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Abstract: The emergence of carbapenem resistance in Enterobacteriaceae represents a major public health concern. We investigated ertapenem-resistant clinical isolates of Klebsiella spp. and Enterobacter spp. referred to the UK''s national reference laboratory for antibiotic resistance. Minimum inhibitory concentrations (MICs) were determined and interpreted according to British Society for Antimicrobial Chemotherapy guidelines. Genes for carbapenemases and CTX-M extended-spectrum β-lactamases (ESBLs) were sought by polymerase chain reaction, and imipenem hydrolysis was determined by spectrophotometry with crude extracts. From June 2004 to April 2006, 95 Klebsiella spp. and 76 Enterobacter spp. isolates resistant to ertapenem (MICs >2mg/L) were received, 40% of which (38 Klebsiella spp. and 30 Enterobacter spp.) were highly resistant to ertapenem (MICs >16mg/L). Imipenem and meropenem were active (geometric mean MICs <2mg/L) against most isolates with low-level ertapenem resistance but were less active against highly ertapenem-resistant isolates. Only one ertapenem-resistant isolate produced a defined carbapenemase, a Klebsiella pneumoniae with IMP-1 enzyme; one Enterobacter sp. also hydrolysed imipenem, but its carbapenemase remains to be identified. Geometric mean MICs of ertapenem for the collection were reduced five-fold by clavulanic acid for Klebsiella spp. compared with eight-fold by cloxacillin for Enterobacter spp. This study highlights the fact that ertapenem resistance is being detected in Klebsiella spp. and Enterobacter spp. in the UK, but that it is rarely mediated by true carbapenemases. Rather, it probably results from combinations of a β-lactamase – often a CTX-M ESBL in Klebsiella spp. or an AmpC enzyme in Enterobacter spp. – plus impermeability and/or increased efflux. Imipenem and meropenem often remain moderately active against isolates with low-level ertapenem resistance. [Copyright &y& Elsevier]

Abstract: It is widely believed that reducing antimicrobial usage should reduce resistance, although observational evidence is mixed. Pneumococci make ideal subjects to test this belief as they are widely surveyed and lack an animal reservoir. Accordingly, susceptibility data for pneumococci in the UK and Ireland were retrieved from the Health Protection Agency''s LabBase/CoSurv system and from the European Antimicrobial Resistance Surveillance System (EARSS) and British Society for Antimicrobial Chemotherapy (BSAC) databases. The BSAC surveillance examines respiratory pneumococci; the other systems focus upon invasive organisms only, with the LabBase/CoSurv system being the most comprehensive, capturing data on most bacteraemias in England and Wales. National pharmacy sales data were obtained from the IMS Health MIDAS database and were modelled to the resistance data by logistic and linear regression analysis. All systems except for the BSAC respiratory surveillance data indicated that penicillin resistance has fallen significantly since 1999 in the UK, whereas macrolide resistance has been essentially stable, or has risen slightly. The data for Ireland were based on smaller sample sizes but suggested a fall in penicillin non-susceptibility from 1999 to 2004, with conflicting evidence for macrolide resistance. The recent decreasing trend in penicillin resistance is in contrast to a rising trend in England and Wales until (at least) 1997 and strongly rising macrolide resistance from 1989 to 1993. UK pharmacy sales of macrolides and oral β-lactams fell by ca. 30% in the late 1990s following increased concern about resistance, before stabilising or rising weakly; sales in Ireland were stable or rose slightly in the study period. We conclude that falling penicillin resistance in pneumococci followed reduced sales of oral β-lactams to pharmacies in the UK, but a similar fall in macrolide sales was not associated with any fall in resistance. Stabilisation or decline in penicillin resistance has occurred in Ireland despite stable or increasing oral β-lactam sales. [Copyright &y& Elsevier]

Abstract: Susceptibility to moxifloxacin, penicillin and erythromycin was determined for 592 invasive Streptococcus pneumoniae collected from 20 English hospitals participating in the European Antimicrobial Resistance Surveillance System (EARSS) during 2003. Resistance to moxifloxacin, penicillin and erythromycin was observed in 0.8%, 5.4% and 13% of the isolates, respectively. These results show that the large majority of pneumococci were susceptible to moxifloxacin in 2003, the year when it was licensed for clinical use in the UK. [Copyright &y& Elsevier]