Distribution of drugs on the nursing unit.
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Nursing Service, Hospital↗
Biomedical subjects
C H Nightingale
Publications and source records attributed to C H Nightingale.
Pharmacokinetics of cephalexin: an evaluation of one- and two-compartment model pharmacokinetics.
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Administration, Oral↗
Cost comparison of beta 2-agonist bronchodilators used in the treatment of asthma.
Because of increases in the morbidity and mortality associated with asthma, coupled with shrinking health care resources, the costs associated with therapy with beta 2-agonists in metered-dose inhalers (MDIs), the most frequently used class of therapeutic agents, were examined. Recent recommendations suggested a change in drug therapy for asthma, away from theophylline and toward patient-administered MDIs containing beta 2-agonists or corticosteroids. These recommendations are expected ultimately to reduce overall costs by decreasing morbidity due to asthma and by reducing hospital services. Furthermore, differences exist among the various beta 2-agonists. For example, for patients treated with albuterol inhalers, total asthma drug costs, the costs of additional asthma drugs, and hospital costs were lower than those for patients treated with metaproterenol inhalers, despite the higher acquisition cost of albuterol. Using the maximum recommended number of daily inhalations and standardized pricing data, the daily costs of nine individual beta 2-agonists in MDIs were calculated. These varied from $0.61 for albuterol to $1.28 for pirbuterol, but would be lower for patients who required fewer daily inhalations on an as-needed basis. In addition, agents that can be dosed as needed (i.e., albuterol) are likely to be more cost-effective choices for formularies than more expensive new bronchodilators such as salmeterol, which must be given twice/day on a regular basis.
Adrenergic beta-Agonists↗
Penetration of cephalosporins into bone.
The penetration characteristics of cefazolin and cephradine in human bone were determined in 35 patients undergoing total knee replacement. The results were compared to previously reported data on patients undergoing total hip replacement. The time required to achieve peak bone levels in total knee replacement was less than in total hip replacement. Importantly, peak bone levels in total knee replacement (cefazolin: 11 mg/kg; cephradine: 7 mg/kg) were significantly less (less than or equal to 50%) than bone levels in total hip replacement (cefazolin: 30 mg/kg; cephradine: 23 mg/kg). The bone half-lives (t 1/2) of cephalosporins were prolonged in total knee replacement compared to total hip replacement because of the tourniquet effect. The reduction in peak bone levels and the bone t 1/2 of cephalosporins should be taken into account in patients receiving prophylaxis for total knee replacement. Therefore, patients undergoing total knee replacement should receive 2 g of a parenteral cephalosporin 30 min prior to surgery in order to achieve the same degree of protection, i. e., peak bone levels, as is achieved with 1 g of a cephalosporin administered prophylactically to patients undergoing total hip replacement. If the critical effect of the tourniquet is not taken into account in antibiotic prophylaxis for patients undergoing total knee replacement, then suboptimal bone cephalosporin levels may result.
Absorption↗
Enhanced killing of methicillin-resistant Staphylococcus aureus in human macrophages by liposome-entrapped vancomycin and teicoplanin.
The antibacterial effects of liposomal vancomycin and teicoplanin against intracellular methicillin-resistant Staphylococcus aureus (MRSA) were evaluated using a macrophage infection model. Human blood-derived monocytes were cultured for 7 days to obtain adherent macrophages. Uptake of each drug by macrophages was markedly enhanced by liposomal encapsulation. Following phagocytosis and removal of residual extracellular MRSA, the infected macrophages were exposed to clinically achievable concentrations of teicoplanin and vancomycin. The free (untrapped) and liposome-entrapped forms of each drug were used at the same concentration. The number of intracellular surviving bacteria was determined by colony counts after lysis of the macrophages at different time intervals following drug treatment. Intracellular antimicrobial effect of each drug was significantly (p < 0.001) increased by entrapment in liposomes. Also, the efficacies of the free and liposomal forms of both drugs were correspondingly comparable (p > 0.05). It is, therefore, concluded that liposomal encapsulation of vancomycin and teicoplanin results in an increased availability of the antibiotics for efficient elimination of intracellular MRSA infection.
Biological Availability↗
A survey of the quality of generic clarithromycin products manufactured in Slovenia and Israel.
This study evaluated the quality of 11 generic clarithromycin products obtained in Poland, Slovakia, Slovenia, or Israel and manufactured in Slovenia or Israel. The generic products were examined visually, assayed by high-pressure liquid chromatography for clarithromycin content and impurities, tested for dissolution properties, and compared with the innovator product manufactured by Abbott Laboratories. Fifty-five percent of generic products fell short of the specifications for the innovator product. Ten percent of the generic products did not contain the amount of clarithromycin claimed in the label; 18% released less drug than did the branded tablets in the standard dissolution assay. In light of these results, it is not possible to conclude that all generic tablets are of the same quality as the innovator product; clinical trial results achieved with branded clarithromycin should not be extrapolated to generic products.
Anti-Bacterial Agents↗
Absorption of ciprofloxacin administered through a nasogastric or a nasoduodenal tube in volunteers and patients receiving enteral nutrition.
The absorption of ciprofloxacin was higher when administered through a nasoduodenal tube than through a nasogastric tube, indicating that even though acidic gastric pH is needed for rapid disintegration, dissolved ciprofloxacin might not be stable in the gastric environment. If the length of exposure or the different gastric environment in each individual affects the overall absorption of ciprofloxacin, this could explain the reported variability in ciprofloxacin absorption and suggests the need for the development of an enteric-coated tablet. Further studies are needed to fully characterize the absorption of ciprofloxacin in patients with different illnesses, gastric transit times, gastrointestinal environments and of different ages.
Absorption↗
Effect of including recommendations for antimicrobial therapy in microbiology laboratory reports.
Innovative approaches are needed to improve cost-effective antibiotic use in hospitals. We established an algorithm to provide a recommendation for both a single oral and a single parenteral antimicrobic, including dosage, to be placed in the bacteriology laboratory report for therapy guidance of 174 episodes of lower respiratory infection in a group of "program" patients with no evidence of infection at other sites. The initial recommendation was based on the Gram-stained direct smear of secretions. The recommendation was updated when preliminary culture results were available, and again with final identification and susceptibility data. We compared the severity of illness, length of stay, and cost of therapy for 68 episodes in program patients who received the recommended therapy with 111 episodes in a control group of patients who received antimicrobial therapy but for whom no recommendations were reported. There was a significantly greater use of the recommendations for sicker patients. Antimicrobial therapy, in general, was more often used for the program patients than for the controls. There was no difference in length of stay or therapy cost. We recommend that this approach be used in settings where there is more problematic use of antimicrobics.
Algorithms↗
Pharmacokinetics of cefotaxime in healthy volunteers and patients.
Cefotaxime is a third-generation cephalosporin that has maintained good susceptibility pattern despite its extensive use. It is available for intravenous and intramuscular administration. Its pharmacokinetic property includes a small volume of distribution with low protein binding. Cefotaxime's half-life is approximately 1.1 h, and it is primarily eliminated by the kidney. It has an active metabolite desacetyl-cefotaxime that displays pharmacokinetic properties similar to cefotaxime. Desacetyl-cefotaxime has a half-life of 1.5 h and also is eliminated by the kidneys by both glomerular filtration and active secretion. The half-life of cefotaxime and its metabolite is altered in patients with severe renal dysfunction requiring dosage adjustment. Despite its relatively short half-life, cefotaxime may be dosed every 12 h based on its pharmacokinetic and pharmacodynamic properties.
Cefotaxime↗
Cephalosporin-metronidazole combinations in the management of intra-abdominal infections.
With our current understanding of antimicrobial pharmacokinetics and pharmacodynamics, optimal antimicrobial dosing strategies can be developed for a variety infectious processes. Herein, we discuss the clinical utility of a combination containing a third-generation cephalosporin plus metronidazole as compared to conventional single agents (cefoxitin and ampicillin-sulbactam) for the management intra-abdominal infections. At present, several studies have been performed that compare the bactericidal activity of such combinations to that of single agents for organisms commonly isolated from these intra-abdominal process. From these studies it appears that the use of a third-generation cephalosporin with strong activity against common aerobic organisms associated with intra-abdominal infections in combination with a potent anaerobic drug such as metronidazole provides improved antibacterial activity and optimizes the pharmacodynamic profile of the agents over the dosing interval compared to conventional single agents. As a result of the pharmacokinetic and pharmaco-dynamic superiority of the combination regimen, considerable pharmacoeconomic advantages may be realized with the clinical implementation of a third-generation cephalosporin plus metronidazole regimen. This approach should result in maximal clinical efficacy and is important not only for individual patient therapy, but also for formulary management decisions.
Abdomen↗
Strategic antibiotic decision-making at the formulary level.
The proliferation of antimicrobial agents introduced for the treatment of increasingly complex infectious diseases, coupled with the obligation to provide the best possible medical care in keeping with hospital fiscal constraints, has created a need for strategic decision-making about antibiotics at the formulary level. The following experience at the Hartford Hospital, a 1,000-bed tertiary-care facility, represents an example of an antibiotic management system based on a multidisciplinary approach that utilizes infectious disease physicians, clinical microbiologists, hospital epidemiologists, and pharmacists.
Anti-Bacterial Agents↗
Tissue penetration and half-life of cefonicid.
The pharmacokinetics of cefonicid in the serum and tissues of patients undergoing open heart surgery, vaginal hysterectomy, and hip replacement was studied and compared with that of cefazolin and cefoxitin. Cefonicid achieved serum and tissue concentrations that were higher and more prolonged than those of cefazolin and cefoxitin. For cefonicid parallelism was observed between the serum and tissue concentration-time curves. Correlations of these properties to clinical efficacy were not attempted.
Adult↗
Potential role of trimethoprim-sulfamethoxazole in the treatment of serious hospital-acquired bacterial infections.
Although trimethoprim-sulfamethoxazole (TMP-SMZ) has become a standard agent for the treatment of a broad range of infections, it may often be overlooked as a choice for treatment of serious hospital-acquired infections. A review of the literature shows that a number of common and uncommon gram-negative and gram-positive organisms susceptible to TMP-SMZ are frequently resistant to cephalosporins. TMP-SMZ has, in addition to its exceptional microbiologic activity, pharmacokinetic characteristics that make it a potentially cost-effective alternative to third-generation cephalosporins in the treatment of serious hospital-acquired infections caused by susceptible organisms.
Bacterial Infections↗
Pharmacodynamics of intermittent- and continuous-infusion cefepime alone and in combination with once-daily tobramycin against Pseudomonas aeruginosa in an in vitro infection model.
Cefepime, a fourth-generation cephalosporin, is currently one of the primary agents used in combination with an aminoglycoside when treating Pseudomonas aeruginosa infections. The bactericidal activity of cefepime administered as intermittent doses (IT) or continuous infusion (CI) both alone and in combination with once-daily tobramycin (ODT) against two clinical strains of P. aeruginosa was compared using an in vitro infection model. Cefepime concentrations simulated human pharmacokinetics after a 1-gram Q12 regimen, or a 1-gram loading dose followed by a 2-gram Q24 CI regimen; the ODT regimen mimicked peak concentrations of >/=10 x MIC. All regimen simulations were run in duplicate over 48 h and a growth control (no antimicrobials added) was run concurrently. Strains tested, PSA5 and PSA10, had MICs of 2 and 8 microg/ml to cefepime, respectively; both MICs to tobramycin were 1.0 microg/ml. CI regimens resulted in concentrations approximately 6x and 2x the MIC for PSA5 and PSA10, respectively. The change in log10 colony-forming units (CFU) per milliliter over time for both P. aeruginosa isolates was compared to initial inocula for all treatment regimens. Initial bolus doses of both IT and CI regimens resulted in a similar decrease in the log10 CFU/ml of both organisms over the first 12 h of the study. After subsequent doses, however, both IT regimens showed greatly diminished bactericidal activity, while both CI regimens were persistently bactericidal without the observation of significant regrowth. As a result, a statistical difference in log10 CFU/ml between both IT and CI regimens with and without ODT was realized at 24, 36 and 48 h for each isolate. Unlike IT dosing, CI cefepime alone or in combination with ODT optimizes bactericidal activity by maximizing the percent of the dosing interval that concentrations remained above the MIC resulting in undiminished bacterial inhibition when compared to IT regimens. These data further suggest that CI is the most efficient method of administration of beta-lactam antibiotics.
Anti-Bacterial Agents↗
Comparison of the bactericidal activity of trovafloxacin and ciprofloxacin, alone and in combination with cefepime, against Pseudomonas aeruginosa.
BACKGROUND: Although ciprofloxacin exhibits more intense microbiological activity against Pseudomonas aeruginosa than does trovafloxacin, the clinical relevance of this observation remains questionable, particularly when the agents are combined with another antipseudomonal agent. METHODS: To evaluate this further, we conducted a four-way crossover trial to compare the bactericidal activities of ciprofloxacin and trovafloxacin, alone and in combination with cefepime, against three clinical isolates of P. aeruginosa. Healthy subjects received the following regimens, dosed to steady state: trovafloxacin 300 mg/24 h; ciprofloxacin 400 mg/12 h; trovafloxacin 300 mg/24 h plus cefepime 2 g/12 h, and ciprofloxacin 400 mg/12 h plus cefepime 2 g/12 h. Serum bactericidal titers were performed with each regimen. RESULTS: As monotherapy, the area under the bactericidal curve for ciprofloxacin exceeded that of trovafloxacin for all isolates. No significant difference in the overall degree of bactericidal activity was noted for two of three P. aeruginosa isolates for the combination regimens. Additionally, both combination regimens provided bactericidal activity for 100% of the dosing interval for all isolates. CONCLUSION: These results indicate that, while in vitro differences exist among these quinolones for P. aeruginosa, when a fluoroquinolone is combined with a beta-lactam, this is likely to be of little clinical significance.
Adult↗
Pharmacokinetics of high-dose meropenem in adult cystic fibrosis patients.
Because patients with cystic fibrosis (CF) have pulmonary exacerbations secondary to multi-antibiotic-resistant Gram-negative bacilli, antibiotics, like meropenem, are often utilized. We studied the pharmacokinetics of meropenem (2 g i.v. administered every 8 h in clinically stable CF patients to determine if the recommended maximum doses could sustain adequate concentrations during the dosing interval. These pharmacokinetic data were similar to those obtained in non-CF populations. Using this regimen, concentrations of meropenem exceed the susceptibility breakpoint (4 microg/ml) for 50% of the dosing interval, and therefore provide optimization of the pharmacodynamic profile of the compound.
Adolescent↗
Circulating tumor necrosis factor-alpha production during the progression of rat endotoxic sepsis.
The endotoxin-mediated tumor necrosis factor-alpha (TNF-alpha) induction was investigated in a rat endotoxin septic shock model. Rats were challenged intravenously with lethal doses of endotoxin. Circulating endotoxin and TNF-alpha concentrations were measured over various times following endotoxin administration. A derivative of human immunoglobulin G, 5S-IgG, was administered at various times relative to endotoxin dosing to test its anti-endotoxin activity. Results showed that endotoxin challenge initiated substantial amounts of TNF-alpha release into the rat circulatory system leading to death. A temporal pattern of TNF-alpha increases following endotoxin administration was observed; the rat plasma TNF-alpha level rapidly increased 60 min after endotoxin injection, peaked around 120 min and returned to low levels by 240 min. A rapid clearance pattern of endotoxin was also observed in rats. 5S-IgG exhibited its moderate anti-endotoxin activity by partially suppressing the endotoxin-mediated TNF-alpha release and decreasing the overall mortality only when given before triggering of TNF-alpha induction. However, this inhibitory effect of 5S-IgG on endotoxin-mediated TNF-alpha release and the resultant protective effect against endotoxin lethality rapidly diminished when 5S-IgG was administered after the occurrence of TNF-alpha induction. Collectively, these results suggest that the timing of the anti-endotoxin treatment is critical in achieving its effectiveness and imply that the endotoxin levels after the onset of the cytokine cascade is of questionable significance.
Animals↗
Interaction of microbiology and pharmacokinetics in the selection of appropriate antibiotic therapy.
Factors that affect a drug's microbiological activity include drug concentration and duration at the binding site and cell wall penetration. Pharmacokinetics can be used as the basis for substituing one drug for another in some cases. By replacing cefoxitin with cefotetan, our hospital saved $120,000-140,000 a year. Several cephalosporins are compared using microbiological and pharmacokinetic data. For example, the microbiological activity of ceftriaxone lasts for at least 12 hours with Staphylococcus aureus and for almost 24 hours with Enterobacteriaceae. Clinical experience with beta lactams has demonstrated that maintaining serum concentrations above the target organism's minimum concentration required to inhibit 90 percent of the organisms for 50 percent or more of the dosing interval is associated with successful therapy.
Anti-Bacterial Agents↗