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Biomedical subjects

I M Gould

Publications and source records attributed to I M Gould.

At least 19 recordsLinked to original sources

Epidemiology of infection due to Escherichia coli O157: a 3-year prospective study.

A 3-year study of Escherichia coli infections in Grampian Region was conducted to ascertain the incidence, document clinical sequelae and identify at-risk groups. Approximately 30,000 stools from patients with acute diarrhoea were screened for E. coli O157, and an epidemiological questionnaire filled in for each patient whose stool was positive. Eighty-three patients were studied. The annual incidence was 6 per 100, 000. Proportionately more infections occurred in people involved in agriculture. Evidence was seen of case-to-case transmission, and contamination of a water supply. Eight cases developed haemolytic uraemic syndrome (HUS). There were 2 deaths due to HUS and 2 due to haemorrhagic colitis (HC). Symptomatic E. coli infection is relatively common in the Grampian Region, more common in the agricultural community, and is the main cause of HUS in this Region.

Adolescent

Phenoxymethyl penicillin versus co-amoxiclav in the treatment of acute streptococcal pharyngitis, and the role of beta-lactamase activity in saliva.

One hundred and sixty-five consecutive patients ( > 2 years of age) with acute group A streptococcal (GAS) pharyngitis randomly received co-amoxyclav (79 patients) or phenoxymethyl penicillin (86 patients). beta-Lactamase activity in saliva was determined for each patient. At follow up after seven days, tonsillar cultures from seven patients (9.6%) in the penicillin V group grew group A streptococcus; three of these patients had tonsillitis clinically. In the co-amoxiclav group these figures were three (3.8%) and two respectively (P > 0.05). Within the 12 month follow up period, there were four clinical recurrences (6.1%) in the penicillin V group and seven (9.3%) in the co-amoxiclav group (P > 0.1). beta-Lactamase activity in the saliva was demonstrated in 29 patients (19.2%). Fourteen (74%) of 19 bacteriological failures or clinical recurrences had beta-lactamase activity, versus 15 (12%) of 129 successfully treated patients (P < 0.001). There is no evidence that oral co-amoxiclav is better than oral penicillin V for the first treatment of acute GAS pharyngitis, but bacteriological failure and clinical recurrence are strongly associated with the presence of beta-lactamase activity in commensal flora.

Acute Disease

The high vaginal swab in general practice: clinical correlates of possible pathogens.

Clinical features, diagnosis and treatment of 286 women whose high vaginal swabs (HVS) submitted by their general practitioners showed pure, heavy growth of Staphylococcus aureus, beta haemolytic streptococci groups A, C or G, Streptococcus milleri, Streptococcus pneumoniae or Haemophilus influenzae were analysed. Women with group A, C and G streptococci frequently had clinical vulvovaginitis and although the numbers were too small for statistical confirmation, S. pneumoniae and H. influenzae appeared to cause clinical disease as well. The association of S. aureus or S. milleri with clinical vulvovaginitis was much less convincing. It seems relevant for laboratories to report sensitivities for group A, C and G streptococci. Further research is needed to determine the pathogenicity of S. pneumoniae and H. influenzae.

Adolescent

Protein binding and serum bactericidal activities of vancomycin and teicoplanin.

In a randomized crossover study, the protein binding and serum bactericidal activities (SBAs) of vancomycin and teicoplanin against Staphylococcus aureus and Streptococcus pyogenes were investigated in six healthy volunteers. Total concentrations in serum 1 h postadministration of vancomycin and teicoplanin were 25.5 +/- 2.7 and 10.8 +/- 8.9 mg/liter, respectively; mean free concentrations were 14.6 +/- 2.0 and 0.6 +/- 0.9 mg/liter, respectively. Protein binding for vancomycin was 36.9% +/- 2.87%, and that for teicoplanin was 97.4% +/- 2.6%. SBA determined in pooled human serum at 1 h against S. aureus ranged from 1:8 to 1:32 for both vancomycin and teicoplanin. Against S. pyogenes SBA at 1 h ranged from 1:16 to 1:128 for vancomycin and 1:256 to 1:2,048 for teicoplanin. In vitro kill curve studies showed that vancomycin is slowly bactericidal and that teicoplanin is bacteriostatic. Despite having less in vitro cidal activity against the study isolates and having low or unrecordable levels of free drug in serum, teicoplanin demonstrated a similar or better SBA than vancomycin. SBA was more closely related to the total drug level (r = 0.77 for S. aureus and r = 0.79 for S. pyogenes) than the free level of teicoplanin (r = 0.59 for S. aureus and r = 0.56 for S. pyogenes). The high level of protein binding of teicoplanin did not seem to impair its antibacterial activity as measured by its SBA.

Adult

Corynebacterium afermentans subsp. lipophilum: multiple abscess formation in brain and liver.

Corynebacterium afermentans, a species recently identified, has previously been isolated from human blood cultures. We report the case of a previously healthy 39-year-old man who developed a brain abscess and a liver abscess due to Corynebacterium afermentans subsp. lipophilum. The liver abscess penetrated through the diaphragm to cause pleural effusion and periostitis of the ribs. We believe this is the first reported case of disseminated infection with abscess formation due to this organism.

Adult

Risk factors for acquisition of multiply drug-resistant gram-negative bacteria.

Some bacteria are naturally resistant to many antibiotics and most can become multiply resistant. Multiply resistant gram-negative bacteria have proved a particular problem over the last 30 years, but the development of new agents has lessened their significance for most clinicians. Now, however, clinical practice is threatened by the lack of new classes of antibiotics, the widespread emergence of resistance and the advent of plasmid-mediated cephalosporinases by which the spread of resistance is likely to be rapid. Increased use of prophylaxis in immunosuppressed and intensive care patients is likely to aggravate the problem, as is the use of new broad-spectrum agents in the community. More directed and restricted antibiotic use and better education of patients and prescriber are necessary to contain the problem of antibiotic resistance. Improved surveillance of sensitivity trends is essential. Many outbreaks also are associated with poor infection control techniques. The cost of outbreaks due to multiply resistant organisms and lack of compliance with infection control procedures needs to be properly studied. While many predisposing factors for the acquisition of these organisms and the development of infection are understood, the multifactorial nature of illness in many patients complicates the issue, necessitating further study of risk factors and preventative and therapeutic measures.

Cross Infection

Comparison of methodologies used in assessing the postantibiotic effect.

The postantibiotic effect (PAE) of the carbapenem antibiotic meropenem was determined for the reference strains of Escherichia coli NCTC 4174 and E. coli NCTC 12210. Regrowth of bacteria after antibiotic exposure was determined by viable counting and bioluminescence alone and in combination with an impedance technique and a morphological technique was also employed. Different methods of calculating the PAE were also used. After exposure of E. coli to 0.1-100 x MIC of meropenem for 2 h, concentration dependent differences in counts by bioluminescence, and viable counting were observed, the latter always being lower. The unexposed control of E. coli NCTC 4174 yielded counts of 1.1 x 10(6) +/- 1.1 x 10(5) and 1.3 x 10(6) +/- 4.7 x 10(5) by viable counting and bioluminescence respectively and E. coli NCTC 12210 gave counts of 4.2 x 10(6) +/- 1.8 x 10(6) and 1.1 x 10(7) +/- 4.3 x 10(6) by the same methods. After exposure to 100 x MIC of meropenem, NCTC 4174 yielded counts of 1.28 x 10(3) +/- 5.35 x 10(2) and 2.59 x 10(5) +/- 8.61 x 10(4) and NCTC 12210 gave counts of 5.22 x 10(3) +/- 9.74 x 10(2) and 5.21 x 10(6) +/- 1.45 x 10(6) by viable counting and bioluminescence, respectively. The discrepancies were due to the inability of the viable counting procedure to detect spheroplasts. Falsely low post exposure counts led to falsely low determinations of PAE by viable counting alone and in combination with the impedance technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents

Automatic procedures for measuring post-antibiotic effect and determining random errors.

Four methods are described for determining the post-antibiotic effect (PAE) automatically using the high resolution capabilities of the conductance measurement of bacterial growth. The time resolution of each method is derived by a statistical procedure for calculating random error from the component errors involved in each determination. The procedures are illustrated using data generated from the measurements of the growth of Escherichia coli NCTC 4174 after exposure of cultures to five antibiotic concentrations. Excellent agreement was found to exist between three of the four methods. However, that based on the determination of the time of peak growth rate is shown to provide better resolution than the other methods, i.e., those based on growth to 10(7) organisms/mL, the duration of the lag phase or the mean retardation of growth averaged over the entire period of observation. The results strongly suggest that PAE may be ascribed entirely to a prolongation of lag time.

Anti-Bacterial Agents

Postantibiotic effect of meropenem on members of the family Enterobacteriaceae determined by five methods.

The postantibiotic effect (PAE) of meropenem was determined for 11 strains, both clinical isolates and reference strains of members of the family Enterobacteriaceae. The study compares PAE results obtained by five methods used to monitor bacterial regrowth, including viable counting, alone and in combination with impedance; bioluminescence, alone and in combination with impedance; and a morphological technique. After exposure of the test organisms to meropenem (0.1 x to 100 x MIC) for 2 h, concentration-dependent differences in counts by bioluminescence and viable counts were observed, the latter always being lower. The differences varied with the test organism. For example, after exposure of Providentia stuartii NCTC 10318 to 0.1 x MIC, the counts were 5.5 x 10(5) and 2.0 x 10(5) whereas after exposure of Citrobacter freundii MR76 to 0.1 x MIC of meropenem the counts were 2.3 x 10(6) and 6.8 x 10(3) by bioluminescence and viable counting, respectively. The discrepancies were probably due to the relative inability of the viable counting procedure to detect fragile aberrant morphologies and resulted in differences in the calculated PAE values. With methods which do not detect fragile morphologies, the PAE may be underestimated. A general trend was observed for the order of magnitude of the PAEs by the following methods (in order of decreasing magnitude of PAE): (i) morphological technique, (ii) bioluminescence technique alone, (iii) bioluminescence in combination with impedance, (iv) viable counting in combination with impedance, and (v) viable counting alone. It is our opinion that of the methods examined in this study, bioluminescence in combination with impedance best reflects the true values for PAEs, and these results were examined more closely.

Bacteriological Techniques

Penetration of amoxycillin/clavulanic acid into bronchial mucosa with different dosing regimens.

BACKGROUND: The efficacy of an antibiotic is related to its concentration at the site of infection. Previous studies of the concentrations of amoxycillin and clavulanic acid (co-amoxiclav) in respiratory secretions or whole lung tissue have suffered from methodological problems. The concentration of amoxycillin and clavulanic acid was determined in bronchial mucosal biopsy samples obtained at bronchoscopy following five different dosing regimens. METHODS: Bronchial biopsy and serum samples were obtained from 50 patients undergoing diagnostic bronchoscopy. Ten patients each received 375 mg, 625 mg, 750 mg, and 3.25 g oral, and 1.2 g intravenous co-amoxiclav 1-3 hours before bronchoscopy. The concentrations of clavulanic acid and amoxycillin were determined by high performance liquid chromatography using a microbore column, solid phase extraction, and preconcentration to improve sensitivity tenfold over previous methods. RESULTS: Concentrations of both clavulanic acid and amoxycillin in bronchial mucosa were dose related and were well above the MIC90 of co-amoxiclav for the common bacterial respiratory pathogens including Haemophilus influenzae, Micrococcus catarrhalis and Streptococcus pneumoniae for all dosing regimens. Mean mucosal levels were 200% and 118% of the corresponding serum levels for amoxycillin and clavulanic acid respectively. CONCLUSIONS: Amoxycillin and clavulanic acid are concentrated in bronchial mucosa and, even at the lowest dose of 375 mg orally, are likely to produce tissue levels in the lung sufficient to inhibit all the common community acquired respiratory pathogens.

Amoxicillin

The post-antibiotic effect.

Pharmacodynamics are being applied increasingly to the design of antibiotic dosing regimens. One characteristic of pharmacodynamics is the post-antibiotic effect (PAE), the delayed regrowth of bacteria following exposure to an antibiotic. In this review the various laboratory techniques which have been used to determine the PAE are critically evaluated and compared with the standard viable counting method. The potential sources of error associated with these methods are considered and recommendations are made for the optimum testing system; on the basis of current evidence the bioluminescence and impedence techniques appear to be the most suitable in terms of being the least labour-intensive and producing the most reliable results. Whichever technique is used, the properties of the growth medium, including osmolality and pH, the size of the bacterial inoculum, the initial antibiotic concentration, the exposure time to the antibiotic and the method of antibiotic removal should be standardized. Other post-(antibiotic) exposure events and their relationships with the PAE and theories concerning the mechanism (or mechanisms) by which antibiotics produce PAEs are discussed. Finally, consideration is given to the clinical significance of the PAE and how it, in conjunction with other pharmacodynamic parameters, might be used to allow antibiotic dosing regimens to be developed on a more scientific basis.

Adenosine Triphosphate

Cost effectiveness of prophylaxis in dental practice to prevent infective endocarditis.

BACKGROUND: Although antimicrobial prophylaxis for infective endocarditis (IE) is common practice for many dental procedures, there is little information on whether it represents value for money. A study was performed to evaluate the effectiveness of prophylaxis for all at risk patients in routine dental practice with published data from the United Kingdom. METHODS: The risk of contracting infective endocarditis was calculated from published data to find (for high risk patients) both the annual number of deaths attributable to infective endocarditis and the number of high risk dental procedures performed without prophylaxis. Costs are estimated by examining the notes of 63 patients with proved IE during the decade 1980-90. RESULTS: Such prophylaxis is highly cost effective before dental extractions, but its value for other invasive dental procedures is unproved. It was calculated that, for every 10,000 extractions in at risk patients, appropriate prophylaxis will prevent 5.7 deaths and a further 22.85 cases of non-fatal IE. This represents a saving in the costs of hospital care of 289,600 pounds for 10,000 extractions. CONCLUSION: Prophylaxis to prevent IE in at risk patients undergoing dental extraction is highly cost effective. Net savings each year throughout the United Kingdom, that might be achieved by improving the existing proportion of such patients given antibiotics from its present level of about 50% would amount to 2.5 million pounds and would prevent over 50 deaths.

Anti-Bacterial Agents

Prevention of endocarditis: communication between doctors and dentists.

Successful implementation of guidelines to prevent infective endocarditis (IE) depends upon the dental practitioner being aware of which of his patients are at risk. This was studied by sending a questionnaire to at risk patients and their dentists in the Grampian area. Of 145 respondents (53% response rate) with predisposing cardiac disorders, only 63 reported having seen their dentist in the past 2 years, although for dentate patients 47/61 had seen a dentist in the past 2 years. The dentists of 59 of these cases were then surveyed and replies received in 53 cases. Nineteen had no record of the patient having a cardiac disorder. In only 17 of the remaining cases was information on the cardiac disorder well enough recorded to warrant prophylaxis for at risk procedures. The dentist was usually told of the disorder only by the patient. Sixty-three per cent of dentists felt that communication between them and the patient's doctor was unsatisfactory. It is necessary to improve doctor/patient/dentist communication so that current recommendations on prophylaxis can be implemented to the full. This should be done through the patient's GP or consultant, who should communicate directly with the dentist. Details could also be inserted on warfarin cards and 'cardiac alert cards' expanded.

Anti-Bacterial Agents

Diagnosis of bacterial vaginosis in a routine diagnostic laboratory.

Vaginal swabs from 299 hospital and general practitioners' patients were examined for Gardnerella vaginalis by Gram film and by culture, G. vaginalis was isolated in 12% of cultures. Comparison between the 'clue' cell and culture methods suggested that the former is a rapid, acceptable routine screening method for the detection of G. vaginalis. The value of the traditional method of identifying G. vaginalis by sensitivity testing is questioned. All specimens were also examined by Gram film and culture, for the presence of Mobiluncus spp, which was detected in 8.4% of specimens by Gram film but only 0.7% by culture. From a questionnaire returned by 84% of clinicians, metronidazole was found to be the most commonly used antimicrobial agent for the treatment of G. vaginalis, and in all but one case appeared to be clinically effective.

Bacteria, Anaerobic

Determination of teicoplanin in plasma using microbore high-performance liquid chromatography and injection-generated gradients.

A reversed-phase isocratic high-performance liquid chromatographic method for the determination of total teicoplanin in plasma is reported. The method developed uses a bracketing injection technique in conjunction with large injection volumes on a 1 mm diameter column to form a limited injection-generated gradient. The chromatography yields adequate resolution among all the major components for individual quantitation and also allows quantitation of total teicoplanin in plasma using ultraviolet detection. Pretreatment is by solid-phase extraction which uses C8 Bond Elut cartridges and gives effective clean up from endogenous materials. The method offers a faster and simplified means to determine total teicoplanin in plasma than those previously reported, and has a detection limit of 50 ng/ml.

Anti-Bacterial Agents