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Biomedical subjects

J A Bosso

Publications and source records attributed to J A Bosso.

At least 19 recordsLinked to original sources
PubMed1992

Advances in the pharmacotherapy of cystic fibrosis.

The quality of life and life-span of cystic fibrosis patients have been improved substantially in the last 20 or 30 years. This has been accomplished largely through improved early diagnosis and advances in traditional pharmacotherapy which mainly consists of antibiotic therapy. In the past few years, the basic cellular defect of cystic fibrosis, as well as the gene determining the disease, have been described. These milestones in the quest for knowledge about the disease open the door for other innovative forms of therapy. While corrective gene therapy may be the ultimate result of advances made based upon this new knowledge, we will probably see earlier breakthroughs in the form of immune reaction inhibition and correction of ion flux disturbances. Each of these present and future forms of therapy is explored in this paper.

4-Quinolones↗
PubMed1992

Treatment options for the pharmacological therapy of neonatal meningitis.

Neonatal bacterial meningitis has a relatively low incidence in developed countries, but continues to cause morbidity and mortality despite advances in antimicrobial therapy. Bacterial pathogens commonly associated with neonatal meningitis include Group B streptococci, Escherichia coli K1 and other coliforms, Listeria monocytogenes and staphylococci. As it can be difficult to differentiate meningitis from septicaemia in neonates, empirical antibiotic therapy should be effective for both. Selection of an empirical antibiotic regimen should be based on: (a) bacterial prevalence and susceptibility; (b) drug characteristics; (c) postnatal age at the onset of disease; and (d) patient-specific factors. A penicillin in combination with an aminoglycoside or cefotaxime is commonly used in empirical therapies. The increased risk of staphylococcal infection in older neonates requires consideration of an antistaphylococcal antibiotic in the empirical therapy regimen. Once a causative organism has been identified, antimicrobial therapy should be directed towards that pathogen. Duration of therapy remains empirical, but should be at least 7 days for documented bacterial meningitis. Viral meningitis continues to have a high mortality despite the availability of antiviral agents. Adjunctive therapies may further reduce the morbidity and mortality of meningitis. While most of these therapeutic options have not been investigated in neonates, they may prove to be of benefit in the future. Anti-inflammatory agents, such as glucocorticoids, nonsteroidal anti-inflammatory agents and immunoglobulin, may modulate the inflammatory response of a meningeal infection. Other possible therapies in neonatal meningitis include cerebral blood flow modulators and disease prevention with maternal vaccines and perinatal antibiotics. Practical aspects of drug therapy such as route of administration and serum drug concentration monitoring can improve both drug therapy and patient outcome. While antibiotics have greatly improved the treatment outcome of neonatal meningitis, it is clear that additional intervention will be required to increase cure rates and reduce sequelae.

Humans↗
PubMed1992

Stability of ondansetron hydrochloride in injectable solutions at -20, 5, and 25 degrees C.

The stability of ondansetron hydrochloride in 5% dextrose injection and in 0.9% sodium chloride injection when stored frozen, refrigerated, and at room temperature was studied. Solutions of ondansetron 0.03 and 0.3 mg/mL (as the hydrochloride salt) were prepared by adding 1.5 or 15 mg of the drug to 50-mL minibags containing 5% dextrose injection or 0.9% sodium chloride injection. All solutions were prepared in triplicate, and each container was tested in duplicate. Testing at the time of preparation and at each subsequent test interval included visual inspection of color and clarity, determination of pH, and a stability-indicating high-performance liquid chromatographic assay to measure the ondansetron concentration. Conditions assessed included storage at -20 degrees C for two weeks to three months, 5 degrees C for 7-14 days, approximately 25 degrees C for up to 48 hours, and various combinations of these conditions. The concentration of ondansetron in each solution remained above 90% of the original concentration at each observation time under all storage conditions. No changes in color or clarity were observed, and there were only minor changes in pH. Ondansetron 0.03 and 0.3 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection was stable when stored (1) for up to three months at -20 degrees C, followed by up to 14 days at 5 degrees C and by 48 hours at 25 degrees C and (2) for up to 14 days at 5 degrees C, followed by up to 48 hours at 25 degrees C.

Drug Stability↗
PubMed1991

Comparative activity of cefepime, alone and in combination, against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from cystic fibrosis patients.

The comparative in vitro activity and synergy of cefepime were evaluated with clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from cystic fibrosis patients. The activity of cefepime, both alone and in combination, was comparable to those of other antibiotics. The clinical efficacy of cefepime in cystic fibrosis patients merits investigation.

Anti-Bacterial Agents↗
PubMed1991

Toxicity of colistin in cystic fibrosis patients.

Pulmonary exacerbations of cystic fibrosis associated with strains of Pseudomonas aeruginosa that are resistant to multiple antibiotics are becoming increasingly common. The search for treatment alternatives continues and may include the reexamination of older antibiotics. Colistin sulfate is a polypeptide antibiotic with good activity against P. aeruginosa. Although its use was largely discontinued in the early 1970s because of reports of frequent renal and neurologic toxicity, intravenous colistin is often prescribed at our institution for patients with P. aeruginosa resistant to multiple-drug therapy. We prospectively monitored 19 patients during 21 courses of colistin therapy to identify the character and incidence of this agent's toxicity. Only one case of renal toxicity occurred. Six cases of neurotoxicity occurred, which were characterized by perioral paresthesia, ataxia, or both. The rate of intolerable renal adverse effects secondary to colistin therapy was appreciably lower among these patients than that reported previously for other patients. It appears that intravenous colistin can be considered for cystic fibrosis patients with strains of P. aeruginosa that are resistant to more commonly used antibiotics.

Adolescent↗
PubMed1991

The use of aztreonam in pediatric patients: a review.

Aztreonam is the first monobactam available for use in this country. A parenteral antibiotic, its antibacterial spectrum is limited to gram-negative aerobic pathogens. The drug's pharmacologic, pharmacokinetic, and toxicologic properties are reviewed. Based on early experience in pediatric patients, certain recommendations can be made for the use of aztreonam.

Adult↗
PubMed1990

Clinical manifestations of exacerbations of cystic fibrosis associated with nonbacterial infections.

The purpose of this study was to determine whether acute pulmonary exacerbations of cystic fibrosis associated with nonbacterial infections are clinically distinguishable from other exacerbations. Eighty exacerbations in 54 patients were studied. Exacerbations associated with influenza (n = 8) were compared with those associated with other nonbacterial infections (n = 15) and those in which no nonbacterial infection was detected (n = 57). Patients with influenza had lower Shwachman scores and were more likely to be seropositive for C-reactive protein than patients in the other two groups. Patients with influenza had a mean decrease in forced expiratory volume per second of 26%, compared with test results obtained before the exacerbation. In contrast, the mean decrease in forced expiratory volume per second was 6% for other nonbacterial infections and 12% for the group without nonbacterial infection (p less than 0.05 for both comparisons). The forced expiratory flow in first 25% of vital capacity decreased 44% in the influenza group compared with 13% and 17% in the other two groups, respectively (p less than 0.01 for both comparisons). The influenza group also had a higher proportion of patients with at least a 20% decrease in forced expiratory volume per second and forced expiratory flow in first 25% of vital capacity than the other two groups had (p less than 0.05 for all comparisons). These data suggest that influenza is associated with severe exacerbations in patients with cystic fibrosis and support recommendations for efforts to prevent influenza in this population.

Adolescent↗
PubMed1990

In vitro activities of combinations of aztreonam, ciprofloxacin, and ceftazidime against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from patients with cystic fibrosis.

The in vitro activities of two-drug combinations of aztreonam, ciprofloxacin, and ceftazidime were studied in 96 clinical isolates of Pseudomonas aeruginosa and in 20 clinical isolates of Pseudomonas cepacia from cystic fibrosis patients. Some synergy was observed with each combination used against P. aeruginosa, but synergy was rare when the combinations were used against P. cepacia.

Aztreonam↗
PubMed1989

Use of ciprofloxacin in cystic fibrosis patients.

In order to evaluate the clinical efficacy and safety of oral ciprofloxacin in the treatment of acute pulmonary exacerbations of cystic fibrosis and trace the possible development of resistance over time, three trials were conducted. In an open-label, uncontrolled trial, 25 courses of ciprofloxacin were administered to 16 patients. Efficacy and safety were assessed based on changes in short-term clinical scores, white blood cell counts, Pseudomonas aeruginosa counts in sputum, pulmonary function tests, and standard serum chemistries and urinalysis that were performed before therapy, weekly during therapy, at the end of therapy, and at a seven-day follow-up visit after therapy. In an open-label, randomized, controlled study, the efficacy and tolerance of oral ciprofloxacin were compared with those of intravenous tobramycin and azlocillin. In another study, the rate of susceptibility of P. aeruginosa isolated from cystic fibrosis patients during more than two years of clinical use was determined. In the uncontrolled trial, ciprofloxacin therapy was associated with clinical improvement in most cases with changes in short-term clinical score and forced expiratory volume in one second being statistically significant (p less than 0.05). Twenty-five patients were entered in the controlled trial with 12 patients in each treatment group being evaluable. The groups were comparable based on admitting demographic and disease characteristics, and no differences in therapeutic response or side effects were noted between the two treatments (p greater than 0.5). Bacterial susceptibility to ciprofloxacin has remained relatively stable over time. Based on these results as well as those from similar evaluations, ciprofloxacin appears to be efficacious in the treatment of acute pulmonary exacerbations in adults with cystic fibrosis, producing responses similar to those observed with standard intravenous antibiotic therapy.

Adult↗
PubMed1989

The comparative in vitro activity of ofloxacin and selected ophthalmic antimicrobial agents against ocular bacterial isolates.

The in vitro activity of ofloxacin, a new fluoroquinolone anti-infective agent, was evaluated against 419 ocular bacterial isolates of 55 species to determine its potential as a topical agent for the treatment of ocular infections. Other agents tested in this study, in which a modified tube-dilution procedure was used, include norfloxacin, gentamicin, tobramycin, chloramphenicol, and polymyxin B. Ofloxacin demonstrated good to excellent activity against a variety of gram-positive and gram-negative pathogens. The minimum inhibitory concentration against 90% of all bacterial strains tested (MIC90) of ofloxacin was 0.5 microgram/ml for Staphylococcus aureus and S. epidermidis, 2 micrograms/ml for Streptococcus pneumoniae, and 4 micrograms/ml for Pseudomonas aeruginosa. These species were more susceptible to ofloxacin than to any of the nonquinolones tested. The MIC90 of ofloxacin was lower than that of norfloxacin, another quinolone, against S. aureus, S. epidermidis, and St. pneumoniae and equal to that of norfloxacin against P. aeruginosa. Because of its broad spectrum of activity and excellent in vitro activity, we concluded that ofloxacin has the potential for development into a superior topical treatment for ocular infection.

Anti-Bacterial Agents↗
PubMed1989

The use of aztreonam in the cystic fibrosis patient.

Eradication of pulmonary infection by Pseudomonas aeruginosa in cystic fibrosis (CF) patients has long presented a significant challenge to the medical community. Many antimicrobial agents have proved incompletely effective against this persistent pathogen, and even the aminoglycosides, which represent the traditional therapy for such infections, have been associated with considerable toxicity and resistance. The monobactam antibacterial agent aztreonam is used both as single-agent therapy and in combination with other drugs. Several controlled, clinical trials have demonstrated the efficacy of aztreonam in the treatment of CF patients with pulmonary exacerbations caused by P. aeruginosa. The only side effect of aztreonam therapy commonly encountered in these studies was elevation of hepatic transaminase concentrations; this effect was of uncertain significance. It was concluded that aztreonam may offer clinical efficacy comparable to that provided by the combination of tobramycin plus azlocillin. Further, there does not seem to be any appreciable difference in the development of resistance to aztreonam compared with traditional therapies.

Aztreonam↗
PubMed1989

Changing susceptibility of Pseudomonas aeruginosa isolates from cystic fibrosis patients with the clinical use of newer antibiotics.

To detect a change in antibiotic susceptibility patterns in Pseudomonas aeruginosa isolates upon the introduction and clinical use of ciprofloxacin, aztreonam, and ceftazidime, MICs for clinical isolates collected before introduction of the antibiotics, during early clinical use, and later were determined for these and seven other antipseudomonal antibiotics. Concomitant resistance to two or more antibiotics was also studied. Over the three study periods, rates of susceptibility to 9 of the 10 antibiotics decreased. The largest decrease occurred with ceftazidime. Analysis of subsets of isolates from patients treated with ciprofloxacin or aztreonam also showed declining susceptibility to the latter but a stabilization of susceptibility to the former after an initial decline. Concomitant resistance within and among antibiotic classes was common.

Anti-Bacterial Agents↗
PubMed1988

Controlled trial of aztreonam vs. tobramycin and azlocillin for acute pulmonary exacerbations of cystic fibrosis.

The efficacy of aztreonam was compared to that of standard therapy consisting of tobramycin and azlocillin in the treatment of acute pulmonary exacerbations of cystic fibrosis in a randomized, open trial. Fifteen patients were randomized to each treatment. Responses were assessed based on changes in pulmonary and clinical scores, white blood cell counts, pulmonary function tests and quantitative bacteriology of sputum which were performed before, every 5 to 7 days during and on the last day of therapy. Patients in both groups responded to therapy and there were no statistically significant differences in changes in the above indicators of response with therapy between the two groups (P greater than 0.05). The incidence of detection of Pseudomonas aeruginosa isolates resistant to all three study antibiotics increased with therapy. Side effects were limited to transient elevations of liver enzymes (both groups) and rash and fever in one patient treated with azlocillin. Aztreonam represents effective therapy for pulmonary exacerbations of cystic fibrosis associated with susceptible pathogens.

Adolescent↗
PubMed1988

Compatibility of clindamycin phosphate with aztreonam in polypropylene syringes and with cefoperazone sodium, cefonicid sodium, and cefuroxime sodium in partial-fill glass bottles.

The stability and compatibility of clindamycin phosphate admixed with four beta-lactams, an experimental monobactam (aztreonam), and three cephalosporins (cefoperazone sodium, cefonicid sodium, and cefuroxime sodium), were studied. Aztreonam alone and the combination of clindamycin phosphate-aztreonam were prepared in duplicate polypropylene syringes. Each cephalosporin antibiotic as well as the three clindamycin phosphate-cephalosporin combinations were admixed in duplicate 100 ml partial-fill glass bottles containing either dextrose 5% in water or NaCl 0.9%. All solutions were examined, antibiotic concentrations were determined, and pH was measured at the time of admixture and 1, 4, 8, 12, 24, and 48 hours later. The solutions were maintained at room temperature under fluorescent lighting for the length of the study. Antibiotic concentrations were determined by drug-specific high performance liquid chromatographic assays. Significant instability or incompatibility was defined as a decrease in concentration of greater than ten percent relative to the initial concentration measured at the time of admixture. All antibiotics were stable for 48 hours. In the combination studies, clindamycin was stable for 48 hours, both in partial-fill glass bottles and syringes. Aztreonam, cefoperazone, cefonicid, and cefuroxime were also stable for 48 hours.

Aztreonam↗