Biomedical subjects

Charles Nightingale

Publications and source records attributed to Charles Nightingale.

5 recordsLinked to original sources

PubMed2003

Does the use of antibiotics in food animals pose a risk to human health? A critical review of published data.

The use of antibiotics in food animals selects for bacteria resistant to antibiotics used in humans, and these might spread via the food to humans and cause human infection, hence the banning of growth-promoters. The actual danger seems small, and there might be disadvantages to human and to animal health. The low dosages used for growth promotion are an unquantified hazard. Although some antibiotics are used both in animals and humans, most of the resistance problem in humans has arisen from human use. Resistance can be selected in food animals, and resistant bacteria can contaminate animal-derived food, but adequate cooking destroys them. How often they colonize the human gut, and transfer resistance genes is not known. In zoonotic salmonellosis, resistance may arise in animals or humans, but human cross-infection is common. The case of campylobacter infection is less clear. The normal human faecal flora can contain resistant enterococci, but indistinguishable strains in animals and man are uncommon, possibly because most animal enterococci do not establish themselves in the human intestine. There is no correlation between the carriage of resistant enterococci of possible animal origin and human infection with resistant strains. Commensal Escherichia coli also exhibits host-animal preferences. Anti-Gram-positive growth promoters would be expected to have little effect on most Gram-negative organisms. Even if resistant pathogens do reach man, the clinical consequences of resistance may be small. The application of the 'precautionary principle' is a non-scientific approach that assumes that risk assessments will be carried out.

Animal Feed↗

PubMed2003

Influence of sex on the pharmacokinetic interaction of fleroxacin and ciprofloxacin with caffeine.

BACKGROUND: Previous pharmacokinetic studies have shown that a number of the quinolones inhibit the metabolism of caffeine. OBJECTIVE: To evaluate the effect of sex on the interaction between two quinolones and caffeine. DESIGN: Multiple-dose, double-blind, randomised, three-period crossover study. PARTICIPANTS: Twelve male and twelve female healthy volunteers. METHODS: Subjects received by mouth either fleroxacin 400 mg once daily and caffeine 100 mg three times daily, ciprofloxacin 500 mg twice daily and caffeine 100 mg three times daily, or caffeine alone, for 3 days. Subjects received each of the other regimens after 12-day washout periods. Plasma and urine concentrations were determined by validated high-performance liquid chromatography procedures and the data were analysed by noncompartmental linear pharmacokinetic methods. RESULTS: Analysis of the interaction by sex revealed that females showed a significant difference in caffeine pharmacokinetics in the presence of ciprofloxacin (area under the concentration-time curve [AUC], peak plasma concentration [C(max)], time to C(max) [t(max)] and apparent total body clearance [CL/F]) and fleroxacin (AUC and CL/F) when compared with males. Significant differences between sexes were also observed in the pharmacokinetics of ciprofloxacin (AUC, elimination rate constant [beta] and CL/F) and fleroxacin (C(max) and beta) in the presence of caffeine. However, these significant differences disappeared when AUC and C(max) were normalised to 70 kg bodyweight and CL/F was expressed as per kg bodyweight. CONCLUSION: The effect of quinolones on the pharmacokinetics of caffeine, and the reciprocal effect, are different between the sexes, due in part to different bodyweights.

Administration, Oral↗

PubMed2002

Pharmacodynamic assessment of ertapenem (MK-0826) against Streptococcus pneumoniae in a murine neutropenic thigh infection model.

The objective of this study was to determine the susceptibility breakpoint of a new carbapenem, ertapenem (MK-0826), against Streptococcus pneumoniae strains based on bacterial density and survival studies in a murine thigh infection model. Sixteen S. pneumoniae isolates for which MICs ranged from 0.015 to 4.0 mg/liter were tested with neutropenic ICR mice. Animals were infected with bacteria at 10(5) to 10(6) CFU per thigh and were treated with ertapenem starting at 2 h postinfection for 4 days. Ertapenem was given subcutaneously at 50 mg/kg of body weight every 6 h, which simulates the human pharmacodynamic profile (in particular, the duration of time that the concentration of free drug remains above the MIC of 2 mg/liter). At 0 and 24 h postinfection, thighs were harvested for bacterial density determination. Survival was assessed during 4 days of therapy and 3 days after the therapy. A protein binding study was conducted with mice by use of the ultrafiltration method. Protein binding in mice was approximately 95%, which is comparable to that in humans. The average change in bacterial density ranged from -0.22 to -4.4 log CFU per thigh over 24 h compared to 0-h controls. The extent of microbial eradication was dependent on the MIC for the S. pneumoniae isolate. Substantial bactericidal activities (i.e., killing of approximately 2 log CFU per thigh) were consistently observed against isolates for which MICs were <or=2 mg/liter, which also resulted in nearly 100% survival during the 4 days of drug dosing and 3 days after the therapy. Less-pronounced and highly variable bactericidal activities were detected against isolates for which the MIC was 4 mg/liter. Substantial enhancement in bactericidal activity was observed for CBA/J mice and is attributed to the contribution of the host defenses in the immunocompetent species. Assessment of the effectiveness of ertapenem by bacterial-density reduction over 24 h and by survival over 4 days of therapy in the murine thigh infection model reveals that the drug maintains maximal efficacy against S. pneumoniae isolates for which the MIC of this agent is <or=2 mg/liter.

Animals↗

PubMed2002

Minimal interaction between gatifloxacin and oxycodone.

Previous studies have demonstrated a significant reduction in the oral bioavailability of trovafloxacin and ciprofloxacin when administered concomitantly with an intravenous opiate, such as morphine. This decrease in absorption results in a 36% and 50% lower AUC for trovafloxacin and ciprofloxacin, respectively, which could cause clinical failures. The authors investigated the possibility of a similar interaction between oxycodone and gatifloxacin. Twelve healthy volunteers were randomized in an open-label, two-way crossover study to receive oxycodone (5 mgpo Q4H) andgatifloxacin (400 mg po 1 h) after starting the oxycodone or gatifloxacin 400 mg po alone. Blood samples were drawn at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours postdosing. No significant difference was noted (p > 0.05) in AUC (31.6 +/- 7.3 vs. 31.7 +/- 7.1) and Cmax (3.2 +/- 0.6 vs. 3.0 +/- 0.6) for gatifloxacin versus gatifloxacin/oxycodone regimens; however, the tmax (1.8 +/- 0.8 vs. 4.3 +/- 1.5) was significantly delayed (p < 0.001). It was concluded that oral oxycodone and gatifloxacin can be administered concomitantly without a significant decrease in bioavailability.

Adolescent↗

PubMed2002

Clinical efficacy and pharmacoeconomics of a continuous-infusion piperacillin-tazobactam program in a large community teaching hospital.

STUDY OBJECTIVE: To compare continuous versus intermittent administration of piperacillin-tazobactam with regard to clinical, microbiologic, and economic outcomes. DESIGN: Prospective, open-label controlled study SETTING: Community teaching hospital. PATIENTS: Ninety-eight hospitalized patients prescribed piperacillin-tazobactam. INTERVENTION: Substitutions were implemented so that 47 patients initially prescribed intermittent infusion of piperacillin-tazobactam were switched to continuous infusion of this drug combination. Dosages varied in accordance with the type of infection and each patient's renal function. Fifty-one other patients with similar demographics and types of infection received intermittent infusion with piperacillin-tazobactam. MEASUREMENTS AND MAIN RESULTS: Clinical success rates were 94% for the continuous-infusion group and 82% for the intermittent-infusion group (p=0.081). Microbiologic success rates were 89% for the continuous-infusion group and 73% for the intermittent-infusion group (p=0.092). Days to normalization of fever were significantly lower (p=0.012) in the continuous-infusion group (1.2 +/- 0.8 days) than in the intermittent-infusion group (2.4 +/- 1.5 days). Level 1 and level 2 costs/patient were both reduced by continuous infusion, although the difference was statistically significant only for level 2 costs ($399.38 +/- 407.22 for continuous infusion vs $523.49 +/- 526.85 for intermittent infusion, p=0.028). CONCLUSION: Continuous infusion of piperacillin-tazobactam provided clinical and microbiologic outcomes equivalent to those for intermittent infusion. Compared with intermittent infusion, continuous infusion significantly shortened the time to temperature normalization, while also offering a significant reduction in level 2 expenditures.

Aged↗