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Biomedical subjects

R P Rapp

Publications and source records attributed to R P Rapp.

At least 19 recordsLinked to original sources

Azithromycin versus erythromycin for community-acquired pneumonia: a cost-minimization analysis.

The costs of i.v. erythromycin versus azithromycin (in terms of medication use and treatment of adverse effects) when these drugs were used with other antimicrobials to treat community-acquired pneumonia (CAP) were compared. The medical records of patients receiving i.v. azithromycin or erythromycin as part of combination antimicrobial therapy for the treatment of CAP at a 473-bed level 1 trauma center in Kentucky were retrospectively reviewed. Data were collected for patients treated from December 1, 1997, through March 31, 1998. Patient data collected included occurrence of phlebitis or pain at the injection site, number of line changes due to phlebitis, and culture results. Cost data collected included drug acquisition cost, pharmacy cost of drug preparation, nursing time to administer the agent, cost of drug supplies, and cost of managing complications. Three time-and-motion studies were conducted to determine technician preparation time and pharmacist verification time. The medical records of 62 patients were identified and reviewed; 50 patients were enrolled in the study (25 in the azithromycin group and 25 in the erythromycin group). The average total days of therapy was 5.1 for the azithromycin group and 5.6 for the erythromycin group. The average total cost, including the cost of complications ($4.36 per patient in the erythromycin group), was $66.46 in the azithromycin group and $96.56 in the erythromycin group. The difference in costs between the two groups was not significant. There was no significant cost difference between azithromycin- and erythromycin-containing combination antimicrobial therapy in the treatment of CAP.

Anti-Bacterial Agents

Vancomycin use in a university medical center: effect of a vancomycin continuation form.

OBJECTIVE: To examine the impact of a new policy to ensure appropriate use of vancomycin in a 461-bed tertiary-care hospital. DESIGN: We instituted a policy that allowed physicians to prescribe vancomycin but that required them to complete a vancomycin continuation form and document that use conformed to Hospital Infection Control Practices Advisory Committee (HICPAC) guidelines if they wished to continue the drug beyond 72 hours. Vancomycin was stopped automatically at 72 hours if use was not consistent with guidelines, if an infectious diseases consultant did not approve the drug, or if the form was not completed. A pharmacist and infectious diseases specialist monitored use of vancomycin prospectively and interacted with prescribers when indicated. Educational efforts were limited to printing the HICPAC guidelines on the form and providing information about the policy in a newsletter. Patterns of prescribing and the economic impact of the form were evaluated over a 6-month period. RESULTS: Only 29% to 48% of vancomycin orders initially met HICPAC guidelines, but 77% to 96% of use was appropriate after 72 hours when the form was used. Inappropriate surgical prophylaxis, empirical therapy of intensive-care unit and transplant patients, and therapy for inadequately documented coagulase-negative staphylococcal infections remained problems. Vancomycin use fell from a mean of 136 (+/-52) g/1,000 patient days in the 12 months before the form to 78 (+/-22) g/1,000 patient days in the 9 months after institution of the form (P<.05). Net vancomycin acquisition costs and costs of ordering vancomycin serum levels fell by $357 and $19 per 1,000 patient days, respectively (P<.05). This represented annualized saving of approximately $47,000 in drug and monitoring costs. No adverse patient outcomes were seen as a result of the program. CONCLUSIONS: A vancomycin continuation form can decrease inappropriate vancomycin use and may save money. Additional educational efforts may be required to increase compliance with HICPAC guidelines during initial prescribing.

Academic Medical Centers

Antimicrobial resistance in gram-positive bacteria: the myth of the MIC. Minimum inhibitory concentration.

Although much progress has occurred in the fight to treat infection, resistant bacteria increasingly are becoming problematic. The minimum inhibitory concentration is easily determined, yet its definition, clinical application, and relevance are confusing. In addition, errors can occur during in vitro susceptibility testing. The mechanism of resistance for different organisms is discussed as are the pitfalls of susceptibility testing and the prescription of antimicrobial agents.

Anti-Bacterial Agents

Intra-arterial urokinase versus surgery for acute peripheral arterial occlusion.

The outcomes of intra-arterial urokinase versus surgery for acute peripheral arterial occlusion (PAO) were compared. Patients at a university hospital who had received intraarterial urokinase for PAO were identified by computer and pair-matched on the basis of comorbidities, age, sex, and site of occlusion to computer-selected patients who had undergone surgery. Only patients with category I or II ischemia were considered. The study period for the urokinase group was February 1995 through January 1996, and the period for the surgery group was June 1993 through January 1996. Twenty-eight patients in each group met the selection criteria. Patients who had received urokinase had a significantly shorter median length of stay (8.5 days) than patients in the surgery group (13 days) and significantly fewer infectious complications (2 versus 10). No differences in amputation rates, total hospital costs, or mortality rates were detected. Patients who received intra-arterial urokinase for PAO had a shorter length of stay in the hospital and fewer infectious complications than those who underwent surgery.

Adult

Amphotericin B lipid complex.

OBJECTIVE: To evaluate the published data on the effectiveness and safety of amphotericin B lipid complex (ABLC) for the treatment of invasive mycosis and to evaluate data describing the pharmacologic properties and pharmacokinetic behavior of ABLC in both animals and humans. DATA SOURCE: A MEDLINE search was conducted to identify literature published from 1965 to January 1997 for amphotericin B deoxycholate (DCAB) and ABLC. In addition, preliminary data published as abstracts and presented at national conferences on infectious disease and hematology within the last 6 years were also included in this review. STUDY SELECTION: Both human and animal studies were reviewed. Animal and in vitro studies were selected to evaluate the pharmacologic and toxicologic properties of ABLC. For the evaluation of the efficacy, safety, and pharmacokinetic behavior of ABLC, large, well-controlled studies were reviewed. In addition, data from open-label and emergency use protocols were also included in the review. DATA EXTRACTION: The study and analytical methods, results, and conclusions of the selected studies were evaluated. Pharmacokinetic data for both ABLC and DCAB that were derived from human subjects were also evaluated. DATA SYNTHESIS: DCAB has been the cornerstone for the treatment of invasive mycosis, even though it has a narrow therapeutic index. Infusion-related toxicities (e.g., fever, chills, rigors) are likely due to DCAB stimulation of cytokine and prostaglandin synthesis. Conversely, nephrotoxicity, the primary non-infusion-related toxicity, likely results from the nonselective cytotoxic interaction between DCAB and cholesterol-containing mammalian cells. ABLC represents a new approach to improving the therapeutic index of DCAB. Mammalian cytotoxicity is attenuated by complexing amphotericin B to a mixture of phospholipids. This alters the affinity of amphotericin B and decreases its selective transfer from the complex to cholesterol-containing mammalian cells. Fungi also possess lipase, which improves the selective transfer from the complex to ergosterol-containing cell membranes. In humans, the lipid formulation increases the volume of distribution of amphotericin B. Thus, compared with DCAB, larger doses of ABLC can be administered for a longer duration with less nephrotoxicity. However, the prevalence of infusion-related toxicities associated with ABLC is similar to that of DCAB. Whether the alteration in distribution improves efficacy by improving tissue concentrations of amphotericin B has not been determined. The cost of this agent will limit its use. CONCLUSIONS: ABLC has been shown to be at least as effective as DCAB, and it has been well tolerated in the clinical studies to date. Despite large dosages and extended courses of administration, there is little nephrotoxicity associated with its use. However, the cost of this agent will limit its use to the treatment of refractory mycosis or to cases where DCAB is contraindicated due to significant renal insufficiency.

Amphotericin B

Intravenous insulin-like growth factor-I (IGF-I) in moderate-to-severe head injury: a phase II safety and efficacy trial.

The purpose of this study was to determine the effect of insulin-like growth factor-I (IGF-I) on the catabolic state and clinical outcome of head-injured patients. Thirty-three patients between the ages of 18 and 59 years with isolated traumatic head injury and Glasgow Coma Scale (GCS) scores of 4 to 10 were randomized to one of two groups. All patients received standard neurosurgical intensive care plus aggressive nutritional support; the patients in the treatment group also received intravenous therapy with continuous IGF-I (0.01 mg/kg/hour). During the 14-day dosing period, the control patients lost weight, whereas treated patients gained weight despite a significantly higher measured energy expenditure and lower caloric intake (p = 0.02). Daily glucose concentrations and nitrogen outputs were greater in control patients (p = 0.03) throughout the study period. During Week 1, only treated patients achieved positive nitrogen balance. Fifteen of 17 treated and 13 of 16 control patients survived the 1st week. No deaths occurred in patients whose serum IGF-I concentrations were higher than 350 ng/ml. Dichotomized Glasgow Outcome Scale scores for patients with baseline GCS scores of 5 to 7 improved from poor to good for eight of 12 treated patients but for only three of 11 control patients (p = 0.06). Eight of 11 treated patients with serum IGF-I concentrations that were at least 350 ng/ml achieved moderate-to-good outcome scores at 6 months, compared to only one of five patients with lower concentrations (p < 0.05). These findings indicate that pharmacological concentrations of IGF-I may improve clinical outcome and nitrogen utilization in patients with moderate-to-severe head injury.

Adolescent

Implementation of a criteria-based antimicrobial formulary system.

The development of a criteria-based antimicrobial formulary system for use in a 432-bed university-based tertiary-care hospital is described. A subcommittee of the hospital's pharmacy and therapeutics committee developed prescribing criteria for antimicrobials thought to have a specific place in the treatment of various infections. The criteria were based primarily on patient needs, but when two therapies were thought to have similar effectiveness and similar toxicity profiles, cost became the deciding factor in drug selection. Educational packets were designed to assist physicians in prescribing criteria-based antimicrobials. An antimicrobial order form was also developed. The program was implemented after an extensive orientation and education period; data on antimicrobial use were collected for the first year of the program. Hospitalwide compliance with the criteria was 89%, although compliance in certain departments was poorer. The database was formulated to be both service- and physician-specific for the purposes of reporting and education.

Anti-Infective Agents

New macrolide antibiotics: usefulness in infections caused by mycobacteria other than Mycobacterium tuberculosis.

OBJECTIVE: To compare the pharmacology, in vitro activity, and clinical use of the new macrolide antibiotics, azithromycin and clarithromycin, in the treatment of infections caused by mycobacteria other than Mycobacterium tuberculosis. DATA IDENTIFICATION: An English-language literature search using MEDLINE (1987-1994), Index Medicus (1987-1994), Program and abstracts of the 31st (1991) and 32nd (1992) Interscience Conference on Antimicrobial Agents and Chemotherapy, and bibliographic reviews of related textbooks, review articles, and professional society publications. STUDY SELECTION: 105 articles were selected. In vitro and in vivo reports on the pharmacokinetics, microbiology, pharmacology, and effectiveness of clarithromycin and azithromycin were assessed to compare their effectiveness and safety. Emphasis was placed on the use of these new drugs in treating infections caused by Mycobacterium avium complex, Mycobacterium chelonae, and Mycobacterium fortuitum infections. RESULTS: A review of the in vitro activity of the new macrolides revealed moderate to very good activity against many strains of mycobacteria other than M. tuberculosis. Early clinical trials show promising results in pulmonary infections, lymphadenitis, cutaneous infections, and disseminated infections. CONCLUSIONS: The new macrolides, azithromycin and clarithromycin, show great promise for treating infections caused by these acid-fast bacteria. Clarithromycin is recommended as a component of combination therapy for the treatment of M. avium complex infections in patients with AIDS. The development of resistance in patients, particularly when these agents are used alone, has been reported.

Anti-Bacterial Agents

Antibiotic agents in critical care.

The practice of infectious disease and the use of antibiotics are becoming more and more complex in the critical care patient. Critical care nurses continue to play an important role in the safe administration and the postadministration monitoring of antibiotics. Important issues include the choice of drug for specific infections, the effect of pharmacokinetics, methods for safe administration, and the postadministration monitoring for effectiveness and for adverse effects.

Anti-Bacterial Agents

Clarithromycin: review of a new macrolide antibiotic with improved microbiologic spectrum and favorable pharmacokinetic and adverse effect profiles.

OBJECTIVE: To compare the new macrolide antibiotic clarithromycin with erythromycin in terms of in vitro activity, pharmacokinetics, pharmacodynamics, clinical efficacy, and toxicity. DATA IDENTIFICATION: An English-language literature search employing MEDLINE (1987-91), Index Medicus (1987-91), Program and Abstracts of the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy (1990), Program and Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy (1991), and bibliographic reviews of related textbooks and review articles. STUDY SELECTION: Eighty-five articles were selected. Clinical trials with clarithromycin have been limited, and emphasis was placed on trials reported in the Program and Abstracts of the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy and Program and Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy. DATA EXTRACTION: Articles were assessed for study quality and specific information addressing the stated purpose. In articles reporting the results of clinical trials, emphasis was placed on comparative efficacy and toxicity. RESULTS OF DATA ANALYSIS: A review of 24 human trials suggests that clarithromycin is equally effective as erythromycin, penicillin VK, ampicillin, or amoxicillin for treatment of a variety of upper and lower respiratory tract or skin infections. Clarithromycin also appears to be better tolerated than these agents, with a lower incidence of gastrointestinal adverse effects. Limited clinical studies in patients with Mycobacterium leprae or Mycobacterium avium-intracellulare complex (MAI) suggest that clarithromycin may prove to be efficacious and well tolerated in the treatment of these infections. CONCLUSIONS: Clarithromycin is as effective in vivo as erythromycin, with less gastrointestinal irritation. Additionally, clarithromycin appears to expand the traditional spectrum of macrolide antibiotics, with promising activity against M. leprae and MAI.

Acquired Immunodeficiency Syndrome

Metronidazole.

Metronidazole has proven to be a useful and inexpensive antibiotic for the treatment of T. vaginalis and bacterial vaginosis. Few alternatives exist for these two specific indications, and metronidazole will continue to play a primary role in therapy. Oral metronidazole continues to be a very inexpensive alternative to oral vancomycin for the treatment of C. difficile-induced pseudomembranous colitis. For the treatment of moderate to severe mixed aerobic/anaerobic pelvic infections, metronidazole should be considered secondarily in patients who have failed other multiple- or single-drug regimens or in patients who are infected. with anaerobic organisms resistant to other commonly used agents including clindamycin, cefoxitin, cefotetan, or ampicillin/sulbactam. Metronidazole is not a first line drug of choice for antibiotic prophylaxis in obstetric and gynecologic patients.

Bacterial Infections

Fat emulsion particle-size distribution in total nutrient admixtures.

The fat particle-size distribution in and physical stability of two commercially available lipid emulsions before and after their use in total nutrient admixtures (TNAs) are reported. Four TNAs without electrolytes and four TNAs with electrolytes were prepared; each type of TNA was prepared with Liposyn II and with Intralipid. Particle size was measured in the < 1-micron range by using photon correlation spectroscopy and in the 2-60-microns range by using light blockage. Admixtures with or without electrolytes were stored for two or nine days at 4 degrees C followed by one day at 25 degrees C. For the fraction of fat particles of < 1 micron in diameter, Intralipid and Liposyn II had a mean particle size of 374 and 313 nm, respectively. The admixtures containing electrolytes showed a decrease in mean particle size of about 7%. Admixtures with Intralipid contained 2 x 10(7) particles larger than 2 microns per milliliter (1.7% of total fat), compared with 1 x 10(6) particles per milliliter (0.05-0.15% of total fat) for admixtures with Liposyn II. The addition of electrolytes increased the particle counts for Liposyn II-containing admixtures. Upon storage, Intralipid-containing admixtures with electrolytes showed an initial increase followed by a decrease in the mean diameter of particles of < 1 micron. All the admixtures were stable in terms of pH and visual appearance. Intralipid-containing admixtures with electrolytes showed a decrease in the number of particles in the 2-60-microns size range, while Liposyn II-containing admixtures with electrolytes showed an increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Incompatibility

Choice of antibiotic in nonelective cesarean section.

The use of antibiotics for prophylaxis against infection among women undergoing nonelective cesarean section has become the standard of care in the United States. Many different antibiotics have been used successfully. Single-dose regimens administered after the cord is clamped have proven just as effective as multiple-dose regimens. Although the most frequently used class of antibiotics is the cephalosporin family, the single best agent has not been determined. This study was a double-blind, randomized trial in which we compared a narrow-spectrum cephalosporin (cefazolin; n = 63) with an expanded-spectrum cephamycin (cefoxitin; n = 66) and with a broad-spectrum cephalosporin (cefotaxime; n = 60) used as a single-dose prophylaxis in patients undergoing a nonelective cesarean section. Of the 194 patients enrolled in the study, 189 were evaluable. There was no significant difference between the groups in mean age, gravidity, parity, duration of labor, duration of ruptured membranes, number of vaginal examinations, or socioeconomic status (socioeconomic status was defined by third-party coverage). There was no significant difference among the antibiotics in the incidence of immediate or delayed postoperative infections. These data indicate that a less expensive, narrow-spectrum cephalosporin is as effective as more expensive, broader-spectrum cephamycins and cephalosporins as prophylaxis for patients undergoing nonelective cesarean section.

Adult