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Biomedical subjects

T R Walsh

Publications and source records attributed to T R Walsh.

At least 37 records · Page 2Linked to original sources
PubMed2001

Use of antimicrobial agents in veterinary medicine and food animal production.

Antimicrobial resistance is a growing area of concern in both human and veterinary medicine. This review presents an overview of the use of antimicrobial agents in animals for therapeutic, metaphylactic, prophylactic and growth promotion purposes. In addition, factors favouring resistance development and transfer of resistance genes between different bacteria, as well as transfer of resistant bacteria between different hosts, are described with particular reference to the role of animals as a reservoir of resistance genes or resistant bacterial pathogens which may cause diseases in humans.

Animal Diseases↗
PubMed2001

Resistance to antibiotics and biocides among non-fermenting Gram-negative bacteria.

OBJECTIVE: To investigate the antibiotic and biocide susceptibilities of clinical isolates of rarely encountered Gram-negative, non-fermenting bacteria. METHODS: Thirty Gram-negative non-fermenting bacterial strains were isolated from blood cultures of oncology patients. These were studied for their resistance to 11 antibiotics. Their susceptibilities to seven biocides used in hospitals were also examined. RESULTS: Isolates of Stenotrophomonas maltophilia and Ochrobactrum anthropi were generally resistant to at least five of the antibiotics, whereas isolates of Comamonas acidivorans, Flavobacterium oryzihabitans, Aeromonas hydrophila, Sphingobacterium spiritivorum, Acinetobacter junii and Acinetobacter lwoffi were generally sensitive to at least nine of the antibiotics. Trovafloxacin and trimethoprim-sulfamethoxazole were the most effective antibacterial agents tested, with 0% and 7%, respectively, of isolates being resistant, whereas 63% of isolates were resistant to aztreonam. Some isolates, sensitive to meropenem and/or ceftazidime in vitro, possessed very high MBC/MIC ratios for these beta-lactams. Two out of three biocides used in hospital pharmacies showed lethal activity towards all strains tested when used at less than one-third of their recommended in-use concentration. Proceine 40 failed to give a 5 log reduction in bacterial cell number for the isolates tested when used at its "in-use" concentration. A concentration of > 500 mg/L chlorhexidine was required to achieve a 5 log reduction for the same isolates. CONCLUSIONS: We have examined the antibiotic susceptibilities of non-fermenting Gram-negative bacterial strains isolated from immunocompromised patients. Despite being sensitive to certain antibiotics in vitro, some isolates were still able to cause serious bacteremia. We have also reported for the first time the susceptibilities of non-fermenting Gram-negative bacteria to common biocides used in hospital infection control, and have shown that some strains are able to persist at the "in-use" concentration of particular biocides. It is therefore important to study further this particular group of organisms, and, in particular, to examine whether there exists a link between resistance to antibiotics and resistance to biocides.

Anti-Bacterial Agents↗
PubMed2001

A modified population analysis profile (PAP) method to detect hetero-resistance to vancomycin in Staphylococcus aureus in a UK hospital.

One hundred methicillin-resistant Staphylococcus aureus (MRSA) strains, isolated between 1983 and 1999, were tested alongside the vancomycin hetero-resistant S. aureus (hVRSA) strain Mu 3, and vancomycin-resistant S. aureus (VRSA) strain Mu 50, for their resistance to vancomycin. This was achieved using the screening method described by Hiramatsu, gradient plates, agar incorporation, standard Etest, macrodilution Etest and a modified population analysis. Using Hiramatsu's screening method, 5% of the 100 MRSA were identified as VRSA and 5% identified as hVRSA, the gradient plates identified 7% hVRSA, and the standard and macrodilution Etests identified no hVRSA. Mu 3 appeared to be vancomycin-susceptible using both the agar incorporation and standard Etest methods, but was classified as hVRSA using the macrodilution Etest. The modified population analysis reliably detected vancomycin hetero-resistance in Mu 3 and identified no hVRSAs within the 100 MRSA sample.

Hospitals↗
PubMed2001

The penetration of ceftriaxone and cefamandole into bone, fat and haematoma and relevance of serum protein binding to their penetration into bone.

Thirteen patients undergoing total hip replacement were given ceftriaxone 1 g and cefamandole 1 g simultaneously, either immediately or 8 h before surgery. For both agents the concentrations seen in the bone and fat during the operation, and for haematoma fluid <or=24 h after the operation, exceeded the MIC for susceptible staphylococci and would be expected to provide adequate prophylaxis. Although ceftriaxone concentrations in bone and fat were significantly higher than those of cefamandole, after correction for the simultaneous blood concentrations, we were unable to detect any differences in the bone or fat penetration of the two agents. We conclude that there is no evidence that cephalosporins with a lower serum protein binding penetrate bone better than ones with higher serum protein binding.

Adipose Tissue↗
PubMed2001

Carriage of antibiotic-resistant bacteria by healthy children.

The frequency of carriage of antibiotic-resistant bacteria in healthy 7- and 8-year-old children in Bristol was studied. Children born in Avon between 1 April 1991 and 31 December 1992, attending the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) 7 year follow-up clinic, formed the study population. Carriage was estimated using mouth and stool samples. None of 105 children on whom information was available had received tetracycline, chloramphenicol, ciprofloxacin or an extended-spectrum cephalosporin in the previous year. Staphylococcus aureus was isolated from mouthwashes from 200 (37.1%) of 539 children sampled. Six (3%) of the isolates were resistant to chloramphenicol or tetracycline and four (2%) were methicillin resistant. Haemophilus spp. were isolated from 369 (72%) of 513 samples and 63 (17%) were ampicillin resistant, 49 (13.3%) were erythromycin resistant and seven (1.9%) were tetracycline resistant. Branhamella catarrhalis was isolated from 333 (74%) of 450 samples. Twenty-eight (8.4%) were erythromycin resistant and 14 (4.2%) strains were tetracycline resistant. Group A beta-haemolytic streptococci were isolated from 17 of 507 children sampled. One (5.9%) was tetracycline resistant. Stool samples were returned from 335 (62%) of 539 children from whom they were requested. Eleven per cent of samples yielded Gram-negative bacilli with high-level resistance to chloramphenicol, which was frequently linked to resistance to ampicillin, spectinomycin and streptomycin. Isolates demonstrating resistance to the third-generation cephalosporin ceftazidime were recovered from 17 subjects (3.2%). Six (35%) of 17 isolates possessed extended-spectrum beta-lactamases. Healthy children carry bacteria resistant to antibiotics to which children are not usually exposed. Resistance to ceftazidime, chloramphenicol and tetracycline may be co-selected by exposure to other antibiotics used in children or may be acquired from family members, pets, other children or food. These results suggest that antibiotic-resistant bacteria are widely disseminated and may be acquired by children before exposure to specific selection pressure.

Bacteria↗
PubMed2001

Characterization, cloning and sequence analysis of the inducible Ochrobactrum anthropi AmpC beta-lactamase.

Ochrobactrum anthropi is resistant to most cephalosporins and penicillins due, at least in part, to the inducible expression of a single beta-lactamase. The beta-lactamase gene has been cloned and sequenced. It encodes an AmpC-type class 1 serine active-site enzyme that hydrolyses mainly cephalosporins and is resistant to inhibition by clavulanic acid. Expression of the ampC gene is inducible via a typical AmpR regulator, which is encoded upstream of ampC. Inducible expression is retained following cloning of O. anthropi ampR-ampC into Escherichia coli, confirming that the signal for AmpR activation in O. anthropi is the same as that used in the Enterobacteriaceae. This is the first reported example of an AmpC beta-lactamase outside of the gamma-subdivision of the bacterial kingdom. Genomic searches of other non-gamma-subdivision bacteria revealed a homologous ampR-ampC cluster in the plant symbiont, Sinorhizobium meliloti.

Amino Acid Sequence↗
PubMed2001

The activity of vancomycin against heterogeneous vancomycin-intermediate methicillin-resistant Staphylococcus aureus explored using an in vitro pharmacokinetic model.

Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) may account for treatment failure with vancomycin and act as a precursor of vancomycin-intermediate or -resistant S. aureus. The activity of vancomycin was assessed against vancomycinsusceptible, hVISA and VISA strains in a dilutional pharmacokinetic model. Over a 48 h period, total bacteria and cells with a vancomycin-intermediate phenotype were quantified. Total counts of hVISA were reduced by vancomycin in a similar way to a vancomycin-susceptible control. The vancomycin-intermediate sub-population was eradicated from the model within one dose interval. Exposure to low vancomycin concentrations did not result in an increase in the proportion of cells which were vancomycin intermediate. Short-term exposure of hVISA to vancomycin at gradient concentrations did not increase the proportion of cells with vancomycin-intermediate phenotype.

Anti-Bacterial Agents↗
PubMed2001

Plasmid location and molecular heterogeneity of the L1 and L2 beta-lactamase genes of Stenotrophomonas maltophilia.

An approximately 200-kb plasmid has been purified from clinical isolates of Stenotrophomonas maltophilia. This plasmid was found in all of the 10 isolates examined and contains both the L1 and the L2 beta-lactamase genes. The location of L1 and L2 on a plasmid makes it more likely that they could spread to other gram-negative bacteria, potentially causing clinical problems. Sequence analysis of the 10 L1 genes revealed three novel genes, L1c, L1d, and L1e, with 8, 12, and 20% divergence from the published strain IID 1275 L1 (L1a), respectively. The most unusual L1 enzyme (L1e) displayed markedly different kinetic properties, with respect to hydrolysis of nitrocefin and imipenem, compared to those of L1a (250- and 100-fold lower k(cat)/K(m) ratios respectively). L1c and L1d, in contrast, displayed levels of hydrolysis very similar to that of L1a. Several nonconservative amino acid differences with respect to L1a, L1b, L1c, and L1d were observed in the substrate binding-catalytic regions of L1e, and this could explain the kinetic differences. Three novel L2 genes (L2b, L2c, and L2d) were sequenced from the same isolates, and their sequences diverge from the published sequence of strain IID 1275 L2 (L2a) by 4, 9, and 25%, respectively. Differences in L1 and L2 gene sequences were not accompanied by similar divergences in 16S rRNA gene sequences, for which differences of <1% were found. It is therefore apparent that the L1 and L2 genes have evolved relatively quickly, perhaps because of their presence on a plasmid.

Alleles↗
PubMed2001

Evaluation of current methods for detection of staphylococci with reduced susceptibility to glycopeptides.

The sensitivity and specificity of seven methods (agar dilution, broth microdilution, Etest at 0.5 and 2.0 McFarland (McF) inocula, two agar screening methods, and population studies [PS]) were evaluated in a double-blind study involving 284 methicillin-resistant Staphylococcus aureus (MRSA) strains and 45 Staphylococcus strains with reduced susceptibilities to vancomycin (SRSV). The results were compared to the population analysis profile-area under the curve ratio method (PAP-AUC ratio compared to that of Mu3) as described by Wootton et al. The agar screening method using brain heart infusion agar (6 microg of vancomycin per ml) gave a sensitivity of 22% and a specificity of 97%. A similar method using Mueller-Hinton agar (5 microg of vancomycin per ml) gave a sensitivity of 20% and a specificity of 99%. The PS method detected 34 false positives (12%) and gave a sensitivity of 71% and a specificity of 88%. Etest using 0.5 and 2.0 McF inocula gave sensitivities and specificities of 82 and 93% and of 96 and 97%, respectively. The best Etest interpretative criteria for the 2.0 McF inoculum was > or =8 mg of vancomycin per liter and > or =8 microg teicoplanin per ml or > or =12 microg of teicoplanin per ml. The direct colony suspension inoculum for this method was found to be equally accurate in detecting (hetero-)glycopeptide-intermediate S. aureus compared to the overnight broth inoculum preparation method. Agar dilution and broth microdilution using the NCCLS breakpoint criteria for vancomycin gave sensitivities and specificities of 20 and 100% and of 11 and 100%, respectively. Using the Etest with a 2.0 McF inoculum, six different media were assessed against a selection of SRSV (n = 48) and MRSA (n = 12). Brain heart infusion agar yielded the highest sensitivity and specificity values: 88 and 88%, respectively.

Anti-Bacterial Agents↗
PubMed2000

beta-lactamase expression in Plesiomonas shigelloides.

We have examined the production of beta-lactamases by 11 clinical and nine environmental isolates of Plesiomonas shigelloides from Czechoslovakia, the Czech Republic and Cuba. Ten isolates (50%) expressed detectable amounts of a chromosomally encoded, non-inducible beta-lactamase, though all isolates showed a broadly similar resistance profile: low-level resistance to ampicillin and higher-level resistance to carbenicillin. All strains were susceptible to cephalosporins and meropenem. Three clinical isolates expressed a beta-lactamase similar to a class 2c carbenicillinase, with a pI of 5.2 and three expressed an enzyme similar to a class 2d oxacillinase, with a pI of 5.3. The environmental isolates produced a variety of penicillinases, indicating that there is a reservoir of heterogeneous beta-lactamase genes in this species.

Anti-Bacterial Agents↗
PubMed2000

Aeromonas hydrophila AmpH and CepH beta-lactamases: derepressed expression in mutants of Escherichia coli lacking creB.

The class 1 cephalosporinase (CepH) and class 2d oxacillinase (AmpH) from an Aeromonas hydrophila clinical isolate, strain T429125, have been cloned and sequenced. Both enzymes are typical of their equivalents in other species of Aeromonas Both cloned beta-lactamase genes were expressed at a low level in a standard laboratory Escherichia coli strain, but when cloned into a cre deletion E. coli mutant, they were expressed at significantly higher levels. Specific disruption of the creB gene resulted in similar increased levels of beta-lactamase expression, so it was concluded that CreB represses the transcription of ampH and cepH in a cre(+) E. coli strain. The expression of cepH was four times that of ampH in the deltacre mutant because of an additional factor encoded on the cloned T429125 chromosomal fragment containing cepH. This factor was able to trans-activate expression of co-resident ampH in the deltacre mutant such that expression of the two genes was approximately equal. The entire cepH-containing fragment was sequenced, but it contained no genes that were obviously related to any known class of DNA-binding protein.

Aeromonas hydrophila↗
PubMed2000

A TEM-2beta-lactamase encoded on an active Tn1-like transposon in the genome of a clinical isolate of Stenotrophomonas maltophilia.

A constitutively expressed beta-lactamase gene from a clinical isolate of Stenotrophomonas maltophilia, J675Ia, has been cloned. Its DNA sequence is almost identical to that of bla(TEM2) (one nucleotide change) and the expressed enzyme is a Bush type 2a penicillinase with an amino acid sequence identical to that of TEM-2. The bla(TEM) gene was present within a novel Tn1/Tn3-type transposon in the genome of isolate J675Ia and the transposon was able to mobilize bla(TEM) on to the broad host-range conjugative plasmid, R388. When transferred to an Escherichia coli recipient, R388::Tn conferred high-level ampicillin resistance. This represents the first identification of a TEM beta-lactamase in S. maltophilia and the first evidence that this important clinical pathogen is able to act as a reservoir for mobile beta-lactamase genes in the hospital environment.

DNA Transposable Elements↗
PubMed2000

The usefulness of electrical stimulation for assessing pedicle screw placements.

The purpose of this study was to further establish the efficacy of pedicle screw stimulation as a monitoring technique to avoid nerve root injury during screw placement. The study population consisted of 662 patients in whom 3,409 pedicle screws were placed and tested by electrical stimulation. If stimulation resulted in a myogenic response at a stimulation intensity of 10 mA or less, the placement of the screw was inspected. Inspection was necessary for 3.9% of the screw placements in 15.4% of the study population. None of the patients in the study experienced any new postoperative neurologic deficits. These findings provide guidelines for the interpretation of stimulation data and support the use of this technique as an easy, inexpensive, and quick method to reliably assess screw placements and protecting neurological function.

Bone Screws↗
PubMed1999

Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out-of-hospital ventricular fibrillation.

CONTEXT: Use of automated external defibrillators (AEDs) by first arriving emergency medical technicians (EMTs) is advocated to improve the outcome for out-of-hospital ventricular fibrillation (VF). However, adding AEDs to the emergency medical system in Seattle, Wash, did not improve survival. Studies in animals have shown improved outcomes when cardiopulmonary resuscitation (CPR) was administered prior to an initial shock for VF of several minutes' duration. OBJECTIVE: To evaluate the effects of providing 90 seconds of CPR to persons with out-of-hospital VF prior to delivery of a shock by first-arriving EMTs. DESIGN: Observational, prospectively defined, population-based study with 42 months of preintervention analysis (July 1, 1990-December 31, 1993) and 36 months of post-intervention analysis (January 1, 1994-December 31, 1996). SETTING: Seattle fire department-based, 2-tiered emergency medical system. PARTICIPANTS: A total of 639 patients treated for out-of-hospital VF before the intervention and 478 after the intervention. INTERVENTION: Modification of the protocol for use of AEDs, emphasizing approximately 90 seconds of CPR prior to delivery of a shock. MAIN OUTCOME MEASURES: Survival and neurologic status at hospital discharge determined by retrospective chart review as a function of early (<4 minutes) and later (> or =4 minutes) response intervals. RESULTS: Survival improved from 24% (155/639) to 30% (142/478) (P=.04). That benefit was predominantly in patients for whom the initial response interval was 4 minutes or longer (survival, 17% [56/321] before vs 27% [60/220] after; P = .01). In a multivariate logistic model, adjusting for differences in patient and resuscitation factors between the periods, the protocol intervention was estimated to improve survival significantly (odds ratio, 1.42; 95% confidence interval, 1.07-1.90; P = .02). Overall, the proportion of victims who survived with favorable neurologic recovery increased from 17% (106/634) to 23% (109/474) (P = .01). Among survivors, the proportion having favorable neurologic function at hospital discharge increased from 71% (106/150) to 79% (109/138) (P<.11). CONCLUSION: The routine provision of approximately 90 seconds of CPR prior to use of AED was associated with increased survival when response intervals were 4 minutes or longer.

Aged↗
PubMed1999

Expression and detection of hetero-vancomycin resistance in Staphylococcus aureus.

Isolates of Staphylococcus aureus resistant to vancomycin have been reported but appear to be extremely rare. However, isolates displaying hetero-resistance to vancomycin (hVRSA) are reportedly common in parts of Japan (9.3% of MRSA isolated from a group of university hospitals). We have investigated the reliability of the proposed method for detection of hetero-resistant isolates and the ability of clinical S. aureus isolates to express vancomycin resistance. The original method for identification of hVRSA was found to have poor reproducibility and may select for, rather than detect, vancomycin resistance. There appears to be a spectrum of heterogeneity in the expression of resistance to vancomycin among S. aureus. Until there is a clearer understanding of the mechanism and control of vancomycin resistance in S. aureus, and reliable tests are devised, the clinical relevance of different degrees of hetero-resistance cannot be assessed.

Anti-Bacterial Agents↗
PubMed1999

Interactions between methicillin and vancomycin in methicillin-resistant Staphylococcus aureus strains displaying different phenotypes of vancomycin susceptibility.

Vancomycin-sensitive, -intermediate, and -heterointermediate methicillin-resistant Staphylococcus aureus isolates were tested by using E-tests to explore the interaction of methicillin and vancomycin. For the vancomycin-intermediate and -heterointermediate strains both drugs showed antagonism at concentrations below their MICs but synergy at methicillin concentrations near the MIC. This property could be used to screen for heterointermediate S. aureus strains.

Anti-Bacterial Agents↗