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D J Platt

Publications and source records attributed to D J Platt.

At least 37 records · Page 2Linked to original sources
PubMed1989

Serratia marcescens outbreak in a paediatric oncology unit traced to contaminated chlorhexidine.

Over an 18-month period we encountered 12 episodes of Serratia marcescens bacteraemia in 10 patients in a paediatric oncology unit. These were associated with long-term indwelling Hickman intravenous catheters (right atrial) and caused three deaths. Seven of the patients had only mild pyrexial illnesses and made a complete recovery. The source was traced to contaminated aqueous chlorhexidine in a bedside container in which plastic clamps were stored. When this was rectified the outbreak ceased. The identity of the causal Serratia strains was confirmed by plasmid analysis and they showed multiple antibiotic resistance, including the aminoglycosides. The study illustrates the emergence of S. marcescens as an opportunistic pathogen and emphasises the dangers of Hickman-associated bacteraemia.

Adolescent↗
PubMed1988

Plasmid profiles and restriction enzyme fragmentation patterns of plasmids of methicillin-sensitive and methicillin-resistant isolates of Staphylococcus aureus from hospital and the community.

The number, frequency distribution and restriction enzyme fragmentation patterns of plasmids harboured by 163 methicillin-sensitive isolates of Staphylococcus aureus (MSSA) and 53 methicillin-resistant isolates (MRSA) were compared. Plasmids were demonstrated in less than half of the MSSA isolates; their frequency distribution did not differ from that predicted by a simple model of plasmid distributions. In contrast, all the MRSA isolates harboured plasmids, their distribution suggesting dissemination of a limited number of clones within the hospital. Among 72 MSSA isolates harbouring plasmids, 38 different restriction patterns were identified. There were fewer patterns among MRSA isolates; 11 were observed, and two predominant patterns accounted for 68% of those identified. These restriction patterns correlated with the presence or absence of aminoglycoside resistance. A multicopy plasmid of 2.6 kb was present in both MSSA and MRSA isolates that harboured more than one plasmid; it had the same restriction pattern irrespective of its source. The importance of these results in choosing a method of studying the spread of staphylococci is discussed.

Cross Infection↗
PubMed1988

Molecular divergence of the serotype-specific plasmid (pSLT) among strains of Salmonella typhimurium of human and veterinary origin and comparison of pSLT with the serotype specific plasmids of S. enteritidis and S. dublin.

Molecular variants of the serotype-specific plasmid (SSP) of Salmonella typhimurium (pSLT) were recognised in clinical and veterinary isolates by restriction enzyme fingerprinting. Three had undergone minor DNA rearrangements, whereas two had acquired resistance determinants to a wide range of antimicrobial agents including gentamicin, trimethoprim, tetracycline, streptomycin, ampicillin (Ap) and kanamycin (Km). One of the latter was the result of co-integrate formation with an IncX, conjugative R-plasmid that specified ApKm resistance. The co-integrate plasmid (pOG669) was incompatible with, and displaced, pSLT and its molecular variants. The restriction fingerprints of SSPs of S. enteritidis and S. dublin were compared with pSLT. All were related at the 35% level on the basis of a Dice coefficient of similarity. The SSPs of S. enteritidis and S. dublin were incompatible with the co-integrate plasmid pOG669. Whereas in S. enteritidis this resulted from incompatibility with the pSLT component (the SSP was compatible with the IncX component), the converse was found with S. dublin.

Animals↗
PubMed1988

Clinical pharmacokinetics of enzyme inhibitors in antimicrobial chemotherapy.

The effectiveness of some antimicrobial agents can be enhanced by using them in combination; such combinations are termed synergistic. Where one compound potentiates the effect of a second drug they may be coformulated. Inhibition of the bacterial degradation of an active antimicrobial is the basis of clavulanate and sulbactam-potentiated penicillin combinations, and inhibition of degradative pathways in the host is the rationale behind imipenem/cilastatin therapy. Trimethoprim/sulphonamide combinations depend on the maintenance of an effective ratio for synergistic action. In order to achieve potentiation the coformulated drugs should have similar pharmacokinetics. Trimethoprim was originally matched with sulphamethoxazole, since these two drugs have similar elimination half-lives, but the significantly poorer penetration of sulphonamides, their greater non-renal clearance, the emergence of resistance, and the adverse reactions attributable to them argue against the rationale that underlies their coformulation. Time-dependent inhibition of bacterial beta-lactamases by clavulanic acid and sulbactam has extended the use of penicillins which are highly susceptible to beta-lactamase inactivation. The beta-lactamase inhibitors must penetrate to the same extent as the penicillin used with them, and be present long enough to effect inhibition; thus, rapid penetration, similar or slower elimination and equivalent volume of distribution are necessary. These requirements are met for amoxycillin/clavulanic acid, ticarcillin/clavulanic acid and ampicillin/sulbactam combinations. Clavulanic acid is absorbed orally and is given with amoxycillin. However, since sulbactam is labile by this route, the combination of sulbactam with ampicillin to form the prodrug sultamicillin has been necessary to enable an oral form to be developed. Imipenem is metabolised by renal brush-border dehydropeptidases, and may cause proximal tubular necrosis. Cilastatin was designed to inhibit this metabolism, which it effectively does, thereby both potentiating the effect of imipenem and avoiding toxicity. Appropriate matching of the kinetics of coformulated drugs is intended to maximise potentiation and minimise the risk of emergent resistance. The kinetics of the above combinations are discussed in the light of these requirements and the effects of age and disease.

Anti-Bacterial Agents↗
PubMed1987

Linkage analysis of von Recklinghausen neurofibromatosis to DNA markers on chromosome 17.

Several recent studies indicate that the von Recklinghausen neurofibromatosis (NF1) gene is located near the centromere of chromosome 17 in some families. However, variable expressivity and a very high mutation rate suggest that defects at several different loci could result in phenotypes categorized as NF1. In order to assess this possibility and to map the NF1 gene more precisely, we have used two polymorphic DNA markers from chromosome 17 to screen several pedigrees for linkage to NF1. We ascertained a large Caucasian pedigree (33 individuals sampled, 17 NF1 affected) as well as eight smaller pedigrees and nuclear families (50 individuals sampled, 30 NF1 affected). Here, we report strong evidence of linkage of NF1 to the centromeric marker D17Z1 (maximum lod = 4.42) and a weaker suggestion of linkage to the ERBA1 oncogene (maximum lod = 0.57), both at a recombination fraction of zero. Since obligate cross-overs with NF1 were not observed for either marker in any of the informative families tested, the possibility of NF1 locus heterogeneity is not supported.

Chromosome Mapping↗
PubMed1987

Patterns of wound colonisation in patients with peripheral vascular disease.

The bacterial colonisation of ulcers related to vascular disease, amputation sites and sites of surgical vascular repair was studied in 122 patients with vascular disorders. Wounds were graded clinically on the basis of inflammation, oedema and exudate. They were sampled at weekly intervals in order to determine the duration of colonisation. The significance of potential pathogens was assessed. Vascular ulcers were of low mean wound grade (1.87), short duration (1.58 weeks) and potential pathogens were isolated from 82% of 38 wounds. Amputation sites were of a higher mean wound grade (2.48) and longer duration (2.52 weeks) when compared to vascular ulcers. Potential pathogens were isolated from 69% of 42 amputation sites. Sites of surgical vascular repair were similar to amputation sites with respect to mean wound grade (2.33) but of a mean duration (1.69 weeks) similar to that of vascular ulcers. Potential pathogens were isolated from 50% of 42 surgical vascular repair sites but they were not evenly distributed among limb (33%), groin (55%) and abdominal wounds (71%). Coliforms were isolated from similar numbers of all wounds. Pseudomonas spp., Staphylococcus aureus and Streptococcus faecalis were evenly distributed with respect to the site of isolation. Pseudomonas spp. and S. aureus were associated more commonly with vascular ulcers and S. faecalis with sites of surgical vascular repair. The use of topical antiseptics and/or systemic antimicrobial agents had a minimal effect in reducing colonisation/infection in the wounds studied.

Amputation Stumps↗
PubMed1987

A comparison of the distribution of pneumococcal types in systemic disease and the upper respiratory tract in adults and children.

The serotype distribution of 874 strains of Streptococcus pneumoniae was determined in relation to patients' age and to frequency of isolation from systemic disease. Types 14 and 18, in pre-school children, and types 1, 4, 7, 8 and 12 in patients over 5 years of age were significantly associated with systemic disease whereas type 23 in pre-school children, and type 6 in older patients was associated with upper respiratory tract carriage. No significant difference was found in the incidence of other types in systemic disease compared to upper respiratory tract carriage. Fifteen diagnostic pneumococcal antisera (to types 1, 3, 4, 6, 7, 8, 9, 11, 12, 14, 17, 18, 19, 22 and 23) sufficed for typing 87% of strains.

Adolescent↗
PubMed1987

Restriction enzyme fingerprinting of trimethoprim resistance plasmids.

Restriction enzyme fingerprinting was applied to 72 transferable trimethoprim resistance plasmids to examine aspects of their epidemiology and molecular relatedness. These plasmids had previously been divided into 25 groups according to differences in mol. wts and in antimicrobial resistance determinants. Restriction enzyme fingerprinting allowed the plasmids to be further divided into 44 different groups. The groups based on molecular weight and resistance patterns often, but not invariably, corresponded with those based on restriction enzyme fingerprints. Some plasmids with the same mol. wt and resistance pattern had different digest fingerprints and conversely, although more rarely, plasmids which differed in molecular weight by as much as 10 MDa or in resistance pattern by one resistance marker, had indistinguishable fingerprints. The plasmids were initially divided into three broad categories according to which restriction enzymes gave fingerprints of 6-20 fragments. These categories differed in the molecular weights of the plasmids contained, the numbers of resistance markers, and the proportions of the plasmids which carried transposon Tn7. Some plasmids were more widespread and persistent than others with the same mol. wt and resistance pattern but with a different restriction enzyme fingerprint. Thus, application of this technique has shown the trimethoprim resistance plasmids studied to be more diverse than was indicated by determination of mol. wt and resistance pattern, and has indicated changes in the plasmid pool over the 3 years during which they were collected.

Molecular Weight↗
PubMed1987

Old and new techniques together resolve a problem of infection by Salmonella typhimurium.

Isolates of Salmonella typhimurium, recovered over a 9-month period from a child with gastroenteritis, were characterized by biotyping, phage-typing and plasmid-profile analysis. Because the data from the different methods were discrepant, it was difficult to establish whether her infection was due to a single strain that had changed character in vivo or was due to recurrent infections with different, unrelated strains. Restriction-enzyme fingerprinting of the plasmids from the different isolates provided an explanation for the initial discrepancy and high-lighted a source of potential confusion in epidemiological studies.

Bacteriophage Typing↗
PubMed1987

A simple statistical approach that represents the frequency distribution of plasmids in clinical isolates of the enterobacteria.

The frequency distribution of plasmids in a representative collection of Escherichia coli and other enterobacteria was compared with the frequencies predicted by the Poisson distribution. The distribution of E. coli plasmids did not differ significantly (p greater than 0.2) whereas the difference between observed and predicted distributions of plasmids in combined populations of other enterobacteria was significant (p less than 0.001). Previous studies had suggested that plasmid-free strains contributed disproportionately to the overall frequency distribution. Therefore, plasmid-free strains were excluded and the frequency distribution of plasmids in plasmid-containing strains compared with frequencies predicted by a modified Poisson distribution conditional upon n not equal to 0. The results obtained showed that the frequency distribution of plasmids in E. coli and in other enterobacteria did not differ significantly from the predicted distribution (p less than 0.2 and p greater than 0.6 respectively). The frequency distribution of plasmids in previously published studies was compared with predicted frequencies by means of the Poisson distribution and the modified Poisson distribution conditional upon n not equal to 0. The results indicate that the modified Poisson distribution described provides an adequate description of plasmid frequency distributions and represents the observed frequencies better than the distribution predicted directly from the Poisson formula.

Enterobacteriaceae↗
PubMed1986

Recognition of the cryptic plasmid, pSLT, by restriction fingerprinting and a study of its incidence in Scottish Salmonella isolates.

The plasmid pSLT is a cryptic plasmid of 60 megadaltons (Md) present in Salmonella typhimurium LT2. We present evidence that it has a characteristic fingerprint when digested with the restriction enzymes PstI and SmaI. Among a representative collection of S. typhimurium isolates it was present in 67% of strains and was widely distributed amongst different phage types (DT) with the exception of DT10 and U285. Furthermore, its prevalence among veterinary isolates was significantly higher than among human isolates. It was not found among any of the 96 strains representative of other salmonella serotypes currently prevalent and thus appears to be serotype-specific.

Chromosome Mapping↗
PubMed1986

The distribution of plasmids among a representative collection of Scottish strains of Salmonellae.

The distribution of plasmids was studied in a representative collection of salmonella strains which comprised 98 Salmonella typhimurium and 96 other serotypes. Plasmids were detected in 72% of strains (mean 1.3 plasmids/strain) and individual strains harboured between 0 and 7 plasmids. They were more common among S. typhimurium than other serotypes (incidence 92 and 53%; mean 1.9 and 0.8 plasmids/strain respectively). Although a higher proportion of S. typhimurium (33%) were antibiotic-resistant compared to other serotypes (14%) the evidence presented indicated that R-plasmids were not responsible for the difference observed in the number and distribution of plasmids in these strains. These results were discussed in comparison with similar studies of Escherichia coli and other enteric genera.

DNA, Bacterial↗
PubMed1986

Restriction enzyme fingerprinting of enterobacterial plasmids: a simple strategy with wide application.

Restriction enzyme fingerprints were generated from purified plasmid DNA from 324 clinical isolates that belonged to 7 enterobacterial genera and 88 single plasmids in Escherichia coli K 12 according to the following strategy. Purified plasmid DNA was digested with PstI. The number of fragments detected in a 0.8 agarose gel was used to determine which 2 of 6 restriction enzymes including PstI was most likely to provide a fingerprint comprising sufficient fragments to ensure specificity but sufficiently few to allow easy visual assessment and minimize coincidental matching. When PstI produced greater than 20 fragments, EcoRI and HindIII were used; when PstI generated less than 6 fragments Bsp 1286 and AvaII were used and SmaI was employed when between 6 and 20 fragments were obtained from PstI digests. Using a minimum of 12 fragments from a combination of 2 enzymes as the criterion for characterizing a strain/plasmid, satisfactory 2-enzyme fingerprints were obtained from 87% of the strains and plasmids studied using PstI and no more than two additional enzymes per strain. Of the remaining 54 strains, 51 harboured only small plasmids (less than 10 kb) and 3 produced satisfactory fingerprints when digested with a fourth enzyme.

Chromosome Mapping↗
PubMed1986

R-plasmid transfer in vivo: a prospective study.

Two hundred and eighty-seven coliform bacteria were isolated from 116 rectal swabs or faecal specimens obtained from 113 patients. By means of plasmid analysis and resistance transfer (R-transfer) Escherichia coli was found to differ from other enteric genera in plasmid distribution. Criteria were proposed that enabled in-vivo "R-transfer potential" and in-vivo "R-transfer rate" to be calculated. From each of 22 of the 113 patients numerous coliforms were isolated, of which at least one per patient contained one or more self-transmissible R-plasmids potentially transferable to 43 other coliforms. Evidence indicated that R-plasmid transfer had occurred in vivo on two of the 43 potential occasions. These results are discussed in the context of plasmid ecology in the human host.

DNA, Bacterial↗
PubMed1986

Distribution and genetic location of Tn7 in trimethoprim-resistant Escherichia coli.

A series of 178 strains of Escherichia coli, highly resistant to trimethoprim, isolated from hospital patients and patients in the community between 1979 and 1983, was examined for the presence of Tn7 on a plasmid or on the chromosome only, by transposition to RP4 and restriction endonuclease digestion with Hind III. Of the isolates, 57% carried Tn7. Comparison of hospital isolates from 1979 to 1980 and 1982 showed that although the proportions that carried Tn7 were similar (63% and 57%) there had been a significant change in the genetic location of the transposon. The proportion of plasmid-mediated Tn7 had fallen from 62% to 30% with a corresponding rise in Tn7 located exclusively on the chromosome from 38% to 70%. This change may be the result of continuing transposition of Tn7 from plasmids to the bacterial chromosome followed by plasmid loss. The consequent reduction in the mobility of trimethoprim-resistance genes may in turn lead to changes in the incidence of resistance.

Chromosomes, Bacterial↗
PubMed1985

Trimethoprim resistance in urinary coliforms from patients in the community: plasmids and R-transfer.

A study of urinary coliform isolates, from patients attending their general practitioner, between 1981 and 1983 showed that 10.2% were resistant to trimethoprim. Forty-four trimethoprim-resistant Escherichia coli were collected for further study and the results compared with those obtained from hospital isolates collected during 1979-80 and 1982. Thirty-two (73%) were highly resistant to trimethoprim (MIC greater than 1024 mg/l) a similar proportion to that in the hospital isolates. The highly resistant isolates bore a close resemblance to the hospital isolates in that 66% carried multiple plasmids, 97% were multiply drug-resistant and all were highly resistant to sulphamethoxazole. The frequency of antimicrobial resistance transfer (59%) was similar to that from the hospital isolates. More than half of the trimethoprim resistance plasmids characterized were indistinguishable in terms of mol.wt and resistance pattern from those found in isolates from the hospital collections. Our results suggest that, whereas trimethoprim-resistant E. coli are less commonly isolated from patients in the community than in hospitals, many of the community isolates may have originated from a hospital source.

Conjugation, Genetic↗