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Biomedical subjects

I Phillips

Publications and source records attributed to I Phillips.

At least 73 records · Page 4Linked to original sources
PubMed1993

Correlation between umuC induction and Salmonella mutagenicity assay for quinolone antimicrobial agents.

Quinolone antimicrobial agents induce the SOS response in bacteria, including the umuDC genes necessary for error-prone repair. Consequently these drugs may be mutagenic in bacteria with a functional SOS response. Differential killing tests with Escherichia coli WP2 (trp) and its repair-deficient derivative CM871 (trp lexA recA uvrA) indicated that a functional DNA repair system was protective against the action of quinolones, implying that quinolones are causing some form of DNA damage (not necessarily directly) and are therefore genotoxic. Dose-dependent reversion from His- to His+ with quinolones was observed in the Ames test with Salmonella typhimurium TA102 (uvr+) but in no other Salmonella tester strains (all uvr-), suggesting that a functional excision repair system is essential for quinolone-induced bacterial mutagenesis. A significant correlation between SOS inducing potential (SOSIP) and mutagenic potential in the Ames test (r = 0.89) indicated that quinolone-induced mutagenic effects in bacteria are almost entirely due to SOS-processed DNA damage.

Anti-Infective Agents↗
PubMed1993

Serological response to coagulase-negative staphylococci in patients with peritonitis on continuous ambulatory peritoneal dialysis.

Sera and dialysis effluent from 20 patients on continuous ambulatory peritoneal dialysis (CAPD) with coagulase-negative staphylococcal (CNS) peritonitis were examined by immunoblotting for antibody activity against CNS. Immunoblotting was highly sensitive and demonstrated significantly greater antibody activity in serum and dialysate of infected patients compared with that of uninfected CAPD patients or healthy volunteers. Fourteen of 20 infected CAPD patients had strong antibody activity (> 7 bands); one patient had equivocal activity. Five patients had weak antibody activity, two of whom suffered from recurrent peritonitis with distinguishable CNS strains despite a satisfactory CAPD technique. One patient with a poor CAPD technique had strong antibody activity, but suffered from recurrent peritonitis. Examination of sequential sera suggested that seroconversion occurred soon after insertion of the Tenckhoff catheter, possibly in the absence of clinical infection. Antibody activity against a 25 kDa staphylococcal protein was significantly associated with peritonitis.

Antibodies, Bacterial↗
PubMed1993

Importance of beta-lactamase induction.

Induction of an enzyme is a temporary phenomenon in which the rate of enzyme synthesis is greatly increased in response to the presence of an inducer in the environment. Induction of beta-lactamase synthesis is important for the resistance of staphylococci to penicillins since the drug both induces synthesis of the enzyme and is hydrolysed by it. Similarly, some compounds both strongly induce and are hydrolysed by the chromosomally-determined beta-lactamases of gram-negative bacilli (e.g. amoxicillin and cefoxitin for Enterobacter cloacae). Other compounds (e.g. piperacillin and cefotaxime) although labile are poor inducers, so that in the case of these drugs the phenomenon of induction is not important but the presence of the enzyme is, since resistant mutants with genetically derepressed synthesis of the enzyme can emerge. Induction can also be important when a strong inducer is present with a poor inducer and antagonises the activity of the latter.

Anti-Bacterial Agents↗
PubMed1993

Towards a statistically oriented decision support system for the management of septicaemia.

The first decision-support system designed for the management of septicaemia was MYCIN. Although MYCIN played a vital role in the conception of knowledge-based systems, it never became an established clinical system. This paper describes an alternative decision-support system for septicaemia management currently under development at St. Thomas' Hospital (London) where a large database of septicaemia episodes has been compiled. The three statistical approaches that have been considered are described. These are (i) relative frequencies, (ii) the naive Bayes method and (iii) logistic regression. We also discuss how the concept of probabilistic influence diagrams could be of benefit to the development and implementation of the decision-support system.

Adult↗
PubMed1993

Occurrence of FIme plasmids in multiply antimicrobial-resistant Escherichia coli isolated from urinary tract infection.

Plasmids belonging to the FIme incompatibility group were found in seven different serogroups of multiply antimicrobial-resistant Escherichia coli isolated from patients with urinary tract infection (UTI) and living in south-east London. Although widespread in Salmonella spp., FIme plasmids have only previously been described in E. coli in a strain of serogroup O15 K52 H1 responsible for an extensive and protracted outbreak of invasive community-acquired infection in south-east London in 1986. Our findings suggest either a wider background occurrence of FIme plasmids in E. coli associated with UTI than previously reported or alternatively, the dissemination and subsequent molecular diversification of the FIme plasmid associated with the epidemic strain of serogroup O15 K52 H1.

DNA Fingerprinting↗
PubMed1993

Chlorhexidine hypersensitivity of ciprofloxacin-resistant variants of Pseudomonas aeruginosa PAO.

Examination of 67 ciprofloxacin-resistant clones of Pseudomonas aeruginosa PAO (ciprofloxacin MIC > 0.5 mg/L) yielded four isolates that were hypersensitive to chlorhexidine (MIC 5 mg/L); none was found among 179 ciprofloxacin-sensitive colonies. Revertant studies and the introduction of a wild-type Escherichia coli DNA gyrase A gene confirmed that ciprofloxacin resistance and chlorhexidine hypersensitivity were not the result of a single mutation. Mutagenicity testing of ciprofloxacin showed no evidence for the supposition that chlorhexidine hypersensitivity was the result of ciprofloxacin-induced mutation in P. aeruginosa PAO.

Chlorhexidine↗
PubMed1993

The application of flow cytometry to the study of bacterial responses to antibiotics.

Experiments were performed to determine whether a modern flow cytometer could be used to study bacterial populations in suspension, with particular reference to their morphological characteristics and their responses to antibiotics. The FACScan, a commercial benchtop flow cytometer fitted with an air-cooled laser, designed primarily for the study of eukaryotic peripheral blood mononuclear cells, yielded reproducible data relating to bacterial shape and internal architecture. It was sensitive enough to detect changes in bacterial morphology on entry into the growth cycle and after exposure to antibiotics. Antibiotic-induced morphological changes affecting subpopulations of bacteria were sufficiently specific to allow differentiation between antibiotics with different cell-wall enzyme targets. Simultaneously, the effect of such antibiotics on the integrity of the outer cell membrane of Escherichia coli was assessed by measurement of the association of the nucleic acid-binding dye propidium iodide with the bacteria. These experiments demonstrated complex patterns of probable cell-wall leakage, related to the modes of action of the antibiotics. The FACScan is a useful and sensitive tool for the study of the morphology and physiology of bacterial populations in suspension, and is especially applicable to the study of antibiotic action.

Amdinocillin↗
PubMed1993

Mupirocin resistance in coagulase-negative staphylococci.

High-level mupirocin resistance in coagulase-negative staphylococci isolated from patients undergoing peritoneal dialysis was investigated by transfer of the resistance determinants, usually in the form of a plasmid, to Staphylococcus aureus strains, cleavage of the plasmid by restriction endonuclease and hybridisation with a probe comprising a 4.05 kb EcoRI fragment of a plasmid from a S. aureus strain. In most instances the mupirocin-resistant staphylococci isolated from each patient were different according to the species, antibiogram and plasmid profile data. The mupirocin resistance determinant was carried on various plasmids as judged by EcoRI restriction fragment length polymorphisms. All hybridised at about 4 kb with the S. aureus probe.

Animals↗
PubMed1993

Clinical index to predict bacteraemia caused by staphylococci.

OBJECTIVES: To define risk factors associated with bacteraemia caused by Staphylococcus aureus or coagulase-negative staphylococci; and to use them to define patients in need of empiric anti-staphylococcal antibiotic treatment. DESIGN: Derivation set: observational, prospective study; validation set: retrospective analysis of a prospectively collected database. SETTING: Derivation set: Beilinson Medical Centre, Petah Tiqva, Israel--a 900-bed university hospital. Validation set: St Thomas's Hospital, London, UK--an 800-bed teaching hospital. SUBJECTS: All episodes of bacteraemia detected at Beilinson Medical Centre between March 1988 and September 1990 (derivation set, n = 1410), and at St Thomas's Hospital during 1987-1990 (validation set, n = 1040). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Percentage of staphylococcal bacteraemia in groups of patients defined by the models. RESULTS: The following factors were associated with Staphylococcus aureus bacteraemia: focus of infection (whether high or low risk), haemodialysis, intravenous drug abuse and infection acquired in the orthopaedic ward. A logistic model was used to divide the derivation set into three groups with percentages of Staphylococcus aureus bacteraemia of 1.8%, 13.2% and 33.7% (P < 0.0001); and the validation group 2.5%, 18.2% and 53.2% (P < 0.0001). Factors associated with coagulase-negative staphylococcal bacteraemia were: central or peripheral intravenous catheter as the focus of infection, a preterm neonate, the presence of a central intravenous catheter, low temperature, and a low white blood cell count. A second model including those factors was used to divide the derivation set into three groups with percentages of coagulase-negative staphylococcal bacteraemia of 1.9%, 22.8%, and 43% (P < 0.0001). In the validation set, the percentages were 2.9%, 22.4% and 31.0% (P < 0.001). CONCLUSIONS: The present study defines groups at high risk for staphylococcal bloodstream infection, in which empiric treatment should include an anti-staphylococcal drug.

Adolescent↗
PubMed1993

In vitro activity of MDL 62,879 (GE2270 A) against aerobic gram-positive and anaerobic bacteria.

The in vitro activity of MDL 62,879, a new peptide antibiotic that inhibits protein synthesis through an interaction with elongation factor Tu, against a wide range of recent clinical isolates of common aerobic gram-positive and anaerobic organisms was determined. MDL 62,879 was highly active against staphylococci (MIC for 90% of isolates [MIC90], 0.125 microgram/ml), streptococci (MIC90, 1 microgram/ml), and enterococci (MIC90, 0.03 microgram/ml). All isolates of peptostreptococci and Mobiluncus spp. were susceptible, as were most isolates of clostridia. MDL 62,879 was not active against isolates of fusobacteria or Bacteroides spp., but some isolates of Prevotella spp. and Porphyromonas asaccharolytica were susceptible.

Anti-Bacterial Agents↗
PubMed1993

Penicillinase producing Neisseria gonorrhoeae from St Thomas' Hospital 1976-1990--the first fifteen years.

OBJECTIVE: To examine the penicillinase producing N. gonorrhoeae (PPNG) collected at St Thomas' Hospital from 1976-1990 and, by determination of antibiotic susceptibility pattern and application of three typing methods, examine the prevalence of different gonococcal types. Also to determine whether there is any relationship between antibiotic sensitivity, plasmid profile, auxotype and serovar. MATERIALS AND METHODS: A total of 665 isolates of PPNG from patients attending the Department of Genitourinary Medicine at St Thomas' Hospital were characterised by antibiotic MIC, plasmid profile, auxotyping and serotyping. RESULTS: Penicillin MICs for 85% of all isolates were between 0.25 and 32 mg/l. The MIC of tetracycline for 60-80% of the isolates was < 1 mg/l. A small number of isolates had tetracycline MICs of 32 mg/l but MICs > 32 mg/l were not seen. Over 90% of the isolates were sensitive to the remaining three antibiotics tested, erythromycin, cefuroxime and spectinomycin. The 3.2 or 4.4 MDa plasmid with or without the 24.5 MDa conjugal plasmid was seen in all isolates until 1989/90 when a 2.9 MDa beta-lactamase encoding plasmid and the 25.2 MDa plasmid mediating tetracycline resistance were also recognised. Ninety-nine percent of all isolates belonged to one of four auxotypes, prototrophic, arginine, proline or proline/arginine requiring. An initial predominance of isolates with the 1A outer membrane protein was reversed in 1982 and 1B has remained predominant. Thirty two different serovars were identified among the 665 isolates, 14 belonged to serogroup 1A and 18 to 1B, and the eight most common accounted for 83.9% (554) of all isolates. Analysis of the results of combined typing methods showed there was an association between antibiotic resistance, plasmid profile and serogroup. The number of auxotypes and serovars detected in the collection, indicates the possibility that PPNG have been introduced from abroad or outside our local population. CONCLUSION: Temporal trends in the distribution of auxotype/serovar classes show that the total population of PPNG isolates is formed by a heterogenous mixture in which certain auxotype/serovar classes appear, disappear and may re-emerge. Others were present throughout in small numbers.

Anti-Bacterial Agents↗
PubMed1993

Intranasal histamine challenge in normality and allergic rhinitis.

A series of investigations was performed in which histamine challenge was used to compare nasal responsiveness in 20 normal subjects and 20 with allergic rhinitis. There was found to be a lower threshold of reactivity (D100) to histamine in allergic subjects as measured by resistance changes (geometric mean, 0.53 mg/ml; normal subjects, 2.15: p = 0.022). This may represent increased number or sensitivity of histamine receptors on the nasal capacitance vessels. The loss of a laser Doppler response to a supramaximal histamine stimulus (normal subjects, 102% increase in flux at 3 minutes; p < 0.05) was observed in patients with allergic rhinitis and indicates either a down-regulation of the capillary system or an altered effect of histamine on superficial vessels, perhaps mediated by a shift in histamine receptor type. There was an observed increase in neutrophils at the mucosal surface under baseline conditions (rhinitis median, 49.6%; normal subjects, 32.72%: p < 0.05), which suggests an important primary role in the pathogenesis of this condition for this active cell. The observed increase in secretory volume response to histamine in allergic subjects, which persisted beyond 40 minutes after a single D100 challenge, may be related to an altered sensitivity of glandular tissue. There are important changes in nasal reactivity to histamine challenge in allergic rhinitis that may have implications for its pathogenesis.

Adult↗