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Objectives: Bacterial skin and skin-structure infections (SSSIs) are frequent settings for antibiotic use. We surveyed their UK aetiology and pathogen susceptibility, including susceptibility to ceftaroline.Methods: Consecutive SSSI isolates were collected at 35 UK hospitals, to a maximum of 60/site, together with 15 'supplementary' MRSA/site. Isolates were re-identified and BSAC susceptibility testing was performed, with parallel CLSI agar testing for ceftaroline.Results: Isolates (n = 1908) were collected from 1756 hospitalized patients, predominantly with surgical and traumatic infections, abscesses and infected ulcers and largely from general medicine and general surgery patients. They included 1271 Staphylococcus aureus (201 MRSA), 162 β-haemolytic streptococci, 269 Enterobacteriaceae, 138 Pseudomonas aeruginosa and 37 enterococci. Most (944/1756) patients had monomicrobial MSSA infections. Rates of resistance to quinolones, gentamicin and cephalosporins were <20% in Enterobacteriaceae and <10% in P. aeruginosa. MRSA rates varied greatly among hospitals and were 2.5-fold higher in general medicine than in general surgery patients. At breakpoint, ceftaroline inhibited: (i) all MSSA and 97.6% of MRSA, with MICs of 2 mg/L for the few resistant MRSA; (ii) all β-haemolytic streptococci; and (iii) 83% of Enterobacteriaceae. High-level ceftaroline resistance in Enterobacteriaceae involved ESBLs or AmpC enzymes. Ceftaroline MICs by CLSI methodology generally equalled those by BSAC or were 2-fold higher, but this differential was 4-16-fold for P. aeruginosa.Conclusions: Irrespective of patient group, SSSIs were dominated by S. aureus. Most pathogens were susceptible, but 15.8% of S. aureus were MRSA, with locally higher prevalence. [ABSTRACT FROM AUTHOR]

Abstract: Carbapenem-resistant Enterobacteriaceae present an increasing and diverse problem, including strains of multiple species with metallo-β-lactamases (IMP, NDM or VIM) and non-metallo (KPC and OXA-48) enzymes as well as those combining an extended-spectrum β-lactamase (ESBL) or AmpC enzyme with porin loss. Most strains, except those with OXA-48 alone, are broadly resistant to β-lactams and have multiple aminoglycoside-modifying enzymes; those with NDM-1 carbapenemase typically also have 16S rRNA methylases, conferring complete aminoglycoside resistance. In this study, the activity of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline was evaluated against 81 carbapenem-resistant Enterobacteriaceae isolates from the UK. Testing was performed by the Clinical and Laboratory Standards Institute (CLSI) agar dilution method. Chloramphenicol, ciprofloxacin and nitrofurantoin inhibited <25% of the isolates at the breakpoint, whereas colistin was active against 75/81 isolates (92.6%), the exceptions being four Klebsiella pneumoniae and Enterobacter cloacae isolates along with members of inherently resistant genera. Fosfomycin was active against 49/81 isolates (60.5%), including 7/7 Escherichia coli, 16/20 Enterobacter and Citrobacter spp., but only 25/52 Klebsiella spp. Tigecycline was active against 38/81 isolates (46.9%) and was intermediate against another 27 (33.3%), with resistance scattered amongst K. pneumoniae and Enterobacter spp. The activity of colistin, fosfomycin and tigecycline was unrelated to the isolates’ carbapenem resistance mechanisms. Temocillin was fully active [minimum inhibitory concentration (MIC) ≤8mg/L] against only 4/81 isolates (4.9%), but inhibited a further 22 isolates (27.2%) at the British Society for Antimicrobial Chemotherapy (BSAC) urinary breakpoint (32mg/L), predominantly comprising those isolates with combinations of impermeability and an ESBL or AmpC enzyme, along with 6/11 isolates producing KPC carbapenemases. Studies with transconjugants and transformants confirmed the small effect of KPC enzymes against temocillin, whereas OXA-48 and NDM-1 conferred clear resistance. [Copyright &y& Elsevier]

The article discusses the case of an 86-year-old man diagnosed with chronic obstructive pulmonary disease who developed four sequential extended-spectrum ̫-lactamase-producing isolates of Klebsiella pneumoniae obtained after treatment using the cultured ertapenem. Ertapenem is a broad-spectrum carbapenem that is active against most common pathogens, except enterococci, nonfermenters, and methicillin-resistant staphylococci. The case is disturbing because of the difference in the characteristics of the four isolates, with the first and fourth isolates being susceptible to ertapenem, whereas the second and third were resistant.

Linezolid, the first oxazolidinone antibacterial agent to be developed for clinical use, was licensed in the UK in early 2001. We report the first three examples of resistant enterococci (two isolates of Enterococcus faecium and one Enterococcus faecalis) isolated in the UK, which were obtained from patients who had received linezolid. The linezolid MICs for the resistant isolates were 64 mg/L. Pulsed-field gel electrophoresis (PFGE) analysis of the linezolid-susceptible and -resistant isolates from two of the patients, combined with sequence analysis of rRNA, indicated that resistance developed in previously susceptible strains, most probably via a point mutation in the 23S rRNA. [ABSTRACT FROM AUTHOR]

A survey was conducted of the antimicrobial susceptibilities of 595 Acinetobacter spp. isolated from routine clinical specimens in 54 sentinel laboratories throughout the UK during 2000. Isolates of the Acinetobacter baumannii complex (genomic groups 2, 3 and 13TU; n = 443) were distinguished from other genomic groups (n = 152) by PCR fingerprinting of tDNA spacer regions. MICs of amikacin, cefotaxime, ceftazidime, ciprofloxacin, colistin, gentamicin, imipenem, meropenem, minocycline, piperacillin, piperacillin/tazobactam, rifampicin, sulbactam and tetracycline were determined on IsoSensitest agar and interpreted, wherever possible, using BSAC breakpoints. Tigecycline (GAR-936), a new glycylcycline, was also tested. Resistance to cephalosporins, aminoglycosides and ciprofloxacin was widespread, but carbapenems, colistin, sulbactam, minocycline and tigecycline were each active against >80% of the isolates. Isolates of A. baumannii were more often resistant to cefotaxime, ceftazidime, piperacillin, piperacillin/tazobactam, ciprofloxacin, gentamicin and tetracyclines than those belonging to other genomic groups, but were less often resistant to colistin; no significant differences between genomic groups were noted in the susceptibilities to amikacin, carbapenems, rifampicin or sulbactam. The relative activities of the tetracyclines were minocycline > tigecycline > tetracycline. Thirteen carbapenem-resistant isolates (MICs > or =8 mg/L; 2.2%) were received from six centres; four centres sent single isolates; one sent three and one sent six. An allele of bla(IMP) was detected in one of these isolates, but the other 12 isolates either had carbapenemase-independent resistance, or undetectable carbapenemase activity combined with other resistance mechanisms. In conclusion, carbapenems, colistin and minocycline retained greatest activity against the Acinetobacter isolates collected. Tigecycline was less active than minocycline, but both agents overcame most tetracycline resistance. [ABSTRACT FROM AUTHOR]

SummaryThe prevalence of antibiotic-resistant bacteria in wild animal and bird populations is largely unknown, with little consistency among the few published reports. We therefore examined intestinal bacteria from magpies (Pica pica) and rabbits (Oryctolagus cuniculus) collected in rural west Wales. Escherichia coli isolates resistant to multiple antibiotics were grown from eight of 20 magpies trapped in spring, 1999 and one of 17 in spring, 2000; the most prevalent resistance trait among these isolates was to tetracycline, but resistances to ampicillin, chloramphenicol, kanamycin, sulphonamide, tetracycline and trimethoprim were also found. Tetracycline-resistant Enterococcus spp. were found in one of 20 magpies in 1999 and three of 17 in 2000. Only one resistant E. coli isolate was detected among gut bacteria from 13 rabbits, and this strain was resistant only to tetracycline. Differences in the prevalence of resistance between bacteria from rabbits and magpies may reflect differences in diet: rabbits graze field edges, whereas magpies are omnivorous and opportunistic. The resistance genes found in E. coli isolates from magpies mostly corresponded to those common among human isolates, but those conferring tetracycline resistance were unique. [ABSTRACT FROM AUTHOR]

A survey was conducted in 1999, first to establish the prevalence of antibiotic resistance among clinical isolates of Pseudomonas aeruginosa in the UK and secondly to test whether the use of the standardized British Society for Antimicrobial Chemotherapy (BSAC) disc testing method improved the accuracy of routine susceptibility testing for this organism. Twenty-five hospitals were each asked to collect up to 100 consecutive, clinically significant isolates of P. aeruginosa and to test their susceptibility to amikacin, gentamicin, ceftazidime, imipenem, meropenem, ciprofloxacin, piperacillin and piperacillin/tazobactam using the new BSAC disc method. A total of 2194 isolate reports were available for analysis and 10% of the isolates represented, plus those with unusual resistances, were re-tested centrally for quality control purposes. The zone distributions were essentially unimodal, indicating the absence of major populations with acquired resistance. The results indicated that resistance rates to the β-lactam, aminoglycoside and quinolone agents tested in P. aeruginosa in the UK remain low (<12%), and were mostly unchanged since a previous survey conducted in 1993. High resistance rates were nevertheless reported for isolates from cystic fibrosis patients. The accuracy of susceptibility testing using the new BSAC disc testing method was better than in previous studies, when Stokes' method was most frequently used. Critically, the proportion of resistant isolates incorrectly reported as susceptible was reduced significantly; nevertheless, depending on the antibiotic, up to 49% of the isolates reported as intermediate or resistant were found susceptible on central re-testing. [ABSTRACT FROM PUBLISHER]

Presents a study which focuses on the antibiotic resistance among enterococci causing endocarditis in Great Britain. Description of the treatment for enterococcal endocarditis; Results of the study; Emergence of frequent resistance to the recommended syngistic combinations.

Background Razupenem (previously known as PTZ601, PZ-601, SMP-601 or SM-216601) is a novel carbapenem, active against Enterobacteriaceae as well as Gram-positive bacteria including methicillin-resistant staphylococci and enterococci. Methods We examined the effect of extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases on the activity of razupenem, using the CLSI agar dilution method to measure MICs for mutants, transconjugants and isolates with and without these enzymes. Results ESBLs had no effect on the activity of razupenem against Escherichia coli and Klebsiella spp., and only a small effect when coupled with outer membrane impermeability. Inducible or, more especially, derepressed AmpC enzymes gave some protection, with most AmpC-derepressed Enterobacter and Citrobacter spp. requiring MICs of ∼8 mg/L. This relative resistance was further increased when porins were lost, restricting drug uptake. Metallo- and class A-carbapenemases conferred resistance, with MICs ≥16 mg/L. Conclusions Razupenem has good activity against ESBL producers, but is affected by AmpC enzymes, especially when derepressed and coupled with outer membrane impermeability; its activity is also compromised by carbapenemases. [ABSTRACT FROM AUTHOR]

Abstract: Twenty-five years after its introduction, ceftazidime remains the most active cephalosporin against Pseudomonas aeruginosa. Nevertheless, resistance arises by upregulation of AmpC β-lactamase, by efflux or, less often, via acquisition of additional β-lactamases. Mutational resistance is especially prevalent among cystic fibrosis (CF) isolates. We examined the activity of a novel oxyimino-aminothiazolyl cephalosporin, CXA-101 (FR264205), against P. aeruginosa strains with defined resistance mechanisms as well as against multiresistant clinical CF isolates of P. aeruginosa and Burkholderia cepacia. Minimum inhibitory concentrations (MICs) of CXA-101 were determined by the Clinical and Laboratory Standards Institute agar dilution method and were 0.25–0.5mg/L for ‘typical’P. aeruginosa strains without acquired resistance, compared with 1–2mg/L for ceftazidime. MICs of CXA-101 were 0.5–2mg/L and 4mg/L, respectively, for isolates with upregulated efflux or total AmpC derepression, compared with 2–16mg/L and 32–128mg/L for ceftazidime. Full activity was retained against OprD mutants resistant to imipenem. Substantive resistance (MICs≥32mg/L) arose for transconjugants with PER, VEB and OXA extended-spectrum β-lactamases and for metallo-β-lactamase producers, with reduced susceptibility (MIC=8mg/L) for transconjugants with OXA-2, OXA-3 and NPS-1 enzymes. MICs of CXA-101 were 2- to 16-fold below those of ceftazidime for multiresistant P. aeruginosa from CF patients, but ranged up to >128mg/L; values for B. cepacia from CF resembled those for ceftazidime. [Copyright &y& Elsevier]