Search PubMed⌕ Search

Biomedical subjects

G L French

Publications and source records attributed to G L French.

At least 19 recordsLinked to original sources
PubMed2006

Bactericidal agents in the treatment of MRSA infections--the potential role of daptomycin.

Over the last decade, methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged as serious pathogens. These strains are often multiresistant to several antibiotic classes and are a major cause of serious hospital- and now community-acquired infections and associated morbidity and mortality. As a result of increasing antimicrobial resistance, glycopeptides, such as vancomycin, are widely used as first-line therapy for serious MRSA infections. However, the emergence of glycopeptide tolerance and resistance has complicated treatment and there remains a clinical need for new antibiotics with suitable pharmacokinetic properties with activity against MRSA and other gram-positive pathogens. Infections caused by MRSA and other bacteria usually respond as well to bacteriostatic agents as to bactericidal ones. Nevertheless, there is evidence that rapid bacterial killing has potential clinical advantages over bacteriostatic therapy in certain infections. Daptomycin, the first of the cyclic lipopeptides, shows rapid bactericidal activity against S. aureus, including strains tolerant or resistant to other agents. This review outlines the methods by which bactericidal and bacteriostatic properties are defined and tested, discusses the potential importance of bactericidal therapy in MRSA and other infections and examines the potential role of daptomycin in treatment.

Anti-Bacterial Agents↗
PubMed2006

Enhanced surveillance of meticillin-resistant Staphylococcus aureus bacteraemia in a London teaching hospital.

In 2001, the UK Department of Health introduced mandatory surveillance of meticillin-resistant Staphylococcus aureus (MRSA) bacteraemias (blood-culture-positive episodes) in English hospitals. We performed enhanced surveillance in their hospital between April 2001 and March 2003 to determine the epidemiology of MRSA bacteraemia across different specialities. There were 267 MRSA-blood-culture-positive episodes, giving a rate of 0.37 per 1000 occupied bed-days (OBD). Thirty-three (12.4%) episodes were false positives due to contaminants and 15 (5.6%) originated in the community or at another institution. Thirty-one (11.6%) episodes were in outpatients or occurred after recent discharge and were designated 'hospital associated'. The remaining 188 cases were clinically significant hospital-acquired episodes in inpatients, with a rate of 0.26 per 1000 OBDs. The highest rates were in the intensive therapy unit (ITU; 2.74 per 1000 OBDs) and the high-dependency unit (HDU; 1.68 per 1000 OBDs). Fifty-five non-ITU, non-HDU episodes occurred in patients who had been discharged from ITU or HDU prior to the development of bacteraemia but during the same admission. The number of MRSA bacteraemias related to ITU/HDU suggests that these wards may be hubs of MRSA infection. Haematology, oncology and renal (HOR) patients had the greatest number of hospital-associated episodes. The most common source of MRSA bacteraemia was a vascular access device (VAD) (108 episodes, 57%, 64% of which were central lines). The high bacteraemia rates in ITU, HDU and HOR patients were associated with high usage of VADs. The majority of episodes occurred in patients who were newly colonized with MRSA after admission. Thus, in this hospital, VADs and stays in ITU or HDU are important risk factors for bacteraemia, and VAD care and prevention of cross-infection are priorities for intervention. We recommend that the mandatory national surveillance scheme should collect additional data on MRSA bacteraemia to provide information for a national strategy for MRSA control and to allow appropriate comparison between institutions.

Adolescent↗
PubMed2005

Guidelines for the control of glycopeptide-resistant enterococci in hospitals.

The increase since the mid 1980s in glycopeptide resistant enterococci (GRE) raised concerns about the limited options for antimicrobial therapy, the implications for ever-increasing numbers of immunocompromised hospitalised patients, and fuelled fears, now realised, for the transfer of glycopeptide resistance to more pathogenic bacteria, such as Staphylococcus aureus. These issues underlined the need for guidelines for the emergence and control of GRE in the hospital setting. This Hospital Infection Society (HIS) and Infection Control Nurses Association (ICNA) working party report reviews the literature relating to GRE prevention and control. It provides guidance on microbiological investigation, treatment and management, including antimicrobial prescribing and infection control measures. Evidence identified to support recommendations has been categorized. A risk assessment approach is recommended and areas for research and development identified.

Anti-Bacterial Agents↗
PubMed2005

Clinical impact and relevance of antibiotic resistance.

Increasing antimicrobial resistance and multiple resistance have resulted in increasing difficulties in the treatment of bacterial infections. Resistance leads to inappropriate empirical therapy, delay in starting effective treatment, and the use of less effective, more toxic, and more expensive drugs. Although studies are not always consistent, antimicrobial resistance in the infecting organisms is associated with treatment failure, prolonged or additional hospitalization, increased costs of care, and increased mortality. Additional costs and lost bed days are incurred by the need to control the spread of antimicrobial-resistant organisms within hospitals. All this has significant direct impact on patients and their families and also secondary effects on the cost effectiveness of healthcare delivery. There is an urgent need to control antimicrobial resistance by improved antibiotic usage and reduction of hospital cross-infection.

Anti-Bacterial Agents↗
PubMed2005

Significant reduction of endemic MRSA acquisition and infection in cardiothoracic patients by means of an enhanced targeted infection control programme.

Due to increasing methicillin-resistant Staphylococcus aureus (MRSA) infection in cardiothoracic patients at St Thomas' Hospital, an enhanced infection control programme was introduced in September 2000. It was based on UK national guidelines on the control of MRSA and targeted additional identified risk factors for surgical site infection (SSI). It included recognition of the problem by senior staff and their taking responsibility for it; intensive support, education and advice from the infection control team; improved ward and theatre hygiene; pre-admission, admission and weekly MRSA screening; isolation and clearance treatment; nursing care pathways for MRSA colonized patients; and teicoplanin plus gentamicin surgical prophylaxis. The effectiveness of the programme was assessed by retrospective analysis of computerized patient data for the 16 months before and after the introduction of the programme. There was no significant change in the number of operations or the proportion of patients admitted with MRSA, although nine patients were cleared of carriage before admission. However, there were significant falls in the proportion of patients acquiring MRSA on the ward [38/1036 to 14/921, P=0.003, RR 2.4 (95%CI 1.32-4.42)] and in the rate of bloodstream MRSA infections [12/1075 to 2/956, P=0.014, RR 5.34 (95%CI 1.20-23.78)]. Sternal and leg wound infections both halved (from 28/1075 to 13/956 and 16/1075 to 7/956, respectively) but this did not reach statistical significance. These results demonstrate that an enhanced, targeted infection control programme based on the UK national guidelines, SSI prevention guidelines and local risk assessment can reduce the incidence of nosocomial MRSA acquisition and invasive infection in cardiothoracic patients in the face of continuing endemic risk.

Antibiotic Prophylaxis↗
PubMed2005

Octreotide induced prolongation of colonic transit increases faecal anaerobic bacteria, bile acid metabolising enzymes, and serum deoxycholic acid in patients with acromegaly.

BACKGROUND: Acromegalic patients have slow colonic transit, increased rates of deoxycholic acid formation, and an increased prevalence of cholesterol gall stones, especially during long term octreotide treatment. However, the effects of this prolonged large bowel transit time on the numbers of faecal anaerobes and the activities of the enzyme systems which biotransform conjugated cholic acid into unconjugated deoxycholic acid (cholylglycine hydrolase and 7alpha-dehydroxylase) are unknown. METHODS: Therefore, in 10 non-acromegalic controls, 11 acromegalic patients not treated with octreotide, and 11 acromegalics on long term (8-48 months) octreotide (100-200 mug three times daily subcutaneously), we measured large bowel transit time and, in freshly voided faeces, the activities of the two bile acid metabolising enzymes, and related the results to the proportion of deoxycholic acid in fasting serum. Moreover, in patients with acromegaly, we measured quantitative bacteriology in faeces. RESULTS: Mean large bowel transit time in acromegalics not treated with octreotide (35 (SEM 6.5) hours) was 66% longer than that in non-acromegalic controls (21 (3.1) hours; NS) and became further prolonged during octreotide treatment (48 (6.6) hours; p<0.001). These octreotide induced changes in transit were associated, in acromegalic patients, with more total (15.0 (2.5) v 6.3 (1.3)x10(9) colony forming units (cfu)/g; p<0.05) and Gram positive (6.3 (2.3) v 3.2 (1.0)x10(9) cfu/g; p<0.05) faecal anaerobes. Mean faecal cholylglycine hydrolase activity in the long term octreotide group (22.0 (6.0)x10(-2) U/mg protein) was 138% greater than that in non-acromegalic controls (12.0 (6.0)x10(-2); p<0.01). Similarly, mean 7alpha-dehydroxylase activity in octreotide treated acromegalics (11.1 (1.18)x10(-4) U/mg protein) was 78% greater than that in patients not receiving long term octreotide (6.3 (0.5)x10(-4); p<0.001). The mean proportion of deoxycholic acid in fasting serum also increased from 18.0 (2.88)% in the untreated group to 29.6 (2.3)% during long term octreotide (p<0.05). There were significant linear relationships between large bowel transit time and: (i) faecal 7alpha-dehydroxylase activity; and (ii) the proportion of deoxycholic acid in fasting serum and between 7alpha-dehydroxylase activity and the proportion of deoxycholic acid in serum.Summary/interpretation: These data suggest that increased deoxycholic acid formation seen in acromegalics during octreotide treatment is due not only to the greater numbers of faecal anaerobes but also to increased activity of the rate limiting enzyme pathway (7alpha-dehydroxylation) converting cholic acid to deoxycholic acid.

Acromegaly↗
PubMed2004

Tackling contamination of the hospital environment by methicillin-resistant Staphylococcus aureus (MRSA): a comparison between conventional terminal cleaning and hydrogen peroxide vapour decontamination.

The hospital environment can sometimes harbour methicillin-resistant Staphylococcus aureus (MRSA) but is not generally regarded as a major source of MRSA infection. We conducted a prospective study in surgical wards of a London teaching hospital affected by MRSA, and compared the effectiveness of standard cleaning with a new method of hydrogen peroxide vapour decontamination. MRSA contamination, measured by surface swabbing was compared before and after terminal cleaning that complied with UK national standards, or hydrogen peroxide vapour decontamination. All isolation rooms, ward bays and bathrooms tested were contaminated with MRSA and several antibiogram types were identified. MRSA was common in sites that might transfer organisms to the hands of staff and was isolated from areas and bed frames used by non-MRSA patients. Seventy-four percent of 359 swabs taken before cleaning yielded MRSA, 70% by direct plating. After cleaning, all areas remained contaminated, with 66% of 124 swabs yielding MRSA, 74% by direct plating. In contrast, after exposing six rooms to hydrogen peroxide vapour, only one of 85 (1.2%) swabs yielded MRSA, by enrichment culture only. The hospital environment can become extensively contaminated with MRSA that is not eliminated by standard cleaning methods. In contrast, hydrogen peroxide vapour decontamination is a highly effective method of eradicating MRSA from rooms, furniture and equipment. Further work is needed to determine the importance of environmental contamination with MRSA and the effect on hospital infection rates of effective decontamination.

Cross Infection↗
PubMed2003

A methicillin-resistant Staphylococcus aureus outbreak in a new University hospital due to a strain transferred with an infected patient from another city six months previously.

Kocaeli University Medical School was established in 1995. The first methicillin resistant Staphylococcus aureus isolate was detected two years later in a patient transferred from a different city. Six months after this, we detected a small MRSA outbreak in the intensive care unit involving four patients, two of whom had bacteremia, and a staff nasal carrier. All isolates, including the first, appeared to be a single outbreak strain, demonstrated by pulsed field gel electrophoresis profiles which different by at most two bands, identical randomly amplified polymorphic DNA profiles, and identical coagulase gene types by PCR. Antibiogram were identical except that one isolate was additionally resistant to cotrimoxazole. These results show that MRSA isolates can spread between hospitals with infected or colonized patients and can apparently persist in the hospital for six months without causing infection. Screening of asymptomatic patients on wards affected by MRSA or transferred from other hospitals may be helpful in controlling these infections.

Aged↗
PubMed2002

Antibiotic resistance: effect of different criteria for classifying isolates as duplicates on apparent resistance frequencies.

OBJECTIVE: To investigate the effect of screening specimens and different criteria for exclusion of duplicate isolates when surveillance of antimicrobial resistances is performed. MATERIALS AND METHODS: Trends in resistance were analysed for recent isolates of selected organisms from Guy's and St Thomas' Hospitals with the use of various criteria for the exclusion of duplicates, including time since the last isolate and antibiogram pattern, and the effect of excluding screening specimens. RESULTS: There was a significant difference of about 8% in the apparent frequency of methicillin resistance in Staphylococcus aureus in inpatients if the time limit for duplicates was set at 5 rather than 30 days; it was about 10% if a 5 day limit was compared with a 365 day limit. There was also a significant difference, of 6-10%, in apparent resistance frequencies if isolates from screening specimens were excluded. Apparent gentamicin resistance rates in Klebsiella spp. varied between 11% and 28%, and the number of apparent patient isolates of gentamicinresistant organisms varied by up to 35%, depending on the duplicate exclusion criteria chosen. Effects were smaller, though still significant, for vancomycin resistance in Enterococcus spp. There was little effect for amoxicillin or cefuroxime resistance in Escherichia coli isolates from general practitioners, where the proportion of duplicates was small. CONCLUSION: Improved surveillance of antibiotic resistance is needed. However, care needs to be taken in setting the criteria for classifying isolates as duplicates and in comparing results where these criteria may be different or unknown.

Bacteria↗
PubMed2002

Validation of the NCCLS proposal to use results only from the first isolate of a species per patient in the calculation of susceptibility frequencies.

OBJECTIVE: A recently proposed guideline from the NCCLS recommends that results only from the first isolate of a species per patient be used in calculation of percentage susceptibilities to antimicrobial agents. Because this is apparently based on the comparison of various calculation methods for results for oxacillin against a fairly small number of isolates of Staphylococcus aureus, we have applied these methods to a wider range of antibiotic/organism combinations. METHODS: Antibiotic susceptibility results from our hospital laboratory database were analysed. Rates of antimicrobial susceptibility were calculated using the various criteria proposed by the NCCLS, including exclusion of results from duplicate isolates and surveillance specimens from the calculations. RESULTS AND CONCLUSION: Analysis of results for methicillin against S. aureus, gentamicin against Klebsiella spp., vancomycin against enterococci (all in-patient specimens), and amoxicillin and cefuroxime against Escherichia coli (general practice specimens) confirm that, if duplicates and surveillance specimens are excluded, results obtained with the various patient- and episode-based methods for the calculation of percentage susceptibility are very similar. Because of its simplicity and non-ambiguity, we agree with the suggestion of the NCCLS group that results for the 'first isolate of a given species per patient per analysis period, irrespective of body site, antimicrobial susceptibility profile or other phenotypic characteristics' should be used in the calculation of susceptibility frequencies.

Anti-Bacterial Agents↗
PubMed2001

Highly epidemic strains of methicillin-resistant Staphylococcus aureus not distinguished by capsule formation, protein A content or adherence to HEp-2 cells.

In order to investigate whether highly epidemic methicillin-resistant Staphylococcus aureus (EMRSA) strains possess special properties that favour their dissemination and survival, a study was undertaken that examined methicillin-sensitive and methicillin-resistant strains of Staphylococcus aureus isolated in the UK. Included in the study were EMRSA types 1, 2, 3, 15 and 16. Phage types EMRSA-15 and -16, in particular, have emerged as significant hospital pathogens in the UK, resisting standard methods of control and spreading widely, while the incidence of other epidemic types has either declined or not changed. All of the strains included in the study were examined for capsule formation, the amount of bound protein A produced, and quantitative adherence to the human continuous epithelial cell line HEp-2. Although all of these properties varied amongst the strains examined, there was no relationship between any of them and methicillin resistance or epidemic type and, incidentally, no relationship between cell wall-bound protein A content and adherence.

Bacterial Adhesion↗
PubMed2001

A simultaneous outbreak on a neonatal unit of two strains of multiply antibiotic resistant Klebsiella pneumoniae controllable only by ward closure.

Two aminoglycoside-resistant strains of Klebsiella pneumoniae caused an outbreak on the neonatal unit at St Thomas' Hospital. One, which affected 18 patients, was capsular type K18 and resistant to newer cephalosporins by the production of the extended-spectrum beta-lactamase SHV-2; the other, which colonized four patients, was capsular non-typeable and did not produce extended-spectrum beta-lactamase. Both strains were probably brought into the unit by carrier patients; the probable carrier of the non-typeable strain was transferred from another hospital but was negative on a single admission screen; the probable carrier of the K18 strain was not screened on admission because he had been born at St Thomas', but his mother had been transferred from another hospital. Despite intensive efforts to control the outbreak by standard methods of hand washing, screening, patient isolation and environmental cleaning, a total of 22 neonates on the unit eventually became colonized or infected. One of three patients with bacteraemia died. A small proportion of samples of expressed breast milk, electronic thermometers and oxygen saturation probes were contaminated by the K18 strain and may have contributed to some of the cross-infection, but this did not explain the extent of the outbreak. The outbreak was controlled only by opening a temporary ward for colonized neonates and another for newly born babies, which allowed the closure and cleaning of the main neonatal unit. Multiply antibiotic resistant klebsiellas may be highly epidemic and cause serious, difficult-to-control outbreaks on neonatal units. All patients, regardless of their admission history, should be screened on admission for carriage of multiply resistant enterobacteria by a sensitive method, and units should have plans for temporary ward closure should outbreaks occur.

Aminoglycosides↗
PubMed2001

Rifampin resistance in Mycobacterium kansasii is associated with rpoB mutations.

Rifampin is the most potent drug used in the treatment of disease due to Mycobacterium kansasii. A 69-bp fragment of rpoB, the gene that encodes the beta subunit of the bacterial RNA polymerase, was sequenced and found to be identical in five rifampin-susceptible clinical isolates of M. kansasii. This sequence showed 87% homology with the Mycobacterium tuberculosis gene, with an identical deduced amino acid sequence. In contrast, missense mutations were detected in the same fragment amplified from five rifampin-resistant isolates. A rifampin-resistant strain generated in vitro also harbored an rpoB gene missense mutation that was not present in the parent isolate. All mutations detected (in codons 513, 526, and 531) have previously been described in rifampin-resistant M. tuberculosis isolates. Rifampin MICs determined by E-test were <1 mg/liter for all rifampin-susceptible isolates and >256 mg/liter for all rifampin-resistant ones. In addition, four of the five rifampin-resistant isolates were also resistant to rifabutin. We have thus shown a strong association between rpoB gene missense mutations and rifampin resistance in M. kansasii. Although our results are derived from a small number of isolates and confirmation with larger numbers would be useful, they strongly suggest that mutations within rpoB form the molecular basis of rifampin resistance in this species.

Amino Acid Sequence↗
PubMed2001

Diagnosis of bacteriuria by detection of volatile organic compounds in urine using an automated headspace analyzer with multiple conducting polymer sensors.

The Osmetech Microbial Analyzer (OMA) is an automated headspace analyzer fitted with a novel detector system consisting of an array of polymer sensors, each of which responds to different volatile organic compounds. The system can be used for screening clinical urine specimens for significant bacteriuria by sampling urine headspace and subjecting the output of the multiple-detector response to principal component analysis. The OMA readily distinguished artificially infected urine samples from sterile controls. The OMA was then used to analyze 534 unselected clinical urine specimens, of which 21.5% had significant bacteriuria (containing >10(5) CFU of bacteria/ml). The sensitivity and specificity of the OMA compared with conventional culture were 83.5 and 87.6%, respectively. The OMA is a promising automated system for the rapid routine screening of urine specimens, and further clinical trials are in progress.

Bacteria↗