Biomedical subjects

C H Nightingale

Publications and source records attributed to C H Nightingale.

269 records · Page 15Linked to original sources

PubMedDate not supplied

Choosing a bronchodilator for asthma therapy: the role of rapid onset of action.

National guidelines for the treatment of asthma recommend anti-inflammatory corticosteroids or cromolyn in patients with mild to moderate disease. A comparison of different bronchodilators demonstrates that beta-adrenergic-receptor agonists, specifically those selective for beta 2 receptors in the airways, are the safest and most effective agents for "rescue" during acute attacks. Because rapid onset of action is a clear advantage for the reversal of bronchoconstriction, a fast-acting agent such as albuterol is preferable to a slow-acting agent such as fenoterol or salmeterol.

Administration, Inhalation↗

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Pharmacokinetic curve fitting when the experimental error of the concentration-time data is represented by a relative error model.

When the experimental error of concentration-time data is represented by the relative error model (i.e. constant coefficient of variation) two approaches (direct input of concentration-time data with 1/C2i as a weighting factor, and input of logarithmically transformed concentration-time data) are equally effective in pharmacokinetic modelling. Advantages of the latter approach are discussed.

Anti-Bacterial Agents↗

PubMedDate not supplied

Review of cefonicid, a long-acting cephalosporin.

The in vitro activity, pharmacokinetics, adverse effects, and clinical efficacy of cefonicid are reviewed. Also discussed are formulary considerations and bacterial resistance. Cefonicid, an investigational agent near approval, is less active than other currently available first- and second-generation cephalosporins against gram-positive cocci, particularly Staphylococcus. Cefonicid and cefamandole have similar activity that is superior to the first-generation cephalosporins against Escherichia coli, Klebsiella, Citrobacter spp., Enterobacter spp., indole-negative Proteus spp., and Providencia spp. Organisms such as Serratia marcescens, Acinetobacter, Pseudomonas, and Bacteroides fragilis are resistant to cefonicid. Despite a small volume of distribution and high protein binding, cefonicid achieves high tissue concentrations. Approximately 90% of an administered dose is excreted unchanged in the urine, and the elimination half-life is approximately four hours. Cefonicid is usually well tolerated. In treating skin infections, cefonicid was usually less effective than cefazolin against Staphylococcus aureus. In genitourinary infections, cefonicid 1 g daily (as the sodium salt) in a single dose has shown comparable efficacy to cefamandole or amoxicillin given in multiple daily doses. Based on available data, single daily dosing of cefonicid in the therapy of Staph. aureus endocarditis is not effective. In studies of patients undergoing hysterectomy, cesarean section, cholecystectomy, and colorectal surgery, cefonicid 1 g given as a single preoperative dose has produced results comparable with those of cefoxitin 1-2 g (as the sodium salt) given preoperatively and for several doses postoperatively. The major clinical uses of cefonicid will probably be as a possible cost-reducing alternative (based on a single daily dose) to currently available first- and second-generation cephalosporins for the treatment of community-acquired pneumonia and infections caused by enteric organisms. It may also be useful as a possible cost-reducing alternative to cefoxitin for prophylaxis in hysterectomy and biliary tract surgery.

Bacterial Infections↗

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Antiemetic efficacy of prochlorperazine, haloperidol, and droperidol in cisplatin-induced emesis.

The antiemetic efficacy of haloperidol, droperidol, and prochlorperazine in preventing cisplatin-induced emesis was evaluated. Twenty-seven patients receiving 51 courses of cisplatin chemotherapy randomly received antiemetic treatment with prochlorperazine (6 mg/sq m), droperidol (1 mg/sq m), or haloperidol (1 mg/sq m) in a double-blind crossover study. Antiemetics were given by intramuscular injection one hour before beginning cisplatin and every three hours thereafter for a total of six doses. The number of emetic episodes, volume of emesis, and duration of the emetic episodes were monitored by oncology nurses. There were no significant differences in the median number of emetic episodes among antiemetic treatments: 3.5 for prochlorperazine, 4.0 for haloperidol, and 3.0 for droperidol. There were also no significant differences among the antiemetics in the median volume of emesis or the median duration of the emetic episodes. At the doses used in this study, the antiemetic efficacy of prochlorperazine, droperidol, and haloperidol appear to be comparable for patients receiving cisplatin chemotherapy.

Aged↗

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Comparison of four methods of predicting serum gentamicin concentrations in adult patients with impaired renal function.

Four methods of predicting serum gentamicin concentrations (SGCs) in adult patients with stable impaired renal function were compared. Serum samples obtained from 17 patients receiving intravenous gentamicin therapy were assayed for gentamicin using a radioimmunoassay. Kinetic variables derived using four different methods were used to predict peak and trough concentrations. The Sawchuk-Zaske method uses individualized apparent volume of distribution (Vapp) and half-life (t1/2) derived from at least three SGCs following a given dose. The fitted method assumes Vapp equals 0.28 liters/kg lean body weight (LBW) and a t1/2 derived by a fitting technique using only one SGC. Both the Tozer and Hull methods assume Vapp equals 0.28 liters/kg LBW, and t1/2 is estimated from equations that take into account the patient's renal function (creatinine clearance). The predicted and measured SGCs for each method were compared using linear regression analysis. The prediction errors, defined as the predicted minus the measured SGC, were compared for the four methods. The correlation coefficients between the measured and predicted SGCs were significant at p less than 0.05 only for the Sawchuk-Zaske and fitted methods. For the Sawchuk-Zaske method, peak and trough r values were 0.73 and 0.91, respectively. For the fitted method, peak and trough r values were 0.53 and 0.71, respectively. No significant differences in the mean prediction errors were observed, except for the Sawchuk-Zaske method, which had significantly less mean prediction error than the Hull method. The Sawchuk-Zaske method was the most reliable and accurate pharmacokinetic technique. However, because it is more costly and less convenient than the other three methods, both the accuracy and cost should be considered when selecting a method for determining serum gentamicin concentrations for a particular patient.

Aged↗

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Pharmacokinetics of vancomycin in anuria.

After a single 1-g intravenous dose of vancomycin, the mean peak concentration in the serum of 29 anephric patients was 48.3 micrograms/ml. An initial rapid decline to 15 micrograms/ml within 3-5 hr was followed by slow elimination, with 3.5 micrograms/ml present after 18 days. Intermittent dialysis had no appreciable effect on drug levels in serum. The biphasic decline in serum concentrations of vancomycin indicates at least two-compartment pharmacokinetics in both anephric and normal patients. In anephric patients the elimination half-life was 7.5 days and the elimination rate constant was 0.32; these values were 8 hr and 10.25, respectively, in normal patients. On the basis of these results, the vancomycin regimen recommended for anephric patients is an initial 1-g intravenous dose followed by 500 mg every eight days. With these dosages peak concentrations are 49 micrograms/ml (well below reported toxic levels) and trough concentrations are 7 micrograms/ml (well above the minimal inhibitory concentrations for susceptible pathogens causing shunt infections).

Adolescent↗

PubMedDate not supplied

Comparison of the pharmacodynamic activity of cefotaxime plus metronidazole with cefoxitin and ampicillin plus sulbactam.

STUDY OBJECTIVE: To compare the pharmacokinetic and pharmacodynamic activity of three drug regimens: cefotaxime plus metronidazole, cefoxitin, and ampicillin-sulbactam against two organisms frequently isolated in intraabdominal infection, Escherichia coli and Bacteroides fragilis. DESIGN: Open-label, three-way crossover study. SETTING: Hartford Hospital Clinical Research Center. PARTICIPANTS: Nine healthy volunteers. INTERVENTIONS: Subjects received the following regimens: (1) a single 1-g intravenous dose of cefotaxime plus a single 500-mg oral dose of metronidazole; (2) two intravenous doses of cefoxitin, 2 g each dose given every 6 hours; and (3) two intravenous doses of ampicillin-sulbactam, 3 g each dose given every 6 hours. MEASUREMENTS AND MAIN RESULTS: Serum bactericidal titers and drug concentrations were measured over a 12-hour period. The cefotaxime-metronidazole regimen showed superior activity against E. coli compared with ampicillin-sulbactam and cefoxitin. The mean areas under the bactericidal activity curve (AUBC) for the three regimens were 550.2, 68.7, and 48.9, respectively (p = 0.0001). There was no significant difference in AUBC among the three regimens for B. fragilis. Serum concentrations of cefotaxime remained above the minimum inhibitory concentration (MIC) for E. coli significantly longer than did concentrations of ampicillin-sulbactam and cefoxitin (p = 0.0002 and p = 0.0023, respectively). Serum concentrations of metronidazole were still at 9 times the MIC for B. fragilis at the end of the 12-hour dosing interval; for ampicillin-sulbactam and cefoxitin concentrations remained above the MIC for one-half and less than one-fourth, respectively, of the dosing interval (p < 0.0001). The ratio of AUC:MIC was also favorable for metronidazole (212.2) compared with 63.4 for ampicillin-sulbactam and 9.2 for cefoxitin. CONCLUSIONS: The combination of cefotaxime-metronidazole, even at the relatively low doses used in this study, provides coverage against gram-negative and anaerobic pathogens that is at least as effective as that of cefoxitin and ampicillin-sulbactam. In addition, its cost is considerably less expensive than that of the other regimens.

Administration, Oral↗

PubMedDate not supplied

Effect of continuous arteriovenous hemodiafiltration on the pharmacokinetics of fluconazole.

In critically ill patients with acute renal failure, continuous arteriovenous hemodiafiltration (CAVHD) has become an increasing popular supportive technique. An adult with acute renal failure during CAVHD therapy received fluconazole. Drug clearance by the hemodiafilter system and its total body clearance during the CAVHD period were 23-28 ml/minute and 22 ml/minute, respectively, indicating that the rate of systemic clearance was solely dependent on CAVHD in this patient. Total body clearance, area under the curve, and half-life values for this patient closely resembled those in healthy subjects. These observations suggest that patients treated with fluconazole during CAVHD should receive standard maintenance dosages, and neither supplementation nor dosage adjustment is required.

Acute Kidney Injury↗

PubMedDate not supplied

Bactericidal activity of low-dose ceftizoxime plus metronidazole compared with cefoxitin and ampicillin-sulbactam.

Eighteen volunteers received ceftizoxime 1 g plus metronidazole 500 mg intravenously every 12 hours, cefoxitin 2 g intravenously every 6 hours, and ampicillin-sulbactam 3 g every 6 hours in a triple-crossover, open-label study to compare serum bactericidal titers (SBTs) against two strains of Escherichia coli and Bacteroides fragilis. Serum was analyzed for drug concentration and bactericidal activity. Ceftizoxime-metronidazole exhibited a significantly greater (p < 0.05) area under the bactericidal curve and percentage of the dosing interval with SBTs of 1:2 or above against E. coli than cefoxitin or ampicillin-sulbactam. The respective values were equal to those of ampicillin-sulbactam for one strain of B. fragilis (both greater than cefoxitin) and greater than cefoxitin and ampicillin-sulbactam for the other strain. A 1-g dose of ceftizoxime given with metronidazole 500 mg every 12 hours should be an effective alternative to standard antibiotic treatment of mixed aerobic-anaerobic bacterial infections.

Adult↗

PubMedDate not supplied

Comparison of the pharmacokinetic and pharmacodynamic activity of piperacillin and mezlocillin.

STUDY OBJECTIVE: To compare serum bactericidal activity over time and pharmacokinetics resulting from single doses of piperacillin (PIP) and a single dose of mezlocillin (MEZ). DESIGN: Open-label, randomized, three-way crossover study. SETTING: Hartford Hospital Clinical Research Center. PATIENTS: Nine healthy volunteers. INTERVENTIONS: Subjects received single doses of PIP 3 and 4 g/70 kg, and a single dose of MEZ 5 g/70 kg. MEASUREMENTS AND MAIN RESULTS: Test organisms were two clinical isolates of Pseudomonas aeruginosa. Pharmacodynamic analysis revealed that PIP 4 g had 2- to 3-fold higher peak serum bactericidal activity at the end of infusion and 4- to 5-fold higher activity at 0.5 hour than did MEZ 5 g, and also provided approximately 1 hour additional activity over MEZ 5 g. Pharmacokinetic analysis revealed that serum concentrations resulting from PIP 4 g remained above the minimum inhibitory concentration of our test strains almost twice as long as MEZ 5 g. CONCLUSION: Since mezlocillin 5 g every 8 hours is currently proving to be effective at many institutions, and since piperacillin 4 g demonstrates superior pharmacokinetic and pharmacodynamic activity, we believe that piperacillin 4 g every 8 hours could be used instead, with resulting cost savings.

Adult↗

PubMedDate not supplied

Pharmacokinetic considerations in quinolone therapy.

It is advisable to switch patients from parenteral to oral therapy as soon as practical. High volumes of distribution, coupled with relatively low protein binding, indicate that the quinolones are widely distributed outside extracellular fluid. Interactions with aluminum- or magnesium-containing antacids may be avoided by administering the antacids at least 2 hours after quinolone dosing. Some quinolones with high bioavailability (e.g., ofloxacin) are absorbed as reliably and completely after oral administration as when given parenterally, and dosage adjustments for these agents are unnecessary after sequential therapy. Treatment strategies may differ according to the route of drug elimination, and dosage adjustments are required in patients with renal failure who receive quinolones excreted primarily by the kidneys. Theophylline interactions may be more problematic in patients given quinolones that are primarily metabolized by the liver. Quinolones, which have concentration-dependent killing and a long postantibiotic effect, should be administered in the highest tolerated dosage. A method to assess the relative antibacterial efficacy of the quinolones uses the ratio of the Cmax:MIC90 of the organism, compared with a ratio derived from the NCCLS breakpoints for susceptibility.

Administration, Oral↗

PubMedDate not supplied

Oral absorption of trimethoprim-sulfamethoxazole in patients with AIDS.

STUDY OBJECTIVE: To determine the bioavailability of trimethoprim-sulfamethoxazole (TMP-SMX) in patients infected with the human immunodeficiency virus (HIV). DESIGN: Open-label, randomized, two-way crossover trial. SETTING: Outpatient clinical research center affiliated with a community-based teaching hospital. PATIENTS: Ten individuals diagnosed with the acquired immunodeficiency syndrome (AIDS) with CD4+ counts less than 200 cells/mm3, receiving TMP-SMX one double-strength tablet 3 times/week as prophylaxis for Pneumocystis carinii pneumonia (PCP), and without documented gastroenteropathy or diarrhea agreed to participate in the trial. One patient withdrew from the study secondary to development of symptomatic PCP. Data were available for analysis from the remaining nine subjects. INTERVENTIONS: Participants received TMP 160 mg and SMX 800 mg orally or intravenously during two study periods. Following dose administration, blood samples were collected at predetermined time points over 36 hours. MEASUREMENTS AND MAIN RESULTS: Analysis of TMP-SMX pharmacokinetic parameters (half-life, total body clearance, area under the serum concentration versus time curve, and peak concentration) failed to reveal any significant differences between intravenous and oral preparations. The calculated bioavailabilities of oral TMP and SMX (mean +/- SD) were 102.7% +/- 19.8% and 109.4% +/- 19.4%, respectively. CONCLUSION: The absorption of TMP-SMX is not adversely affected by HIV infection in the absence of HIV-induced gastroenteropathy or diarrhea.

Acquired Immunodeficiency Syndrome↗

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Treating allergic rhinitis with second-generation antihistamines.

Allergic rhinitis afflicts close to 40% of the nation's population and costs more than $1.8 billion a year. The toll exacted by this disorder has been greatly alleviated by nonsedating second-generation antihistamines loratadine, terfenadine, and astemizole. The three agents effectively reduce symptoms without the sometimes intolerable adverse effects of older drugs, but they are not completely equivalent. For example, terfenadine requires twice/day dosing, whereas the others can be given once/day. Astemizole has a slow onset and extremely prolonged duration of action. Both terfenadine and astemizole may have cardiotoxic effects (e.g., torsades de pointes) when serum concentrations rise due to overdosing or drug interactions. Cetirizine, a recently approved second-generation antihistamine, has sedative and anticholinergic effects, although to a lesser degree than the first-generation antihistamines.

Astemizole↗

PubMedDate not supplied

Cost of oral antibiotic therapy.

Many bacterial infections can be managed effectively with oral agents rather than parenteral therapy, significantly reducing treatment costs. With renewed interest in oral therapy, and with the importance of cost containment in the managed care environment, it is necessary to evaluate costs associated with different oral antimicrobials. Comparison of per-dose cost and baseline treatment cost (cost/dose x doses/day x days of treatment) is straightforward. More difficult to determine is the overall treatment cost, which is influenced by probabilities that therapy will be effective, safe, and complete. Tolerability, complexity of dosage regimen, and potential for drug-drug interactions may all affect therapeutic efficacy and overall cost. Compared with older agents, newer antibiotics are generally better tolerated and less likely to produce adverse reactions, resulting in better patient compliance, greater efficacy, and often lower overall cost of antimicrobial therapy.

Administration, Oral↗

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Ceftibuten: an overview.

Ceftibuten is an orally active third-generation cephalosporin that exhibits good microbiologic activity against many gram-negative and select gram-positive organisms. It is stable against plasmid-mediated beta-lactamases, including extended-spectrum beta-lactamases. Ceftibuten has been shown to be effective in the treatment of upper and lower respiratory tract infections and, although not approved indications, complicated and uncomplicated urinary tract infections in both adults and children. It is readily absorbed (75-90%) after oral administration, with peak serum levels of 17 microg/ml in healthy volunteers. Its half-life is 2.5 hours in healthy volunteers and is increased in elderly patients to approximately 3.2 hours. Elimination occurs primarily through the kidneys, requiring dosage adjustments to be made when creatinine clearance falls below 50 ml/minute. The drug's safety profile is favorable and similar to that of most other cephalosporins. Based on pharmacokinetic information and clinical trial data, ceftibuten can be dosed once/day for most infections. It is an alternative to other currently available antimicrobial agents in the treatment of indicated upper and lower respiratory tract infections.

Adult↗

PubMedDate not supplied

Pharmacoeconomic impact of once-daily aminoglycoside administration.

A retrospective cost analysis compared hospital costs of standard gentamicin dosing and once-daily regimens in 1127 patients. Hospital costs compared were drug/supply/preparation/administration (DSPA; $4.56/500 mg once-daily dose and $3.32/100 mg every 8 hrs standard dose); therapeutic drug monitoring (TDM) ($25/gentamicin level); and nephrotoxicity management. The mean length of therapy was 4.5 days with both regimens. The mean number of blood samples drawn to measure drug levels was 0.65 for once-daily dosing and 1.7 for standard dosing. Mean DSPA and TDM costs/patient for a 4.5-day course of once-daily therapy were $20.52 and $16.25, respectively ($36.77/course of therapy). In comparison, estimated mean DSPA and TDM costs for 4.5 days standard therapy were $44.82 and $42.50, respectively ($87.32/course of therapy). We observed an overall reduction in nephrotoxicity from approximately 4% to 1.2% with the once-daily program, resulting in a nephrotoxicity management cost reduction from $182 to $55/patient exposed to aminoglycosides. The once-daily program resulted in a 58% reduction in aminoglycoside-associated hospital cost and a nephrotoxicity management savings of 70%/patient.

Anti-Bacterial Agents↗

PubMedDate not supplied

Comparison of bactericidal activities of intermittent and continuous infusion dosing of vancomycin against methicillin-resistant Staphylococcus aureus and Enterococcus faecalis.

STUDY OBJECTIVE: To describe the pharmacokinetic profiles of vancomycin administered by continuous infusion and intermittent dosing and compare the duration of activity of the regimens. DESIGN: Randomized, open-label, crossover study. SETTING: Clinical research center at an academic medical center. SUBJECTS: Twelve healthy, nonpregnant volunteers age 27.6 +/- 2.3 years. INTERVENTION: Subjects received the following intravenous vancomycin regimens: 1 g every 12 hours; 2 g continuous infusion over 24 hours; and 1 g continuous infusion over 24 hours. Dosages were administered with and without gentamicin 2 mg/kg. MEASUREMENTS AND MAIN RESULTS: Serum samples were collected, drug concentrations determined, and bactericidal activity measured against two isolates each of methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. Subjects had poor tolerability for continuous infusions. Trough concentration for the intermittent regimen was 5.5 +/- 1.9 mg/ml, and steady-state concentrations were 8.8 +/- 1.6 and 16.9 +/- 1.9 mg/ml for 1 and 2 g continuous infusions, respectively. In general, all regimens provided bactericidal activity throughout the study interval. Against one isolate of E. faecalis, 2 g continuous infusion plus gentamicin provided cidal activity for a significantly greater percentage of the dosing interval (p<0.001). CONCLUSION: Continuous infusion does not greatly improve the activity of vancomycin and should not be routinely administered. However, it may prove useful against isolates with reduced susceptibility to the agent.

Adult↗