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PubMed2005

Quantitative determination of azithromycin in plasma, blood and isolated neutrophils by liquid chromatography using pre-column derivatization with 9-fluorenylmethyloxycarbonyl-chloride and fluorescence detection.

In this study, a high-performance liquid chromatographic method with pre-column derivatization and fluorescence detection was optimised and validated for the quantification of azithromycin (AZM) in plasma. Clarithromycin (CLM) was used as an internal standard. Pre-column derivatization was done with 9-fluorenylmethyloxycarbonyl-chloride. Recovery from blood and polymorphonuclear neutrophils (PMNNs) isolated by a gravity separation procedure was also assessed. Analytical separation was carried out using a C18 column as stationary phase and acetonitril-phosphatebuffer as mobile phase. Peak quantification was carried out by excitation at 26 7 nm and detection at 317 nm. A lower limit of quantitation of 0.042+/-0.017 mg/l in plasma, 0.119+/-0.065 mg/l in blood and 0.072+/-0.036 in water was achieved. Linearity was assessed from 0 to 1.5mg/l in plasma and blood and from 0-9 mg/l in water. The analytical method proved to be applicable in a pharmacokinetic study of AZM in a Cystic Fibrosis patient.

Anti-Bacterial Agents↗
PubMed2005

A new on-line, in-tube pre-column derivatization technique for high performance liquid chromatographic determination of azithromycin in human serum.

Pre-column derivatization methods for high performance liquid chromatographic assay of specific pharmaceutical agents using 9-fluorenylmethyl chloroformate (FMOC-Cl) have received special attention because highly fluorescent and stable adducts are provided by these methods. However, unlike the post-column on-line techniques, long derivatization time is needed and the reaction cannot be well controlled. A new, sensitive and fast pre-column on-line derivatization technique coupled with high-performance liquid chromatography using FMOC-Cl as labeling agent is described and validated for determination of azithromycin in human serum. After extraction of the drug from serum, the residue was reconstituted in mixture of acetonitrile-phosphate buffer (3:1, v/v; pH 8.5) and directly injected onto the chromatographic system. Continuous on-line derivatization and analysis of the compounds were successfully performed using in-tube elution of FMOC-Cl. The total time needed for derivatization and chromatographic analysis of the drug was 13 min. The assay was reliable and reproducible, with limit of quantification of 10 ng/ml. The described technique may offer significant advantages over existing off-line derivatization methods using FMOC-Cl.

Azithromycin↗
PubMed2005

Regression of subcorneal pustular dermatosis type of IgA pemphigus lesions with azithromycin.

We present our experience with a 56-year-old man who complained for generalized dermatopathy, manifested by skin lesions with diameter from 0.5 to 5 cm. The lesions did not respond to a 20-day systemic steroid regimen. The results of biopsies of three excised lesions, in combination with the clinical manifestations, led to the diagnosis of subcorneal pustular dermatosis type of IgA pemphigus. An unexpected improvement was noted after treatment with azithromycin (which was provided for management of concurrent non-specific urethritis) and local non-potent steroid plus keratolytic agent ointment.

Anti-Bacterial Agents↗
PubMed2005

Antimicrobial therapy for children with adenotonsillar hypertrophy and obstructive sleep apnea: a prospective randomized trial comparing azithromycin vs placebo.

OBJECTIVE: Multiple clinical trials demonstrate the value of administering antibiotics for recurrent tonsillitis. However, there is no consensus as to the role of antibiotics in the management of adenotonsillar hypertrophy and obstructive sleep apnea (OSA). It has been suggested that antibiotics may reduce adenotonsillar size, improve obstructive symptoms, and obviate the need for surgery. The goal of this pilot study was to evaluate the efficacy of a broad-spectrum antibiotic in the management of adenotonsillar hypertrophy and OSA. METHODS: Twenty-two children ages 2 through 12, with evidence of OSA, were enrolled in this double-blinded, prospective clinical trial. Children were randomly assigned into 1 of 2 groups. Group I received azithromycin for a 30-day period (12 mg/kg on days 1-5; the regimen was repeated on days 11-15 and days 21-25). Group II received a placebo administered in the same regimen for a 30-day period. Overnight polysomnography was performed before and within 2 weeks after drug administration. RESULTS: Polysomnographic indices of OSA severity appear to indicate an improvement in the antibiotic as compared to the placebo group, but a comparison of mean +/- standard error for each parameter failed to demonstrate statistical significance using the paired t test. Only 1 of 11 (9%) children had normalization of their polysomnographic parameters. CONCLUSIONS: These results suggest that a course of a broad-spectrum antibiotic may be effective in temporarily improving OSA due to adenotonsillar hypertrophy, but does not appear to obviate the need for surgery.

Adenoids↗
PubMed2005

Simplification and improvement of height-based azithromycin treatment for paediatric trachoma.

Recent data showing that azithromycin is safe at higher dosages than previously documented provide an opportunity to explore several important improvements in the efficiency and effectiveness of height-based treatment of paediatric trachoma. The purpose of this study is to examine the feasibility of a single standardised schedule for application in any trachoma-endemic region. Data for 60813 children from Asia, North and sub-Saharan Africa were analysed. A height schedule maximizing the number of children receiving treatment of 20-40 mg/kg, a conservative estimate of the safe and effective treatment range for paediatric trachoma, was developed. Using the standardised schedule, 97.7% of children aged 6 to 59 months receiving oral suspension and 96.7% of children aged 60 months to 15 years receiving tablets would have received treatment within a dosage range of 20-40 mg/kg. Less than 1% of all children would have received treatment less than 20 mg/kg. These findings suggest that the schedule presented in this paper is likely to yield safe and effective treatment for a broad range of populations vulnerable to trachoma while substantially improving the efficiency of height-based treatment.

Administration, Oral↗
PubMed2004

[Azithromycin therapy in cystic fibrosis].

Progressive lung disease, caused by chronic endobronchial colonization, is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). Several pathogens, including Staphylococcus aureus and Pseudomonas aeruginosa are responsible for this effect. The steadily improving prognosis of CF has been attributed to the use of antibiotics with activity against these organisms. Despite a significant increase in the amount of published material demonstrating the potential role of macrolide antibiotics as antiinflammatory agents and their effects on bacterial virulence, their mechanism of action in CF patients is still unknown. Although there is a limited number of clinical trials assessing the efficacy and safety of azithromycin (AZM) in CF, increasing evidence suggests that 3 to 6-month AZM treatment in CF patients is safe and well tolerated. This treatment results in clinical improvement, decreasing the number of pulmonary exacerbations and increasing pulmonary function. Therefore, chronic treatment with AZM should be considered in CF patients added to conventional therapy. Clinical experience with macrolides other than AZM in CF patients is very limited.

Anti-Bacterial Agents↗
PubMed2003

Targeted mass treatment for syphilis with oral azithromycin.

From mid 1997 to end of 1999, there was a sexually-transmitted infectious syphilis outbreak mainly in heterosexual people in British Columbia, Canada, that was concentrated in Vancouver. The rate across the province increased from less than 0.5 to 3.4 per 100000, and the rate in Vancouver reached 12.9 per 100000. We aimed to eliminate the syphillis outbreak by treating people at risk of infection. In 2000, a targeted mass treatment programme provided azithromycin (1.8 g orally) to 4384 at-risk residents in this city. After the programme, syphilis frequency fell significantly for 6 months (p=0.016), but rose again in 2001. Results from curve fitting analyses showed that the number of cases in 2001 (177) was higher than expected (0.0001<p<0.0044). This rate rebound and the absence of a sustained effect suggest that targeted mass treatment for syphilis, even though feasible, should not be done routinely.

Adolescent↗
PubMedDate not supplied

Treatment of nontuberculous mycobacterial infections: role of clarithromycin and azithromycin.

The incidence of identification of nontuberculous mycobacteria has increased since the advent of the acquired immunodeficiency syndrome epidemic. Although Mycobacterium avium complex appears to be responsible for most episodes of nontuberculous disease, several other previously rare species are increasingly being detected, including Mycobacterium kansasii, Mycobacterium fortuitum/chelonei complex, and Mycobacterium genavense. This review briefly summarizes the epidemiology and clinical features of these infections, as well as therapeutic and preventive strategies in immunosuppressed patients with nontuberculous mycobacterial infections. Of clinical relevance, nontuberculous mycobacterial infections are difficult to treat and do not respond to traditional antituberculous agents. The search for more effective treatment regimens is ongoing in an attempt to enhance survival and reduce morbidity among immunocompromised patients. Novel antimicrobial combinations that include clarithromycin or azithromycin have been shown to be effective in treating several nontuberculous mycobacterial infections.

AIDS-Related Opportunistic Infections↗
PubMed2002

A new HPLC method for azithromycin quantitation.

A simple liquid chromatographic method was developed for the estimation of azithromycin raw material and in pharmaceutical forms. The sample was chromatographed on a reverse phase C18 column and eluants monitored at a wavelength of 215 nm. The method was accurate, precise and sufficiently selective. It is applicable for its quantitation, stability and dissolution tests.

Anti-Bacterial Agents↗
PubMed2003

LC determination of impurities in azithromycin tablets.

A LC method with UV detection for determining azithromycin impurities in tablets as pharmaceutical form has been developed. It is to be employed in routine and stability tests. A linear gradient elution was employed starting with 47% A and 53% B to reach 28% A and 72% B at 48 min. Mobile phase A was KH2PO4 10 mM (H2O) at pH 7.00. B was a mixture methanol:acetonitrile 1:1 (v/v). UV detection was performed at 210 nm. The chromatographic column was Phenomenex Synergi MAX-RP 4 microm 250 x 460 mm kept at 50 degrees C. Six impurities were separated and identified and it was possible to quantify five out of the six with reasonable accuracy and precision.

Acids↗
PubMed1998

Synthesis of 6-O-methyl-azithromycin and its ketolide analogue via Beckmann rearrangement of 9(E)-6-O-methyl-erythromycin oxime.

The synthesis of 6-O-methyl-azithromycin and its aza-ketolide analogue have been achieved by carrying out the Beckmann rearrangement of the readily available 9(E)-6-O-methyl-erythromycin oxime 1. In contrast to the C14 ketolides like HMR 3647, the aza-ketolide turns out to be inactive, thus demonstrating that the addition of a 3 keto function and ring expansion, from 14 to 15 membered ring, could be deleterious for the antibacterial activity.

Anti-Bacterial Agents↗
PubMed1997

Roxithromycin, clarithromycin, and azithromycin attenuate the injurious effects of bioactive phospholipids on human respiratory epithelium in vitro.

The effects of the bioactive phospholipids (PL), platelet-activating factor (PAF), lyso-PAF, and lysophosphatidylcholine (LPC) on the beat frequency and structural integrity of human ciliated respiratory epithelium were studied in vitro, in the presence or absence of polymorphonuclear leukocytes (PMNL), the antimicrobial agents, roxithromycin, clarithromycin, and azithromycin and the antioxidative enzymes catalase and superoxide dismutase (SOD). All three PL caused dose-dependent slowing of ciliary beat frequency (CBF) and epithelial damage (ED) at concentrations > or = 1 microgram/ml, which were unaffected by inclusion of the antimicrobial agents and antioxidative enzymes. When epithelial strips were exposed to the combination of PMNL and PL, there was significant potentiation of ciliary dysfunction and ED, which was ameliorated by pretreatment of the PMNL with the antimicrobial agents or by inclusion of catalase, but not SOD. These results demonstrate that LPC, PAF, and lyso-PAF cause epithelial damage by direct mechanisms which are oxidant-independent, as well as by indirect mechanisms involving phagocyte-derived reactive oxidants. Macrolides and azalide antimicrobial agents may have beneficial effects on airway inflammation in asthma and microbial infections by protecting ciliated epithelium against oxidative damage inflicted by PL-sensitized phagocytes.

Anti-Bacterial Agents↗
PubMed1997

Cryptosporidiosis after CD34-selected autologous peripheral blood stem cell transplantation (PBSCT). Treatment with paromomycin, azithromycin and recombinant human interleukin-2.

We report two cases of cryptosporidiosis after CD34-selected PBSCT for lymphoma. While the first patient died of pulmonary cryptosporidiosis, treatment with paromomycin, azithromycin and subcutaneous low-dose rhIL-2 to improve numerical and functional T lymphocyte defects completely eliminated infection in the second patient. We conclude, that the removal of mature T lymphocytes by positive selection of CD34+ cells bears the risk of a delayed immune reconstitution resulting in an increased incidence of severe and sometimes fatal opportunistic infections. IL-2 might be useful in this situation by accelerating immune reconstitution and reducing the danger of opportunistic infections.

Adult↗
PubMed2006

In vitro efficacy, resistance selection, and structural modeling studies implicate the malarial parasite apicoplast as the target of azithromycin.

Azithromycin (AZ), a broad-spectrum antibacterial macrolide that inhibits protein synthesis, also manifests reasonable efficacy as an antimalarial. Its mode of action against malarial parasites, however, has remained undefined. Our in vitro investigations with the human malarial parasite Plasmodium falciparum document a remarkable increase in AZ potency when exposure is prolonged from one to two generations of intraerythrocytic growth, with AZ producing 50% inhibition of parasite growth at concentrations in the mid to low nanomolar range. In our culture-adapted lines, AZ displayed no synergy with chloroquine (CQ), amodiaquine, or artesunate. AZ activity was also unaffected by mutations in the pfcrt (P. falciparum chloroquine resistance transporter) or pfmdr1 (P. falciparum multidrug resistance-1) drug resistance loci, as determined using transgenic lines. We have selected mutant, AZ-resistant 7G8 and Dd2 parasite lines. In the AZ-resistant 7G8 line, the bacterial-like apicoplast large subunit ribosomal RNA harbored a U438C mutation in domain I. Both AZ-resistant lines revealed a G76V mutation in a conserved region of the apicoplast-encoded P. falciparum ribosomal protein L4 (PfRpl4). This protein is predicted to associate with the nuclear genome-encoded P. falciparum ribosomal protein L22 (PfRpl22) and the large subunit rRNA to form the 50 S ribosome polypeptide exit tunnel that can be occupied by AZ. The PfRpl22 sequence remained unchanged. Molecular modeling of mutant PfRpl4 with AZ suggests an altered orientation of the L75 side chain that could preclude AZ binding. These data imply that AZ acts on the apicoplast bacterial-like translation machinery and identify Pfrpl4 as a potential marker of resistance.

Amodiaquine↗
PubMed2003

Pattern of antibiotic use in a trachoma-endemic region of Nepal: implications for mass azithromycin distribution.

PURPOSE: To investigate antibiotic utilization in a rural district of western Nepal that is currently receiving azithromycin as part of a trachoma program and is being monitored by the Centers for Disease Control and Prevention (CDC) for drug resistance. METHODS: Antibiotic purchase receipts were collected for 3 months from all medicine halls, pharmacies, and government sub-health posts in a sub-district of Western Nepal. Supplementary surveys of antibiotic sales were performed in different seasons. RESULTS: Macrolides account for 3.9% of total antibiotic use, far less than quinolones, penicillins, tetracyclines, and sulfonamides. CONCLUSIONS: If trachoma programs in Western Nepal generate transient macrolide resistance in pneumococcus and other bacteria, the epidemiological impact may not be great, as macrolides are not commonly used in the area.

Anti-Bacterial Agents↗
PubMed2000

Bacteremic pneumonia due to multidrug-resistant pneumococci in 3 patients treated unsuccessfully with azithromycin and successfully with levofloxacin.

Three patients with bacteremic pneumonia caused by multidrug-resistant Streptococcus pneumoniae were treated unsuccessfully with azithromycin. One S. pneumoniae isolate carried a mef determinant for an efflux pump; a second isolate had an erm determinant. All 3 patients were successfully treated with levofloxacin, an antipneumococcal fluoroquinolone.

Adult↗
PubMed2000

Rationale and design of a secondary prevention trial of antibiotic use in patients after myocardial infarction: the WIZARD (weekly intervention with zithromax [azithromycin] for atherosclerosis and its related disorders) trial.

Mounting evidence supports the contention that atherosclerosis is an inflammatory disease. Recently a possible role for infectious microorganisms has gathered attention. Chlamydia pneumoniae is one possible pathogen. If C. pneumoniae is a target organism, antibiotics with antichlamydial activity may be able to ameliorate plaque instability. The WIZARD trial is a secondary prevention study that is assessing the impact of a 3-month course of azithromycin compared with placebo on the progression of clinical coronary heart disease. The study will enroll 3300 patients who have had a prior myocardial infarction and who have a C. pneumoniae IgG titer of >/=1:16. The primary end point is a composite of time to either recurrent myocardial infarction, death, a revascularization procedure, or hospitalization for angina. This study is the first of a series of adequately powered clinical trials that will attempt to bridge insights from preclinical investigations to interventions applicable to patient care.

Anti-Bacterial Agents↗
PubMed2000

Breakthrough pneumococcal bacteremia in patients being treated with azithromycin and clarithromycin.

Streptococcus pneumoniae strains have exhibited decreasing susceptibility to penicillins and macrolides during the past several years. We reviewed the medical charts of all patients with pneumococcal bacteremia who were admitted to a university hospital over a period of 1 year, to identify failures of outpatient therapy. Of 41 patients admitted with pneumococcal bacteremia, 4 had previously taken either azithromycin or clarithromycin for 3-5 days. All 4 had pneumococcal strains that exhibited low-level resistance to macrolide antibiotics. Among pneumococci, low-level resistance to macrolides can lead to clinical failure, and resistance to macrolides should be considered during the selection of empiric therapy for patients with presumed pneumococcal infections.

Aged↗