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Biomedical subjects

P Noone

Publications and source records attributed to P Noone.

At least 37 records · Page 2Linked to original sources

Comparative analysis of two rapid automated methods and a semiautomated version of the urease method for determining aminoglycoside concentrations in serum.

The Syva EMIT Autolab 6000 and the Abbott TDX automated methods for measuring serum aminoglycoside concentrations were compared with each other and with a new semiautomated version of the urease technique. Each was evaluated for accuracy, reproducibility, cost, and ease of use. All three methods gave satisfactory results, although the Abbott TDX was the most accurate. Both automated methods gave results within minutes, whereas the new urease method, which involved more initial manipulation, took 1.25 h to complete (mainly incubation time). There was no difference in accuracy of performance between experienced and inexperienced operators. The new urease method was much cheaper in terms of initial capital expenditure and in cost per test and needed no provision of manufacturer's back-up maintenance services. This could prove invaluable in situations where financial resources are at a premium. Otherwise, the Abbott TDX is currently our method of choice, and reasons for its preference to the EMIT system are listed.

Anti-Bacterial Agents↗

A prospective randomised comparison of cefotaxime vs. netilmicin vs. cefotaxime plus netilmicin in the treatment of hospitalised patients with serious sepsis.

93 patients were enrolled into a prospective randomised study to determine the efficacy and safety of netilmicin, cefotaxime or their combination in the treatment of sepsis caused by susceptible strains of Enterobacteriaceae or staphylococci. 83 patients were evaluable for safety, 74 for clinical efficacy and 63 for microbiological response including 36 patients (57%) with positive blood cultures. There were significantly more clinical failures with cefotaxime than with netilmicin even when urinary tract sepsis was excluded. Microbiological failures occurred more frequently in the cefotaxime arm and were associated with Klebsiella and Enterobacter spp. Four cefotaxime failures were subsequently successfully treated with netilmicin. More mixed infections were however enrolled by chance into the cefotaxime arm. The statistical difference between netilmicin and cefotaxime is not significant if mixed infections are excluded. There was no difference in efficacy between the netilmicin and combination groups although superinfection was seen in the latter group. The incidence of nephrotoxicity was greater in the netilmicin group but not significantly so. Only one minor case of ototoxicity was detected in the 41 patients receiving netilmicin who had serial audiograms. The results suggest that netilmicin is a more effective agent than cefotaxime for treating life-threatening infections with susceptible Enterobacteriaceae or staphylococci particularly with infections in non-urinary tract sites. If dosage of netilmicin is closely monitored by measuring serum concentrations, toxicity is minimal.

Adolescent↗

Biliary lavage with corticosteroids in primary sclerosing cholangitis. A clinical, cholangiographic and bacteriological study.

Bile duct perfusion with corticosteroids is reported to improve the cholangiographic and biochemical abnormalities in some patients with primary sclerosing cholangitis. In a randomised placebo controlled trial, thirteen consecutive patients received continuous bile duct irrigation with either normal saline (1 l/day) or normal saline plus hydrocortisone (100 mg daily) via a nasobiliary tube placed in a hepatic duct at endoscopic retrograde cholangio-pancreatography. Eleven patients completed lavage for 2 weeks but no cholangiographic changes were observed in either group. Liver function tests deteriorated during lavage, but later returned to pre-treatment levels. Although bile was sterile at start of lavage, a wide range of bacteria was isolated from bile in all patients during treatment, and cholangitis with septicaemia occurred in 2 patients. We conclude that nasobiliary lavage is not beneficial in treating primary sclerosing cholangitis.

Adult↗

The comparative in-vitro activity of norfloxacin, ciprofloxacin, enoxacin and nalidixic acid against 423 strains of gram-negative rods and staphylococci isolated from infected hospitalised patients.

The in-vitro activities of four quinolone carboxylic acids against 423 clinical isolates of Gram-negative rods and staphylococci from infected hospitalised patients were compared. The antibiotics included nalidixic acid and the newer compounds, norfloxacin (MK-0366), ciprofloxacin (Bay 09867) and enoxacin (AT 2266 or CI919). Norfloxacin showed slightly more activity than enoxacin, but both agents had markedly greater potencies and broader antibacterial spectrums than nalidixic acid. Ciprofloxacin was the most active quinolone tested against both gentamicin-susceptible and gentamicin-resistant stains, having an MIC90 equal or less than 1 mg/l for all species studied.

Acinetobacter↗

Ceftazidime in the treatment of serious Pseudomonas aeruginosa sepsis.

28 patients with serious Pseudomonas aeruginosa sepsis were enrolled into a prospective open study using ceftazidime (CAZ). 10 patients had rapidly fatal underlying pathology, including 5 neutropenic (neutrophils less than 1.0 X 10(9)/l) patients with malignancy. 9 patients including all those with neutropenia also received concomitant therapy with other active antipseudomonal antibiotics (mainly aminoglycosides). All isolates were initially sensitive to CAZ. A favourable response was seen in 18/27 (67%) evaluable cases. Genitourinary infection and osteomyelitis responded well with 100% and 83% favourable responses respectively. Soft tissue and respiratory tract infection responded less well. Results with biliary sepsis were disappointing (all 3 failed therapy). Of the 9 patients failing treatment 5 responded to alternative antibiotics (usually combination therapy of ureidopenicillin plus aminoglycoside). 2 died primarily from underlying pathology and 2 as a direct result of Ps. aeruginosa sepsis. Toxicity was minimal. In the few cases observed other agents and underlying pathology possibly contributed. The most disturbing feature of the study was the emergence of multiple beta-lactam resistance in organisms whilst treated with CAZ. 5 cases occurred, 4 in the infected strain and 1 in a superinfecting strain, occurring in 4 patients within 10 days of starting therapy. 2 cases occurred in patients receiving concomitant aminoglycosides.

Adolescent↗

Netilmicin in gram-negative sepsis: comparative abilities of a dosage nomogram and clinical microbiologists to predict the preferred individual dose.

The preferred dose of netilmicin was determined in each of 39 patients with severe gram-negative sepsis treated at two centres. The dose was based upon the attainment of recommended serum concentrations. Patient age varied from 18 to 87 years (mean 58), estimated creatinine clearance from 20 to 150 ml/min (mean 71), and the preferred dose from 100 to 750 mg/24 h. The dose generated by a nomogram for netilmicin was compared in retrospect with the initial dose assigned to each patient by the clinical microbiologist concerned. With respect to the preferred dose, the nomogram underdosed, on the average, by 40 mg/24 h, and the microbiologists, by 30 mg/24 h. The correlation with the preferred dose was stronger for the nomogram dose (r = 0.66; p less than 0.001, 37 df) than for the microbiologists' dose (r = 0.47; p less than 0.005, 37 df) but there was no significant difference between the two in the frequency with which they predicted the preferred dose to within 50 mg/24 h (nomogram 19/39; microbiologists 16/39). The prescription of a fixed dose of 450 mg/day to all patients would have had a similar success rate (15/39). The performance of the nomogram was better in patients with serum creatinine concentrations of greater than or equal to 100 microM (r = 0.82; p less than 0.001, 13 df; 10/15 within 50 mg/24 h of preferred dose) than in those with creatinine concentrations less than 100 microM (r = 0.55; p less than 0.01, 22 df; 9/24 within 50 mg/24 h of preferred dose).

Adolescent↗

Disseminated infection associated with corticosteroid therapy after transduodenal sphincteroplasty.

Treatment with oral prednisolone appears to have precipitated an episode of ascending cholangitis in an asymptomatic 55-year-old patient. He had undergone a Pólya partial gastrectomy, a cholecystectomy and a sphincteroplasty 19, 6 and 2 years earlier, respectively. The cholangitis was complicated by septicaemia with six different enteric organisms including aerobes and anaerobes. He developed liver and lung abscesses, and an indolent Pseudomonas aeruginosa septic arthritis of both hip joints. The patient eventually made a complete recovery, but required surgical replacement of both hips.

Ampulla of Vater↗

The comparative activity of eleven aminocyclitol antibiotics against 773 aerobic gram-negative rods and staphylococci isolated from infected hospitalized patients.

The minimum inhibitory concentrations (MICs) of 11 aminocyclitol antibiotics were determined for 773 recent clinical isolates from infected hospital patients, most of whom were immunocompromised. There was a bias towards aminoglycoside-resistant organisms, and 21% of Pseudomonas aeruginosa isolates were resistant to gentamicin. The antibiotics included the natural agents gentamicin, tobramycin, sissomicin and kanamycin and the semi-synthetic compounds amikacin, netilmicin and dibekacin with some newer agents, including O-demethyl fortimicin, Hapa gentamicin B and 5-epi-sissomicin, not available commercially. Tobramycin, sissomicin and gentamicin had similar spectra with tobramycin more active against Ps. aeruginosa, sissomicin more active against proteus and gentamicin more active against serratia. The differences in spectrum between amikacin and netilmicin were marginal, reflecting the relatively low prevalence of acetyltransferase-producing organisms in our collection. Hapa-gentamicin B was the most active aminoglycoside against staphylococci and indole-positive proteus, netilmicin against Escherichia coli and 5-epi-sissomicin against Ps. aeruginosa. Overall 5-epi-sissomicin was the most active aminoglycoside tested. Both Hapa-gentamicin B and 5-epi-sissomicin have potentially valuable antibacterial spectra which merit clinical studies.

Anti-Bacterial Agents↗

Intragastric bacterial activity and nitrosation before, during, and after treatment with omeprazole.

Ten healthy volunteers were studied before, during, and after treatment with omeprazole 30 mg daily for two weeks. On the 14th night mean nocturnal (2100-0700) intragastric acidity was significantly decreased by 75% (p less than 0.001). At 0700, 22 hours after the last dose of omeprazole, there were significant increases in the bacterial count and the nitrite and N-nitrosamine concentrations in the gastric juice (p less than 0.001). Three days later these changes had resolved. Short term treatment of healthy volunteers with omeprazole is associated with a short lived increase in the gastric bacterial flora, with endogenous production of N-nitroso compounds.

Adult↗

Prevention of post-appendicectomy sepsis by mezlocillin and metronidazole: a prospective, randomized, double-blind trial.

In a double-blind trial a 6% infection rate resulted from the use of a single peroperative dose of mezlocillin in emergency appendicectomy for non-perforated disease. No advantage was demonstrated by mezlocillin over the 8% infection rate achieved with metronidazole. There was only one anaerobic infection in the mezlocillin group although Bacteroides fragilis had been isolated at operation from all three infected cases and many other uninfected patients. No anaerobic infections were detected in the metronidazole group.

Adolescent↗

Sisomicin, netilmicin and dibekacin. A review of their antibacterial activity and therapeutic use.

Sisomicin is a naturally occurring aminoglycoside antibiotic produced by Micromonospora inyoensis, while dibekacin and netilmicin are both semisynthetic aminoglycosides. Dibekacin is 3',4'-dideoxykanamycin B and netilmicin is 1-N-ethyl sisomicin. In both cases, these modifications render the agents insusceptible to some of the enzymes found in resistant strains of bacteria which inactivate the parent compounds. Antibacterial activity: All 3 drugs show bactericidal activity against a wide range of Gram-negative bacteria (including E. coli, Enterobacter, Klebsiella and Proteus spp. and Ps. aeruginosa) and also against staphylococci; however, in common with other amino-glycosides, streptococci are usually resistant (except when beta-lactam antibiotics are used in combination) and anaerobic organisms are not sensitive. Sisomicin is closely related structurally to gentamicin Cla, but in vitro studies have shown it to have superior activity to gentamicin against Ps. aeruginosa, closely paralleling the activity of tobramycin, while still possessing the high activity of gentamicin against Serratia and other Gram-negative rods. However, sisomicin is inactivated by virtually all bacterial enzymes which inactivate gentamicin and tobramycin. Nevertheless, it retains useful activity against a number of gentamicin-resistant strains of Ps. aeruginosa which are resistant by non-enzymatic (possibly permeability barrier) mechanisms; in this respect it closely resembles tobramycin. Dibekacin closely resembles tobramycin structurally and in vitro it seems to have a very similar antibacterial spectrum, including activity against some strains of Ps. aeruginosa resistant to gentamicin. Netilmicin has a generally broader antibacterial spectrum than gentamicin, tobramycin, sisomicin or debekacin and is resistant to inactivation by phosphorylating and adenylylating enzymes; however, it is inactivated by all acetylases, apart from acetylase 3-I. Its spectrum is therefore not as wide as that of amikacin against 'gentamicin-resistant' strains. Nonetheless, it is intrinsically more active than amikacin, weight-for-weight, against sensitive strains, apart possibly from Ps. aeruginosa. In fact, its activity against species of the Enterobacteriaceae and staphylococci sensitive to gentamicin is of the same order as the latter and possibly better for Klebsiella-Enterobacter species. All 3 agents show marked antibacterial synergy with a variety of beta-lactam antibiotics against a range of bacteria. Pharmacokinetically, sisomicin, netilmicin and dibekacin all behave like gentamicin. All 3 drugs are excreted in the urine unchanged and have beta-phase elimination half-lives of around 2 to

Aging↗