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Biomedical subjects

R C George

Publications and source records attributed to R C George.

At least 19 recordsLinked to original sources

Diphtheria immunity in UK blood donors.

Immunity to diphtheria was determined in serum samples from 1000 UK-born blood donors at the North London Blood Transfusion Centre during a three-month period in 1993; 125 women and 125 men were stratified in 10-year age groups, from 20 to 59. A tissue (vero cell)-culture toxin-neutralisation assay was used to measure serum diphtheria antitoxin concentrations. According to internationally accepted definitions (antitoxin < 0.01 IU/mL = susceptibility, 0.01-0.09 IU/mL = basic protection, and > or = 0.1 IU/mL = full protection), 37.6% of donors were susceptible to diphtheria, 31.5% had basic protection, and 30.9% were fully protected. Log-linear modelling of the influence of age and sex on population immunity showed a significant trend (p < 0.001) of decreasing immunity with increasing age: 25.2% of donors aged 20-29 were susceptible compared with 52.8% of those aged 50-59. There was a small sex effect (p = 0.052); similar proportions of men and women were susceptible, but fewer women had full protection. There was no age-sex interaction on immunity (p = 0.454). Our results suggest that booster immunisation of adults is necessary to increase herd immunity of the adult population.

Adult

Pneumococcal bacteraemia and meningitis in England and Wales 1982 to 1992.

In the 11 years from 1982 to 1992, microbiology laboratories in England and Wales reported 22,567 episodes of serious illness in which Streptococcus pneumoniae was isolated from blood and 3500 in which it was isolated from cerebrospinal fluid. Half of the reported cases of bacteraemia occurred in people of over 65 years (11,299 cases). A predisposing cause was seldom reported. Annual totals of reports of pneumococcal bacteraemia and meningitis have risen in parallel with other serious infections. The rates of pneumococcal infections reported in very young and elderly people have risen much more rapidly and, although this observation may be artefactual, it may be associated with an observed increase in reports of antibiotic resistance. The proportion of pneumococcal isolates resistant to penicillin rose from 0.3% in 1989 to 1.9% in 1992 (p < 0.05). We suggest that the role of pneumococcal vaccination should be re-evaluated.

Adolescent

Distribution of serovariants of group B streptococci in isolates from England and Norway.

The distribution of capsular polysaccharide antigen (CHO) types, surface-exposed c proteins alpha (c alpha) and beta (c beta) and an R-protein antigen was examined in 334 group B streptococci (GBS) isolates from three groups of patients hospitalised in England and Wales or Norway. The isolates were from 108 carriers, 67 cases of neonatal infection and 154 cases of adult infection. Each group contained all CHO types (Ia, Ib, II, III, IV, V and NT); type III strains predominated except in the adult infected group. Strains within each CHO type could be further subdivided by the protein markers into five subtypes by a combined typing system. The proportion of type Ib and type III strains in the neonatal infection cases and of type Ib strains in the adult infection cases significantly outnumbered isolates of these serotypes among the carrier strains. Twenty-nine different serovariants were identified; 24, 13 and 23 serovariants among the carrier, neonatal infection and adult infection isolates, respectively. Certain CHO antigen-protein associations were identified, notably those between Ia/c alpha, Ib/c alpha beta and III/R. The proportion of invasive isolates that expressed protein was not higher than in the carrier isolates. All CHO-type Ib isolates contained a c protein, but 7% of the Ib isolates did not contain any of these proteins. These findings indicate that this combined typing approach may be useful in examining epidemiological problems associated with GBS.

Adult

Molecular epidemiology of Corynebacterium diphtheriae from northwestern Russia and surrounding countries studied by using ribotyping and pulsed-field gel electrophoresis.

A selection of 100 Corynebacterium diphtheriae isolates from asymptomatic carriers and clinical cases from five regions in northwestern Russia were examined. Six additional isolates from patients in Finland and Estonia with epidemiological links to Russia were also examined. All isolates were characterized by biotyping, toxigenicity testing, ribotyping, and pulsed-field gel electrophoresis (PFGE). Hybridization of genomic DNA digested with BstEII revealed five ribotype patterns among the biotype gravis isolates (G1 through G5) and two patterns among the biotype mitis isolates (M1 and M2). PFGE using SfiI was not able to distinguish between ribotypes G1, G2, and G4. The predominant ribotype pattern, G1, found in cases of disease in all the areas studied, appears to be disseminating, in view of the isolates received from imported cases in Finland and Estonia. Among the 106 isolates examined, 68 produced pattern G1 and 24 produced pattern M1. Most of the M1 isolates were from the Leningrad Oblast region. Distinct ribotypes such as G2, G3, G4, G5, and M2 could represent endemic disease.

Bacterial Typing Techniques

The in-vitro susceptibilities of toxigenic strains of Corynebacterium diphtheriae isolated in northwestern Russia and surrounding areas to ten antibiotics.

The in-vitro activities of ten antibiotics against 83 toxigenic strains of Corynebacterium diphtheriae recently isolated in northwestern Russia and surrounding areas were determined by an agar dilution method. All of the strains were susceptible to erythromycin, penicillin, ampicillin, cefuroxime, chloramphenicol, ciprofloxacin, gentamicin and tetracycline. Trimethoprim and rifampicin were each active against 81 isolates, the two strains resistant to the latter agent having been isolated from two members of the same family.

Anti-Bacterial Agents

Gentamicin resistance in clinical isolates of Escherichia coli encoded by genes of veterinary origin.

Seven (27%) of 26 gentamicin-resistant human clinical isolates of Escherichia coli were resistant to the veterinary aminoglycoside antibiotic apramycin. A gentamicin-resistant Klebsiella pneumoniae isolate from a patient infected with gentamicin/apramycin-resistant E. coli was also resistant to apramycin. DNA hybridisation studies showed that all gentamicin/apramycin-resistant isolates contained a gene encoding the enzyme 3-N-aminoglycoside acetyltransferase type IV (AAC[3]IV) that mediates resistance to gentamicin and apramycin in bacteria isolated from animals. Seven of the eight gentamicin/apramycin-resistant isolates were also resistant to the veterinary antihelminthic agent hygromycin B, a phenomenon observed previously in gentamicin/apramycin-resistant Enterobacteriaceae isolated from animals. Resistance to gentamicin/apramycin and hygromycin B was co-transferable in six of the isolates. Restriction enzyme analysis of plasmids in apramycin-resistant transconjugants derived from E. coli and K. pneumoniae isolates from the same patient were virtually identical, suggesting that inter-generic transfer of plasmids encoding apramycin resistance had occurred in vivo. These findings support the view that resistance to gentamicin and apramycin in clinical isolates of E. coli results from the spread of resistant organisms from animals to man, with subsequent inter-strain or inter-species spread, or both, of resistance genes on transferable plasmids.

Acetyltransferases

Genetics of oxacillin resistance in clinical isolates of Streptococcus pneumoniae that are oxacillin resistant and penicillin susceptible.

It has recently been reported that penicillin-sensitive pneumococci may exhibit reduced susceptibility to oxacillin, resulting in their misclassification as being penicillin resistant by oxacillin disk testing. Intermediate oxacillin resistance (MIC, 1.0 microgram/ml) in three of these apparently unrelated penicillin-susceptible clinical isolates of Streptococcus pneumoniae isolated in the United Kingdom and in four Spanish isolates was shown to be solely due to the acquisition of a gene encoding an altered penicillin-binding protein (PBP), PBP2X. PBP2X genes cloned from typical penicillin-resistant isolates of S. pneumoniae that possessed high-level oxacillin resistance were shown to be able to transform susceptible isolates of S. pneumoniae to intermediate oxacillin resistance. In all instances, the intermediately oxacillin-resistant PBP2X transformants retained susceptibility to penicillin (MIC, 0.06 microgram/ml). Under appropriate selective pressure, the acquisition of a low-affinity PBP2X by penicillin-susceptible pneumococci could result in an increasing number of false positives for penicillin resistance among isolates of S. pneumoniae screened with oxacillin. Additionally, these intermediately oxacillin-resistant isolates showed reduced susceptibility to cefotaxime, an agent likely to be prescribed in place of penicillin for the treatment of serious infections due to these apparently penicillin-resistant organisms.

Bacterial Proteins

The emergence of vancomycin resistance in renal dialysis.

Intraperitoneal vancomycin is used in the treatment of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). We describe the emergence of low-level glycopeptide-resistance in five Gram-positive species over a one-year period. Isolation of these organisms was associated with vancomycin treatment failure in four patients who had had numerous episodes of peritonitis. Clinicians and microbiologists should be aware that repeated administration of glycopeptides to such patients might lead to the emergence of organisms resistant to these antibiotics.

Aged

Nosocomial spread of Staphylococcus aureus showing intermediate resistance to methicillin.

A nosocomial outbreak of infection and colonization involving six patients and caused by a strain of Staphylococcus aureus showing intermediate resistance to methicillin (MIC = 4-8 mg l-1) is described. The outbreak was associated with skin-carriage of the epidemic strain by a nurse suffering from severe eczema. The reduced susceptibility of the outbreak strain to methicillin was associated with beta-lactamase production. Elimination or inhibition of beta-lactamase activity produced a two-fold decrease in methicillin MIC. There was no evidence for the presence of either penicillin-binding protein 2a or the corresponding mec gene, which mediate resistance in fully methicillin-resistant strains.

Carrier State

In-vitro characteristics of glycopeptide resistant strains of Staphylococcus epidermidis isolated from patients on CAPD.

The low-level resistance of three clinical isolates of Staphylococcus epidermidis to glycopeptide antibiotics was found to be constitutive, not inducible, and was not increased by passage in the presence of either vancomycin or teicoplanin. There was no loss of resistance on repeated passage in antibiotic-free broth. In contrast, the susceptibility to these antibiotics declined for S. epidermidis NCTC 6513 that been sequentially passaged in either vancomycin or teicoplanin whereas the variants reverted to being susceptible on further passage in antibiotic-free broth. Antibiotic activity was almost completely abolished when cultures of the resistant S. epidermidis strains were exposed overnight to sub-MIC concentrations. No evidence of drug-modifying activity was obtained. Experiments of antibiotic-binding activity indicated that the resistant strains exhibited an increased ability to sequester antibiotics which was particularly rapid in stationary phase cultures when most of the antibiotic activity disappeared from the growth medium within 30 min of exposure to the drugs. Teicoplanin was sequestered more efficiently than vancomycin and some loss of activity was also observed when stationary phase cultures of S. epidermidis NCTC 6513 were exposed to glycopeptides. These results suggest that glycopeptide-resistant isolates of S. epidermidis are able to bind large amounts of these antibiotics, possibly at sites unassociated with the D-alanyl-D-alanine target, and that teicoplanin is bound more avidly than vancomycin.

Anti-Bacterial Agents