JAC增刊打包：英国抗感染治疗协会耐药监测计划1999/2000-2006/7

David

Journal of Antimicrobial Chemotherapy

Contents: Volume 62, Supplement 2, November 2008   
The British Society for Antimicrobial Chemotherapy Resistance Surveillance Project 1999/2000-2006/7
英国抗感染治疗协会耐药监测计划1999/2000-2006/7

Anthony R. White on behalf of the BSAC Working Parties on Resistance Surveillance
The British Society for Antimicrobial Chemotherapy Resistance Surveillance Project: a successful collaborative model

J. Antimicrob. Chemother. 2008 62: ii3-ii14; doi:10.1093/jac/dkn348 [Abstract] [FREE Full Text] [PDF] [Request Permissions]   

Get checked abstract Rosy Reynolds, Russell Hope, and Laura Williams on behalf of the BSAC Working Parties on Resistance Surveillance
Survey, laboratory and statistical methods for the BSAC Resistance Surveillance Programmes
J. Antimicrob. Chemother. 2008 62: ii15-ii28; doi:10.1093/jac/dkn349 [Abstract] [FREE Full Text] [PDF] [Request Permissions]   

Get checked abstract Rosy Reynolds, Paul C. Lambert, and Paul R. Burton on behalf of the BSAC Extended Working Parties on Resistance Surveillance
Analysis, power and design of antimicrobial resistance surveillance studies, taking account of inter-centre variation and turnover
J. Antimicrob. Chemother. 2008 62: ii29-ii39; doi:10.1093/jac/dkn350 [Abstract] [FREE Full Text] [PDF] [Request Permissions]   

Get checked abstract David M. Livermore, Russell Hope, Geraldine Brick, Mark Lillie, and Rosy Reynolds on behalf of the BSAC Working Parties on Resistance Surveillance
Non-susceptibility trends among Enterobacteriaceae from bacteraemias in the UK and Ireland, 2001–06
J. Antimicrob. Chemother. 2008 62: ii41-ii54; doi:10.1093/jac/dkn351 [Abstract] [FREE Full Text] [PDF] [Request Permissions]   

Get checked abstract David M. Livermore, Russell Hope, Geraldine Brick, Mark Lillie, and Rosy Reynolds on behalf of the BSAC Working Parties on Resistance Surveillance
Non-susceptibility trends among Pseudomonas aeruginosa and other non-fermentative Gram-negative bacteria from bacteraemias in the UK and Ireland, 2001–06
J. Antimicrob. Chemother. 2008 62: ii55-ii63; doi:10.1093/jac/dkn352 [Abstract] [FREE Full Text] [PDF] [Request Permissions]   

Get checked abstract Russell Hope, David M. Livermore, Geraldine Brick, Mark Lillie, and Rosy Reynolds on behalf of the BSAC Working Parties on Resistance Surveillance
Non-susceptibility trends among staphylococci from bacteraemias in the UK and Ireland, 2001–06
J. Antimicrob. Chemother. 2008 62: ii65-ii74; doi:10.1093/jac/dkn353 [Abstract] [FREE Full Text] [PDF] [Request Permissions]   

Get checked abstract Derek F. J. Brown, Russell Hope, David M. Livermore, Geraldine Brick, Karen Broughton, Robert C. George, and Rosy Reynolds on behalf of the BSAC Working Parties on Resistance Surveillance
Non-susceptibility trends among enterococci and non-pneumococcal streptococci from bacteraemias in the UK and Ireland, 2001–06
J. Antimicrob. Chemother. 2008 62: ii75-ii85; doi:10.1093/jac/dkn354 [Abstract] [FREE Full Text] [PDF] [Request Permissions]   

Get checked abstract David J. Farrell, David Felmingham, Jemma Shackcloth, Laura Williams, Kirsty Maher, Russell Hope, David M. Livermore, Robert C. George, Geraldine Brick, Siobhan Martin, and Rosy Reynolds on behalf of the BSAC Working Parties on Resistance Surveillance
Non-susceptibility trends and serotype distributions among Streptococcus pneumoniae from community-acquired respiratory tract infections and from bacteraemias in the UK and Ireland, 1999 to 2007
J. Antimicrob. Chemother. 2008 62: ii87-ii95; doi:10.1093/jac/dkn355 [Abstract] [FREE Full Text] [PDF] [Request Permissions]   

Get checked abstract Ian Morrissey, Kirsty Maher, Laura Williams, Jemma Shackcloth, David Felmingham, and Rosy Reynolds on behalf of the BSAC Working Parties on Resistance Surveillance
Non-susceptibility trends among Haemophilus influenzae and Moraxella catarrhalis from community-acquired respiratory tract infections in the UK and Ireland, 1999–2007
J. Antimicrob. Chemother. 2008 62: ii97-ii103; doi:10.1093/jac/dkn356 [Abstract] [FREE Full Text] [PDF] [Request Permissions]   

Get checked abstract Alasdair P. MacGowan on behalf of the BSAC Working Parties on Resistance Surveillance
Clinical implications of antimicrobial resistance for therapy
J. Antimicrob. Chemother. 2008 62: ii105-ii114; doi:10.1093/jac/dkn357 [Abstract] [FREE Full Text] [PDF] [Request Permissions]

David

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The British Society for Antimicrobial Chemotherapy Resistance Surveillance Project: a successful collaborative model
英国抗感染治疗协会耐药监测计划：成功合作的典范
Anthony R. White* on behalf of the BSAC Working Parties on Resistance Surveillance
Tony White Ltd, Newport, Essex, UK
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The British Society for Antimicrobial Chemotherapy (BSAC) Resistance Surveillance Project was initiated in light of the need for UK-wide surveillance of antibacterial resistance in key clinical pathogens. The Project comprises two defined-protocol programmes that cover a range of important pathogens and antibacterials related to community-acquired respiratory tract infection and bloodstream infection, respectively. The Respiratory Programme has reported quantitative susceptibility data for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis collected from across the UK and Ireland since 1999. The Bacteraemia Programme has reported the susceptibility of a wide range of Gram-positive and -negative organisms since 2001. The sustainability of the Programmes relies on a unique collaborative funding model: sponsorship is provided by a number of pharmaceutical companies in return for the inclusion of their investigational or marketed agents in the study alongside a core panel of established antibacterials. The sponsors have changed over time according to their interest in participating. Results for marketed agents are communicated in a timely manner through the BSAC web site and by presentation and publication, and for investigational agents with the agreement of their sponsors. The Project satisfies the requirement for sustainable defined-protocol high-quality resistance surveillance across the UK and Ireland.
Keywords: respiratory , bacteraemia , longitudinal , national , standardized

David

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Survey, laboratory and statistical methods for the BSAC Resistance Surveillance Programmes
英国抗感染治疗协会耐药监测计划的调查，实验室分析和统计方法
Rosy Reynolds1,*, Russell Hope2, Laura Williams3 on behalf of the BSAC Working Parties on Resistance Surveillance
1 Department of Medical Microbiology, Southmead Hospital, Southmead Road, Bristol BS10 5NB, UK 2 Health Protection Agency Centre for Infections, 61 Colindale Avenue, London NW9 5EQ, UK 3 Quotient Bioresearch Ltd, Microbiology, 7-9 William Road, London NW1 3ER, UK
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Objectives: The British Society for Antimicrobial Chemotherapy (BSAC) Bacteraemia and Respiratory Resistance Surveillance Programmes are designed for long-term surveillance of antimicrobial resistance in key pathogens of bloodstream and community-acquired respiratory infection in the UK and Ireland. This paper describes their methods in detail.
Methods: Sentinel laboratories across the UK and Ireland contributed up to a fixed quota of isolates of defined bacterial groups. Collecting laboratories were compared with national benchmarks for size of Hospital Trust and distribution of bacteraemia pathogens. A central laboratory for each programme confirmed the identification of isolates, measured MICs by the BSAC agar dilution method and undertook further testing by standard methods. The variability of the MIC method was assessed by repeated annual testing of a panel of control isolates. Classification as susceptible, intermediate or resistant was by BSAC and European Committee on Antimicrobial Susceptibility Testing breakpoints. Statistical analysis was adjusted for inter-centre variation using random effects logistic regression.
Results: Thirty-two laboratories contributed 16 550 respiratory isolates from 1999–2000 to 2006–07; 30 laboratories contributed 15 812 bacteraemia isolates from 2001 to 2006. Although large and teaching hospitals were over-represented, the pattern of bacteraemia organisms seen in the collecting laboratories in England and Wales was similar to that in national data reported to the Health Protection Agency. Replicate MIC measurements showed that 90% agreed within ±1, and 98% within ±2, doubling dilutions.
Conclusions: These surveillance programmes have provided reliable information on antimicrobial susceptibility in the UK and Ireland over six and eight seasons, respectively, so far. Detailed results showing non-susceptibility trends, and relationships with potential predictive factors, are presented in six linked papers in this Supplement.
Keywords: MIC , breakpoint , agar dilution , statistical analysis , antimicrobial resistance

David

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Analysis, power and design of antimicrobial resistance surveillance studies, taking account of inter-centre variation and turnover
耐药监测研究的分析，效能和设计，同时考虑医院之间的取样和收入差异
Rosy Reynolds1,*, Paul C. Lambert2, Paul R. Burton2 on behalf of the BSAC Extended Working Parties on Resistance Surveillance
1 Department of Medical Microbiology, Southmead Hospital, Southmead Road, Bristol BS10 5NB, UK 2 Centre for Biostatistics and Genetic Epidemiology, Department of Health Sciences, University of Leicester, 2nd Floor Adrian Building, University Road, Leicester LE1 7RH, UK
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Objectives: Logistic regression is commonly used to analyse resistance surveillance studies, but variation between collecting centres undermines its assumption that isolates are independent. We studied the impact of this problem and the ability of alternative methods to overcome it. We also investigated different study designs and estimated the statistical power of the BSAC Resistance Surveillance Programmes.
Methods: We simulated datasets with various combinations of study design, inter-centre variation, annual centre turnover, initial resistance level and odds ratio, and analysed 1000 repetitions of each for trends in resistance by five variants of logistic regression.
Results: Traditional analysis by unadjusted logistic regression was invalid because it gave very high type 1 (false-positive) error rates, up to 49%, in the presence of high levels of inter-centre variation and turnover. Of the other methods investigated, logistic regression with random effects for centre performed best: it had appropriate error rates for all study designs assessed and generally had higher power than fixed-effects or cluster-robust approaches. A ‘Diffuse’ study with more centres contributing fewer isolates was less susceptible to the ill-effects of inter-centre variation than a study of equal overall size with fewer centres contributing more, and had slightly higher power.
Conclusions: Unadjusted logistic regression, ignoring inter-centre variation, is unsuitable for the analysis of trends in typical resistance surveillance studies, often leads to erroneous conclusions and should be avoided. Random effects logistic regression is an appropriate, widely applicable alternative, available in most standard statistical software. Collecting isolates from a larger number of centres has both statistical and scientific advantages.
Keywords: trend , random effects model , simulation , type 1 error , statistical analysis

David

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Non-susceptibility trends among Enterobacteriaceae from bacteraemias in the UK and Ireland, 2001–06
英国和爱尔兰2001-06菌血症样本中肠杆菌科的不敏感趋势
David M. Livermore1,*, Russell Hope1, Geraldine Brick1, Mark Lillie1, Rosy Reynolds2 on behalf of the BSAC Working Parties on Resistance Surveillance
1 Health Protection Agency Centre for Infections, 61 Colindale Avenue, London NW9 5EQ, UK 2 Department of Medical Microbiology, Southmead Hospital, Bristol BS10 5NB, UK
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Background: Enterobacteriaceae are common agents of bacteraemia, with Escherichia coli accounting for 20% of the cases. Reflecting this importance, members of the family constitute 4 of the 12 collection groups in the British Society for Antimicrobial Chemotherapy (BSAC) Bacteraemia Surveillance Programme.
Methods: MICs from the BSAC surveillance programme were reviewed, along with bacteraemia reports received by the Health Protection Agency (HPA) via its CoSurv/LabBase system. Isolates with unusual resistances were subjected to molecular analysis.
Results: The BSAC and HPA systems both revealed dramatically increasing resistance to cephalosporins, ciprofloxacin and gentamicin among E. coli and Klebsiella spp., with cephalosporin resistance largely contingent on the spread of CTX-M extended-spectrum β-lactamases (ESBLs); fluoroquinolone resistance also increased among Proteus mirabilis and ESBL-negative E. coli. Carbapenem resistance remained extremely rare, but two Enterobacter spp., from the same patient in different years, had KPC carbapenemases, while a few isolates had carbapenem resistance contingent upon combinations of β-lactamase and impermeability, and ertapenem MICs for AmpC-derepressed Enterobacter spp. rose over time. Three new agents—ceftobiprole, doripenem and tigecycline—were tested. Ceftobiprole was broadly active, except against ESBL producers and Klebsiella oxytoca hyperproducing K1 enzyme, and was variable against AmpC-derepressed Enterobacter spp. and against Proteus vulgaris. Doripenem was more potent than imipenem. Tigecycline was almost universally active against E. coli, but low-level non-susceptibility (MIC 2 mg/L) was frequent among Klebsiella spp.
Conclusions: E. coli and Klebsiella spp. showed dramatic shifts, with sharply rising non-susceptibility to cephalosporins, ciprofloxacin and gentamicin. The rise in cephalosporin resistance reflected dissemination of CTX-M ESBLs. Carbapenems remain broadly active and new agents offer potential.
Keywords: BSAC , HPA , surveillance

David

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Non-susceptibility trends among Pseudomonas aeruginosa and other non-fermentative Gram-negative bacteria from bacteraemias in the UK and Ireland, 2001–06
英国和爱尔兰2001-06年菌血症样本中铜绿假单胞菌及其他非发酵革兰阴性杆菌的不敏感趋势
David M. Livermore1,*, Russell Hope1, Geraldine Brick1, Mark Lillie1, Rosy Reynolds2 on behalf of the BSAC Working Parties on Resistance Surveillance
1 Health Protection Agency Centre for Infections, 61 C olindale Avenue, London NW9 5EQ, UK 2 Department of Medical Microbiology, Southmead Hospital, Bristol BS10 5NB, UK
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Background: Pseudomonas and Acinetobacter spp. are important opportunists, notorious for resistance. Pseudomonas spp. are collected in the British Society for Antimicrobial Chemotherapy (BSAC) bacteraemia surveillance, with Acinetobacter spp. and Stenotrophomonas maltophilia well represented in the ‘other Gram-negatives’ group.
Methods: Data for collected isolates were reviewed together with LabBase bacteraemia reports to the Health Protection Agency (HPA). Isolates with unusual resistances were subjected to molecular investigation.
Results: From 2001 to 2006, the BSAC surveillance collected 1226 Pseudomonas aeruginosa, 240 Acinetobacter spp.—125 of them Acinetobacter calcoaceticus/baumannii (Acb) complex—and 165 S. maltophilia. Among P. aeruginosa, non-susceptibility rates to β-lactams and gentamicin fluctuated, without trend, below 10%; those to ciprofloxacin ranged from 16% to 22%. One P. aeruginosa isolate from 2001 had VIM-2 metallo-β-lactamase. For Acb, the BSAC data indicated frequent non-susceptibility, except to imipenem, where only five non-susceptible isolates were collected, all after 2003, four of them belonging to the OXA-23 clone 1 lineage which is prevalent in Southeast England. Reports to the HPA indicated rising imipenem non-susceptibility in Acb (P < 0.0001). Co-trimoxazole retained near-universal activity against S. maltophilia. Among new antibiotics, doripenem MICs were 4 mg/L for most imipenem-resistant P. aeruginosa but 16 mg/L for Acb OXA-23 clone 1. Ceftobiprole had higher MICs than ceftazidime for P. aeruginosa, but 81% of the isolates were inhibited at 4 mg/L. Tigecycline had activity against most Acb, including OXA-23 clone 1, and also against S. maltophilia.
Conclusions: Most P. aeruginosa from bacteraemias in the UK and Ireland remain relatively susceptible by international standards; in contrast, multiresistance is widespread in Acb, with imipenem non-susceptibility emerging.
Keywords: bacteraemia , Pseudomonas aeruginosa , Acinetobacter spp. antibiotic resistance

David

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Non-susceptibility trends among staphylococci from bacteraemias in the UK and Ireland, 2001–06
英国和爱尔兰2001-06菌血症样本中葡萄球菌的不敏感趋势
Russell Hope1,*, David M. Livermore1, Geraldine Brick1, Mark Lillie1, Rosy Reynolds2 on behalf of the BSAC Working Parties on Resistance Surveillance
1 Health Protection Agency Centre for Infections, 61 Colindale Avenue, London NW9 5EQ, UK 2 Department of Medical Microbiology, Southmead Hospital, Southmead Road, Bristol BS10 5NB, UK
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Objectives: Investigation of the antibiotic susceptibilities and trends for staphylococci collected from bacteraemia cases in the UK and Ireland, from 2001 to 2006, as part of the British Society for Antimicrobial Chemotherapy's Bacteraemia Surveillance Programme.
Methods: Twenty-five hospitals from the UK and Ireland each collected up to 10 consecutive isolates of both Staphylococcus aureus and coagulase-negative staphylococci (CoNS) per year from 2001 to 2006. MIC determination and identification to species level were carried out centrally. mecA and also mupA alleles were sought by PCR in S. aureus and CoNS from 2005 and 2006, respectively.
Results: One thousand four hundred and forty-eight S. aureus and 1214 CoNS were collected. The overall prevalence of methicillin resistance was 42% (with 6% annual fluctuation) for S. aureus and 67% (range 54% to 80%) for CoNS. Resistance to aminoglycosides, macrolides, quinolones and tetracyclines was strongly associated with methicillin resistance in both species groups. Many (20.8%) CoNS and three (0.2%) S. aureus isolates were non-susceptible to teicoplanin, but there was no vancomycin non-susceptibility found in S. aureus and only one vancomycin-intermediate CoNS isolate. There was little evidence of susceptibility trends over time for any antibiotic, with the surveillance period preceding the recent fall in methicillin-resistant S. aureus (MRSA) prevalence indicated by the mandatory surveillance of MRSA bacteraemia in England. The newer antibiotics, ceftobiprole, daptomycin, linezolid, telavancin and tigecycline, all had excellent activity against staphylococci.
Conclusions: Multiresistant staphylococci remain abundant in the UK and Ireland but many new antimicrobials are becoming available and these may prove effective alternatives to glycopeptides.
Keywords: Prevalence , MRSA , surveillance

David

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Non-susceptibility trends among enterococci and non-pneumococcal streptococci from bacteraemias in the UK and Ireland, 2001–06
英国和爱尔兰2001-06菌血症样本中场球菌和其他链球菌（肺链除外）的不敏感趋势
Derek F. J. Brown1,*, Russell Hope2, David M. Livermore2, Geraldine Brick2, Karen Broughton3, Robert C. George3, Rosy Reynolds4 on behalf of the BSAC Working Parties on Resistance Surveillance
1 Health Protection Agency, Clinical Microbiology and Public Health Laboratory, Addenbrooke's Hospital, Cambridge CB2 2QW, UK 2 Antibiotic Resistance Monitoring and Reference Laboratory, Health Protection Agency, 61 Colindale Avenue, London NW9 5HT, UK 3 Respiratory and Systemic Infection Laboratory, Health Protection Agency, 61 Colindale Avenue, London NW9 5HT, UK 4 Department of Medical Microbiology, Southmead Hospital, Bristol BS10 5NB, UK
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* Corresponding author. Tel: +44-1223-257020; Fax: +44-1223-242775; E-mail: dfjb2@cam.ac.uk
Objectives: To describe the current patterns and trends in antimicrobial susceptibility in enterococci and streptococci (excepting pneumococci) from bacteraemia in the UK and Ireland from 2001 to 2006.
Methods: In each year 2001–06, blood culture isolates were collected by 25 laboratories distributed across the UK and Ireland. In total, there were 1408 isolates of enterococci, 1332 of β-haemolytic streptococci and 1012 of - and non-haemolytic streptococci. A single central laboratory re-identified the isolates and measured MICs by the BSAC agar dilution method.
Results: The prevalence of reduced susceptibility in streptococci and enterococci did not change significantly for most antibiotics, but trends were noted to increased ampicillin, imipenem and vancomycin resistance in Enterococcus faecium. The prevalence of reduced susceptibility to macrolides and tetracycline in streptococci, to tetracycline and gentamicin (high level) in enterococci and to β-lactams and glycopeptides in E. faecium were all high, with some differences in the prevalence among species or groups.
Conclusions: Reduced susceptibility to some antimicrobial agents among streptococci and enterococci remains common and continued surveillance is warranted.
Keywords: bacteraemia , antimicrobial agents , resistance , epidemiology

David

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Non-susceptibility trends and serotype distributions among Streptococcus pneumoniae from community-acquired respiratory tract infections and from bacteraemias in the UK and Ireland, 1999 to 2007
英国和爱尔兰1999-2007年社区获得性呼吸道感染和菌血症样本中肺炎链球菌的血清型分布和不敏感趋势
David J. Farrell1,*, David Felmingham1, Jemma Shackcloth1, Laura Williams1, Kirsty Maher1, Russell Hope2, David M. Livermore2, Robert C. George2, Geraldine Brick2, Siobhan Martin2, Rosy Reynolds3 on behalf of the BSAC Working Parties on Resistance Surveillance
1 Quotient Bioresearch, Microbiology, 7-9 William Road, London NW1 3ER, UK 2 Health Protection Agency Centre for Infections, 61 Colindale Avenue, London NW9 5EQ, UK 3 Department of Medical Microbiology, Southmead Hospital, Southmead Road, Bristol BS10 5NB, UK
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* Corresponding author. Present address: Ontario Public Health Laboratories, Ministry of Health and Long-Term Care, 81 Resources Road, Toronto, Ontario, Canada M9P 3T1. Tel: +1-416-235-5703; Fax: +1-416-235-6550; E-mail: david.farrell@oahpp.ca
Objectives: Pneumococcal disease is prevalent and is a cause of significant morbidity and mortality in the UK and Ireland. We describe the antimicrobial susceptibility and serotype distributions of Streptococcus pneumoniae causing bacteraemia and community-acquired pneumonia in these countries from 1999/2000 to 2006/7, predominantly prior to the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) into the standard vaccination schedule in September 2006.
Methods: The BSAC Respiratory and Bacteraemia Resistance Surveillance Programmes collected S. pneumoniae from sentinel laboratories distributed across the UK and Ireland. A central laboratory for each programme re-identified the isolates, determined their serotypes and measured MICs by the BSAC agar dilution method.
Results: The prevalence of antimicrobial non-susceptibility, although significant, was generally below the global average. There was no convincing evidence of increasing non-susceptibility over time in either study. The results showed clear differences in the serotype distribution between respiratory and blood isolates, but suggested that PCV7 would provide adequate coverage of invasive isolates in the UK and Ireland. A significant and rapid increase of the non-vaccine serotype 1 among blood isolates from 2001 to 2006 was worrying, given the spread of hypervirulent serotype 1 clones elsewhere in the world.
Conclusions: Continued surveillance of both antimicrobial non-susceptibility and serotype distribution changes following the introduction of PCV7 into the routine immunization schedule in the UK and Ireland is imperative. The data presented here, largely obtained prior to the introduction of PCV7 in the UK, provide a valuable baseline against which to monitor changes in antimicrobial non-susceptibility and serotype distribution and hence to identify the expansion of any significant clones.
Keywords: surveillance , susceptibility tests , respiratory

David

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Non-susceptibility trends among Haemophilus influenzae and Moraxella catarrhalis from community-acquired respiratory tract infections in the UK and Ireland, 1999–2007
英国和爱尔兰1999-2007年社区获得性呼吸道感染中流感嗜血杆菌和卡他莫拉菌的不敏感趋势
Ian Morrissey1,*, Kirsty Maher1, Laura Williams1, Jemma Shackcloth1, David Felmingham1, Rosy Reynolds2 on behalf of the BSAC Working Parties on Resistance Surveillance
1 Quotient Bioresearch Limited, Microbiology, 7-9 William Road, London NW1 3ER, UK 2 Department of Medical Microbiology, Southmead Hospital, Southmead Road, Bristol BS10 5NB, UK
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Objectives: To determine the antimicrobial susceptibility of Haemophilus influenzae and Moraxella catarrhalis causing community-acquired respiratory tract infections in the UK and Ireland from 1999/2000 to 2006/07.
Methods: Sentinel laboratories across the UK and Ireland contributed up to a fixed quota of isolates of defined organisms per annum. A central laboratory confirmed the isolates' identities, measured MICs by the BSAC agar dilution method and undertook further testing by standard methods. The variability of the MIC method was assessed by repeated annual testing of control isolates. BSAC and EUCAST breakpoints were used. Statistical analysis adjusted for inter-centre variation by random effects logistic regression.
Results: A total of 7371 H. influenzae and 2529 M. catarrhalis isolates were investigated. Over 90% of the H. influenzae isolates were susceptible to most of the antimicrobials tested, the exceptions being ampicillin (84.6% susceptible), trimethoprim (84.0%), cefuroxime (82.9%), amoxicillin (77.2%) and cefaclor (11.7%). For M. catarrhalis, resistance was solely due to β-lactamase (prevalence over 91%) reducing susceptibility to penicillins only. There was little evidence of decreased antimicrobial susceptibility between 1999 and 2007 in either pathogen, except for a reduction in susceptibility to trimethoprim in H. influenzae (90.3% to 82.6%, P < 0.00001). On the other hand, tetracycline susceptibility in H. influenzae increased over this period in the UK and Ireland (96.5 to 98.8%, P = 0.00008).
Conclusions: Despite increased resistance in respiratory pathogens from other parts of the world, the susceptibility of H. influenzae and M. catarrhalis to all agents, except tetracycline and trimethoprim in the case of H. influenzae, has remained constant during this longitudinal study.
Keywords: resistance , surveillance , MIC , breakpoint

David

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Clinical implications of antimicrobial resistance for therapy
抗生素耐药性对临床治疗的启示
Alasdair P. MacGowan1,2,* on behalf of the BSAC Working Parties on Resistance Surveillance
1 Bristol Centre for Antimicrobial Research and Evaluation, North Bristol NHS Trust, Bristol, UK 2 Department of Medical Microbiology, University of Bristol, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK
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* Corresponding author. Tel: +44-117-959-5651/2; Fax: +44-117-959-3154; E-mail: alasdair.macgowan@nbt.nhs.uk
The last decade has seen a significant improvement in published evidence to show the clinical predictive value of phenotypic susceptibility testing with categorization of pathogens as ‘susceptible’ or ‘resistant’ based on clinical breakpoints. Most of the published data are based on retrospective or prospective observational clinical studies of patients treated with appropriate [pathogen(s)-susceptible] or inappropriate [pathogen(s)-resistant] chemotherapy. Appropriate therapy has been shown to improve outcomes in infections occurring in hospitals, such as bloodstream infection (BSI) and pneumonia in the intensive care unit. Infections due to specific pathogens such as extended-spectrum β-lactamase-producing Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus also respond better to appropriate than inappropriate antibiotics. The situation with vancomycin-resistant enterococci is less clear, perhaps due to the increased importance of patient confounders. Streptococcus pneumoniae when causing acute pneumonia with or without BSI is a well-known exception to the predictive value of laboratory-defined resistance. Antibiotic resistance also impacts on outcomes in the community where the evidence is best for urinary tract infection. The clinical studies are compatible with the current pharmacokinetic/pharmacodynamic paradigm used to explain and predict antibacterial effects and therefore have a sound basis in antimicrobial science. These data underline the importance of well-constructed epidemiological studies to determine the prevalence of antimicrobial resistance in clinical practice and the central place of laboratory-based susceptibility testing in dictating antimicrobial therapy and so optimizing patient outcomes.
Keywords: clinical outcomes , bacteraemia , hospital infection