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Mandy Wootton

Publications and source records attributed to Mandy Wootton.

9 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↗
PubMed2006

Comparative bactericidal activities of daptomycin and vancomycin against glycopeptide-intermediate Staphylococcus aureus (GISA) and heterogeneous GISA isolates.

Staphylococcus aureus strains from the U.S. SENTRY Antimicrobial Surveillance Program, 2002-2003, glycopeptide-intermediate S. aureus (GISA) strains, and heterogeneous GISA (hGISA) strains were used to compare bactericidal activities of daptomycin and vancomycin using MICs and minimum bactericidal concentrations. Glycopeptide-susceptible S. aureus and hGISA strains were further studied by using time-kill curves. For all isolates, the daptomycin MIC50 and MIC90 are four times lower and the log drops in viable counts at 6 h and 24 h are significantly greater than those for vancomycin.

Anti-Bacterial Agents↗
PubMed2005

Reduced expression of the atl autolysin gene and susceptibility to autolysis in clinical heterogeneous glycopeptide-intermediate Staphylococcus aureus (hGISA) and GISA strains.

OBJECTIVES: To assess a link between resistance to Triton X-100 induced autolysis (TIA) and lowered atl expression in a collection of clinical glycopeptide-intermediate Staphylococcus aureus (GISA) and heterogeneous GISA (hGISA). METHODS: Nine clinical GISA, 11 hGISA and 11 glycopeptide-susceptible S. aureus (GSSA), including three pairs of related isolates, were analysed using TIA assays. Lysostaphin MICs were determined by a broth microdilution technique and reverse transcriptase PCR was used to compare atl expression levels in all isolates. RESULTS: Eight of nine clinical GISA and six of 11 hGISA exhibited lower susceptibility to TIA and higher MICs of lysostaphin than GSSA. Eight of nine GISA and all hGISA strains had lowered atl expression levels compared with GSSA. CONCLUSIONS: The majority of GISA and hGISA isolates exhibited lowered susceptibility to TIA and lysostaphin and reduced atl expression when compared with GSSA isolates. These factors could contribute to, or predispose to the development of, a thickened cell wall and glycopeptide-intermediate resistance.

Anti-Bacterial Agents↗
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↗
PubMed1999

In vitro assessment of colistin's antipseudomonal antimicrobial interactions with other antibiotics.

OBJECTIVE: To study the interactions of colistin (MIC 2 mg/L) at concentrations of 0.5 and 5 mg/L with ceftazidime (1 and 75 mg/L, MIC 0.5 mg/L), aztreonam (1 and 30 mg/L, MIC 0.12 mg/L), meropenem (1 and 25 mg/L, MIC 0.03 mg/L), gentamicin (1 and 10 mg/L, MIC 2 mg/L), piperacillin (5 and 100 mg/L, MIC 4 mg/L) and ciprofloxacin (0.25 and 4 mg/L, MIC 1 mg/L) using a representative strain of Pseudomonas aeruginosa isolated from a cystic fibrosis patient. METHODS: The method used was a bacterial time kill curve with single agents and combinations. Using inocula of 106 CFU/mL, multiple sampling was performed over 6 h and in triplicate. The AUBKC of the time versus viable count curve, with single agents and combinations of agents, was taken as the endpoint for comparison. RESULTS: For colistin plus ceftazidime, colistin plus aztreonam, colistin plus meropenem and colistin plus ciprofloxacin, the pattern was for all the combinations (high or low concentrations) to produce smaller AUBKCs than single agents. In experiments using a bacteriostatic agent such as ceftazidime, the AUBKCs (log CFU/µL per h) for colistin 0.5 mg/L or 5 mg/L alone were 32.3±0.8 or 12.7±0.5, and for ceftazidime 1 mg/L or 75 mg/L alone they were 24.3±1.5 or 20.9±2.7. Combinations of colistin 0.5 mg/L plus either ceftazidime 1 mg/L or 75 mg/L produced AUBKCs of 23.8±1.8 or 16.1 mg/L. Combinations of colistin 5 mg/L plus ceftazidime 1 mg/L or 75 mg/L produced AUBKCs of 12.2±0.8 or 8.7±1.0. The AUBKCs for colistin 5 mg/L plus 75 mg/L are significantly smaller than those for the single agents, indicating synergy. In experiments using the bactericidal agent ciprofloxacin, the AUBKCs (log CFU/mL per h) for colistin 0.5 mg/L or 5 mg/L alone were 33.6±1.9 or 11.2±2.4, and for ciprofloxacin 0.25 mg/L or 4 mg/L alone they were 32.8±1.3 or 5.0±0.7. Combinations of colistin 0.5 mg/L plus either ciprofloxacin 0.25 mg/L or 4 mg/L produced AUBKCs of 32.2±0.9 or 4.3±1.4. Combinations of colistin 5 mg/L plus ciprofloxacin 0.25 mg/L or 4 mg/L produced AUBKCs of 10.7±1.5 or 4.2±0.6. Although combination AUBKCs were smaller than those for single agents, in no case did this reach statistical significance (p<0.05). CONCLUSIONS: These studies indicate that addition of colistin to other antipseudomonal drugs tends to produce smaller AUBKCs and hence greater killing of Pseudomonas aeruginosa than monotherapy.

Journal Article↗
PubMed1999

The in vitro activity of moxifloxacin against Haemophilus influenzae and Moraxella catarrhalis explored using a pharmacodynamic model.

OBJECTIVE: To assess the antibacterial action of moxifloxacin on Haemophilus influenzae and Moraxella catarrhalis using an in vitro pharmacodynamic model of infection. METHODS: Serum concentrations in humans associated with doses of 400 mg once a day for 48 h were simulated and the antibacterial effect measured by the log change in viable count at intervals through the simulation compared to time zero and also the area under the bacterial kill curve (AUBKC). Wild-type strains of H. influenzae and M. catarrhalis with varying beta-lactam susceptibilities (moxifloxacin MICs </=0.1 mg/L) and laboratory-generated mutants with moxifloxacin MICs of 0.5-1.0 mg/L were tested. RESULTS: H. influenzae strains with MICs of </=0.06 mg/L were eradicated by 12 h; strains with MICs of 0.5-1.0 mg/L were eradicated by 24-36 h. M. catarrhalis strains with MICs of </=0.08 mg/L were eradicated by 24-36 h, while the less susceptible laboratory mutant (MIC 1.0 mg/L) was not eradicated even at 48 h. Although we used only a single dosing simulation, the AUC/MIC ratio was strongly related to the AUBKC. CONCLUSIONS: These data indicated that once daily dosing of moxifloxacin holds promise for the treatment of infection due to H. influenzae or M. catarrhalis but bacterial killing is related to MIC.

Journal Article↗