PubMed Health⌕ Search

Biomedical subjects

S R Norrby

Publications and source records attributed to S R Norrby.

At least 19 recordsLinked to original sources
PubMed1995

Comparative antibacterial activity of L-695,256, a carbapenem active against methicillin-resistant staphylococci.

The activity of a new prototype carbapenem, L-695,256, against clinical isolates of gram-positive and gram-negative aerobes was studied in vitro by agar dilution. L-695,256 was highly active against methicillin-resistant and -susceptible isolates of staphylococci (MICs, 0.016 to 2 micrograms/ml) and against penicillin-resistant pneumococci (MICs, 0.016 to 0.064 micrograms/ml), irrespective of penicillin susceptibility. Activity against members of the family Enterobacteriaceae was less than that of imipenem, while Proteus mirabilis and Morganella morganii were more susceptible to L-695,256.

Anti-Bacterial Agents↗
PubMed1992

Design of clinical trials in patients with urinary tract infections.

This overview deals with the optimization of the design of clinical trials in patients with urinary tract infections (UTIs). Despite the fact that UTI is one of the most common types of infection and that the main end-point (elimination or persistence of bacteriuria) is objective and easy to register, the quality of studies performed and published has generally been less than optimal. Problems that should always be addressed in the study protocol are definitions of terms used, for example bacteriuria, level of the infection (cystitis or pyelonephritis), and uncomplicated and complicated infections; dimension of the patient's sample to allow adequate testing of a null hypothesis; procedures before, during and after treatment; methods for analysis of the results.

Bias↗
PubMed1992

Ecological effects of short-term ciprofloxacin treatment of travellers' diarrhoea.

Forty-two subjects travelling to Mexico for 11 days were enrolled in a randomized, double-blind, placebo-controlled trial comparing ciprofloxacin 250 mg twice daily for three days or placebo for treatment of travellers' diarrhoea. Seventeen (41%) subjects were randomized to treatment. By the last treatment day, all seven evaluable subjects in the ciprofloxacin group, and three of eight evaluable subjects in the placebo group were cured (P = 0.04). The mean time to cure was 26 h for ciprofloxacin and 60 h for placebo-treated patients (P = 0.03). Faecal specimen were collected pre-travel, after four days in Mexico, 48 h post-travel and four weeks post-travel. Potentially pathogenic Escherichia coli strains carrying diarrhoeagenic virulence genes were detected by DNA hybridization tests, during or after travel, in 41% of treated and 31% of asymptomatic travellers. Travel, irrespective of diarrhoea and type of treatment, had a minor impact on the aerobic and anaerobic microflora. In travellers with ongoing diarrhoea, a suppression of the numbers of anaerobic bacteria was found, but the microflora was otherwise virtually unaffected. Significantly increased frequencies of E. coli resistant to ampicillin, doxycycline, chloramphenicol and co-trimoxazole were found during and after travel in all categories of travellers, though more frequently in subjects who experienced diarrhoea. The susceptibility of Bacteroides spp. remained unchanged. The sensitivity of E. coli to ciprofloxacin was not affected by travel, except in four ciprofloxacin-treated subjects who acquired multiresistant E. coli with ciprofloxacin MICs of > or = 0.125 mg/L post-travel. Bacteroides strains with MICs of > or = 64 mg/L were isolated post-travel from four ciprofloxacin-treated patients, and from one of the other 34 travellers not treated with ciprofloxacin.

Administration, Oral↗
PubMed1992

Pharmacokinetics of cefepime dihydrochloride arginine in subjects with renal impairment.

In this study, the safety, tolerance, and pharmacokinetics of a single 1-g intravenous dose of cefepime (BMY-28142) were investigated. Twenty-three volunteers with various degrees of renal function were assigned to four trial groups according to glomerular filtration rates (GFR). Group IV consisted of five patients with end-stage renal disease undergoing treatment with hemodialysis. Cefepime concentrations in samples from plasma, urine, and infusion solutions were assayed with high-pressure liquid chromatography. The volume of distribution corresponded to the assumed extracellular fluid volume and did not differ significantly between the four groups. The area under the concentration-time curve increased as renal function decreased; in group II (GFR, 31 to 80 ml/[min x 1.73 m2]; n = 6), it was already three times higher than in group I (GFR, > or = 80 ml/[min x 1.73 m2]; n = 5). Mean residence time was 2.4, 6.8, 11.4, and 31.6 h for the four groups, respectively. Total clearance decreased (97.2, 34.6, 19.8, and 6.3 ml/[min x 1.73 m2]) with decreasing renal function, and a linear relationship between total plasma clearance and GFR was found with the regression equation y = 0.92x-2.0 (r = 0.991). Renal clearance was linearly correlated to GFR with the regression equation y = 0.87x-6.1 (r = 0.989), indicating that renal elimination is mainly by glomerular filtration. During hemodialysis, the extraction ratios were between 0.40 and 0.65. Dialysis clearance varied between 69.9 and 94.6 ml/(min x 1.73 m2).

Adult↗
PubMed1992

Pharmacokinetics of meropenem in subjects with various degrees of renal impairment.

Five healthy volunteers and 18 patients with various degrees of renal impairment received 500 mg of meropenem intravenously as a 30-min infusion. Five dialysis patients were dosed 2 h prior to hemodialysis, and four of them were also dosed between hemodialysis treatments. Plasma and urine samples were collected for up to 48 h and 12 h, respectively. Concentrations of meropenem and its open ring metabolite ICI 213,689 were determined by high-performance liquid chromatography and radioimmunoassay, respectively. The subjects were divided into four groups with glomerular filtration rates (GFR) of greater than 80, 30 to 80, 5 to 29, or less than 5 ml/min. There were linear correlations between the GFR and the rates for total plasma clearance as well as renal clearance of meropenem (group mean values for total clearance of 186, 74, 53, and 19 ml/min/1.73 m2, respectively). In subjects with normal renal function, nonrenal clearance accounted for approximately 20% of total elimination, increasing to about 50% in patients with GFR between 5 and 29 ml/min/1.73 m2. The terminal half-life of meropenem increased from 0.9 h in the healthy volunteers to 6.8 h in patients with end-stage renal disease. The half-life of ICI 213,689 was 2.31 h in the healthy volunteers and increased to 23.6 h in patients with GFR of 5 to 29 ml/min. In patients with end-stage renal disease, half-lives could not be measured, as concentrations were hardly declining during the 48-h observation period. The area under the concentration-time curve for meropenem increased more than 10-fold. Both meropenem and its open ring metabolite were readily dialyzable, with dialysis clearances of 79 and 81 ml/min/1.73 m2, respectively.

Adult↗
PubMed1992

Future trends in antibiotic therapy.

The 1990s will probably see fewer new antibiotics being registered than occurred during the 1970s and 1980s. The main reason for this is the excessive costs involved in the development of a new chemical entity. It is probable that more fluoroquinolones will be introduced and some of them will have improved antibacterial activities compared to current derivatives. Another class of antibiotics likely to develop during the next decade is the macrolides, with the emergence of drugs like azithromycin. Among the beta-lactams, new carbapenems and extended spectrum cephalosporins will be developed to meet the problems of increasing numbers of enterobacteria producing class I beta-lactamases, as well as the new broad-spectrum TEM enzymes. These resistance mechanisms against beta-lactams are also likely to give rise to a new era for beta-lactamase inhibitors. A field which presently looks less promising is that of drugs which are active against methicillin-resistant staphylococci; teicoplanin and daptomycin seem to have only minor advantages over vancomycin. Other developments that can be expected are those facilitating the administration of antibiotics, especially once-daily injectable antibiotics for intensive home care.

Anti-Bacterial Agents↗
PubMed1991

Pharmacokinetics of meropenem compared to imipenem-cilastatin in young, healthy males.

Imipenem combined with cilastatin and meropenem was given as intravenous infusions of 1 g to eight young, healthy males on two separate occasions. Blood and urine samples were collected for up to 12 h. The terminal half-lives in plasma were 0.98 h and 1.11 h for meropenem and imipenem, respectively. The volume of distribution was smaller for meropenem than for imipenem (12.5 l and 14.4 l, respectively). The plasma clearance for meropenem was 188 (SD 31) ml/min and for imipenem 183 (SD 25) ml/min. Renal clearance was on average 139 (SD 24) ml/min and 135 (SD 11) ml/min, respectively. About 75% of the administered dose of both compounds was eliminated unchanged in urine. Non-renal clearance accounted for approximately 25% of the total clearance for both drugs. The kinetics of meropenem are very similar to those of imipenem given with cilastatin, and meropenem is as stable against renal metabolic degradation as imipenem combined with cilastatin.

Adult↗
PubMed1991

Side-effects of quinolones: comparisons between quinolones and other antibiotics.

Fluoroquinolones are generally very safe antibiotics which do not cause serious or life-threatening adverse reactions. The most frequent side-effects are gastrointestinal reactions (nausea, dyspepsia, vomiting) and CNS reactions such as dizziness, insomnia and headache. Many of the more severe CNS reactions seem to be due to metabolic interaction with theophylline, especially when enoxacin is used. Of the potentially serious side-effects, photoxicity has been reported in varying frequencies with the different fluoroquinolones. Caution is necessary when this group of drugs, especially pefloxacin, is prescribed to patients who will have intensive exposure to UV light during treatment. The finding in juvenile animals of cartilage damage after administration of high doses have resulted in recommendations that fluoroquinolones should not be used in children. Carefully monitored studies should be performed in paediatric patients to assess whether there is a real risk of such adverse reactions.

4-Quinolones↗
PubMed1991

Pharmacokinetics of meropenem and its metabolite ICI 213,689 in healthy subjects with known renal metabolism of imipenem.

Six healthy male subjects who had received imipenem without cilastatin in previous studies, were given 500 mg meropenem as single 30 min intravenous infusions. Plasma and urine samples were collected for 12 h and meropenem and its metabolite were assayed by HPLC and RIA, respectively. The mean plasma half-life of meropenem was 0.8 h, mean plasma clearance 277 ml/min and the mean volume of distribution 20.4 l. The metabolite reached mean peak plasma concentrations of 1.5 mg/l. Renal clearance of meropenem averaged 200 ml/min. The mean urinary recovery of the metabolite was 20% and of unchanged drug 72% of the dose given. The recovery of meropenem ranged from 62.2% to 78.2% and was correlated to the urinary recovery of imipenem when given without cilastatin to the same subjects in previous studies (range 15.2-32.2%, rank correlation coefficient = 0.934). The results indicate that meropenem is much less susceptible to renal metabolism than imipenem. The inter-subject variability observed with meropenem correlates with the extent of urinary recovery of imipenem observed in previous studies with imipenem alone, indicating some susceptibility of meropenem to renal dehydropeptidase-I.

Adult↗
PubMed1991

Neurotoxicity of beta-lactam antibiotics: predisposing factors and pathogenesis.

Neurotoxic reactions caused by beta-lactam antibiotics occur frequently following direct application of antibiotic to the brain surface or into the cerebral cisterns. Epileptogenic reactions have also been observed after administration of very high systemic doses. There seem to be considerable differences in the neurotoxic potential of the various beta-lactams; benzylpenicillin, cefazolin and, lately, imipenem/cilastatin appear to be drugs with higher neurotoxic potential than other compounds. There is now strong evidence that the concentration of beta-lactam in the brain, and not that in the cerebrospinal fluid, is the decisive factor for the risk of neurotoxic reactions. Factors known to increase the risk of neurotoxicity are excessive doses, decreased renal function, damage to the blood-brain barrier, preexisting diseases of the central nervous system, old age and concurrent use of drugs that are nephrotoxic or that may lower the seizure threshold. Another factor that may be of importance is blockage of the transport system that is responsible for transport of beta-lactams out of the central nervous system.

Animals↗
PubMed1991

Assessment of adverse events during drug development: experience with temafloxacin.

The safety of temafloxacin was evaluated in 753 subjects in phase I trials and in 2602 patients included in phase II and III studies. Comparative treatment was given to 153 subjects in phase I who received placebo and to 2031 patients in phase II and III trials who were given other quinolones (n = 1169) or non-quinolone comparators (n = 862). Adverse events were collated by spontaneous reporting by the patients or observations by investigators and, additionally in some studies, by the use of diary cards filled in by the patients. The results showed that temafloxacin was at least as safe as the comparators. Dose related gastrointestinal adverse reactions were found only in patients with reduced renal function who received a high temafloxacin dose. There was a low incidence of quinolone-related adverse reactions (photosensitivity, CNS-toxicity, or theophylline drug-drug interactions). The most common adverse reactions were gastrointestinal ones which occurred in 13.4% of the patients included in phase II and III trials. The corresponding frequencies in patients randomized to quinolone and non-quinolone comparators were 15.7% and 11.6% (P less than 0.05) [corrected], respectively. In conclusion, temafloxacin was shown to be at least as safe as the comparators used in the extensive phase I to III programme for evaluation of this new quinolone.

Aged↗
PubMed1991

Susceptibility of anaerobic bacteria to BAY v 3522.

The activity of BAY v 3522 against 340 strains of anaerobic bacteria was determined by an agar dilution method. Its activity was compared with those of amoxicillin, amoxicillin-clavulanate, cefaclor, cefadroxil, cefoxitin, cefuroxime, cephalexin, clindamycin, doxycycline, and metronidazole. BAY v 3522, amoxicillin-clavulanate, cefoxitin, clindamycin, and metronidazole were the most active agents tested. On the basis of these results, BAY v 3522 appears to have an antibacterial activity that warrants further investigation in clinical trials.

Anti-Bacterial Agents↗
PubMed1991

Treatment failures with broad-spectrum antibiotics.

Three main reasons for clinical failures of antibiotic therapy are reviewed and discussed: antibiotic resistance, pharmacokinetic properties of the drug used and host factors. Of these, antibiotic resistance is the easiest to study but probably not the most common cause of unsuccessful therapy. Inability of an antibiotic to achieve sufficient concentrations at the site of an infection is most likely also an uncommon reason for lack of response to treatment. In most cases, it seems justified to assume that host factors are the most important explanation when clinical failures of antibiotic therapy are encountered. However, firm data to prove these assumptions are lacking and it is imperative that analysis of failures be included in all clinical trials; in doing such analyses it is likely that considerably more valuable information will be generated than just by analysis of frequencies of favourable therapy outcome.

Age Factors↗
PubMed1990

The design of clinical trials with antibiotics.

Clinical trials to test antibiotics are normally of a less than satisfactory quality. Examples of common errors in the design and execution of trials with antibiotics are inclusion of too few patients to allow conclusions to be drawn, open uncontrolled design leading to a risk of considerable investigator bias, and inclusion of heterogeneous patient samples. This article suggests minimum requirements for antibiotic studies. Guidelines for such trials are needed and should have the widest possible international application in order to permit studies involving centres in various countries and to reduce the costs for development of new drugs.

Anti-Bacterial Agents↗
PubMed1990

Comparative in vitro activity of the new oral cephalosporin Bay v 3522 against aerobic and anaerobic bacteria.

The in vitro activity of the new oral cephalosporin Bay v 3522 against 229 aerobic and 330 anaerobic clinical isolates was determined using the agar dilution technique. For comparison, amoxicillin, amoxicillin/clavulanate, cefaclor, cefadroxil, cefuroxime, cephalexin, ciprofloxacin, clindamycin, co-trimoxazole, doxycycline, erythromycin and metronidazole (only anaerobic bacteria) were tested. Bay v 3522 was found to have high activity against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pneumoniae, Streptococcus pyogenes, Branhamella catarrhalis, Haemophilus influenzae, anaerobic cocci, Propionibacterium acnes, Clostridium perfringens and fusobacteria. When tested against a higher inoculum or using the broth dilution technique, the activity of Bay v 3522 showed little dependence on inoculum size and the bactericidal activity was similar to inhibitory activity in most bacterial groups. Bay v 3522 may be useful in the treatment of skin, soft tissue and respiratory tract infections. Clinical studies are thus warranted.

Aminoglycosides↗