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C H Nightingale

Publications and source records attributed to C H Nightingale.

At least 109 records · Page 6Linked to original sources
PubMed1995

Clinical pharmacokinetics of newer cephalosporins.

Several new cephalosporins have been developed in recent years. These agents include several oral and parenteral agents with extended activity against Gram-negative pathogens. The pharmacokinetic literature for these agents is quite extensive; therefore, we have summarised this information and presented it in tabular form for critical comparison. With a few exceptions, the newer cephalosporins share similar pharmacokinetic properties. Cefixime, cefetamet pivoxil and ceftibuten differ from the others in that they exhibit nonlinear pharmacokinetic properties. The nonlinear nature of these agents is reflected by decreasing maximal concentrations with escalating doses of cefixime and cefetamet pivoxil, decreasing area under the serum concentration-time curve with increasing doses for cefixime, and a reduced bioavailability with large doses of ceftibuten. Attention to such characteristics aid the clinician in selecting appropriate dosage regimens that will optimise drug absorption. The majority of agents are primarily renally eliminated; however, renal elimination accounts for only 20% of cefixime elimination. The pharmacokinetic parameters noted for the newer cephalosporins are not influenced by multiple-dose administration, suggesting lack of drug accumulation over time. The pharmacodynamics of antimicrobials should be considered when extrapolating pharmacokinetic information into the clinical arena. In the case of the beta-lactams, the time which drug concentrations remain above some critical threshold, such as the minimal inhibitory concentration, appears to have the greatest influence on bactericidal activity. Therefore, it is important to select dosage regimens that will optimise the time serum concentrations remain above this threshold. We present an evaluation of these agents with respect to their activity against a variety of pathogens in an effort to demonstrate a pharmacokinetically-based process of antimicrobial selection.

Animals↗
PubMed1995

In vitro elution of ofloxacin from a bioabsorbable polymer.

A drawback with antibiotic-loaded polymethylmethacrylate (PMMA) beads is the second surgical procedure that may be required to remove the beads. We explored alternatives for the local delivery of antimicrobials and studied the release characteristics of ofloxacin (10 mg) when incorporated into either 30 or 50 mg beads of two different molar ratios of a bioabsorbable lactide: glycolide polymer. An elution method was employed over a 60-day period at 37 degrees C. After 60 days, about half of the ofloxacin had been released from the composites containing 50 mg and 30 mg of the 85:15 polymer, whereas nearly all of the ofloxacin had been released from both sizes of the 50:50 polymer composites.

Biodegradation, Environmental↗
PubMed1995

Implementation of a once-daily aminoglycoside program in a large community-teaching hospital.

Recently, there has been an emergence of interest in the use of once-daily aminoglycoside dosing. In an attempt to take advantage of the pharmacodynamic properties of these agents and to reduce the potential for toxicity, a once-daily aminoglycoside program was developed at this institution. This program uses a fixed intravenous dose of 7 mg/kg with dosing interval adjustments based on estimates of creatinine clearance or a single random serum aminoglycoside concentration. Because this automatic conversion program was initiated hospital-wide, more than 2,400 patients received the regimen with no apparent alteration in clinical success and the incidence of toxicity was lower than that previously observed. The purpose of this report was to describe the implementation process and unique features of this hospital-wide once-daily aminoglycoside program in a 850-bed community-teaching hospital.

Aminoglycosides↗
PubMed1995

Disposition kinetics of aspirin in female New Zealand white rabbits.

Limited information exists on the disposition of aspirin in rabbits. Such information is of value not only for treatment but also for development of experimental protocols with human applications. We evaluated the pharmacokinetics of aspirin at different doses by monitoring serum concentrations of the major metabolite, salicylic acid (SA). Four groups of six female New Zealand white rabbits received 2.5, 10, 20, or 50 mg of aspirin/kg of body weight. Aspirin was given once daily via the oral-gastric route, and blood samples were obtained after the third dose. Samples were collected before the last dose, then at 0.25, 0.50, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 h after dosing. Analysis of SA was completed by a validated assay on a high-performance liquid chromatography system. Mean maximal serum SA concentration was 7.54, 22.65, 43.2, and 70 micrograms/ml for the 2.5, 10, 20, and 50 mg/kg doses respectively. The total systemic clearance of SA was not altered by increasing doses of aspirin, but statistically significant differences were noted in the volume of distribution. The SA elimination half-life also increased proportionally with the aspirin dose. Bleeding tendency was associated with the highest dose of aspirin. Results of this study suggest that the 20 and 50 mg/kg dosages produced serum SA concentrations that simulate those observed in humans after 600-mg and 1.2-g aspirin doses respectively.

Animals↗
PubMed1994

Serum bactericidal activity of ceftriaxone plus metronidazole against common intra-abdominal pathogens.

The activity of ceftriaxone plus metronidazole against pathogens usually involved in intra-abdominal infections was studied. Metronidazole 1 g and ceftriaxone 1 g (as the sodium salt) were simultaneously administered i.v. over 30 minutes every 24 hours to 12 healthy volunteers for three doses. Serum samples were collected at baseline, just before the last dose, and 12, 16, 20, 22, and 24 hours after the start of infusion of the last dose. Serum bactericidal titers (SBTs) were performed in duplicate for each serum sample from 12 hours on. Serum ceftriaxone and metronidazole concentrations were determined by high-performance liquid chromatography, and the elimination rate and half-life were calculated for each antimicrobial in each volunteer. The minimum inhibitory concentrations (MICs) of each antibiotic for two strains each of Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, and Bacteroides fragilis were determined by microdilution. Eleven volunteers completed the study. Ceftriaxone and metronidazole maintained SBTs of at least 1:4. Serum ceftriaxone concentrations remained above the MICs for E. coli, P. mirabilis, and K. pneumoniae, and serum metronidazole concentrations remained above the MIC for B. fragilis throughout the study. Ceftriaxone combined with metronidazole resulted in intense and prolonged activity against E. coli, P. mirabilis, K. pneumoniae, and B. fragilis.

Abdomen↗
PubMed1994

Stability of aztreonam and ampicillin sodium-sulbactam sodium in 0.9% sodium chloride injection.

The stability of aztreonam, ampicillin sodium, and sulbactam sodium admixed in 0.9% sodium chloride injection and stored at room temperature and under refrigeration was studied. Each of the following admixtures was prepared in 0.9% sodium chloride injection: (1) aztreonam 10 mg/mL; (2) ampicillin 20 mg/mL (as the sodium salt) and sulbactam 10 mg/mL (as the sodium salt); and (3) aztreonam 10 mg/mL, ampicillin 20 mg/mL, and sulbactam 10 mg/mL. Three minibags of each admixture were stored at room temperature and three were refrigerated. Every 12 hours, up to 96 hours, the admixtures were visually inspected and 5-mL samples were withdrawn for high-performance liquid chromatography and pH testing. No color change or precipitation was observed in any sample. In admixtures containing ampicillin, ampicillin was the first or only drug to lose more than 10% of initial concentration. In the ampicillin-sulbactam admixture, ampicillin was stable for 32 hours at room temperature and 68 hours refrigerated. In the aztreonam-ampicillin-sulbactam admixture, ampicillin was stable for 30 hours at room temperature and 94 hours refrigerated. Aztreonam 10 mg/mL, ampicillin 20 mg/mL (as the sodium salt), and sulbactam 10 mg/mL (as the sodium salt) in 0.9% sodium chloride injection were stable in combination for up to 30 hours at room temperature and 94 hours under refrigeration.

Ampicillin↗
PubMed1994

Loss of bactericidal activities of quinolones during the post-antibiotic effect induced by rifampicin.

The post-antibiotic effect (PAE) is the phenomenon of persisting suppression of bacterial growth as a result of prior antimicrobial exposure. In antimicrobial therapy, multiple doses of either a single drug or a combination of drugs are common. Accordingly, the following question may arise: what impact might the PAE induced by the previous dose impose on the subsequent bactericidal action of a cycle-specific antibiotic. To answer the question, a study was conducted using pefloxacin, norfloxacin, ciprofloxacin and ofloxacin as test drugs, rifampicin as the PAE inducer and Escherichia coli ATCC 25922 as the test organism. Bacterial kill kinetics were determined for each quinolone at 4 x MIC before rifampicin treatment and during the PAE period following rifampicin challenge. The relative bactericidal activity of the quinolones during the PAE period was calculated. During the PAE period, pefloxacin, norfloxacin, ciprofloxacin and ofloxacin displayed only 6%, 8%, 7% and 33% of their normal activities, respectively. The results were compared to those obtained at low temperature (4 degrees C) and when the cells were challenged simultaneously with a quinolone and with rifampicin. The findings of this study suggest that prolonging the dosing interval by taking the PAE into account may not only lower the cost of antimicrobial therapy and the risk of toxicity, but also ensure the efficacy of subsequent doses.

4-Quinolones↗
PubMed1994

Efficacies of liposome-encapsulated clarithromycin and ofloxacin against Mycobacterium avium-M. intracellulare complex in human macrophages.

The therapeutic efficacies of liposome-encapsulated ofloxacin and clarithromycin against Mycobacterium avium-M. intracellulare (MAI) were evaluated in a model of intramacrophage infection. Liposome encapsulation was found to markedly enhance the uptake of each of the drugs by human macrophages. The human blood-derived macrophages were infected at day 7 of culture with MAI. Treatment was initiated 24 h after the infection, and the number of intracellular bacteria was determined at days 2, 3, and 4. Liposome entrapment of either ofloxacin or clarithromycin significantly (P < 0.005) enhanced the activities of the drugs when compared with the antimycobacterial effects of equivalent concentrations of the free (unentrapped) drugs. The drugs were used at concentrations close to their clinically achievable peak levels. The efficacy of clarithromycin, either in the free or liposome-entrapped form, was markedly higher than that of ofloxacin. Liposome-encapsulated ofloxacin or clarithromycin plus ethambutol was, in each case, more effective in organism eradication (P < 0.005) than each agent used singly. These results suggest that liposome-encapsulated clarithromycin may be more effective than the free form of the drug against MAI infections in vivo, and the use of a combination therapy with ethambutol could further enhance the efficacy.

Clarithromycin↗
PubMed1994

Optimal times above MICs of ceftibuten and cefaclor in experimental intra-abdominal infections.

The duration of time that serum drug levels remain above the MIC (time above the MIC) for the pathogen has been shown to be the most significant parameter determining the efficacies of beta-lactam antibiotics. In the described study, we investigated the optimal time above the MIC of ceftibuten and cefaclor using a nonneutropenic mouse model of intra-abdominal infections caused by Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Streptococcus pneumoniae. The abilities of the drugs to protect mice against the organisms were determined in mouse protection tests, and the doses were fractionated to produce various dosing regimens with different times above the MIC. All drug-organism combinations showed a significant correlation (r > 0.9) between drug efficacy and the time above the MIC. Also, with ceftibuten treatment, the different dosing regimens that produced equal times above the MIC resulted in the same efficacy, whereas with cefaclor, an apparent dose-dependent effect was observed. These results showed that for a 100% recovery from K. pneumoniae and E. coli infections, the optimal times above the MIC with ceftibuten treatment were 2.2 and 1.6 h, respectively. Relatively high doses of both antibiotics were required to ensure recovery from S. pneumoniae infections. In vitro time-kill studies demonstrated that cefaclor exhibits a marked inoculum effect against the pathogens, and there was a concentration-dependent killing at a large inoculum size. On the other hand, ceftibuten showed no inoculum effect. It is suggested that optimization of both dose and time above the MIC appears to be necessary for the treatment of S. aureus infections with cefaclor, and this may apply to other beta-lactams tht exhibit marked inoculum effects.

Abdomen↗
PubMed1994

Minocycline versus vancomycin for treatment of experimental endocarditis caused by oxacillin-resistant Staphylococcus aureus.

The purpose of this study was to determine the penetration of minocycline and vancomycin into cardiac vegetations and to determine their efficacy in a rabbit model of endocarditis caused by oxacillin-resistant Staphylococcus aureus. Animals were randomized into three groups: control (no antibiotic), minocycline (6 mg/kg given intravenously every 8 h), and vancomycin (50 mg/kg given intravenously every 8 h). Penetration of the antibiotics into aortic valve vegetations was determined by using the tissue/serum area under the concentration-time curve ratio. The reductions in the bacterial density of the vegetations caused by both vancomycin (4.8 +/- 1.2 CFU/g) and minocycline (5.3 +/- 1.6 CFU/g) were significantly different from that of controls (8.7 +/- 1.8 CFU/g). Although the penetration of minocycline was twice that of vancomycin, they were equally effective in reducing the bacterial density of the vegetations, since the concentrations of both agents in tissue remained above their MICs for oxacillin-resistant S. aureus. For organisms for which the MICs are higher, however, these penetration differences may result in treatment differences.

Animals↗
PubMed1994

How to develop critical paths and prepare for other formulary management changes.

Changes occurring in the health care marketplace are changing the way clinicians are managing patients. Cost, quality, and efficiency of care are increasingly being focused upon. One patient care management strategy that keeps these three factors in mind and is growing in popularity is the use of critical paths. This article describes the 7-step critical path development process followed by clinicians at Hartford Hospital. Additionally, the effect of health care marketplace changes on the formulary decision-making process, P & T Committee structure and function, and new drug development is also presented.

Clinical Protocols↗
PubMed1994

An improved HPLC assay for ciprofloxacin in biological samples.

A simple and sensitive high performance liquid chromatographic method was developed for determination of ciprofloxacin (Cip) in 0.1 ml of rabbit and human serum and CSF. Separation of Cip and pipemidic acid (internal standard) was achieved on Nucleosil C18 (4.6 mm x 250 mm) using fluorescence detection with lambda exc 274 nm and lambda emi 418 nm. The mobile phase was composed of acetonitrile and phosphate buffer 10 mmol.L-1 (pH 2.7) containing tetrabutylammonium hydrogen sulfate 5 mmol.L-1 (18:82, vol:vol) and the flow rate was set at 1.0 ml.min-1. The retention times were 5.9 min for Cip and 4.0 min for pipemidic acid. The inter-day coefficient of variation was < 6.97% (n = 5) and the intra-day coefficient of variation was < 3.33% (n = 5). The limits of detection were 3 ng.ml-1 serum and 5 ng.ml-1 CSF, (r > or = 0.9996). Application of this method was demonstrated with simultaneous measurements of concentration-time profiles of Cip in rabbit serum and CSF during iv infusions at constant rates of 0.33, 1.0, and 2.5 mg.kg-1.h-1.

Animals↗