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Biomedical subjects

D M Livermore

Publications and source records attributed to D M Livermore.

At least 55 records · Page 3Linked to original sources
PubMed2001

Antibiotic resistance in bacteria from magpies (Pica pica) and rabbits (Oryctolagus cuniculus) from west Wales.

The 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.

Animals↗
PubMed2001

Activity of moxifloxacin against clinical isolates of Streptococcus pneumoniae from England and Wales.

The activity of moxifloxacin was assessed against 1269 isolates of Streptococcus pneumoniae, comprising 462 isolates referred from UK hospitals, primarily for confirmation of resistance to first line agents, and 807 isolates from an enhanced surveillance of invasive infections. Resistance rates to penicillin, erythromycin, tetracycline and chloramphenicol were 88.7% (32.6% intermediate and 56.1% fully resistant), 50, 48 and 22.7%, respectively, for the former, and 8.0 (4.5% intermediate and 3.5% fully resistant), 14.7, 9.0 and 0.6% for the latter. Ninety-four per cent of the referred isolates and 99% of the surveillance isolates were susceptible to moxifloxacin at <or=1 mg/L. Moxifloxacin may therefore be a useful drug for the treatment of patients with pneumococcal infections due to antibiotic-resistant strains or those with severe invasive disease.

Anti-Infective Agents↗
PubMed2001

Antimicrobial susceptibility of Pseudomonas aeruginosa: results of a UK survey and evaluation of the British Society for Antimicrobial Chemotherapy disc susceptibility test.

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 beta-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.

Anti-Bacterial Agents↗
PubMed2001

Detection of beta-lactamase-mediated resistance.

beta-Lactams are the most widely used antibiotics, and beta-lactamases are the greatest source of resistance to them. An understanding of beta-lactamase detection and identification is therefore valuable. Colorimetric, acidimetric and iodometric tests of beta-lactamase production are good, rapid indicators of penicillin and ampicillin resistance in Haemophilus, Moraxella and Neisseria spp. These methods can also be applied to Gram-negative aerobic bacilli but are less useful, since the usual question is not whether a beta-lactamase is produced by these organisms, but which beta-lactamase? Accurate identification of the beta-lactamases of Enterobacteriaceae demands gene or protein sequencing, but the broad type of enzyme produced by an isolate can often be inferred from antibiotic susceptibility data. Resistance to ceftazidime or cefpodoxime implies extended-spectrum beta-lactamase (ESBL) production in Escherichia coli and Klebsiella spp., especially if susceptibility to cefoxitin is retained. ESBL production can be confirmed with double disc tests or with various commercial kits. Derepression of AmpC beta-lactamases in Enterobacter spp. and Citrobacter freundii is another important mechanism and can be inferred from cross-resistance to beta-lactamase inhibitor combinations and to all cephalosporins except fourth-generation agents. Antagonism between cefoxitin and cefotaxime can be used to infer the presence of inducible AmpC enzymes in these species, indicating the risk of segregation of derepressed mutants, but in general this risk is better predicted from accurate speciation.

Bacteria↗
PubMed2001

Interpretative reading: recognizing the unusual and inferring resistance mechanisms from resistance phenotypes.

If isolates are speciated and if a sufficient range of antibiotics is tested, underlying resistance mechanisms can often be inferred from the antibiogram data. This allows: (i) anomalous combinations of phenotype and organism to be reconsidered; (ii) prediction of further antibiotics that deserve testing; and (iii) the suppression of susceptibilities that are anomalous in the light of the inferred mechanism. This 'interpretative reading' is widely undertaken in France but is largely precluded in the UK by limited speciation and the testing of narrow ranges of antibiotics. Nevertheless, UK laboratories should be aware of: (i) grossly anomalous combinations of species and phenotype, demanding reference laboratory confirmation; (ii) useful indicator drugs, where resistance implies a mechanism conferring other resistances that may be less obvious in direct tests; and (iii) antibiotics that are prone to select resistant mutants of particular species during therapy. Details of these combinations of organism and resistance are presented. Relationships between antibiogram and mechanism are also presented to allow full interpretative reading for those testing wide panels of drugs versus speciated isolates.

Aminoglycosides↗
PubMed2001

SHV-14, a novel beta-lactamase variant in Klebsiella pneumoniae isolates from Nijmegen, The Netherlands.

Four ceftazidime-resistant isolates of a Klebsiella pneumoniae strain were collected from intensive care unit patients in Nijmegen, The Netherlands. These isolates had TEM-29 and SHV-14 beta-lactamases. SHV-14 is a novel variant, with two substitutions compared with the sequence of SHV-1: Ile8Phe and Arg43Ser. Its gene also had a silent C-->T mutation at nucleotide 481. The SHV-14 enzyme had slightly higher V(max) rates than SHV-1 for oxyimino-aminothiazolyl cephalosporins, but this activity was insufficient for the enzyme to count as an extended-spectrum beta-lactamase.

Kinetics↗
PubMed2001

Complexity and diversity of Klebsiella pneumoniae strains with extended-spectrum beta-lactamases isolated in 1994 and 1996 at a teaching hospital in Durban, South Africa.

beta-Lactamase production was investigated in cultures of 25 Klebsiella pneumoniae isolates isolated at a hospital in Durban, South Africa, in 1994 and 1996. Twenty of these isolates gave ceftazidime MIC/ceftazidime plus clavulanate MIC ratios of >/=8, implying production of extended-spectrum beta-lactamases (ESBLs), and DNA sequencing identified an ESBL gene (bla(TEM-53)) in a further two isolates. Pulsed-field gel electrophoresis (PFGE) defined 4 distinct strains among the 12 isolates collected in 1994 and 9 distinct strains among the 13 isolates collected in 1996. In three cases, multiple isolates from single patients varied in their PFGE profiles and antibiograms, implying mixed colonization or infection. Isoelectric focusing and DNA hybridization found both TEM and SHV enzymes and their genes in all 25 isolates. Many isolates had multiple identical or different beta-lactamase gene variants, with at least 84 bla(SHV) and bla(TEM) gene copies among the 25 organisms. Sequencing identified the genes for the SHV-1, -2, and -5 enzymes and for four new SHV types (SHV-19, -20, -21, and -22). These new SHV variants had novel mutations remote from sites known to affect catalytic activity. Sequencing also found the genes for TEM-1, TEM-53, and one novel type, TEM-63. All the isolates had multiple and diverse plasmids. These complex and diverse patterns of ESBL production and strain epidemiology are far removed from the concept of an ESBL outbreak and suggest a situation in which ESBL production has become endemic and in which evolution is generating a wide range of enzyme combinations. This complexity and diversity complicates patient management and the design of antibiotic use policies.

Amino Acid Substitution↗
PubMed2001

Activity of ertapenem (MK-0826) versus Enterobacteriaceae with potent beta-lactamases.

Ertapenem (MK-0826; L-749,345), a new carbapenem with a long serum half-life, was tested, in vitro, against beta-lactamase-producing bacteria. The new compound had a MIC at which 90% of the isolates were inhibited of 0.06 microg/ml for extended-spectrum beta-lactamase (ESBL)-producing klebsiellas, compared with 0.5 microg/ml for imipenem, 16 microg/ml for cefepime, and >128 microg/ml for ceftazidime and piperacillin-tazobactam. MICs of ertapenem for AmpC-derepressed mutant Enterobacteriaceae were 0.015 to 0.5 microg/ml, whereas imipenem MICs were 0.25 to 1 microg/ml and those of cefepime were 0.5 to 4 microg/ml, and resistance to ceftazidime and piperacillin-tazobactam was generalized. Despite this good activity, the MICs of ertapenem for ESBL-positive klebsiellas mostly were two- to fourfold above those for ESBL-negative strains, and the MICs for AmpC-hyperproducing Enterobacter cloacae and Citrobacter freundii mutants exceeded those for the corresponding AmpC-basal mutants. These differentials did not increase when the inoculum was raised from 10(4) to 10(6) CFU/spot, contraindicating significant lability. Carbapenemase producers were also tested. The IMP-1 metallo-beta-lactamase conferred substantial ertapenem resistance (MIC, 128 microg/ml) in a porin-deficient Klebsiella pneumoniae strain, whereas a MIC of 6 microg/ml was recorded for its porin-expressing revertant. SME-1 carbapenemase was associated with an ertapenem MIC of 2 microg/ml for Serratia marcescens S6, compared with <0.03 microg/ml for Serratia strains lacking this enzyme. In summary, ertapenem had good activity against strains with potent beta-lactamases, except for those with known carbapenemases.

Bacterial Proteins↗
PubMed2001

Characterization of OXA-25, OXA-26, and OXA-27, molecular class D beta-lactamases associated with carbapenem resistance in clinical isolates of Acinetobacter baumannii.

Carbapenem resistance in Acinetobacter spp. is increasingly being associated with OXA-type beta-lactamases with weak hydrolytic activity against imipenem and meropenem. Such enzymes were characterized from Acinetobacter isolates collected in Belgium, Kuwait, Singapore, and Spain. The isolates from Spain and Belgium had novel class D beta-lactamases that were active against carbapenems. These were designated OXA-25 and OXA-26, respectively, and had >98% amino acid homology with each other and with the OXA-24 enzyme recently described by others from an Acinetobacter isolate collected elsewhere in Spain. The isolate from Singapore had OXA-27 beta-lactamase, another novel class D type with only 60% homology to OXA-24, -25, and -26, but with 99% homology to OXA-23 (ARI-1), described previously from an Acinetobacter baumannii isolate collected in Scotland. Sequence data were not obtained for the carbapenem-hydrolyzing OXA enzyme from the isolate from Kuwait; nevertheless, the enzyme was phenotypically similar to OXA-25 and -26. The enzymes OXA-23, -24, -25, -26, and -27 retained the STFK and SXV motifs typical of class D beta-lactamases, but the YGN motif was altered to FGN. The KTG motif was retained by OXA-27 and -23 but was replaced by KSG in OXA-24, -25, and -26. OXA-25 and -26 enzymes were strongly active against oxacillin, but unusually for an OXA-type beta-lactamase, OXA-27 had apparently weak activity, although measurement was complicated by biphasic kinetics. None of the new enzymes was transmissible to Escherichia coli recipients. Many Acinetobacter isolates are multiresistant to other antibiotics, and the emergence of class D enzymes with carbapenem-hydrolyzing activity is a disturbing development for antimicrobial chemotherapy.

Acinetobacter↗
PubMed2001

IMP-4, a novel metallo-beta-lactamase from nosocomial Acinetobacter spp. collected in Hong Kong between 1994 and 1998.

Between 1994 and 1998, 97 imipenem-resistant Acinetobacter isolates were identified at the Prince of Wales Hospital, Hong Kong, China. A bla(IMP) PCR product was obtained from 23 of 35 viable cultures; 12 isolates belonged to genomic DNA group 3, 8 belonged to group 2 (Acinetobacter baumannii), 2 belonged to group 13TU, and 1 belonged to group 1. The bla(IMP) homologues were sequenced from two isolates from genomic DNA group 2 and one isolate each from groups 3 and 13TU. The four sequences included an identical 738-bp open reading frame, predicted to encode a polypeptide of 246 amino acids, with 95.6% homology to IMP-1 and 89.3% homology to IMP-2. The new enzyme, designated IMP-4, was partially purified. It had a pI of 8.0 and was strongly active against imipenem and meropenem, with V(max) values 53 and 8% of that for penicillin G, respectively. Strong activity was also seen against oxyimino-aminothiazolyl cephalosporins but not against aztreonam. Hydrolytic activity was inhibited by EDTA but not by clavulanate or tazobactam. Carbapenem MICs for most bla(IMP)-positive isolates were 4 to 32 microg/ml, but one isolate with the intact gene was susceptible, with imipenem and meropenem MICs of 0.25 and 0.5 microg/ml, respectively. The latter isolate did not produce the band with a pI of 8.0, and gene expression was inferred to have been lost. None of the isolates studied in detail contained extrachromosomal DNA, and carbapenem resistance was not transmissible to Escherichia coli. Nevertheless, the presence of bla(IMP-4) in different genomic DNA groups implies horizontal transfer, and sequences resembling a GTTRRRY integrase-dependent recombination motif were identified in the flanking regions of bla(IMP-4).

Acinetobacter↗
PubMed2001

In vitro activities of ertapenem (MK-0826) against recent clinical bacteria collected in Europe and Australia.

Ertapenem (MK-0826, L-749,345) is a 1-beta-methyl carbapenem with a long serum half-life. Its in vitro activity was determined by broth microdilution against 3,478 bacteria from 12 centers in Europe and Australia, with imipenem, cefepime, ceftriaxone, and piperacillin-tazobactam used as comparators. Ertapenem was the most active agent tested against members of the family Enterobacteriaceae, with MICs at which 90% of isolates are inhibited (MIC(90)s) of < or =1 microg/ml for all species. Ertapenem also was more active than imipenem against fastidious gram-negative bacteria and Moraxella spp.; on the other hand, ertapenem was slightly less active than imipenem against streptococci, methicillin-susceptible staphylococci, and anaerobes, but its MIC(90)s for these groups remained < or =0.5 microg/ml. Acinetobacter spp. and Pseudomonas aeruginosa were also much less susceptible to ertapenem than imipenem, and most Enterococcus faecalis strains were resistant. Ertapenem resistance, based on a provisional NCCLS MIC breakpoint of > or =16 microg/ml, was seen in only 3 of 1,611 strains of the family Enterobacteriaceae tested, all of them Enterobacter aerogenes. Resistance was also seen in 2 of 135 anaerobes, comprising 1 Bacteroides fragilis strain and 1 Clostridium difficile strain. Ertapenem breakpoints for streptococci have not been established, but an unofficial susceptibility breakpoint of < or =2 microg/ml was adopted for clinical trials to generate corresponding clinical response data for isolates for which MICs were as high as 2 microg/ml. Of 234 Streptococcus pneumoniae strains tested, 2 required ertapenem MICs of 2 microg/ml and one required an MIC of 4 microg/ml, among 67 non-Streptococcus pyogenes, non-Streptococcus pneumoniae streptococci, single isolates required ertapenem MICs of 2 and 16 microg/ml. These streptococci also had diminished susceptibilities to other beta-lactams, including imipenem as well as ertapenem. The Etest and disk diffusion gave susceptibility test results in good agreement with those of the broth microdilution method for ertapenem.

Anti-Bacterial Agents↗
PubMed2000

Bacteraemia and antibiotic resistance of its pathogens reported in England and Wales between 1990 and 1998: trend analysis.

OBJECTIVES: Determination of causes, trends, and antibiotic resistance in reports of bacterial pathogens isolated from blood in England and Wales from 1990 to 1998. DESIGN: Description of bacterial isolates from blood, judged to be clinically significant by microbiology staff, reported to the Communicable Disease Surveillance Centre. SETTING: Microbiology laboratories in England and Wales. SUBJECTS: Patients yielding clinically significant isolates from blood. MAIN OUTCOME MEASURES: Frequency and Poisson regression analyses for trend of reported causes of bacteraemia and proportions of antibiotic resistant isolates. RESULTS: There was an upward trend in total numbers of reports of bacteraemia. The five most cited organisms accounted for over 60% of reports each year. There was a substantial increase in the proportion of reports of Staphylococcus aureus resistant to methicillin, Streptococcus pneumoniae resistance to penicillin and erythromycin, and Enterococcus faecalis and Enterococcus faecium resistance to vancomycin. No increase was seen in resistance of Escherichia coli to gentamicin. CONCLUSIONS: Reports from laboratories provide valuable information on trends and antibiotic resistance in bacteraemia and show a worrying increase in resistance to important antibiotics.

Bacteremia↗