zithromax and dirithromycin

Erythromycins have been part of our armamentarium against selected bacterial infections since they were discovered in 1952 and approved by the Food and Drug Administration (FDA) in 1964. In 1991, two newer, long-acting erythromycin analogues, azythromycin (brand name: Zithromax) and clarithromycin (brand name: Biaxin) were approved by the FDA. They were joined a few years later by a third long-acting form, dirithromycin (brand name: Dynabac).

Topics: Ambulatory Care; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Clarithromycin; Delayed-Action Preparations; Erythromycin; Humans; Tooth Diseases

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Clinical Trials as Topic; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Drug Interactions; Erythromycin; Humans; Macrolides; Mixed Function Oxygenases; Substrate Specificity

When treating oral infections, clinicians have used the macrolide antibiotic erythromycin as an alternative antibiotic for patients who have documented allergic reactions to penicillins. In this article, the author reports on his assessment of the pharmacology of erythromycin and the newer macrolide antibiotics, as well as of their indications for the prevention of bacterial endocarditis and their possible use for oral-dental infections.. The author reviewed the current clinical pharmacology literature with specific emphasis on reports indicating these antibiotics' efficacy in treating oral-dental infections.. Azithromycin, clarithromycin and dirithromycin are erythromycin analogues that are currently marketed in the United States. All three have the therapeutic advantages over erythromycin of longer durations of action, enhanced acid stabilities and improved tissue distributions. A lower incidence of gastrointestinal distress and abdominal cramping is reported for all three of these newer agents than for erythromycin. Azithromycin and dirithromycin do not appear to compete for the same hepatic drug-metabolizing enzymes as erythromycin and therefore are not associated with the same drug interactions.. The newer macrolide antibiotics offer the advantage of fewer adverse gastrointestinal effects than erythromycin and dosing regimens of only once or twice a day. Yet, the extremely high price of the newer macrolides compared with that of erythromycin limits their routine use.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Clarithromycin; Cytochrome P-450 Enzyme System; Delayed-Action Preparations; Dental Care for Chronically Ill; Drug Costs; Endocarditis, Bacterial; Erythromycin; Focal Infection, Dental; Humans; Liver; Macrolides; Prodrugs; Tissue Distribution

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.. A MEDLINE search of English-language literature during the years 1966-1996, and an extensive review of journals were conducted to prepare this article.. 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.. 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.. 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.

Topics: Anti-Bacterial Agents; Azithromycin; Bacteria, Anaerobic; Clarithromycin; Drug Interactions; Erythromycin; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Macrolides; Respiratory Tract Infections

The determination of the French breakpoints (< or = c, > C) were selected by the use of different criteria including bacteriological, pharmacokinetic and obviously clinical criteria. Concerning the bacteriological results, azithromycin, being an acid stable orally administered antimicrobial drug, is in vitro marginally less active than erythromycin against Gram-positive organisms including beta-haemolytic streptococci and Staphylococcus aureus. But in contrast, this azalide is more active than erytromycin against many Gram-negative pathogens, notably Neisseria gonorrhoeae, H. influenzae, Branhamella (Moraxella) catarrhalis, Ureaplasma urealyticum, and Borrelia burgdorferi. The activity of azithromycin is unaffected by the inoculum, unlike of pH, serum, and presence of CO2 for anaerobes. However, erythromycin-resistant micro-organisms are also resistant to azithromycin. Considering the pharmacokinetic criteria and the clinical results such as infections of the lower and upper respiratory tracts, skin and soft tissues, uncomplicated urethritis/cervicitis associated with N. gonorrhoeae, Chlamydia trachomatis or U. urealyticum, the preliminary breakpoints of azithromycin are defined by the following concentrations (< or = 0.12 and > 4 mg/l). Additional experimental and clinical results are required to confirm the in vitro activity against some other bacterial species (E. faecalis, L. monocytogenes, Brucella, P. multocida, or even Salmonella and Shigella).

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Erythromycin; Gram-Negative Bacteria; Gram-Positive Bacteria; Hydrogen-Ion Concentration; In Vitro Techniques; Macrolides

To review the chemistry, antimicrobial spectrum, pharmacokinetics, clinical trials, adverse effects, and drug interactions of four new macrolide antibiotics: azithromycin, clarithromycin, dirithromycin, and roxithromycin.. Information was obtained from comparative clinical trials, abstracts, conference proceedings, and review articles. Indexing terms included azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, and macrolide antibiotics.. Emphasis was placed on comparative clinical trials involving the new macrolide antibiotics.. Data from human studies published in the English language were evaluated. Trials were assessed by sample size, macrolide dosage regimen, and therapeutic response.. The erythromycins have gained widespread use in treating a variety of infections. Although they are effective, limitations include the need to administer four times a day and the intolerable adverse gastrointestinal effects. Four of the more extensively studied agents, azithromycin, clarithromycin, dirithromycin, and roxithromycin, are currently being studied in patients. Based on the studies to date, the newer macrolides may offer several advantages over erythromycin, including: (1) greater antimicrobial activity against certain organisms; (2) longer elimination half-life, thus allowing less frequent administration; and (3) lower incidence of adverse gastrointestinal effects.. The new macrolide antibiotics appear to offer an improvement over erythromycin. Definitive conclusions about the role of these drugs should await completion of ongoing clinical studies.

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Clinical Trials as Topic; Drug Interactions; Erythromycin; Humans; Macrolides; Roxithromycin

Short-term use of antibiotics has become a common component of the management of acute exacerbations of chronic bronchitis (AECB), particularly in complex cases with productive cough or purulent phlegm. The macrolide antibiotics, particularly second-generation agents such as dirithromycin and azithromycin, are among the antibiotic classes frequently recommended and used to treat upper and lower respiratory infections, including AECB.. This study compared the clinical efficacy and tolerability of 5-day courses of dirithromycin and azithromycin given once daily for the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD).. This randomized, investigator-blinded, parallel-group clinical trial was conducted at 5 centers in the United States. Eligible patients were adult (age >35 years) smokers or ex-smokers (smoking history of at least 10 pack-years) with chronic bronchitis and an acute exacerbation, defined by the occurrence of increased dyspnea and/or productive cough and feverishness within 48 hours of enrollment. Before randomization, an attempt was made to obtain a sputum specimen from each patient for Gram's staining and culture. Patients were randomized to receive dirithromycin 500 mg QD for 5 days or azithromycin 500 mg QD on day 1 and 250 mg QD on days 2 to 5. Clinical efficacy was assessed separately by patients and physicians at early (days 7-10) and late (days 25-35) posttreatment visits.. Eighty-six patients (48 women, 38 men; mean age, 55 years) with a mean smoking history of 31 pack-years were included in the intent-to-treat analysis. Forty-six (54%) patients were randomized to dirithromycin and 40 (47%) patients to azithromycin. Clinical efficacy was reported in a high proportion of patients in both treatment groups, both at the early posttreatment visit (84.8% dirithromycin, 75.7% azithromycin; difference dirithromycin - azithromycin, 9.1%; 95% CI, -8.2 to 26.4) and the late posttreatment visit (95.5% and 86.5%, respectively; difference dirithromycin - azithromycin, 9.0%; 95% CI, -3.7 to 21.6). A similar proportion of patients required a second course of antibiotics over the study period (20.5% dirithromycin, 27.0% azithromycin; difference dirithromycin - azithromycin, -6.6%; 95% CI, -25.2 to 12.1). Only 42 (48.8%) patients were able to produce a sputum sample before receiving study treatment, and of these, only 20 (47.6%) demonstrated a preponderance of neutrophils on Gram's staining. Both treatments were well tolerated.. The results of this study suggest comparable clinical efficacy between 5-day courses of once-daily dirithromycin and azithromycin in acute exacerbations of COPD. There were insufficient data to permit meaningful comparison of the bacteriologic efficacy of these macrolide antibiotics.

Topics: Acute Disease; Administration, Oral; Anti-Bacterial Agents; Azithromycin; Drug Administration Schedule; Erythromycin; Female; Humans; Macrolides; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Single-Blind Method; Time Factors; Treatment Outcome

We compared the clinical and microbiological efficacy of dirithromycin with that of azithromycin in outpatients with acute bacterial exacerbations of chronic bronchitis who could be graded into stage III according to Ball's system of stratification. A total of 80 patients was studied. Of these, 40 were treated with dirithromycin as a once-daily dose of 500 mg for 5 days, and 40 with azithromycin as a once-daily dose of 500 mg for 3 days. At post-therapy, treatment success (cure or improvement) was achieved in 36 out of 40 (90%) patients receiving dirithromycin compared with 37 out of 40 (92.5%) in the azithromycin group. At the late post-therapy visit, 34 out of 36 (94.4%) dirithromycin-treated patients were cured as were 33 of 37 (89.2%) azithromycin-treated patients. A small proportion of patients treated with dirithromycin (10%) or with azithromycin (12.5%) suffered mild side effects. Gastrointestinal disorders, including abdominal cramps, nausea, or diarrhea, were common adverse effects. The main pathogens isolated before treatment were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Eradication rates at the end of treatment were 90% (36 out of 40) for the dirithromycin group and 92.5% (37 out of 40) for the azithromycin group. Persistence of H. influenzae isolates was found in 3 out of 11 (27.3%) patients treated with dirithromycin and in 2 out of 9 (22.2%) who had received azithromycin. At the late post-therapy visit, eradication occurred in 34 out of 36 (94.4%) strains in the dirithromycin group and in 33 out of 37 (89.2%) in the azithromycin group. We conclude that dirithromycin and azithromycin appear to be equally effective in the treatment of acute bacterial exacerbations of chronic bronchitis.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchitis; Drug Costs; Erythromycin; Female; Haemophilus influenzae; Humans; Macrolides; Male; Middle Aged; Moraxella catarrhalis; Streptococcus pneumoniae; Treatment Outcome

Due to the emergency and uncontrolled situation caused by the COVID-19 pandemic that arising in the entire world, it is necessary to choose available drugs that can inhibit or prevent the disease. Therefore, the repurposing of the commercial antibiotic, dirithromycin has been screened for the first time against fifteen receptors and compared to the azithromycin using a molecular docking approach to identify possible SARS-CoV-2 inhibitors. Our docking results showed that dirithromycin fit significantly in the Furin catalytic pocket having the lowest binding score (-9.9 Kcal/mol) with respect to azithromycin (-9.4 Kcal/mol) and can interact and block both Asp154 and Ser368 residues by Van der Walls interaction as well as bound to His194 and Ser368 residues via hydrogen bonds. Good results were also obtained with the Tmprss-2 receptor. A Molecular Dynamic simulation was assessed to confirm this interaction. Additionally, detailed receptor-ligand interactions with SARS-CoV-2 and pro-inflammatory mediators were investigated suggesting more target information with interesting results. The findings of this study are very efficient and provide a basis for the development of dirithromycin for clinical trial applications to be efficient in treating SARS-CoV-2 infections.

Topics: Antiviral Agents; Azithromycin; COVID-19 Drug Treatment; Erythromycin; Humans; Molecular Docking Simulation; Molecular Dynamics Simulation; Pandemics; SARS-CoV-2; Viral Nonstructural Proteins

Topics: Animals; Antiprotozoal Agents; Azithromycin; Entamoeba histolytica; Erythromycin; Parasitic Sensitivity Tests

The potential of 14/15 membered macrolides to cause phospholipidosis has been prospectively assessed, and structure-effects examined, using combined experimental and conformational approaches. Biochemical studies demonstrated drug binding to phosphatidylinositol-containing liposomes and inhibition of the activity of lysosomal phospholipase A1 toward phosphatidylcholine included in the bilayer, in close correlation with the number of cationic groups carried by the drugs (erythromycin A

Topics: Anti-Bacterial Agents; Azithromycin; Cell-Free System; Cells, Cultured; Computer Simulation; Enzyme Inhibitors; Erythromycin; Macrolides; Molecular Conformation; Phospholipases A; Phospholipases A1; Phospholipids; Roxithromycin

We evaluated a human monocyte cell line (HL-60) as a model for testing the intracellular activity of anti-Legionella antibiotics; 1.5 x 10(6) HL-60 cells/well were differentiated into adherent cells and infected with 1.5 x 10(7) cfu of Legionella pneumophila. The most active agents against L. pneumophila as judged by broth dilution MICs were (in order of activity) azithromycin, clarithromycin, roxithromycin, quinupristin/dalfopristin, erythromycin and dirithromycin. The most active inhibitors of L. pneumophila intracellular multiplication were (in order of activity) azithromycin, erythromycin, quinupristin/dalfopristin, roxithromycin, dirithromycin and clarithromycin. All the agents were highly active against Legionella micdadei and Legionella bozemanii when compared with L. pneumophila.

Topics: Anti-Bacterial Agents; Azithromycin; Cell Line; Clarithromycin; Erythromycin; HL-60 Cells; Humans; Legionella; Legionella pneumophila; Macrolides; Microbial Sensitivity Tests; Monocytes; Roxithromycin; Virginiamycin

Agar dilution with incubation in air and CO2 was used to determine the MICs of erythromycin, dirithromycin, azithromycin, clarithromycin, roxithromycin, and clindamycin for 79 penicillin-susceptible, 72 penicillin-intermediate, and 74 penicillin-resistant pneumococci (158 erythromycin-susceptible and 67 erythromycin-resistant pneumococci). MICs obtained in air were usually 1 to 3 dilutions lower than those obtained in CO2. In air, the respective MICs at which 50% (MIC50s) and 90% (MIC90s) of penicillin-susceptible, -intermediate, and -resistant strains are inhibited were as follows: erythromycin, 0.016 and 0.5, 0.03 and > 64, and 2 and > 64 microg/ml; dirithromycin, 0.03 and 0.5, 0.06 and > 64, and 8 and > 64 microg/ml; azithromycin, 0.03 and 0.5, 0.06 and > 64, and 2 and > 64 microg/ml; clarithromycin, 0.016 and 0.06, 0.03 and > 64, and 2 and > 64 microg/ml; roxithromycin, 0.06 and 2, 0.06 and > 64, and 2 and > 64 microg/ml; and clindamycin, 0.03 and 0.06, 0.06 and > 64, and 0.06 and > 64 microg/ml. The MICs of erythromycin, azithromycin, and dirithromycin were very similar; however, clarithromycin MICs were generally 1 to 2 dilutions lower and roxithromycin MICs were 1 to 2 dilutions higher than those of the other compounds tested. Strains resistant to one macrolide were resistant to all macrolides; however, not all macrolide-resistant strains were resistant to clindamycin, and 32 macrolide-resistant (MICs, > or = 28 microg/ml), clindamycin-susceptible (MICs, < or = 0.25 microg/ml) strains were encountered. Time-kill testing of six strains showed similar killing kinetics for all compounds, with 99.9% killing of all strains observed with the compounds only at or above the MIC after 24 h.

Topics: Aminoglycosides; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Clindamycin; Erythromycin; Macrolides; Microbial Sensitivity Tests; Penicillin Resistance; Penicillins; Roxithromycin; Streptococcus pneumoniae

The purpose of this study was to compare the in vitro activity of a new ketolide, HMR 3004 (RU64004), to that of three macrolides and one azalide against 608 Streptococcus pneumoniae and 202 Haemophilus influenzae. Macrolide-resistant pneumococci were susceptible to HMR 3004, even if they were resistant to clindamycin. Against Haemophilus influenzae, HMR 3004 and azithromycin were nearly identical in potency; the macrolides were 8- to 16-fold less active. HMR 3004 may be useful for treating respiratory tract infections if sufficient concentrations can be achieved at the local sites of infection.

Topics: Ampicillin Resistance; Anti-Bacterial Agents; Azithromycin; beta-Lactamases; Clarithromycin; Clindamycin; Drug Resistance, Microbial; Erythromycin; Haemophilus influenzae; Ketolides; Macrolides; Microbial Sensitivity Tests; Roxithromycin; Streptococcus pneumoniae

Azithromycin was shown to specifically inhibit the protein synthesis of Toxoplasma gondii in experimental systems by using free tachyzoites and T. gondii-infected mouse macrophages. RNA synthesis of the parasite was not affected by azithromycin. Inhibition of protein synthesis was also proportional to the relative anti-Toxoplasma activity of three macrolides.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Cells, Cultured; Erythromycin; Macrolides; Macrophages; Methionine; Mice; Protozoan Proteins; RNA, Protozoan; Sulfur Radioisotopes; Time Factors; Toxoplasma

MICs and MBCs of four new macrolides (azithromycin, clarithromycin, dirithromycin and roxithromycin) and two older macrolides (erythromycin and josamycin) for Bordetella pertussis and Bordetella parapertussis were determined. The activity of the new macrolides was as good as that of erythromycin, while josamycin was slightly less active. Bordetella parapertussis was more resistant than Bordetella pertussis.

Topics: Anti-Bacterial Agents; Azithromycin; Bordetella; Bordetella pertussis; Clarithromycin; Drug Resistance, Microbial; Erythromycin; Leucomycins; Macrolides; Microbial Sensitivity Tests