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Biomedical subjects

C H Nightingale

Publications and source records attributed to C H Nightingale.

At least 73 records · Page 4Linked to original sources
PubMed1997

Cost comparison of single daily i.v. doses of ceftriaxone versus continuous infusion of cefotaxime.

The costs of administering ceftriaxone 1 g in a once-daily 30-minute infusion were compared with the costs of administering cefotaxime 2 g/day (with an additional 1 g given on day 1) by continuous intravenous infusion. Time and motion studies were conducted to determine the pharmacy and nursing labor required to prepare and administer the intermittent and continuously infused antimicrobials. Mean times were multiplied by the mean New England hourly wage for pharmacy technicians, pharmacists, and nurses to determine the total labor costs of each regimen. Hospital acquisition costs of items used in preparing antimicrobial doses for administration by each method were also compared. Wholesale acquisition costs of the two drugs were used in the analysis. Labor costs were higher for the continuously infused antimicrobial because of the additional nursing time required for monitoring. Supply costs were greater for continuous infusion. Drug acquisition cost was the major component of the overall cost of therapy and was lower for continuous infusion. A cost analysis showed that continuous i.v. infusion of cefotaxime 2 g/day was less expensive from day 2 onward than intermittent daily i.v. doses of ceftriaxone 1 g.

Cefotaxime↗
PubMed1997

Disposition of ofloxacin in female New Zealand white rabbits.

Limited information exists regarding the disposition of ofloxacin in rabbits. Pharmacokinetic information is necessary for the design of appropriate therapeutic regimens for the treatment of organisms (e.g. Pasteurella multocida) commonly infecting this species. This study evaluated the pharmacokinetics of ofloxacin following intravenous (i.v.) and subcutaneous (s.c.) administration. Two groups of three female New Zealand White rabbits received a single dose of 20 or 40 mg/kg by the i.v. and s.c. routes. Samples were collected prior to drug administration, then 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 h postdose. Ofloxacin concentrations in serum were determined using a validated HPLC assay. Mean maximum concentrations were 66.86 +/- 10.83 mg/L and 14.1 +/- 2.20 mg/L for the i.v. and s.c. administration of 20 mg/kg. The 40 mg/kg dose produced maximum concentrations of 154.96 +/- 35.45 mg/L and 23.83 +/- 4.01 mg/L for the i.v. and s.c. doses, respectively. The area under concentration-time curve increased proportionally with the dose, while the half-life was unaltered and ranged from 1.5-1.9 h. From these data, it appears that a 20 mg/kg dose administered every 8 h by the s.c. route would optimize the pharmacodynamic profile of ofloxacin and provide an appropriate regimen for the treatment of many susceptible organisms which commonly infect this species.

Animals↗
PubMed1997

Streamlining antimicrobial therapy for lower respiratory tract infections.

Antimicrobial streamlining is the practice of converting a broad-spectrum empirical regimen to therapy with either a single, narrow-spectrum parenteral agent or an oral agent as soon as possible. This practice results in many benefits for the patient and the hospital. When intravenous catheters can be removed early, the frequencies of catheter-associated bacteremias and phlebitis are reduced, thus making it possible to avoid incurring major costs. With the availability of newer oral agents with favorable pharmacokinetic, pharmacodynamic, and microbiological profiles, such as the fluoroquinolones, the macrolides/azalides, and the cephalosporins, the clinician has greater opportunity to employ streamlining tactics. The patient who is hospitalized with a lower respiratory tract infection (LRTI) often requires empirical antimicrobial therapy before the pathogen is identified. By day 3 of the hospital course, the pathogen is often known, the patient's condition may have stabilized, or both events may have occurred. At this point, streamlining is possible. At present, data suggest that rapid conversion from intravenous to oral antimicrobial therapy is safe and efficacious and should be considered for appropriate patients requiring hospitalization for LRTIs.

Administration, Oral↗
PubMed1997

Influence of gentamicin dosing interval on the efficacy of penicillin-containing regimens in experimental Enterococcus faecalis endocarditis.

The influence of the gentamicin dosing regimen was studied in experimental Enterococcus faecalis endocarditis. After inoculation, animals received penicillin, or penicillin plus once-daily gentamicin, or penicillin plus thrice-daily gentamicin, or no treatment. After the treatment period, bacterial densities within the vegetations (mean +/- SEM) were 6.06 +/- 0.30, 5.42 +/- 0.29, 4.98 +/- 0.10 and 9.97 +/- 0.16 log cfu/g for the four groups. All regimens produced significant reductions in bacterial density when compared with controls; penicillin plus thrice-daily gentamicin resulted in a significant difference from penicillin alone. Although once-daily regimens have proved effective in trials involving other organisms, such regimens do not appear to be so optimal for the treatment of enterococcal endocarditis.

Animals↗
PubMed1997

Once-daily dosing of aminoglycosides: review and recommendations for clinical practice.

The use of higher-dose, extended interval (i.e., once-daily) aminoglycoside regimens to optimize bacterial killing is justified by a pharmacodynamic principle of aminoglycosides, namely concentration-dependent killing, and by the partial attribution of the toxicity of aminoglycosides to prolonged serum concentrations. Numerous in-vitro and animal studies have supported using once-daily aminoglycoside dosing. Clinical studies show at least equal effectiveness and no greater toxicity when compared with traditional regimens. A dose of 5-7 mg/kg of gentamicin, tobramycin, or netilmicin, with at least a 24 h dosing interval should be employed and a similar regimen can be applied to amikacin dosing. As yet, there are some patient populations that have not been adequately studied to determine whether or not once-daily aminoglycoside dosing would be a better choice than traditional dosing regimens.

Aminoglycosides↗
PubMed1997

Pharmacokinetics and pharmacodynamics of newer macrolides.

Requirements for the antimicrobial activity of an antibiotic are: (1) binding of the drug to a specific site in the bacteria; (2) occupation of a critical number of binding sites; and (3) persistence at these binding sites for a sufficient time. With concentration-dependent antibiotics the ratio of the peak serum drug concentration to the MIC of a pathogen is the primary determinant of bacterial killing; with concentration-independent antibiotics it is the length of time serum concentration remains above the MIC, rather than the peak level. The pharmacokinetics of the new macrolides azithromycin and clarithromycin differ notably from those of conventional antibiotics in a more rapid and extensive distribution to body tissues. Because of these unique tissue pharmacokinetics, the pharmacodynamic models that apply to other classes of antibiotics may not explain the antimicrobial activity and clinical efficacy of azithromycin and clarithromycin.

Adolescent↗
PubMed1997

In vitro synergistic activities of tobramycin and selected beta-lactams against 75 gram-negative clinical isolates.

The microdilution checkerboard technique was utilized to distinguish synergistic activity between tobramycin and four beta-lactams: piperacillin-tazobactam, ticarcillin-clavulanate, ceftazidime, and ceftriaxone. Beta-lactam-aminoglycoside combinations were tested against 75 clinical isolates of Pseudomonas aeruginosa, Acinetobacter baumanii, Citrobacterfreundii, Serratia marcescens, and Enterobacter cloacae. Despite in vitro susceptibilities, all isolates demonstrated either synergism or indifference; no antagonism was observed. Against pathogenic gram-negative nosocomial isolates, a greater percentage of synergy was consistently observed with combination regimens containing tobramycin and piperacillin-tazobactam or ticarcillin-clavulanate than with the cephalosporin-containing regimens.

Anti-Bacterial Agents↗
PubMed1997

Comparison of the bactericidal activities of piperacillin-tazobactam, ticarcillin-clavulanate, and ampicillin-sulbactam against clinical isolates of Bacteroides fragilis, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa.

Owing to the broad spectrum of activity afforded by beta-lactam-beta-lactamase inhibitor preparations, these agents are frequently selected as empiric therapy for the treatment of mixed infections such as intra-abdominal and diabetic foot infections, either alone or in combination with an aminoglycoside. Twelve healthy volunteers were enrolled in a randomized, open-label, four-way crossover trial comparing the bactericidal activities of piperacillin-tazobactam, ticarcillin-clavulanate, and ampicillin-sulbactam against microorganisms commonly isolated from mixed infections. Subjects received the following regimes: (i) 3.375 g of piperacillin-tazobactam intravenously (i.v.) every 6 h (q6h) (ii) 4.5 g of piperacillin-tazobactam i.v. q8h, (iii) 3.1 g of ticarcillin-clavulanate i.v. q6h, and (iv) 3.0 g of ampicillin-sulbactam i.v. q6h. Serum bactericidal titers were determined and used to calculate the duration of measurable bactericidal activity over the dosing interval of each of the regimens against two clinical isolates of Bacillus fragilis, Escherichia coli, Enterococcus faecalis, and Pseudomonas aeruginosa. The percentage of the dosing interval over which drug concentrations in serum remained above the MIC for each organism was determined and compared with the observed duration of bactericidal activity was noted (r = 0.78; P < 0.001). All of the regimens demonstrated good activity against B. fragilis and E. coli. Against E. faecalis and P. aeruginosa, however, all of the regimens provided bactericidal activity for less than 50% of the respective dosing intervals. These data suggest that use of shorter dosing intervals or continuous-infusion regimens should be considered in combination with an aminoglycoside to improve the bactericidal profiles of these agents for E. faecalis and P. aeruginosa.

Adult↗
PubMed1997

Bactericidal activity of low-dose clindamycin administered at 8- and 12-hour intervals against Staphylococcus aureus, Streptococcus pneumoniae, and Bacteroides fragilis.

Twelve volunteers received 300 mg of clindamycin intravenously (i.v.) or orally (p.o.) administered every 8 h (q8h) or q12h by random assignment over four study periods. Serum bactericidal titers were determined for each regimen against two isolates each of Staphylococcus aureus, Streptococcus pneumoniae (one penicillin-sensitive isolate and one penicillin-resistant isolate), and Bacteroides fragilis. The duration of measurable bactericidal activity over the dosing interval (expressed as a percentage of the dosing interval) was determined for each isolate. No significant differences in the duration of activity were observed between i.v. and p.o. regimens dosed according to the same interval (P > 0.05). All regimens provided bactericidal activity against S. pneumoniae for 100% of their respective dosing intervals. Against B. fragilis, bactericidal activity was observed for greater than 80% of the dosing interval for each of the regimens. Although a statistically significant difference favoring the q8h i.v. regimen (P < 0.05) was detected, this difference is not believed to be clinically significant. The q8h and q12h regimens provided measurable bactericidal activity against S. aureus for greater than 85 and 50% of the dosing intervals, respectively (P < 0.001). Clindamycin dosed at 300 mg i.v. or p.o., q8h or q12h, provides adequate coverage against S. aureus, S. pneumoniae, and B. fragilis.

Administration, Oral↗
PubMed1997

Antifungal pharmacodynamic characteristics of fluconazole and amphotericin B tested against Candida albicans.

Time-kill curves were determined for three isolates of Candida albicans tested against fluconazole and amphotericin B at multiples of the MIC. Fluconazole produced fungistatic activity, with concentration-related growth effects observed over a narrow range of concentrations. Amphotericin B exhibited fungicidal activity, with enhancement of activity over a broader range of concentrations.

Amphotericin B↗
PubMed1997

Oral bioavailability and pharmacokinetics of ciprofloxacin in patients with AIDS.

Few reports on the effects of AIDS on the absorption of orally (p.o.) administered agents exist. To help fill this informational gap, we administered ciprofloxacin to 12 patients with AIDS by two dosing regimens (400 mg given intravenously [i.v.] and 500 mg given p.o. every 12 h) in a randomized, crossover fashion. Pharmacokinetic parameters were determined by noncompartmental methods. Mean values (+/- standard deviations [SD]) for p.o. ciprofloxacin were as follows: peak concentration of drug in serum (Cmax), 2.94 +/- 0.51 microg/ml; time to Cmax, 1.38 +/- 0.43 h; area under the concentration-time curve from 0 to 12 h (AUC(0-12)), 12.13 +/- 3.21 microg x h/ml; and half-life (t(1/2)), 3.86 +/- 0.48 h. Mean values (+/- SD) for i.v. ciprofloxacin were as follows: Cmax, 3.61 +/- 0.82 microg/ml; time to Cmax, 1.0 h; AUC(0-12), 11.92 +/- 2.92 microg x h/ml; and t(1/2), 3.98 +/- 0.94 h. The mean percent absolute bioavailability for ciprofloxacin was calculated to be 82% +/- 13%, similar to the value for healthy volunteers. We conclude that ciprofloxacin when administered p.o. to patients with AIDS is well absorbed, as evidenced by excellent bioavailability and is not affected by gastrointestinal changes in the absence of infectious gastroenteritis and severe diarrhea.

AIDS-Related Opportunistic Infections↗
PubMed1997

In vitro reduction of endotoxin concentrations with the 5S fragment of immunoglobulin G.

Endotoxin has long been implicated as an inducer for the development and progression of gram-negative sepsis. Accordingly, antiendotoxin therapy has been considered one of the major targets for the treatment of sepsis. To investigate the influence of a human immunoglobulin G (IgG) derivative, the 5S fragment of IgG (5S-IgG; Gamma-Venin, Centeon Pharma GmbH, Frankfurt-Niederrad, Germany), on endotoxin release during bacterial proliferation and under antibiotic bactericidal action, time-kill studies were performed by using Escherichia coli ATCC 25922 starting inocula of 10(3), 10(5), and 10(7) CFU/ml with cefotaxime (120 microg/ml) alone and in combination with 5S-IgG (2,100 microg/ml). Samples were collected for bacterial colony count and endotoxin concentration determinations; the area under the free endotoxin concentration curve (AUFEC) was calculated by using the trapezoidal rule. Colony counts showed that cefotaxime had a rapid bactericidal effect because it achieved greater than a 4-log decrease in the numbers of E. coli CFU per milliliter over the first 2 h; the addition of 5S-IgG did not appear to alter the kinetics of killing. Comparison of the AUFEC revealed that the addition of 5S-IgG resulted in a mean reduction of 50, 66, and 27% in the free endotoxin concentration at starting inocula of 10(3), 10(5), and 10(7) CFU/ml, respectively. Moreover, experiments were conducted with a starting inoculum of 10(5) CFU/ml and various amounts of 5S-IgG (2 to 20 mg/ml) to further investigate the dose-effect relation of 5S-IgG on endotoxin release. Decreased AUFECs were observed with increasing concentrations of 5S-IgG, suggesting the dose-dependent antiendotoxin activity of 5S-IgG. Further study is required to investigate the mechanism(s) responsible for this observation, the biological significance of this antiendotoxin activity, and the potential utility of 5S-IgG as an adjuvant therapy in the treatment of gram-negative sepsis.

Cefotaxime↗
PubMed1996

Serum bactericidal activity of ceftizoxime and ceftriaxone against pathogens associated with community-acquired and nosocomial pneumonias.

The serum bactericidal activities of ceftizoxime and ceftriaxone against organisms commonly implicated in community-acquired and nosocomial pneumonias were studied. Ceftizoxime 1 g (as the sodium salt) every 12 hours for two doses and ceftriaxone 1 g (as the sodium salt) every 24 hours for two doses were administered to 20 healthy volunteers in a crossover fashion. Blood samples were drawn immediately before and 2,4,6,8,10, and 12 hours after the second ceftizoxime dose and immediately before and 8,12,16,18,20, and 24 hours after the second ceftriaxone dose. Serum drug concentrations were determined by validated high-performance liquid chromatography. Serum bactericidal titers were determined in duplicate for each serum sample against four clinical isolates of each of the following organisms: Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, and Serratia marcescens. The median duration of serum bactericidal activity during the dosage interval was significantly different between antimicrobial regimens only for S. pneumoniae (92% of the dosage interval for ceftizoxime, versus 100% for ceftriaxone). This difference does not appear to be clinically important since ceftizoxime provides adequate serum bactericidal activity for more than 50% of the dosage interval and its effectiveness against pneumococcal pneumonia has been supported in clinical trials. The ceftriaxone and ceftizoxime regimens did not differ significantly in their duration of serum bactericidal activity against six of the seven organisms tested.

Adolescent↗
PubMed1996

Once-daily aminoglycoside dosing: impact on requests and costs for therapeutic drug monitoring.

Recently, much interest has focused on the use of once-daily aminoglycosides (ODA) in the medical literature. In late 1992, we implemented a hospital-wide ODA program for adult patients at our 850-bed community-teaching hospital. In the first phase of implementation, therapeutic drug monitoring (TDM) was accomplished with the use of a random serum concentration and a nomogram that had been developed at our institution. In the second phase, serum drug concentrations were eliminated on patients with normal renal function. The fully implemented program resulted in a 40% decrease in the request for gentamicin and tobramycin serum concentrations as compared with historic ordering patterns for conventional aminoglycoside dosing regimens. In addition, the incidence of nephrotoxicity was also reduced from 3 to 5% with conventional aminoglycoside dosing, to 1.2 and 1.3% for phases 1 and 2, respectively. Furthermore, the elimination of TDM requests totaling 300 for gentamicin and 50 for tobramycin per month is expected to result in an annual institutional savings of > $100,000.

Adult↗
PubMed1996

Efficacy of vancomycin and teicoplanin alone and in combination with streptomycin in experimental, low-level vancomycin-resistant, VanB-type Enterococcus faecalis endocarditis.

The efficacy of vancomycin (VM) and teicoplanin (TE), alone and in combination with streptomycin (SM), against enterococci that express low-level VanB-type VM resistance was investigated in experimental endocarditis using isogenic strains of Enterococcus faecalis susceptible to glycopeptides and aminoglycosides or inducibly resistant to low levels of VM (MIC = 16 micrograms/ml). VM was significantly less active against the resistant strain than against the susceptible strain, establishing that low-level VanB-type VM resistance can influence therapeutic efficacy. By contrast, TE had equally good activity against both strains. VM or TE combined with SM was synergistic and bactericidal against the resistant strain in vitro. While both combinations were efficient in reducing bacterial density in vivo, TE plus SM was significantly superior to VM plus SM if valve sterilization was considered. These data suggest that despite the presence of low-level VanB-type resistance, combination therapy with a glycopeptide and SM (and presumably other aminoglycosides to which there is not high-level resistance) will nevertheless provide effective bactericidal activity.

Animals↗