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Biomedical subjects

C H Nightingale

Publications and source records attributed to C H Nightingale.

At least 91 records · Page 5Linked to original sources
PubMed1996

Serum bactericidal activity of ceftazidime: continuous infusion versus intermittent injections.

Since beta-lactam antibiotics have concentration-independent killing, bacterial eradication is a function of the time the serum drug concentration remains above the drug's MIC (T > MIC). We compared the serum bactericidal titers (SBTs) of ceftazidime given by continuous infusion (CI) or by intermittent bolus dosing (BD) against two clinical isolates each of Pseudomonas aeruginosa and Escherichia coli to determine if CI would allow lower daily dosing while still providing equal bactericidal activity compared with BD. This was an open-labeled, randomized, steady-state, four-way crossover study with 12 healthy volunteers. The ceftazidime regimens were 1 g every 8 h (q8h) BD, 1 g q12h BD, 3 g over 24 h CI, and 2 g over 24 h CI. The areas under the bactericidal curves were calculated by the trapezoidal rule using the reciprocal of the SBT. For all organisms the areas under the bactericidal curves for intermittent versus the CI regimens were the same for equal doses (P > 0.05). For both strains of E. coli all four regimens provided SBTs of > or = 1:2 over the dosing interval and 100% T > MIC. The 1-g q8h BD and q12h BD regimens provided T > MIC of 82 and 52%, respectively, for both P. aeruginosa isolates (MICs, 4 micrograms/ml). In comparison, the 2- and 3-g CI regimens always maintained SBTs of > or = 1:2 and T > MIC over the 24-h period as serum drug concentrations were 12.8 +/- 3.0 and 18.2 +/- 4.5 micrograms/ml, respectively. CI optimizes the pharmacodynamic and pharmacoeconomic profile of ceftazidime by providing adequate antibacterial activity over the 24-h dosing period with a reduction in the total daily dose of the antimicrobial agent.

Adult↗
PubMed1996

Comparison of bronchopulmonary pharmacokinetics of clarithromycin and azithromycin.

The bronchopulmonary and plasma pharmacokinetics of clarithromycin (CLA; 500 mg given twice daily for nine doses) or azithromycin (AZ; 500 mg for the first dose and then 250 mg once daily for four doses) were assessed in 41 healthy nonsmokers. Bronchoalveolar lavage was performed at 4, 8, 12, or 24 h after administration of the last dose. The concentrations (mean +/- standard deviation) of CLA, 14-hydroxyclarithromycin, and AZ were measured in plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) cells by high-performance liquid chromatography assay. The concentrations of CLA achieved in ELF were 34.02 +/- 5.16 micrograms/ml at 4 h, 20.63 +/- 4.49 micrograms/ml at 8 h, 23.01 +/- 11.9 micrograms/ml at 12 h, and 4.17 +/- 0.29 microgram/ml at 24 h, whereas at the same time points AZ concentrations remained below the limit of assay sensitivity (0.01 microgram/ml) for all but two subjects. The concentrations of CLA in the AM cells were significantly higher than those of AZ at 8 h (703 +/- 235 and 388 +/- 53 micrograms/ml, respectively). However, the ratio of the concentration in AM cells/concentration in plasma was significantly higher for AZ than for CLA for all time points because of the lower concentration of AZ in plasma. These results indicate that while AZ has higher tissue concentration to plasma ratios, as shown by other investigators, the absolute concentrations of CLA in AM cells and ELF are higher for up to 8 and 12 h, respectively, after administration of the last dose.

Adult↗
PubMed1996

Comparative serum bactericidal activities of ceftizoxime and cefotaxime against intermediately penicillin-resistant Streptococcus pneumoniae.

In a randomized crossover study involving 12 healthy volunteers, 1 g of ceftizoxime or cefotaxime was administered intravenously every 12 h for a total of three doses on two separate weekends. The duration of serum bactericidal titers (SBTs) greater than 1:2 and the time serum drug concentrations remained above the MIC (T > MIC) were determined against three clinical isolates of Streptococcus pneumoniae with intermediate resistance to penicillin. The duration of SBTs and T > MIC for both antimicrobial agents exceeded 50% of the dosing interval for all isolates. Ceftizoxime's T > MIC was statistically greater than that of cefotaxime, indicating that its longer half-life in serum (1.7 h) compared with that of cefotaxime (approximately 1 h) compensates for its slightly lower microbiologic activity against the penicillin-resistant pneumococci tested in this study.

Adult↗
PubMed1996

Characterization of bactericidal activity of clindamycin against Bacteroides fragilis via kill curve methods.

Kill curves were determined for five isolates of Bacteroides fragilis with clindamycin at concentrations equal to the MIC or to 4, 16, and 64 times the MIC. Examination of plots of log CFU per milliliter versus time revealed no association between the clindamycin concentration and the rate and extent of the bactericidal activity against B. fragilis at or below 64 times the MIC.

Anti-Bacterial Agents↗
PubMed1996

Pharmacoeconomics of Pneumocystis carinii pneumonia in HIV-infected and HIV-noninfected patients.

Despite the proven effectiveness of Pneumocystis carinii pneumonia (PCP) prophylaxis in both HIV-infected and HIV-noninfected patients, PCP remains an important cause of serious pulmonary infection. Because PCP is a frequent event requiring inpatient admission at our institution, we conducted a study to define the pharmacoeconomics of this infection and the incidence of adverse events associated with anti-PCP therapy. In a retrospective review, 133 patients (101 HIV-positive, 32 HIV-negative) with documented PCP were identified. Significant differences in age, initial arterial oxygen tension (paO2), intensive care unit admission and mortality were evident between HIV-infected and non-HIV-infected patients; however, there were no differences in the duration of hospitalisation or the duration of anti-PCP therapy. The incidence of biochemical abnormalities was similar between the groups. Leucopenia occurred at an incidence of 52 and 31%, while thrombocytopenia occurred at a rate of 7 and 44%, in HIV-positive and HIV-negative patients, respectively. Drug toxicity or treatment failure necessitated a change of therapy in 43% of HIV-positive and 59% of HIV-negative patients. PCP treatment cost, pharmacy cost, hospital cost and net loss (i.e. the difference between hospital cost and reimbursement) were all significantly greater in HIV-negative than in HIV-positive patients. The duration of anti-PCP therapy and the hospital cost for cotrimoxazole (trimethoprim-sulfamethoxazole)- and pentamidine-treated patients were similar, although the treatment cost and pharmacy cost were statistically different in favour of cotrimoxazole. Overall, cotrimoxazole is an inexpensive treatment option. However, the high incidence of adverse events attributed to this agent often necessitates a change to a more costly therapy.

AIDS-Related Opportunistic Infections↗
PubMed1996

Evaluation of myoglobin clearance during continuous hemofiltration in a swine model of acute renal failure.

Rhabdomyolysis is characterized by extensive damage of striated muscle, while the major complication of this disease is the development of acute myoglobinuric renal failure. Although first described more than five decades ago very little has changed with regard to the management of this entity as conventional hemodialysis has not been shown to effect myoglobin elimination. However, continuous arteriovenous hemofiltration (CAVH) offers an alternative to conventional hemodialysis as this procedure is more effective particularly for removing larger molecular weight substances such as myoglobin. We studied the effect of CAVH on myoglobin clearance in an animal model of acute myoglobinuric renal failure. Swine (n = 6) were given 4 grams of equine myoglobin intravenously and underwent the CAVH procedure for six hours each. Once the filtering process was initiated there was a rapid and sustained production of ultrafiltrate. The clearance of myoglobin via the hemofilter was 2.05 +/- 1.48 L/day. The amount of myoglobin excreted in the ultrafiltrate over the six hour filtering period was 410 +/- 234 mg which accounts for 10.27 +/- 5.85 percent of the administered dose. Based on these findings, it appears that the hemofiltration system is a viable option for the removal of myoglobin from the systemic circulation.

Acute Kidney Injury↗
PubMed1996

Modification of an ion-paired high pressure liquid chromatography for ticarcillin in human serum.

AIM: To develop a new HPLC assay for the clinical pharmacokinetic study of ticarcillin in human. METHODS: Reverse phase ion-paired HPLC was developed with a Novapak C18 column. The mobile phase consisted of 20% of acetonitrile and 80% of phosphate buffer 10 mmol.L-1 (pH 2.0-2.5) containing tetrapentylammonium bromide of 1 mmol.L-1. The analysis was monitored at 225 nm and the flow rate of the mobile phase was 0.8 mL.min-1. Cefoxitin was used as an internal standard. The sample volume was 200 microL of serum. RESULTS: The assay was linear in the range of 2-80 mg.L-1. The intrarun coefficients of variation (CV) for a ticarcillin 5 mg.L-1 check sample was 4.2% (n = 10), and 2.7% for a 60 mg.L-1 check sample (n = 10), respectively. The inter-run CV (n = 6) were 1.6% (5 mg.L-1) and 2.3% (60 mg.L-1), respectively. The average recovery of the assay was 96.6%. CONCLUSION: This assay was sensitive, precise, and accurate for evaluating the clinical pharmacokinetics of ticarcillin.

Chromatography, High Pressure Liquid↗
PubMed1995

Antibiotic kinetics and dynamics for the clinician.

In recent decades considerable data have been acquired concerning the complex interactions of the organism-antimicrobial-host triad. Using the current understanding of drug disposition in the body, pharmacokinetics, and in vitro microbiologic activity, optimal dosing strategies can be derived to maximize clinical efficacy and minimize potential toxicities. This article discusses pharmacokinetics, pharmadynamics, and the application of this principle in clinical practice.

Algorithms↗
PubMed1995

Activities of clarithromycin, azithromycin, and ofloxacin in combination with liposomal or unencapsulated granulocyte-macrophage colony-stimulating factor against intramacrophage Mycobacterium avium-Mycobacterium intracellulare.

The effects of ofloxacin, clarithromycin, and azithromycin in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) against Mycobacterium avium-Mycobacterium intracellulare (MAI) were evaluated in an in vitro human macrophage infection model. Treatment of MAI-infected macrophages with GM-CSF alone induced a maximal killing effect at 1000 U/mL, and the potency was increased 100-fold by encapsulating the cytokine within liposomes. Antibiotics were applied at concentrations close to their clinically achievable serum trough and peak levels. Addition of GM-CSF to azithromycin and therapeutic trough concentrations of ofloxacin and clarithromycin was associated with significant (P < .01) augmentation of antimycobacterial activity compared with the effects of the agents alone. However, the enhancement effect by GM-CSF was not seen with therapeutic peak concentrations of ofloxacin and clarithromycin. Thus, GM-CSF may be a useful adjunct in the treatment of MAI infections with azithromycin, clarithromycin, and ofloxacin.

Azithromycin↗
PubMed1995

Bioavailability of fluconazole administered via a feeding tube in intensive care unit patients.

Fluconazole, a triazole compound with potent activity against many medically important fungi, undergoes rapid oral absorption, and has been shown in healthy volunteers to exhibit virtually complete bioavailability. The purpose of this study is to evaluate the bioavailability of fluconazole administered via a feeding tube with concomitant enteral feeds in intensive care unit patients. Once prescribed by the attending physician, fluconazole was administered either as an intravenous infusion over 1 h or the tablet was crushed and given via a feeding tube with concomitant enteral feeds. Once blood samples were obtained (not before the fifth dose) of the first regimen, the patient could be switched over to the alternate route and blood samples were again obtained after at least five doses. All patients had normal gastrointestinal motility, normal renal, and hepatic function. Serum concentrations were determined by a validated HPLC method. The area under concentration-time curve (AUC) was calculated using the trapezoidal rule; bioavailability was determined from the ratio of AUC(tube)/AUC(intravenous). The bioavailability for five patients was calculated to be 97.2 +/- 9.8%. Fluconazole retained excellent bioavailability when crushed and administered via a feeding tube with or without concomitant enteral feeding in critically ill patients. This alternative route of administration promotes cost savings and decreases the chance for secondary infection from indwelling intravenous catheters.

Adult↗
PubMed1995

Determination of the in vivo post-antibiotic effects of ciprofloxacin and rifampicin.

A modified rabbit meningitis model is described for determining the PAE in vivo, which utilised a self-standing device for repeatedly sampling pure CSF. The model allowed the PAEs of ciprofloxacin and rifampicin on Escherichia coli ATCC 25922 to be determined following PAE induction in vitro, or in vivo in CSF after intrathecal injection or during the last 1.5 h of a 7 h iv continuous infusion. The estimated volumes of distribution of ciprofloxacin and rifampicin in CSF were 0.68 +/- 0.24 mL and 0.74 +/- 0.04 mL, respectively, and the terminal elimination half lives were 1.8 +/- 0.5 h and 2.2 +/- 0.3 h, respectively. PAEs of approximately 2 h were obtained in vivo and in vitro after exposing E. coli to 3 x MIC of ciprofloxacin in vitro and to 1 x MIC of drug in vivo. When the organism was exposed to rapidly declining concentrations in vivo, only a minimal PAE was observed for both antibiotics. Moreover, a PAE of 3.1 +/- 1.3 h of rifampicin was obtained in vivo, being smaller than the 4.8 h PAE observed in vitro, which might be explained by the binding of 45 +/- 6.5% rifampicin to proteins in the CSF.

Animals↗
PubMed1995

Comparison of the bactericidal activities of ofloxacin and ciprofloxacin alone and in combination with ceftazidime and piperacillin against clinical strains of Pseudomonas aeruginosa.

On the basis of MIC data, ciprofloxacin exhibits superior activity against Pseudomonas aeruginosa than the other currently available fluoroquinolones do. Despite the antipseudomonal advantage noted for ciprofloxacin monotherapy, it is unknown whether this advantage is maintained when the fluoroquinolones are used in combination with antipseudomonal beta-lactams such as ceftazidime and piperacillin. Twelve healthy volunteers were enrolled in this open-label, randomized, steady-state, six-way cross-over, comparative trial. All subjects received the following regimens: (i) 400 mg of ofloxacin given intravenously (i.v.) every 12 h (q12h), (ii) 400 mg of ciprofloxacin given i.v. q12h, (iii) 400 mg of ofloxacin given i.v. q12h plus 1 g of ceftazidime given i.v. every 8 h (q8h), (iv) 400 mg of ciprofloxacin given i.v. q12h plus 1 g of ceftazidime given i.v. q8h, (v) 400 mg of ofloxacin given i.v. q12h plus 4 g of piperacillin given i.v. q8h, and (vi) 400 mg of ciprofloxacin given i.v. q12h plus 4 g of piperacillin given i.v. q8h. Serum bactericidal titers with subsequent calculation of the area under the bactericidal curve were determined against three clinical isolates of P. aeruginosa. As monotherapy, ciprofloxacin demonstrated superior antipseudomonal activity than ofloxacin did; however, combination of these agents with ceftazidime yielded remarkably similar and statistically comparable activity profiles. In contrast, ciprofloxacin-piperacillin retained a bactericidal advantage over ofloxacin-piperacillin. Although ciprofloxacin exhibits superior antipseudomonal activity when used as monotherapy, combination of ofloxacin or ciprofloxacin with ceftazidime yielded equivalent activity profiles against susceptible strains of P. aeruginosa.

Adult↗
PubMed1995

Experience with a once-daily aminoglycoside program administered to 2,184 adult patients.

Once-daily aminoglycoside (ODA) regimens have been instituted to maximize bacterial killing by optimizing the peak concentration/MIC ratio and to reduce the potential for toxicity. We initiated an ODA program at our institution that utilizes a fixed 7-mg/kg intravenous dose with a drug administration interval based on estimated creatinine clearance: > or = 60 ml/min every 24 h (q24h), 59 to 40 ml/min q36h, and 39 to 20 ml/min q48h. Subsequent interval adjustments are made by using a single concentration in serum and a nomogram designed for monitoring of ODA therapy. Since initiation of the program, 2,184 patients have received this ODA regimen. The median dose was 450 (range, 200 to 925) mg, while the median length of therapy was 3 (range, 1 to 26) days. The median age of the population was 46 (range, 13 to 97) years. Gentamicin accounted for 94% of the aminoglycoside use, and the majority (77%) of patients received the drug q24h. The 36-, 48-, and > 48-h intervals were used for 15, 6, and 2% of this population, respectively. Three patients exhibited clinically apparent ototoxicity. Twenty-seven patients (1.2%) developed nephrotoxicity (the Hartford Hospital historical rate is approximately 3 to 5%) after a median of 7 (range, 3 to 19) days of therapy. On the basis of a prospective evaluation of 58 patients and follow-up of additional patients via clinician reports, we have noted no apparent alterations in clinical response with our ODA program. This ODA program appears to be clinically effective, reduces the incidence of nephrotoxicity, and provides a cost-effective method for administration of aminoglycosides by reducing ancillary service time and serum aminoglycoside determinations.

Adolescent↗
PubMed1995

Influence of aspirin on development and treatment of experimental Staphylococcus aureus endocarditis.

Previously, we have shown that a 5-mg/kg of body weight daily dose of aspirin (ASA) caused reductions in the bacterial densities and weights of aortic vegetations in a rabbit model of Staphylococcus aureus endocarditis. We sought to determine (i) whether ASA dosage influences the development of vegetations and (ii) whether ASA given with antimicrobial therapy improves the treatment outcome of infective endocarditis. To study the influence of ASA dosage, animals received either no ASA (control) or oral doses of 2.5, 10, 20, and 50 mg/kg daily. The 2.5- and 10-mg/kg groups had statistically significant reductions in vegetation weight compared with untreated controls. The 10-mg/kg dose also resulted in a significant decrease in bacterial densities compared with those of the controls. Although reductions in weight and bacterial density were observed in other ASA-treated groups, these did not achieve statistical significance. To study the influence of ASA and antimicrobial therapy, the animals received either vancomycin alone or vancomycin with ASA. When ASA was given prior to and during antimicrobial therapy, a significant reduction in vegetation weight was observed. Additionally, the rate of sterilization was directly proportional to this observed reduction in weight. ASA's impact on the reduction of both the bacterial density and the weight of aortic vegetations is a dose-dependent phenomenon. When given with antimicrobial therapy, ASA not only reduces vegetation weight but also improves the rate of sterilization. This study provides additional data regarding the role of ASA in the treatment of endocarditis.

Animals↗
PubMed1995

Absorption of ciprofloxacin in patients with diabetic gastroparesis.

The purpose of this study was to assess the pharmacokinetic profile of ciprofloxacin in 12 patients with diabetic gastroparesis. Patients received both a single 500-mg oral (p.o.) dose and a single 400-mg intravenous (i.v.) dose of ciprofloxacin separated by a 1-week washout period. Pharmacokinetic parameters (means +/- standard deviations) for the p.o. and i.v. doses were as follows: areas under the concentration-time curve from 0 h to infinity, 9.74 +/- 2.59 and 11.78 +/- 3.18 micrograms.h/ml, respectively; maximum concentrations of drug in serum, 2.13 +/- 0.67 and 4.21 +/- 1.07 micrograms/ml, respectively; and half-lives, 4.03 +/- 0.58 and 4.20 +/- 0.58 h, respectively. The ratio of the areas under the concentration-time curves from 0 h to infinity for the p.o. and i.v. doses was 0.84, with a 90% confidence interval of 0.68 to 0.98; the mean absolute bioavailability was calculated to be 67% (range, 43 to 82%). From these data it appears that ciprofloxacin is adequately absorbed in patients with diabetic gastroparesis.

Adult↗
PubMed1995

Rifampin-fluconazole interaction in critically ill patients.

OBJECTIVE: To report the influence of rifampin coadministration on the pharmacokinetics of fluconazole in 2 critically ill patients. CASE SUMMARIES: The pharmacokinetics of fluconazole are reported in 5 patients in the intensive care unit (ICU), 2 of whom received rifampin and 3 who received only fluconazole. Patient 1 was a 52 year-old man with bilateral pneumonia who received rifampin for 9 days in addition to other antibiotics when fluconazole was added for suspected fungal superinfection. Patient 2, a 39-year-old man with steroid-dependent asthma was admitted to the ICU with a right middle lobe pneumonia and ventilatory insufficiency. Because of rapid clinical deterioration, intravenous rifampin 600 mg q12h and fluconazole 100 mg q24h were added to conventional antibacterial therapy. Patients 3-5 received intravenous fluconazole therapy, but were never administered rifampin prior to their antifungal therapy. DISCUSSION: Fluconazole has gained wide use as an antifungal agent because of its efficacy, limited toxicity, and the paucity of reported drug interactions. In some clinical situations, however, the drug must be coadministered with rifampin. Limited data in healthy volunteers suggest that the coadministration of rifampin and fluconazole results in a 23% reduction in the fluconazole area under the concentration-time curve (AUC). In this report, we found a statistically significant lowering of the AUC (52%) and a 93% higher total body clearance of fluconazole in patients treated with rifampin. CONCLUSIONS: Although limited data are available describing the magnitude of the interaction between fluconazole and rifampin in patients, our data suggest a more significant interaction than previously reported. If the concurrent administration of the 2 drugs in unavoidable, the patient's clinical response to treatment should be monitored closely, as the unexpectedly large reduction in fluconazole serum concentrations may lead to poor treatment outcomes.

Adult↗