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Biomedical subjects

G L French

Publications and source records attributed to G L French.

At least 55 records · Page 3Linked to original sources
PubMed1996

Hospital outbreak of Klebsiella pneumoniae resistant to broad-spectrum cephalosporins and beta-lactam-beta-lactamase inhibitor combinations by hyperproduction of SHV-5 beta-lactamase.

An aminoglycoside- and ceftazidime-resistant strain of Klebsiella pneumoniae K2 producing the extended-spectrum beta-lactamase SHV-5 infected or colonized 14 pediatric patients at Guy's Hospital. The patients were mostly neonates recovering from cardiac surgery for congenital defects. The organism was also isolated from a nurse and from the father of one of the children. Four patients had septicemia, and two septicemic neonates with postoperative renal failure died. Aminoglycoside and cephalosporin resistance transferred to Escherichia coli in vitro on a 160-kb plasmid, and a similar resistant E. coli strain was isolated from the stools of one of the affected children. The epidemic organism colonized the bowel and skin and was probably transmitted via staff hands. Five wards were involved because of extensive patient movements. The outbreak was controlled by patient isolation and attention to handwashing. All of the isolates of the outbreak strain were identical by phage typing, ribotyping, plasmid profiling, and biochemical and serological testing, but they varied in their production of SHV-5. Some isolates produced normal amounts of SHV-5 and were susceptible to beta-lactam-beta-lactamase inhibitor combinations. Others, including the single isolate of multiresistant E. coli, produced up to five times as much enzyme as "normal" isolates. This hyperproduction resulted in increased resistance to several penicillins and cephalosporins and to the beta-lactam-beta-lactamase inhibitor combinations amoxicillin-clavulanic acid, ampicillin-sulbactam, piperacillin-tazobactam, and ceftazidime-clavulanic acid. The hyperproduction of SHV-5 by K. pneumoniae and E. coli seen in this outbreak suggests that beta-lactam-beta-lactamase inhibitor combinations may be unreliable for the treatment of organisms producing extended-spectrum beta-lactamases.

Adolescent↗
PubMed1995

Aeromonas septicaemia in Hong Kong species distribution and associated disease.

During a 5-year study of 2211 patients with clinically significant positive blood cultures in Hong Kong. Aeromonas spp. were isolated in 40 cases. Among 26 episodes in which a single species was isolated. 17 (65.4%) were identified as Aeromonas hydrophila. 8 (30.8%) as A. sobria and one (3.8%) as A. caviae. There were 14 episodes with a mixture of species. Of these, nine (64.3%) were identified as A. hydrophila, two (14.3%) as A. sobria, and two (14.3%) as A. caviae. One (7.1%) was an infection with both A. sobria and A. hydrophila. These polymicrobial infections were usually combined with the presence of Enterobacteriaceae. Hepatobiliary disease was the underlying problem in 24 cases (60.0%) and malignant neoplasia in 14 (35.0%) cases. Most patients presented with fever and leucocytosis. The mortality rate for A. sobria septicaemia was not significantly different from the average rate for all septicaemias. A total of 30 isolates was available for sensitivity testing with 17 antibiotics. More than 86.0% were resistant to ampicillin, and the addition of the beta-lactamase inhibitor sulbactam did not restore its activity. All strains tested were sensitive to cefotaxime, ceftazidime, aztreonam, imipenem, norfloxacin and ciprofloxacin.

Aeromonas↗
PubMed1995

vanA genes in vancomycin-resistant clinical isolates of Oerskovia turbata and Arcanobacterium (Corynebacterium) haemolyticum.

We report the cloning and sequencing of vanA genes present in the high-level vancomycin- and teicoplanin-resistant clinical isolates Oerskovia turbata 892 and Arcanobacterium (Corynebacterium) haemolyticum 872. The presence of vanA was detected by Southern blotting and PCR and confirmed by DNA sequencing. vanA-like sequences were encoded on plasmids of 15 and 20 kb respectively. The A. haemolyticum 872 DNA sequence was identical to the published vanA sequence of vancomycin-resistant Enterococcus faecium BM4147, but the O. turbata 892 sequence showed three coding changes. Induction experiments indicated that vancomycin resistance in A. haemolyticum 872 and O. turbata 892 was constitutive. SDS-PAGE analysis of membrane proteins showed the presence of a c. 39 kD protein in both clinical isolates whose expression was unaltered in the presence of vancomycin, while a similar protein in E. faecium BM4147 was inducible. Since A. haemolyticum and O. turbata are naturally susceptible to vancomycin, the high-level constitutive resistance seen in these isolates appears to be mediated by vanA. This is the first report confirming the presence of vanA in genera other than Enterococcus.

Actinomycetaceae↗
PubMed1994

In-vitro antimicrobial susceptibility and beta-lactamases of ampicillin-resistant Escherichia coli in Hong Kong.

Three hundred and forty isolates of ampicillin-resistant Escherichia coli isolated from blood, bile and urine were collected during 1984 and 1988 in the Prince of Wales Hospital, Hong Kong and MICs of 21 beta-lactam antibiotics were determined. beta-Lactamases were identified by isoelectric focusing, and TEM-1 was found in 89.1% of isolates, PSE-1 in 3.2%, and OXA-1 in 2.9% of strains. Ten isolates (2.9%) possessed both TEM-1 and PSE-1. Five isolates (1.5%) produced only chromosomal enzymes and one produced an unidentified enzyme which focussed at pI 6.0. All but seven of 274 TEM-1 producers and all nine OXA-1 producers reacted with oligonucleotide probes in a colony blot technique. All isolates contained plasmids and 229 of 318 (72.0%) isolates transferred the ampicillin resistance factor. Of 42 transconjugants of TEM-1 producers selected for study, 39(92.9%) had only a single transferable plasmid bearing the TEM-1 gene.

Ampicillin Resistance↗
PubMed1994

The human gastric pathogen Helicobacter pylori has a gene encoding an enzyme first classified as a mucinase in Vibrio cholerae.

The human bacterial pathogen Helicobacter pylori has been suggested to be the causative agent of the most common chronic infection of man. Since its first isolation in 1982, H. pylori has been associated with gastric and duodenal ulcer disease, and more recently, gastric cancer. The proteolytic digestion of gastric mucus by this microorganism has been suggested as an important mechanism by which its pathogenicity is at least partly exerted. Here we report the detection of protease activity in H. pylori total-cell and supernatant extracts. On the basis that zinc metalloproteases are common microbial pathogenicity factors, we identified a single protein in H. pylori protein extracts with antibodies to the Pseudomonas aeruginosa elastase (a secreted zinc metalloprotease). This same protein was identified by pooled serum from patients infected with H. pylori. We used the functional and immunological relationship between the P. aeruginosa elastase and the Vibrio cholerae haemagglutinin/protease (HAP) to clone the H. pylori hap gene, which was over 99% similar to the V. cholerae hap gene in the coding region. A 4 kb DNA fragment containing the entire cloned gene was highly unstable in Escherichia coli and Bacillus subtilis cloning vectors. We also demonstrated that a hap-like gene sequence is present in all nine Helicobacter species so far discovered. The V. cholerae HAP was first classified on the basis of its mucinase activity.

Amino Acid Sequence↗
PubMed1993

Closing the loop: audit in infection control.

The audit cycle has four parts: setting standards, testing practice and outcome against these standards, correcting practice where it falls short, and re-auditing to confirm that standards are now met. The last two steps complete the audit cycle or 'close the loop'. Infection control can be audited for whether written guidelines exist for each procedure, whether these guidelines are acceptable and whether they are followed in practice. This form of audit is relatively simple provided there are authoritative model guidelines available, produced by organizations such as the Hospital Infection Society. The best outcome measure of infection control is the nosocomial infection rate, but this is the most difficult to audit in practice. If audit results are to be compared between hospitals or between different time periods in the same hospital, infection rates should be adjusted for the underlying risks of infection in the patient population. This type of audit can be done by repeated prevalence surveys.

Cross Infection↗
PubMed1993

Molecular studies of plasmids of multiply-resistant Shigella spp. in Hong Kong.

One hundred and two Shigella spp. isolated in two hospitals in Hong Kong were analysed for antibiotic resistances, resistance plasmids and plasmid profiles. Three quarters of the isolates were S. flexneri. All isolates harboured plasmids, up to a maximum of ten within one strain. Plasmids of 220 kb encoding resistances to tetracycline, chloramphenicol and sulphonamide and probably also associated with invasiveness in the Sereny test were found in 80 strains and were transferable in 18% of cases. Resistance plasmids of 92 and 99 kb were found in 27 and 15 strains respectively and encoded resistances to ampicillin, tetracycline, chloramphenicol, kanamycin, sulphonamide, trimethoprim, cotrimoxazole and gentamicin; these plasmids were usually transferable. Four plasmids of 3.9, 2.8, 2.2 and 1.8 kb were commonly found in S. flexneri strains, but were rare in other species. In contrast, there was no predominant plasmid profile in S. sonnei. S. flexneri is endemic in Hong Kong and these plasmid studies suggest that the strains in circulation are derived from only a few clones.

Animals↗
PubMed1992

Effect of biliary obstruction on the hepatic excretion of imipenem-cilastatin.

The biliary excretion of imipenem-cilastatin studied by endoscopic cannulation of the common bile duct in patients with complete obstruction and in a group without obstruction showed that despite a 24-h prophylaxis, the bile obtained from patients with obstruction immediately after cannulation contained neither imipenem nor cilastatin, while there were 2 and 5% of peak concentrations in serum for imipenem and cilastatin, respectively, in the bile from patients without obstruction. Biliary excretion of both compounds increased rapidly after decompression, reaching a maximum of 15% of peak levels in serum within 2 h. Twenty-four hours after drainage, the biliary excretion of the drugs further improved. We conclude that since biliary obstruction impairs excretion of antibiotics, drainage is necessary for the control of sepsis in obstructed cholangitis.

Adult↗
PubMed1992

Development of trimethoprim-resistance in Salmonella typhi during therapy.

A typhoid patient was infected with a fully-sensitive, plasmidless strain of Salmonella typhi which acquired resistance to kanamycin, sulfamethoxazole and trimethoprim during cotrimoxazole therapy. The resistant post-treatment strain harboured 4 plasmids of 62, 4.1, 3.8 and 3.0 Md in size. Kanamycin-, sulfamethoxazole- and trimethoprim-resistance were borne on a transferable 62 Md plasmid which was compatible with groups FI, FIme, FII, FIV, H1, H2, B, I1, I2, J, K, M, N, T, X, W and P. Sulfamethoxazole-resistance was also borne on the 4.1 Md plasmid. The 3.8 Md plasmid was not transferable; the 3.0 Md plasmid was transferable but did not confer antibiotic resistance. Excluding the strain described here, only 5 out of 35 other S typhi isolates contained plasmids. This is the first report of trimethoprim-resistant S typhi in Hong Kong.

Adult↗
PubMed1991

Measurement of the costs of hospital infection by prevalence surveys.

Data from seven single-day prevalence surveys were used to assess the costs of hospital-acquired infection (HAI) by matching infected cases with controls and reviewing patient case notes for details of mortality, length of hospitalization and antibiotic treatment costs. Many cases with a high risk of HAI could not be matched and probably had inevitable infection. Cases that could be matched had the same risks of HAI as the controls, and these infections were potentially avoidable. Compared with controls, infected patients had an excess mortality rate of 7.4%, an average excess hospital stay of 23 days and an average excess antibiotic expenditure of US$190. By extrapolation we calculate that the annual costs of avoidable HAI at Prince of Wales Hospital is now approximately 130 lives, 42 000 bed-days and US$0.3m of antibiotics; costs of a similar magnitude have already been saved by a programme of hospital infection control. We conclude that hospital-acquired infection is very expensive, infection control is highly cost-effective, and prevalence surveys are practical tools for the measurement of rates and costs of hospital infection.

Adult↗
PubMed1991

The use of personal computers in hospital infection control.

The storage, retrieval and analysis of hospital infection data is best performed by using computers. Many laboratory mainframe systems have infection control modules and there are some commercial programs for personal computers (PCs). An alternative is to use business and statistical PC software. Because of their large customer base these programs are reliable and easy to use yet extremely sophisticated and flexible, and they can be easily customized for use in infection control. Many combinations of software and hardware are available but the ones described here have been used successfully for several years at the Prince of Wales Hospital in Hong Kong.

Computer Graphics↗
PubMed1991

Pharmacokinetics of parenteral imipenem/cilastatin in patients on continuous ambulatory peritoneal dialysis.

We investigated the pharmacokinetics of two intravenous (iv) dose regimens of imipenem/cilastatin in Chinese patients on chronic ambulatory peritoneal dialysis (CAPD), who had an average creatinine clearance of 3.2 ml/min/1.73 m2. Doses of 0.5 and 1.0 g produced mean peak serum imipenem concentrations of 30 and 70 mg/l respectively, about 60% of cilastatin. Peritoneal dialysis fluid (PDF) imipenem concentrations reached 20-30% of the serum peak 4-5 h after iv injection, and the lowest maximum PDF concentrations were 2 mg/l after the 0.5 g dose and 14 mg/l after 1.0 g. Thus both regimes produced PDF imipenem concentrations above the MICs of susceptible pathogens. The half-life of imipenem was 6.4 h and the plasma clearance 66 ml/min; serum and PDF imipenem were in equilibration after about 5 h. Cilastatin had a prolonged half-life of 19 h and a plasma clearance of 10 ml/min, and accumulated in both serum and PDF. With a 0.5 g dose, the pharmacokinetics of imipenem/cilastatin suggest that the combination may prove an effective treatment for peritonitis associated with CAPD.

Adult↗