Efficacy of ototopical ciprofloxacin in pediatric patients with otorrhea.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of topical ciprofloxacin in patients with recurrent otorrhea that was unresponsive to other antibiotics. METHODS: Pediatric patients with otorrhea and confirmed Pseudomonas aeruginosa in the ear fluid were enrolled. Topical ciprofloxacin, three drops three times daily for 14 days, was prescribed with aural care. Efficacy and safety were evaluated on days 7 and 14. A phone follow-up was conducted monthly thereafter for 8.6 months. RESULTS: Twenty-nine pediatric patients were enrolled. On day 14, 18 were cured, 8 were improved, 2 were changed to an alternate therapy and cured, and 1 showed no improvement, perhaps due to a small external ear canal. Two additional patients were cured at day 21. None of the patients reported any adverse effects. Twelve patients had no recurrence at 3 to 15 months after the study. CONCLUSION: The use of topical ciprofloxacin in pediatric patients was curative in nearly 70% of patients with otorrhea associated with P. aeruginosa who were previously unresponsive to other antimicrobials. No adverse reactions were reported in the study population.

Phosphorylated zidovudine concentrations in mononuclear cells in pediatric patients with human immunodeficiency virus infections.

PURPOSE: The efficacy of zidovudine (ZDV) in patients with HIV-1 infection may decrease over time due to its decreased activation. The objectives of this study were to determine ZDV concentrations in plasma, active phosphorylated zidovudine (pZDV) concentrations in mononuclear cells, and assess the markers of immune function and drug toxicity during extended therapy. METHODS: Pediatric patients (aged 3 months to 18 years) with HIV-1-infection were enrolled in the study. For each patient, one blood sample was collected at each of eight routine visits to measure plasma ZDV and ZDV concentrations by a radioimmunoassay. Data including demographic information, immunological markers (CD2+, CD3+, CD4+, CD5+/19+, CD8+, CD16+, CD19+, CD38+/8+ lymphocytes), hematologic function (absolute neutrophil count, white blood cell with differential, hemoglobin, and red blood cell count), concurrent medications, and dosage regimens were obtained. RESULTS: The data from 13 patients were as follows: age: 2-18 years; range of ZDV dose: 76-238 mg/m2, total ZDV daily dosage: 264-720 mg/m2; duration of ZDV therapy prior to study: 1 to 37 months; time in study: 180-394 days; plasma ZDV concentration range: 5-1021 ng/ml; and pZDV concentration range: 0-5.382 pmol/10(6) cells. Both plasma ZDV and intracellular pZDV concentrations had a marked inter- and intrapatient variability. The pZDV concentrations decreased significantly over time in one pediatric patient (p < 0.05), tended to decrease but not significantly in three patients, and no decrease was detected in nine patients due to high variability. In our population, neither immunological nor drug toxicity markers changed over time. CONCLUSIONS: Marked inter- and intrapatient variability in pZDV concentrations was observed. The ability to phosphorylate ZDV, however, did not appear to change significantly in 12 of 13 pediatric patients with HIV-1 infection during the study period of 6-13 months.

Dirithromycin: a new macrolide.

OBJECTIVE: To review the clinical microbiology and therapeutic use of dirithromycin, emphasizing comparative data between dirithromycin and the standard macrolide erythromycin, as well as clarithromycin and azithromycin. DATA SOURCES: A MEDLINE search of English-language literature during the years 1966-1996, and an extensive review of journals were conducted to prepare this article. DATA EXTRACTION: The data on pharmacokinetics, adverse effects, and drug interactions were obtained from open and controlled studies. Controlled single- or double-blind studies were evaluated to assess the efficacy of dirithromycin in the treatment of various upper and lower respiratory tract infections, as well as skin and soft tissue infections. DATA SYNTHESIS: The spectrum of activity of dirithromycin is similar to that of erythromycin, clarithromycin, or azithromycin, with some notable exceptions. Dirithromycin was more active in vitro against Campylobacter jejuni and Borrelia burgdorferi than was erythromycin or clarithromycin, but in general demonstrated less activity than erythromycin, clarithromycin, or azithromycin against a majority of microorganisms. The pharmacokinetic profile of dirithromycin offers the advantages of once-daily dosing and high and prolonged tissue concentrations; dosing adjustments are not needed in the elderly or in patients with renal or mild hepatic impairment. Clinical efficacy and bacteriologic eradication rates with dirithromycin and erythromycin are comparable for the treatment of respiratory and skin and soft tissue infections due to susceptible pathogens. Dirithromycin appears to have adverse effect profiles similar to those of the other macrolides, with reported problems most often related to the gastrointestinal tract. Dirithromycin does not seem to cause clinically important interactions with drugs such as theophylline, oral contraceptives, cyclosporine, or terfenadine. CONCLUSIONS: Dirithromycin offers some attractive pharmacokinetic properties. The long elimination half-life of dirithromycin allows once-daily dosing and higher and more prolonged tissue concentrations than are achievable with erythromycin. The spectrum of activity, adverse effect profile, clinical efficacy, and bacteriologic eradication rate of dirithromycin may be similar to those of erythromycin. No significant drug interactions with dirithromycin have been reported. Based on available data, dirithromycin may not offer any unique clinical advantage over clarithromycin or azithromycin. Future clinical trials may reveal a special role for dirithromycin in patient care.

Stability of flucytosine in an extemporaneously compounded oral liquid.

The stability of flucytosine in an oral liquid prepared from capsules was studied. Flucytosine 10-mg/ml oral liquid was prepared from 500-mg capsules (with distilled water as the diluent) and transferred to 10 glass and 10 plastic amber bottles. Five of each type of bottle were stored at 4 degrees C and five of each at 25 degrees C. Samples were taken at 0, 7, 14, 28, 42, 56, 70, and 91 days, and flucytosine concentration was measured by stability-indicating high-performance liquid chromatography. Flucytosine was stable in the liquid formulation for at least 70 days under all the study conditions. The physical appearance of the liquid stored at 4 degrees C did not change during the study period. Flocculation was observed both in glass and in plastic bottles stored at 25 degrees C on day 14 and thereafter. Flucytosine 10 mg/mL in an extemporaneously prepared oral liquid was stable for 70 days in glass or plastic prescription bottles kept at 4 or 25 degrees C.

Alcaligenes xylosoxidans subsp xylosoxidans in children with chronic otorrhea.

Because other known pathogens are frequently isolated with AXX, its clinical significance may be overlooked. AXX should not be considered a colonizer or contaminant, particularly in the presence of clinical signs and symptoms of infection. For a pediatric patient with AXX in the ear fluid, the choice of an antibiotic regimen should be based on in vitro activity of both AXX and other concurrent pathogens. Although the sensitivity of AXX may be highly variable, a number of antibiotics appear to be clinically useful.

Rimantadine: a clinical perspective.

OBJECTIVE: To provide a review of rimantadine, including its antiviral activity, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage and administration. Information on influenza A virus and clinical features of influenza disease are presented. Comparative data on rimantadine and amantadine are described. DATA SOURCES: A MEDLINE search restricted to English-language literature published from 1966 through 1994 and an extensive review of journals was conducted. DATA EXTRACTION: The data on antiviral activity, pharmacokinetics, adverse effects, and drug interactions were obtained from various articles on rimantadine in open and controlled studies. Controlled double-blind studies were evaluated to assess the efficacy of rimantadine in prophylaxis and treatment of influenza A infection. DATA SYNTHESIS: Over 90% of a rimantadine dose was absorbed in 3-6 hours in healthy adults. Steady-state plasma concentrations have ranged from 0.10 to 2.60 micrograms/mL at doses of 3 mg/kg/d in infants to 100 mg twice daily in the elderly. Nasal fluid concentrations of rimantadine at steady-state were 1.5 times higher than plasma concentrations, which may explain the effectiveness of rimantadine despite a low plasma concentration. Over 75% of a rimantadine dose was metabolized in the liver, and the parent compound and metabolites were almost completely eliminated by the kidneys. The elimination half-life ranged from 24.8 to 36.5 hours, which allows once-daily dosing. Dosage adjustment is recommended for patients with severe renal impairment (creatinine clearance < or = 0.17 mL/s), severe hepatic dysfunction, or elderly nursing home patients. Drug-resistant strains of influenza A virus to rimantadine occurred in several studies with children and/or adults. Clinical significance of drug-resistant strains has not been established. Rimantadine appeared to be effective in 85-90% of individuals for prevention of influenza A illness and in 50-65% for prevention of influenza A infection. Rimantadine reduced the time to a 50% reduction in symptoms by 1-3 days versus placebo. Differences in symptom reduction between rimantadine and placebo after the first 3 days of treatment was not generally clinically significant. The most common adverse effects of rimantadine administration were associated with the central nervous system (CNS) and the gastrointestinal (GI) tract. CNS-related adverse effects occurred in 3.2% of children younger than 10 years of age and 8.4% of adults. In elderly patients, the incidence of CNS-related adverse effects ranged from 4.9% at 100 mg/d to 12.5% at 200 mg/d. GI adverse effects occurred in 8.4% of children younger than 10 years of age, 3.1% of adults, and 2.9% at 100 mg/d and 17.0% at 200 mg/d in the elderly. CONCLUSIONS: Rimantadine offers some desirable features for the treatment and prophylaxis of influenza A infection. It appears to be an attractive choice in elderly patients with a history of CNS adverse effects from amantadine and in patients with mild or moderate renal impairment. Although approved for twice-daily dosing, rimantadine has a pharmacokinetic profile that would allow once-daily dosing. It is effective for prophylaxis (not postexposure prophylaxis) and treatment of influenza A virus. It also has a low incidence of adverse effects.

Chronic suppurative otitis media.

OBJECTIVE: To review various aspects of chronic suppurative otitis media (CSOM). DATA SOURCES: A MEDLINE search and extensive review of articles provided the information for this review. DATA EXTRACTION: Studies describing the epidemiology, microbiology, risk factors, pathology, diagnosis, treatment, complications, and recurrence of CSOM were included. DATA SYNTHESIS: Pseudomonas aeruginosa and anaerobes are the most predominant bacteria found in CSOM. Treatment with otic, oral, or parenteral drugs (e.g., neomycin/polymyxin B/hydrocortisone otic, ciprofloxacin, ceftazidime, or aminoglycosides) should be guided by ear fluid culture results. Prompt treatment with effective and safe antibiotics may prevent complications of CSOM. CONCLUSIONS: Treatment of CSOM has improved as a result of availability of effective otic and oral antibiotics. Treatment of the anaerobic infection with antibiotics should be studied further.

Whole-cell and acellular pertussis vaccines.

OBJECTIVE: To provide a review of pertussis vaccines, including information on efficacy, adverse reactions, and antibody production following administration of both whole-cell and acellular pertussis vaccines. DATA SOURCES: A MEDLINE search and extensive review of journals was conducted to identify the information for this review. DATA EXTRACTION: Pertinent studies reporting experience with pertussis vaccinations were reviewed. DATA SYNTHESIS: The differences in efficacy, adverse reactions, and antibody responses between whole-cell and acellular pertussis vaccines are emphasized. The status of acellular pertussis vaccination in the US is defined. CONCLUSIONS: Acellular (chemically detoxified or recombinant) pertussis vaccine formulation appears to cause fewer adverse reactions than whole-cell vaccine in most studies. Clinical efficacy and safety in the very young has not been well established. Thus, acellular pertussis vaccine is reserved for the 4th and 5th doses in the US. Oral or intranasal formulations of the pertussis vaccine are being evaluated.