The influence of renal function on hydroxyurea pharmacokinetics in adults with sickle cell disease.

This was an open-label, nonrandomized, 2-center study conducted to assess the influence of renal function on the pharmacokinetics of hydroxyurea in adults with sickle cell disease (SCD). Seventeen patients were divided into 5 groups: normal renal function (n = 7), mild renal impairment (n = 2), moderate renal impairment (n = 3), severe renal impairment (n = 2), and end-stage renal disease (ESRD, n = 3). Except for patients with ESRD, all the patients received a 15-mg/kg single oral dose of hydroxyurea. Patients with ESRD received a 15-mg/kg oral dose of hydroxyurea on 2 occasions. Blood and urine samples were collected for the assessment of hydroxyurea pharmacokinetics. The results indicate that the systemic exposure increases and the urinary recovery decreases as the degree of renal insufficiency worsens. On the basis of the exposure and the apparent clearance from the current and 2 historical studies, the authors have proposed an initial dosing regimen of hydroxyurea (7.5 mg/kg/day) for SCD patients with CL(cr) <60 mL/min. This dosing strategy is anticipated to provide a safe dose for SCD patients with renal impairment.

Gatifloxacin in community-based treatment of acute respiratory tract infections in the elderly.

The elderly are at increased risk for respiratory tract infections. To evaluate the safety and efficacy of gatifloxacin in adults of any age with community-acquired respiratory tract infections, this open-label, multicenter, noncomparative study in community-based practices enrolled male and female outpatients at least 18 years old with a clinical diagnosis of community-acquired pneumonia (CAP), acute-bacterial exacerbation of chronic bronchitis (AECB), or acute uncomplicated maxillary sinusitis. Gatifloxacin 400 mg was administered once daily for seven to 14 days. Of 14781 clinically evaluable patients, 2505 were at least 65 years old, 499, at lest 80. Cure rates for CAP, AECB, and sinusitis ranged from 91.6% to 95.5% for patients less than 65 years old, 91.1% to 96.2% for those 65 to 79 years of age, and 89.5% to 94.8% for those at least 80 years old. Each age group, including patients with concomitant cardiovascular or diabetic conditions, tolerated treatment well. Gatifloxacin is efficacious and well tolerated in adult outpatients of any age with respiratory tract infections and is an important therapeutic option, particularly in communities with a high prevalence of resistant pathogens.

Efficacy and safety of gatifloxacin in elderly outpatients with community-acquired pneumonia.

To evaluate the safety and efficacy of gatifloxacin in adults <65, 65 to 79, or > or =80 years old with community-acquired pneumonia, adult male and female outpatients from general community-based practices were enrolled in an open-label, multicenter, noncomparative study. Gatifloxacin 400 mg once daily was administered for seven to 14 days. Medical history, physical examination, signs and symptoms of infection, Gram stain and culture if specimen available, clinical response, and safety were determined. Of 1655 treated patients, 1103 were at least 65 years old, 405 were 65 to 79, and 147 were at least 80. Patients > or =80 years old presented with chills, chest pain, fever, or headache less often than younger patients. Cure rates were 95.5% for patients <65 years old, 96.2% for those 65 to 79, and 90.2% for those at least 80 years old. Neither the frequency nor susceptibility of isolated pathogens appeared to differ with age. Between 93.7% and 100% of subsets of the two younger groups with verified Streptococcus pneumoniae or Hemophilus influenzae were cured. All oldest-group patients in the subset with verified S. pneumoniae and 71.4% (7) of patients with H. influenzae were cured. Each age group, including current or past smokers and patients receiving medications for concomitant conditions, tolerated treatment well. Gatifloxacin is safe and efficacious in adults of any age with community-acquired pneumonia, including the elderly up to 100 years old and patients with S. pneumoniae including penicillin-resistant strains.

Oral gatifloxacin in outpatient community-acquired pneumonia: results from TeqCES, a community-based, open-label, multicenter study.

Gatifloxacin is an 8-methoxy fluoroquinolone with broad activity against respiratory tract pathogens, including those commonly associated with community-acquired pneumonia (CAP). To evaluate the efficacy and safety of oral gatifloxacin 400 mg once daily for seven to 14 days, community-based physicians enrolled adult outpatients with confirmed or suspected CAP in a prospective, single-arm, open-label, noncomparative study. Of 1488 clinically evaluable patients with radiographically confirmed or clinically suspected CAP, 1417 (95.2%) were cured. All strains of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, the most commonly isolated pathogens, were susceptible to gatifloxacin. Penicillin nonsusceptibility was seen in 32.6% of S. pneumoniae isolates, and beta-lactamase production was detected in H. influenzae (26.9%) and M. catarrhalis (88%) isolates. Clinical cure rates of 91%, 94%, and 92% were achieved in patients with S. pneumoniae, H. influenzae, and M. catarrhalis, respectively. All seven patients with fully penicillin-resistant S. pneumoniae (MIC > or =2 micro g/ml) were cured. Gatifloxacin was well tolerated, with the most common drug-related adverse events being nausea (2.8%) and diarrhea (1.7%). Gatifloxacin is effective and well tolerated as empiric therapy for CAP in the outpatient community setting.

Gatifloxacin used for therapy of outpatient community-acquired pneumonia caused by Streptococcus pneumoniae.

Gatifloxacin is an advanced-generation fluoroquinolone with demonstrated efficacy and safety as therapy for community-acquired pneumonia (CAP). As part of a phase IV postmarketing surveillance program (TeqCES), 136 outpatients with CAP whose sputum was culture-positive for Streptococcus pneumoniae were enrolled in an open-label trial of oral gatifloxacin 400 mg daily for 7 to 14 days. An antibiogram of isolates showed 100% susceptibility to gatifloxacin (MIC(90) 0.5 micro g/mL) and respective susceptibilities of 67%, 70%, and 80% to penicillin, erythromycin, and tetracycline. Clinical cure was achieved in 95.3% of evaluable patients, including seven patients infected with penicillin-resistant S. pneumoniae (MIC > or =2 micro g/mL). The bacteriologic eradication rate for S. pneumoniae was 94.5%. Diarrhea, nausea, and dizziness, the most common adverse events in CAP patients (<3%), were generally mild to moderate; no serious adverse events were recorded. These results support recommendations to treat CAP, particularly due to S. pneumoniae including multidrug-resistant strains, with the newer 8-methoxy-fluoroquinolone, gatifloxacin.