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Biomedical subjects

R H Drew

Publications and source records attributed to R H Drew.

At least 19 recordsLinked to original sources
PubMed2001

Safety of aerosolized amphotericin B lipid complex in lung transplant recipients.

BACKGROUND: Fungal infections remain an important cause of morbidity and mortality in lung transplant recipients. Aerosolized amphotericin B lipid complex (ABLC) may be more efficacious than conventional amphotericin B in the prevention of fungal infections in animal models, but experience with aerosolized ABLC in humans is lacking. METHODS: We conducted a prospective, noncomparative study designed to evaluate safety of aerosolized ABLC in lung or heart-lung transplant recipients. RESULTS: A total of 381 treatments were administered to 51 patients. Complete spirometry records were available for 335 treatments (69 in intubated patients, 266 in extubated patients). ABLC was subjectively well tolerated in 98% of patients. Pulmonary mechanics worsened by 20% or more posttreatment in less than 5% of all treatments. There were no significant adverse events related to study medication in any patient, and 1-year survival for all enrolled patients was 78%. CONCLUSION: Administration of nebulized ABLC is safe in the short-term and well-tolerated in lung transplant recipients. Additional prospective, randomized studies are needed to determine the efficacy of aerosolized ABLC alone or in conjunction with systemic therapies in the prevention of fungal infections in lung transplant recipients.

Adult↗
PubMed2000

Agents for treatment of invasive fungal infections.

The incidence of fungal infections continues to rise as the population of immunocompromised individuals increases. Despite the enlarging numbers of infections, there are only a few antifungal agents for treatment of deep-seated, invasive infections. These agents include amphotericin B, flucytosine, terbinafine, and several azoles. Progress has been made in understanding the role of these agents in a variety of infections and this article examines in detail these agents and their prophylactic, empiric, and therapeutic uses in invasive mycoses. This article focuses on general concepts of antifungal therapies and provides a detailed review of each antifungal agent available for treatment of deep-seated mycoses.

Antifungal Agents↗
PubMed2000

Treatment of methicillin-resistant staphylococcus aureus infections with quinupristin-dalfopristin in patients intolerant of or failing prior therapy. For the Synercid Emergency-Use Study Group.

Safety and efficacy of quinupristin-dalfopristin (an injectable streptogramin antibiotic) were evaluated in the treatment of a variety of infections due to methicillin-resistant Staphylococcus aureus (MRSA) in patients either intolerant of or failing prior therapy. The influence of resistance phenotypes on treatment outcome was also assessed. This worldwide, multicentre, open-label, non-comparative, emergency-use clinical study enrolled patients with one or more of nine predefined, culture-confirmed infections with MRSA, who had no clinically appropriate alternative antibiotic therapy. The recommended quinupristin-dalfopristin dose was 7.5 mg/kg administered iv every 8 h for a duration judged appropriate by the investigator. There were no restrictions on prior or concomitant treatment with other antibiotics. Clinical, microbiological and laboratory assessments were performed at baseline, during study drug treatment, within 24 h after the last dose, and 7-21 days post-therapy. Ninety patients [age (mean +/- S.D.) 57.4 +/- 18.5 years] with significant underlying medical illnesses were treated at 63 centres in five countries. The most common indications were bone and joint infection (44.4% of patients) and skin and skin structure infection (16.7%). The mean (+/- S.D.) daily dose and treatment duration was 20.2 +/- 2.9 mg/kg/day for 28.5 +/- 22.3 days, most frequently administered every 8 h. The overall success rate (defined as a clinical outcome of either cure or improvement and a bacteriological outcome of eradication or presumed eradication) was 71.1% in the all-treated population (n = 90) and 66.7% in patients who were both clinically and bacteriologically evaluable (n = 27). Success rates for endocarditis, respiratory tract infection and bacteraemia of unknown source were below the population mean. The macrolide-lincosamide-streptogramin type B resistance phenotype did not appear to alter the response rate. The most common non-venous adverse events related to study medication were arthralgias (10.8%), myalgias (8.6%) and nausea (8.6%). Quinupristin-dalfopristin should be considered as a treatment option for infections caused by MRSA, especially in patients intolerant of or failing alternate therapy.

Adolescent↗
PubMed2000

Antifungal pharmacodynamics: review of the literature and clinical applications.

Invasive fungal infections are seen with growing frequency, likely due to increases in numbers of patients at risk of infection. Optimal selection and dosing of antifungal agents are important, as these infections are often refractory to available therapy. In contrast to antibacterials, studies examining the pharmacodynamic properties of antifungals and their application in treating invasive disease often are lacking. Agents administered for invasive infections are amphotericin B, flucytosine, and azole antifungals. Several drugs are under investigation, such as posiconazole, voriconazole, and the echinocandins, and preliminary pharmacodynamic data likely will help shape dosing regimens. Clinical trials that investigated dosage and administration, as well as the potential benefits of combination and sequential therapy, are addressed. In addition, antifungal susceptibility and animal models of infection are discussed.

Animals↗
PubMed1998

Programs promoting timely sequential antimicrobial therapy: an American perspective.

Interventional programs promoting the timely conversion of intravenous to oral antimicrobial therapy have been reported from several hospitals in the U.S.A. and elsewhere. Factors influencing the initiation and conduct of these programs include technological advances, changes in health care delivery or reimbursement, publication of supportive clinical data and growth of clinical pharmacy services. Successful programs employ comprehensive, multidisciplinary strategies to contain antimicrobial-related expenditures using interventions based on structured criteria. Future emphasis on cost-effective drug therapy, advances in computer-based information technology and development of care maps can have favourable influences on the growth of these programs in the U.S.A.

Administration, Oral↗
PubMed1998

Ceftriaxone once daily for four weeks compared with ceftriaxone plus gentamicin once daily for two weeks for treatment of endocarditis due to penicillin-susceptible streptococci. Endocarditis Treatment Consortium Group.

This randomized, multicenter, open-label study compared the efficacy and safety of monotherapy with 2 g of intravenous ceftriaxone once daily for 4 weeks with those of combination therapy with 2 g of intravenous ceftriaxone and 3 mg of intravenous gentamicin/kg once daily for 2 weeks as therapy for endocarditis due to penicillin-susceptible streptococci. Sixty-one patients were enrolled in the study. Clinical cure was observed for 51 evaluable patients both at termination of therapy and at the 3-month follow-up: 25 (96.2%) of 26 monotherapy recipients and 24 (96%) of 25 combination therapy recipients. Of the 23 patients in each treatment group who were microbiologically evaluable, 22 (95.7%) in each group were considered cured. No patient had evidence of relapse. Fourteen patients (27.5%) required cardiac surgery after initiation of treatment, including five monotherapy recipients and nine combination therapy recipients. Adverse effects were minimal in both treatment groups. We conclude that 2 g of ceftriaxone once daily for 4 weeks and 2 g of ceftriaxone in combination with 3 mg of gentamicin/kg once daily for 2 weeks are both effective and safe for the treatment of streptococcal endocarditis.

Adolescent↗
PubMed1993

Pharmacotherapy of disseminated histoplasmosis in patients with AIDS.

OBJECTIVE: To review the pharmacotherapy of disseminated histoplasmosis (DH) in patients with AIDS. The article provides an overview of the pathophysiology, epidemiology, clinical presentation and diagnosis of this disease. Clinical trials reporting intervention with antifungal therapy are reviewed, with an emphasis on efficacy and toxicity of these agents. DATA SOURCES: A MEDLINE search from 1976 to the present was performed to identify pertinent biomedical literature, including reviews. STUDY SELECTION: All available reviews and clinical trials in AIDS patients were evaluated, as were all available case series and interventional clinical trials. DATA SYNTHESIS: DH in patients with HIV infection is an AIDS-defining opportunistic infection caused by Histoplasma capsulatum. It is most frequently observed in HIV-infected patients living in or traveling to endemic regions. The clinical presentation most often includes fever and weight loss, but may be complicated by comorbid illness such as other opportunistic infections. Diagnosis is best established by histologic examination of peripheral blood smear or bone marrow aspirate, or isolation of the organism in cultures of blood, bone marrow, and respiratory secretions. Serologic examinations may provide supportive diagnostic information. Detection of histoplasma polysaccharide antigen (HPA) in serum or urine may prove to be a promising approach for the rapid diagnosis and therapeutic monitoring of DH in AIDS patients. In contrast to immunocompetent hosts, high relapse rates are reported after therapy in AIDS patients. Therefore, initial (induction) therapy is routinely followed by long-term (maintenance) therapy to prevent relapse. Issues regarding the selection, dosage, and duration of therapy, as well as prophylaxis of patients at highest risk, still need to be addressed by controlled clinical trials. CONCLUSIONS: Amphotericin B is presently the drug of choice for induction therapy. Maintenance therapy with either amphotericin B or an oral azole antifungal agent active against H. capsulatum is necessary to prevent relapse. Itraconazole, a triazole antifungal agent, may provide effective alternative therapy for both induction and maintenance treatment of DH.

AIDS-Related Opportunistic Infections↗
PubMed1992

Azithromycin--spectrum of activity, pharmacokinetics, and clinical applications.

Azithromycin is an azalide antimicrobial agent. Structurally related to the macrolide antibiotic erythromycin, its mechanism of activity (similar to erythromycin) is interference with bacterial protein synthesis by binding to the 50S component of the 70S ribosomal subunit. Although slightly less potent than erythromycin against gram-positive organisms, azithromycin demonstrates superior activity in vitro against a wide variety of gram-negative bacilli, including Haemophilus influenzae. Absorption is approximately 37% after a 500-mg oral dose. The large volume of distribution (23 L/kg) and low peak serum level (0.4 micrograms/ml) are consistent with data demonstrating extensive tissue distribution and intracellular accumulation. Metabolism is predominantly hepatic (to inactive metabolites), with biliary excretion a major pathway of elimination. Drug elimination is biphasic, with a terminal half-life of up to 5 days. Published trials have examined the efficacy and safety of azithromycin in the treatment of adults with upper and lower respiratory tract infections, skin and skin structure infections, streptococcal pharyngitis, and sexually transmitted diseases. Many used a 5-day course of 250 mg once daily, supplemented with a 250-mg dose on the first day of therapy. Selected trials in sexually transmitted diseases examined single 1-g doses. Promising results also were obtained with oral daily doses of 500 mg in patients with human immunoviral infection who also had Mycobacterium avium complex infection and in animals with toxoplasmosis. Adverse reactions are primarily gastrointestinal (nausea, diarrhea, abdominal pain), with minimal laboratory abnormalities reported. Gastrointestinal tolerance is better than that of erythromycin. Drug interactions have not been observed to date, although coadministration of azithromycin with a large meal may reduce absorption by up to 50%.

Azithromycin↗
PubMed1989

Comparison of the safety and efficacy of intravenous ciprofloxacin and intravenous ceftazidime in the treatment of selected infections.

A study was conducted to determine the comparative safety and efficacy of intravenous ciprofloxacin with that of intravenous ceftazidime in the treatment of selected infections. Male and female inpatients 18 years or older had bacterial infections of the blood, skin or skin/structure, intra-abdominal region, lower respiratory tract, or urinary tract (considered complicated) caused by organisms susceptible to both ciprofloxacin and ceftazidime. Patients were randomly assigned to receive either ciprofloxacin 200 mg intravenously every 12 hours or ceftazidime 0.5 to 2 g intravenously every eight to 12 hours. Clinical evaluations were performed daily during therapy and within five to nine days after therapy was complete. For patients with urinary tract infection, urine for culture was obtained during (Day 3 or 4) and after (five to nine days and three to five weeks) therapy. A total of 86 patients were enrolled into the study. Forty-three received ciprofloxacin and 43 received ceftazidime. There were 22 evaluable patients in the ciprofloxacin group with 24 infection sites: skin/skin structure (eight), respiratory tract (nine), blood (two), urinary tract (five). In the ceftazidime group, there were 26 evaluable patients with 29 infection sites: skin/skin structure (15), respiratory tract (nine), blood (three), and urinary tract (two). The mean duration of therapy with ciprofloxacin and ceftazidime was 7.5 days (range, four to 28 days) and 8.4 days (range, three to 25 days), respectively. Bacteriologic eradication of the causative organisms occurred at 17 infection sites (70.8 percent) in the ciprofloxacin-treated patients and 21 infection sites (72.4 percent) in the ceftazidime group. Clinically, resolution or improvement in signs/symptoms was demonstrated in 22 patients (91.7 percent) in the ciprofloxacin group and 26 patients (89.7 percent) in the ceftazidime group. Bacteriologic response (by organism) and overall response were comparable in both groups. All enrolled patients were evaluated for determination of safety. Adverse events considered possibly or probably related to the study drugs were reported in 16 of 43 patients (37.2 percent) in the ciprofloxacin group and four of 43 patients (9.3 percent) in the ceftazidime group. Ciprofloxacin and ceftazidime were equally efficacious in the treatment of selected infections, but ciprofloxacin was associated with a higher incidence of adverse reactions probably or possibly related to drug administration. Further studies with larger sample sizes in selected patient populations will be required to identify differences in efficacy among the two antibiotics.

Adult↗
PubMed1989

Bioequivalence assessment of zidovudine (Retrovir) syrup, solution, and capsule formulations in patients infected with human immunodeficiency virus.

The objectives of this open-labeled, multiple-dose, three-way-crossover trial were to evaluate the safety and tolerance of zidovudine (Retrovir) oral syrup and to assess the bioequivalence of this formulation relative to zidovudine solution and capsule formulations in human immunodeficiency virus-infected patients. Over the 7-day study, 12 adult male subjects received 12 administrations each of the capsule, solution, and syrup formulations every 4 h (six times daily) in a randomized sequence. Frequent blood samples were collected over the 4-h period after dose 12 was administered. Zidovudine concentrations in plasma were determined by a specific and sensitive radioimmunoassay. Results from statistical analyses indicated that all three formulations were bioequivalent with respect to systemic availability (area under the time-concentration curve) and that the syrup was also equivalent to the solution with respect to the maximum peak concentration in serum. The lower relative maximum peak concentration in serum (approximately 81%) and small delays in time to peak concentration (less than 30 min) of the capsule formulation as compared with the liquid formulations are thought to be due to the additional processes of disintegration and dissolution associated with capsule administration. All three preparations were well tolerated during the 7-day study.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Ofloxacin: its pharmacology, pharmacokinetics, and potential for clinical application.

Ofloxacin is a 4-quinolone antibiotic with rapid bactericidal activity against a wide variety of organisms. Its proposed mechanism of activity is interference with DNA gyrase, an enzyme essential for the replication of bacterial DNA. In vitro activity of ofloxacin includes a variety of aerobic and anaerobic bacteria. Enteric gram-negative bacilli and cocci are generally sensitive to ofloxacin; nonaeruginosa strains of Pseudomonas are less so. Numerous bacterial pathogens of the gastrointestinal tract are also sensitive to the drug. Although its MIC values for gram-positive aerobic organisms are generally higher, ofloxacin's bactericidal activity against these organisms is considered by some to be adequate, and superior to that of most other fluoroquinolones. Ofloxacin is well absorbed after oral administration. Wide tissue and body fluid distribution is demonstrated. Urinary excretion is thought to be the primary route of elimination, with 80% of the dose recovered in the urine within 24 hours. The serum half-life ranges between 2.9 and 9 hours in a dose-dependent manner. Only modest accumulation is reported after multiple-dose administration. Clinical trials using daily dosages of 100-800 mg/day in single or divided doses have been reported in the treatment of a variety of conditions such as skin and soft tissue infections, tonsillitis, sexually transmitted disease, respiratory tract infections, cystitis, and complicated and uncomplicated urinary tract infections. English reports of these trials, however, are generally limited to abstract form, making evaluation of trial design difficult. Side effects most frequently encountered include gastrointestinal and central nervous system reactions.

Anti-Bacterial Agents↗
PubMed1986

Neuropsychological deficits in active licensed professional boxers.

Young, active, licensed professional boxers (N = 19) were found to display a pattern of neuropsychological deficits consistent with the more severe punch-drunk syndrome of years past. These deficits resulted in significantly lower test performance than that of control athletes (N = 10) matched for race, age, and level of education. Tests that showed significant differences between groups include subtests of the Quick Neurological Screening Test, subtests of the Halstead-Reitan Neuropsychological Test Battery, and the Randt Memory Test. Fifteen of the 19 boxers scored in the impaired range of the Reitan Impairment Index, as compared to 2 of the 10 controls.

Adolescent↗
PubMed1983

The use of hydroxocobalamin in the prophylaxis and treatment of nitroprusside-induced cyanide toxicity.

The use of OHB12 in the prophylaxis of CN intoxication resulting from SNP infusions is well documented in the literature. However, data is lacking to support its use as an antidote once signs and symptoms have developed. Because of the efficacy of oxygen therapy combined with supportive therapy and nitrite/sodium thiosulfate administration, the use of OHB12 as an antidote cannot be recommended at this time. Further studies are needed to determine efficacy, dosing, mode of administration and comparative trials to other antidotes.

Animals↗