PubMed Health⌕ Search

Biomedical subjects

Robin A Howe

Publications and source records attributed to Robin A Howe.

7 recordsLinked to original sources
PubMed2006

A multicenter study evaluating the current strategies for isolating Staphylococcus aureus strains with reduced susceptibility to glycopeptides.

Glycopeptide-intermediate Staphylococcus aureus (GISA) and heterogeneous GISA (hGISA) strains are notoriously difficult to detect in the diagnostic laboratory. The clinical importance of GISA, and particularly hGISA, will only be obvious when a definitive detection method is available. A few novel GISA and hGISA detection methods have been proposed; however, their validity has never been tested on a significant scale and in different laboratories. This study compares three screening methods for detecting GISA and hGISA strains in 12 laboratories, using a blind panel of 48 strains with known glycopeptide susceptibilities. The three screening methods used were brain heart infusion agar with 6 mg/liter vancomycin (BHIA6V) (CDC/CLSI), Mueller-Hinton agar with 5 mg/liter teicoplanin (MHA5T) (European Antimicrobial Resistance Surveillance System [EARSS]), and the macrodilution method Etest (MET) (EARSS), with population analysis profile-area under the curve analysis as the gold standard. Sensitivity and specificity were highest for MHA5T and MET, which identified 82.5% and 85.9% of strains, respectively. BHIA6V had poor sensitivity, particularly for hGISA (11.5% of strains were detected), and gave the largest interlaboratory variation in performance. MET exhibited the least interlaboratory variation. It is essential that laboratories use appropriate methods to detect GISA/hGISA strains so that the prevalence and clinical importance of these strains can be assessed properly.

Agar↗
PubMed2004

Analysis of sequence variation among smeDEF multi drug efflux pump genes and flanking DNA from defined 16S rRNA subgroups of clinical Stenotrophomonas maltophilia isolates.

OBJECTIVES: To determine the level of variation in the smeDEF efflux pump and smeT transcriptional regulator genes among three defined 16S rRNA sequence subgroups of clinical Stenotrophomonas maltophilia isolates. METHODS: smeDEF sequencing used a PCR genome walking approach. Determination of the sequence surrounding smeDEF used a flanking primer PCR method and specific primers anchored in smeD or smeF together with random primers. RESULTS: smeDEF is chromosomal and located in the same position in the chromosome in all three subgroups of isolates. Flanking smeD is a gene, smeT, encoding a putative transcriptional repressor for smeDEF. Variation at these loci among the isolates is considerably lower (up to 10%) than at intrinsic beta-lactamase loci (up to 30%) in the same isolates, implying greater functional constraint. The smeD-smeT intergenic region contains a highly conserved section, which maps with previously predicted promoter/operator regions, and a hypervariable untranslated region, which can be used to subgroup clinical isolates. CONCLUSIONS: These data provide further evidence that it is possible to group clinical isolates of the inherently variable species, S. maltophilia, based on genotypic properties. Isolate D457, in which most work concerning smeDEF expression has been performed, does not fall into S. maltophilia subgroup A, which is the most typical.

Base Sequence↗
PubMed2004

Vancomycin susceptibility within methicillin-resistant Staphylococcus aureus lineages.

Methicillin-resistant Staphylococcus aureus (MRSA) with reduced vancomycin susceptibility vancomycin-intermediate S. aureus (VISA) has been reported from many countries. Whether resistance is evolving regularly in different genetic backgrounds or in a single clone with a genetic predisposition, as early results suggest, is unclear. We have studied 101 MRSA with reduced vancomycin susceptibility from nine countries by multilocus sequence typing (MLST), characterization of SCCmec (staphylococcal chromosomal cassette mec), and agr (accessory gene regulator). We found nine genotypes by MLST, with isolates within all five major hospital MRSA lineages. Most isolates (88/101) belonged to two of the earliest MRSA clones that have global prevalence. Our results show that reduced susceptibility to vancomycin has emerged in many successful epidemic lineages with no clear clonal disposition. Increasing antimicrobial resistance in genetically distinct pandemic clones may lead to MRSA infections that will become increasingly difficult to treat.

Anti-Bacterial Agents↗
PubMed2003

Activity of AZD2563, a novel oxazolidinone, against Staphylococcus aureus strains with reduced susceptibility to vancomycin or linezolid.

The susceptibilities of clinical vancomycin-intermediate Staphylococcus aureus (VISA), heterogeneous VISA, and laboratory-generated linezolid-resistant S. aureus strains to the new oxazolidinone AZD2563 were assessed by agar dilution MIC determination. All clinical strains were susceptible to linezolid, and the linezolid MICs for them were equal to or twofold higher than those of AZD2563. Cross-resistance with linezolid was seen in laboratory-generated mutants, and for these strains the MIC of AZD2563 was twofold higher than that of linezolid.

Acetamides↗
PubMed2002

The prevalence and mechanisms of vancomycin resistance in Staphylococcus aureus.

The emergence of Staphylococcus aureus resistant to vancomycin has caused considerable concern. Such strains are currently rare, although they have been isolated from many areas of the world. Considerable controversy surrounds strains of S. aureus displaying heterogeneous resistance to vancomycin regarding their definition and methods for detection. This has led to considerable variance in estimates of prevalence (0-1.3%-20% in Japan) and has hindered efforts to define the clinical relevance of these strains. The mechanism of resistance involves a complex reorganization of cell wall metabolism, leading to a grossly thickened cell wall with reduced peptidoglycan cross-linking. There may be many different ways in which strains achieve this endpoint. Current knowledge and theories are summarized.

Anti-Bacterial Agents↗
PubMed2002

Preliminary analysis of the genetic basis for vancomycin resistance in Staphylococcus aureus strain Mu50.

Glycopeptides, such as vancomycin, are frequently the antibiotics of choice for treatment of infections caused by the now common methicillin-resistant Staphylococcus aureus (MRSA). Incidences of vancomycin resistance in S. aureus (VRSA) have been increasing worldwide for the last 5 years. Complex mechanisms producing changes in cell wall content and composition generate the VRSA phenotype, but the genetic basis of these changes has not yet been determined. To facilitate the genetic investigation, entire genome sequences of the archetypal VRSA (Mu50), and vancomycin-susceptible MRSA strains N315, EMRSA 16 and COL were compared. The in silico analysis revealed several loss-of-function mutations in Mu50, affecting important cell wall biosynthesis and intermediary metabolism genes, not previously reported. The new findings provide further evidence for the hypothesis that vancomycin resistance in Mu50 is due to fundamental changes, important to metabolic pathways that impinge on peptidoglycan biosynthesis. These observations will inform targeted experiments aimed at a complete understanding of the mechanism(s) of vancomycin resistance in S. aureus Mu50 and other VRSA strains.

Humans↗