Biomedical subjects

David M Livermore

Publications and source records attributed to David M Livermore.

8 recordsLinked to original sources

PubMed2025

Two decades of resistance surveillance by the British Society for Antimicrobial Chemotherapy: design, development, delivery, deficiencies and future directions.

The British Society for Antimicrobial Chemotherapy Antimicrobial Surveillance Project was established in the United Kingdom (UK) and Ireland in response to dissatisfaction with existing antimicrobial surveillance which, in the 1990s, was fragmented and poorly informative for clinical and public heath purposes. The model developed into an integrated Project that was novel in its management and financing, being a true collaboration between a medical charity, pharmaceutical companies and the laboratories contracted to perform the testing. Separate 'Programmes' within an overall 'Project' collected and tested community- and hospital-acquired respiratory and bloodstream infection isolates. Cooperation with public sector bodies allowed data collection from the Project to be compared to routinely collected data from National Health Service laboratories. Between 1999 and 2019 the Project delivered test results on almost 100 000 isolates, from 17 bacterial genera to 44 antimicrobial agents. The results were made available annually on a specially constructed web site. In this supplement, we summarize the data collected in a series of papers relevant to the two programmes, discussing the Project's strengths and deficiencies. Support for the Project declined in the period after 2010, and collection ceased after 20 years, its demise related to changing priorities within the partner organizations. However, the bacterial collection remains and is to be maintained to assist in future work in combating antimicrobial resistance.

United Kingdom↗

PubMed2025

The British Society for Antimicrobial Chemotherapy Resistance Surveillance Project: methods and limitations.

OBJECTIVES: The BSAC Bacteraemia and Respiratory Resistance Surveillance Programmes provided long-term surveillance of antibiotic resistance in key pathogens of bloodstream and both community- and hospital-acquired respiratory infections in the UK and Ireland. This paper details the methodologies used. Data limitations are discussed. METHODS: Sentinel laboratories across the UK and Ireland contributed up to a fixed annual quota of isolates of defined bacterial groups. For each Programme, a Central Laboratory confirmed bacterial identifications, measured MICs by the BSAC agar dilution method, investigated mechanisms of resistance and determined serotypes of Streptococcus pneumoniae. Identification methods evolved over time, e.g. with adoption of MALDI-TOF. Classification of susceptibility and resistance follows the 2022 (not contemporaneous) EUCAST guidance. RESULTS: Seventy-nine laboratories contributed 30 716 community respiratory isolates from 1999/2000 to 2018/19; 65 laboratories contributed 13 508 hospital respiratory isolates from 2008/09 to 2018/19; 81 laboratories contributed 56 064 bacteraemia isolates from 2001 to 2019. Although large and teaching hospitals were over-represented, the resistance rates for bacteraemia organisms collected in England mirror more extensive (but less standardized or detailed) national data gathered from laboratories by the UK Health Security Agency and its predecessor organizations, which provided a bespoke data extract. CONCLUSIONS: These surveillance Programmes have provided comprehensive and reliable information on antibiotic susceptibility in the UK and Ireland over two decades. Detailed results, showing resistance trends and mechanisms of antibiotic resistance, are presented in five papers in this Supplement.

Antimicrobial Stewardship↗

PubMed2025

Antimicrobial resistance among Gram-positive agents of bacteraemia in the UK and Ireland: trends from 2001 to 2019.

OBJECTIVES: The BSAC Bacteraemia Resistance Surveillance collected isolates from UK and Irish hospitals for central testing. Concurrent UKHSA surveillance collated English hospitals' own susceptibility data. Results were collated and compared. METHODS: BSAC Surveillance collected quotas of isolates per site annually from 2001 to 2019. MIC testing was by BSAC agar dilution, with resistance mechanisms identified by synergy tests, interpretive reading and PCR. The UKHSA sought hospitals' data on all bacteraemia isolates. RESULTS: Both surveillance systems recorded dramatic falls in MRSA, from c. 40% of bloodstream Staphylococcus aureus in 2001 to <10% by 2019. Both noted rises in the proportion of MRSA (especially) and MSSA resistant to fusidic acid, along with declines of ciprofloxacin and macrolide resistance amongst MRSA. Methicillin resistance also fell among coagulase-negative staphylococci, albeit only modestly; fusidic acid resistance rose. Shifts for pneumococci were complex, reflecting vaccine-contingent serotype displacements; resistance rates remained low, with high-dose penicillin almost universally active. Enterococcus faecium became more prevalent relative to Enterococcus faecalis; vancomycin resistance averaged 29% among E. faecium versus 2% in E. faecalis, without trend. Erythromycin resistance rose among groups B, C and G (but not group A) streptococci. Oxazolidinones, tigecycline, daptomycin and anti-PBP2' cephalosporins retained near-universal activity against target species, except that tigecycline has been compromised by breakpoint reductions for streptococci. CONCLUSIONS: Gram-positive pathogens were the dominant historical pathogens of bacteraemia. The trends seen here-with many near-universally active antibiotics-indicate little hazard of this situation returning. Nevertheless, few treatments exist in some settings, notably multi-resistant E. faecium endocarditis.

Humans↗

PubMed2025

Antimicrobial resistance among Gram-negative agents of bacteraemia in the UK and Ireland: trends from 2001 to 2019.

OBJECTIVES: The BSAC Bacteraemia Resistance Surveillance Programme collected isolates from UK and Irish hospitals for central testing. Concurrent UKHSA surveillance collected English hospitals' own susceptibility data. Results were reviewed and compared. METHODS: The BSAC surveillance collected fixed quotas of isolates per site annually from 2001 to 2019. MIC testing was by BSAC agar dilution. Resistance mechanisms were investigated by synergy tests, interpretive reading and PCR. The UKHSA seeks data on all bacteraemia isolates in England. RESULTS: For Escherichia coli, which now causes >30% of all bacteraemias, there were marked early (2002-06) rises in resistance to cephalosporins, fluoroquinolones and gentamicin, followed by small falls, stabilization, then from around 2015, very slow rises, with similar patterns seen for Klebsiella pneumoniae. Most cephalosporin resistance in these two species involved ESBLs, principally CTX-M types. Both species had frequent co-amoxiclav resistance. Cephalosporin resistance-mostly AmpC-mediated-declined in Enterobacter and Serratia spp., as did fluoroquinolone resistance, likely reflecting reduced use and selection pressure. Proteeae showed few changes; increasing dominance of Proteus mirabilis in the BSAC collection was not confirmed by the UKHSA dataset. Resistance in Pseudomonas aeruginosa was uncommon and showed little temporal change in either dataset. Carbapenemases remained extremely rare in all species. Newer and developmental agents covered many resistance types, but none covered all types. CONCLUSIONS: Except for early rises of cephalosporin, fluoroquinolone and gentamicin resistance in E. coli and K. pneumoniae, there was little evidence for rising resistance and some evidence of declining resistance, notably in species where it predominantly involves AmpC derepression.

Humans↗

PubMed2025

Antimicrobial resistance among agents of hospital-acquired lower respiratory tract infection in the UK and Ireland: trends from 2008/2009 to 2018/2019.

OBJECTIVES: To survey trends in antimicrobial resistance among the pathogens of hospital-acquired lower respiratory tract infection (HA-LRTI), which causes significant mortality and morbidity, particularly among ventilated patients. METHODS: The BSAC Surveillance collected quotas of major HA-LRTI pathogens from sentinel sites from 2008/09 (October to September) to 2018/19. MIC testing was by BSAC agar dilution. Resistance mechanisms were inferred from synergy tests, interpretive reading and PCR. RESULTS: Target numbers of Staphylococcus aureus, Pseudomonas aeruginosa and Enterobacterales-dominated by Escherichia coli and Klebsiella spp.-were reliably collected. Acinetobacter spp. collections were small, reflecting low incidence. Resistance rates fell or fluctuated, with no major rises. Notable declines included: (i) a fall in the proportion of MRSA among S. aureus from c. 40% to 10%; (ii) a halving, since 2012/13, in 'triple-resistance' to carbapenems, aminoglycosides and fluoroquinolones among Acinetobacter baumannii sensu stricto, from c. 24% to 9%; (iii) reductions in AmpC-associated cephalosporin resistance among Enterobacter cloacae and Serratia isolates, and (iv) falls in fluoroquinolone resistance among Enterobacterales, except Klebsiella pneumoniae. Resistance rates in P. aeruginosa remained low, though higher than in bacteraemia. Cephalosporin resistance in E. coli and K. pneumoniae was largely ESBL associated and, unlike AmpC-associated resistance in Enterobacter and Serratia spp., did not decline notably. Except for OXA-23 in A. baumannii, carbapenemases remained extremely rare. Antistaphylococcal oxazolidinones, tigecycline, ceftolozane/tazobactam, ceftazidime/avibactam and ceftobiprole retained uneroded activity. CONCLUSIONS: From 2008/09 to 2018/19, there were no major rises in resistance among the principal agents of HA-LRTI; for several important organisms/resistance combinations there were notable declines.

Humans↗

PubMed2025

Antimicrobial resistance among agents of community-associated lower respiratory tract infection in the UK and Ireland: trends from 1999/2000 to 2018/2019.

OBJECTIVES: The BSAC Respiratory Surveillance Programme examined resistance trends among Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis from patients with community-acquired lower respiratory tract infection (CA-LRTI). METHODS: Quotas of isolates were sought per collecting site from 1999/00 to 2018/19; an annual October start date captured winter infection peaks within single years. MIC testing was by BSAC agar dilution. β-Lactamase detection with nitrocefin and pneumococcal serotyping by classical methods or WGS. RESULTS: Resistances were uncommon, except that β-lactamases occurred in c. 20% of H. influenzae from 2012/13 following earlier rises, and in >90% of M. catarrhalis throughout. Only 0.11% (12/10881) of S. pneumoniae were fully resistant to penicillin; co-amoxiclav inhibited 97.8% of 13526 H. influenzae and >99.9% of 6309 M. catarrhalis isolates. Cefotaxime inhibited >99% of all isolates at breakpoint, as did relevant fluoroquinolones in the fewer years tested. Tetracycline inhibited >98% of H. influenzae and M. catarrhalis and 85% of S. pneumoniae. Significant shifts were: (i) fluctuating resistances to tetracyclines, macrolides and penicillin in pneumococci, reflecting serotype replacements; (ii) expansion, from 2012/13, in the proportion of H. influenzae with β-lactamase-independent amoxicillin/co-amoxiclav resistance; and (iii) increasing high-level amoxicillin resistance (MIC  > 64 mg/L) among β-lactamase-positive H. influenzae. MIC differentials were seen for cephalosporins between β-lactamase-positive and β-lactamase-negative M. catarrhalis, greatest (512-fold) for ceftaroline. CONCLUSIONS: CA-LRTI remains eminently treatable, yet shifts are occurring in the serotypes of S. pneumoniae most associated with resistance and in the nature of amoxicillin resistance in H. influenzae. β-Lactamase-related cephalosporin MIC differentials for M. catarrhalis are striking but their clinical significance remains uncertain.

Humans↗

PubMed2025

Trends of serotypes and resistance among Streptococcus pneumoniae in the UK and Ireland (1999-2019).

OBJECTIVES: This study aimed to report the serotype distribution of Streptococcus pneumoniae isolates from UK and Irish patients with bacteraemia or community-associated lower respiratory tract infections (CA-LRTI). Depending upon the year, these were from 23 to 39 sentinel laboratories and were collected between 1999 and 2019, thus spanning the introduction of pneumococcal conjugate vaccines, PCV7 and PCV13. METHODS: Pneumococcal identification, susceptibility testing and serotyping were undertaken by a central laboratory. Changes in serotype distributions and among the predominant types showing antibiotic non-susceptibility were reviewed in relation to vaccine deployment. RESULTS: Following the introduction of PCV7 (2006) and PCV13 (2010), major shifts occurred in serotype prevalence for both bacteraemia and CA-LRTI. PCV7 types and most PCV13 types (but not 3 and 19A) were largely or wholly displaced. Many of the displaced types (e.g. 6B, 9V, 14, 19F and 23B) had been internationally prevalent and were associated with antibiotic resistance. Other serotypes-many included within the older pneumococcal polysaccharide vaccine, PPV23-expanded into the space, with serotype 8 becoming especially prominent in bacteraemia, though not respiratory infections. Further increasingly prevalent types included 9N, 10A, 12F and 22F. Serotype 15A, often multi-resistant, rose then fell in relative importance after deployment of PCV13. Among the currently most prevalent types, serotype 3 is rarely resistant to agents besides tetracyclines and bloodstream serotype 8 isolates mostly are fully susceptible. CONCLUSIONS: These data offer a comparison of serotypes associated with bacteraemia and respiratory disease over two decades in the UK and Ireland.

Humans↗

PubMed2025

Applications and benefits of the British Society for Antimicrobial Chemotherapy Resistance Surveillance Project-legacy and future.

The BSAC Resistance Surveillance Project ran from 1999 to 2019, amassing an unrivalled collection of almost 100 000 bacterial isolates from bloodstream and lower respiratory tract infections in the UK and Ireland. It was initiated in response to increasing antimicrobial resistance and supplemented existing surveillance schemes, enhancing the understanding of resistance epidemiology by estimating species prevalence within collection groups together with levels of antibacterial resistance, presented in terms of MICs and percentage susceptibility for each species/antibiotic combination tested. Generated data were explored to monitor and identify factors shaping resistance trends, and to profile antibacterial resistance patterns in specific geographies, settings and patient populations. The release of data and/or bacterial isolates led to a rich repository of published peer-reviewed papers. Additionally, the promotion of the BSAC standardized susceptibility testing method resulted in greater uniformity of antimicrobial susceptibility testing in hospital microbiology laboratories. Over time, public health laboratories' surveillance systems became increasingly comprehensive, and the BSAC Project ceased in 2019. This invaluable collection is now housed in the University of Dundee, in collaboration with the University of St Andrews. We highlight the collection's unique timeliness, and how the BSAC Project contributed to key interventions for infection prevention and control, public health and antimicrobial stewardship. We demonstrate the utility and benefits of the Project outlining the collection's future applications as an important bioresource. It comprises well-defined bacterial isolates-many now sequenced-with MIC data and demographic information. This legacy is available to researchers via the Tayside Biorepository and custodian contacts.

Humans↗