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Biomedical subjects

D M Livermore

Publications and source records attributed to D M Livermore.

At least 73 records · Page 4Linked to original sources
PubMed2000

Epidemiology of antibiotic resistance.

Three biological processes contribute to the accumulation of bacterial drug resistance: new selection, gene epidemics and strain epidemics. New resistance emerges by (i) the advantaging of entire species, (ii) by mutation, and (iii) by the escape of resistance genes to mobile DNA. Organisms to have 'benefited' from modern patterns of cephalosporins and quinolone use include enterococci, Clostridium difficile, coagulase-negative staphylococci and Enterobacter spp. Mutational resistance notoriously occurs with certain antibiotic/organism combinations and allows rapid multifocal accumulation of resistance. At worst, therapy can fail when resistant mutants are selected in individual patients. Escape of new genes to mobile DNA is rare but, having occurred, permits massive 'gene epidemics', as the same genes and plasmids spread into diverse pathogens. Strain epidemics notoriously occur in individual units, reflecting break-downs of hygiene. Some strains achieve a much wider distribution: thus, much of the MRSA problem in the UK depends on the dissemination of two epidemic strains, EMRSA15 and 16; penicillin resistant pneumococci of serotypes 6 and 23 have disseminated internationally from Spain and a serotype K25 strain of Klebsiella pneumoniae with SHV-4 beta-lactamase has spread widely in France. It remains unknown why some strains and genes achieve wide spread whereas others, equally resistant, fail to do so. There is no simple cure for resistance but the best opportunities for control lie in lesser and better use of antibiotics backed by swifter and more accurate microbiology; in developing new antibiotics; and in protecting old ones from resistance determinants. All this must be supported by good local knowledge of the epidemiology of infections and resistance and of the likelihood of particular antibiotics to select resistance.

Anti-Bacterial Agents↗
PubMed2000

Antibiotic resistance in staphylococci.

When penicillin was introduced in 1944 over 94% of Staphylococcus aureus isolates were susceptible; by 1950 half were resistant. By 1960 many hospitals had outbreaks of virulent multi-resistant S. aureus. These were overcome with penicillinase-stable penicillins, but victory was brief; methicillin-resistant S. aureus (MRSA) were recorded in the year of the drug's launch. MRSA owe their behaviour to an additional, penicillin-resistant peptidoglycan transpeptidase, PBP-2', encoded by mecA. Their spread is clonal, with transfer of mecA being extremely rare. MRSA accumulated and then declined in the 1960s and 1970s, but became re-established in the early 1980s. Some early MRSA strains were colonists rather than invaders and the proportion of MRSA among S. aureus bacteraemias in England remained under 3% until 1992. However, this proportion rose to 34-37% by 1998-1999, reflecting the dissemination of two new epidemic strains, EMRSA 15 and 16. These may be more virulent than earlier MRSA, or their success may reflect changing hospital practice. Until 1996, glycopeptides were universally active against S. aureus; then glycopeptide-intermediate S. aureus (GISA) were found in Japan, France, and the USA. This resistance is associated with increased wall synthesis. Coagulase-negative staphylococci (CNS) are less pathogenic than S. aureus but are important in line-associated bacteraemias and prosthetic device infections. They are even more often resistant than S. aureus, notably to teicoplanin. Few anti-staphylococcal agents were launched from 1970 to 1995, but the situation is now improving. Dalfopristin/quinupristin inhibits virtually all S. aureus, although its bactericidal activity is impaired against strains with constitutive MLSB-type resistance; other new agents are in advanced development. New agents give a renewed opportunity for control, but S. aureus is a resilient foe, able to regain its importance if drugs are used profligately or if hygiene is slackened.

Anti-Bacterial Agents↗
PubMed2000

Carbapenemases: a problem in waiting?

Carbapenems are stable to most prevalent beta-lactamases, and chromosomal carbapenemases are restricted to Stenotrophomonas maltophilia, to a few Bacteroides fragilis, and to rare pathogens. Nevertheless, an acquired metallo-beta-lactamase called IMP-1 is beginning to emerge in Pseudomonas aeruginosa and Enterobacteriaceae isolates in Japan, and has also been found in isolates from Singapore. Furthermore, IMP-producing Acinetobacter spp. have been identified in Italy and Hong Kong. Recently a second group of acquired metallo-carbapenemases, the VIM types, has been recorded from P. aeruginosa isolates in five Eurasian countries. Weak carbapenemases belonging to molecular class D are emerging in A. baumannii world-wide, with two sub-groups apparent. A few acquired carbapenemases belonging to molecular class A also have been reported. Finally it has also been shown that enzymes with feeble carbapenemase activity (e.g. AmpC types and some SHV enzymes) may confer resistance in exceptionally impermeable strains; counterwise, even potent carbapenemases, such as IMP-1, may only give a small reduction in susceptibility in Enterobacteriaceae that lack permeability lesions. Is the emergence of carbapenemase a problem waiting to happen?

Carbapenems↗
PubMed2000

Effect of conalbumin on the activity of Syn 2190, a 1,5 dihydroxy-4-pyridon monobactam inhibitor of AmpC beta-lactamases.

Syn 2190, a 1,5 dihydroxy-4-pyridon monobactam inhibitor of AmpC enzymes, was tested against beta-lactamase-producing bacteria with piperacillin, piperacillin-tazobactam and ceftazidime as partner drugs. In the presence of conalbumin as an iron chelator, Syn 2190 potentiated these drugs against most AmpC producers, although Klebsiella spp. with plasmidic AmpC enzymes were an exception. Potentiation was much weaker without conalbumin, suggesting that Syn 2190 exploits a ferric uptake pathway, as do catecholic cephalosporins. Syn 2190 had little ability to potentiate partner drugs against strains with other beta-lactamase types but, with conalbumin, increased the activity of piperacillin-tazobactam against Escherichia coli transconjugants producing various class A or D enzymes.

Bacterial Proteins↗
PubMed2000

Antimicrobial resistance amongst Klebsiella spp. collected from intensive care units in Southern and Western Europe in 1997-1998.

A 1994 survey of 35 intensive care units (ICUs) in Western and Southern Europe found extended-spectrum beta-lactamases (ESBLs) in 220/966 (23%) klebsiellae. A follow-up survey from May 1997 to October 1998 collected klebsiellae from 24 ICUs, including 23 that participated in 1994. Twenty-one ICUs sent 433 eligible isolates, of which 110 (25%) had ESBLs. The prevalence of ESBLs had not changed significantly from 1994 but the proportion of ESBL-producers resistant to piperacillin/tazobactam had risen from 31% to 63% (P < 0.001), and most of this resistance was high level (MICs >/= 128 + 4 mg/L). The proportion of Klebsiella oxytoca isolates hyperproducing K1 beta-lactamase rose from 8% in 1994 to 21% in 1997-1998 (P < 0. 001). Most klebsiellae (99%) were very susceptible to meropenem (mode MIC 0.03 mg/L) but three had decreased susceptibility (MICs 2-4 mg/L). These could not hydrolyse carbapenems. Aminoglycoside resistance was not significantly changed in prevalence from 1994; ciprofloxacin resistance occurred in 31% of ESBL-producers in both years, but had increased among non-producers (2% in 1994 versus 7% in 1997-1998, P < 0.001).

Anti-Bacterial Agents↗
PubMed2000

Are routine sensitivity test data suitable for the surveillance of resistance? Resistance rates amongst Escherichia coli from blood and CSF from 1991-1997, as assessed by routine and centralized testing.

Surveillance of antibiotic resistance can be undertaken by compilation of routine data or by central testing of isolates. Routine results can be obtained cheaply and in sufficient quantities for correlation with population and prescribing denominators but there is concern about their quality. As one of a series of ongoing studies to assess this quality, we compared the proportions of resistance amongst Escherichia coli from patients with bacteraemia or meningitis between 1991 and 1997 (i) as recorded in routine data reported to the PHLS and (ii) as found in tests performed at the PHLS Laboratory of Enteric Pathogens (LEP). These two data sets both showed an overall upward trend in the proportion of isolates resistant to ampicillin, trimethoprim, gentamicin and ciprofloxacin. The average annual percentage increase in resistance was estimated in separate logistic regression models, and 95% confidence intervals (CI) were determined. The annual percentage increases in the proportions of isolates reported resistant were similar in the two data sets for trimethoprim, gentamicin and ciprofloxacin but differed for ampicillin. The upward trends were statistically significant except for gentamicin resistance in the LEP data set, where the 95% CI straddled zero. The proportions of resistant isolates for each antibiotic in the two data sets each year were in poorer agreement than the trends; however, the 95% CI of the difference of proportions resistant between the routine and LEP data sets straddled zero in 4 or 5 of the 7 years studied. Some discrepancies might be explained by geographical bias in the sampling or by differences in definitions of resistance. Thus (i) the proportion of resistant isolates tested at LEP almost always fell within the ranges bounded by the highest and lowest proportions for individual Regional Health Authorities, as recorded in the routine data, and (ii) the fact that LEP consistently recorded less gentamicin resistance but more ciprofloxacin resistance than the routine could be explained by breakpoint differences. We conclude that routine susceptibility data for ampicillin, ciprofloxacin, gentamicin and trimethoprim appear sound for E. coli and might be suitable for correlation with other data, e.g. for prescribing.

Bacteremia↗
PubMed2000

Activity of linezolid against multi-resistant gram-positive bacteria from diverse hospitals in the United Kingdom.

The in vitro activity of linezolid, an oxazolidinone, was assessed against 374 gram-positive cocci, with an emphasis on testing multi-resistant, epidemiologically unrelated isolates. MICs of linezolid for staphylococci, pneumococci and streptococci had a narrow range, from 0.5 to 2 mg/L, whereas MICs for enterococci were uniformly 4 mg/L. For all the species tested, the MICs of linezolid were unrelated to those of other antimicrobials. Linezolid appears to be a potentially useful drug for infections caused by gram-positive cocci.

Acetamides↗
PubMed2000

Susceptibility to quinupristin/dalfopristin and other antibiotics of vancomycin-resistant enterococci from the UK, 1997 to mid-1999.

Susceptibility to quinupristin/dalfopristin and other antibiotics was studied for clinical isolates of vancomycin-resistant enterococci (VRE) referred by UK hospitals between January 1997 and June 1999. Single isolates of VRE from 858 patients in 136 hospitals were received, of which 76% were Enterococcus faecium and 21% were Enterococcus faecalis, the remainder comprising minor species. Most isolates were multi-resistant. After allowing for the effect of blood, which raised the MICs of quinupristin/dalfopristin four-fold, 98.3% of E. faecalis isolates and all the Enterococcus avium, Enterococcus casseliflavus and Enterococcus gallinarum appeared resistant to quinupristin/dalfopristin, whereas 98.8% of the E. faecium isolates and the single Enterococcus raffinosus isolate were susceptible.

Drug Therapy, Combination↗
PubMed2000

Regional variation in ampicillin and trimethoprim resistance in Escherichia coli in England from 1990 to 1997, in relation to antibacterial prescribing.

Over 200 hospitals in England report resistance data for bacteraemia and meningitis isolates to the Public Health Laboratory Service. We reviewed ampicillin and trimethoprim resistance rates from 1990 to 1997 for Escherichia coli, which is the species reported most frequently from these bacteraemias. Ampicillin resistance was relatively stable over time, but varied between Health Regions. The proportion of ampicillin-resistant E. coli in the East Anglia region remained </=42% in all years except one and that in the South Western region always remained <50%. At the other extreme, the proportions of ampicillin-resistant isolates in the Northern and Trent regions never fell below 59%. The prevalence of resistance to trimethoprim rose over time in most regions; again, however, the prevalence of resistant isolates was lowest in the East Anglia and South Western regions, whereas the highest resistance rates were reported from Mersey, NW Thames, NE Thames and North Western regions. These observations were related to data for community prescribing, which accounts for most ampicillin and trimethoprim use. Prescribing data for ampicillin and trimethoprim from 1987 to 1997 were obtained from the IMS-HEALTH Medical Data Index, and data for all antibacterial drugs between 1995 and 1997 from the Prescription Pricing Authority. Correlations between resistance rates and prescribing of specific antibiotics were weak, although there was some trend for regions with high total prescribing to have higher rates of ampicillin resistance. The South Western region was conspicuous both for low rates of resistance and low prescribing. Several factors may determine the lack of wider and more obvious relationships between resistance and prescribing. In particular, regions may be inappropriately large areas to test the relationship, isolates from bacteraemias may not be representative of those experiencing selection pressure in the community and the resistance data may have been distorted by nosocomial strains, although this seems unlikely with E. coli.

Ampicillin↗
PubMed2000

Susceptibility of gram-positive cocci from 25 UK hospitals to antimicrobial agents including linezolid. The Linezolid Study Group.

The prevalence of antibiotic resistance amongst Gram-positive cocci from 25 UK hospitals was studied over an 8 month period in 1999. A total of 3770 isolates were tested by the sentinel laboratories using the Etest; these bacteria comprised 1000 pneumococci, 1005 Staphylococcus aureus, 769 coagulase-negative staphylococci (CNS) and 996 enterococci. To ensure quality, 10% of the isolates were retested centrally, as were any found to express unusual resistance patterns. The prevalence of penicillin-resistant Streptococcus pneumoniae, vancomycin-resistant enterococci and methicillin-resistant S. aureus (MRSA) varied widely amongst the sentinel laboratories. The resistance rates to methicillin among S. aureus and CNS were 19.2 and 38.9%, respectively, with MRSA rates in individual sentinel sites ranging from 0 to 43%. No glycopeptide resistance was seen in S. aureus, but 6.5% of CNS isolates were teicoplanin resistant and 0.5% were vancomycin resistant. Vancomycin resistance was much more frequent among Enterococcus faecium (24.1%) than E. faecalis (0.5%) (P<0.05), with most resistant isolates carrying vanA. The rate of penicillin resistance in pneumococci was 8.9%, and this resistance was predominantly intermediate (7.9%), with only six hospitals reporting isolates with high level resistance. The prevalence of erythromycin resistance among pneumococci was 12.3%, with the majority of resistant isolates having the macrolide efflux mechanism mediated by mefE. All the organisms tested were susceptible to linezolid with MICs in the range 0.12-4 mg/L. The modal MICs of linezolid were 1 mg/L for CNS and pneumococci, and 2 mg/L for S. aureus and enterococci. Linezolid was the most potent agent tested against Gram-positive cocci, including multiresistant strains, and as such may prove a valuable therapeutic option for the management of Gram-positive infections in hospitals.

Acetamides↗
PubMed2000

SHV-13, a novel extended-spectrum beta-lactamase, in Klebsiella pneumoniae isolates from patients in an intensive care unit in Amsterdam.

Eleven clonally related Klebsiella pneumoniae isolates were examined. These had been isolated at an intensive care unit in Amsterdam in 1994. Their resistance was associated with a conjugative 170-kb plasmid which encoded a novel SHV beta-lactamase designated SHV-13. The SHV-13 enzyme had two substitutions compared with SHV-1: Leu35Gln and Gly238Ala. It hydrolyzed cefotaxime much more rapidly than ceftazidime or aztreonam.

Anti-Bacterial Agents↗
PubMed2000

Carbapenemases of Chryseobacterium (Flavobacterium) meningosepticum: distribution of blaB and characterization of a novel metallo-beta-lactamase gene, blaB3, in the type strain, NCTC 10016.

Genes encoding carbapenemases in 15 reference strains of Chryseobacterium (Flavobacterium) meningosepticum from the United Kingdom National Collection of Type Cultures and in one recent clinical isolate were investigated. All the strains hydrolyzed imipenem, but their levels of resistance to carbapenems varied, with imipenem and meropenem MICs ranging from 2 to >32 microg/ml. The blaB gene, which encodes a molecular-class B carbapenemase, was detected in only six reference strains and in clinical isolate 97/P/5448. The gene from 97/P/5448 had 98% nucleotide identity with the published sequence of blaB (from strain NCTC 10585) and was designated blaB2. A distinct carbapenemase gene, designated blaB3, was cloned from the type strain of C. meningosepticum, NCTC 10016. blaB3 had an open reading frame of 750 bp with 82% nucleotide identity to blaB and blaB2 and encoded a beta-lactamase of 249 amino acids, including the putative signal peptide. This beta-lactamase showed 87.6 and 86.7% amino acid homology with BlaB and BlaB2, respectively. blaB3 was detected in one other reference strain besides NCTC 10016, but the genetic basis of the carbapenemase activity detected in the other seven reference strains was not defined. Thus, neither blaB nor blaB3 was ubiquitous in the strains of C. meningosepticum studied, indicating that the reference strains may represent more than one bacterial species, each with its own intrinsic metallo-beta-lactamase. Further taxonomic studies of C. meningosepticum are necessary to resolve this topic. Chryseobacterium spp. are environmental organisms and occasional opportunist pathogens. They apparently represent a reservoir of diverse metallo-beta-lactamases, which potentially spread to gram-negative bacteria of greater clinical significance.

Amino Acid Sequence↗
PubMed2000

Detection of extended-spectrum beta-lactamases in klebsiellae with the Oxoid combination disk method.

The Oxoid combination disk method for detecting extended-spectrum beta-lactamases (ESBLs) depends on comparing the inhibition zones of cefpodoxime (10-microg) and cefpodoxime-plus-clavulanate (10- plus 1-microg) disks. The presence of clavulanate enlarged the zones for all of 180 ESBL-producing klebsiellae by >/=5 mm, whereas zones for cefpodoxime-susceptible isolates and cefpodoxime-resistant isolates with AmpC and K1 beta-lactamases were enlarged by </=1 mm. Good discrimination was achieved with either the NCCLS or the British disk method.

Bacterial Proteins↗
PubMed2000

Outbreak of infections caused by Pseudomonas aeruginosa producing VIM-1 carbapenemase in Greece.

Resistance to imipenem and meropenem was observed in 211 (16.5%) isolates of Pseudomonas aeruginosa recovered in a Greek university hospital during 1996 to 1998. In six isolates selected from throughout this period, high-level resistance to both carbapenems (MICs >/= 128 microg/ml) was associated with production of the class B beta-lactamase VIM-1. bla(VIM)-bearing isolates belonged to serotype O:12 and were indistinguishable by pulsed-field gel electrophoresis.

Anti-Bacterial Agents↗