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Biomedical subjects

R C George

Publications and source records attributed to R C George.

At least 91 records · Page 5Linked to original sources

Distribution and transferability of plasmids encoding trimethoprim resistance in urinary pathogens from Greece.

Of 505 strains of Enterobacteriaceae responsible for significant bacteriuria and isolated from hospital patients in two Greek cities in 1989, 151 strains (30%) were resistant to trimethoprim (MIC greater than or equal to 4 mg/L) and 220 (44%) were resistant to sulphamethoxazole (MIC greater than or equal to 64 mg/L); 127 (84%) of the trimethoprim-resistant strains exhibited high-level resistance (MIC greater than 1024 mg/L) and 121 (80%) were additionally resistant to four or more other antibiotics. Plasmids were detected in 141 (93%) of the trimethoprim-resistant strains. Trimethoprim resistance was encoded on self-transmissible plasmids in 79 (52%) of the resistant strains, and in a further seven strains (5%), plasmids coding for trimethoprim resistance could be mobilised by X+ factor. Co-transfer of various other antimicrobial resistances with trimethoprim resistance was observed, tetracycline resistance being the most common. The low degree of linkage observed between trimethoprim resistance and resistance to streptomycin and spectinomycin suggests that Tn7 is relatively uncommon in Greece. Classification of trimethoprim-resistance plasmids on the basis of their antimicrobial-resistance patterns and molecular mass revealed 39 different profiles. Overall, these findings differ from those from other European countries where the prevalence of transferable high-level trimethoprim resistance is low and where chromosomal Tn7-encoded trimethoprim resistance is common.

Bacteriuria↗

Penicillin-resistant viridans streptococci have obtained altered penicillin-binding protein genes from penicillin-resistant strains of Streptococcus pneumoniae.

Penicillin-resistant strains of Streptococcus pneumoniae possess altered forms of penicillin-binding proteins (PBPs) with decreased affinity for penicillin. The PBP2B genes of these strains have a mosaic structure, consisting of regions that are very similar to those in penicillin-sensitive strains, alternating with regions that are highly diverged. Penicillin-resistant strains of viridans groups streptococci (e.g., S. sanguis and S. oralis) that produce altered PBPs have also been reported. The PBP2B genes of two penicillin-resistant clinical isolates of S. sanguis were identical in sequence to the mosaic class B PBP2B genes found in penicillin-resistant serotype 23 strains of S. pneumoniae. Emergence of penicillin resistance appears to have occurred by the horizontal transfer of an altered PBP2B gene from penicillin-resistant S. pneumoniae into S. sanguis. The PBP2B genes of three penicillin-resistant S. oralis strains were similar to the mosaic class B PBP2B gene of penicillin-resistant strains of S. pneumoniae but possessed an additional block of diverged sequence. Penicillin resistance in S. oralis has also probably arisen by horizontal transfer of this variant form of the class B mosaic PBP2B gene from a penicillin-resistant strain of S. pneumoniae.

Amino Acid Sequence↗

Susceptibility to ciprofloxacin of nosocomial gram-negative bacteria and staphylococci isolated in the UK.

At the end of 1989 the Division of Hospital Infection of the Central Public Health Laboratory completed five years of continuous surveillance of ciprofloxacin susceptibility amongst strains of Staphylococcus aureus and Pseudomonas aeruginosa. The strains studied were referred from many different UK laboratories for epidemiological or other typing. Between 1987 and 1989, referred cultures of coagulase-negative staphylococci, Klebsiella spp. and Enterobacter spp. were also examined. In total, 25,728 cultures from 254 different laboratories were included in the study, and S. aureus was the most common species amongst the survey material. Resistance to non-quinolone antimicrobials was common amongst the isolates. Over the study period there has been a gradual decline in the percentage of cultures received that were fully susceptible to ciprofloxacin and an increase in the number of laboratories referring strains with resistance or reduced sensitivity. Full susceptibility of S. aureus to ciprofloxacin has declined from 99.6% of 8981 cultures isolated in the two years before launch to 92.8% of 1968 cultures isolated during 1989. Amongst the coagulase-negative staphylococci there has been a similar decline in susceptibility from 99.4% of 658 cultures examined in 1987 to 92.6% of 433 cultures studied in 1989. There was also a decrease in susceptibility of P. aeruginosa isolates to ciprofloxacin from 98.6% of 2579 cultures isolated in 1985 and 1986 to 86.3% of 1152 cultures examined during 1989. Most of this decrease was attributable to the appearance of strains of intermediate susceptibility to ciprofloxacin (MICs 2 or 4 mg/l). Virtually no resistance to ciprofloxacin was observed amongst isolates of Klebsiella spp. and Enterobacter spp. referred between 1987 and 1989. The emergence of ciprofloxacin resistance, and by implication cross resistance to many of the other fluoroquinolones, is a worrying development and suggests that caution should be exerted in the use of these compounds for the treatment of infections due to staphylococci and P. aeruginosa.

Ciprofloxacin↗

Mathematical modeling of antimicrobial susceptibility data of Staphylococcus haemolyticus for 11 antimicrobial agents, including three experimental glycopeptides and an experimental lipoglycopeptide.

Antimicrobial MIC data were obtained for 96 strains of Staphylococcus haemolyticus and the following 11 antimicrobial agents: methicillin, gentamicin, rifampin, fusidic acid, ciprofloxacin, vancomycin, teicoplanin; three experimental glycopeptides, MDL 62,873, MDL 62,208, and MDL 62,224; and an experimental lipoglycopeptide, ramoplanin. Resistance to methicillin and gentamicin was present in over 50% of the strains, although resistance to the other agents was present in less than 10%. It is shown how application of mathematical modeling techniques can add to the understanding of such MIC data. MICs of methicillin and gentamicin were highly correlated, suggesting that evolutionary pressures for development of resistance to these agents were similar. The structural relationships among the glycopeptides were accurately reflected in their spatial relationships within the model. MICs of ramoplanin were negatively correlated with MICs of some other antimicrobial agents, particularly gentamicin, suggesting that this agent is more active against gentamicin-resistant strains. Methicillin-resistant strains were more tightly clustered than were methicillin-susceptible strains, suggesting that methicillin-resistant strains were more closely related to each other than were methicillin-susceptible strains. Mathematical modeling techniques enable more detailed analysis of MIC data.

Anti-Bacterial Agents↗

Resistance to vancomycin and teicoplanin: an emerging clinical problem.

Vancomycin and teicoplanin are glycopeptides active against a wide range of gram-positive bacteria. For 30 years following the discovery of vancomycin in 1956, vancomycin resistance was not detected among normally susceptible bacteria recovered from human specimens. Since 1986, however, bacteria resistant to vancomycin or teicoplanin or both have been described. Strains of the genera Leuconostoc, Lactobacillus, Pediococcus, and Erysipelothrix seem inherently resistant to glycopeptides. Species and strains of enterococci and coagulase-negative staphylococci appear to have acquired or developed resistance. There are at least two categories of glycopeptide resistance among enterococci, characterized by either high-level resistance to vancomycin (MIC, greater than or equal to 64 mg/liter) and teicoplanin (MIC, greater than or equal to 8 mg/liter) or lower-level vancomycin resistance (MIC, 32 to 64 mg/liter) and teicoplanin susceptibility (MIC, less than or equal to 1 mg/liter). The two categories appear to have similar resistance mechanisms, although genetic and biochemical studies indicate that they have arisen independently. Among coagulase-negative staphylococci, strains for which vancomycin MICs are up to 20 mg/liter or teicoplanin MICs are 16 to 32 mg/liter have been reported, but cross-resistance between these glycopeptides varies. The selective advantage accorded to glycopeptide-resistant bacteria and the observation that high-level resistance in enterococci is transferable suggest that such resistance may be expected to increase in incidence. Clinicians and microbiologists need to be aware of this emerging problem.

Animals↗

A community outbreak of group A beta haemolytic streptococci with transferable resistance to erythromycin.

Erythromycin resistance amongst group A streptococci (GAS) in Great Britain is a relatively rare occurrence and outbreaks have been sporadically reported. Over an 8-month period in 1986 ten associated cases occurred in the town of Bridgewater in Somerset. Isolates were group A, type M4 and resistant to erythromycin (MIC 8 mg/l) but sensitive to lincomycin and clindamycin. Erythromycin resistance was transferable from all isolates to a group A recipient strain. No plasmid DNA could be detected in the original isolates or transconjugants.

Adult↗

High-level vancomycin-resistant enterococci causing hospital infections.

Nosocomial infection or colonization due to enterococci with high-level resistance to vancomycin (minimal inhibitory concentrations [MICs] between 64 and greater than 2000 mg/L) has occurred in 41 patients with renal disease. These vancomycin-resistant enterococci were cultured from many sources including blood. All but one strain contained one or more plasmids ranging in molecular weight from 1.0 to 40 Megadaltons (MDa). Vancomycin resistance was transferable by conjugation to a susceptible recipient strain of Enterococcus faecalis but this was not always associated with plasmid DNA. The emergence of transferable high-level vancomycin resistance in enterococci causing significant clinical infections is of particular importance since vancomycin is widely regarded as a reserve drug for the management of infections with multi-resistant Gram-positive organisms.

Acute Kidney Injury↗

Horizontal transfer of penicillin-binding protein genes in penicillin-resistant clinical isolates of Streptococcus pneumoniae.

Resistance to penicillin in clinical isolates of Streptococcus pneumoniae has occurred by the development of altered penicillin-binding proteins (PBPs) that have greatly decreased affinity for the antibiotic. We have investigated the origins of penicillin-resistant strains by comparing the sequences of the transpeptidase domain of PBP2B from 6 penicillin-sensitive and 14 penicillin-resistant strains. In addition we have sequenced part of the amylomaltase gene from 2 of the sensitive and 6 of the resistant strains. The sequences of the amylomaltase gene of all of the strains and of the PBP2B gene of the penicillin-sensitive strain show that S. pneumoniae is genetically very uniform. In contrast the PBP2B genes of the penicillin-resistant strains show approximately equal to 14% sequence divergence from those of the penicillin-sensitive strains and the development of penicillin resistance has involved the replacement, presumably by transformation, of the original PBP2B gene by a homologous gene from an unknown source. This genetic event has occurred on at least two occasions, involving different sources, to produce the two classes of altered PBP2B genes found in penicillin-resistant strains of S. pneumoniae. There is considerable variation among the PBP2B genes of the resistant strains that may have arisen by secondary transformation events accompanied by mismatch repair subsequent to their original introductions into S. pneumoniae.

Aminoacyltransferases↗

Antimicrobial susceptibility testing of Streptococcus pneumoniae: quality assessment results.

Six strains of Streptococcus pneumoniae were distributed to 405 United Kingdom laboratories who were asked to test the susceptibility of the strains to penicillin, tetracycline, chloramphenicol and erythromycin and to provide details of methodology to test the standards of susceptibility testing. High error rates were seen only in failure to detect moderate resistance to penicillin (12%) and resistance to chloramphenicol (16%). Increased error rates were associated with several methods or practices. These included the use of certain culture media; failure to standardise the inoculum; inoculation by loop rather than by swab; failure to use control organisms; failure to measure zone sizes; the use of discs containing a high content of penicillin to test susceptibility to penicillin, and the use of high content discs for testing erythromycin, tetracycline, and chloramphenicol.

Chloramphenicol↗

Antibiotic resistance monitoring, with particular reference to methicillin-resistant Staphylococcus aureus.

Two surveys of antibiotic resistance in hospital pathogens are described. The first is a long-term, multi-center, laboratory based investigation in which antibiotic resistance data from laboratories with computerized reporting is collected. The difficulties of this type of investigation are discussed and some solutions suggested. In the second investigation reports of the isolation of methicillin-resistant Staphylococcus aureus (MRSA) were collected from microbiological laboratories on a nation-wide basis. The results were useful in monitoring the spread of the organism and in its control.

Cross Infection↗

Pneumococcal pneumonia with bacteraemia.

Fourteen cases of pneumococcal pneumonia with bacteraemia have been studied. Thirteen of the patients were older than 50 years and in ten there was evidence of pre-existing disease. Pneumococci of six serotypes were responsible for these infections but type 3 was the commonest and was associated with three of the four fatal cases. The patients who died all had evidence of renal failure. Eight of the ten survivors had prerenal failure which responded to treatment. Hyponatraemia was a common finding. Despite prompt antibiotic treatment and intensive therapy there is still a high morbidity and mortality from this condition.

Adult↗

The effect of influenza virus on the adherence of Haemophilus influenzae to human cells in tissue culture.

The adherence of eleven strains of Haemophilus influenzae to MRC5 cells was studied and compared with adherence of the same eleven strains to MRC5 cells infected with influenza A/NWS/33 virus. Per cent Adhesion (the proportion of cells to which more than two bacteria were adhering) was estimated. Organisms grown on solid media adhered better than those grown in liquid media though the difference was not statistically significant (t test for independent means). A wide range of % Adhesion values for organisms grown on solid media to control cells was exhibited (1-88%). Ten of eleven strains grown on solid media or in broth showed increased adherence to influenza virus infected cells; this difference was significant (P less than 0.05, t test for independent means). The effect of virus infection in increasing % Adhesion was inversely proportional to the adhesiveness of the strain in question to uninfected cells. Strains that adhered most efficiently to control cells showed little increase in % Adhesion following virus infection, while strains that adhered poorly to control cells showed large increases in % Adhesion following virus infection.

Adhesiveness↗