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R C George

Publications and source records attributed to R C George.

At least 19 recordsLinked to original sources
PubMed1992

Antibiotic-resistant pneumococci in the United Kingdom.

Pneumococcal pneumonia and meningitis remain common infections with significant morbidity and mortality. For many years, penicillins or cephalosporins, erythromycin and chloramphenicol have been the mainstay of chemotherapy for these and other pneumococcal infections. Resistance to these antimicrobial agents has increased worldwide and resistant pneumococci are now isolated with increasing frequency in the United Kingdom. This article reviews the results of antimicrobial susceptibility and serotyping studies carried out over the last five years on UK isolates of Streptococcus pneumoniae referred to the Streptococcus and Antibiotic Reference Laboratories of the Division of Hospital Infection for serotyping or confirmation of antibiotic resistance. During this period there has been a marked increase in the referral of pneumococcal isolates resistant to one or more of the antimicrobials commonly used for treatment. The implications for antimicrobial therapy and vaccination policy are discussed.

Drug Resistance, Microbial↗
PubMed1992

Multiresistant Klebsiella pneumoniae in a neonatal nursery: the importance of maintenance of infection control policies and procedures in the prevention of outbreaks.

During a 3-week period, nine babies in the neonatal unit of a large teaching hospital in Durban were infected or colonized with Klebsiella pneumoniae resistant to a range of antimicrobial agents including amikacin and cefotaxime. Resistance to cefotaxime was reduced by clavulanic acid in vitro suggesting production of extended-spectrum beta-lactamase activity. All the isolates had the same antibiotic resistance profile, belonged to the same serotype (K17), were non-typable with bacteriophages, and had identical plasmid profiles indicating that they belonged to the same strain. During a 1-day microbiological survey of the ward, the outbreak strain was isolated from the nose and hands of a doctor based in the nursery and from the hands of a nurse and the mother of an infected baby. The strain was also isolated from nine of 67 environmental samples. Investigation revealed that infection control practices which had been instituted following a previous outbreak in the nursery with multi-resistant methicillin-resistant Staphylococcus aureus (MRSA) were not being adhered to. The re-introduction and strict enforcement of these procedures under the supervision of an Infection Control Nurse resulted in the abrupt end of the outbreak.

Amikacin↗
PubMed1992

Outbreak of infection in two UK hospitals caused by a strain of Klebsiella pneumoniae resistant to cefotaxime and ceftazidime.

During an 8-month period, Klebsiella pneumoniae resistant to cefotaxime and ceftazidime were isolated from 18 elderly patients in two closely-situated UK hospitals. Amongst these 18 patients, the organisms were isolated from urine samples of 17, from blood cultures of two and from a wound swab of one. The infected patients were located in nine different wards and several of the patients had been transferred between wards, within and between the two hospitals. All the bacterial isolates belonged to serotype K62, were non-typable or reacted only weakly with bacteriophage, showed similar plasmid profiles and were resistant to tetracycline and trimethoprim, thus indicating they were the same strain. Resistance to cefotaxime and ceftazidime was inhibited by clavulanic acid suggesting the involvement of extended-spectrum beta-lactamase (ESBL) enzyme activity. This was confirmed by analytical isoelectric focusing, which showed that isolates each produced two beta-lactamases with isoelectric points of 7.0(SHV-3) and 7.6 (SHV-1/2) respectively.

Cefotaxime↗
PubMed1992

High-level resistance to gentamicin in Enterococcus faecium.

During a six-month period in a hospital in Ireland, four patients were infected (isolation from blood cultures) and two were colonized (isolation from rectal swabs) with strains of Enterococcus faecium highly resistant to gentamicin. MICs of gentamicin were greater than 1000 mg/L for all six strains, and each possessed a plasmid of approximately 50 MDa. Resistance to gentamicin was transferable by conjugation from two of the six strains, and was associated with transfer of the 50 MDa plasmid. This plasmid hybridized with a DNA probe specific for the bifunctional AAC(6')-APH(2") aminoglycoside-modifying enzyme. The mechanism of high-level gentamicin resistance in these strains appeared therefore, to be identical to that encountered in Enterococcus faecalis strains worldwide and reported in E. faecium strains in the USA.

Conjugation, Genetic↗
PubMed1991

Direct enantiomeric separation of terfenadine and its major acid metabolite by high-performance liquid chromatography, and the lack of stereoselective terfenadine enantiomer biotransformation in man.

Direct enantiomeric separation of terfenadine and its major acid metabolite was achieved by using two different chiral stationary phase columns with two different mobile phase systems. Further, the enantiomeric composition of the human urinary acid metabolite has been determined, indicating a non-stereoselective biotransformation in man.

Biotransformation↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗