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Biomedical subjects

C H Nightingale

Publications and source records attributed to C H Nightingale.

At least 145 records · Page 8Linked to original sources
PubMed1992

Considerations in dosage selection for third generation cephalosporins.

Pharmacokinetic parameters of third generation cephalosporins vary widely, requiring different dosage regimens and adjustment methods for each agent. Although their antibacterial spectrum favours their usage in infections caused by aerobic Gram-negative organisms, due to their limited post-antibiotic effect against these organisms, dosage regimens should ensure that free drug concentrations at the site of infection remain above the minimum inhibitory concentration for as much of the dosage interval as possible in patients with normal host defence mechanisms and for the entire dosage interval in immunocompromised patients. Altered protein binding encountered in various disease states can affect both microbiological and pharmacokinetic properties especially for drugs with high protein binding. Since the concentrations at the site of action are often different from those in serum, a higher or lower range of dosages needs to be selected depending on the target site. Decreased renal function affects the elimination of most third generation cephalosporins, whereas the presence of hepatic disease does not generally necessitate dosage adjustment. Because of the complex age-related physiological changes in paediatric and elderly patients, dosage should be adjusted on the basis of the reported pharmacokinetic data in these populations. The usual recommended dose may or may not be optimal in a given condition depending on the complex interactions between pharmacokinetic, microbiological and other host factors.

Acute Kidney Injury↗
PubMed1992

Determining the formulary status of quinolone antibiotics: one institution's approach.

Streamlining antibiotic therapy--ie, simplifying regimens, route of administration, or both--is necessary in the modern treatment of hospitalized patients with infectious diseases. Due to their pharmacokinetic profiles and comparative efficacy and safety, the quinolone class of antibiotics is an ideal class for which to direct streamlining efforts. Including only one agent of this class on the formulary, however, is inadequate. Having several quinolones available, and thus expanding the local hospital market for them, enables more physicians to be contacted and educated by manufacturers' sales representatives as part of the hospital's antibiotic management program. By assisting in the education efforts, pharmaceutical representative help to conserve hospital resources, both in terms of cost and personnel. In addition, having more than one supplier of quinolones encourages competition, which favors price reductions.

Anti-Bacterial Agents↗
PubMed1992

Ofloxacin vs ciprofloxacin: a comparison.

Ofloxacin and ciprofloxacin are fluoroquinolones with similar characteristics. However, important differences can be observed in their antimicrobial activity, clinical utility, and pharmacokinetic and interaction profiles. Ofloxacin is more active in urethral chlamydia infections; it also may more effectively eradicate staphylococcal infections and Streptococcus pneumoniae pulmonary infections. Furthermore, ofloxacin does not significantly alter theophylline concentrations. Ciprofloxacin has better activity against gram-negative bacilli, an advantage which may be negated by ofloxacin's longer half-life and higher serum levels. Therefore, while both drugs are effective as treatment of infections due to gram-negative organisms, ofloxacin is also appropriate in the treatment of: 1) infections where both aerobic gram-negative rods and staphylococci or S. pneumoniae are documented or suspected, 2) urethritis, particularly when C. trachomatis is documented or suspected, 3) infections in patients concomitantly receiving theophylline.

Bacterial Infections↗
PubMed1991

Quantification of in-vitro post-antibiotic effect based on the mean recovery-time. I: Theoretical perspectives and a practical procedure.

An empirical description of the post-antibiotic effect has been previously proposed on the basis of the time required for the bacterial density to increase by one log10 following antimicrobial exposure. In this study, a set of theoretical perspectives are established and the post-antibiotic effect quantitatively defined based on the mean-recovery time. The mean recovery-time can be determined by measuring the area above the growth curve of a bacterial population following antimicrobial exposure. It can be shown that the previously proposed description of the post-antibiotic effect may be regarded as a special case of the definition based on the mean-recovery. Furthermore, a practical procedure is described for the quantitation of the post-antibiotic effect from a given set of data in the form of a growth curve.

Anti-Bacterial Agents↗
PubMed1991

Quantification of in-vitro post-antibiotic effect based on the mean recovery-time. II: A comparison of colony counting versus photometric methods for the determination of bacterial growth.

In the preceding paper, a method for the quantification of the post-antibiotic effect (PAE) has been developed based upon the mean recovery-time of an antibiotic-treated bacterial population, showing that the mean recovery-time is determined by the area above a growth curve of the bacterial population. Such an area determination of PAE implies that this method is less likely to be influenced by the early portion of a growth curve and therefore less dependent on the ability of a technique to detect a minimum bacterial density (sensitivity limit). In this study, this implication is further demonstrated in theory and through experimentation. As a result, an approach to estimation of contribution of the early portion of a growth curve to the quantitation of PAE based on the mean recovery-time is derived. The PAE of ciprofloxacin on Escherichia coli ATCC 25922 was determined under different test conditions using colony count and optical density measurements for determining bacterial growth. Differences in durations of the PAE quantitated by the mean recovery-time from the colony count measured and optical density measured growth curves were not statistically significant (P greater than 0.05).

Anti-Bacterial Agents↗
PubMed1991

Bioavailability and pharmacokinetics of ofloxacin in healthy volunteers.

The pharmacokinetics and bioavailability of ofloxacin in 20 healthy male volunteers were studied in an open-label, randomized, two-way crossover study. Ofloxacin (400 mg) was administered either as a 1-h infusion or as an oral tablet. The mean peak concentration after intravenous infusion was 4.30 +/- 0.69 microgram/ml, and that after oral administration was 3.14 +/- 0.53 microgram/ml, occurring 1.74 +/- 0.57 h after dosing. The bioavailability (F) of the oral dosage form of ofloxacin was virtually identical to that of the intravenous form (F = 105% +/- 7%). This complete bioavailability of ofloxacin is supportive of the use of the oral dosage form for the treatment of infections in hospitalized patients either as a replacement for intravenous ofloxacin therapy or in streamlining therapy from the intravenous to the oral route.

Administration, Oral↗
PubMed1991

Antimicrobials and therapeutic decision making: an historical perspective.

In an effort to remedy inappropriate and excessive use of antimicrobials and to control costs, most hospitals have developed some type of antimicrobial management program. At Hartford Hospital, our most effective approaches have been those that reduce the chances for physician error, decrease the burden on ancillary services, and encourage short hospital stays. These include automatic correction of dose and dosing intervals of antimicrobials and, if possible, their conversion by pharmacy to cost-effective alternative agents; daily review of patients who are taking the drugs by an antimicrobial team; and replacement of parenteral with oral agents as soon as possible. Physician acceptance of these approaches will require significant changes in traditional prescribing styles and willingness to allow pharmacists to implement the recommendations of therapeutic and medical staff committees.

Anti-Bacterial Agents↗
PubMed1990

Teicoplanin pharmacokinetics in healthy volunteers after administration of intravenous loading and maintenance doses.

Teicoplanin is an investigational glycopeptide antibiotic that is structurally and microbiologically similar to vancomycin. Since teicoplanin possesses a very long elimination half-life, the manufacturer suggests that the drug be administered every 12 h for the first day of therapy and once daily thereafter. We studied the multiple-dose (6 mg/kg per dose) pharmacokinetics of teicoplanin in volunteers following intravenous administration every 12 h for 5 days and then every 24 h for 9 days in an attempt to identify the optimal duration of the every-12-h loading-dose regimen. Multiple serum samples were obtained throughout the study, including intensive sampling after the first and last doses; urine was collected during the entire study. A three-exponential equation was fitted to the serum concentration data. The mean terminal-phase half-life was 157 +/- 93 h. Concentrations of teicoplanin in serum similar to those observed after the administration of the last dose (day 14) were observed following the fourth or fifth dose given every 12 h. Therefore, it is suggested that for clinical dosing regimens for teicoplanin, dosing every 12 h for approximately 48 h should be used, followed by once-daily dosing thereafter.

Adult↗
PubMed1990

Developing staff into clinical practitioners.

Developing clinical skills in pharmacy staff is a process that can enhance the services of a pharmacy department and improve the professional development and interest of the staff. Staff should be included in the development of a clinical philosophy and a training and ongoing development program that will achieve the desired goals should be planned. An MBO process may help to track the individual pharmacist's progress. Knowledgeable, motivated staff are the key ingredient in achieving success in providing pharmacy services.

Clinical Competence↗
PubMed1989

Metabolism and the fluoroquinolones.

Quinolones differ considerably with respect to the relative importance of nonrenal drug elimination mechanisms. The extent to which the fluoroquinolones undergo biotransformation in the liver ranges from approximately 50 percent for pefloxacin to about 6 percent for ofloxacin. Although glucuronide conjugates have been identified as minor metabolites for some agents, most metabolic reactions involving quinolones occur through microsomal oxidative mechanisms at the cytochrome P-450 site. These metabolic alterations involve the piperazinyl moiety and usually result in compounds with significantly less microbiologic activity than the parent drugs. Of particular importance is the varying extent of formation of the oxoquinolone metabolite with all fluoroquinolones except ofloxacin. Available evidence suggests that the inhibition of metabolism of drugs such as theophylline and caffeine by quinolones is related to the production of the oxoquinolone metabolite. With all antibiotics, differences in microbiologic activity and pharmacokinetics influence the choice of one agent over another for individual patient selection or consideration for hospital formulary inclusion. For the quinolones the degree and type of metabolism may be a strong factor in this selection process.

4-Quinolones↗
PubMed1989

Pharmacokinetics and pharmacodynamics of total and unbound cefoxitin and cefotetan in healthy volunteers.

Cefotetan is a semisynthetic cephalosporin with a broad spectrum of Gram-negative and anaerobic activity. We compared the pharmacokinetics and serum inhibitory activity of 2 g doses of cefotetan and cefoxitin in six healthy volunteers. The half-life of cefotetan (176 min) was significantly longer than that of cefoxitin (49 min). Despite higher protein binding (85% versus 50%), free cefotetan serum concentrations 12 h post dose (1.6 mg/l) were higher than free cefoxitin serum concentrations 6 h post dose (0.32 mg/l). Total and free serum inhibitory titres for Escherichia coli were greater than 1:8 for 12 h post dose for cefotetan, but only 1 h post dose for cefoxitin. Against Bacteroides fragilis, neither cefoxitin nor cefotetan exhibited free serum inhibitory titres greater than 1:8 at the end of their respective dosing intervals. However, cefotetan titres were equivalent or superior to those of cefoxitin over the entire 6 or 12 h dosing interval. Despite relatively high protein binding, cefotetan demonstrates comparable or superior activity 12 h after dosing to cefoxitin 6 h after dosing. More studies comparing the clinical outcome of cefoxitin and cefotetan are needed but our results support the clinical recommendations that cefoxitin should be given every 6 h, and cefotetan every 12 h.

Adult↗
PubMed1989

Pharmacokinetics of single- and multiple-dose teicoplanin in healthy volunteers.

Teicoplanin, an investigational glycopeptide antibiotic related chemically and microbiologically to vancomycin, has in vitro and in vivo activity against gram-positive aerobic and anaerobic bacteria. We compared the single- and multiple-dose pharmacokinetics of intravenous teicoplanin in healthy volunteers. Serum and urine samples were collected for 35 days after single-dose (3 mg/kg) and 72 days after multiple-dose (3 mg/kg per day for 21 days) administration. A three-exponent equation with zero-order input was fitted to concentrations in serum. The mean half-lives (t1/2s) were significantly different (P = 0.0075) after single- and multiple-dose administration (130 +/- 14.9 and 176 +/- 29.8 h, respectively). The clinically relevant t1/2 obtained from multiple-dose data was approximately 61 h. Total and renal clearances determined at steady state were not statistically different, indicating that teicoplanin is eliminated almost entirely by renal mechanisms.

Adult↗
PubMed1989

Relative bioavailability in healthy volunteers of ciprofloxacin administered through a nasogastric tube with and without enteral feeding.

The bioavailability of ciprofloxacin after its administration through a nasogastric (NG) feeding tube was studied in six healthy volunteers. Each subject received, on separate occasions, an intact 750-mg ciprofloxacin tablet, a crushed tablet as a suspension through an NG tube, and a crushed tablet as a suspension through an NG tube while receiving enteral feeding. No statistically significant differences were observed in the area under the curve, maximum concentration in serum, and time to peak concentration among these three modes of administration. These findings suggest that ciprofloxacin is well absorbed after administration via an NG tube (compared with an orally administered intact tablet) even in the presence of enteral feeding.

Adult↗
PubMed1989

Formulary conversion of cefoxitin usage to cefotetan: experience at a large teaching hospital.

The pharmacy and therapeutics committee at Hartford Hospital recommended replacement of cefoxitin with cefotetan, based on data reported in the literature regarding antimicrobial activity, pharmacokinetic profile, and adverse reactions. Once the recommendation was approved by the medical staff, an intense educational program was instituted, and all orders for cefoxitin were converted to cefotetan with appropriate dosage modifications. A total of 960 patients were treated in the first year; no major patterns of ineffectual therapy or adverse events associated with cefotetan usage have emerged. The mean cost of cefotetan therapy was $180.59, which is $130.26 less per patient than a comparable regimen of cefoxitin (mean cost of therapy $310.85). Based on the data analysis of cefotetan usage for a 12-month period, the actual annual savings due to therapeutic substitution of cefotetan for cefoxitin was $124.961. To further evaluate the clinical efficacy, safety, and savings of this therapeutic interchange, two separate retrospective reviews of patient medical records were performed. The first audit has been previously published in its entirety. In the subsequent audit, 284 additional patient medical charts have been reviewed. These patients received either cefotetan therapy or concomitant therapy of an aminoglycoside combined with either clindamycin or mezlocillin. Clinical outcomes were classified as an empiric cure or improvement for 99.4, 98.5, and 92.9 percent of patients, respectively. In this audit, elevated prothrombin time/partial thromboplastin time values and bleeding episodes were noted infrequently, as were other adverse reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Disorders↗
PubMed1989

Clinical pharmacokinetics of ceftriaxone.

Ceftriaxone is a third-generation cephalosporin that exhibits saturable plasma protein binding, which influences its pharmacokinetic parameters depending on the dose. Systemic clearance and volume of distribution of total drug show dependence on both concentration and time, whereas for unbound drug these parameters remain constant. The decrease in renal or non-renal clearance with age or in the presence of disease states is often compensated by the concurrent increase in free fraction, resulting in no apparent changes in half-life and no need for dose adjustment. Because of its unusually long plasma half-life, the availability of intramuscular administration and its high intrinsic activity against many organisms, ceftriaxone has become a popular agent in once-daily therapy of infections in paediatric patients, gonococcal infections and outpatient management of pneumonia and osteomyelitis.

Ceftriaxone↗