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Biomedical subjects

D S Reeves

Publications and source records attributed to D S Reeves.

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

Bacterial resistance to cephalosporins as a function of outer membrane permeability and access to their target.

Resistance of Gram-negative bacteria to cephalosporins, as with other beta-lactam antibiotics, is a function of a combination of outer-membrane permeability, affinity and stability to beta-lactamases, and their activity against target sites (penicillin-binding proteins). Permeation through the outer-membrane is largely governed by the presence and properties of porins, which are water-filled channels facilitating the movement of hydrophilic molecules across the membrane. The properties of porins vary considerably between wild-type bacterial species, and their numbers (and hence the ability of a bacterial cell to exclude the antibiotic) may be reduced in strains with acquired resistance. In the case of cephalosporins, ability to cross the outer-membrane is related to physico-chemical properties such as molecular size, hydrophobicity and the number and charge of ionised groups. Thus, for example, dianionic compounds have in general lower permeability rates than dipolar cephalosporins. These relationships are discussed in detail. The phenotypically expressed susceptibility of a particular bacterial strain to a cephalosporin is brought about by a dynamic combination of permeation, the ability of the agent to resist degradation or binding to the beta-lactamases in the periplasmic space which act upon the relatively low concentration of cephalosporin present there, and target affinity. The interplay of these factors is discussed.

Bacterial Outer Membrane Proteins↗
PubMed1995

Typing of Listeria monocytogenes by random amplified polymorphic DNA (RAPD) analysis.

The aim of the study was to determine the effectiveness of random amplified polymorphic DNA analysis in typing Listeria monocytogenes from human infections. Twenty-five L. monocytogenes serogroup 1/2 and 70 serogroup 4 including 14 serovar 4b(x) were typed by RAPD-PCR analysis. Six primers were used to type each L. monocytogenes isolate and the DNA amplification performed with supertaq DNA polymerase in a Hybaid Thermal Reactor. Each bacterial strain was analysed separately with all primers and the profiles were judged by eye and designated to a group by comparison to other strains. Bands were classified as major or minor. Based on analysis of major band patterns, the 25 serogroup 1/2 isolates gave rise to 12 different groups. The groups only contained serovar 1/2a or 1/2b with a single exception. Using minor bands all isolates could be distinguished. All the serogroup 4 isolates gave the same major band patterns. The 14 serovar 4b(x) isolates which were epidemiologically related gave identical profiles with the exception of one isolate. Of the remaining strains, 41 produced individual patterns on minor band analysis. RAPD analysis with multiple primers is low cost, discriminatory and is most ideally suited to testing small (< 50) numbers of strains. We have shown that serogroup 1/2 L. monocytogenes strains are a more diverse group than serovar 4b strains and RAPD-PCR will provide a technique of considerable value in typing L. monocytogenes in the future.

Bacteriophage Typing↗
PubMed1995

Mycobacterial contamination of fibreoptic bronchoscopes.

Because of the increasing numbers of immunosuppressed patients and the general resurgence of mycobacterial infection, diagnostic bronchoalveolar lavage (BAL) using a fibreoptic bronchoscope is an important and frequent procedure. A contaminated bronchoscope may introduce spurious mycobacteria into specimens causing diagnostic confusion, infect the patient with mycobacteria, or be a vehicle for cross-infection. Bronchoscopes are difficult to disinfect adequately if they are not properly cleaned (which may include stripping down channel valves) or are damaged. Bronchoscope washers have also contributed to the problem when glutaraldehyde becomes too dilute or they become heavily contaminated with environmental mycobacteria. Future solutions to prevent contamination include the regular maintenance of bronchoscopes and washers, having adequate cleaning and disinfection protocols and ensuring that they are adhered to, improving bronchoscope and washer design, and developing alternative disinfectants or new ways of using current ones. All these will probably have considerable cost implications for hospitals.

Bronchoalveolar Lavage Fluid↗
PubMed1995

The comparative inhibitory and bactericidal activities of meropenem and imipenem against Acinetobacter spp. and Enterobacteriaceae resistant to second generation cephalosporins.

The inhibitory and bactericidal activities of meropenem and imipenem were compared using Acinetobacter spp. and Enterobacteriaceae resistant to second generation cephalosporins. The inhibitory activity of both agents was similar for Acinetobacter spp. but meropenem was more active against the Enterobacteriaceae. Bactericidal activities were compared employing time-kill curves which indicated meropenem was more bactericidal than imipenem against Enterobacteriaceae at pharmacologically achievable concentrations while imipenem was more bactericidal than meropenem against Acinetobacter spp.

Acinetobacter↗
PubMed1995

A critical assessment of the agar dilution chequerboard technique for studying in-vitro antimicrobial interactions using a representative beta-lactam, aminoglycoside and fluoroquinolone.

The agar dilution chequerboard technique of studying antimicrobial interactions was assessed by testing a representative beta-lactam (piperacillin/tazobactam), aminoglycoside (gentamicin) and fluoroquinolone (ciprofloxacin) against themselves, that is piperacillin/tazobactam plus piperacillin/tazobactam, gentamicin plus gentamicin and ciprofloxacin plus ciprofloxacin. In addition, combinations of piperacillin/tazobactam plus gentamicin or ciprofloxacin were also tested against Enterobacteriaceae and Acinetobacter spp. in triplicate. The agar dilution chequerboard technique did not reliably show addition when agents were combined with themselves, and there was also considerable variation when beta-lactam plus aminoglycoside or fluoroquinolone combinations when tested in triplicate. These observations, and problems with the design of the method, indicate that the chequerboard technique should be used only with adequate controls and replication, and then interpreted with extreme caution; ideally, it should not be used as a method of assessing antimicrobial interactions.

Acinetobacter↗
PubMed1995

The pharmacokinetics of meropenem in surgical patients with moderate or severe infections.

The pharmacokinetics of meropenem were studied in a group of 11 surgical patients (four male, seven female; mean age 63 years; mean weight 72 kg) all of whom had moderate or severe infection and who received a mean dose of 14.5 mg/kg +/- 2.7 meropenem 8-hourly iv for a minimum of 4 days. Venous blood samples were collected at timed intervals after the first dose on day 1 and the second dose on the fourth or fifth day of therapy. Serum meropenem concentrations were assayed by HPLC and fitted to a two compartment pharmacokinetic model. The mean pharmacokinetic parameters (+/- standard deviation) on day 1 were T1/2 84.6 +/- 24.1 min, Vdss 0.22 +/- 0.06 L/kg, AUC 6028 +/- 1983.2 mg.min/L, Cltot 188 +/- 67 mL/min and MRT 89.1 +/- 67.8 min. On the fourth or fifth days of therapy the values were T1/2 79.9 +/- 18.2 min, Vdss 0.17 +/- 0.8 L/kg, AUC 6000.7 +/- 2417 mg.min/L, Cltot 190 +/- 60 mL/min and MRT 67.8 +/- 30.4 min. Although the T1/2, Vdss and MRT decreased from day 1 to day 4 or 5 these changes were not statistically significant (Student's t-test, P > 0.05). Total clearance of meropenem was linearly related to creatinine clearance or patient age on the first day of therapy. Although the T1/2 and MRT were longer and the Cltot lower than those reported for young healthy volunteers, they were similar to those found in elderly volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

An audit of ciprofloxacin use in a district general hospital.

An audit of ciprofloxacin use at Southmead Hospital, Bristol was carried out for forty patients treated in early 1992 employing a modified Delphi technique with six assessors. Most patients assessed (20/40, 50%) had urinary tract infections (UTIs), 5/40 (12.5%) had chest infections, 4/40 (10%) had bacterial gastroenteritis and 3/40 (7.5%) had either bacteraemia or infection following an orthopaedic procedure. A likely bacterial pathogen was isolated from 32/40 (80%) of patients; 14/32 (44%) had Pseudomonas aeruginosa infections and from the remainder Enterobacteriaceae including Salmonella spp. (non-typhoid) were cultured. Oral therapy with ciprofloxacin was used in 37 (93%) of the 40 patients, and the three others received iv treatment. In 21/35 (60%) of patients where an assessment was made by majority scoring, a quinolone was felt to be clinically justified. A quinolone was least likely to be thought justified if the patient had a chest infection. The assessors had few concerns about the effectiveness or toxicity of ciprofloxacin but for 41% (14/34) of patients, where there was a majority opinion, a cheaper alternative was felt to be available; most of these patients had hospital-acquired UTIs caused by Enterobacteriaceae. The duration of therapy was felt to be too long in 35% (10/29) of patients, mainly because of prolonged treatment of UTIs. In some cases of P. aeruginosa infection the assessors would have used higher doses than those prescribed. Ciprofloxacin was the quinolone of choice in 24/32 (75%) of assessable cases. Norfloxacin was chosen to treat UTI due to multi-resistant Enterobacteriaceae in 6.2% (2/32) cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Infective Agents↗
PubMed1995

Do blood cultures need continuous monitoring so that clinical action can be taken outside normal working hours?

Many automated blood culture reading systems monitor bacterial growth 24 hours a day but it is unclear if reacting to prompts indicating bacterial growth outside normal laboratory hours is of clinical benefit. An analysis of 50 blood cultures from 43 patients which had organisms seen on Gram films and had triggered positive out-of-hours showed that examination of the Gram film altered management of seven patients and the results of culture or sensitivity testing altered that of a further four. However, after review, it was felt the clinical outcome would not have been influenced by earlier intervention in any of these patients. We therefore consider that an out-of-hours service for dealing with positive blood cultures is not justified in our hospital. This conclusion may not apply universally, especially in hospitals where potential pathogens show less predictable antimicrobial sensitivity patterns.

Adult↗
PubMed1994

Prevalence of fluoroquinolone resistance in Europe. Study Group 'Bacterial Resistance' of the Paul-Ehrlich-Society for Chemotherapy e. V.

Since 1984, when the first fluoroquinolone, norfloxacin, was marketed in Europe, there has been a marked increase in the usage of this class of drugs. In order to evaluate the influence of this drug usage on the prevalence of resistance to fluoroquinolones in clinical isolates of the family Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus, coagulase-negative staphylococci and Enterococcus faecalis we reviewed the susceptibility data from four collaborative surveys conducted between 1983 and 1990 by the Study Group 'Bacterial Resistance' of the Paul-Ehrlich-Society for Chemotherapy. All participating laboratories used the same standardized methods. Minimal inhibitory concentrations were determined by the broth microdilution method. More than 20,000 bacterial strains were tested. The results are presented for ciprofloxacin, which is regarded as the representative of the fluoroquinolones. Using > or = 4 mg/l as a breakpoint for resistance to ciprofloxacin, the prevalence of resistant strains of the family Enterobacteriaceae in Central Europe between 1983 and 1990 remained below 1%. In contrast, the resistance rates in P. aeruginosa were 0.7%, 1.0%, 3.8% and 7.0%, in S. aureus 0%, 0.5%, 6.6% and 6.8%, and in E. faecalis 2.2%, 0.7%, 4.9% and 7.7% in 1983, 1986, 1989 and 1990, respectively. The latest study carried out in cooperation with 78 laboratories from 12 European countries revealed great differences in the prevalence of resistance to fluoroquinolones from one species to another ranging from 0% with Proteus vulgaris and Salmonella spp. to 26.7% with Providencia stuartii.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Infective Agents↗
PubMed1994

The occurrence and seasonal changes in the isolation of Listeria spp. in shop bought food stuffs, human faeces, sewage and soil from urban sources.

Eight hundred and twenty-two shop-bought food specimens, 136 soil and 692 faecal specimens were cultured for Listeria spp. in a regular, year round survey. 19.7% (162/822) of the foods, 93.9% (108/115) of the sewage, 14.7% (20/136) soils and 1% (7/692) of faeces yielded Listeria spp. with 10.5% foods, 60.0% sewage, 0.7% soils and 0.6% faeces containing L. monocytogenes. No seasonal variation was noted in isolates from either sewage or foods, with L. monocytogenes and L. innocua being the commonest species in both L. ivanovii when isolated from foods was strongly associated with mutton. Poultry was most likely to contain L. monocytogenes (65.6%, 21/32) and in the greatest numbers. A high percentage of beef (34.6%, 9/26), lamb (40%, 8/20), pork (28.1%, 9/32) and sausages (34.7%, 8/23) also contained L. monocytogenes. L. monocytogenes was rarely isolated from paté (1/40) or soft cheeses (1/251), both of which have been involved with foodborne listeriosis outbreak in the UK. Listeria spp. were commonest in faeces and soils in July to September but the predominant species isolated were different with L. monocytogenes and L. innocua the commonest from faeces and L. ivanovii and L. seeligeri the most common from soil.

Animals↗
PubMed1994

A review of the clinical presentation, laboratory features, antimicrobial therapy and outcome of 77 episodes of pneumococcal meningitis occurring in children and adults.

Seventy-seven episodes of pneumococcal meningitis in 69 patients were reviewed. Twelve (15.6%) episodes occurred in those over 60 years old, 14 (18.2%) in patients between 10 and 60 years, 22 (28.6%) in patients between 2 and 10 years and 29 (37.7%) in those under 2 years. Overall mortality was 13.0% (10/77) and age of > 60 years was significantly associated with mortality (P < 0.05). Twelve episodes resulted in disabilities, eight of which were in those under 2 years, and took the form of hearing impairment in nine. Many patients had predisposing conditions with aural pathology, malignancy and diabetes mellitus being commonest in those over 10 years of age and aural pathology, preceding viral infection, renal disease, sinusitis or recent lower respiratory tract infection commonest in those aged between 2 and 10 years. Three of five patients with recurrent meningitis had CSF leaks. The most common features at presentation were fits, irritability, diarrhoea, and bulging fontanelles in those under 6 months; vomiting, drowsiness and poor feeding in those between 6 months and 2 years; neck stiffness, vomiting and drowsiness in those between 2 and 10 years while neck stiffness, focal neurology, headache and vomiting were commonest in those over 10 years old. Fever was common in all age groups as were foci of infection outside the CSF, with chest infections being significantly associated with mortality (P < 0.05). Of the laboratory parameters measured, low platelets (< 100 x 10(9)/l and high blood urea (> 7 mmol/l) were associated with mortality (P < 0.05). Blood cultures grew Streptococcus pneumoniae in 79.7% patients. Seventy-four (96%) patients had CSF taken of which 81% had gram films which were positive and interpreted correctly as showing pneumococci. Pneumococci were grown in 87.8% CSF cultures and all were sensitive to penicillin but a single isolate was chloramphenicol resistant. Many different antimicrobial drugs were used but penicillin plus chloramphenicol was the most commonly employed after the results of CSF microscopy were known and penicillin alone after culture results were available. Penicillin mono-therapy was associated with a low mortality.

Adolescent↗
PubMed1994

Ciprofloxacin resistant Serratia marcescens endocarditis as a complication of non-Hodgkin's lymphoma.

We report a case of endocarditis caused by a ciprofloxacin-resistant strain of Serratia marcescens in a 50-year-old female neutropenic patient with non-Hodgkin's lymphoma which occurred while receiving ciprofloxacin prophylaxis. She made poor progress on first line therapy with azlocillin and gentamicin by bolus injection t.d.s. The infection was finally eliminated by a regimen of continuous infusion of azlocillin and once daily gentamicin.

Azlocillin↗
PubMed1994

A 10 year survey of the epidemiology and clinical aspects of listeriosis in a provincial English city.

Between January 1983 and December 1992 29 cases of human listeriosis were recorded in Bristol, giving an incidence for the decade of 0.35 infections/10(5) population/annum. For those less than a year old the incidence was 5.2/10(5) population/annum and for adults increased from 0.029/10(5)/annum for those aged 20-49 years to 0.65/10(5)/annum for those over 80 years of age. Social classes I and II were over represented in those infected while classes IV and V were under represented when compared to the general population. Infection was seasonal with most infections occurring in October and 75.9% cases in the last two quarters of the year. Altogether, 13 (45%) cases were associated with pregnancy while 16 (55%) arose in non-pregnant persons. The incidence of pregnancy-associated infection was 1.23 per 10(4) births. In the first half of the decade, pregnancy-associated infection (62.5%) was more common than infection in non-pregnant adults or juveniles but this preponderance was reversed in the second half (23.1%). Among juvenile/adult infections not associated with pregnancy, bacteraemia became more common than CNS infection as the decade progressed. Among the pregnancy-associated infections were five infected abortions, seven neonatal infections (six systemic and one local) and one maternal infection during pregnancy in which the baby was not infected. The juvenile and adult infections in non-pregnant adults presented as primary bacteraemia in 10 (62.5%) patients and CNS infection in six (37.5%) patients. The overall mortality, excluding abortions, was 27.6% (8/29), being 14.3% (1/7) among affected neonates and 37.5% (6/16) among juveniles and non-pregnant adults. Sequelae of infection were not noted in the neonates but a third of the juveniles or adults with CNS infection were left with residual defects.

Adolescent↗