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Biomedical subjects

R C George

Publications and source records attributed to R C George.

At least 73 records · Page 4Linked to original sources

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↗

Comparison of high-level gentamicin-resistant Enterococcus faecium isolates from different continents.

Eight clinical isolates of Enterococcus faecium highly resistant to gentamicin (MIC, > 1,000 mg/liter) from patients in six hospitals on three continents were investigated for evidence of spread of either a clone of high-level gentamicin-resistant (HLGR) E. faecium or wide dissemination of a gentamicin resistance (Gmr) plasmid. A combination of ribotypes, plasmid profiles, and extended antimicrobial susceptibilities enabled us to distinguish all but two of the isolates and did not suggest clonal dissemination of a single strain. Two isolates from hospitals situated close together appeared identical by these methods. All of the isolates carried Gmr plasmids which appeared to be closely related following digestion with restriction endonucleases. Cross-hybridization studies confirmed extensive DNA homology between these plasmids. The fragments of these plasmids which hybridized with a probe specific for the aac6'aph2" resistance gene did not resemble those seen in the Gmr transposon Tn5281, which was characterized previously in E. faecalis HH22. This study suggests that there has been widespread dissemination of a single Gmr plasmid and its derivatives amongst isolates of HLGR E. faecium, although a Gmr plasmid from an HLGR E. faecium isolated in the United States showed little homology with the other Gmr plasmids studied.

Conjugation, Genetic↗

Application of DNA probes for rRNA and vanA genes to investigation of a nosocomial cluster of vancomycin-resistant enterococci.

DNA probes specific for genes encoding rRNA and the glycopeptide resistance gene vanA were used to investigate a cluster of vancomycin-resistant (MICs, > 512 mg/liter) Enterococcus faecalis and Enterococcus faecium isolated from separate patients in a renal unit in a London hospital. When digested with BamHI, 12 of 13 vancomycin-resistant E. faecalis isolates exhibited a common restriction fragment length polymorphism pattern of rRNA genes (ribotype). A vanA probe hybridized with chromosomal DNA in these 12 isolates. The other isolate of vancomycin-resistant E. faecalis had a different ribotype and the vanA gene was located on plasmid DNA. These data suggest that cross-infection with a single strain of vancomycin-resistant E. faecalis occurred in most instances. In contrast, 23 vancomycin-resistant E. faecium isolates showed greater heterogeneity, comprising 8 ribotypes, suggesting that multiple strains were present in the unit. Twenty-one of these 23 isolates harbored a 24-MDa plasmid which hybridized with the vanA probe, implying that interstrain dissemination of a vancomycin resistance plasmid may have occurred among E. faecium isolates in the renal unit.

Bacterial Proteins↗

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↗

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↗

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↗

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↗

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↗