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Biomedical subjects

S T Chambers

Publications and source records attributed to S T Chambers.

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

Adaptive resistance to tobramycin in Pseudomonas aeruginosa lung infection in cystic fibrosis.

Aminoglycoside antibiotics have been shown to induce adaptive resistance in Pseudomonas aeruginosa in vitro and in a mouse model of infection, but adaptive resistance has not been described in human infections. Seven patients with cystic fibrosis were treated with inhaled tobramycin to determine whether adaptive resistance occurred in P. aeruginosa in their sputum. In three patients who had not recently taken antibiotics, 80 mg tobramycin was administered by nebuliser and resulting peak sputum tobramycin concentrations were 90-240 mg/L (elimination half-life 1.9-2.1 h). Adaptive resistance was detected in P. aeruginosa 1-4 h after the dose of tobramycin. Moderate resistance was present at 24 h and full susceptibility returned between 24 and 48 h. In four other patients on long-term twice-daily inhaled aminoglycoside treatment, adaptive resistance was present before, and 4 h after, 80 mg of tobramycin administered by nebuliser. The presence and time course of adaptive resistance in humans may have implications for improving aminoglycoside dosing regimens.

Adolescent↗
PubMed1996

The effect of aminoglycoside-induced adaptive resistance on the antibacterial activity of other antibiotics against Pseudomonas aeruginosa in vitro.

The effect of gentamicin-induced adaptive resistance on the antibacterial activity of six non-aminoglycoside antibiotics was studied. Adaptive resistance was induced in Pseudomonas aeruginosa in a dynamic in-vitro model of infection. The bactericidal effect of ceftazidime, imipenem, aztreonam, ciprofloxacin, and piperacillin was not altered in the presence of adaptive resistance but the effect of rifampicin was increased.

Anti-Bacterial Agents↗
PubMed1996

Vertebral osteomyelitis due to Staphylococcus lugdunensis.

We present the first reported case of vertebral osteomyelitis due to Staphylococcus lugdunensis. The infection occurred in an 80-year-old woman who had been taking glucocorticosteroids. S. lugdunensis is a coagulase-negative staphylococcus with considerable potential as a human pathogen. Isolation of this organism should be regarded as significant unless evidence suggests otherwise.

Aged↗
PubMed1996

Community acquired pneumonia: aetiology and usefulness of severity criteria on admission.

BACKGROUND: Community acquired pneumonia remains an important cause of hospital admission and carries an appreciable mortality. Criteria for the assessment of severity during admission have been developed by the British Thoracic Society (BTS). A study was performed to determine the sensitivity and specificity of a severity rule based on a modification of the BTS prognostic rules applied on admission, to compare severity as assessed by medical staff with the modified rule, and to determine the microbiological cause of community acquired pneumonia in Christchurch. METHODS: A 12 month study of all adults admitted to Christchurch Hospital with community acquired pneumonia was undertaken. Three hundred and sixteen consecutive patients with suspected community acquired pneumonia were screened for inclusion. Variables obtained from the history, examination, investigations, and initial treatment were examined for association with mortality. RESULTS: Two hundred and fifty five patients met the inclusion criteria. Their mean age was 58 years (range 18-97). A microbiological diagnosis was made in 181 cases (71%), Streptococcus pneumonia (39%), Mycoplasma pneumoniae (16%), Legionella species (11%), and Haemophilus influenzae (11%) being the most commonly identified organisms. Patients had a 36-fold increased risk of death if any two of the following were present on admission: respiratory rate > or = 30/min, diastolic BP < or = 60 mm Hg, urea > 7 mmol/l, or confusion. The severity rule identified 19 of the 20 patients who died and six of eight patients admitted to the intensive care unit as having life threatening community acquired pneumonia. The sensitivity of the modified rule for predicting death was 0.95 and the specificity 0.71. In 47 cases (21%) the clinical team appeared to underestimate the severity of the illness. CONCLUSIONS: The organisms responsible for community acquired pneumonia in Christchurch are similar to those reported from other centres except for Legionella species which were more common than in most studies. The modification of the BTS prognostic rules applied as a severity indicator at admission performed well and could be incorporated into management guidelines.

Adolescent↗
PubMed1996

Accumulation of natural and synthetic betaines by a mammalian renal cell line.

Intracellular accumulation of different betaines was compared in osmotically stressed Madin Darby canine kidney (MDCK) cells to model the betaine accumulation specificity of the mammalian inner medulla and to show how this accumulation differed from that of bacteria. All betaines accumulated less than glycine betaine. Arsenobetaine (the arsenic analogue of glycine betaine) accumulated to 12% of the glycine betaine levels and the sulphur analogue dimethylthetin accumulated to >80%. Most substituted glycine betaine analogues accumulated to 2-5% of intracellular glycine betaine concentrations, however, serine betaine accumulated to <0.5% of glycine betaine levels. Inhibition studies to distinguish the betaine ports were performed by the addition of proline. Butyrobetaine and carnitine accumulation was not proline sensitive, whereas that of other betaines was. As with glycine betaine, the accumulation of propionobetaine and dimethylthetin was proline sensitive and osmoregulated. Pyridinium betaine was accumulated by both proline-sensitive and -insensitive systems, with a small increase under osmotic stress. High concentrations (10 times that of glycine betaine) of the dietary betaines proline betaine and trigonelline inhibited total betaine accumulation. Because alpha-substituted betaines are accumulated by bacteria and not by MDCK cells, these betaines may be the basis for design of antimicrobial agents.

Animals↗
PubMed1996

Prospective, randomized, controlled study comparing two dosing regimens of gentamicin/oral ciprofloxacin switch therapy for acute pyelonephritis.

Aminoglycosides are drugs of choice for severe gram-negative urinary tract sepsis. Recent evidence suggests that they are just as efficacious, but less nephrotoxic and ototoxic, if given as a single daily dose rather than in divided doses. We considered that a single, large dose of an aminoglycoside followed by oral therapy with a different antibiotic might be equally effective and possibly less toxic. This randomized, controlled study compared a single large i.v. dose (10 mg/kg) of gentamicin (S) with a standard multiple dose regimen (M) of gentamicin (2.5 mg/kg i.v. stat and then computer generated divided doses aiming for peak and trough concentrations of 8 and 1.5 mg/l respectively) for the treatment of patients with suspected acute pyelonephritis requiring hospitalization for parenteral antibiotic treatment. All patients were switched to oral ciprofloxacin either four hours after the S dose or when clinically appropriate in the M regimen. For all patients the total duration of treatment was five days. Fifty-three patients (48 women; mean age 32 yr) were enrolled. Clinical and bacteriological efficacy could be assessed in 41 patients. Thirteen of 16 in the S arm and 24 of 25 in the M arm were clinically cured and the other four clinically improved. Fifteen of 16 in the S arm and 23 of 25 in the M arm were cured bacteriologically (sterile urine 7-10 days after treatment). In 41 patients high tone audiometry was carried out before or very soon after the start of treatment, and again at the end of treatment. Ototoxicity (> or = 10 dB loss in > or = 2 frequencies in both ears) was observed in 3 of 18 in the S group (17%) and 7 of 23 in the M group (30%) (NS). Other side-effects and toxicity were mild and not different between groups. Substantial cost savings occurred in the S group. In summary, a large single dose of gentamicin was comparable in efficacy and toxicity to a standard regimen, but cheaper and more convenient to use.

Acute Disease↗
PubMed1995

Competitive accumulation of betaines by Escherichia coli K-12 and derivative strains lacking betaine porters.

Escherichia coli was grown in hyperosmotic media containing both glycine betaine and one other betaine. E. coli K-12 derivative WG439 (putP- proP- proU-) did not accumulate any of 15 betaines. Strains WG445 (putP- proP- proU+), WG443 (putP- proP+ proU-) and the control strains all accumulated less betaine, (CH3)3N(+)-(CH2)n-COO-, when n was greater than 1. Accumulation was not detectable when n = 5. Both L- and D-isomers of alpha-substituted betaines were accumulated by both strains WG443 and WG445, the D-isomers more slowly. Hydroxylated alpha-substituted betaines were accumulated relatively more through the osmoregulated transport protein ProU than through ProP. In actively growing cultures glycine betaine appeared to be the preferred substrate for accumulation, but the proportion of the second accumulated betaine increased as cultures approached stationary phase.

Amino Acid Transport Systems↗
PubMed1995

Quinolones.

Explore the source record for details and available documents.

Bacteria↗
PubMed1995

Treatment of chronic hepatitis C with interferon alpha.

AIM: To evaluate the response to interferon alpha in patients with chronic hepatitis C in Christchurch. METHOD: Fifteen patients with chronic HCV were given interferon alpha 3 million units subcutaneously three times a week for up to 24 weeks. A complete and partial biochemical response was defined by relative changes in the serum alanine aminotransferase (ALT) during the treatment period. Detection of HCV RNA by the polymerase chain reaction was used to determine the virological response to treatment. RESULT: A complete or partial response was seen in nine of the 15 patients (60%). Histological improvement was demonstrated in all patients for whom paired liver biopsies were taken. Following treatment two of the five complete responders have shown a sustained biochemical response but only one has remained PCR negative, ie, a sustained virological responder. The other three, complete responders and all four partial responders relapsed. CONCLUSION: The response to treatment and relapse was comparable with other studies. It remains to be shown whether investigation of the viral titre and/or viral type will help to explain the high relapse rate in these patients with chronic HCV.

Adult↗
PubMed1995

Improved efficacy with nonsimultaneous administration of first doses of gentamicin and ceftazidime in vitro.

First doses of aminoglycoside and beta-lactam antibiotics, when used in combination, are usually given simultaneously; however, nonsimultaneous administration may be more efficacious. We used a dynamic in vitro model, which simulates in vivo serum kinetics, to assess the effect of spacing the first doses of gentamicin and ceftazidime used against Pseudomonas aeruginosa ATCC 27853 and two clinical isolates of P. aeruginosa, PA1 and PA2. The following dose regimens against P. aeruginosa ATCC 27853 were compared: (i) gentamicin given alone, (ii) ceftazidime given alone, (iii) gentamicin and ceftazidime given simultaneously, (iv) gentamicin followed by ceftazidime at 15 or 50 min or at 2, 4, or 8 h, and (v) ceftazidime which was followed by gentamicin at 4 h. The effects of regimen iii and the 4-h interval in regimen iv against PA1 and PA2 were also compared. Initial peak concentrations used were 8 mg/liter for gentamicin and 80 mg/liter for ceftazidime, with drug half-lives of 2.5 and 1.8 h, respectively. Compared with simultaneous administration, nonsimultaneous administration (regimens iv and v) produced greater overall bacterial killing and was associated with a delay in bacterial regrowth (p < 0.005) of up to 6.6 to 8.3 h, regardless of the order in which the drugs were given. The optimal interval between gentamicin and ceftazidime doses, which maximized initial bactericidal effect and the time before regrowth, appeared to be 2 to 4 h.

Ceftazidime↗
PubMed1995

Short-term response of nonurea organic osmolytes in human kidney to a water load and water deprivation.

The cells of the inner medulla of the mammalian kidney accumulate high concentrations of nonurea organic osmolytes. The organic osmolytes found in the kidney include glycine betaine and sorbitol. This study was designed to measure changes in the urinary excretion of glycine betaine and sorbitol and the plasma concentration of glycine betaine in response to an acute water load (20 ml/kg) or acute water deprivation in young healthy males. In response to a water load the urinary excretion of glycine betaine and sorbitol increased parallel with or shortly after urinary urea excretion. The increase in urinary urea and sorbitol excretions preceded maximum minute volume, whereas peak glycine betaine excretion was closely related to maximum urine minute volume. Subsequently, urea, sorbitol, and glycine betaine excretion rates returned to baseline. In contrast, during water deprivation no change in glycine betaine, sorbitol, and urea urinary excretions occurred during the study period. Plasma glycine betaine concentration was stable during both diuresis and antidiuresis. We conclude that the organic osmolytes glycine betaine and sorbitol are components of a physiological and dynamic system in response to an acute water diuresis.

Adult↗
PubMed1995

Clinical and economic considerations in the use of third-generation oral cephalosporins.

A number of oral third-generation cephalosporins (cefixime, cefetamet pivoxil, ceftibuten and cefpodoxime proxetil) have been widely trialled and are becoming available. In addition, cefdinir may also be marketed. Compared with first- and second-generation agents, the oral third-generation cephalosporins have an improved antibacterial spectrum and reduced minimum inhibitory concentrations against common Gram-negative pathogens. In contrast, with the exception of cefdinir, they are less active against Staphylococcus aureus. They have favourable pharmacokinetic profiles and are generally administered in once- or twice-daily regimens. They are well tolerated, but cefixime has been associated with a particularly high rate of diarrhoea. Possible clinical indications for the use of oral third-generation cephalosporins include upper and lower respiratory, genitourinary and soft-tissue infections and follow-on treatment of severe infections requiring hospitalisation. At present, these drugs offer no particular clinical advantages over standard therapy in most circumstances. However, they may be considered where there is hypersensitivity to penicillins, a high incidence of resistance to first-line therapy in the community, or failure of standard therapy. Further studies are needed to define the efficacy of oral third-generation agents in the prevention of rheumatic fever and as follow-on therapy for severe infections. The oral third-generation cephalosporins are generally more expensive than standard agents, but detailed studies that include extended costs (e.g. treatment of adverse effects, treatment of clinical failure, return visits to physicians) have yet to be reported.

Administration, Oral↗
PubMed1994

Abnormal glycine betaine content of the blood and urine of diabetic and renal patients.

In normal human plasma the concentrations of the renal osmolyte, glycine betaine, are usually between 20 and 70 mumol/l, in adult males (median 44 mumol/l) higher than in females (34 mumol/l). Concentrations are lower in renal disease (median 28 mumol/l) and normal in diabetes. Urinary excretion of glycine betaine shows no sex difference and is frequently elevated both in renal disease and in diabetes (medians: normal, 6.2, renal 12.3 and diabetes, 39.7 mmol/mol creatinine). The elevation in diabetes does not strongly correlate with known renal disease, nor with either urinary microalbumin or plasma creatinine. There is no correlation with glycated haemoglobin. The positive correlation with the excretions of another renal osmolyte, sorbitol, was highly significant in diabetic subjects. In the diabetic group there was also a significant negative correlation between plasma glycine betaine and urine microalbumin.

Adult↗