Pharmacokinetics of azithromycin in serum, bronchial washings, alveolar macrophages and lung tissue following a single oral dose of extended or immediate release formulations of azithromycin.

OBJECTIVES: Antibacterial efficacy of azithromycin could be improved by achieving higher concentrations at the sites of infection. Azithromycin extended release (azithromycin-ER) formulation was developed to enable a higher dosage of 2 g to be administered as a single oral dose without decreasing the safety profile. The aim of this study was to compare the pharmacokinetics of azithromycin in serum, epithelial lining fluid (ELF), alveolar macrophages (AMs) and lung tissue following a single oral dose of azithromycin-ER or azithromycin immediate release (azithromycin-IR) formulation. PATIENTS AND METHODS: A total of 64 patients, diagnosed with lung cancer, requiring open-chest surgery for lung resection, completed the study. Subjects were randomized to receive oral administration of either a single 2 g dose of azithromycin-ER (32 subjects) or a single 500 mg dose of azithromycin-IR (32 subjects). Simultaneously, subjects within each treatment group were randomized to one of eight specific nominal post-dose time points for bronchoalveolar lavage and lung tissue sampling. Results For azithromycin-IR formulation, the AUC(0-24) in serum, ELF, AMs and lung tissue was 3.1, 2.3, 1674 mg.h/L and 130 mg.h/kg, respectively. For azithromycin-ER formulation, the AUC(0-24) in serum, ELF, AMs and lung tissue were 10.0, 17.6, 7028 mg.h/L and 505 mg.h/kg, respectively. The AUC(0-24) ratio following administration of azithromycin-ER relative to azithromycin-IR was 3.2, 7.7, 4.2 and 3.9 in serum, ELF, AMs and lung tissue, respectively. CONCLUSIONS: Within the first 24 h, a single 2 g azithromycin-ER dose produced dose-related increase in systemic exposure compared with a single 500 mg azithromycin-IR dose, which resulted in higher levels of azithromycin in ELF, AMs and lung tissue. Both formulations had similar safety profiles. By achieving high azithromycin exposure early in the course of treatment, without compromising tolerability, azithromycin-ER shows the potential for improved antibacterial efficacy compared with azithromycin-IR.

Clinical and bacteriological outcomes in hospitalised patients with community-acquired pneumonia treated with azithromycin plus ceftriaxone, or ceftriaxone plus clarithromycin or erythromycin: a prospective, randomised, multicentre study.

This study compared patients with moderate-to-severe community-acquired pneumonia (CAP) requiring hospitalisation, who received initial therapy with either intravenous ceftriaxone plus intravenous azithromycin, followed by step-down to oral azithromycin (n = 135), with patients who received intravenous ceftriaxone combined with either intravenous clarithromycin or erythromycin, followed by step-down to either oral clarithromycin or erythromycin (n = 143). Clinical and bacteriological outcomes were evaluated at the end of therapy (EOT; day 12-16) or at the end of study (EOS; day 28-35). At baseline, mean APACHE II scores were 13.3 and 12.6, respectively, with >50% of patients classified as Fine Pneumonia Severity Index (PSI) category IV or V. Clinical success rates (cure or improvement) in the modified intent-to-treat (MITT) population at EOT were 84.3% in the ceftriaxone/azithromycin group and 82.7% in the ceftriaxone/clarithromycin or erythromycin group. At EOS, MITT success rates (cure only) were 81.7% and 75.0%, respectively. Equivalent success rates in the clinically evaluable population were 83% and 87%, respectively, at EOT, and 79% and 78%, respectively, at EOS. MITT bacteriological eradication rates were 73.2% and 67.4%, respectively, at EOT, and 68.3% vs. 60.9%, respectively, at EOS. Mean length of hospital stay (LOS) was 10.7 and 12.6 days, and the mean duration of therapy was 9.5 and 10.5 days, respectively. The incidence of infusion-related adverse events was 16.3% and 25.2% (p 0.04), respectively. An intravenous-to-oral regimen of ceftriaxone/azithromycin was at least equivalent in efficacy and safety to the comparator regimen and appeared to be a suitable treatment option for hospitalised patients with CAP.

Pediatric AIDS and advanced directives: a three-year prospective study in New York State.

Most HIV-infected families currently receive their care in an ambulatory setting. Ambulatory care provides greater means of medical care, and planning for the infected family members. Advanced Directives (AD) and Do Not Resuscitate (DNR) for adults are now discussed in an ambulatory setting rather than under the duress of a hospital admission. We felt it is important to examine the practice of discussing AD/DNR with the families of pediatric AIDS patients in an out patient setting. Twenty-one and 26 AIDS-designated centers in New York State and five major hospitals in New York City were contacted through a telephone survey in 1991 and 1994, respectively. Questions were designed to obtain demographics of the hospital, pediatric AIDS population, and their DNR/AD policies. In 1991 and 1994, the survey was conducted with the pediatric unit of hospitals with pediatric AIDS. In 1991, only 12 (75%) hospitals had an existing policy on pediatric DNR. No hospital had admitted a patient with AD/DNR obtained as an outpatient, nor were there guidelines at any hospital to approach the issue in an outpatient setting. In 1994, 20 (95%) hospitals had a DNR policy for pediatric patients. We found that even though six patients were admitted with AD obtained as outpatients, no outpatient guidelines existed for AD/DNR for pediatrics. The number of cases of pediatric AIDS in New York State increased by 29.7% for the 1991-1994 period. While pediatric DNR existed in 1991/1994, we found there were presently no guidelines for obtaining AD/DNR for pediatric AIDS patients in an ambulatory setting. Families infected with HIV should have a caring atmosphere to help them address pediatric AD/DNR with their primary care providers. However, we believe that guidelines should be developed to address this issue.

First-trimester spontaneous abortions and the incidence of human immunodeficiency virus seropositivity.

OBJECTIVE: To examine the human immunodeficiency virus (HIV) seropositivity rates and HIV risk factors in women with a confirmed diagnosis of first-trimester spontaneous abortion in a community hospital. STUDY DESIGN: Patients admitted with confirmed diagnoses of spontaneous incomplete first-trimester abortions at Lutheran Medical Center, Brooklyn, New York, from September 1991 to September 1992, were asked to anonymously complete an epidemiologic questionnaire, which was used to study HIV risk factors in our study population. Routine blood work done on admission was used to ascertain the incidence of HIV infection. These rates were compared to the maternal HIV infection rates as determined by the New York City Department of Health. RESULTS: Of the 145 patients enrolled in our study, 11% of patients had HIV risk factors. The seropositivity rate was 0.689% in patients with spontaneous incomplete abortions. CONCLUSION: There was no statistically significant difference between the rate of HIV seropositivity in patients with spontaneous incomplete first-trimester abortions and the overall maternal HIV seropositivity rate, 0.56% (P = .36%) at our institution.