Search PubMed⌕ Search

Biomedical subjects

A P MacGowan

Publications and source records attributed to A P MacGowan.

At least 19 recordsLinked to original sources
PubMed2006

European Committee on Antimicrobial Susceptibility Testing (EUCAST) Technical Notes on antimicrobial susceptibility testing.

The main objectives of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are to harmonise breakpoints for antimicrobial agents in Europe, and to act as the breakpoint committee for the European Medicines Agency (EMEA) during the registration of new antimicrobial agents. Detailed EUCAST procedures for harmonising and setting breakpoints for antimicrobial agents are available on the EUCAST website. Beginning with the current issue, a series of EUCAST Technical Notes will be published in CMI, based on the rationale documents produced by EUCAST for each of the antimicrobial agents studied, with the aim of highlighting important background information underlying decisions on breakpoints made by EUCAST.

Advisory Committees↗
PubMed2004

The use and therapeutic drug monitoring of teicoplanin in the UK.

Teicoplanin dosage recommendations for specific infections have been modified in recent years. However, there was no significant increase in the proportion of pre-dose concentrations > 20 mg/L between 1994 and 1998 in samples sent for teicoplanin assay at the Regional Antimicrobial Reference Laboratory, Bristol, UK. A questionnaire on the use of teicoplanin and therapeutic drug monitoring (TDM) was sent to all UK National External Quality Assurance Scheme antibiotic assay users. Teicoplanin was widely used in the UK, although vancomycin was more popular as a choice of glycopeptide. Fewer than 25% recommended teicoplanin TDM during routine use, the main reasons being perceived lack of toxicity and lack of evidence for the use of teicoplanin TDM. Pre-dose concentrations < 20 mg/L were considered appropriate for treatment of bacteraemia caused by methicillin-resistant Staphylococcus aureus by 53% of those responding. Data sheet advice was relied upon more than TDM as an indication of therapeutic dosing. Microbiologists who mainly used vancomycin tended to perform more TDM and seek higher serum concentrations when using teicoplanin than those who preferentially used teicoplanin.

Anti-Bacterial Agents↗
PubMed2004

Elements of design: the knowledge on which we build.

The time the free drug serum concentration of antibiotic remains above the pathogen MIC (T > MIC) determines bacteriological efficacy and emergence or selection of resistance for penicillin and amoxicillin with or without clavulanate. Multiple studies in animal and in-vitro models now support this conclusion. The size of the T > MIC (the pharmacokinetic/-dynamic target) is > 40-50% to maximise antibacterial effect and pathogen eradication for Streptococcus pneumoniae and probably also Haemophilus influenzae. The size of the T > MIC for optimal antibacterial effect is changed by host immune status but not by bacterial inoculum or mechanism of resistance. There is good animal evidence to support the prediction that, as long as the target T > MIC is achieved, strains of S. pneumoniae with amoxicillin MICs of 0.016 mg/L will respond to amoxicillin in the same way as those with MICs of 1-2 mg/L. Emergence of resistance to amoxicillin/clavulanate in S. pneumoniae is related to low T > MIC (< 20%) and also to the degree of population heterogeneity to amoxicillin. Selection of resistant strains of S. pneumoniae is also related to T > MIC. Monte Carlo simulations based on the pharmacokinetics of amoxicillin with or without clavulanate in humans are needed to best predict the likely efficacy of different amoxicillin dosing regimens. This approach adequately allows the considerable pharmacokinetic variability in amoxicillin handling by infected patients to be accounted for as well as differences in pathogen beta-lactam susceptibility.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2003

In vitro activities of nine peptide deformylase inhibitors and five comparator agents against respiratory and skin pathogens.

The activity of nine peptide deformylase (PDF) inhibitors undergoing clinical evaluation were compared with co-amoxiclav, levofloxacin, moxifloxacin, erythromycin and telithromycin against a range of respiratory and skin pathogens (n=166). The PDF inhibitor showed good activity against Streptococcus pneumoniae, Moxarella catarrhalis, Group A streptococci and Staphylococcus aureus irrespective of beta-lactam or fluoroquinolone susceptibility. Against Haemophilus influenzae, MIC(90) values were generally higher. BB-88488 was the most active compound. Overall these data suggest that PDF inhibitors are an interesting new class of antimicrobial worthy of further investigation in the treatment of respiratory tract and skin infections.

Amidohydrolases↗
PubMed2003

Cefuroxime resistance in non-beta-lactamase Haemophilus influenzae is linked to mutations in ftsI.

The penicillin binding protein (PBP) genes dacA, dacB and ftsI from 14 cefuroxime-resistant (CXM(R)) isolates and three clinical isolates with low CXM MIC for non-beta-lactamase-producing Haemophilus influenzae type b were molecularly characterized. One strain, 5788, was used to transform H. influenzae Rd to CXM(R) for direct comparison of the pbps in the same genetic background. No obvious mutations in the dacA and dacB gene products could be associated with CXM(R). One amino acid substitution in the ftsI gene product in particular, S357N, could give rise to CXM(R). Sequence analysis from the CXM(R) transformants also implicated FtsI; in this case, the substitutions were V511A and R517H. To verify S357N substitution, the protein sequence of H. influenzae FtsI was threaded through the S. pneumoniae PBP 2X structure giving an average root mean square deviation of the alpha-carbon chains of 0.5 A. The S357N substitution alters both the residue size and charge. One explanation for the contribution of S357N to CXM(R) is that the asparagine side-chain produces unfavourable steric hindrance with the side chain of Val-362 changing the torsion angles of the asparagine residue, which in turn may influence the position of the loop V362-P366 adjacent to the active site. Whilst other groups have examined the contribution of H. influenzae PBPs in ampicillin resistance, this is the first report analysing their role in CXM(R).

Anti-Bacterial Agents↗
PubMed2002

BAL 9141, a new broad-spectrum pyrrolidinone cephalosporin: activity against clinically significant anaerobes in comparison with 10 other antimicrobials.

The in vitro potency of BAL 9141, a new pyrrolidinone cephalosporin, was tested against non-duplicate strains of anaerobic bacteria. The MIC(50) was 1 mg/L against Actinomyces species, Clostridium species, Gram-positive anaerobic cocci, Porphyromonas species, Fusobacterium species, Lactobacillus species, Prevotella species and Veillonella species. The MIC(50) was 16 mg/L for Bacteroides fragilis and other Bacteroides species. BAL 9141 was not active against cefoxitin-resistant Bacteroides fragilis.

Bacteria, Anaerobic↗
PubMed2002

Penetration of linezolid into bone, fat, muscle and haematoma of patients undergoing routine hip replacement.

Twelve patients undergoing total hip replacement were given 600 mg of linezolid as a 20 min iv infusion along with conventional prophylaxis of 1 g of cefamandole immediately before surgery. Routine total hip arthroplasty was carried out, and at timed intervals during surgery samples of bone, fat, muscle and blood were collected for assay by high-performance liquid chromatography analysis. Samples of the haematoma fluid that formed around the operation site and further blood samples for assay were also collected at timed intervals following the operation. The penetration of linezolid into bone was rapid, with mean concentrations of 9.1 mg/L (95% CI 7.7-10.6 mg/L) achieved at 10 min after the infusion, decreasing to 6.3 mg/L (95% CI 3.9-8.6 mg/L) at 30 min. Correction for the simultaneous blood concentrations gave mean values for bone penetration of 51% at 10 min, 60% at 20 min and 47% at 30 min. Although the penetration of linezolid into fat was also rapid, mean concentrations and degree of penetration were c. 60% of those in bone; at 10 min they were 4.5 mg/L (95% CI 3.0-6.1 mg/L; penetration 27%); at 20 min they were 5.2 mg/L (95% CI 4.0-6.4 mg/L; penetration 37%); and at 30 min, 4.1 mg/L (95% CI 3.3-4.8 mg/L; penetration 31%). For muscle the corresponding values were 10.4 mg/L (95% CI 8.1-12.7 mg/L; penetration 58%) at 10 min, 13.4 mg/L (95% CI 10.2-16.5 mg/L; penetration 94%) at 20 min and 12.0 mg/L (95% CI 9.2-14.8 mg/L; penetration 93%) at 30 min. Mean concentrations of linezolid in the haematoma fluid drained from around the operation site were 8.2 mg/L at 6-8 h and 5.6 mg/L at 10-12 h after the infusion, and 7.0 mg/L at 2-4 h following a second 600 mg infusion given 12 h post-operatively. We conclude that linezolid exhibits rapid penetration into bone, fat and muscle of patients undergoing hip arthroplasty, to achieve levels in excess of its MIC for susceptible organisms (< or=4 mg/L); therapeutic concentrations were maintained in the haematoma fluid that surrounds the operation site for >16 h.

Acetamides↗
PubMed2002

Vancomycin therapeutic drug monitoring: is there a consensus view? The results of a UK National External Quality Assessment Scheme (UK NEQAS) for Antibiotic Assays questionnaire.

This study investigated vancomycin therapeutic drug monitoring (TDM) and issues related to patient management. Questionnaires were distributed to 310 participants in the UK National External Quality Assessment Scheme (NEQAS) for Antibiotic Assays. The response rate was 57.4%. The majority (76%) had an 'in-house' assay service based, almost exclusively, in the microbiology department, and a fluorescence polarization immunoassay (FPIA) was used by 97%. Almost half (48.7%) had an assay service available for 24 h/day, 7 days/week and 92.7% expected same-day results. The majority (80%) had issued guidelines for vancomycin use. A 12 hourly initial dosing regimen was used by 89%. Trough assay samples were taken <10 min before the dose by 91.5%. For post-dose assay samples, 44% took a sample at 1 h, 28% at 2 h and the remainder at 'other' times. For trough target ranges, 93% quoted <10 mg/L or 5-10 mg/L. There was no consensus with regard to post-dose assay sample times and 23 ranges were quoted. The majority (74.4%) regarded a trough level of >or=10 mg/L as 'toxic' but 13 concentrations were quoted as toxic post-dose measurements. In conclusion, there was a wide variability and poor consensus with regard to post-dose vancomycin assay sampling times, target ranges and what constituted a toxic level.

Drug Monitoring↗
PubMed2002

Expression of lux genes in a clinical isolate of Streptococcus pneumoniae: using bioluminescence to monitor gemifloxacin activity.

A clinical isolate of Streptococcus pneumoniae was transformed with a plasmid containing the lux operon of Photorhabdus luminescens that had been modified to function in gram-positive bacteria. Cells containing this plasmid produced light stably and constitutively, without compromising the growth rate. Light output was correlated with measurements of optical density and viable counts during exponential growth and provided a sensitive, real-time measure of the pharmacodynamics of the fluoroquinolone gemifloxacin.

Anti-Infective Agents↗
PubMed2001

Role of pharmacokinetics and pharmacodynamics: does the dose matter?

Antibiotic dose is important in determining serum area-under-the-curve (AUC) and peak serum concentration (C(max)), as well as the time the serum concentration remains over the pathogen minimum inhibitory concentration (T>MIC). However, dose is not the sole determinant of these factors; they are modified by absorption, clearance, and frequency of dosing. It is difficult to relate dose to clinical outcome in humans, but pharmacodynamic parameters (AUC/MIC, C(max)/MIC, or T>MIC) have been related to clinical and bacteriological efficacy or emergence of resistance to aminoglycosides, fluoroquinolones, glycopeptides, and beta-lactams.

Aminoglycosides↗
PubMed2001

Epidemiology and resource utilization for patients hospitalized for lower respiratory tract infection.

OBJECTIVES: To determine referral rates, patient characteristics, and resource utilization for patients admitted to hospital with community-acquired lower respiratory tract infections (LRTI). METHODS: Six hundred and thirteen patients, accounting for 704 LRTI episodes, were included in the study, if the referral diagnosis was LRTI and if both signs and symptoms on admission and patient management were consistent with this diagnosis. Patient records were abstracted to collect information on co-morbidities, patient demographics, resource utilization, episode outcome, pharmacy prescribing and diagnostic service utilization. RESULTS: Annual hospital admissions for LRTI ranged from 15 per 10 000 population in the age range 16-40 years to over 300 per 10 000 in the population aged >79 years, with a population average of 62.3 per 10 000. Less than 37% of admissions were for community-acquired pneumonia and the majority of episodes were in patients with pre-existing respiratory disease (41.2%). Marital status, gender, diabetic status, type of infection and number of days in hospital within the past year were all significantly associated with changes in mean length of stay. CONCLUSIONS: Hospital episodes of LRTI are seen predominantly in the over-60 age group, which account for almost 90% of bed day utilization, yet represent only 27% of the adult population. Referral of patients to hospital with LRTI represents a major resource implication for secondary health-care provision.

Adolescent↗