having two of three risk factors, who may be at risk for specific resistant pathogens, such as Pseudomonas aeruginosa. Therapy should include an antipseudomonal ß-lactam with a similarly active fluoroquinolone, plus either vancomycin or linezolid to cover MRSA. These recommendations remain under review.
Epidemiological consequences of pneumococcal vaccination
Keith Klugman reviewed the epidemiological consequences of pneumococcal conjugate vaccination, illustrating the associated reductions in invasive pneumococcal disease, not only within the target paediatric vaccination population, but also in the elderly (>65 years). However, not unexpectedly, the vaccine-engendered pneumococcal serotype void is being filled by the multidrug-resistant 19A clone, which bears additional resistance mechanisms to confound antibiotic choices. He also highlighted the frequently fatal role of pneumococcal superinfection in the 1918 influenza pandemic.
Special session: the future regulatory environment for antibiotic development in RTI
The development of new antibiotics for RTIs is still considered a pressing need, yet uncertainties of progress towards registration of some recent candidates during evaluation by the US FDA, European Agency for the Evaluation of Medicinal Products and other authorities have posed difficulties for the pharmaceutical industry, challenging the commitment to and viability of research and development in this area. Several new compounds have been rejected, restricted in indication or have had indications withdrawn. In an industry with clamouring shareholders, it is of note that a number of major pharmaceutical companies have reduced or discontinued research and development in the anti-infective sector. The evidence for such difficulties, the changing regulatory environment and the potential consequences for the management of human infective disease in an era of increasing resistance to standard therapies were discussed by Glenn Tillotson and Roger Echols (USA). The effect of these recent decisions could be significant, if investors choose not to support antibiotic development programmes in favour of alternative investments in easier, more-predictably profitable therapeutic classes that promise larger, initially more rapid and longer-term capital gains.
Patient-reported outcomes in acute exacerbations of COPD
One new constraint under discussion by the FDA was a requirement to develop, clinically assess and, thereby, to validate ‘patient-reported outcome’ (PRO) measures as outcome parameters of co-primary importance with conventional clinical assessment at test of cure. PRO instruments, based on functionality, psychological and classical clinical parameters, but orientated to the patients' attitude to outcomes, exist for many other therapeutic areas, including rheumatic diseases, and have been applied to RTIs, for example, in CAP. Sanjay Sethi (USA) described the rationale behind their extension into other RTIs and the development of instruments for assessment of acute exacerbations of COPD as a result of an alliance between the FDA, a Contract Research Organization and academia. Parallel developments had also been initiated by a number of pharmaceutical companies. He outlined the various components of a PRO, its likely impact on drug development and the ongoing validation programme, following successful completion of which it will be applied to drug evaluation. However, such instruments will not be available until at the earliest late 2007 and this, in the meantime, is acting as a brake on antibiotic development.
Acute exacerbations of COPD and related conditions
Acute exacerbations of COPD (AECOPD) were discussed inter alia by Toni Anzueto, highlighting the need to identify and treat bacterial exacerbations appropriately and urgently. Most guidelines recognize the benefit of antibacterial therapy. Procalcitonin measurement may assist identification of bacterial exacerbations in the future but, in the meantime, sputum colour remains a useful indicant, i.e. green–yellow being strongly indicative of bacterial infection and reflecting leucocyte esterase release in response to bacterial infection. Broad-spectrum agents were recommended for the elderly with co-morbidity and forced expiratory volume (FEV) < 50% of predicted. As the COPD population is being more aggressively managed with a range of new airway-active drugs, the benefit of preventing bacterial infections is becoming apparent. Niels Høiby (Denmark) described parallels between infection-mediated inflammation, associated tissue damage and potential prevention of progressive damage by appropriate acute or chronic suppressive antibiotic therapy, in cystic fibrosis patients and those with chronic bronchitis.
Bronchiectasis is a relatively uncommon, difficult-to-treat condition, for which there are no agreed guidelines. Major issues surround diagnosis, infection control, antibiotic prophylaxis and mode of delivery of antibiotics. Robert Wilson (UK) discussed management of exacerbations in the light of colonization pathogens, noting the use of macrolides as quorum-sensing inhibitors in disrupting the colonizing flora and thus extending the period between acute episodes. However, antibiotic treatment plans, either as aggressive therapy or prophylaxis, must be tailored to the individual patient. The use of high-resolution computed tomography has now identified bronchiectasis in up to half of some bronchitic populations. Although mostly mild, its recognition demands attention to antibiotic therapy and mucus clearance.
Finally, new antibiotics suitable for the management of AECOPD were discussed by Antoni Torres (Spain), with reference to their possible inclusion in guidelines, and the significance of P. aeruginosa as a marker of more severe infection or potential for more severe exacerbation was illustrated by Eduardo Monso (Spain).
Issues in Gram-positive pneumonia
The dramatic increase in MRSA in the community in the USA and elsewhere, together with its association with severe CAP in young people, was described by Dilip Nathwani (UK). CA-MRSA possessing the Panton–Valentine leucocidin causes 85% of such cases, which are rapid-onset, severe, necrotizing infections and may potentially be associated with influenza. Recognition of the possible role of CA-MRSA, resistant to ß-lactams, macrolides and, occasionally, clindamycin, is now paramount in all with severe CAP. Potential alternative therapies include vancomycin, quinupristin/dalfopristin, tetracyclines and linezolid, but there is a clear need for a new agent active in lung infections due to CA-MRSA, among which are possibly tigecycline, telavancin, dalbavancin, doripenem, ceftibiprole or oritavancin.
Tobias Welte (Germany) commented that hospital-acquired MRSA is endemic in most European hospitals and may comprise > 20% of staphylococcal isolates. The percentage of MRSA in blood cultures is also increasing. Pulmonary infections pose particular problems due to the poor penetration of glycopeptides into tissues, although results may be improved by combination with rifampicin, fosfomycin or fusidic acid. Linezolid, a bacteriostatic oxazolidinone, has excellent penetration and efficacy, but potential haematological adverse drug reactions and neurotoxicity may follow prolonged (>28 days) usage, thus limiting its application. In some patients, it may be difficult to differentiate colonization from infection: low serological infection parameters and negative procalcitonin tests indicate infection to be unlikely.
Hartmut Lode (Germany) reviewed the current new drugs for severe ventilator-associated pneumonia (VAP), highlighting the superiority of linezolid over vancomycin in MRSA infection, but noted the inactivation of daptomycin, an otherwise potentially useful agent in lung disease, by surfactants. Promising anti-Gram-positive agents included ceftobiprole, dalbavancin and telavancin and doripenem—all of which were in Phase II/III studies. Tigecycline, currently available as an intravenous formulation, had proven equivalent to levofloxacin in CAP and results versus imipenem in hospital-associated pneumonia (HAP) were eagerly awaited. Antoni Torres (Spain) noted its broad-spectrum potency against Gram-positive bacteria and important extended spectrum against Gram-negative pathogens, including H. influenzae, Escherichia coli and Klebsiella pneumoniae.
Nosocomial and intensive care unit pneumonia
The session on nosocomial and intensive care unit (ICU) pneumonia concentrated on specific aspects of these diseases. Jean-Yves Fagon (France) related improvements in diagnosis to optimized outcomes and described algorithms, based on distal airway sampling and quantitative cultures, intended to reduce over-prescribing for non-bacterial disease. Carlos Agusti (Spain) discussed the pulmonary complications of stem cell transplants in haematology and the role of (i) early fibreoptic bronchoscopy in aetiologically appropriate prescribing, (ii) CT scanning for minimal lesion disease and invasive aspergillosis and (iii) non-invasive ventilation in early hypoxaemic respiratory failure. Hartmut Lode (Germany) emphasized the potentially fatal nature (15% to 20%) of aspiration pneumonia and lung abscess and improved results with agents having anti-anaerobic activity, including clindamycin and ampicillin/sulbactam. Recently available data indicating a role for moxifloxacin (68% cure rate) were presented.
A further new parenteral agent, ceftobiprole, with novel long-lasting inhibition of penicillin-binding protein PBP2a, has excellent broad-spectrum potency, including MRSA, vancomycin-resistant S. aureus, coagulase-negative staphylococci, enterococci and multiresistant pneumococci. According to Javier Garau (Spain), it may well find a significant role in nosocomial pneumonia (including VAP) when MRSA is suspected and in CAP. He had earlier discussed cefditoren pivoxil, a pro-drug, which has various attributes including resistance to many ß-lactamases, activity against penicillin- and cephalosporin-resistant pneumococci and good activity in clinical trials of CAP. Finally, de-escalation therapy was reviewed, in terms of improved adequacy and minimized resistance, by Jordi Rello (Spain). Patient-based approaches, based on prompt appropriate initial broad-spectrum therapy, followed by streamlining on receipt of bacteriology, can improve survival and minimize resistance.
Two plenary sessions addressed CAP, the first in terms of the role of glucocorticoids in severe disease in both CAP and HAP; the second in respect of guidelines. Antoni Torres (Spain) presented data to show improved resolution and lowered septic complication rates after steroid therapy of severe CAP ICU patients. Further studies are needed but encouraging results of systemic inflammatory modulation by steroid may also apply to HAP. However, potential risks include rebound phenomena after premature withdrawal of therapy and possible interference with phagocytic function. Future studies should also investigate possible adreno-cortical dysfunction in severe CAP. Mark Woodhead (UK) addressed issues in guidelines for CAP and highlighted the multiplicity and conflicting incongruities of the many publications from various countries, societies and organizations. Robust evidence for guideline recommendations is increasing, but is still required for many aspects, including chest X-ray diagnosis, the role of microbiology and severity grading systems, in addition to the continued paucity of evidence from double-blind randomized controlled trials. Route and duration of therapy remain important areas for investigation.
A specific symposium on CAP followed. The dominant pharmacodynamic indices (t > MIC, AUC/MIC and Cmax/MIC) of new drugs for CAP and the increasing body of evidence linking clinical and bacteriological outcomes to these parameters were discussed by Alasdair MacGowan (UK). Modelling, using Monte Carlo simulation techniques and population pharmacokinetic data, allowed prediction of likely outcomes, which required correlation with clinical trial data. New oral penems were of considerable interest in a number of respiratory infections, not least in CAP—commented Ethan Rubinstein (Canada). Faropenem had excellent activity against respiratory isolates (notably S. pneumoniae) was resistant to degradation by almost all ß-lactamases and had an oral bioavailability of 72% to 84%. Clinical efficacy in CAP was 86% to 91% and this agent clearly offers a potential further oral option for the management of RTI. The German CAPNETZ project was reviewed by Santiago Ewig and Tobias Welte (both Germany), who described the organization of the various sites and results from clinical projects, including the assessment of severity in stratifying management of CAP patients. Santiago Ewig reviewed various scoring systems applied to determining the likely outcomes of CAP patients, including CURB (a system incorporating Confusion, Urea, Respiratory rate, low Blood pressure) and CRB-65 (Confusion, Respiratory rate, low Blood pressure and age 65 years or greater) versus the standard Pneumonia Severity Index (PSI). CRB-65 was validated as an easy to use and reliable predictive severity index, in ambulatory and hospitalized patients, especially in association with procalcitonin measurement to detect patients at low risk of death. In those with a CRB-65 > 0, a cutoff of 0.22 ng differentiated the need to manage in or out of hospital. Tobias Welte gave more details on the CAPNETZ project in terms of how this large network of community- and hospital-based physicians managed thousands of CAP cases annually providing up-to-date information on likely pathogens, their resistance profiles and outcomes of therapy (W. Welte et al. Internist 2005; 260: 93–101). The standardized approach to determining clinical response has been erratic in CAP. Rosario Menendez (Spain) reviewed the various pro-inflammatory bio-markers, which may be useful in assessing patients, including pro-adrenomedullin, which is potentially more sensitive than procalcitonin.
Risk factors for development of resistance in S. pneumoniae
Johan van Eldere (Belgium) considered the 10 year Belgian experience as a paradigm of changes elsewhere, identifying risk factors for and modulators of multiresistant pneumococci, including childhood infection, population density, conjugate vaccine, location and isolate source and previous antibiotic exposure (macrolides and cephalosporins). The expansion of multiresistant strains explained most of the overall 2-fold increase in resistance between 1994 and 2000, and both high population density and proximity to the border with an area of high resistance in France were independent predictors of multiple resistance. Total antimicrobial exposure of the population (and individually macrolide exposure) was an independent predictor with a 1 year delay in effect on resistance rates.
The threatened demise of antibiotics in RTI
Bacterial resistance in RTI pathogens has been a major spur for antibiotic development for decades. Donald Low (Canada) discussed various drivers of resistance, including volume usage, co-selection and pharmacodynamic adequacy—or otherwise, while commenting on the beneficial effects of appropriate (and reduced) prescribing and those of pneumococcal conjugate vaccine. Pneumococcal resistance appeared to have plateaued in some areas, albeit at dangerously high levels, but clonal spread was occurring, notably of the 19A strain not represented in current vaccines and exhibiting an amoxicillin MIC of 4 mg/L. The apparent peak may represent only a pause in resistance evolution. The Canadian Bacterial Surveillance Network has identified remarkable changes over two decades: overall antibiotic use, notably ß-lactam usage, has decreased markedly—with a concurrent decrease in ß-lactam resistance. However, tetracycline resistance increased despite decreased usage and both macrolide use and resistance significantly increased. Differential fluoroquinolone use has been reflected by a significant decline in pneumococcal resistance, perhaps driven by a reduction in use of less pharmacodynamically active drugs, such as ciprofloxacin and levofloxacin, and marked increase in use of the more active moxifloxacin.
The later thought-provoking series of presentations addressed initiatives attempting to achieve appropriate use of existing antibiotics. Richard Wise (UK) noted the slow-down in antibiotic discovery, the value of prevention in hospital cross-infection and the community, and various initiatives, partially successful in some countries, in reducing antibiotic usage. He further considered the risks of ill-considered overall restriction and of unexpected events, including treatment failure and perhaps increased mortality, following such initiatives. Quantification of such risks is lacking but must be addressed. Tony White (UK) discussed policies and strategies within the European Union, including calls (commonly unheard) for increased incentives and funding to aid pharmaceutical innovation, prescribing principles, advice and guidelines/policies, notably diagnostic and antibacterial research under the Framework Programme. The scope of such policies varied between member states. In Turkey, a nationwide antibiotic restriction programme was launched in 2003. Serhat Unal (Turkey) described the restrictions now in place and noted a fall in both usage of and resistance rates to carbapenems (prescribable only by infectious disease physicians). However, during the period, overall primary care usage of antibiotics increased.
In Malaysia, a Ministry National strategy for containment of resistance, supported by WHO, had had dramatic effects in identifying subsequent prescribing rates, but Victor Lim (Malaysia) found the significance of such changes difficult to assess, notably in terms of the lack of available information as to ‘acceptable’ prescribing rates for specific diseases and varying populations. Targeted surveillance of MRSA and ESBL-producing K. pneumoniae had resulted in moderate decreases in prevalence. Use of antibiotics in agriculture and the marketing activities of the pharmaceutical industry were more difficult to control, but the medical response to Infection and Antibiotic Control Committees had been good. Government, non-government organizations and mass-media education programmes had proved troublesome to coordinate.
In a comprehensive final presentation, Francesco Scaglione (President, Italian Chemotherapy Society) linked the role of new antibiotics to resistance control and emphasized judicious use. Restriction to appropriate indications remained the mainstay of strategies to limit the spread of bacterial resistance.
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Transparency declarations |
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TopAbstractIntroductionIntroductory symposia--impact of...The BSAC Lecture--Avian...Symposia and plenary sessionsTransparency declarationsDate of next meeting |
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G. S. T. is the Executive Director of Scientific Affairs for and an employee of Replidyne Inc., Louisville, CO, USA and has no other interests or conflicts to declare. P. B. is a retired physician, who is in receipt of honoraria in recognition of Chairmanship of and contributions to the organization of the Forum.
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Date of next meeting |
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TopAbstractIntroductionIntroductory symposia--impact of...The BSAC Lecture--Avian...Symposia and plenary sessionsTransparency declarationsDate of next meeting |
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The Organizers plan to host the Fifth Forum on Respiratory Tract Infection in Sitges, Spain, 5–8 February 2009 (details from www.aim-internationalgroup.com/2007/respinf).
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Acknowledgements |
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Generous financial sponsorship and scientific content support were received from (in alphabetical order): Astellas Pharma, Bayer AG, Daiichi-Sankyo Group, GlaxoSmithKline, Janssen-Cilag, Pfizer Inc., Replidyne and Wyeth Pharmaceuticals.
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