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Sample records for azithromycin suppresses interleukin-12p40

  1. Azithromycin suppresses interleukin-12p40 expression in lipopolysaccharide and interferon-γ stimulated macrophages

    PubMed Central

    Yamauchi, Keiko; Shibata, Yoko; Kimura, Tomomi; Abe, Shuichi; Inoue, Sumito; Osaka, Daisuke; Sato, Michiko; Igarashi, Akira; Kubota, Isao

    2009-01-01

    Azithromycin (AZM), a 15-member macrolide antibiotic, possesses anti-inflammatory activity. Macrophages are important in innate and acquired immunity, and produce pro-inflammatory cytokines such as interleukin (IL)-12, which are composed of subunit p40 and p35. The key function of IL-12 is the induction and maintenance of T-helper-1 responses, which is associated with the pathogenesis of chronic inflammatory diseases. We investigated the effect of azithromycin on IL-12p40 production in macrophages after lipopolysaccharide (LPS)/interferon (IFN)-γ stimulation. RAW264.7 macrophage cell line was pre-treated with vehicle or AZM, followed by the stimulation with LPS/IFN-γ. We measured IL-12 production by RT-PCR and ELISA. IL-12 transcriptional regulation was assessed by electrophoretic mobility shift assay and reporter assay. Phosphorylation of activator protein (AP)-1 and interferon consensus sequence binding protein (ICSBP) was assessed by immunoprecipitation using phosphotyrosine antibody, and immunoblotting using specific antibodies against JunB and ICSBP. AZM reduced the induction of IL-12p40 by LPS/IFN-γ in a dose dependent manner. AZM inhibited the binding of AP-1, nuclear factor of activated T cells (NFAT), and ICSBP, to the DNA binding site in the IL-12p40 promoter. AZM also reduced LPS/IFN-γ-induced IL-12p40 promoter activity. Phosphorylation of JunB and ICSBP was inhibited by azithromycin-treatment in stimulated cells. In conclusion, AZM reduced IL-12p40 transcriptional activity by inhibiting the binding of AP-1, NFAT, and ICSBP to the promoter site. This may represent an important mechanism for regulating the anti-inflammatory effects of AZM in macrophages. PMID:19893639

  2. A protease-activated receptor 2 agonist (AC-264613) suppresses interferon regulatory factor 5 and decreases interleukin-12p40 production by lipopolysaccharide-stimulated macrophages: Role of p53.

    PubMed

    Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Ishimaru, Yasuji; Narahara, Shinji; Sugiuchi, Hiroyuki; Yamaguchi, Yasuo

    2016-06-01

    The transcription factor interferon regulatory factor 5 (IRF5) has a key role in the production of interleukin (IL)-12 by macrophages. IRF5 is also a central mediator of toll-like receptor signaling and is a direct target of p53. Activation of protease-activated receptor 2 (PAR-2) upregulates p53 and suppresses apoptosis. This study investigated the influence of human neutrophil elastase (HNE) and PAR-2 agonists on expression of IRF5 and IL-12p40 by macrophages stimulated with lipopolysaccharide. Granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent macrophages showed upregulation of IRF5 expression, while HNE reduced expression of p53 and IRF5 in a concentration-dependent manner. HNE also caused a concentration-dependent decrease of IRF5 in macrophages transfected with small interfering RNA to silence p53, while silencing of β-arrestin 2 blunted the reduction of p53 or IRF5 by HNE. Incubation of macrophages with a PAR-2 agonist, AC-264613, caused a decrease of IRF5 expression and also significantly reduced p53 protein expression. HNE upregulated the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) and caused transactivation of TLR4, while AC-264613 did not promote TLR4 transactivation. In conclusion, the PAR-2 agonist AC-264613 attenuated IRF5-associated IL-12p40 production by macrophages. PMID:26833899

  3. Azithromycin

    MedlinePlus

    ... full dose of medication.If you receive azithromycin powder for suspension in the single-dose, 1-gram ... receive azithromycin extended-release suspension as a dry powder you must first add water to the bottle ...

  4. Azithromycin

    MedlinePlus

    ... of lung infection that often affects people with human immunodeficiency virus (HIV)]. Azithromycin is in a class ... blood infection; heart failure; cystic fibrosis; AIDS or human immunodeficiency virus (HIV) infection; myasthenia gravis (a condition ...

  5. Azithromycin suppresses CD4+ T-cell activation by direct modulation of mTOR activity

    PubMed Central

    Ratzinger, F.; Haslacher, H.; Poeppl, W.; Hoermann, G.; Kovarik, J. J.; Jutz, S.; Steinberger, P.; Burgmann, H.; Pickl, W. F.; Schmetterer, K. G.

    2014-01-01

    Advanced macrolides, such as azithromycin (AZM) or clarithromycin (CLM), are antibiotics with immunomodulatory properties. Here we have sought to evaluate their in vitro influence on the activation of CD4+ T-cells. Isolated CD4+ T-cells were stimulated with agonistic anti-CD3/anti-CD28 monoclonal antibodies in the presence of 0.6 mg/L, 2.5 mg/L, 10 mg/L or 40 mg/L AZM or CLM. Cell proliferation, cytokine level in supernatants and cell viability was assessed. Intracellular signaling pathways were evaluated using reporter cell lines, FACS analysis, immunoblotting and in vitro kinase assays. AZM inhibited cell proliferation rate and cytokine secretion of CD4+ T-cells in a dose-dependent manner. Similarly, high concentrations of CLM (40 mg/L) also suppressed these T-cell functions. Analysis of molecular signaling pathways revealed that exposure to AZM reduced the phosphorylation of the S6 ribosomal protein, a downstream target of mTOR. This effect was also observed at 40 mg/L CLM. In vitro kinase studies using recombinant mTOR showed that AZM inhibited mTOR activity. In contrast to rapamycin, this inhibition was independent of FKBP12. We show for the first time that AZM and to a lesser extent CLM act as immunosuppressive agents on CD4+ T-cells by inhibiting mTOR activity. Our results might have implications for the clinical use of macrolides. PMID:25500904

  6. Azithromycin Can Prolong QT Interval and Suppress Ventricular Contraction, but Will Not Induce Torsade de Pointes.

    PubMed

    Ohara, Hiroshi; Nakamura, Yuji; Watanabe, Yudai; Cao, Xin; Yamazaki, Yukiko; Izumi-Nakaseko, Hiroko; Ando, Kentaro; Yamazaki, Hiroshi; Yamazaki, Junichi; Ikeda, Takanori; Sugiyama, Atsushi

    2015-07-01

    Azithromycin has been reported to increase the risk of death from cardiovascular causes among patients with high baseline risk. Since the information is still limited to bridge the gap between electrophysiological properties of azithromycin in vitro and cardiac death in patients, we initially assessed its electropharmacological effects in doses of 3 and 30 mg/kg, i.v., with the halothane-anesthetized dogs (n = 4). The low dose provided 5.2 times higher than the therapeutic concentration, whereas the high dose attained 17.0 times higher. The high dose delayed the ventricular repolarization in a reverse use-dependent manner, reflecting blockade of the rapid component of delayed rectifier K(+) current, and the potency was relatively weak; namely, maximum change in QTc was +20 ms (+5.6%). The high dose also induced the negative inotropic effect possibly through Ca(2+) channel-independent pathway. In order to clarify proarrhythmic risk, 30 mg/kg, i.v., of azithromycin was examined with the chronic atrioventricular block dogs (n = 4). Azithromycin neither induced torsade de pointes nor affected beat-to-beat variability of repolarization. Thus, azithromycin can be considered to lack proarrhythmic potential, but caution has to be paid on its use for patients with left ventricular dysfunction. PMID:25367413

  7. Inflammation and Elevation of Interleukin-12p40 in Patients with Schizophrenia.

    PubMed

    Bedrossian, Nora; Haidar, Mariam; Fares, Jawad; Kobeissy, Firas H; Fares, Youssef

    2016-01-01

    Schizophrenia is a serious mental illness with chronic symptoms and significant impairment in psychosocial functioning, which suggests that it likely has neurodegenerative characteristics. Inflammatory markers such as pro-inflammatory cytokines are well-known etiological contributors for psychiatric disorders, including schizophrenia. Although, the role of inflammation in schizophrenia is becoming evident, the number of studies in this area is relatively scarce, especially in Lebanon, and increased procedural thoroughness is needed. Cytokines play a key role in the activation of the immune system and strongly influence neurotransmission. Previous investigation of plasma levels showed dysregulation of interleukin (IL)-12. However, genotypical variations of this interleukin have not been investigated for patients with schizophrenia yet. Thus, in this paper, we aimed to compute and assess IL-12p40 levels in the sera of individuals with schizophrenia from different provinces in Lebanon and compare it to controls. Healthy subjects comprised 60 individuals with a male/female (M/F) ratio of 31/29, whereas patients with schizophrenia consisted of 63 subjects with an M/F ratio of 30/33. The mean age for healthy controls was 30 years, whereas that for patients with schizophrenia was 35 years. A standardized enzyme-linked immunosorbent assay (ELISA) technique was used to measure the concentration of IL-12p40 in all collected sera (n = 123). The mean IL-12p40 levels in patients with schizophrenia were significantly higher than in healthy controls (p = 0.002). Healthy females had a significantly higher concentration of IL-12p40 than healthy males (p = 0.009). Female patients with schizophrenia had significantly higher concentrations of IL-12p40 than their male counterparts (p < 0.001), healthy females (p = 0.018), and healthy males (p < 0.001), respectively. Male patients with schizophrenia had significantly higher concentrations of IL-12p40 than healthy males (p = 0.023). The study's results suggest that IL-12p40 has a putative role as a potential marker in schizophrenia and that its elevation may participate in its pathogenesis. IL-12p40 may be included in a panel to be evaluated in the sera of patients with schizophrenia and an appreciation of its independent function is important for improving our understanding of both protective and pathogenic immune responses. Future research should aim to assess this interleukin and understand its role in other mental illnesses that share a similar etiology to schizophrenia. PMID:27047333

  8. Inflammation and Elevation of Interleukin-12p40 in Patients with Schizophrenia

    PubMed Central

    Bedrossian, Nora; Haidar, Mariam; Fares, Jawad; Kobeissy, Firas H.; Fares, Youssef

    2016-01-01

    Schizophrenia is a serious mental illness with chronic symptoms and significant impairment in psychosocial functioning, which suggests that it likely has neurodegenerative characteristics. Inflammatory markers such as pro-inflammatory cytokines are well-known etiological contributors for psychiatric disorders, including schizophrenia. Although, the role of inflammation in schizophrenia is becoming evident, the number of studies in this area is relatively scarce, especially in Lebanon, and increased procedural thoroughness is needed. Cytokines play a key role in the activation of the immune system and strongly influence neurotransmission. Previous investigation of plasma levels showed dysregulation of interleukin (IL)-12. However, genotypical variations of this interleukin have not been investigated for patients with schizophrenia yet. Thus, in this paper, we aimed to compute and assess IL-12p40 levels in the sera of individuals with schizophrenia from different provinces in Lebanon and compare it to controls. Healthy subjects comprised 60 individuals with a male/female (M/F) ratio of 31/29, whereas patients with schizophrenia consisted of 63 subjects with an M/F ratio of 30/33. The mean age for healthy controls was 30 years, whereas that for patients with schizophrenia was 35 years. A standardized enzyme-linked immunosorbent assay (ELISA) technique was used to measure the concentration of IL-12p40 in all collected sera (n = 123). The mean IL-12p40 levels in patients with schizophrenia were significantly higher than in healthy controls (p = 0.002). Healthy females had a significantly higher concentration of IL-12p40 than healthy males (p = 0.009). Female patients with schizophrenia had significantly higher concentrations of IL-12p40 than their male counterparts (p < 0.001), healthy females (p = 0.018), and healthy males (p < 0.001), respectively. Male patients with schizophrenia had significantly higher concentrations of IL-12p40 than healthy males (p = 0.023). The study’s results suggest that IL-12p40 has a putative role as a potential marker in schizophrenia and that its elevation may participate in its pathogenesis. IL-12p40 may be included in a panel to be evaluated in the sera of patients with schizophrenia and an appreciation of its independent function is important for improving our understanding of both protective and pathogenic immune responses. Future research should aim to assess this interleukin and understand its role in other mental illnesses that share a similar etiology to schizophrenia. PMID:27047333

  9. [Azithromycin: tissue pharmacology].

    PubMed

    Bergogne-Bérézin, E

    1995-06-01

    Among macrolide derivatives, azithromycin which is an azalide, is a totally original new drug as to its pharmacokinetics in serum and tissues. Compared to reference compounds such as erythromycin or roxithromycin, pharmacokinetic parameters of azithromycin are characterized by: (i) much lower serum concentrations; (ii) a much longer elimination half-life (48-96 h); (iii) high and persistent tissue concentrations. The latter characteristic has been demonstrated in animal models (experimental H. influenzae pneumonia in mice) and in human studies. In lung parenchyma, azithromycin concentrations were higher and more persistent (72 h) in infected mice (12 mg/kg) as compared to non infected mice (controls) receiving the same dose of azithromycin (50 mg/kg); this may result from high intracellular concentrations in polymorphonuclear leucocytes and release of the drug at pulmonary sites of infection. In man, concentrations of azithromycin have been measured in lung parenchyma, bronchial secretions, tonsils, during exploratory or surgical conditions. After a single dose of 500 mg of azithromycin, local levels may reach up to 10 mg/kg with persistence of high levels for > or = 72 h in lungs, tonsils, sinus and bronchial secretions (1.5 to 8.6 mg/kg or mg/l). Five consecutive doses of azithromycin (500 mg per day) maintained for 10 days tonsil concentrations higher than the MICs for susceptible bacteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8539071

  10. Spectrophotometric estimation of azithromycin in tablets.

    PubMed

    Jayanna, B K; Nagendrappa, G; Arunkumar; Gowda, N

    2012-07-01

    The present manuscript describes a simple, sensitive, accurate, precise and economical visible spectrophotometric method for the estimation of azithromycin from tablet formulation. The method is based on the reduction of potassium permanganate in alkaline medium with azithromycin. The measurement of decrease in absorbance of potassium permanganate at 547 nm was done, as it decolourises upon reduction by azithromycin. The method was used to determine between 2 and 20 μg/ml of azithromycin in the final measured solution. There is no interference from the ingredients commonly found in azithromycin tablets with this method. The results for the determination of azithromycin in tablets were in good agreement with the labelled quantities and related analytical parameters are calculated. PMID:23626394

  11. Spectrophotometric Estimation of Azithromycin in Tablets

    PubMed Central

    Jayanna, B. K.; Nagendrappa, G.; Arunkumar; Gowda, N.

    2012-01-01

    The present manuscript describes a simple, sensitive, accurate, precise and economical visible spectrophotometric method for the estimation of azithromycin from tablet formulation. The method is based on the reduction of potassium permanganate in alkaline medium with azithromycin. The measurement of decrease in absorbance of potassium permanganate at 547 nm was done, as it decolourises upon reduction by azithromycin. The method was used to determine between 2 and 20 μg/ml of azithromycin in the final measured solution. There is no interference from the ingredients commonly found in azithromycin tablets with this method. The results for the determination of azithromycin in tablets were in good agreement with the labelled quantities and related analytical parameters are calculated. PMID:23626394

  12. Evaluation of azithromycin induced cardiotoxicity in rats

    PubMed Central

    Atli, Ozlem; Ilgin, Sinem; Altuntas, Hakan; Burukoglu, Dilek

    2015-01-01

    Although there are possible cardiovascular adverse effects associated with the azithromycin treatment according to some case reports and cohort studies, there is no experimental study evaluating cardiotoxicity in repeated pharmacological doses of this drug. In our study, 15 mg/kg and 30 mg/kg azithromycin were orally administered to rats for 14 days to evaluate the cardiotoxicity of this drug. ECGs of the azithromycin-treated and control animals were recorded. Blood samples were assayed to determine LDH and CK-MB levels. Additionally, CAT, SOD, GSH and MDA levels of heart tissues were measured. According to our ECG recordings, decreased heart rate, prolonged PR and QT intervals, QRS complex and T wave abnormalities were observed in 30 mg/kg azithromycin-administered group significantly when compared with control group. Plasma CK-MB and LDH levels were increased in 30 mg/kg azithromycin-administered group significantly when compared to the control group. In heart tissues, CAT, SOD and GSH levels were decreased while MDA levels were increased in both azithromycin-administered groups significantly when compared with the control group. In conclusion, our findings supported the possible cardiotoxicity risk with azithromycin treatment and also, oxidative stress, which was induced by azithromycin in our study, was thought to be occurred secondary to cardiac toxicity of the drug. PMID:26064263

  13. Interferon Consensus Sequence Binding Protein–deficient Mice Display Impaired Resistance to Intracellular Infection Due to a Primary Defect in Interleukin 12 p40 Induction

    PubMed Central

    Scharton-Kersten, Tanya; Contursi, Cristina; Masumi, Atsuko; Sher, Alan; Ozato, Keiko

    1997-01-01

    Mice lacking the transcription factor interferon consensus sequence binding protein (ICSBP), a member of the interferon regulatory factor family of transcription proteins, were infected with the intracellular protozoan, Toxoplasma gondii. ICSBP-deficient mice exhibited unchecked parasite replication in vivo and rapidly succumbed within 14 d after inoculation with an avirulent Toxoplasma strain. In contrast, few intracellular parasites were observed in wild-type littermates and these animals survived for at least 60 d after infection. Analysis of cytokine synthesis in vitro and in vivo revealed a major deficiency in the expression of both interferon (IFN)-γ and interleukin (IL)-12 p40 in the T. gondii exposed ICSBP−/− animals. In related experiments, macrophages from uninfected ICSBP−/− mice were shown to display a selective impairment in the mRNA expression of IL-12 p40 but not IL-1α, IL-1β, IL-1Ra, IL-6, IL-10, or TNF-α in response to live parasites, parasite antigen, lipopolysaccharide, or Staphylococcus aureus. This selective defect in IL-12 p40 production was observed regardless of whether the macrophages had been primed with IFN-γ. We hypothesize that the impaired synthesis of IL-12 p40 in ICSBP−/− animals is the primary lesion responsible for the loss in resistance to T. gondii because IFN-γ–induced parasite killing was unimpaired in vitro and, more importantly, administration of exogenous IL-12 in vivo significantly prolonged survival of the infected mice. Together these findings implicate ICSBP as a major transcription factor which directly or indirectly regulates IL-12 p40 gene activation and, as a consequence, IFN-γ–dependent host resistance. PMID:9348310

  14. The Glycogen Synthase Kinase 3α and β Isoforms Differentially Regulates Interleukin-12p40 Expression in Endothelial Cells Stimulated with Peptidoglycan from Staphylococcus aureus

    PubMed Central

    Huante-Mendoza, Alejandro; Bravo-Patiño, Alejandro; Valdez-Alarcón, Juan J.; Finlay, B. Brett; Baizabal-Aguirre, Víctor M.

    2015-01-01

    Glycogen synthase kinase 3 (GSK3) is a constitutively active regulatory enzyme that is important in cancer, diabetes, and cardiovascular, neurodegenerative, and psychiatric diseases. While GSK3α is usually important in neurodegenerative and psychiatric diseases GSK3β is fundamental in the inflammatory response caused by bacterial components. Peptidoglycan (PGN), one of the most abundant cell-wall structures of Gram-positive bacteria, is an important inducer of inflammation. To evaluate whether inhibition of GSK3α and GSK3β activity in bovine endothelial cells (BEC) regulates the expression of the pro-inflammatory cytokine IL-12p40, we treated BEC with SDS-purified PGN from Staphylococcus aureus. We found that PGN triggered a TLR2/PI3K/Akt-dependent phosphorylation of GSK3α at Ser21, GSK3β at Ser9, and NF-κB p65 subunit (p65) at Ser536, and the phosphorylation of GSK3α was consistently higher than that of GSK3β. The expression of IL-12p40 was inhibited in BEC stimulated with PGN and pre-treated with a specific neutralizing anti-TLR2 antibody that targets the extracellular domain of TLR2 or by the addition of Akt-i IV (an Akt inhibitor). Inhibition of GSK3α and GSK3β with LiCl or SB216763 induced an increase in IL-12p40 mRNA and protein. The effect of each isoform on IL-12p40 expression was evaluated by siRNA-gene expression silencing of GSK3α and GSK3β. GSK3α gene silencing resulted in a marked increase in IL-12p40 mRNA and protein while GSK3β gene silencing had the opposite effect on IL-12p40 expression. These results indicate that the TLR2/PI3K/Akt-dependent inhibition of GSK3α activity also plays an important role in the inflammatory response caused by stimulation of BEC with PGN from S. aureus. PMID:26200352

  15. The new macrolides. Azithromycin and clarithromycin.

    PubMed Central

    Kanatani, M S; Guglielmo, B J

    1994-01-01

    Clarithromycin and azithromycin are among the new generation of macrolides that have recently been approved for use. Compared with currently available antibiotics, these agents may be given less frequently and, in the case of azithromycin, for a shorter duration. In vitro data suggest an antimicrobial advantage of both clarithromycin and azithromycin against atypical mycobacterial and toxoplasmal species and possibly Haemophilus influenzae. The cost of both these agents is substantially higher than that of erythromycin and doxycycline, although the convenience of single-dose azithromycin is appealing compared with a 7-day course of doxycycline for chlamydial urethritis and cervicitis. These agents appear to offer advantages over erythromycin in the treatment of Mycobacterium avium-intracellulare. Additional data are needed to establish their role in other bacterial infections. PMID:8128699

  16. Azithromycin use in paediatrics: A practical overview

    PubMed Central

    Ovetchkine, Philippe; Rieder, Michael J

    2013-01-01

    Azithromycin is an antibiotic that is commonly prescribed for upper and lower respiratory tract infections in children. While it has proven benefits, some concerns regarding azithromycin use have arisen in recent years. This practice point considers azithromycin therapy for acute respiratory infections in otherwise healthy children. Pharmacokinetics, spectrum of activity, the problem of resistant bacteria and clinical aspects are considered, along with recommendations for use and contraindications. Azithromycin should be avoided in patients with a significant risk of bacteremia. It is associated with pneumococcal resistance and, with stated exceptions, is generally not recommended for the treatment of acute pharyngitis, acute otitis media or pneumococcal community-acquired pneumonia in the paediatric population. PMID:24421702

  17. Azithromycin and the Risk of Cardiovascular Complications.

    PubMed

    Maisch, Nicole M; Kochupurackal, Jenny G; Sin, Jonathan

    2013-12-31

    The purpose of this review was to evaluate the literature to assess the incidence and true clinical relevance of recent Food and Drug Administration warnings regarding QT prolongation with azithromycin, given its widespread use, with over 40 million US outpatient prescriptions written in 2011. A literature search of MEDLINE (1946 to May 2013) and International Pharmaceutical Abstracts (1970 to May 2013) was conducted using the terms azithromycin, QT prolongation, torsades de pointes, arrhythmia, and cardiovascular death. A bibliographic search was also performed. Several relevant studies and case reports were identified and reviewed. One cohort study revealed an increased risk of cardiovascular death with azithromycin compared to no antibiotic, especially in those with higher cardiovascular risk. Another cohort study comparing azithromycin, penicillin V, and no antibiotic in a younger Danish population with less cardiac risk found no increased cardiovascular death associated with azithromycin use. The majority of case reports involved ill and/or elderly patients with multiple comorbidities and concomitant medications who were already at a higher risk of cardiovascular events. Although there is evidence that azithromycin may induce QT prolongation and adverse cardiac events, the incidence is fairly limited to patients with high baseline risk, including those with preexisting cardiovascular conditions and concomitant use of other QT-prolonging drugs. PMID:24381242

  18. Azithromycin and the risk of cardiovascular complications.

    PubMed

    Maisch, Nicole M; Kochupurackal, Jenny G; Sin, Jonathan

    2014-10-01

    The purpose of this review was to evaluate the literature to assess the incidence and true clinical relevance of recent Food and Drug Administration warnings regarding QT prolongation with azithromycin, given its widespread use, with over 40 million US outpatient prescriptions written in 2011. A literature search of MEDLINE (1946 to May 2013) and International Pharmaceutical Abstracts (1970 to May 2013) was conducted using the terms azithromycin, QT prolongation, torsades de pointes, arrhythmia, and cardiovascular death. A bibliographic search was also performed. Several relevant studies and case reports were identified and reviewed. One cohort study revealed an increased risk of cardiovascular death with azithromycin compared to no antibiotic, especially in those with higher cardiovascular risk. Another cohort study comparing azithromycin, penicillin V, and no antibiotic in a younger Danish population with less cardiac risk found no increased cardiovascular death associated with azithromycin use. The majority of case reports involved ill and/or elderly patients with multiple comorbidities and concomitant medications who were already at a higher risk of cardiovascular events. Although there is evidence that azithromycin may induce QT prolongation and adverse cardiac events, the incidence is fairly limited to patients with high baseline risk, including those with preexisting cardiovascular conditions and concomitant use of other QT-prolonging drugs. PMID:25374989

  19. Pharmacokinetics, Safety, and Biologic Effects of Azithromycin in Extremely Preterm Infants at Risk for Ureaplasma Colonization and Bronchopulmonary Dysplasia

    PubMed Central

    Hassan, Hazem E.; Othman, Ahmed A.; Eddington, Natalie D.; Duffy, Lynn; Xiao, Li; Waites, Ken B.; Kaufman, David A.; Fairchild, Karen D.; Terrin, Michael L.; Viscardi, Rose M.

    2014-01-01

    Ureaplasma spp. respiratory tract colonization is a significant risk factor for bronchopulmonary dysplasia (BPD), a chronic lung disorder in preterm infants. As an initial step preparatory to future clinical trials to evaluate the clinical efficacy of azithromycin to prevent BPD, we characterized the pharmacokinetics, safety, and biological effects of a single intravenous dose of azithromycin (10 mg/kg) in preterm neonates (n=12) 24–28 weeks gestation at risk for Ureaplasma infection and BPD. A two-compartment structural model with the clearance and volume of peripheral compartment (V2) allometrically scaled on body weight (WT) best described the pharmacokinetics of azithromycin in preterm neonates. The estimated parameters were: clearance [0.18 L/h × WT(Kg)0.75], intercompartmental clearance [1.0 L/h], volume of distribution of central compartment [0.93 L] and V2 [14.2 L × WT(Kg)]. There were no serious adverse events attributed to azithromycin. A single dose of azithromycin did not suppress inflammatory cytokines or myeloperoxidase activity in tracheal aspirates. Our results demonstrated the safety of azithromycin and developed a PK model that is useful for future simulation-based clinical trials for eradicating Ureaplasma and preventing BPD in preterm neonates. PMID:21098694

  20. Pharmacokinetics, safety, and biologic effects of azithromycin in extremely preterm infants at risk for ureaplasma colonization and bronchopulmonary dysplasia.

    PubMed

    Hassan, Hazem E; Othman, Ahmed A; Eddington, Natalie D; Duffy, Lynn; Xiao, Li; Waites, Ken B; Kaufman, David A; Fairchild, Karen D; Terrin, Michael L; Viscardi, Rose M

    2011-09-01

    Ureaplasma spp. respiratory tract colonization is a significant risk factor for bronchopulmonary dysplasia (BPD), a chronic lung disorder in preterm infants. As an initial step preparatory to future clinical trials to evaluate the clinical efficacy of azithromycin to prevent BPD, the authors characterized the pharmacokinetics, safety, and biological effects of a single intravenous dose of azithromycin (10 mg/kg) in preterm neonates (n = 12) 24 to 28 weeks gestation at risk for Ureaplasma infection and BPD. A 2-compartment structural model with the clearance and volume of peripheral compartment (V2) allometrically scaled on body weight (WT) best described the pharmacokinetics of azithromycin in preterm neonates. The estimated parameters were clearance [0.18 L/h × WT(kg)(0.75)], intercompartmental clearance [1.0 L/h], volume of distribution of central compartment [0.93 L], and V2 [14.2 L × WT(kg)]. There were no serious adverse events attributed to azithromycin. A single dose of azithromycin did not suppress inflammatory cytokines or myeloperoxidase activity in tracheal aspirates. These results demonstrated the safety of azithromycin and developed a pharmacokinetic model that is useful for future simulation-based clinical trials for eradicating Ureaplasma and preventing BPD in preterm neonates. PMID:21098694

  1. Azithromycin for Prevention of Exacerbations of COPD

    PubMed Central

    Albert, Richard K.; Connett, John; Bailey, William C.; Casaburi, Richard; Cooper, J. Allen D.; Criner, Gerard J.; Curtis, Jeffrey L.; Dransfield, Mark T.; Han, MeiLan K.; Lazarus, Stephen C.; Make, Barry; Marchetti, Nathaniel; Martinez, Fernando J.; Madinger, Nancy E.; McEvoy, Charlene; Niewoehner, Dennis E.; Porsasz, Janos; Price, Connie S.; Reilly, John; Scanlon, Paul D.; Sciurba, Frank C.; Scharf, Steven M.; Washko, George R.; Woodruff, Prescott G.; Anthonisen, Nicholas R.

    2011-01-01

    BACKGROUND Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases. METHODS We performed a randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval. RESULTS A total of 1577 subjects were screened; 1142 (72%) were randomly assigned to receive azithromycin, at a dose of 250 mg daily (570 participants), or placebo (572 participants) for 1 year in addition to their usual care. The rate of 1-year follow-up was 89% in the azithromycin group and 90% in the placebo group. The median time to the first exacerbation was 266 days (95% confidence interval [CI], 227 to 313) among participants receiving azithromycin, as compared with 174 days (95% CI, 143 to 215) among participants receiving placebo (P<0.001). The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group, as compared with 1.83 per patient-year in the placebo group (P=0.01), and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 (95% CI, 0.63 to 0.84; P<0.001). The scores on the St. George’s Respiratory Questionnaire (on a scale of 0 to 100, with lower scores indicating better functioning) improved more in the azithromycin group than in the placebo group (a mean [±SD] decrease of 2.8±12.8 vs. 0.6±11.4, P=0.004); the percentage of participants with more than the minimal clinically important difference of −4 units was 43% in the azithromycin group, as compared with 36% in the placebo group (P=0.03). Hearing decrements were more common in the azithromycin group than in the placebo group (25% vs. 20%, P=0.04). CONCLUSIONS Among selected subjects with COPD, azithromycin taken daily for

  2. Pharmacokinetics of azithromycin in rats and dogs.

    PubMed

    Shepard, R M; Falkner, F C

    1990-01-01

    After intravenous or oral administration to rats and dogs, azithromycin was rapidly distributed into the tissues, where concentrations frequently exceeded those in serum by 100-fold or more within 24 h of a single dose. Tissue concentrations were proportional to the dose following single administrations of 10 to 40 mg/kg in rats and dogs. Tissue concentrations were higher after multiple dosing and became greater as the dose was increased from 10 to 40 mg/kg. Elimination half-lives were similar in most tissues and were about 40 h in rats after seven doses of 20 mg/kg and about 90 h in dogs after five doses of 30 mg/kg. Serum concentrations declined in a multi-exponential manner, reflecting initial rapid distribution into tissues and then slow return to serum from tissues. Azithromycin had good oral bioavailability in rats and dogs (46% and 97%, respectively). Rapid uptake of azithromycin by tissues from serum and slow redistribution from tissues to serum are apparently factors governing the pharmacokinetics of azithromycin in rats and dogs. Serum concentrations do not reflect the availability of azithromycin in tissues. PMID:2154438

  3. Cardiac risks associated with antibiotics: azithromycin and levofloxacin

    PubMed Central

    Lu, Zhiqiang Kevin; Yuan, Jing; Li, Minghui; Sutton, S Scott; Rao, Gowtham A; Jacob, Sony; Bennett, Charles L

    2015-01-01

    Introduction Azithromycin and levofloxacin have been shown to be efficacious in treating infections. The adverse drug events associated with azithromycin and levofloxacin were considered rare. However, the US FDA released warnings regarding the possible risk of QT prolongation with azithromycin and levofloxacin. Areas covered Case reports/case series, observational studies and clinical trials assessing cardiovascular risks associated with azithromycin and levofloxacin were critically reviewed, including 15 case reports/series, 5 observational studies and 5 clinical trials that investigated the cardiac risks associated azithromycin and levofloxacin. Expert opinion Results are discordant. Two retrospective studies utilizing large databases demonstrated an increased risk of cardiovascular death with azithromycin, when azithromycin was compared with amoxicillin. Two other retrospective studies found no difference in cardiovascular death associated with azithromycin and other antibiotics. For levofloxacin, the increased risk of cardiovascular death was only found in one retrospective study. Therefore, the risks and benefits of antibacterial therapies should be considered when making prescription decisions. This study should not preclude clinicians from avoiding azithromycin and levofloxacin. If a patient has an indication to receive an antibiotic and if azithromycin or levofloxacin is needed, it may be used, but the potential risks must be understood. PMID:25494485

  4. Use and safety of azithromycin in neonates: a systematic review

    PubMed Central

    Smith, Coral; Egunsola, Oluwaseun; Choonara, Imti; Kotecha, Sailesh; Jacqz-Aigrain, Evelyne; Sammons, Helen

    2015-01-01

    Objectives To identify the use and adverse drug reactions associated with azithromycin in neonates. Setting Databases MEDLINE (1948–August 2015), EMBASE (1980–August 2015) and Pubmed (August 2015) were searched for studies on azithromycin in neonates. Participants All studies involving neonates (<28 days old) who have received at least a single dose of azithromycin for which safety was evaluated. Primary and secondary outcome measures The primary outcome was adverse event (AE) associated with use of azithromycin. Use of azithromycin in neonates was the secondary outcome. Results A total of 11 articles involving 473 neonates were identified. 371 AEs were reported. Adverse events were mainly respiratory (358/1000 neonate), neurological (273/1000 neonates) and gastrointestinal (196/1000 neonates) in origin. Azithromycin significantly reduced the risk of bronchopulmonary dysplasia (BPD) in extremely premature neonates (RR=0.83, 95% CI 0.71 to 0.98, p=0.02). There was no significant difference in the incidence of elevated liver enzymes between the azithromycin and placebo group (p=0.76). There were four cases of infantile hypertrophic pyloric stenosis (IHPS). Conclusions Azithromycin significantly reduces the risk of BPD in preterm neonates. The relationship between azithromycin and IHPS requires further investigation. PMID:26656010

  5. Azithromycin pharmacokinetics and penetration to lymph.

    PubMed

    Bergan, T; Jørgensen, N P; Olszewski, W; Zhang, Y

    1992-01-01

    The study of pharmacokinetics of azithromycin and penetration to peripheral human lymph was carried out in 14 healthy male volunteers taking 1 g orally after overnight fasting. Samples were analyzed by microbiological assay. The mean peak concentrations were 0.82 +/- 0.23 mg/l after 1.7 +/- 0.5 h in serum and 0.22 +/- 0.07 mg/l after 3.1 h in lymph. Nine of the 14 subjects showed a second and lower serum peak indicating the existence of enterohepatic circulation. The total areas under the serum concentrations curves (AUCs) till infinity were 7.9 +/- 3.1 mg. h/l compared to 4.4 +/- 1.2 mg.h/l in lymph. The mean lymph AUC was 68.1 +/- 20.7% of the serum AUC indicating a penetration ratio of 0.68. However, the actual amounts penetrating the tissues were much higher than this ratio suggests. Thus, after 6 h 81% of the drug was within the tissue compartment and after 120 h, 63% of the azithromycin was still present in the tissue compartment. The urinary recovery of azithromycin was 14.7 +/- 7.7% during the first 48 h. The serum curves and lymph curves displayed a distinctly slower phase of elimination after 12 h. The mean serum half-life was 5.4 +/- 3.4 h during the first 12 h (after the peak), whereas the value was 44.2 +/- 10.1 h during the interval 12-120 h. The corresponding half-life values for the peripheral lymph were 5.4 +/- 2.2 h and 50.8 +/- 11.6 h. Azithromycin possesses key pharmacokinetic properties that are prerequisites for a convenient once-daily dosage schedule which may improve patient compliance. PMID:1336891

  6. Azithromycin induced bullous fixed drug eruption

    PubMed Central

    Das, Anupam; Sancheti, Karan; Podder, Indrashis; Das, Nilay Kanti

    2016-01-01

    Fixed drug eruption (FDE) is a common type of drug eruption seen in skin clinics. It is characterized by solitary or multiple, round to oval erythematous patches with dusky red centers, some of which may progress to bulla formation. Bullous FDE may be caused by a number of drugs. We hereby describe a case of azithromycin-induced bullous FDE; to the best of our knowledge, this is the first such case being reported. PMID:26997729

  7. Characterization of suppressive oligodeoxynucleotides that inhibit Toll-like receptor-9-mediated activation of innate immunity

    PubMed Central

    Peter, Mirjam; Bode, Konrad; Lipford, Grayson B; Eberle, Florian; Heeg, Klaus; Dalpke, Alexander H

    2008-01-01

    Synthetic oligodeoxynucleotides containing unmethylated CpG sequences (CpG-ODNs) stimulate Toll-like receptor-9 (TLR-9), thereby activating innate immunity. Stimulatory CpG-ODNs have been shown to be valuable in modifying immune responses in allergy, infection and cancer. Recently, it has been reported that the stimulation of TLR-9 by endogenous DNA might contribute to the pathogenesis of autoimmune diseases. We here report the identification of a suppressive, guanosine-rich ODN (G-ODN) that inhibited the activation of TLR-9 by stimulatory CpG-ODNs. The G-ODN was suppressive in murine macrophages and dendritic cells as well as in human plasmacytoid dendritic cells in vitro. G-ODN blocked the secretion of tumour necrosis factor-α (TNF-α) and interleukin-12p40 and interfered with the up-regulation of major histocompatibility complex (MHC) class II and costimulatory molecules. G-ODN was inhibitory even at a molar ratio of 1 : 10 (G-ODN:CpG-ODN) and when administered up to 7 hr after stimulation with CpG. G-ODN specifically inhibited TLR-9 but not other TLRs. Inhibition was dependent on a string of five guanosines. G-ODN was also inhibitory in an in vivo model of CpG/galactosamin (GalN) lethal shock. G-ODN interfered with upstream TLR-9 signalling. However, by extensive analysis we can exclude that G-ODN acts at the stage of cellular uptake. G-ODN therefore represents a class of suppressive ODNs that could be of therapeutic use in situations with pathologic TLR-9 activation, as has been proposed for certain autoimmune diseases. PMID:17961163

  8. Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long-term azithromycin or placebo.

    PubMed

    Hare, K M; Grimwood, K; Chang, A B; Chatfield, M D; Valery, P C; Leach, A J; Smith-Vaughan, H C; Morris, P S; Byrnes, C A; Torzillo, P J; Cheng, A C

    2015-11-01

    Although long-term azithromycin decreases exacerbation frequency in bronchiectasis, increased macrolide resistance is concerning. We investigated macrolide resistance determinants in a secondary analysis of a multicenter randomized controlled trial. Indigenous Australian children living in remote regions and urban New Zealand Māori and Pacific Islander children with bronchiectasis were randomized to weekly azithromycin (30 mg/kg) or placebo for up to 24 months and followed post-intervention for up to 12 months. Nurses administered and recorded medications given and collected nasopharyngeal swabs 3-6 monthly for culture and antimicrobial susceptibility testing. Nasopharyngeal carriage of Haemophilus influenzae and Moraxella catarrhalis was significantly lower in azithromycin compared to placebo groups, while macrolide-resistant Streptococcus pneumoniae and Staphylococcus aureus carriage was significantly higher. Australian children, compared to New Zealand children, had higher carriage overall, significantly higher carriage of macrolide-resistant bacteria at baseline (16/38 versus 2/40 children) and during the intervention (69/152 versus 22/239 swabs), and lower mean adherence to study medication (63 % versus 92 %). Adherence ≥70 % (versus <70 %) in the Australian azithromycin group was associated with lower carriage of any pathogen [odds ratio (OR) 0.19, 95 % confidence interval (CI) 0.07-0.53] and fewer macrolide-resistant pathogens (OR 0.34, 95 % CI 0.14-0.81). Post-intervention (median 6 months), macrolide resistance in S. pneumoniae declined significantly in the azithromycin group, from 79 % (11/14) to 7 % (1/14) of positive swabs, but S. aureus strains remained 100 % macrolide resistant. Azithromycin treatment, the Australian remote setting, and adherence <70 % were significant independent determinants of macrolide resistance in children with bronchiectasis. Adherence to treatment may limit macrolide resistance by suppressing carriage. PMID

  9. Comparison of tulathromycin, azithromycin and azithromycin-rifampin for the treatment of mild pneumonia associated with Rhodococcus equi.

    PubMed

    Venner, M; Credner, N; Lämmer, M; Giguère, S

    2013-10-26

    The objectives of the present study were to determine the relative efficacy of tulathromycin, azithromycin, or azithromycin with rifampin for the treatment of pulmonary abscesses on a farm with endemic infections caused by Rhodococcus equi. Foals with ultrasonographic evidence of pulmonary abscesses (abscess score 8.0-15 cm; n=120) were randomly allocated in four equal treatment groups: (1) tulathromycin intramuscularly; (2) azithromycin monotherapy, orally; (3) azithromycin with rifampin, orally; (4) saline intramuscularly as a placebo. Physical examination and thoracic ultrasonography were performed by individuals unaware of treatment group assignment. Foals that worsened were removed from the study. The proportion of foals that recovered without the need for a change in therapy was significantly higher for foals treated with azithromycin (29 of 30) or azithromycin with rifampin (28 of 30) than for foals treated with a placebo (20 of 30). Additionally, azithromycin or azithromycin with rifampin resulted in a significantly faster decrease in the number of abscesses and abscess score compared with a placebo. The proportion of foals treated with tulathromycin that recovered (27 of 30) was not significantly different from that of foals treated with a placebo. Azithromycin alone or in combination with rifampin was beneficial in the study population. PMID:24106244

  10. Pharmacokinetics and preliminary safety evaluation of azithromycin in adult horses.

    PubMed

    Leclere, M; Magdesian, K G; Cole, C A; Szabo, N J; Ruby, R E; Rhodes, D M; Edman, J; Vale, A; Wilson, W D; Tell, L A

    2012-12-01

    Azithromycin is widely used in foals but has not been studied in adult horses. The goals of this study were to determine the pharmacokinetic profile and to make a preliminary assessment of the safety of azithromycin in adult horses. Azithromycin was administered intravenously (5 mg/kg) and intragastrically (10 mg/kg) to six healthy mares in a crossover design. Serial plasma samples, blood neutrophils, and pulmonary macrophages were collected for the measurement of azithromycin concentrations. Azithromycin was also administered orally (10 mg/kg) once a day for 5 days to five healthy mares for preliminary evaluation of safety in adult horses. The bioavailability of azithromycin following intragastric administration was 45 ± 12%. Concentrations within peripheral neutrophils and bronchoalveolar macrophages were several fold higher than that of plasma. Mild decreases in appetite (n = 3) and alterations in fecal consistency (n = 3) were noted following repeated oral administration. The pharmacokinetic profiles of azithromycin in adult horses, especially the slow elimination rate and intraneutrophil and intrapulmonary macrophage accumulation, demonstrate that it is conducive to use in this age group. Because of the gastrointestinal alterations noted, further studies are warranted before azithromycin can be recommended for use in adult horses. PMID:22136612

  11. Carmine hypersensitivity masquerading as azithromycin hypersensitivity.

    PubMed

    Greenhawt, Matthew; McMorris, Marc; Baldwin, James

    2009-01-01

    Macrolide hypersensitivity is a rarely reported event. However, carmine dye has become increasingly important as a provocative agent. We present a case of a woman with documented carmine hypersensitivity, who reported anaphylaxis 90 minutes after ingestion of a generic azithromycin. Our investigations revealed that this was an allergy to the carmine dye in the tablet's coating rather than to the antibiotic. Seven extracts were prepared including carmine dye, crushed dried female cochineal insects, crushed tablets of Zithromax (Pfizer Inc.) and generic azithromycin (Teva Pharmaceuticals), and the crushed colored coatings from both tablets. These were suspended in preservative-free normal saline, and then applied as a skin-prick test and read at 30 minutes. The skin-prick skin test results were 4+ to histamine and carmine dye, but negative to cochineal insect extract, Pfizer crushed tablets, and negative control. The patient was 1+ to the Teva crushed tablet, but was 4+ to the Teva brand coating and negative to the Pfizer brand coating, which did not contain carmine. The patient subsequently ingested Pfizer Zithromax without any sequelae. To our knowledge, this is the first reported case of carmine anaphylaxis attributed to carmine-containing medication. Careful history and skin-prick testing to the appropriate agents allowed elucidation of the subtlety of the true offending agent without unnecessary avoidance of the medication class. Patients with a carmine hypersensitivity should actively check with their pharmacy or prescribing physician to verify their medications are free of this offending agent. PMID:19331724

  12. Pharmacokinetics, oral bioavailability and tissue distribution of azithromycin in cats.

    PubMed

    Hunter, R P; Lynch, M J; Ericson, J F; Millas, W J; Fletcher, A M; Ryan, N I; Olson, J A

    1995-02-01

    Azithromycin is the first of a class of antibiotics classified as azalides. In an initial experiment four cats were given a single dose of azithromycin 5 mg/kg orally (p.o.), followed 2 weeks later by a single intravenous bolus (i.v.) dose of 5 mg/kg. Subsequently, six cats were given [14C]azithromycin p.o. in a single dose of 5.4 mg/kg for the study of tissue distribution and metabolism. In both experiments, serial blood samples were collected and the plasma assayed for unchanged azithromycin to determine various pharmacokinetic parameters. After p.o. administration, bioavailability was 58% and absorption rapid with a tmax of 0.85 +/- 0.72 h and a Cmax of 0.97 +/- 0.65 microgram/mL. The harmonic mean terminal t1/2 after i.v. administration was 35 h. Tissue half-lives varied from 13 h in fat to 72 h in cardiac muscle. Three metabolites were identified in bile. Unchanged azithromycin accounted for 100% of the total radioactivity in lung and skin tissues when assayed. In comparison with other species, the bioavailability in cats is higher than in humans but lower than in dogs. As in the dog, > 50% of the azithromycin-related material in feline bile was unchanged azithromycin. PMID:7752305

  13. Intracellular accumulation of azithromycin by cultured human fibroblasts.

    PubMed Central

    Gladue, R P; Snider, M E

    1990-01-01

    Azithromycin was shown to achieve high concentrations in human skin fibroblasts. Intracellular penetration occurred rapidly (10 micrograms/mg of cellular protein after 3 h) and then increased progressively over a 3-day period; azithromycin accumulated up to 21 times more than erythromycin (61.1 versus 2.9 micrograms/mg of protein). Uptake was dependent on the extracellular concentration, was inhibited at 4 degrees C, did not occur in nonviable cells, and was reduced by a low pH. Intracellular accumulation was not affected by the metabolic inhibitor 2,4-dinitrophenol or sodium fluoride or by the nucleoside transport inhibitor 2-chloradenosine. Once concentrated in cells, azithromycin remained intracellular and was released slowly in the absence of extracellular drug, compared with erythromycin (17 versus 78% released after 1 h). After 48 h of incubation in drug-free medium, 27% of the initial amount of azithromycin remained cell associated. The release of azithromycin was not affected by various monokines reported to stimulate fibroblasts (interleukin-1 or tumor necrosis factor) or by exposure to bacteria. Incubation of azithromycin-loaded fibroblasts with human polymorphonuclear leukocytes resulted in a higher intracellular accumulation of azithromycin in polymorphonuclear leukocytes than in cells incubated with free nonintracellular azithromycin for the same time (8.3 versus 2.2 micrograms/ml after 2 h), suggesting a more efficient or rapid uptake through cell-to-cell interaction. The widespread distribution of fibroblasts in tissues suggests a potential for these cells, and possibly other lysosome-containing tissue cells, to serve as a reservoir for azithromycin, slowly releasing it for activity against extracellular organisms at sites of infection and passing it to phagocytes for activity against intracellular pathogens and potential transport to sites of infection. PMID:2168141

  14. Time-resolved binding of azithromycin to Escherichia coli ribosomes.

    PubMed

    Petropoulos, Alexandros D; Kouvela, Ekaterini C; Starosta, Agata L; Wilson, Daniel N; Dinos, George P; Kalpaxis, Dimitrios L

    2009-01-30

    Azithromycin is a semisynthetic derivative of erythromycin that inhibits bacterial protein synthesis by binding within the peptide exit tunnel of the 50S ribosomal subunit. Nevertheless, there is still debate over what localization is primarily responsible for azithromycin binding and as to how many molecules of the drug actually bind per ribosome. In the present study, kinetic methods and footprinting analysis are coupled together to provide time-resolved details of the azithromycin binding process. It is shown that azithromycin binds to Escherichia coli ribosomes in a two-step process: The first-step involves recognition of azithromycin by the ribosomal machinery and places the drug in a low-affinity site located in the upper part of the exit tunnel. The second step corresponds to the slow formation of a final complex that is both much tighter and more potent in hindering the progression of the nascent peptide through the exit tunnel. Substitution of uracil by cytosine at nucleoside 2609 of 23S rRNA, a base implicated in the high-affinity site, facilitates the shift of azithromycin to this site. In contrast, mutation U754A hardly affects the binding process. Binding of azithromycin to both sites is hindered by high concentrations of Mg(2+) ions. Unlike Mg(2+) ions, polyamines do not significantly affect drug binding to the low-affinity site but attenuate the formation of the final complex. The low- and high-affinity sites of azithromycin binding are mutually exclusive, which means that one molecule of the drug binds per E. coli ribosome at a time. In contrast, kinetic and binding data indicate that in Deinococcus radiodurans, two molecules of azithromycin bind cooperatively to the ribosome. This finding confirms previous crystallographic results and supports the notion that species-specific structural differences may primarily account for the apparent discrepancies between the antibiotic binding modes obtained for different organisms. PMID:19071138

  15. PA3297 Counteracts Antimicrobial Effects of Azithromycin in Pseudomonas aeruginosa

    PubMed Central

    Tan, Hao; Zhang, Lu; Weng, Yuding; Chen, Ronghao; Zhu, Feng; Jin, Yongxin; Cheng, Zhihui; Jin, Shouguang; Wu, Weihui

    2016-01-01

    Pseudomonas aeruginosa causes acute and chronic infections in human. Its increasing resistance to antibiotics requires alternative treatments that are more effective than available strategies. Among the alternatives is the unconventional usage of conventional antibiotics, of which the macrolide antibiotic azithromycin (AZM) provides a paradigmatic example. AZM therapy is associated with a small but consistent improvement in respiratory function of cystic fibrosis patients suffering from chronic P. aeruginosa infection. Besides immunomodulating activities, AZM represses bacterial genes involved in virulence, quorum sensing, biofilm formation, and motility, all of which are due to stalling of ribosome and depletion of cellular tRNA pool. However, how P. aeruginosa responds to and counteracts the effects of AZM remain elusive. Here, we found that deficiency of PA3297, a gene encoding a DEAH-box helicase, intensified AZM-mediated bacterial killing, suppression of pyocyanin production and swarming motility, and hypersusceptibility to hydrogen peroxide. We demonstrated that expression of PA3297 is induced by the interaction between AZM and ribosome. Importantly, mutation of PA3297 resulted in elevated levels of unprocessed 23S-5S rRNA in the presence of AZM, which might lead to increased susceptibility to AZM-mediated effects. Our results revealed one of the bacterial responses in counteracting the detrimental effects of AZM. PMID:27014238

  16. PA3297 Counteracts Antimicrobial Effects of Azithromycin in Pseudomonas aeruginosa.

    PubMed

    Tan, Hao; Zhang, Lu; Weng, Yuding; Chen, Ronghao; Zhu, Feng; Jin, Yongxin; Cheng, Zhihui; Jin, Shouguang; Wu, Weihui

    2016-01-01

    Pseudomonas aeruginosa causes acute and chronic infections in human. Its increasing resistance to antibiotics requires alternative treatments that are more effective than available strategies. Among the alternatives is the unconventional usage of conventional antibiotics, of which the macrolide antibiotic azithromycin (AZM) provides a paradigmatic example. AZM therapy is associated with a small but consistent improvement in respiratory function of cystic fibrosis patients suffering from chronic P. aeruginosa infection. Besides immunomodulating activities, AZM represses bacterial genes involved in virulence, quorum sensing, biofilm formation, and motility, all of which are due to stalling of ribosome and depletion of cellular tRNA pool. However, how P. aeruginosa responds to and counteracts the effects of AZM remain elusive. Here, we found that deficiency of PA3297, a gene encoding a DEAH-box helicase, intensified AZM-mediated bacterial killing, suppression of pyocyanin production and swarming motility, and hypersusceptibility to hydrogen peroxide. We demonstrated that expression of PA3297 is induced by the interaction between AZM and ribosome. Importantly, mutation of PA3297 resulted in elevated levels of unprocessed 23S-5S rRNA in the presence of AZM, which might lead to increased susceptibility to AZM-mediated effects. Our results revealed one of the bacterial responses in counteracting the detrimental effects of AZM. PMID:27014238

  17. Azithromycin versus Doxycycline for Urogenital Chlamydia trachomatis Infection

    PubMed Central

    Geisler, William M.; Uniyal, Apurva; Lee, Jeannette Y.; Lensing, Shelly Y.; Johnson, Shacondra; Perry, Raymond C.W.; Kadrnka, Carmel M.; Kerndt, Peter R.

    2016-01-01

    BACKGROUND Urogenital Chlamydia trachomatis infection remains prevalent and causes substantial reproductive morbidity. Recent studies have raised concern about the efficacy of azithromycin for the treatment of chlamydia infection. METHODS We conducted a randomized trial comparing oral azithromycin with doxycycline for the treatment of urogenital chlamydia infection among adolescents in youth correctional facilities, to evaluate the noninferiority of azithromycin (1 g in one dose) to doxycycline (100 mg twice daily for 7 days). The treatment was directly observed. The primary end point was treatment failure at 28 days after treatment initiation, with treatment failure determined on the basis of nucleic acid amplification testing, sexual history, and outer membrane protein A (OmpA) genotyping of C. trachomatis strains. RESULTS Among the 567 participants enrolled, 284 were randomly assigned to receive azithromycin, and 283 were randomly assigned to receive doxycycline. A total of 155 participants in each treatment group (65% male) made up the per-protocol population. There were no treatment failures in the doxycycline group. In the azithromycin group, treatment failure occurred in 5 participants (3.2%; 95% confidence interval, 0.4 to 7.4%). The observed difference in failure rates between the treatment groups was 3.2 percentage points, with an upper boundary of the 90% confidence interval of 5.9 percentage points, which exceeded the prespecified absolute 5-percentage-point cutoff for establishing the noninferiority of azithromycin. CONCLUSIONS In the context of a closed population receiving directly observed treatment for urogenital chlamydia infection, the efficacy of azithromycin was 97%, and the efficacy of doxycycline was 100%. The noninferiority of azithromycin was not established in this setting. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00980148.) PMID:26699167

  18. Pulmonary disposition of erythromycin, azithromycin, and clarithromycin in foals.

    PubMed

    Suarez-Mier, G; Giguère, S; Lee, E A

    2007-04-01

    The objectives of the present study were to determine and compare the pulmonary disposition of azithromycin, clarithromycin, and erythromycin in foals. A single dose (10 mg/kg) of azithromycin, clarithromycin, or erythromycin was administered intragastrically to six healthy 1- to 3-month-old foals using an orthogonal design. Activity of the drugs was measured in serum, pulmonary epithelial lining fluid (PELF), and bronchoalveolar lavage (BAL) cells by use of a microbiologic assay. Peak drug activity in PELF was significantly higher in foals treated with clarithromycin (48.96+/-13.26 microg/mL) than in foals treated with azithromycin (10.00+/-7.46 microg/mL). Quantifiable erythromycin activity in PELF was only found in two of six foals. Peak drug activity in BAL cells was not significantly different between azithromycin (49.92+/-26.94 microg/mL) and clarithromycin (74.20+/-45.80 microg/mL) but activity for both drugs was significantly higher than that of erythromycin (1.02+/-1.11 microg/mL). Terminal half-life of azithromycin in serum (25.7+/-15.4 h), PELF (34.8+/-30.9 h), and BAL cells (54.4+/-17.5 h) was significantly longer than that of both clarithromycin and erythromycin. Peak azithromycin and clarithromycin activity was significantly higher in BAL cells, followed by PELF, and serum. In contrast, peak erythromycin activity in BAL cells was not significantly different from that of serum. PMID:17348895

  19. The Efficacy and Safety of Gentamicin Plus Azithromycin and Gemifloxacin Plus Azithromycin as Treatment of Uncomplicated Gonorrhea

    PubMed Central

    Kirkcaldy, Robert D.; Weinstock, Hillard S.; Moore, Page C.; Philip, Susan S.; Wiesenfeld, Harold C.; Papp, John R.; Kerndt, Peter R.; Johnson, Shacondra; Ghanem, Khalil G.; Hook, Edward W.; Newman, Lori M.; Dowell, Deborah; Deal, Carolyn; Glock, Jonathan; Venkatasubramanian, Lalitha; McNeil, Linda; Perlowski, Charlotte; Lee, Jeannette Y.; Lensing, Shelly; Trainor, Nikole; Fuller, Shannon; Herrera, Amelia; Carlson, Jonathan S.; Harbison, Hanne; Lenderman, Connie; Dixon, Paula; Whittington, Allison; Macio, Ingrid; Priest, Carol; Jett, Abi; Campbell, Tracy; Uniyal, Apurva; Royal, LaShawnda; Mejia, Marisol; Vonghack, Jennifer; Tobias, Susan; Zenilman, Jonathan; Long, Jill; Harvey, Alesia; Pettus, Kevin; Sharpe, Samera

    2014-01-01

    Background. Ceftriaxone is the foundation of currently recommended gonorrhea treatment. There is an urgent need for backup treatment options for patients with cephalosporin allergy or infections due to suspected cephalosporin-resistant Neisseria gonorrhoeae. We evaluated the efficacy and tolerability of 2 combinations of existing noncephalosporin antimicrobials for treatment of patients with urogenital gonorrhea. Methods. We conducted a randomized, multisite, open-label, noncomparative trial in 5 outpatient sexually transmitted disease clinic sites in Alabama, California, Maryland, and Pennsylvania. Patients aged 15–60 years diagnosed with uncomplicated urogenital gonorrhea were randomly assigned to either gentamicin 240 mg intramuscularly plus azithromycin 2 g orally, or gemifloxacin 320 mg orally plus azithromycin 2 g orally. The primary outcome was microbiological cure of urogenital infections (negative follow-up culture) at 10–17 days after treatment among 401 participants in the per protocol population. Results. Microbiological cure was achieved by 100% (lower 1-sided exact 95% confidence interval [CI] bound, 98.5%) of 202 evaluable participants receiving gentamicin/azithromycin, and 99.5% (lower 1-sided exact 95% CI bound, 97.6%) of 199 evaluable participants receiving gemifloxacin/azithromycin. Gentamicin/azithromycin cured 10 of 10 pharyngeal infections and 1 of 1 rectal infection; gemifloxacin/azithromycin cured 15 of 15 pharyngeal and 5 of 5 rectal infections. Gastrointestinal adverse events were common in both arms. Conclusions. Gentamicin/azithromycin and gemifloxacin/azithromycin were highly effective for treatment of urogenital gonorrhea. Gastrointestinal adverse events may limit routine use. These non-cephalosporin-based regimens may be useful alternative options for patients who cannot be treated with cephalosporin antimicrobials. Additional treatment options for gonorrhea are needed. Clinical Trials Registration. NCT00926796. PMID

  20. Azithromycin: mechanisms of action and their relevance for clinical applications.

    PubMed

    Parnham, Michael J; Erakovic Haber, Vesna; Giamarellos-Bourboulis, Evangelos J; Perletti, Gianpaolo; Verleden, Geert M; Vos, Robin

    2014-08-01

    Azithromycin is a macrolide antibiotic which inhibits bacterial protein synthesis, quorum-sensing and reduces the formation of biofilm. Accumulating effectively in cells, particularly phagocytes, it is delivered in high concentrations to sites of infection, as reflected in rapid plasma clearance and extensive tissue distribution. Azithromycin is indicated for respiratory, urogenital, dermal and other bacterial infections, and exerts immunomodulatory effects in chronic inflammatory disorders, including diffuse panbronchiolitis, post-transplant bronchiolitis and rosacea. Modulation of host responses facilitates its long-term therapeutic benefit in cystic fibrosis, non-cystic fibrosis bronchiectasis, exacerbations of chronic obstructive pulmonary disease (COPD) and non-eosinophilic asthma. Initial, stimulatory effects of azithromycin on immune and epithelial cells, involving interactions with phospholipids and Erk1/2, are followed by later modulation of transcription factors AP-1, NFκB, inflammatory cytokine and mucin release. Delayed inhibitory effects on cell function and high lysosomal accumulation accompany disruption of protein and intracellular lipid transport, regulation of surface receptor expression, of macrophage phenotype and autophagy. These later changes underlie many immunomodulatory effects of azithromycin, contributing to resolution of acute infections and reduction of exacerbations in chronic airway diseases. A sub-group of post-transplant bronchiolitis patients appears to be sensitive to azithromycin, as may be patients with severe sepsis. Other promising indications include chronic prostatitis and periodontitis, but weak activity in malaria is unlikely to prove crucial. Long-term administration of azithromycin must be balanced against the potential for increased bacterial resistance. Azithromycin has a very good record of safety, but recent reports indicate rare cases of cardiac torsades des pointes in patients at risk. PMID:24631273

  1. Efficacy of azithromycin in preventing pulmonary abscesses in foals.

    PubMed

    Venner, Monica; Reinhold, Birte; Beyerbach, Martin; Feige, Karsten

    2009-02-01

    The prophylactic application of azithromycin to prevent pulmonary abscesses in foals was evaluated on a stud with endemic Rhodococcus equi pneumonia. Forty-five foals served as untreated controls in two groups. Twenty-five foals were given azithromycin (10mg/kg) orally once daily for 4 weeks. The foals were examined once a week from birth to the age of 5 months. If clinical signs or leucocytosis were noted and pulmonary sonographic findings (diameter >10 mm) were observed, the diagnosis of abscessing pneumonia was made. The prevalence of pulmonary abscesses was similar in the control groups (31/45 foals), and in the azithromycin group (15/25 foals), but the foals in the azithromycin group were affected significantly later (median: day 83, range 67-123 days) (control groups: day 54, range 52-82; and 46, range 28-86 days). It was concluded that the application of azithromycin for 28 days post-natally does not reduce the prevalence of pulmonary abscesses in foals on a stud with endemic pneumonia. PMID:18023599

  2. Azithromycin efficacy in the treatment of Chlamydia trachomatis among detained youth.

    PubMed

    Beyda, Rebecca M; Benjamins, Laura J; Symanski, Elaine; Swartz, Michael; Risser, William L; Eissa, Mona

    2014-10-01

    We assessed the efficacy of azithromycin among detained adolescents with Chlamydia trachomatis. Infected adolescents took azithromycin and submitted a test of cure. Of the 128 youth, 5 patients experienced treatment failure. We found that azithromycin was 96.1% (95% confidence interval, 91.1%-98.8%) effective in treating chlamydia infections, supporting its continued use. PMID:25211253

  3. Optimal Seasonal Timing of Oral Azithromycin for Malaria

    PubMed Central

    Gao, Daozhou; Amza, Abdou; Nassirou, Baidou; Kadri, Boubacar; Sippl-Swezey, Nicholas; Liu, Fengchen; Ackley, Sarah F.; Lietman, Thomas M.; Porco, Travis C.

    2014-01-01

    Mass administration of azithromycin for trachoma has been shown to reduce malarial parasitemia. However, the optimal seasonal timing of such distributions for antimalarial benefit has not been established. We performed numerical analyses on a seasonally forced epidemic model (of Ross-Macdonald type) with periodic impulsive annual mass treatment to address this question. We conclude that when azithromycin-based trachoma elimination programs occur in regions of seasonal malaria transmission, such as Niger, the optimal seasonal timing of mass drug administration (MDA) may not occur during the season of maximum transmission. PMID:25223942

  4. Mechanism of azithromycin inhibition of HSL synthesis in Pseudomonas aeruginosa.

    PubMed

    Zeng, Jianming; Zhang, Ni; Huang, Bin; Cai, Renxin; Wu, Binning; E, Shunmei; Fang, Chengcai; Chen, Cha

    2016-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen and a leading cause of nosocomial infections. Unfortunately, P. aeruginosa has low antibiotic susceptibility due to several chromosomally encoded antibiotic resistance genes. Hence, we carried out mechanistic studies to determine how azithromycin affects quorum sensing and virulence in P. aeruginosa. lasI and rhlI single and double mutants were constructed. We then undertook a quantitative approach to determine the optimal concentration of azithromycin and culture time that can affect the expression of HSLs. Furthermore, based on the above results, the effect on quorum sensing was analyzed at a transcriptional level. It was found that 2 μg/mL azithromycin caused a 79% decrease in 3-oxo-C12-HSL secretion during cultivation, while C4-HSL secretion was strongly repressed in the early stages. Azithromycin acts on ribosomes; to determine whether this can elicit alternative modes of gene expression, transcriptional regulation of representative virulence genes was analyzed. We propose a new relationship for lasI and rhlI: lasI acts as a cell density sensor, and rhlI functions as a fine-tuning mechanism for coordination between different quorum sensing systems. PMID:27075730

  5. Mechanism of azithromycin inhibition of HSL synthesis in Pseudomonas aeruginosa

    PubMed Central

    Zeng, Jianming; Zhang, Ni; Huang, Bin; Cai, Renxin; Wu, Binning; E, Shunmei; Fang, Chengcai; Chen, Cha

    2016-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen and a leading cause of nosocomial infections. Unfortunately, P. aeruginosa has low antibiotic susceptibility due to several chromosomally encoded antibiotic resistance genes. Hence, we carried out mechanistic studies to determine how azithromycin affects quorum sensing and virulence in P. aeruginosa. lasI and rhlI single and double mutants were constructed. We then undertook a quantitative approach to determine the optimal concentration of azithromycin and culture time that can affect the expression of HSLs. Furthermore, based on the above results, the effect on quorum sensing was analyzed at a transcriptional level. It was found that 2 μg/mL azithromycin caused a 79% decrease in 3-oxo-C12-HSL secretion during cultivation, while C4-HSL secretion was strongly repressed in the early stages. Azithromycin acts on ribosomes; to determine whether this can elicit alternative modes of gene expression, transcriptional regulation of representative virulence genes was analyzed. We propose a new relationship for lasI and rhlI: lasI acts as a cell density sensor, and rhlI functions as a fine-tuning mechanism for coordination between different quorum sensing systems. PMID:27075730

  6. Azithromycin differentially affects the IL-13-induced expression profile in human bronchial epithelial cells.

    PubMed

    Mertens, Tinne C J; Hiemstra, Pieter S; Taube, Christian

    2016-08-01

    The T helper 2 (Th2) cytokine interleukin(IL)-13 is a central regulator in goblet cell metaplasia and induces the recently described Th2 gene signature consisting of periostin (POSTN), chloride channel regulator 1 (CLCA1) and serpin B2 (SERPINB2) in airway epithelial cells. This Th2 gene signature has been proposed as a biomarker to classify asthma into Th2-high and Th2-low phenotypes. Clinical studies have shown that the macrolide antibiotic azithromycin reduced clinical symptoms in neutrophilic asthma, but not in the classical Th2-mediated asthma despite the ability of azithromycin to reduce IL-13-induced mucus production. We therefore hypothesize that azithromycin differentially affects the IL-13-induced expression profile. To investigate this, we focus on IL-13-induced mucin and Th2-signature expression in human bronchial epithelial cells and how this combined expression profile is affected by azithromycin treatment. Primary bronchial epithelial cells were differentiated at air liquid interface in presence of IL-13 with or without azithromycin. Azithromycin inhibited IL-13-induced MUC5AC, which was accompanied by inhibition of IL-13-induced CLCA1 and SERPINB2 expression. In contrast, IL-13-induced expression of POSTN was further increased in cells treated with azithromycin. This indicates that azithromycin has a differential effect on the IL-13-induced Th2 gene signature. Furthermore, the ability of azithromycin to decrease IL-13-induced MUC5AC expression may be mediated by a reduction in CLCA1. PMID:27246785

  7. Insights into the mechanism of azithromycin interaction with an Escherichia coli functional ribosomal complex.

    PubMed

    Dinos, G P; Michelinaki, M; Kalpaxis, D L

    2001-06-01

    Azithromycin, a derivative of erythromycin with improved activity against Gram-negative bacteria, exhibits a marginal inhibition effect in a model system derived from Escherichia coli, in which a peptide bond is formed between puromycin and AcPhe-tRNA bound at the P-site of poly(U)-programmed ribosomes. This renders the study of azithromycin interaction with Ac[(3)H]Phe-tRNA. poly(U). 70S ribosome complex (complex C) impossible, if we analyze its effect on peptide bond formation. To overcome this problem, we have used an alternative approach to investigate kinetically the azithromycin interaction with complex C and to compare the azithromycin binding properties with those of erythromycin. This approach was based on the ability of azithromycin to compete with tylosin, a macrolide antibiotic strongly inhibiting the puromycin reaction. Detailed kinetic analysis revealed that the encounter complex CA between complex C and azithromycin (A) undergoes a slow isomerization to a tighter complex C*A, which remains active toward puromycin. The determination of inhibition and isomerization rate constants enabled us to classify azithromycin as a slow-binding ligand of ribosomes. Compared with erythromycin, azithromycin is a better inducer and stabilizer of the C*A complex. This finding may explain the superiority of azithromycin as inhibitor of translation in E. coli cells and many other Gram-negative bacteria. PMID:11353804

  8. Interleukin-12 gene-expression of macrophages is regulated by nitric oxide.

    PubMed

    Rothe, H; Hartmann, B; Geerlings, P; Kolb, H

    1996-07-01

    Interleukin-12 is a heterodimeric cytokine, mainly produced by macrophages. In our present study we demonstrate that interleukin-12 expression is regulated by nitric oxide. Incubation of the macrophage cell line IC 21 with interferon-gamma gave rise to both interleukin-12 p40 mRNA and nitric oxide production. The concurrent addition of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine inhibited nitrite production and in parallel completely suppressed interleukin-12 p40 mRNA formation. This indicated that endogenous nitric oxide synthase activity was required for IL-12 p40 gene expression. Exposure of the cells towards the nitric oxide generating compounds nitroprusside or S-nitroso-N-acetyl-penicillamine induced interleukin-12 p40 mRNA. Maximal mRNA levels were induced with nitric oxide donors at 1 microM concentration. We conclude that nitric oxide may exert an autoregulatory and paracrine control of interleukin-12 gene expression. PMID:8694804

  9. Pharmaceutical development and optimization of azithromycin suppository for paediatric use.

    PubMed

    Kauss, Tina; Gaubert, Alexandra; Boyer, Chantal; Ba, Boubakar B; Manse, Muriel; Massip, Stephane; Léger, Jean-Michel; Fawaz, Fawaz; Lembege, Martine; Boiron, Jean-Michel; Lafarge, Xavier; Lindegardh, Niklas; White, Nicholas J; Olliaro, Piero; Millet, Pascal; Gaudin, Karen

    2013-01-30

    Pharmaceutical development and manufacturing process optimization work was undertaken in order to propose a potential paediatric rectal formulation of azithromycin as an alternative to existing oral or injectable formulations. The target product profile was to be easy-to-use, cheap and stable in tropical conditions, with bioavailability comparable to oral forms, rapidly achieving and maintaining bactericidal concentrations. PEG solid solution suppositories were characterized in vitro using visual, HPLC, DSC, FTIR and XRD analyses. In vitro drug release and in vivo bioavailability were assessed; a study in rabbits compared the bioavailability of the optimized solid solution suppository to rectal solution and intra-venous product (as reference) and to the previous, non-optimized formulation (suspended azithromycin suppository). The bioavailability of azithromycin administered as solid solution suppositories relative to intra-venous was 43%, which compared well to the target of 38% (oral product in humans). The results of 3-month preliminary stability and feasibility studies were consistent with industrial production scale-up. This product has potential both as a classical antibiotic and as a product for use in severely ill children in rural areas. Industrial partners for further development are being sought. PMID:23220079

  10. Pharmaceutical development and optimization of azithromycin suppository for paediatric use

    PubMed Central

    Kauss, Tina; Gaubert, Alexandra; Boyer, Chantal; Ba, Boubakar B.; Manse, Muriel; Massip, Stephane; Léger, Jean-Michel; Fawaz, Fawaz; Lembege, Martine; Boiron, Jean-Michel; Lafarge, Xavier; Lindegardh, Niklas; White, Nicholas J.; Olliaro, Piero; Millet, Pascal; Gaudin, Karen

    2013-01-01

    Pharmaceutical development and manufacturing process optimization work was undertaken in order to propose a potential paediatric rectal formulation of azithromycin as an alternative to existing oral or injectable formulations. The target product profile was to be easy-to-use, cheap and stable in tropical conditions, with bioavailability comparable to oral forms, rapidly achieving and maintaining bactericidal concentrations. PEG solid solution suppositories were characterized in vitro using visual, HPLC, DSC, FTIR and XRD analyses. In vitro drug release and in vivo bioavailability were assessed; a study in rabbits compared the bioavailability of the optimized solid solution suppository to rectal solution and intra-venous product (as reference) and to the previous, non-optimized formulation (suspended azithromycin suppository). The bioavailability of azithromycin administered as solid solution suppositories relative to intra-venous was 43%, which compared well to the target of 38% (oral product in humans). The results of 3-month preliminary stability and feasibility studies were consistent with industrial production scale-up. This product has potential both as a classical antibiotic and as a product for use in severely ill children in rural areas. Industrial partners for further development are being sought. PMID:23220079

  11. Inhaled therapies, azithromycin and Mycobacterium abscessus in cystic fibrosis patients.

    PubMed

    Catherinot, Emilie; Roux, Anne-Laure; Vibet, Marie-Anne; Bellis, Gil; Lemonnier, Lydie; Le Roux, Evelyne; Bernède-Bauduin, Claire; Le Bourgeois, Muriel; Herrmann, Jean-Louis; Guillemot, Didier; Gaillard, Jean-Louis

    2013-05-01

    Cystic fibrosis (CF) patients are at particularly high risk of developing lung disease caused by Mycobacterium abscessus complex (MABSC). Over the last 10 years, changes in CF treatment, with increasing use of inhaled therapies and low-dose azithromycin, have been accompanied by an increase in the prevalence of MABSC infections in CF patients. There is therefore some concern about the role of new CF treatments in the emergence of MABSC infections. We addressed this issue by means of a case-control study including 30 MABSC-positive cases and 60 nontuberculous mycobacteria-negative CF controls matched for age, sex and centre. We also compared practices at the CF centres with the highest prevalence of MABSC with those at the other centres. No positive association was found between MABSC lung disease and the use of inhaled therapies or low-dose azithromycin in the 4 years preceding MABSC isolation. These treatments were not significantly more frequently used at the CF centres with the highest MABSC prevalence rates. In conclusion, there is no evidence for a link between M. abscessus complex lung disease and inhaled therapies or low-dose azithromycin in patients with CF. PMID:22936714

  12. Azithromycin induces anti-viral effects in cultured bronchial epithelial cells from COPD patients.

    PubMed

    Menzel, Mandy; Akbarshahi, Hamid; Bjermer, Leif; Uller, Lena

    2016-01-01

    Rhinovirus infection is a major cause of chronic obstructive pulmonary disease (COPD) exacerbations and may contribute to the development into severe stages of COPD. The macrolide antibiotic azithromycin may exert anti-viral actions and has been reported to reduce exacerbations in COPD. However, little is known about its anti-viral actions on bronchial epithelial cells at clinically relevant concentrations. Primary bronchial epithelial cells from COPD donors and healthy individuals were treated continuously with azithromycin starting 24 h before infection with rhinovirus RV16. Expression of interferons, RIG-I like helicases, pro-inflammatory cytokines and viral load were analysed. Azithromycin transiently increased expression of IFNβ and IFNλ1 and RIG-I like helicases in un-infected COPD cells. Further, azithromycin augmented RV16-induced expression of interferons and RIG-I like helicases in COPD cells but not in healthy epithelial cells. Azithromycin also decreased viral load. However, it only modestly altered RV16-induced pro-inflammatory cytokine expression. Adding budesonide did not reduce interferon-inducing effects of azithromycin. Possibly by inducing expression of RIG-I like helicases, azithromycin increased rhinovirus-induced expression of interferons in COPD but not in healthy bronchial epithelium. These effects would reduce bronchial viral load, supporting azithromycin's emerging role in prevention of exacerbations of COPD. PMID:27350308

  13. Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells.

    PubMed

    Schögler, Aline; Kopf, Brigitte S; Edwards, Michael R; Johnston, Sebastian L; Casaulta, Carmen; Kieninger, Elisabeth; Jung, Andreas; Moeller, Alexander; Geiser, Thomas; Regamey, Nicolas; Alves, Marco P

    2015-02-01

    Virus-associated pulmonary exacerbations, often associated with rhinoviruses (RVs), contribute to cystic fibrosis (CF) morbidity. Currently, there are only a few therapeutic options to treat virus-induced CF pulmonary exacerbations. The macrolide antibiotic azithromycin has antiviral properties in human bronchial epithelial cells. We investigated the potential of azithromycin to induce antiviral mechanisms in CF bronchial epithelial cells. Primary bronchial epithelial cells from CF and control children were infected with RV after azithromycin pre-treatment. Viral RNA, interferon (IFN), IFN-stimulated gene and pattern recognition receptor expression were measured by real-time quantitative PCR. Live virus shedding was assessed by assaying the 50% tissue culture infective dose. Pro-inflammatory cytokine and IFN-β production were evaluated by ELISA. Cell death was investigated by flow cytometry. RV replication was increased in CF compared with control cells. Azithromycin reduced RV replication seven-fold in CF cells without inducing cell death. Furthermore, azithromycin increased RV-induced pattern recognition receptor, IFN and IFN-stimulated gene mRNA levels. While stimulating antiviral responses, azithromycin did not prevent virus-induced pro-inflammatory responses. Azithromycin pre-treatment reduces RV replication in CF bronchial epithelial cells, possibly through the amplification of the antiviral response mediated by the IFN pathway. Clinical studies are needed to elucidate the potential of azithromycin in the management and prevention of RV-induced CF pulmonary exacerbations. PMID:25359346

  14. Efficacy of combined atovaquone and azithromycin for therapy of chronic Babesia gibsoni (Asian genotype) infections in dogs.

    PubMed

    Birkenheuer, Adam J; Levy, Michael G; Breitschwerdt, Edward B

    2004-01-01

    Babesiosis caused by Babesia gibsoni (Asian genotype) is an emerging disease in dogs in the United States. To date, no drugs have been shown to eliminate B. gibsoni (Asian genotype) infections from dogs. Twenty-two dogs that remained persistently infected with B. gibsoni (Asian genotype) after either imidocarb diproprionate and or diminazine aceturate therapy were identified and randomly and evenly distributed into 2 groups. One group was treated with atovaquone and azithromycin combination therapy, and the other group received a placebo. Eight of 10 dogs in the treatment group had no detectable B. gibsoni (Asian genotype) DNA, as determined by a sensitive and specific polymerase chain reaction (PCR) assay, in any of their posttreatment samples. In contrast, B. gibsoni (Asian genotype) DNA was detectable by PCR in the posttreatment samples from 11 of 11 of the placebo-treated dogs. One dog in the treatment group was excluded from the treatment outcome analysis. This dog had 2 consecutive negative PCR assay results and was euthanized because of ongoing degenerative joint disease prior to completion of the study. No adverse effects of treatment were reported in any dog during the study period. A combination of atovaquone and azithromycin is the 1st described treatment that will either eliminate B. gibsoni (Asian genotype) infections or suppress the parasitemia below the limit of detection in the majority of treated dogs. PMID:15320586

  15. Azithromycin in the treatment of a dog infected with Giardia intestinalis.

    PubMed

    Zygner, W; Jaros, D; Gójska-Zygner, O; Wedrychowicz, H

    2008-01-01

    Giardia intestinalis infection is a common cause of diarrhoea in humans and other mammalian species throughout the world. This report describes a case of a dog suffering from diarrhoea, infected with G. intestinalis, effectively treated with azithromycin. Azithromycin is an azalide, semisynthetic macrolide antibiotic having a large spectrum of activity against bacterial pathogens and some protozoa. In this case, Giardia infection in a dog was confirmed by microscopic examination and PCR. Sequencing of the detected Giardia amplicon confirmed infection with assemblage A-I. The dog received azithromycin administered at dose of 10 mg/kg per os, once a day for 5 days. After the therapy, the diarrhoea stopped. Effectiveness of the treatment was also confirmed by PCR and microscopic examination. This is the first report on the therapy of canine giardiosis with azithromycin. It seems that azithromycin can be considered as promising antibiotic for the control of Giardia infection in dogs. PMID:18942546

  16. Clinically and microbiologically derived azithromycin susceptibility breakpoints for Salmonella enterica serovars Typhi and Paratyphi A.

    PubMed

    Parry, Christopher M; Thieu, Nga Tran Vu; Dolecek, Christiane; Karkey, Abhilasha; Gupta, Ruchi; Turner, Paul; Dance, David; Maude, Rapeephan R; Ha, Vinh; Tran, Chinh Nguyen; Thi, Phuong Le; Be, Bay Pham Van; Phi, La Tran Thi; Ngoc, Rang Nguyen; Ghose, Aniruddha; Dongol, Sabina; Campbell, James I; Thanh, Duy Pham; Thanh, Tuyen Ha; Moore, Catrin E; Sona, Soeng; Gaind, Rajni; Deb, Monorama; Anh, Ho Van; Van, Sach Nguyen; Tinh, Hien Tran; Day, Nicholas P J; Dondorp, Arjen; Thwaites, Guy; Faiz, Mohamed Abul; Phetsouvanh, Rattanaphone; Newton, Paul; Basnyat, Buddha; Farrar, Jeremy J; Baker, Stephen

    2015-05-01

    Azithromycin is an effective treatment for uncomplicated infections with Salmonella enterica serovar Typhi and serovar Paratyphi A (enteric fever), but there are no clinically validated MIC and disk zone size interpretative guidelines. We studied individual patient data from three randomized controlled trials (RCTs) of antimicrobial treatment in enteric fever in Vietnam, with azithromycin used in one treatment arm, to determine the relationship between azithromycin treatment response and the azithromycin MIC of the infecting isolate. We additionally compared the azithromycin MIC and the disk susceptibility zone sizes of 1,640 S. Typhi and S. Paratyphi A clinical isolates collected from seven Asian countries. In the RCTs, 214 patients who were treated with azithromycin at a dose of 10 to 20 mg/ml for 5 to 7 days were analyzed. Treatment was successful in 195 of 214 (91%) patients, with no significant difference in response (cure rate, fever clearance time) with MICs ranging from 4 to 16 μg/ml. The proportion of Asian enteric fever isolates with an MIC of ≤ 16 μg/ml was 1,452/1,460 (99.5%; 95% confidence interval [CI], 98.9 to 99.7) for S. Typhi and 207/240 (86.3%; 95% CI, 81.2 to 90.3) (P < 0.001) for S. Paratyphi A. A zone size of ≥ 13 mm to a 5-μg azithromycin disk identified S. Typhi isolates with an MIC of ≤ 16 μg/ml with a sensitivity of 99.7%. An azithromycin MIC of ≤ 16 μg/ml or disk inhibition zone size of ≥ 13 mm enabled the detection of susceptible S. Typhi isolates that respond to azithromycin treatment. Further work is needed to define the response to treatment in S. Typhi isolates with an azithromycin MIC of >16 μg/ml and to determine MIC and disk breakpoints for S. Paratyphi A. PMID:25733500

  17. Azithromycin May Antagonize Inhaled Tobramycin When Targeting Pseudomonas aeruginosa in Cystic Fibrosis

    PubMed Central

    Nick, Jerry A.; Moskowitz, Samuel M.; Chmiel, James F.; Forssén, Anna V.; Kim, Sun Ho; Saavedra, Milene T.; Saiman, Lisa; Taylor-Cousar, Jennifer L.

    2014-01-01

    Rationale: Recent studies of inhaled tobramycin in subjects with cystic fibrosis (CF) find less clinical improvement than previously observed. Nonhuman data suggest that in some strains of Pseudomonas aeruginosa, azithromycin can antagonize tobramycin. Objectives: We tested the hypothesis that concomitant azithromycin use correlates with less improvement in key outcome measures in subjects receiving inhaled tobramycin while not affecting those receiving a comparative, nonaminoglycoside inhaled antibiotic. Methods: We studied a cohort of 263 subjects with CF enrolled in a recent clinical trial comparing inhaled tobramycin with aztreonam lysine. We performed a secondary analysis to examine key clinical and microbiologic outcomes based on concomitant, chronic azithromycin use at enrollment. Measurements and Main Results: The cohort randomized to inhaled tobramycin and reporting azithromycin use showed a significant decrease in the percent predicted FEV1 after one and three courses of inhaled tobramycin when compared with those not reporting azithromycin use (28 d: −0.51 vs. 3.43%, P < 0.01; 140 d: −1.87 vs. 6.07%, P < 0.01). Combined azithromycin and inhaled tobramycin use was also associated with earlier need for additional antibiotics, lesser improvement in disease-related quality of life, and a trend toward less reduction in sputum P. aeruginosa density. Subjects randomized to inhaled aztreonam lysine had significantly greater improvement in these outcome measures, which were unaffected by concomitant azithromycin use. Outcomes in those not using azithromycin who received inhaled tobramycin were not significantly different from subjects receiving aztreonam lysine. Azithromycin also antagonized tobramycin but not aztreonam lysine in 40% of P. aeruginosa clinical isolates tested in vitro. Conclusions: Oral azithromycin may antagonize the therapeutic benefits of inhaled tobramycin in subjects with CF with P. aeruginosa airway infection. PMID:24476418

  18. Azithromycin analogue CSY0073 attenuates lung inflammation induced by LPS challenge

    PubMed Central

    Balloy, V; Deveaux, A; Lebeaux, D; Tabary, O; le Rouzic, P; Ghigo, J M; Busson, P F; Boëlle, P Y; Guez, J Guez; Hahn, U; Clement, A; Chignard, M; Corvol, H; Burnet, M; Guillot, L

    2014-01-01

    Background and Purpose Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulating effects. Long-term azithromycin therapy in patients with chronic lung diseases such as cystic fibrosis has been associated with increased antimicrobial resistance, emergence of hypermutable strains, ototoxicity and cardiac toxicity. The aim of this study was to assess the anti-inflammatory effects of the non-antibiotic azithromycin derivative CSY0073. Experimental Approach We compared the effects of CSY0073 with those of azithromycin in experiments on bacterial cultures, Pseudomonas aeruginosa biofilm, lung cells and mice challenged intranasally with P. aeruginosa LPS. Key Results In contrast to azithromycin, CSY0073 did not inhibit the growth of P. aeruginosa, Staphylococcus aureus or Haemophilus influenzae and had no effect on an established P. aeruginosa biofilm. Bronchoalveolar lavage (BAL) fluids and lung homogenates collected after the LPS challenge in mice showed that CSY0073 and azithromycin (200 mg·kg−1, i.p.) decreased neutrophil counts at 24 h and TNF-α, CXCL1 and CXCL2 levels in the BAL fluid after 3 h and IL-6, CXCL2 and IL-1β levels in the lung after 3 h compared with the vehicle. However, only azithromycin reduced IL-1β levels in the lung 24 h post LPS challenge. CSY0073 and azithromycin similarly diminished the production of pro-inflammatory cytokines by macrophages, but not lung epithelial cells, exposed to P. aeruginosa LPS. Conclusions and Implications Unlike azithromycin, CSY0073 had no antibacterial effects but it did have a similar anti-inflammatory profile to that of azithromycin. Hence, CSY0073 may have potential as a long-term treatment for patients with chronic lung diseases. PMID:24417187

  19. Clinically and Microbiologically Derived Azithromycin Susceptibility Breakpoints for Salmonella enterica Serovars Typhi and Paratyphi A

    PubMed Central

    Thieu, Nga Tran Vu; Dolecek, Christiane; Karkey, Abhilasha; Gupta, Ruchi; Turner, Paul; Dance, David; Maude, Rapeephan R.; Ha, Vinh; Tran, Chinh Nguyen; Thi, Phuong Le; Be, Bay Pham Van; Phi, La Tran Thi; Ngoc, Rang Nguyen; Ghose, Aniruddha; Dongol, Sabina; Campbell, James I.; Thanh, Duy Pham; Thanh, Tuyen Ha; Moore, Catrin E.; Sona, Soeng; Gaind, Rajni; Deb, Monorama; Anh, Ho Van; Van, Sach Nguyen; Tinh, Hien Tran; Day, Nicholas P. J.; Dondorp, Arjen; Thwaites, Guy; Faiz, Mohamed Abul; Phetsouvanh, Rattanaphone; Newton, Paul; Basnyat, Buddha; Farrar, Jeremy J.; Baker, Stephen

    2015-01-01

    Azithromycin is an effective treatment for uncomplicated infections with Salmonella enterica serovar Typhi and serovar Paratyphi A (enteric fever), but there are no clinically validated MIC and disk zone size interpretative guidelines. We studied individual patient data from three randomized controlled trials (RCTs) of antimicrobial treatment in enteric fever in Vietnam, with azithromycin used in one treatment arm, to determine the relationship between azithromycin treatment response and the azithromycin MIC of the infecting isolate. We additionally compared the azithromycin MIC and the disk susceptibility zone sizes of 1,640 S. Typhi and S. Paratyphi A clinical isolates collected from seven Asian countries. In the RCTs, 214 patients who were treated with azithromycin at a dose of 10 to 20 mg/ml for 5 to 7 days were analyzed. Treatment was successful in 195 of 214 (91%) patients, with no significant difference in response (cure rate, fever clearance time) with MICs ranging from 4 to 16 μg/ml. The proportion of Asian enteric fever isolates with an MIC of ≤16 μg/ml was 1,452/1,460 (99.5%; 95% confidence interval [CI], 98.9 to 99.7) for S. Typhi and 207/240 (86.3%; 95% CI, 81.2 to 90.3) (P < 0.001) for S. Paratyphi A. A zone size of ≥13 mm to a 5-μg azithromycin disk identified S. Typhi isolates with an MIC of ≤16 μg/ml with a sensitivity of 99.7%. An azithromycin MIC of ≤16 μg/ml or disk inhibition zone size of ≥13 mm enabled the detection of susceptible S. Typhi isolates that respond to azithromycin treatment. Further work is needed to define the response to treatment in S. Typhi isolates with an azithromycin MIC of >16 μg/ml and to determine MIC and disk breakpoints for S. Paratyphi A. PMID:25733500

  20. Azithromycin in DuraSite for the treatment of blepharitis.

    PubMed

    Luchs, Jodi

    2010-01-01

    Blepharitis is a common inflammatory disease of the eyelid. Posterior blepharitis affects the posterior lamella of the eyelid and involves inflammation of the meibomian glands, whereas anterior blepharitis affects the anterior lamella of the eyelid and the eyelashes; either version can be inflammatory or infectious in nature. Each of these conditions can incite or propagate the other; anterior blepharitis, if not treated, can lead to meibomian gland disease, and vice versa. Blepharitis is typically chronic, and can be associated with a variety of systemic diseases such as dermatitis, as well as ocular diseases such as dry eye, conjunctivitis, or keratitis. The standard treatment regimen historically consists of lid hygiene with warm compresses and eyelid scrubs, although these treatment modalities may have limited efficacy for many patients, especially those with more severe disease. Adjunctive treatment includes systemic and topical antibiotics, topical corticosteroids, and tear replacement therapy. Topical antibiotics are recommended to decrease the bacterial load, and topical corticosteroids may help in cases of severe inflammation. Azithromycin ophthalmic solution 1% in DuraSite((R)) (AzaSite((R)); Inspire Pharmaceuticals, Durham, North Carolina, USA) has been proposed as a novel treatment for posterior blepharitis, based on its well-known anti-infective profile, its anti-inflammatory properties, its excellent tissue penetration, and its regulatory approval for the treatment of bacterial conjunctivitis. This review focuses on an off-label indication for topical azithromycin 1% in DuraSite for the treatment of blepharitis. PMID:20689782

  1. Azithromycin increases phagocytosis of apoptotic bronchial epithelial cells by alveolar macrophages.

    PubMed

    Hodge, S; Hodge, G; Brozyna, S; Jersmann, H; Holmes, M; Reynolds, P N

    2006-09-01

    Chronic obstructive pulmonary disease (COPD) is associated with increased apoptosis and defective phagocytosis in the airway. As uncleared cells can undergo secondary necrosis and perpetuate inflammation, strategies to improve clearance would have therapeutic significance. There is evidence that the 15-member macrolide antibiotic azithromycin has anti-inflammatory properties. Its effects may be increased in the lung due to its ability to reach high concentrations in alveolar macrophages (AMs). The present study investigated the effects of low-dose (500 ng x mL(-1)) azithromycin on the phagocytosis of apoptotic bronchial epithelial cells and neutrophils by AMs. Flow cytometry was applied to measure phagocytosis and receptors involved in AM recognition of apoptotic cells. Cytokines were investigated using cytometric bead array. Baseline phagocytosis was reduced in COPD subjects compared with controls. Azithromycin significantly improved the phagocytosis of epithelial cells or neutrophils by AMs from COPD subjects by 68 and 38%, respectively, often up to levels comparable with controls. The increase in phagocytosis was partially inhibited by phosphatidylserine, implicating the phosphatidylserine pathway in the pro-phagocytic effects of azithromycin. Azithromycin had no effect on other recognition molecules (granulocyte-macrophage colony-stimulating factor, CD44, CD31, CD36, CD91, alphavbeta3 integrin). At higher doses, azithromycin decreased levels of pro-inflammatory cytokines. Thus, low-dose azithromycin therapy could provide an adjunct therapeutic option in chronic obstructive pulmonary disease. PMID:16737992

  2. Azithromycin is able to control Toxoplasma gondii infection in human villous explants

    PubMed Central

    2014-01-01

    Background Although Toxoplasma gondii infection is normally asymptomatic, severe cases of toxoplasmosis may occur in immunosuppressed patients or congenitally infected newborns. When a fetal infection is established, the recommended treatment is a combination of pyrimethamine, sulfadiazine and folinic acid (PSA). The aim of the present study was to evaluate the efficacy of azithromycin to control T. gondii infection in human villous explants. Methods Cultures of third trimester human villous explants were infected with T. gondii and simultaneously treated with either PSA or azithromycin. Proliferation of T. gondii, as well as production of cytokines and hormones by chorionic villous explants, was analyzed. Results Treatment with either azithromycin or PSA was able to control T. gondii infection in villous explants. After azithromycin or PSA treatment, TNF-α, IL-17A or TGF-β1 levels secreted by infected villous explants did not present significant differences. However, PSA-treated villous explants had decreased levels of IL-10 and increased IL-12 levels, while treatment with azithromycin increased production of IL-6. Additionally, T. gondii-infected villous explants increased secretion of estradiol, progesterone and HCG + β, while treatments with azithromycin or PSA reduced secretion of these hormones concurrently with decrease of parasite load. Conclusions In conclusion, these results suggest that azithromycin may be defined as an effective alternative drug to control T. gondii infection at the fetal-maternal interface. PMID:24885122

  3. Pharmacokinetics of azithromycin in the blue and gold macaw (Ara ararauna) after intravenous and oral administration.

    PubMed

    Carpenter, James W; Olsen, John H; Randle-Port, Mary; Koch, David E; Isaza, Ramiro; Hunter, Robert P

    2005-12-01

    Azithromycin is classified as an azalide, a subclass of macrolide antimicrobials with a broad spectrum of activity in vitro against many potential bacterial pathogens including spirochetes, anaerobes, and Chlamydia trachomatis. Because of limited data on the use of azithromycin in avian medicine, this study was designed to determine the pharmacokinetics of azithromycin in blue and gold macaws (Ara ararauna), a species commonly seen in clinical practice. Azithromycin (10 mg/kg) was administered via crop lavage to five birds and intravenously to five birds, and blood samples were obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hr post-azithromycin administration. Following a 4-wk washout period, the study was repeated with a complete crossover study performed. Concentration of azithromycin in plasma samples was quantified using a validated liquid chromatography/mass spectrometry assay. Pharmacokinetic parameters were determined using noncompartmental analysis. Based on the pharmacokinetic data generated from this study, a starting dose of azithromycin at 10 mg/kg p.o. every 48 hr for susceptible bacterial infections in blue and gold macaws is recommended. PMID:17312716

  4. Azithromycin: assessment of intrinsic cytotoxic effects on corneal epithelial cell cultures

    PubMed Central

    Mencucci, Rita; Pellegrini-Giampietro, Domenico E; Paladini, Iacopo; Favuzza, Eleonora; Menchini, Ugo; Scartabelli, Tania

    2013-01-01

    Purpose To compare the cytotoxic effects of preservative-free azithromycin on corneal epithelial cells in vivo with those of preservative-free netilmicin and levofloxacin, and the preservative benzalkonium chloride (BAK). Methods Rabbit corneal epithelial cells in vitro were incubated for 15 minutes or 6 hours with commercially available ophthalmic preservative-free netilmicin 0.3%, levofloxacin 0.3%, or azithromycin 1.5% preparations or different concentrations of unpreserved azithromycin and different concentrations of BAK. Qualitative analysis was undertaken using phase-contrast optics to examine the morphological aspects of cell cultures and quantitative analysis was undertaken by measuring the release of the cytoplasmic enzyme lactate dehydrogenase into the medium immediately and 24 hours after exposure to drugs. Finally, we observed the wound-healing rate of mechanically injured corneal epithelial cells exposed to each antibiotic ophthalmic preparation for 48 hours. Results Our results show that both the commercially available unpreserved mono-dose preparation of azithromycin and ophthalmic preparations of azithromycin up to a concentration of 1.5% were virtually devoid of harmful effects under our experimental conditions. This was not significantly different from the results obtained for the other antibiotic preparations (P > 0.05) tested, but was unlike the results obtained for BAK. Azithromycin 1.5% also showed good recovery properties after a mechanical wound test. Conclusion Under our experimental conditions, unpreserved azithromycin 1.5% showed a much lower toxicity than BAK and did not interfere with the wound-healing process. PMID:23737659

  5. Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection

    PubMed Central

    Renna, Maurizio; Schaffner, Catherine; Brown, Karen; Shang, Shaobin; Tamayo, Marcela Henao; Hegyi, Krisztina; Grimsey, Neil J.; Cusens, David; Coulter, Sarah; Cooper, Jason; Bowden, Anne R.; Newton, Sandra M.; Kampmann, Beate; Helm, Jennifer; Jones, Andrew; Haworth, Charles S.; Basaraba, Randall J.; DeGroote, Mary Ann; Ordway, Diane J.; Rubinsztein, David C.; Floto, R. Andres

    2011-01-01

    Azithromycin is a potent macrolide antibiotic with poorly understood antiinflammatory properties. Long-term use of azithromycin in patients with chronic inflammatory lung diseases, such as cystic fibrosis (CF), results in improved outcomes. Paradoxically, a recent study reported that azithromycin use in patients with CF is associated with increased infection with nontuberculous mycobacteria (NTM). Here, we confirm that long-term azithromycin use by adults with CF is associated with the development of infection with NTM, particularly the multi-drug-resistant species Mycobacterium abscessus, and identify an underlying mechanism. We found that in primary human macrophages, concentrations of azithromycin achieved during therapeutic dosing blocked autophagosome clearance by preventing lysosomal acidification, thereby impairing autophagic and phagosomal degradation. As a consequence, azithromycin treatment inhibited intracellular killing of mycobacteria within macrophages and resulted in chronic infection with NTM in mice. Our findings emphasize the essential role for autophagy in the host response to infection with NTM, reveal why chronic use of azithromycin may predispose to mycobacterial disease, and highlight the dangers of inadvertent pharmacological blockade of autophagy in patients at risk of infection with drug-resistant pathogens. PMID:21804191

  6. Azithromycin induces anti-viral effects in cultured bronchial epithelial cells from COPD patients

    PubMed Central

    Menzel, Mandy; Akbarshahi, Hamid; Bjermer, Leif; Uller, Lena

    2016-01-01

    Rhinovirus infection is a major cause of chronic obstructive pulmonary disease (COPD) exacerbations and may contribute to the development into severe stages of COPD. The macrolide antibiotic azithromycin may exert anti-viral actions and has been reported to reduce exacerbations in COPD. However, little is known about its anti-viral actions on bronchial epithelial cells at clinically relevant concentrations. Primary bronchial epithelial cells from COPD donors and healthy individuals were treated continuously with azithromycin starting 24 h before infection with rhinovirus RV16. Expression of interferons, RIG-I like helicases, pro-inflammatory cytokines and viral load were analysed. Azithromycin transiently increased expression of IFNβ and IFNλ1 and RIG-I like helicases in un-infected COPD cells. Further, azithromycin augmented RV16-induced expression of interferons and RIG-I like helicases in COPD cells but not in healthy epithelial cells. Azithromycin also decreased viral load. However, it only modestly altered RV16-induced pro-inflammatory cytokine expression. Adding budesonide did not reduce interferon-inducing effects of azithromycin. Possibly by inducing expression of RIG-I like helicases, azithromycin increased rhinovirus-induced expression of interferons in COPD but not in healthy bronchial epithelium. These effects would reduce bronchial viral load, supporting azithromycin’s emerging role in prevention of exacerbations of COPD. PMID:27350308

  7. Pharmacokinetics of azithromycin in foals after i.v. and oral dose and disposition into phagocytes.

    PubMed

    Davis, J L; Gardner, S Y; Jones, S L; Schwabenton, B A; Papich, M G

    2002-04-01

    The properties of azithromycin suggest that it may be an alternative to erythromycin for treatment of Rhodococcus equi pneumonia in foals. To investigate this possibility, the disposition of azithromycin in plasma, polymorphonuclear leukocytes (PMN), and alveolar cells was examined after a single administration in foals. Azithromycin suspension was administered orally (p.o.) at a dose of 10 mg/kg to five healthy 2-3-month-old foals. Two weeks later, azithromycin for injection was administered by intravenous (i.v.) infusion at a dose of 5 mg/kg to the same foals. Plasma samples were collected after p.o. and i.v. administration. Peripheral blood PMN and bronchoalveolar lavage fluid and alveolar cells were collected after p.o. administration. Azithromycin concentrations were determined by reverse-phase high-performance liquid chromatography (HPLC) with coulometric electrochemical detection. Azithromycin p.o. absorption was variable with a mean systemic availability of 39% (+/-20%). The plasma half-life was 16 and 18.3 h after i.v. and p.o. administration, respectively. Azithromycin had a very large volume of distribution (V(d)) of 11.6 L/kg [V(d(ss))] and 12.4 L/kg [V(d(area))]. The large V(d) can be attributed to high tissue and intracellular concentrations, exhibited by the high concentration of azithromycin in PMN and alveolar cells. The PMN half-life was 49.2 h. Dosage of 10 mg/kg of azithromycin p.o. once daily for foals with R. equi pneumonia is recommended for further study. PMID:12000529

  8. High-level azithromycin-resistant Neisseria gonorrhoeae clinical isolate in France, March 2014.

    PubMed

    Bercot, B; Belkacem, A; Goubard, A; Mougari, F; Sednaoui, P; La Ruche, G; Cambau, E

    2014-01-01

    We report the first case in France of a high-level azithromycin-resistant Neisseria gonorrhoeae (minimum inhibitory concentration (MIC) = 96 mg/L) assigned to MLST7363 (NG-MAST ST6360), also resistant to ciprofloxacin and tetracycline but susceptible to ceftriaxone. The patient was a 51 year-old heterosexual man who returned following 1g azithromycin monotherapy. Mechanisms of azithromycin resistance were a C2599T mutation in the four copies of the rrl gene and a novel mutation in the promoter of the mtrR gene. PMID:25394255

  9. Ureaplasma, bronchopulmonary dysplasia, and azithromycin in European neonatal intensive care units: a survey.

    PubMed

    Pansieri, Claudia; Pandolfini, Chiara; Elie, Valery; Turner, Mark A; Kotecha, Sailesh; Jacqz-Aigrain, Evelyne; Bonati, Maurizio

    2014-01-01

    A survey was set up to gauge the opinions of neonatologists on the role of Ureaplasma in bronchopulmonary dysplasia (BPD) development, the use of azithromycin for BPD prevention, and the factors influencing azithromycin use in European neonatal intensive care units (NICUs). 167 NICUs participated in the survey, representing 28 European countries. For respondents, the two major perceived risk factors for BPD were prematurity of <28 weeks and high oxygen requirements. Only 38% of NICUs had a protocol for BPD prevention and 47% routinely tested for Ureaplasma. In cases of infection, macrolides were the first choice. Most (78%) NICUs were interested in participating in a trial evaluating azithromycin safety and efficacy in reducing BPD rates. Opinions and clinical practice varied between European neonatal units, and differences in Ureaplasma treatment and prevention of BPD highlight the need for further azithromycin evaluation and for improved therapeutic knowledge in preterms. PMID:24518104

  10. Mass Spectrometry Analysis of Pseudomonas aeruginosa Treated with Azithromycin

    NASA Astrophysics Data System (ADS)

    Phelan, Vanessa V.; Fang, Jinshu; Dorrestein, Pieter C.

    2015-06-01

    In microbiology, changes in specialized metabolite production (cell-to-cell signaling metabolites, virulence factors, and natural products) are measured using phenotypic assays. However, advances in mass spectrometry-based techniques including imaging mass spectrometry (IMS) now allow researchers to directly visualize the production of specialized metabolites from microbial colony biofilms. In this study, a combination of IMS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to visualize the effect of the macrolide antibiotic azithromycin (AZM) on colony biofilms of Pseudomonas aeruginosa. Although previous research suggested that AZM may inhibit cell-to-cell signaling of P. aeruginosa and thereby reduce pathogenicity, we observed no clear decrease in specialized metabolite production.

  11. Mass Spectrometry Analysis of Pseudomonas aeruginosa Treated With Azithromycin

    PubMed Central

    Phelan, Vanessa V.; Fang, Jinshu; Dorrestein, Pieter C.

    2015-01-01

    In microbiology, changes in specialized metabolite production (cell-to-cell signaling metabolites, virulence factors and natural products) are measured using phenotypic assays. However, advances in mass spectrometry based techniques including imaging mass spectrometry (IMS) now allow researchers to directly visualize the production of specialized metabolites from microbial colony biofilms. In this study, a combination of IMS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to visualize the effect of the macrolide antibiotic azithromycin (AZM) on colony biofilms of Pseudomonas aeruginosa. While previous research suggested that AZM may inhibit cell-to-cell signaling of P. aeruginosa and thereby reducing pathogenicity, we observed no clear decrease in specialized metabolite production. PMID:25801585

  12. [Treatment of pneumonia caused by Legionella with azithromycin].

    PubMed

    Sánchez, F; Mensa, J; Martínez, J A; Badia, R; Albarracín, M; Losa, J E; Ruiz, M; Marcos, M A; Torres, A; Soriano, E

    1998-06-01

    Nineteen patients with pneumonia caused by Legionella, who did not need to be admitted to ICU were treated with 500 mg/day of azithromycin. The etiological diagnosis was made retrospectively by detecting Legionella pneumophila in the urine of nine patients and/or by serology (seroconversion or single titer 1/256) in 19 cases. None of them met the criteria for ICU admittance nor had received prior treatment with antibiotics which were potentially active against L. pneumophila. Serology tests and radiography of the thorax were carried out on all the patients in the study during their convalescence period. The average age (+/- SD) of the group was 58.5 +/- 16.2 years. The average respiratory frequency (+/- SD) 26 +/- 6 breaths per minute; the radiologic extension was of one lobule in 18 cases and two lobules in one case. No patients showed bilateral disease. Arterial gasometry (FiO2 0.21) showed a pO2 average of (+/- SD) 53 +/- 14 mmHg and the hemogram an average of 6.700 leukocytes/mm3 (range: 4,200-41-800). All the patients progressed favorably. The average duration of fever was 1.8 days; the average stay (+/- SD) was 6.1 +/- 2 days. The treatment was well tolerated. One month after discharge radiographies were clear for all patients. There were no relapses. In conclusion, 3-day administration of azithromycin was found to be a useful guide in the treatment of community acquired pneumonia caused by Legionella in patients whose clinical situation does not require ICU administration and allows for oral administration. PMID:9795300

  13. Azithromycin has a direct relaxant effect on precontracted airway smooth muscle.

    PubMed

    Daenas, Christos; Hatziefthimiou, Apostolia A; Gourgoulianis, Konstantinos I; Molyvdas, Paschalis Adam

    2006-12-28

    Macrolides have been proven to have beneficial bacteriostatic and anti-inflammatory properties, but very little is known about the potential value of their bronchodilatory effect. Therefore, in the present study we investigated the effect of azithromycin on contractile responses of isolated rabbit tracheal strips to carbachol or KCl. Azithromycin has a relaxant, concentration-dependent effect on tracheal strips precontracted with carbachol (300 nM), significant from the concentration of 1 muM. The mechanical removal of epithelium did not alter the effect of azithromycin. Azithromycin (100 microM) also relaxed tracheal strips precontracted with KCl (80 mM) even in the presence of atropine (100 microM). Moreover, azithromycin (100 microM) decreased contractions induced by 300 nM and 10 microM carbachol to 55.4% and 80.5% of initial contraction, respectively. The relaxant effect of azithromycin persisted in both calcium free solution and in the presence of the calcium channel antagonist, verapamil. The relaxant effect of azithromycin was not altered by the pre-treatment of preparations with the inhibitors of Ca(2+)-ATPase (cyclopiazonic acid), Na(+)-K(+) ATPase (ouabain), Rho-associated kinase [(R)-(+)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride] (Y-27632) or the non-specific cAMP and cGMP phosphodiesterases inhibitor 3-isobutyl-1-methyl-2,6(1H,3H)-purinedione (IBMX). These results suggest that azithromycin has a concentration-dependent, epithelium-independent, direct relaxant effect on precontracted tracheal strips that is not mediated via inhibition of Ca(2+) influx or Ca(2+) release from intracellular stores. Also, it is not due to alteration of the function of Na(+)-K(+) ATPase and does not depend on the formation of cAMP/cGMP or the Rho/Rho-activated kinase pathway. PMID:17070799

  14. A Case of Prolonged Cholestatic Hepatitis Induced by Azithromycin in a Young Woman

    PubMed Central

    Maggioli, Caterina; Santi, Luca; Zaccherini, Giacomo; Bevilacqua, Vittoria; Giunchi, Francesca; Caraceni, Paolo

    2011-01-01

    Azithromycin, a semisynthetic macrolides, is frequently prescribed for the treatment of middle ear and upper respiratory tract infections, bronchitis, and community-acquired pneumonia. This antibiotic is usually well tolerated, and a rapid resolving cholestatic hepatitis has been described up to now only in six patients all, except one, over 65 years of age. We here report the case of a prolonged cholestatic hepatitis after administration of azithromycin in a young woman with no history of liver disease. PMID:25954540

  15. Comparison of therapeutic effects of topical azithromycin solution and systemic doxycycline on posterior blepharitis

    PubMed Central

    Zandian, Mehdi; Rahimian, Neda; Soheilifar, Sanaz

    2016-01-01

    AIM To compare the effect of azithromycin drop and doxycycline capsule on treatment of posterior blepharitis. METHODS Fifty patients (100 eyes) with moderate posterior blepharitis, randomly divided into two therapeutic groups; all the patients got warm eyelid compress and massage three times a day for 3wk. In addition the first group got azithromycin 1% drop, twice daily for 1wk and then one drop daily for 2wk. The second group got oral doxycycline 100 mg daily for 3wk. At the end of the research, patients' signs and symptoms were compared together. ANOVA, Chi-square and Mann-Whitney tests were used for statistical analysis. RESULTS Topical therapy with azithromycin and oral therapy with doxycycline relieved signs and symptoms after 3wk. There were no significant differences between symptoms healing rate and foreign body sensation healing in these two groups (P>0.05). However, azithromycin drop was more effective in reduction of eye redness and doxycycline was more effective in meibomian glands plugging healing and reducing the corneal staining. CONCLUSION Topical azithromycin could have similar effects as oral doxycycline on posterior blepharitis in improving subjective symptoms. However, doxycycline can reduce objective signs such as ocular surface staining and meibomian gland plugging more than azithromycin. PMID:27500111

  16. Comparison of azithromycin, roxithromycin, and cephalexin penetration kinetics in early and mature abscesses.

    PubMed

    Girard, D; Bergeron, J M; Milisen, W B; Retsema, J A

    1993-06-01

    During the process of abscess formation, a myriad of changes are observed histologically that impede the penetration of antimicrobial agents into infection loci. A Staphylococcus aureus foreign body abscess, developed in rats, was employed to evaluate the penetration kinetics of azithromycin, roxithromycin and cephalexin at various stages of abscess development; the progressive patho-histological changes of abscess formation were also characterized in this model. In an early abscess (18 h post-challenge), azithromycin penetration into inflammatory fluid was enhanced (AUC of 351 vs 130 mg.h/kg) and residence prolonged relative to an inflammation control (half-life of 88 vs 27 h). In contrast, roxithromycin and cephalexin penetration into, and residence in, inflammatory fluid were unaltered in the early abscess. However, penetration into, and egress from, a mature abscess (ten days post-challenge) were impeded for all three antimicrobials (P < or = 0.03). The penetration kinetics of azithromycin into inflammatory fluid in an early abscess were independent of the dose regimen, but dependent on the total dose. The persistently high concentrations of azithromycin in inflammatory fluid within abscess were associated with the infiltration of phagocytic cells and encapsulation by fibrous tissue. These data are consistent with a phagocytic delivery mechanism for azithromycin, whereby the presence of high concentrations of azithromycin in inflammatory fluid are a consequence of augmented drug distribution via the release of accumulated intracellular drug from the infiltrating phagocytic cells and fibroblasts associated with abscess formation. PMID:8396089

  17. Household willingness to pay for azithromycin treatment for trachoma control in the United Republic of Tanzania.

    PubMed Central

    Frick, Kevin D.; Lynch, Matthew; West, Sheila; Munoz, Beatriz; Mkocha, Harran A.

    2003-01-01

    OBJECTIVE: Household willingness to pay for treatment provides important information for programme planning. We tested for relationships between socioeconomic status, risk of trachoma, perceptions of the effects of azithromycin, and the household willingness to pay for future mass treatment with azithromycin. METHODS: We surveyed 394 households in 6 villages located in central United Republic of Tanzania regarding their willingness to pay for future azithromycin treatment. A random sample of households with children under 8 years of age was selected and interviewed following an initial treatment programme in each village. Data were gathered on risk factors for trachoma, socioeconomic status, and the perceived effect of the initial azithromycin treatment. Ordered probit regression analysis was used to test for statistically significant relationships. FINDINGS: 38% of responding households stated that they would not be willing to pay anything for future azithromycin treatment, although they would be willing to participate in the treatment. A proxy for cash availability was positively associated with household willingness to pay for future antibiotic treatment. Cattle ownership (a risk factor) and being a household headed by a female not in a polygamous marriage (lower socioeconomic status) were associated with a lower willingness to pay for future treatment. A perceived benefit from the initial treatment was marginally associated with a willingness to pay a higher amount. CONCLUSIONS: As those at greatest risk of active trachoma indicated the lowest willingness to pay, imposing a cost recovery fee for azithromycin treatment would likely reduce coverage and could prevent control of the disease at the community level. PMID:12751418

  18. Dynamics of Clarithromycin and Azithromycin Efficacies against Experimental Haemophilus influenzae Pulmonary Infection

    PubMed Central

    Alder, J. D.; Ewing, P. J.; Nilius, A. M.; Mitten, M.; Tovcimak, A.; Oleksijew, A.; Jarvis, K.; Paige, L.; Tanaka, S. K. T.

    1998-01-01

    The dynamics of clarithromycin and azithromycin efficacy against pulmonary Haemophilus influenzae infection in rats were evaluated. Efficacy was measured by reduction in pulmonary H. influenzae burden on days 3 and 7 postinoculation. Clarithromycin therapy was effective on day 3 or 7 of therapy, while azithromycin was effective on day 7 but not on day 3 of therapy. Both macrolides produced marked efficacy against all six strains of H. influenzae tested, including four strains for which MICs were above the susceptible breakpoint (8 μg/ml) concentration of clarithromycin. The two macrolides demonstrated markedly different pharmacokinetic characteristics, with clarithromycin present in both blood and tissue, while azithromycin was concentrated primarily in tissue. During pulmonary infection in rats, H. influenzae was found in both intracellular locations and an extracellular location in the lung. Blood concentrations of clarithromycin and azithromycin approximated human pharmacokinetics, and the blood concentrations for either macrolide rarely exceeded MICs for H. influenzae. At dosages producing blood concentrations similar to values achieved clinically, clarithromycin produced efficacy on day 3 of therapy, while both clarithromycin and azithromycin were equally effective on day 7. The different dynamics of clarithromycin and azithromycin suggest that length of therapy should be considered as a key parameter in evaluations of drug efficacy. PMID:9736568

  19. Prophylactic Azithromycin Therapy After Lung Transplantation: Post hoc Analysis of a Randomized Controlled Trial.

    PubMed

    Ruttens, D; Verleden, S E; Vandermeulen, E; Bellon, H; Vanaudenaerde, B M; Somers, J; Schoonis, A; Schaevers, V; Van Raemdonck, D E; Neyrinck, A; Dupont, L J; Yserbyt, J; Verleden, G M; Vos, R

    2016-01-01

    Prophylactic azithromycin treatment has been demonstrated to improve freedom from bronchiolitis obliterans syndrome (BOS) 2 years after lung transplantation (LTx). In the current study, we re-evaluated the long-term effects of this prophylactic approach in view of the updated classification system for chronic lung allograft dysfunction (CLAD). A retrospective, intention-to-treat analysis of a randomized controlled trial comparing prophylactic treatment with placebo (n = 43) versus azithromycin (n = 40) after LTx was performed. Graft dysfunction (CLAD), graft loss (retransplantation, mortality), evolution of pulmonary function and functional exercise capacity were analyzed 7 years after inclusion of the last study subject. Following LTx, 22/43 (51%) patients of the placebo group and 11/40 (28%) patients of the azithromycin group ever developed CLAD (p = 0.043). CLAD-free survival was significantly longer in the azithromycin group (p = 0.024). No difference was present in proportion of obstructive versus restrictive CLAD between both groups. Graft loss was similar in both groups: 23/43 (53%) versus 16/40 (40%) patients (p = 0.27). Long-term pulmonary function and functional exercise capacity were significantly better in the azithromycin group (p < 0.05). Prophylactic azithromycin therapy reduces long-term CLAD prevalence and improves CLAD-free survival, pulmonary function, and functional exercise capacity after LTx. PMID:26372728

  20. Azithromycin plus chloroquine: combination therapy for protection against malaria and sexually transmitted infections in pregnancy

    PubMed Central

    Chico, R Matthew; Chandramohan, Daniel

    2011-01-01

    Introduction: The first-line therapy for the intermittent preventive treatment of malaria in pregnancy (IPTp) is sulphadoxine-pyrimethamine (SP). There is an urgent need to identify safe, well-tolerated and efficacious alternatives to SP due to widespread Plasmodium falciparum resistance. Combination therapy using azithromycin and chloroquine is one possibility that has demonstrated adequate parasitological response > 95% in clinical trials of non-pregnant adults in sub-Saharan Africa and where IPTp is a government policy in 33 countries. Areas covered: Key safety, tolerability and efficacy data are presented for azithromycin and chloroquine, alone and/or in combination, when used to prevent and/or treat P. falciparum, P. vivax, and several curable sexually transmitted and reproductive tract infections (STI/RTI). Pharmacokinetic evidence from pregnant women is also summarized for both compounds. Expert opinion: The azithromycin-chloroquine regimen that has demonstrated consistent efficacy in non-pregnant adults has been a 3-day course containing daily doses of 1 g of azithromycin and 600 mg base of chloroquine. The pharmacokinetic evidence of these compounds individually suggests that dose adjustments may not be necessary when used in combination for treatment efficacy against P. falciparum, P. vivax, as well as several curable STI/ RTI among pregnant women, although clinical confirmation will be necessary. Mass trachoma-treatment campaigns have shown that azithromycin selects for macrolide resistance in the pneumococcus, which reverses following the completion of therapy. Most importantly, no evidence to date suggests that azithromycin induces pneumococcal resistance to penicillin. PMID:21736423

  1. One man's poison is another man's meat: using azithromycin-induced phospholipidosis to promote ocular surface health.

    PubMed

    Liu, Yang; Kam, Wendy R; Ding, Juan; Sullivan, David A

    2014-06-01

    Drug-induced phospholipidosis (PLD) is a common adverse effect which has led to the termination of clinical trials for many candidate pharmaceuticals. However, this lipid-inducing effect may be beneficial in the treatment of meibomian gland dysfunction (MGD). MGD is the major cause of dry eye disease (DED), which affects 40 million people in the USA and has no cure. Azithromycin (AZM) is a PLD-inducing antibiotic that is used off-label to treat MGD, and is presumably effective because it suppresses the MGD-associated conjunctival inflammation (i.e. posterior blepharitis) and growth of lid bacteria. We hypothesize that AZM can act directly to promote the function of human meibomian gland epithelial cells by inducing PLD in these cells, characterized by the accumulation of lipids and lysosomes. Immortalized human meibomian gland epithelial cells (HMGEC) were cultured with or without azithromycin for 5 days. Cells were evaluated for cholesterol (Filipin) and neutral lipid (LipidTox) staining, as well as the appearance of lysosomes (LysoTracker) and lamellar bodies (transmission electron microscopy, TEM). The lipid composition of cellular lysates was analyzed by high performance thin-layer chromatography. Our findings demonstrate that AZM stimulates the accumulation of free cholesterol, neutral lipids and lysosomes in HMGEC. This AZM-induced increase of neutral lipid content occurred predominantly within lysosomes. Many of these vesicles appeared to be lamellar bodies by TEM, which is the characteristic of PLD. Our findings also show that AZM promotes an accumulation of free and esterified cholesterol, as well as phospholipids in HMGECimmortalized. Our results support our hypothesis and confirm the beneficial effect of PLD induced by AZM on HMGEC. Our discovery reveals a new potential use of PLD-inducing drugs, and makes this adverse effect a beneficial effect. PMID:24613571

  2. Oral azithromycin versus its combination with miltefosine for the treatment of experimental Old World cutaneous leishmaniasis.

    PubMed

    Amer, Eglal I; Eissa, Maha M; Mossallam, Shereen F

    2016-06-01

    Leishmaniasis is one of the neglected infectious diseases included in the World Health Organization's list of the top guns of antimicrobial resistance. Miltefosine is the first and the only available oral effective therapy for leishmaniasis. For fear of its potential resistance, identification of alternative, effective and safe drugs is urgently needed. Therefore, in view of azithromycin promising activity against a number of Leishmania species, this work was carried out to evaluate the efficacy of oral azithromycin alone versus its combination with miltefosine against experimental Old World Cutaneous leishmaniasis thus, can provide another alternative oral therapy or for the first time an oral combination therapy for leishmaniasis. The experiment were carried out on Swiss strain albino mice which were treated either with miltefosine for 20 days, Azithromycin for 20 days or both drugs in combination therapy for shorter duration of 10 days. Efficacy of azithromycin mono and combination therapy with miltefosine was evaluated clinically, parasitologically and by examination of the cutaneous lesions by Transmission Electron Microscopy. The current work demonstrated superior activity of oral azithromycin over oral miltefosine in the treatment of experimentally infected mice with Leishmania major (MHOM/IL/81/FEBNI). Unfortunately, oral combination therapy of azithromycin and miltefosine for short duration though, induced dramatic clinical improvement yet, relapse rapidly developed after cessation of therapy. Oral azithromycin could be a promising oral antileishmanial agent. Further research is recommended to investigate its leishmanicidal activity against other Leishmania species thus; another alternative oral therapy for leishmaniasis can be rapidly available. PMID:27413324

  3. Activity and local delivery of azithromycin in a mouse model of Haemophilus influenzae lung infection.

    PubMed Central

    Vallée, E; Azoulay-Dupuis, E; Pocidalo, J J; Bergogne-Bérézin, E

    1992-01-01

    We compared the activities of azithromycin and erythromycin against Haemophilus influenzae in a mouse model of nonparenchymatous lower respiratory tract infection. In vitro and in vivo efficacy data for both drugs were analyzed relative to their pharmacokinetics in lungs and in vivo uptake by phagocytes. Aged C57BL/6 mice (mean age, 15.1 +/- 1.9 months) were infected intratracheally with 10(8) CFU of H. influenzae serotype b. Oral drug administration was initiated 4 h after infection by various dosage regimens. In terms of bacterial killing in the lung, azithromycin was much more active than erythromycin (P less than 0.01). Its in vivo activity was also more durable after a single administration relative to the durability of three doses of erythromycin given at 6-h intervals. The MIC of azithromycin was eightfold lower than that of erythromycin, and better penetration and a longer half-life in lung tissue were achieved after a single oral administration. Phagocytes delivered increased amounts of both drugs to the infected lungs, particularly at the site of infection (bronchoalveolar airspaces), and detectable levels of azithromycin were maintained locally for long periods. The fact that the efficacy of azithromycin coincided with the arrival of large numbers of polymorphonuclear leukocytes within the airspaces suggests that active extracellular concentrations were provided by the release of azithromycin from these cells. This further supports the potential value of once-daily azithromycin regimens for the treatment of lower respiratory tract infections in humans, provided that inhibitory concentrations against common pathogens such as H. influenzae are maintained for adequate periods of time. PMID:1324644

  4. Clinical efficacy of azithromycin for male nongonococcal urethritis.

    PubMed

    Takahashi, Satoshi; Matsukawa, Masanori; Kurimura, Yuichiro; Takeyama, Koh; Kunishima, Yasuharu; Iwasawa, Akihiko; Koroku, Mikio; Tanda, Hitoshi; Suzuki, Nobukazu; Takagi, Yoshio; Hirose, Takaoki; Nishimura, Masahiro; Tsukamoto, Taiji

    2008-12-01

    The aim of this study was to confirm the clinical efficacy of a single-dose azithromycin (AZM) regimen (1000 mg) for patients with nongonococcal urethritis in real-life practice. The study finally evaluated 55 patients, 42 who were symptomatic and 13 who were asymptomatic, after excluding 40 who visited clinics only once. Sixteen of the symptomatic patients were diagnosed as having nongonococcal chlamydial urethritis, 7 as having nongonococcal nonchlamydial urethritis, and 19 as having urethritis without any microbial detection. Chlamydia trachomatis was detected in 11 asymptomatic patients, Mycoplasma genitalium in 1, and Ureaplasma urealyticum in 1. Of the patients who were microbiologically evaluated before and after single-dose AZM, microbiological cure was achieved in 87% (20/23) of those with symptomatic nongonococcal urethritis and in 100% (13/13) of those with asymptomatic nongonococcal urethritis. The clinical cure rate was 86% for the 42 symptomatic patients with detectable and undetectable pathogens. There were adverse events in 5 (9%) patients but they were commonly mild and self-limited. In conclusion, the single-dose AZM regimen was well tolerated and eradicated the estimated and potential pathogens of nongonococcal urethritis. PMID:19089553

  5. Comparison of minocycline and azithromycin for the treatment of mild scrub typhus in northern China.

    PubMed

    Zhao, Minxing; Wang, Ting; Yuan, Xiaoyu; Du, Weiming; Lin, Miaoxin; Shen, Yanbo

    2016-09-01

    Scrub typhus, caused by Orientia tsutsugamushi, has recently emerged in northern China where the disease had not been known to exist. Although doxycycline and azithromycin are the recommended agents for the treatment of scrub typhus, clinical responses depend both on the susceptibilities of various O. tsutsugamushi strains and the severity of the disease. A retrospective analysis was conducted on patients diagnosed with mild scrub typhus from August 2013 to January 2016 in the Affiliated Hospital of Nantong University, northern China. A total of 40 patients who received minocycline treatment and 34 patients who received azithromycin treatment were included in the analysis. All patients except one defervesced within 120 h after initiating antimicrobial therapy. Kaplan-Meier curves in association with log-rank test showed that the median time to defervescence was significantly shorter for the minocycline-treated group than the azithromycin-treated group (P = 0.003). There were no serious adverse events during treatment. No relapse occurred in either group during the 1-month follow-up period. In conclusion, both minocycline and azithromycin are effective and safe for the treatment of mild scrub typhus, but minocycline is more active than azithromycin against O. tsutsugamushi infection acquired in northern China. PMID:27449540

  6. Azithromycin therapy of papillomatosis in dogs: a prospective, randomized, double-blinded, placebo-controlled clinical trial.

    PubMed

    Yağci, Buğrahan Bekir; Ural, Kerem; Ocal, Naci; Haydardedeoğlu, Ali Evren

    2008-08-01

    Azithromycin, an azalide subclass macrolide antibiotic, is an effective, well-tolerated and safe therapeutic option for treatment of papillomatosis in humans. This study reports the clinical and histopathological results from a prospective, randomized, double-blinded, placebo-controlled trial of 17 dogs of various breeds with diagnosis of oral (n = 12) and cutaneous papillomatosis (n = 5) treated with azithromycin. Papillomas appeared as whitish, verrucous, hyperkeratotic papules 1-2.7 mm in size. The cases were randomly assigned to azithromycin (n = 10) and placebo treatment groups (n = 7). Both owners and investigators were blinded to the allocation to the groups. Azithromycin (10 mg/kg) was administered per os every 24 h for 10 days. Clinical evaluations were done by the same investigator throughout the trial. Azithromycin treatment significantly decreased clinical scores (P < 0.001), whereas there was no change seen in the placebo group. In the azithromycin treatment group, skin lesions disappeared in 10-15 days. One case in the placebo had spontaneous regression of its papillomas by day 41, but lesions were still evident at day 50 in the remaining six cases. There was no recurrence of papillomatosis in the azithromycin treated dogs (follow up 8 months). No adverse effects were seen in either group. In conclusion, azithromycin appears to be a safe and effective treatment for canine papillomatosis. PMID:18494759

  7. Screening paediatric rectal forms of azithromycin as an alternative to oral or injectable treatment

    PubMed Central

    Kauss, Tina; Gaudin, Karen; Gaubert, Alexandra; Ba, Boubakar; Tagliaferri, Serena; Fawaz, Fawaz; Fabre, Jean-Louis; Boiron, Jean-Michel; Lafarge, Xavier; White, Nicholas J.; Olliaro, Piero L.; Millet, Pascal

    2012-01-01

    The aim of this study was to identify a candidate formulation for further development of a home or near-home administrable paediatric rectal form of a broad-spectrum antibiotic – specially intended for (emergency) use in tropical rural settings, in particular for children who cannot take medications orally and far from health facilities where injectable treatments can be given. Azithromycin, a broad-spectrum macrolide used orally or intravenously for the treatment of respiratory tract, skin and soft tissue infections, was selected because of its pharmacokinetic and therapeutic properties. Azithromycin in vitro solubility and stability in physiologically relevant conditions were studied. Various pharmaceutical forms, i.e. rectal suspension, two different rectal gels, polyethylene glycol (PEG) suppository and hard gelatin capsule (HGC) were assessed for in vitro dissolution and in vivo bioavailability in the rabbit. Azithromycin PEG suppository appears to be a promising candidate. PMID:22868232

  8. Azithromycin protects mice against ischemic stroke injury by promoting macrophage transition towards M2 phenotype.

    PubMed

    Amantea, Diana; Certo, Michelangelo; Petrelli, Francesco; Tassorelli, Cristina; Micieli, Giuseppe; Corasaniti, Maria Tiziana; Puccetti, Paolo; Fallarino, Francesca; Bagetta, Giacinto

    2016-01-01

    To develop novel and effective treatments for ischemic stroke, we investigated the neuroprotective effects of the macrolide antibiotic azithromycin in a mouse model system of transient middle cerebral artery occlusion. Intraperitoneal administration of azithromycin significantly reduced blood-brain barrier damage and cerebral infiltration of myeloid cells, including neutrophils and inflammatory macrophages. These effects resulted in a dose-dependent reduction of cerebral ischemic damage, and in a remarkable amelioration of neurological deficits up to 7 days after the insult. Neuroprotection was associated with increased arginase activity in peritoneal exudate cells, which was followed by the detection of Ym1- and arginase I-immunopositive M2 macrophages in the ischemic area at 24-48 h of reperfusion. Pharmacological inhibition of peritoneal arginase activity counteracted azithromycin-induced neuroprotection, pointing to a major role for drug-induced polarization of migratory macrophages towards a protective, non-inflammatory M2 phenotype. PMID:26518285

  9. Screening paediatric rectal forms of azithromycin as an alternative to oral or injectable treatment.

    PubMed

    Kauss, Tina; Gaudin, Karen; Gaubert, Alexandra; Ba, Boubakar; Tagliaferri, Serena; Fawaz, Fawaz; Fabre, Jean-Louis; Boiron, Jean-Michel; Lafarge, Xavier; White, Nicholas J; Olliaro, Piero L; Millet, Pascal

    2012-10-15

    The aim of this study was to identify a candidate formulation for further development of a home or near-home administrable paediatric rectal form of a broad-spectrum antibiotic - specially intended for (emergency) use in tropical rural settings, in particular for children who cannot take medications orally and far from health facilities where injectable treatments can be given. Azithromycin, a broad-spectrum macrolide used orally or intravenously for the treatment of respiratory tract, skin and soft tissue infections, was selected because of its pharmacokinetic and therapeutic properties. Azithromycin in vitro solubility and stability in physiologically relevant conditions were studied. Various pharmaceutical forms, i.e. rectal suspension, two different rectal gels, polyethylene glycol (PEG) suppository and hard gelatin capsule (HGC) were assessed for in vitro dissolution and in vivo bioavailability in the rabbit. Azithromycin PEG suppository appears to be a promising candidate. PMID:22868232

  10. Pilot study of the use of community volunteers to distribute azithromycin for trachoma control in Ghana.

    PubMed Central

    Solomon, A. W.; Akudibillah, J.; Abugri, P.; Hagan, M.; Foster, A.; Bailey, R. L.; Mabey, D. C.

    2001-01-01

    OBJECTIVE: To assess the skills of community health volunteers in diagnosing active trachoma and distributing azithromycin in the Northern Region of Ghana. METHODS: Six community health volunteers from Daboya were trained to diagnose trachoma and to treat the disease using azithromycin. They were also informed of the drug's possible side-effects. Under supervision, each volunteer then examined, and if necessary treated, 15 households. The dose of azithromycin was determined by weight; height was also measured. Tablets were given in preference to suspension when possible. RESULTS: The volunteers' diagnostic sensitivity for active trachoma was 63%; their specificity was 96%. At the household level, their "decision to treat" was correct in 83% of households. In 344 treatment episodes, volunteers planned a dose of azithromycin outside the range 15-30 mg/kg on only seven occasions (2.0% of all planned treatments). The volunteers' drug management skills were good, the response of the community was excellent, and adverse reactions were infrequent. Diagnosis of active trachoma, record-keeping skills, and knowledge of side-effects were found to need greater emphasis in any future education programme. Most people aged four years or older were able to swallow tablets. For those taking tablets, the correlation between the data gathered for height and weight shows that calculating azithromycin doses by height is a valid alternative to calculating it by weight. CONCLUSION: Trained community health volunteers have a potential role in identifying active trachoma and distributing azithromycin. To simplify training and logistics, it may be better to base dosage schedules on height rather than weight for those taking tablets, which included most people aged four years or more in the population studied. PMID:11217675

  11. Azithromycin reduces spontaneous and induced inflammation in ΔF508 cystic fibrosis mice

    PubMed Central

    Legssyer, Rachida; Huaux, François; Lebacq, Jean; Delos, Monique; Marbaix, Etienne; Lebecque, Patrick; Lison, Dominique; Scholte, Bob J; Wallemacq, Pierre; Leal, Teresinha

    2006-01-01

    Background Inflammation plays a critical role in lung disease development and progression in cystic fibrosis. Azithromycin is used for the treatment of cystic fibrosis lung disease, although its mechanisms of action are poorly understood. We tested the hypothesis that azithromycin modulates lung inflammation in cystic fibrosis mice. Methods We monitored cellular and molecular inflammatory markers in lungs of cystic fibrosis mutant mice homozygous for the ΔF508 mutation and their littermate controls, either in baseline conditions or after induction of acute inflammation by intratracheal instillation of lipopolysaccharide from Pseudomonas aeruginosa, which would be independent of interactions of bacteria with epithelial cells. The effect of azithromycin pretreatment (10 mg/kg/day) given by oral administration for 4 weeks was evaluated. Results In naive cystic fibrosis mice, a spontaneous lung inflammation was observed, characterized by macrophage and neutrophil infiltration, and increased intra-luminal content of the pro-inflammatory cytokine macrophage inflammatory protein-2. After induced inflammation, cystic fibrosis mice combined exaggerated cellular infiltration and lower anti-inflammatory interleukin-10 production. In cystic fibrosis mice, azithromycin attenuated cellular infiltration in both baseline and induced inflammatory condition, and inhibited cytokine (tumor necrosis factor-α and macrophage inflammatory protein-2) release in lipopolysaccharide-induced inflammation. Conclusion Our findings further support the concept that inflammatory responses are upregulated in cystic fibrosis. Azithromycin reduces some lung inflammation outcome measures in cystic fibrosis mice. We postulate that some of the benefits of azithromycin treatment in cystic fibrosis patients are due to modulation of lung inflammation. PMID:17064416

  12. Azithromycin novel drug delivery system for ocular application

    PubMed Central

    Gilhotra, Ritu Mehra; Nagpal, Kalpana; Mishra, Dina Nath

    2011-01-01

    Background: Azithromycin (AZT) is a macrolide antibiotic derived from and similar in structure to erythromycin. Oral administration of AZT is effective for the treatment of trachoma; however, topical formulations are difficult to develop because of the drug's hydrophobicity. The aim of this study is to formulate a novel topical ophthalmic delivery system of AZT. Materials and Methods: In the present study, ocular inserts of AZT are prepared using alginate, carbopol, and hydroxypropyl methylcellulose (HPMC) to solve the said formulation problem of drug and to facilitate ocular bioavailability. Ocular inserts were prepared by film casting method and the prepared films were subjected to investigations for their physical and mechanical properties, swelling behaviors, ex vivo bioadhesion, and in vitro drug release. Ocular irritation of the developed formulation was also checked by hen's egg chorioallantoic membrane test for ocular irritation potential. Results: The physicochemical, bioadhesive, and swelling properties of films were found to vary significantly depending on the type of polymers used and their combinations. The alginate films exhibited greater bioadhesion and showed higher tensile strength and elasticity than the carbopol films. HPMC addition to the films significantly affected the properties of ocular inserts. Carbopol:HPMC (30:70)-based ocular inserts sustained drug release for longest span of 6 h. The release profile of AZT showed that drug release was by both diffusion and swelling. The formulation was found to be practically nonirritant in ocular irritation studies. Conclusion: AZT can therefore be developed as an ocular insert delivery system for the treatment of ocular surface infections. PMID:23071916

  13. Leaky lysosomes in lung transplant macrophages: azithromycin prevents oxidative damage

    PubMed Central

    2012-01-01

    Background Lung allografts contain large amounts of iron (Fe), which inside lung macrophages may promote oxidative lysosomal membrane permeabilization (LMP), cell death and inflammation. The macrolide antibiotic azithromycin (AZM) accumulates 1000-fold inside the acidic lysosomes and may interfere with the lysosomal pool of Fe. Objective Oxidative lysosomal leakage was assessed in lung macrophages from lung transplant recipients without or with AZM treatment and from healthy subjects. The efficiency of AZM to protect lysosomes and cells against oxidants was further assessed employing murine J774 macrophages. Methods Macrophages harvested from 8 transplant recipients (5 without and 3 with ongoing AZM treatment) and 7 healthy subjects, and J774 cells pre-treated with AZM, a high-molecular-weight derivative of the Fe chelator desferrioxamine or ammonium chloride were oxidatively stressed. LMP, cell death, Fe, reduced glutathione (GSH) and H-ferritin were assessed. Results Oxidant challenged macrophages from transplants recipients without AZM exhibited significantly more LMP and cell death than macrophages from healthy subjects. Those macrophages contained significantly more Fe, while GSH and H-ferritin did not differ significantly. Although macrophages from transplant recipients treated with AZM contained both significantly more Fe and less GSH, which would sensitize cells to oxidants, these macrophages resisted oxidant challenge well. The preventive effect of AZM on oxidative LMP and J774 cell death was 60 to 300 times greater than the other drugs tested. Conclusions AZM makes lung transplant macrophages and their lysososomes more resistant to oxidant challenge. Possibly, prevention of obliterative bronchiolitis in lung transplants by AZM is partly due to this action. PMID:23006592

  14. Azithromycin buccal patch in treatment of chronic periodontitis

    PubMed Central

    Latif, Sajith Abdul; Vandana, K. L.; Thimmashetty, J.; Dalvi, Priyanka Jairaj

    2016-01-01

    Aim: This study aims to explore the clinical, microbiological, and biochemical impact of azithromycin (AZM) buccal patch in chronic generalized patients as a monotherapy as well as an adjunct to nonsurgical therapy. Materials and Methods: A parallel design was used forty periodontitis patients were randomly allocated into five groups, namely Group 1 scaling root planing (SRP) alone, Group 2 (SRP + AZM patch group), Group 3 (SRP + AZM tablet group), Group 4 (AZM patch monotherapy), and Group 5 (AZM tablet as monotherapy). Plaque index, gingival bleeding index, modified gingival index, probing pocket depth (PPD), and clinical attachment level (CAL) were assessed at baseline and 21 and 90 days. Subgingival pooled plaque sample was collected to assess periodontopathogens like Porphyromonas gingivalis and Prevotella intermedia (Pi) by anaerobic culture method. Tumor necrosis factor alpha (TNF-α) was also evaluated at baseline and 21 days. Periodontal maintenance was performed in Group 1 until 90th day, and clinical parameter was assessed at the end of 90th day. Results: SRP + AZM tablets showed greater reduction in clinical parameters (P < 0.05) AZM as monotherapy did not offer clinical benefits over SRP. Baseline data were compared at the end, i.e., 90th day a significant reduction in plaque scores, gingival bleeding, and PPD was observed however no significant gain in the clinical attachment was observed. Conclusion: The monotherapy resulted in no improvement of periodontal parameters, microbial parameters, and TNF-α level. It is safe to use AZM + SRP as a mode of nonsurgical treatment in periodontitis patients. PMID:27127325

  15. Influence of Body Weight, Ethnicity, Oral Contraceptives, and Pregnancy on the Pharmacokinetics of Azithromycin in Women of Childbearing Age

    PubMed Central

    Habibi, Mitra; Kilpatrick, Sarah J.; Tuomala, Ruth E.; Shier, Janice M.; Wollett, Lori; Fischer, Patricia A.; Khorana, Kinnari S.; Rodvold, Keith A.

    2012-01-01

    Women of childbearing age commonly receive azithromycin for the treatment of community-acquired infections, including during pregnancy. This study determined azithromycin pharmacokinetics in pregnant and nonpregnant women and identified covariates contributing to pharmacokinetic variability. Plasma samples were collected by using a sparse-sampling strategy from pregnant women at a gestational age of 12 to 40 weeks and from nonpregnant women of childbearing age receiving oral azithromycin for the treatment of an infection. Pharmacokinetic data from extensive sampling conducted on 12 healthy women were also included. Plasma samples were assayed for azithromycin by high-performance liquid chromatography. Population data were analyzed by nonlinear mixed-effects modeling. The population analysis included 53 pregnant and 25 nonpregnant women. A three-compartment model with first-order absorption and a lag time provided the best fit of the data. Lean body weight, pregnancy, ethnicity, and the coadministration of oral contraceptives were covariates identified as significantly influencing the oral clearance of azithromycin and, except for oral contraceptive use, intercompartmental clearance between the central and second peripheral compartments. No other covariate relationships were identified. Compared to nonpregnant women not receiving oral contraceptives, a 21% to 42% higher dose-adjusted azithromycin area under the plasma concentration-time curve (AUC) occurred in non-African American women who were pregnant or receiving oral contraceptives. Conversely, azithromycin AUCs were similar between pregnant African American women and nonpregnant women not receiving oral contraceptives. Although higher levels of maternal and fetal azithromycin exposure suggest that lower doses be administered to non-African American women during pregnancy, the consideration of azithromycin pharmacodynamics during pregnancy should guide any dose adjustments. PMID:22106226

  16. Clinical Efficacy of Intravenous followed by Oral Azithromycin Monotherapy in Hospitalized Patients with Community-Acquired Pneumonia

    PubMed Central

    Plouffe, Joseph; Schwartz, Douglas B.; Kolokathis, Antonia; Sherman, Bruce W.; Arnow, Paul M.; Gezon, John A.; Suh, Byungse; Anzuetto, Antonio; Greenberg, Richard N.; Niederman, Michael; Paladino, Joseph A.; Ramirez, Julio A.; Inverso, Jill; Knirsch, Charles A.

    2000-01-01

    The purpose of this study was to evaluate intravenous (i.v.) azithromycin followed by oral azithromycin as a monotherapeutic regimen for community-acquired pneumonia (CAP). Two trials of i.v. azithromycin used as initial monotherapy in hospitalized CAP patients are summarized. Clinical efficacy is reported from an open-label randomized trial of azithromycin compared to cefuroxime with or without erythromycin. Bacteriologic and clinical efficacy results are also presented from a noncomparative trial of i.v. azithromycin that was designed to give additional clinical experience with a larger number of pathogens. Azithromycin was administered to 414 patients: 202 and 212 in the comparative and noncomparative trials, respectively. The comparator regimen was used as treatment for 201 patients; 105 were treated with cefuroxime alone and 96 were given cefuroxime plus erythromycin. In the comparative trial, clinical outcome data were available for 268 evaluable patients with confirmed CAP at the 10- to 14-day visit, with 106 (77%) of the azithromycin patients cured or improved and 97 (74%) of the comparator patients cured or improved. Mean i.v. treatment duration and mean total treatment duration (i.v. and oral) for the clinically evaluable patients were significantly (P < 0.05) shorter for the azithromycin group (3.6 days for the i.v. group and 8.6 days for the i.v. and oral group) than for the evaluable patients given cefuroxime plus erythromycin (4.0 days for the i.v. group and 10.3 days for the i.v. and oral group). The present comparative study demonstrates that initial therapy with i.v. azithromycin for hospitalized patients with CAP is associated with fewer side effects and is equal in efficacy to a 1993 American Thoracic Society-suggested regimen of cefuroxime plus erythromycin when the erythromycin is deemed necessary by clinicians. PMID:10858333

  17. Azithromycin and erythromycin ameliorate the extent of colonic damage induced by acetic acid in rats

    SciTech Connect

    Mahgoub, Afaf . E-mail: afaf_mahgoub@yahoo.com; El-Medany, Azza; Mustafa, Ali; Arafah, Maha; Moursi, Mahmoud

    2005-05-15

    Ulcerative colitis is a common inflammatory bowel disease (IBD) of unknown etiology. Recent studies have revealed the role of some microorganisms in the initiation and perpetuation of IBD. The role of antibiotics in the possible modulation of colon inflammation is still uncertain. In this study, we evaluated the effects of two macrolides, namely azithromycin and erythromycin, at different doses on the extent and severity of ulcerative colitis caused by intracolonic administration of 3% acetic acid in rats. The lesions and the inflammatory response were assessed by histology and measurement of myeloperoxidase (MPO) activity, nitric oxide synthetase (NOS) and tumor necrosis factor alpha (TNF{alpha}) in colonic tissues. Inflammation following acetic acid instillation was characterized by oedema, diffuse inflammatory cell infiltration and necrosis. Increase in MPO, NOS and TNF{alpha} was detected in the colonic tissues. Administration of either azithromycin or erythromycin at different dosage (10, 20 and 40 mg/kg orally, daily for 5 consecutive days) significantly (P < 0.05) reduced the colonic damage, MPO and NOS activities as well as TNF{alpha} level. This reduction was highly significant with azithromycin when given at a dose of 40 mg/kg. It is concluded that azithromycin and erythromycin may have a beneficial therapeutic role in ulcerative colitis.

  18. Decline in Decreased Cephalosporin Susceptibility and Increase in Azithromycin Resistance in Neisseria gonorrhoeae, Canada

    PubMed Central

    Sawatzky, P.; Liu, G.; Allen, V; Lefebvre, B.; Hoang, L.; Drews, S.; Horsman, G.; Wylie, J.; Haldane, D.; Garceau, R.; Ratnam, S.; Wong, T.; Archibald, C.; Mulvey, M.R.

    2016-01-01

    Antimicrobial resistance profiles were determined for Neisseria gonorrhoeae strains isolated in Canada during 2010–2014. The proportion of isolates with decreased susceptibility to cephalosporins declined significantly between 2011 and 2014, whereas azithromycin resistance increased significantly during that period. Continued surveillance of antimicrobial drug susceptibilities is imperative to inform treatment guidelines. PMID:26689114

  19. Antimicrobial susceptibility to azithromycin among Salmonella enterica isolated from the United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Due to emerging resistance to traditional antimicrobial agents such as ampicillin, trimethoprim-sulfamethoxazole and chloramphenicol, azithromycin is increasingly used for the treatment of invasive Salmonella infections. In the present study, 696 isolates of non-Typhi Salmonella collected from human...

  20. Shigella spp. with reduced azithromycin susceptibility, Quebec, Canada, 2012-2013.

    PubMed

    Gaudreau, Christiane; Barkati, Sapha; Leduc, Jean-Michel; Pilon, Pierre A; Favreau, Julie; Bekal, Sadjia

    2014-05-01

    During 2012-2013 in Montreal, Canada, 4 locally acquired Shigella spp. pulse types with the mph(A) gene and reduced susceptibility to azithromycin were identified from 9 men who have sex with men, 7 of whom were HIV infected. Counseling about prevention of enteric sexually transmitted infections might help slow transmission of these organisms. PMID:24750584

  1. Azithromycin-Resistant Syphilis-Causing Strains in Sydney, Australia: Prevalence and Risk Factors

    PubMed Central

    Jeoffreys, Neisha; Tagg, Kaitlin; Guy, Rebecca J.; Gilbert, Gwendolyn L.; Donovan, Basil

    2014-01-01

    Azithromycin has shown high efficacy in randomized trials when used for treating infectious syphilis in Africa. However, its use in clinical practice has been limited by the development of antimicrobial drug resistance. Resistance has not previously been reported from Australasia. The aim of this study was to determine the prevalence of and risk factors for azithromycin-resistant syphilis-causing strains in Sydney, Australia. We evaluated 409 samples that were PCR positive for Treponema pallidum DNA collected between 2004 and 2011 for the presence of the A2058G mutation, which confers resistance to macrolide antibiotics such as azithromycin. Overall, 84% of samples harbored the mutation. The prevalence of the mutation increased during the study period (P trend, 0.003). We also collected clinical and demographic data on 220 patients from whom these samples had been collected to determine factors associated with the A2058G mutation; 97% were from men who have sex with men. Reporting sex in countries other than Australia was associated with less macrolide resistance (adjusted odds ratio, 0.25; 95% confidence interval, 0.09 to 0.66; P = 0.005), with other study factors showing no association (age, HIV status, recent macrolide use, stage of syphilis, or history of prior syphilis). Azithromycin cannot be recommended as an alternative treatment for syphilis in Sydney. PMID:24850356

  2. Azithromycin inhibits IL-1 secretion and non-canonical inflammasome activation

    PubMed Central

    Gualdoni, Guido A.; Lingscheid, Tilman; Schmetterer, Klaus G.; Hennig, Annika; Steinberger, Peter; Zlabinger, Gerhard J.

    2015-01-01

    Deregulation of inflammasome activation was recently identified to be involved in the pathogenesis of various inflammatory diseases. Although macrolide antibiotics display well described immunomodulatory properties, presumably involved in their clinical effects, their impact on inflammasome activation has not been investigated. We compared the influence of macrolides on cytokine induction in human monocytes. The role of intracellular azithromycin-accumulation was examined by interference with Ca++-dependent uptake. We have also analysed the signalling cascades involved in inflammasome activation, and substantiated the findings in a murine sepsis model. Azithromycin, but not clarithromycin or roxithromycin, specifically inhibited IL-1α and IL-1β secretion upon LPS stimulation. Interference with Ca++-dependent uptake abolished the cytokine-modulatory effect, suggesting a role of intracellular azithromycin accumulation in the modulatory role of this macrolide. Azithromycin’s inhibiting effects were observed upon LPS, but not upon flagellin, stimulation. Consistent with this observation, we found impaired induction of the LPS-sensing caspase-4 whereas NF-κB signalling was unaffected. Furthermore, azithromycin specifically affected IL-1β levels in a murine endotoxin sepsis model. We provide the first evidence of a differential impact of macrolides on the inflammasome/IL-1β axis, which may be of relevance in inflammasome-driven diseases such as chronic obstructive pulmonary disease or asthma. PMID:26152605

  3. Shigella spp. with Reduced Azithromycin Susceptibility, Quebec, Canada, 2012–2013

    PubMed Central

    Barkati, Sapha; Leduc, Jean-Michel; Pilon, Pierre A.; Favreau, Julie; Bekal, Sadjia

    2014-01-01

    During 2012–2013 in Montreal, Canada, 4 locally acquired Shigella spp. pulse types with the mph(A) gene and reduced susceptibility to azithromycin were identified from 9 men who have sex with men, 7 of whom were HIV infected. Counseling about prevention of enteric sexually transmitted infections might help slow transmission of these organisms. PMID:24750584

  4. The Effect of Intravitreal Azithromycin on the Albino Newborn Rabbit Retina

    PubMed Central

    Cam, Duygu; Saatci, Ali Osman; Micili, Serap Cilaker; Ergur, Bekir Ugur; Karabag, Revan Yildirim; Durak, Ismet; Berk, Ayse Tulin

    2016-01-01

    Purpose: To evaluate the effect of intravitreal azithromycin on the retina in a newborn rabbit model. Methods: Twelve, two-week old New Zealand albino rabbits were divided into two groups (six in each). The right eyes of six rabbits received 0.75 mg (0.05 mL) azithromycin and the right eyes of the remaining six rabbits 1.5 mg (0.1 mL) azithromycin intravitreally. Left eyes were served as the control and received the same volume of saline. All eyes were enucleated at the third postinjection week. Retinal histology was examined by light microscopy. Apoptosis of the retinal cells was further evaluated by immunohistochemical staining for caspase-3 and in situ terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) of DNA fragments. Results: Light microscopy demonstrated no retinal abnormalities in all eyes. However, retinal nuclear DNA fragmentation was evident in both study groups (33.6% with 1.5 mg and 21.4% with 0.75 mg azithromycin) with the TUNEL method. TUNEL staining ratio was statistically higher only in the second group treated with 1.5 mg azithromycin when compared to the control group (p=0.01 Mann Whitney U test). The ratio of caspase-3 positive cells in the two study groups was 21.5% and 20.2%, respectively. Caspase-3 staining ratio was statistically higher in both study groups when compared to the control eyes (p=0.00, p=0.00 respectively). The difference of TUNEL staining ratio between the two study groups was statistically significant (p=0.028), but there were no statistically significant differences in the two study groups by caspase-3 staining (p=0.247). Conclusion: In newborn rabbits, intravitreal azithromycin injection resulted in an apoptotic activity in the photoreceptor, bipolar and ganglion cells. Immunohistochemical analysis suggested that doses of 0.75 mg and 1.5 mg azithromycin, administered intravitreally might be toxic to the newborn rabbit retina. PMID:27014381

  5. Development of a population pharmacokinetic model characterizing the tissue distribution of azithromycin in healthy subjects.

    PubMed

    Zheng, Songmao; Matzneller, Peter; Zeitlinger, Markus; Schmidt, Stephan

    2014-11-01

    Recent clinical trials indicate that the use of azithromycin is associated with the emergence of macrolide resistance. The objective of our study was to simultaneously characterize free target site concentrations and correlate them with the MIC90s of clinically relevant pathogens. Azithromycin (500 mg once daily [QD]) was administered orally to 6 healthy male volunteers for 3 days. The free concentrations in the interstitial space fluid (ISF) of muscle and subcutaneous fat tissue as well as the total concentrations in plasma and polymorphonuclear leukocytes (PMLs) were determined on days 1, 3, 5, and 10. All concentrations were modeled simultaneously in NONMEM 7.2 using a tissue distribution model that accounts for nonlinear protein binding and ionization state at physiological pH. The model performance and parameter estimates were evaluated via goodness-of-fit plots and nonparametric bootstrap analysis. The model we developed described the concentrations at all sampling sites reasonably well and showed that the overall pharmacokinetics of azithromycin is driven by the release of the drug from acidic cell/tissue compartments. The model-predicted unionized azithromycin (AZM) concentrations in the cytosol of PMLs (6.0 ± 1.2 ng/ml) were comparable to the measured ISF concentrations in the muscle (8.7 ± 2.9 ng/ml) and subcutis (4.1 ± 2.4 ng/ml) on day 10, whereas the total PML concentrations were >1,000-fold higher (14,217 ± 2,810 ng/ml). The total plasma and free ISF concentrations were insufficient to exceed the MIC90s of the skin pathogens at all times. Our results indicate that the slow release of azithromycin from low pH tissue/cell compartments is responsible for the long terminal half-life of the drug and thus the extended period of time during which free concentrations reside at subinhibitory concentrations. PMID:25155592

  6. Revisit of fluoroquinolone and azithromycin susceptibility breakpoints for Salmonella enterica serovar Typhi.

    PubMed

    Das, Surojit; Ray, Ujjwayini; Dutta, Shanta

    2016-07-01

    In recent years, increase in occurrence of fluoroquinolone (FQ)-resistant S almonella Typhi isolates has caused considerable inconvenience in selecting appropriate antimicrobials for treatment of typhoid. The World Health Organization (WHO) recommends azithromycin for the empirical treatment option of uncomplicated typhoid. The CLSI updated the breakpoints of disc diffusion (DD) and MIC results of FQs and azithromycin for Salmonella Typhi in 2015, but DD breakpoints of ofloxacin and levofloxacin were not included. In this study, the inhibition zone diameters and MICs of nalidixic acid, ciprofloxacin, ofloxacin, levofloxacin and azithromycin were determined in Salmonella Typhi Kolkata isolates (n =146) over a 16-year period (1998 to 2013) and the data were compared with the available CLSI breakpoints. Very major error and major error (ME) of FQs were not observed in the study isolates, but the minor error of ciprofloxacin (15.8 %) and ME of azithromycin (3.5 %) exceeded the acceptable limit. A positive correlation between MICs of FQ and mutations in the quinolone-resistance-determining region (QRDR) showed the reliability of MIC results to determine FQ susceptibility of Salmonella Typhi (n =74). Isolates showing decreased ciprofloxacin susceptibility (MIC 0.125-0.5 µg  ml-1) were likely to have at least one mutation in the QRDR region. The results on DD breakpoints of ofloxacin (resistant, ≤15 mm; intermediate, 16-24 mm, and susceptible, ≥25 mm) and levofloxacin (resistant, ≤18 mm; intermediate, 19-27 mm, and susceptible, ≥28 mm) corroborated those of earlier studies. In view of the emerging FQ- and azithromycin-resistant Salmonella Typhi isolates, DD and MIC breakpoints of those antimicrobials should be revisited routinely. PMID:27221661

  7. Impact of Community Mass Treatment with Azithromycin for Trachoma Elimination on the Prevalence of Yaws

    PubMed Central

    Marks, Michael; Vahi, Ventis; Sokana, Oliver; Chi, Kai-Hua; Puiahi, Elliot; Kilua, Georgina; Pillay, Allan; Dalipanda, Tenneth; Bottomley, Christian; Solomon, Anthony W.; Mabey, David C.

    2015-01-01

    Background Community mass treatment with 30mg/kg azithromycin is central to the new WHO strategy for eradicating yaws. Both yaws and trachoma— which is earmarked for elimination by 2020 using a strategy that includes mass treatment with 20mg/kg azithromycin—are endemic in the Pacific, raising the possibility of an integrated approach to disease control. Community mass treatment with azithromycin for trachoma elimination was conducted in the Solomon Islands in 2014. Methods We conducted a study to assess the impact of mass treatment with 20mg/kg azithromycin on yaws. We examined children aged 5-14 years and took blood and lesion samples for yaws diagnosis. Results We recruited 897 children, 6 months after mass treatment. There were no cases of active yaws. Serological evidence of current infection was found in 3.6% (95% CI= 2.5-5.0%). This differed significantly between individuals who had and had not received azithromycin (2.8% vs 6.5%, p=0.015); the prevalence of positive serology in 5-14 year-olds had been 21.7% (95% CI=14.6%-30.9%) 6 months prior to mass treatment. Not receiving azithromycin was associated with an odds of 3.9 for infection (p=0.001). National figures showed a 57% reduction in reported cases of yaws following mass treatment. Discussion Following a single round of treatment we did not identify any cases of active yaws in a previously endemic population. We found a significant reduction in latent infection. Our data support expansion of the WHO eradication strategy and suggest an integrated approach to the control of yaws and trachoma in the Pacific may be viable. PMID:26241484

  8. Efficacy and safety of short duration azithromycin eye drops versus azithromycin single oral dose for the treatment of trachoma in children: a randomised, controlled, double‐masked clinical trial

    PubMed Central

    Cochereau, Isabelle; Goldschmidt, Pablo; Goepogui, André; Afghani, Tayyab; Delval, Laurent; Pouliquen, Pascale; Bourcier, Tristan; Robert, Pierre‐Yves

    2007-01-01

    Aims Efficacy and safety of a short‐duration treatment of azithromycin 1.5% eye drops versus oral azithromycin to treat active trachoma. Methods Randomised, controlled, double‐masked, double‐dummy, non‐inferiority explanatory study including 670 children from Guinea Conakry and Pakistan if: 1–10 years old; active trachoma (TF+TI0 or TF+TI+ on simplified World Health Organisation (WHO) scale). Three groups received either: azithromycin 1.5% eye drops twice daily for 2 days, for 3 days or azithromycin single 20 mg/kg oral dose. Patients' contacts were treated whenever possible. Clinical evaluation was performed using a binocular loupe. Primary efficacy variable was the cure (no active trachoma (TF0)) at day 60. Non‐inferiority margin for difference between cure rates was 10%. Results Cure rate in per protocol set was as follows: 93.0%, 96.3% and 96.6% in 2‐day group 3‐day group, and oral treatment group, respectively. Azithromycin 1.5% groups were non‐inferior to oral azithromycin. The intend to treat (ITT) analysis supported the results. Clinical re‐emergence rate was low: 4.2%. Ocular tolerance was similar for all groups. No treatment related adverse events were reported. Logistic regression analyses found prognostic factors such as: country (p<0.001) and trachoma severity (p = 0.003). Conclusions In active trachoma, azithromycin eye drops twice daily for 2 or 3 days are as efficient as the WHO's reference treatment and represent an innovative alternative to oral azithromycin. PMID:17005549

  9. In Vitro and In Vivo Antimicrobial Activities of Minocycline in Combination with Azithromycin, Clarithromycin, or Tigecycline against Pythium insidiosum

    PubMed Central

    Jesus, Francielli P. K.; Loreto, Érico S.; Ferreiro, Laerte; Driemeier, David; Souza, Suyene O.; França, Raqueli T.; Lopes, Sonia T. A.; Pilotto, Maiara B.; Ludwig, Aline; Azevedo, Maria I.; Ribeiro, Tatiana C.; Tondolo, Juliana S. M.

    2015-01-01

    The present study investigated the in vitro and the in vivo interactions among azithromycin, clarithromycin, minocycline, and tigecycline against Pythium insidiosum. In vitro antimicrobial activities were determined by the broth microdilution method in accordance with CLSI document M38-A2, and the antibiotic interactions were assayed using the checkerboard MIC format. In vivo efficacy was determined using a rabbit infection model. The geometric mean MICs of azithromycin, clarithromycin, minocycline, and tigecycline against P. insidiosum were, respectively, 1.91, 1.38, 0.91, and 0.79 μg/ml. By checkerboard testing, all combinations resulted in in vitro synergistic interactions (>60%). Antagonism was not observed. The in vivo studies showed that azithromycin (20 mg/kg/day twice daily) alone or in combination with minocycline (10 mg/kg/day twice daily) significantly decreased the fungal burden. This study demonstrates that azithromycin possesses potent curative efficacy against subcutaneous pythiosis in the rabbit model. PMID:26459895

  10. In Vitro and In Vivo Antimicrobial Activities of Minocycline in Combination with Azithromycin, Clarithromycin, or Tigecycline against Pythium insidiosum.

    PubMed

    Jesus, Francielli P K; Loreto, Érico S; Ferreiro, Laerte; Alves, Sydney H; Driemeier, David; Souza, Suyene O; França, Raqueli T; Lopes, Sonia T A; Pilotto, Maiara B; Ludwig, Aline; Azevedo, Maria I; Ribeiro, Tatiana C; Tondolo, Juliana S M; Santurio, Janio M

    2016-01-01

    The present study investigated the in vitro and the in vivo interactions among azithromycin, clarithromycin, minocycline, and tigecycline against Pythium insidiosum. In vitro antimicrobial activities were determined by the broth microdilution method in accordance with CLSI document M38-A2, and the antibiotic interactions were assayed using the checkerboard MIC format. In vivo efficacy was determined using a rabbit infection model. The geometric mean MICs of azithromycin, clarithromycin, minocycline, and tigecycline against P. insidiosum were, respectively, 1.91, 1.38, 0.91, and 0.79 μg/ml. By checkerboard testing, all combinations resulted in in vitro synergistic interactions (>60%). Antagonism was not observed. The in vivo studies showed that azithromycin (20 mg/kg/day twice daily) alone or in combination with minocycline (10 mg/kg/day twice daily) significantly decreased the fungal burden. This study demonstrates that azithromycin possesses potent curative efficacy against subcutaneous pythiosis in the rabbit model. PMID:26459895

  11. High Resistance to Azithromycin in Clinical Samples from Patients with Sexually Transmitted Diseases in Guangxi Zhuang Autonomous Region, China.

    PubMed

    Zhu, Bangyong; Bu, Jin; Li, Wei; Zhang, Jie; Huang, Geng; Cao, Juan; Tang, Zhongshu; Gan, Quan; Wei, Pingjiang

    2016-01-01

    Azithromycin is used as an alternative medicine in patients with syphilis who are intolerant to penicillin. Nevertheless, the report of treatment failure of azithromycin for patients with syphilis has raised concerns in China in the past years. In this study, 178 patients with early syphilis, who were treated in sexually transmitted infections clinics in four cities in Guangxi Zhuang Autonomous Region were enrolled to investigate the regional prevalence of Treponema pallidum strain resistant to azithromycin. Nested PCR was performed to amplify the 23S ribosomal RNA (23SrRNA) gene. The point mutation of A2058G in 23SrRNA, which confers Treponema pallidum resistance to azithromycin, was measured by endonuclease digestion of PCR amplification products using MboII. A2058G point mutation was detected in 91.0% (162/178; 95% CI, 86.8%, 95.2%) of the specimens, but no difference in prevalence of azithromycin resistance was found between the patients who had taken antibiotics before enrollment and the patients who had not (91.8% vs. 89.4%), nor between the patients with and without past sexually transmitted infections (87.1% vs. 93.1%). We concluded that azithromycin may not be suitable for syphilis as a treatment option in Guangxi Zhuang Autonomous Region because of the extremely high prevalence of resistance in the general syphilis population. PMID:27467164

  12. High Resistance to Azithromycin in Clinical Samples from Patients with Sexually Transmitted Diseases in Guangxi Zhuang Autonomous Region, China

    PubMed Central

    Zhu, Bangyong; Li, Wei; Zhang, Jie; Huang, Geng; Cao, Juan; Tang, Zhongshu; Gan, Quan; Wei, Pingjiang

    2016-01-01

    Azithromycin is used as an alternative medicine in patients with syphilis who are intolerant to penicillin. Nevertheless, the report of treatment failure of azithromycin for patients with syphilis has raised concerns in China in the past years. In this study, 178 patients with early syphilis, who were treated in sexually transmitted infections clinics in four cities in Guangxi Zhuang Autonomous Region were enrolled to investigate the regional prevalence of Treponema pallidum strain resistant to azithromycin. Nested PCR was performed to amplify the 23S ribosomal RNA (23SrRNA) gene. The point mutation of A2058G in 23SrRNA, which confers Treponema pallidum resistance to azithromycin, was measured by endonuclease digestion of PCR amplification products using MboII. A2058G point mutation was detected in 91.0% (162/178; 95% CI, 86.8%, 95.2%) of the specimens, but no difference in prevalence of azithromycin resistance was found between the patients who had taken antibiotics before enrollment and the patients who had not (91.8% vs. 89.4%), nor between the patients with and without past sexually transmitted infections (87.1% vs. 93.1%). We concluded that azithromycin may not be suitable for syphilis as a treatment option in Guangxi Zhuang Autonomous Region because of the extremely high prevalence of resistance in the general syphilis population. PMID:27467164

  13. The Pharmacokinetic-Pharmacodynamic Model of Azithromycin for Lipopolysaccharide-Induced Depressive-Like Behavior in Mice

    PubMed Central

    Hao, Kun; Qi, Qu; Hao, Haiping; Wang, Guangji; Chen, Yuancheng; Liang, Yan; Xie, Lin

    2013-01-01

    A mechanism-based model was developed to describe the time course of lipopolysaccharide-induced depressive-like behavior and azithromycin pharmacodynamics in mice. The lipopolysaccharide-induced disease progression was monitored by lipopolysaccharide, proinflammatory cytokines, and kynrenine concentration in plasma. The depressive-like behavior was investigated by forced swimming test and tail suspension test. Azithromycin was selected to inhibit the surge of proinflammatory cytokines induced by lipopolysaccharide. Disease progression model and azithromycin pharmacodynamics were constructed from transduction and indirect response models. A delay in the onset of increased proinflammatory cytokines, kynrenine, and behavior test compared to lipopolysaccharide was successfully characterized by series transduction models. The inhibition of azithromycin on proinflammatory cytokines was described by an indirect response model. After lipopolysaccharide challenging, the proinflammatory cytokines, kynrenine and behavior tests would peak approximately at 3, 12, and 24 h respectively, and then the time courses slowly declined toward a baseline state after peak response. During azithromycin administration, the peak levels of proinflammatory cytokines, kynrenine and behavior indexes decreased. Model parameters indicated that azithromycin significantly inhibited the proinflammatory cytokines level in plasma and improved the depressive-like behavior induced by inflammation. The integrated model for disease progression and drug intervention captures turnovers of proinflammatory cytokines, kynrenine and the behavior results in the different time phases and conditions. PMID:23358536

  14. Evaluation of the preventive capacities of a topically applied azithromycin formulation against Lyme borreliosis in a murine model

    PubMed Central

    Knauer, Jens; Krupka, Inke; Fueldner, Christiane; Lehmann, Joerg; Straubinger, Reinhard K.

    2011-01-01

    Objectives Systemic antibiotic treatment of Lyme borreliosis is effective during the early stages of the infection, while chronic manifestations of the disease may remain refractory and difficult to treat. This study was carried out in order to evaluate the potential of topically applied azithromycin to eliminate the spirochaetal organisms in the skin of the freshly bitten host and thereby prevent Lyme borreliosis. Methods Laboratory mice were challenged with Borrelia burgdorferi sensu stricto by needle inoculation or via infected ticks as vectors. Then, an azithromycin-containing formulation was applied once daily to the sites of exposure for three consecutive days. In the case of needle inoculation, a 5% azithromycin formulation was applied starting 1 h, 3 days and 5 days after infection. In the case of tick exposure, 4%, 10% and 20% azithromycin formulations were applied, starting directly after the detachment of the engorged ticks. Subsequently, the infection status of the mice was determined. Results Concentrations of azithromycin in murine skin were >3800-fold higher than the published minimal inhibitory concentration for B. burgdorferi as soon as 3 h after the first application. After needle inoculation, spirochaetes were not detectable in all infected mice after treatment, if the first application started 1 h or even after 3 days post-infection. Furthermore, no borrelial organisms were detected after topical treatment when ticks were used for spirochaete inoculation. Conclusions Our data indicate that topical treatment with a formulation containing azithromycin is a promising approach to prevent Lyme borreliosis shortly after a tick bite. PMID:21921078

  15. Babesia gibsoni: detection during experimental infections and after combined atovaquone and azithromycin therapy.

    PubMed

    Jefferies, R; Ryan, U M; Jardine, J; Robertson, I D; Irwin, P J

    2007-10-01

    Babesia gibsoni is a protozoan parasite of dogs worldwide yet both an effective treatment and a reliable method for detecting subclinical cases of this emerging infection remain elusive. Experimental B. gibsoni infections were established in vivo to investigate the efficacy of combined atovaquone and azithromycin drug therapy and to determine the detection limits of a nested-PCR, IFAT and microscopy during various stages of infection. While atovaquone and azithromycin produced a reduction in parasitaemia, it did not eliminate the parasite and drug resistance appeared to develop in one dog. Polymerase chain reaction was found to be most useful in detecting infection in the pre-acute and acute stages, while IFAT was most reliable during chronic infections. Microscopy is suggested to be only effective for detecting acute stage infections. This study also describes the detection of B. gibsoni in tissue samples during chronic infections for the first time, suggesting possible sequestration of this parasite. PMID:17543304

  16. Comparison of two azithromycin distribution strategies for controlling trachoma in Nepal.

    PubMed Central

    Holm, S. O.; Jha, H. C.; Bhatta, R. C.; Chaudhary, J. S.; Thapa, B. B.; Davis, D.; Pokhrel, R. P.; Yinghui, M.; Zegans, M.; Schachter, J.; Frick, K. D.; Tapert, L.; Lietman, T. M.

    2001-01-01

    OBJECTIVE: The study compares the effectiveness of two strategies for distributing azithromycin in an area with mild-to-moderate active trachoma in Nepal. METHODS: The two strategies investigated were the use of azithromycin for 1) mass treatment of all children, or 2) targeted treatment of only those children who were found to be clinically active, as well as all members of their household. FINDINGS: Mass treatment of children was slightly more effective in terms of decreasing the prevalence of clinically active trachoma (estimated by clinical examination) and of chlamydial infection (estimated by DNA amplification tests), although neither result was statistically significant. CONCLUSION: Both strategies appeared to be effective in reducing the prevalence of clinically active trachoma and infection six months after the treatment. Antibiotic treatment reduced the prevalence of chlamydial infection more than it did the level of clinically active trachoma. PMID:11285662

  17. Retrospective comparison of azithromycin, clarithromycin, and erythromycin for the treatment of foals with Rhodococcus equi pneumonia.

    PubMed

    Giguère, Steeve; Jacks, Stephanie; Roberts, Gregory D; Hernandez, Jorge; Long, Maureen T; Ellis, Christina

    2004-01-01

    The objective of this retrospective study was to compare the efficacy of azithromycin-rifampin, clarithromycin-rifampin, and erythromycin-rifampin for the treatment of pneumonia caused by Rhodococcus equi in foals. Eighty-one foals with naturally acquired pneumonia caused by R. equi were included in the study. Information on age, sex, breed, physical examination findings, laboratory testing, and thoracic radiography was abstracted from each medical record. Foals were divided in 3 groups based on the antimicrobial agent selected for therapy. Short-term (discharge from the hospital) and long-term (apparently healthy as a yearling) success rates, days of hospitalization, days with fever, days with tachypnea, and percentage of radiographic improvement were compared among groups. Foals treated with clarithromycin-rifampin had significantly (P = .02) higher odds of overall short-term (odds ratio [OR] = 12.2) and long-term (OR = 20.6) treatment success and significantly fewer days with fever than foals treated with erythromycin-rifampin. Foals treated with clarithromycin-rifampin had a significantly (P = .03) higher percentage of radiographic improvement and a tendency (P = .06) toward higher odds of overall short-term (OR = 8.1) and long-term (OR = 11.8) treatment success compared to foals treated with azithromycin-rifampin. Among foals with severe radiographic lesions, the success rates of foals treated with clarithromycin-rifampin both short-term (88%) and long-term (83%) were significantly (P = .02) higher than that of foals treated with azithromycin-rifampin (0%). For each treatment group, the only reported adverse effect was diarrhea that was mild and self-limiting in most cases. The combination clarithromycin-rifampin is superior to azithromycin-rifampin or erythromycin-rifampin for the treatment of pneumonia caused by R. equi in foals in a referral population. PMID:15320600

  18. High prevalence of azithromycin resistance to Treponema pallidum in geographically different areas in China.

    PubMed

    Chen, X-S; Yin, Y-P; Wei, W-H; Wang, H-C; Peng, R-R; Zheng, H-P; Zhang, J-P; Zhu, B-Y; Liu, Q-Z; Huang, S-J

    2013-10-01

    Treatment with effective antibiotics is one important strategy for syphilis control in China. This study aimed to evaluate the prevalence of azithromycin resistance to T. pallidum in China. A cross-sectional study was conducted among 391 patients with early syphilis recruited from STD clinics in eight cities during October 2008 and October 2011. The swabs were obtained from the moist lesions of the participating patients. A touchdown/nested PCR of the 23S ribosomal RNA (rRNA) gene was performed on DNA samples extracted from these specimens. The presence or absence of the A2058G point mutation, conferring resistance to azithromycin, was determined by restriction enzyme digestion analysis of the PCR amplicon by MboII. Two hundred and eleven patients with primary or secondary syphilis were found to have T. pallidum DNA in their moist lesions by PCR assays. The A2058G mutation was present in 91.9% (194/211, 95% CI, 87.2-95.1%) of these patients, with no significant differences noted between patients from the eastern part (93.8%), southern part (88.6%) and northern part (95.2%) of China (χ(2) = 2.303, p 0.316). Compared with patients who had not taken macrolides in previous years before study entry, the patients who had taken the antibiotics had a significantly higher prevalence of azithromycin resistance (97.0% vs. 62.5%), with an odds ratio of 19.65 (95% CI, 5.77-66.93). It can be concluded that prevalence of azithromycin resistance is substantial in China and consequently that the macrolides should not be used as a treatment option for early or incubating syphilis in China. PMID:23231450

  19. Restoration of Chloride Efflux by Azithromycin in Airway Epithelial Cells of Cystic Fibrosis Patients▿

    PubMed Central

    Saint-Criq, Vinciane; Rebeyrol, Carine; Ruffin, Manon; Roque, Telma; Guillot, Loïc; Jacquot, Jacky; Clement, Annick; Tabary, Olivier

    2011-01-01

    Azithromycin (AZM) has shown promising anti-inflammatory properties in chronic obstructive pulmonary diseases, and clinical studies have presented an improvement in the respiratory condition of cystic fibrosis (CF) patients. The aim of this study was to investigate, in human airway cells, the mechanism by which AZM has beneficial effects in CF. We demonstrated that AZM did not have any anti-inflammatory effect on CF airway cells but restored Cl− efflux. PMID:21220528

  20. Higher organism load associated with failure of azithromycin to treat rectal chlamydia.

    PubMed

    Kong, F Y S; Tabrizi, S N; Fairley, C K; Phillips, S; Fehler, G; Law, M; Vodstrcil, L A; Chen, M; Bradshaw, C S; Hocking, J S

    2016-09-01

    Repeat rectal chlamydia infection is common in men who have sex with men (MSM) following treatment with 1 g azithromycin. This study describes the association between organism load and repeat rectal chlamydia infection, genovar distribution, and efficacy of azithromycin in asymptomatic MSM. Stored rectal chlamydia-positive samples from MSM were analysed for organism load and genotyped to assist differentiation between reinfection and treatment failure. Included men had follow-up tests within 100 days of index infection. Lymphogranuloma venereum and proctitis diagnosed symptomatically were excluded. Factors associated with repeat infection, treatment failure and reinfection were investigated. In total, 227 MSM were included - 64 with repeat infections [28·2%, 95% confidence interval (CI) 22·4-34·5]. Repeat positivity was associated with increased pre-treatment organism load [odds ratio (OR) 1·7, 95% CI 1·4-2·2]. Of 64 repeat infections, 29 (12·8%, 95% CI 8·7-17·8) were treatment failures and 35 (15·4%, 95% CI 11·0-20·8) were reinfections, 11 (17·2%, 95% CI 8·9-28·7) of which were definite reinfections. Treatment failure and reinfection were both associated with increased load (OR 2·0, 95% CI 1·4-2·7 and 1·6, 95% CI 1·2-2·2, respectively). The most prevalent genovars were G, D and J. Treatment efficacy for 1 g azithromycin was 83·6% (95% CI 77·2-88·8). Repeat positivity was associated with high pre-treatment organism load. Randomized controlled trials are urgently needed to evaluate azithromycin's efficacy and whether extended doses can overcome rectal infections with high organism load. PMID:27180823

  1. DEVELOPMENT, CHARACTERIZATION AND SOLUBILITY STUDY OF SOLID DISPERSIONS OF AZITHROMYCIN DIHYDRATE BY SOLVENT EVAPORATION METHOD

    PubMed Central

    Arora, S.C.; Sharma, P.K.; Irchhaiya, Raghuveer; Khatkar, Anurag; Singh, Neeraj; Gagoria, Jagbir

    2010-01-01

    Azithromycin Dihydrate (Poorly water soluble drug), when prepared as solid dispersion showed improved solubility and dissolution. So the main purpose of this investigation was to increase the solubility and dissolution rate of Azithromycin Dihydrate by the preparation of its solid dispersion with urea using solvent evaporation method. Physical mixtures and solid dispersions of Azithromycin Dihydrate were prepared by using urea as water-soluble carrier in various proportions (1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7 by weight), by employing solvent evaporation method. The drug release profile was studied and it was found that the dissolution rate and the dissolution parameters of the drug from the physical mixture as well as solid dispersion were higher than those of the intact drug. FT- IR spectra revealed no chemical incompatibility between drug and urea. Drug-polymer interactions were investigated using differential scanning calorimetry (DSC) and Powder X-Ray Diffraction (PXRD). PMID:22247849

  2. Efficacy of doxycycline, azithromycin, or trovafloxacin for treatment of experimental Rocky Mountain spotted fever in dogs.

    PubMed

    Breitschwerdt, E B; Papich, M G; Hegarty, B C; Gilger, B; Hancock, S I; Davidson, M G

    1999-04-01

    Dogs were experimentally inoculated with Rickettsia rickettsii (canine origin) in order to compare the efficacies of azithromycin and trovafloxacin to that of the current antibiotic standard, doxycycline, for the treatment of Rocky Mountain spotted fever. Clinicopathologic parameters, isolation of rickettsiae in tissue culture, and PCR amplification of rickettsial DNA were used to evaluate the response to therapy or duration of illness (untreated infection control group) in the four groups. Concentrations of the three antibiotics in plasma and blood cells were measured by high-performance liquid chromatography. Doxycycline and trovafloxacin treatments resulted in more-rapid defervescence, whereas all three antibiotics caused rapid improvement in attitudinal scores, blood platelet numbers, and the albumin/total-protein ratio. Based upon detection of retinal vascular lesions by fluorescein angiography, trovafloxacin and doxycycline substantially decreased rickettsia-induced vascular injury to the eye, whereas the number of ocular lesions in the azithromycin group did not differ from that in the infection control group. As assessed by tissue culture isolation, doxycycline resulted in the earliest apparent clearance of viable circulating rickettsiae; however, rickettsial DNA could still be detected in the blood of some dogs from all four groups on day 21 postinfection, despite our inability to isolate viable rickettsiae at that point. As administered in this study, trovafloxacin was as efficacious as doxycycline but azithromycin proved less efficacious, possibly due to the short duration of administration. PMID:10103185

  3. Re-emergence of Babesia conradae and effective treatment of infected dogs with atovaquone and azithromycin.

    PubMed

    Di Cicco, Michael F; Downey, Megan E; Beeler, Emily; Marr, Henry; Cyrog, Peter; Kidd, Linda; Diniz, Pedro Paulo V P; Cohn, Leah A; Birkenheuer, Adam J

    2012-06-01

    Babesia conradae (B. conradae) causes hemolytic anemia in dogs. This organism has not been reported clinically since it was originally described in southern California in 1991. To date, no anti-protozoal therapies have been associated with clearance of B. conradae. This report describes the use of atovaquone and azithromycin for the treatment of dogs naturally infected with B. conradae and report the re-emergence of B. conradae in southern California. Twelve dogs naturally infected with B. conradae were identified by practicing veterinarians and public health officials in southern California. Treatments consisted of a 10 day course of atovaquone (13.3mg/kg PO q 8h) and azithromycin (10-12.5mg/kg PO q 24h). Four dogs were treated in a randomized blinded placebo-controlled fashion, four additional cases were treated in a non-random, non-blinded fashion and one dog received no treatment. All dogs were tested for B. conradae DNA by polymerase chain reaction (PCR) initially and then once or 3 times post treatment (60-210 days). B. conradae infected dogs that received treatment did not have any detectable Babesia DNA by PCR after treatment. In contrast, dogs receiving placebo had detectable Babesia DNA by PCR throughout the study period. Combination therapy with atovaquone and azithromycin appears to be effective for acute and chronic babesiosis caused by B. conradae. PMID:22305297

  4. Review of Azithromycin Ophthalmic 1% Solution (AzaSite®) for the Treatment of Ocular Infections

    PubMed Central

    Opitz, Dominick L.; Harthan, Jennifer S.

    2012-01-01

    AzaSite® (azithromomycin 1.0%) ophthalmic solution was approved in 2007 by the US Food and Drug Administration (FDA) as the first commercially available formulation of ophthalmic azithromycin for the treatment of bacterial conjunctivitis. AzaSite® utilizes a vehicle delivery system called DuraSite®, which stabilizes and sustains the release of azithromycin to the ocular surface, leading to a longer drug residence time, less frequent dosing, and an increase in patient compliance. AzaSite® is a broad spectrum antibiotic, effective against Gram-positive, Gram-negative, and atypical bacteria. AzaSite® has been studied for the treatment of ocular conditions beyond its clinical indication. A number of clinical studies have evaluated its efficacy and safety in the management of ocular conditions such as bacterial conjunctivitis and blepharitis on both the pediatric and adult populations. This article aims to evaluate the peer-reviewed published literature on the use of azithromycin 1.0% ophthalmic for current and possible future ophthalmic uses. PMID:23650453

  5. Azithromycin-chloroquine and the intermittent preventive treatment of malaria in pregnancy

    PubMed Central

    Chico, R Matthew; Pittrof, Rudiger; Greenwood, Brian; Chandramohan, Daniel

    2008-01-01

    In the high malaria-transmission settings of sub-Saharan Africa, malaria in pregnancy is an important cause of maternal, perinatal and neonatal morbidity. Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) reduces the incidence of low birth-weight, pre-term delivery, intrauterine growth-retardation and maternal anaemia. However, the public health benefits of IPTp are declining due to SP resistance. The combination of azithromycin and chloroquine is a potential alternative to SP for IPTp. This review summarizes key in vitro and in vivo evidence of azithromycin and chloroquine activity against Plasmodium falciparum and Plasmodium vivax, as well as the anticipated secondary benefits that may result from their combined use in IPTp, including the cure and prevention of many sexually transmitted diseases. Drug costs and the necessity for external financing are discussed along with a range of issues related to drug resistance and surveillance. Several scientific and programmatic questions of interest to policymakers and programme managers are also presented that would need to be addressed before azithromycin-chloroquine could be adopted for use in IPTp. PMID:19087267

  6. Azithromycin for the treatment of eosinophilic nasal polyposis: Clinical and histologic analysis

    PubMed Central

    Borges Crosara, Paulo Fernando Tormin; Cassali, Geovanni Dantas; dos Reis, Diego Carlos; Rodrigues, Danilo Santana; Nunes, Flavio Barbosa; Guimarães, Roberto Eustáquio Santos

    2016-01-01

    Introduction: Macrolides used as immunomodulators are a promising tool for chronic inflammatory airway diseases. Eosinophilic nasal polyposis (ENP) is still considered a disease that is difficult to control with the currently standardized treatments. Objectives: To evaluate prolonged treatment with low-dose azithromycin for ENP based on clinical and histopathologic variables. Methods: The present investigation was a self-paired case study of 33 patients with ENP. A comparison was performed between patients before and after treatment with azithromycin for 8 weeks. The patients were subjected to clinical examinations, staging (three-dimensional imaging by endoscopy), application of the questionnaire, and biopsy of nasal polyps at the beginning and at the end of the treatment. Results: The treatment yielded a clinical improvement regarding the two variables studied: polyposis staging (69.7%) and questionnaire (57.6%). We did not find significant differences in the inflammatory pattern and in the percentage or absolute number of eosinophils per field between samples obtained before and after the treatment (p > 0.05). There was no difference between the answers obtained from groups with and without asthma and/or aspirin intolerance (p > 0.3). The patients with advanced initial staging exhibited lower subjective improvement index and staging reduction (p = 0.031 and p = 0.012, respectively). Conclusion: Based on this study, azithromycin may be considered as another therapeutic option for ENP. However, further studies are necessary to define the real mechanism of action involved. PMID:27465667

  7. Population Pharmacokinetics of Azithromycin in Whole Blood, Peripheral Blood Mononuclear Cells, and Polymorphonuclear Cells in Healthy Adults

    PubMed Central

    Sampson, M R; Dumitrescu, T P; Brouwer, K L R; Schmith, V D

    2014-01-01

    Azithromycin's extensive distribution to proinflammatory cells, including peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs), may be important to its antimicrobial and anti-inflammatory properties. The need to simultaneously predict azithromycin concentrations in whole blood (“blood”), PBMCs, and PMNs motivated this investigation. A single-dose study in 20 healthy adults was conducted, and nonlinear mixed effects modeling was used to simultaneously describe azithromycin concentrations in blood, PBMCs, and PMNs (simultaneous PK model). Data were well described by a four-compartment mamillary model. Apparent central clearance and volume of distribution estimates were 67.3 l/hour and 336 l (interindividual variability of 114 and 122%, respectively). Bootstrapping and visual predictive checks showed adequate model performance. Azithromycin concentrations in blood, PBMCs, and PMNs from external studies of healthy adults and cystic fibrosis patients were within the 5th and 95th percentiles of model simulations. This novel empirical model can be used to predict azithromycin concentrations in blood, PBMCs, and PMNs with different dosing regimens. PMID:24599342

  8. Azithromycin treatment for nongonococcal urethritis negative for Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum.

    PubMed

    Maeda, Shin-ichi; Yasuda, Mitsuru; Ito, Shin; Seike, Kensaku; Ito, Shin-ichi; Deguchi, Takashi

    2009-02-01

    Some patients with nongonococcal urethritis (NGU) are negative for Chlamydia trachomatis, mycoplasmas, and ureaplasmas. The optimal antimicrobial chemotherapy for such NGU has not fully been clarified. We assessed the efficacy of azithromycin for treatment of nonmycoplasmal, nonureaplasmal, nonchlamydial NGU (NMNUNCNGU). Thirty-eight men whose first-pass urine was negative for Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum were treated with a single dose of 1 g azithromycin. Urethritis symptoms and polymorphonuclear leukocytes in urethral smears or in first-pass urine were assessed before and after treatment with azithromycin. Thirty-two (84.2%) of the 38 men with NMNUNCNGU showed no signs of urethral inflammation after treatment. The efficacy of this azithromycin regimen was comparable to that of the 7-day regimen of levofloxacin, gatifloxacin, minocycline, or clarithromycin reported previously. A single dose of 1 g azithromycin, which is effective not only for NGU due to specific pathogens but also for NMNUNCNGU, is an appropriate treatment for NGU. PMID:19228227

  9. Antimicrobial interference with bacterial mechanisms of pathogenicity: effect of sub-MIC azithromycin on gonococcal piliation and attachment to human epithelial cells.

    PubMed Central

    Gorby, G L; McGee, Z A

    1990-01-01

    The effects of subinhibitory concentrations of azithromycin (CP-62,993) on the piliation and attachment properties of Neisseria gonorrhoeae were examined. Subinhibitory concentrations of azithromycin significantly reduced the percentage of gonococci that expressed assembled pili on their surfaces by decreasing pilin subunit synthesis and substantially decreased gonococcal adherence to human mucosal cells. Images PMID:1982402

  10. On the pathway to better birth outcomes? A systematic review of azithromycin and curable sexually transmitted infections

    PubMed Central

    Chico, R Matthew; Hack, Berkin B; Newport, Melanie J; Ngulube, Enesia; Chandramohan, Daniel

    2013-01-01

    The WHO recommends the administration of sulfadoxine-pyrimethamine (SP) to all pregnant women living in areas of moderate (stable) to high malaria transmission during scheduled antenatal visits, beginning in the second trimester and continuing to delivery. Malaria parasites have lost sensitivity to SP in many endemic areas, prompting the investigation of alternatives that include azithromycin-based combination (ABC) therapies. Use of ABC therapies may also confer protection against curable sexually transmitted infections and reproductive tract infections (STIs/RTIs). The magnitude of protection at the population level would depend on the efficacy of the azithromycin-based regimen used and the underlying prevalence of curable STIs/RTIs among pregnant women who receive preventive treatment. This systematic review summarizes the efficacy data of azithromycin against curable STIs/RTIs. PMID:24191955

  11. Pharmacokinetic and in vivo studies with azithromycin (CP-62,993), a new macrolide with an extended half-life and excellent tissue distribution.

    PubMed

    Girard, A E; Girard, D; English, A R; Gootz, T D; Cimochowski, C R; Faiella, J A; Haskell, S L; Retsema, J A

    1987-12-01

    Azithromycin (CP-62,993), a new acid-stable 15-membered-ring macrolide, was well absorbed following oral administration in mice, rats, dogs, and cynomolgus monkeys. This compound exhibited a uniformly long elimination half-life and was distributed exceptionally well into all tissues. This extravascular penetration of azithromycin was demonstrated by tissue/plasma area-under-the-curve ratios ranging from 13.6 to 137 compared with ratios for erythromycin of 3.1 to 11.6. The significance of these pharmacokinetic advantages of azithromycin over erythromycin was shown through efficacy in a series of animal infection models. Azithromycin was orally effective in treating middle ear infections induced in gerbils by transbulla challenges with amoxicillin-resistant Haemophilus influenzae or susceptible Streptococcus pneumoniae; erythromycin failed and cefaclor was only marginally active against the H. influenzae challenge. Azithromycin was equivalent to cefaclor and erythromycin against Streptococcus pneumoniae. In mouse models, the new macrolide was 10-fold more potent than erythromycin and four other antibiotics against an anaerobic infection produced by Fusobacterium necrophorum. Similarly, azithromycin was effective against established tissue infections induced by Salmonella enteritidis (liver and spleen) and Staphylococcus aureus (thigh muscle); erythromycin failed against both infections. The oral and subcutaneous activities of azithromycin, erythromycin, and cefaclor were similar against acute systemic infections produced by Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, or S. aureus, whereas azithromycin was more potent than erythromycin and cefaclor against the intracellular pathogen Listeria monocytogenes. The pharmacokinetic advantage of azithromycin over erythromycin in half-life was clearly demonstrated in prophylactic treatment of an acute mouse model of S. aureus infection. These properties of azithromycin strongly support the

  12. Effect of azithromycin on the LPS-induced production and secretion of phospholipase A2 in lung cells.

    PubMed

    Kitsiouli, Eirini; Antoniou, Georgia; Gotzou, Helen; Karagiannopoulos, Michalis; Basagiannis, Dimitris; Christoforidis, Savvas; Nakos, George; Lekka, Marilena E

    2015-07-01

    Azithromycin is a member of macrolides, utilized in the treatment of infections. Independently, these antibiotics also possess anti-inflammatory and immunomodulatory properties. Phospholipase A2 isotypes, which are implicated in the pathophysiology of inflammatory lung disorders, are produced by alveolar macrophages and other lung cells during inflammatory response and can promote lung injury by destructing lung surfactant. The aim of the study was to investigate whether in lung cells azithromycin can inhibit secretory and cytosolic phospholipases A2, (sPLA2) and (cPLA2), respectively, which are induced by an inflammatory trigger. In this respect, we studied the lipopolysaccharide (LPS)-mediated production or secretion of sPLA2 and cPLA2 from A549 cells, a cancer bronchial epithelial cell line, and alveolar macrophages, isolated from bronchoalveolar lavage fluid of ARDS and control patients without cardiopulmonary disease or sepsis. Pre-treatment of cells with azithromycin caused a dose-dependent decrease in the LPS-induced sPLA2-IIA levels in A549 cells. This inhibition was rather due to reduced PLA2G2A mRNA expression and secretion of sPLA2-IIA protein levels, as observed by western blotting and indirect immunofluorescence by confocal microscopy, respectively, than to the inhibition of the enzymic activity per se. On the contrary, azithromycin had no effect on the LPS-induced production or secretion of sPLA2-IIA from alveolar macrophages. The levels of LPS-induced c-PLA2 were not significantly affected by azithromycin in either cell type. We conclude that azithromycin exerts anti-inflammatory properties on lung epithelial cells through the inhibition of both the expression and secretion of LPS-induced sPLA2-IIA, while it does not affect alveolar macrophages. PMID:25791017

  13. Comparison of Azithromycin and Clarithromycin Triple Therapy Regimens for Helicobacter Pylori Eradication in Hemodialysis Patients

    PubMed Central

    Jalalzadeh, Mojgan; Nazarian, Morteza; Vafaeimanesh, Jamshid; Mirzamohammadi, Fatemeh

    2012-01-01

    Background Helicobacter pylori eradication with clarithromycin is more expensive than with azithromycin. Objectives This study aimed to compare the effectiveness of these two antibiotics in eradicating H. pylori in hemodialysis (HD) patients. Patients and Methods This is a prospective, randomized, double-blinded clinical trial analysis of HD patients. Patients who had dyspepsia and showed positive results for two of three tests, anti-H. pylori serology, H. pylori stool antigen (HpSAg), or Urease Breath Test (UBT), were included in the study. The subjects consisted of 39 dialysis patients who were randomly divided into two groups that received medication twice daily. Group OAC received 20 mg omeprazol, 500 mg amoxycilin, and 250 mg clarithromycin, and Group OAAz received 20 mg omeprazol, 500 mg amoxicillin, and 250 mg azithromycin. Both regimens were administered for 14 days. Eradication was investigated by performing the UBT and the HpSAg test eight weeks later. Results This study began with 39 patients, 37 of which completed the treatment schedule (20 males and 17 females, mean age 59 years). Two patients died due to MI before beginning treatment. In the OAC group, negative results on the UBT and HpSAg tests were found in 82.4% and 88.2% of the participants, respectively. In the OAAz group, these values were 80% and 85%, respectively. The data showed that the difference between the two regimens was not significant (P = 1.0). Conclusions According to the data, no differences in eradication rates were apparent between the azitromycin and the claritromycin regimens. However, lower cost and fewer complaints could be considered as an advantage of the triple therapy with azithromycin. PMID:23573488

  14. Effects of Fluoroquinolones and Azithromycin on Biofilm Formation of Stenotrophomonas maltophilia

    PubMed Central

    Wang, Aihua; Wang, Qinqin; Kudinha, Timothy; Xiao, Shunian; Zhuo, Chao

    2016-01-01

    Stenotrophomonas maltophilia is an opportunistic pathogen that causes respiratory and urinary tract infections, as well as wound infections in immunocompromised patients. This pathogen is difficult to treat due to increased resistance to many antimicrobial agents. We investigated the in vitro biofilm formation of S. maltophilia, including effects of fluoroquinolones (FQs) and azithromycin on biofilm formation. The organism initiated attachment to polystyrene surfaces after a 4 h incubation period, and reached maximal growth at 18–24 h. In the presence of FQs (moxifloxacin, levofloxacin or ciprofloxacin), the biofilm biomass was significantly reduced (P < 0.05). A lower concentration of moxifloxacin (10 μg/mL) exhibited a better inhibiting effect on biofilm formation than 100 μg/mL (P < 0.01), but with no difference in effect compared to the 50 μg/mL concentration (P > 0.05). However, the inhibitory effects of 10 μg/mL of levofloxacin or ciprofloxacin were slightly less pronounced than those of the higher concentrations. A combination of azithromycin and FQs significantly reduced the biofilm inhibiting effect on S. maltophilia preformed biofilms compared to azithromycin or FQs alone. We conclude that early use of clinically acceptable concentrations of FQs, especially moxifloxacin (10 μg/mL), may possibly inhibit biofilm formation by S. maltophilia. Our study provides an experimental basis for a possible optimal treatment strategy for S. maltophilia biofilm-related infections. PMID:27405358

  15. Effects of Fluoroquinolones and Azithromycin on Biofilm Formation of Stenotrophomonas maltophilia.

    PubMed

    Wang, Aihua; Wang, Qinqin; Kudinha, Timothy; Xiao, Shunian; Zhuo, Chao

    2016-01-01

    Stenotrophomonas maltophilia is an opportunistic pathogen that causes respiratory and urinary tract infections, as well as wound infections in immunocompromised patients. This pathogen is difficult to treat due to increased resistance to many antimicrobial agents. We investigated the in vitro biofilm formation of S. maltophilia, including effects of fluoroquinolones (FQs) and azithromycin on biofilm formation. The organism initiated attachment to polystyrene surfaces after a 4 h incubation period, and reached maximal growth at 18-24 h. In the presence of FQs (moxifloxacin, levofloxacin or ciprofloxacin), the biofilm biomass was significantly reduced (P < 0.05). A lower concentration of moxifloxacin (10 μg/mL) exhibited a better inhibiting effect on biofilm formation than 100 μg/mL (P < 0.01), but with no difference in effect compared to the 50 μg/mL concentration (P > 0.05). However, the inhibitory effects of 10 μg/mL of levofloxacin or ciprofloxacin were slightly less pronounced than those of the higher concentrations. A combination of azithromycin and FQs significantly reduced the biofilm inhibiting effect on S. maltophilia preformed biofilms compared to azithromycin or FQs alone. We conclude that early use of clinically acceptable concentrations of FQs, especially moxifloxacin (10 μg/mL), may possibly inhibit biofilm formation by S. maltophilia. Our study provides an experimental basis for a possible optimal treatment strategy for S. maltophilia biofilm-related infections. PMID:27405358

  16. In Vitro Synergism between Azithromycin or Terbinafine and Topical Antimicrobial Agents against Pythium insidiosum.

    PubMed

    Itaqui, Sabrina R; Verdi, Camila M; Tondolo, Juliana S M; da Luz, Thaisa S; Alves, Sydney H; Santurio, Janio M; Loreto, Érico S

    2016-08-01

    We describe here in vitro activity for the combination of azithromycin or terbinafine and benzalkonium, cetrimide, cetylpyridinium, mupirocin, triclosan, or potassium permanganate. With the exception of potassium permanganate, the remaining antimicrobial drugs were active and had an MIC90 between 2 and 32 μg∕ml. The greatest synergism was observed for the combination of terbinafine and cetrimide (71.4%). In vivo experimental evaluations will clarify the potential of these drugs for the topical treatment of lesions caused by Pythium insidiosum. PMID:27216049

  17. Azithromycin, Ureaplasma and chronic lung disease of prematurity: a case study for neonatal drug development.

    PubMed

    Turner, Mark A; Jacqz-Aigrain, Evelyne; Kotecha, Sailesh

    2012-06-01

    Chronic lung disease of prematurity (CLD) remains a major cause of morbidity and mortality in preterm infants. Ureaplasma has received intermittent attention over the last two decades as a possible contributory factor. In addition, pulmonary inflammation is associated with the development of CLD. The macrolide azithromycin provides an attractive option to determine if it can decrease the development of CLD as it has both anti-inflammatory and anti-infective properties. In this article, the authors review the evidence for the role of Ureaplasma in the development of CLD and the obstacles faced in the development of a drug before it reaches clinical practice. PMID:21697219

  18. Ion-activated In Situ Gelling Ophthalmic Delivery Systems of Azithromycin

    PubMed Central

    Vijaya, C.; Goud, K. Swetha

    2011-01-01

    Gelation of pectin caused by divalent cations especially calcium ions has been applied to develop an ophthalmic formulation of azithromycin in the present study. Rapid elimination of drug on instillation into cul de sac would be minimal with in situ gelling ophthalmic solution leading to increased precorneal contact time and prolonged drug delivery. In the formulation development studies pectin was used in different concentrations (1-5% w/v) and different proportions of the hydrocolloids hydroxypropyl methylcellulose and sodium carboxymethyl cellulose of different grades of viscosity were used. The primary criteria for formulation optimization were gelling capacity and rheological behaviour. In addition, formulations were evaluated for pH, and antimicrobial efficacy and drug release. The clarity, pH, gelation in simulated tear fluid and rheological properties of the optimized formulations were satisfactory. The formulations inhibited the growth of Staphylococcus aureus effectively in cup–plate method and were proved to be safe and non irritant on rabbit eyes. The results indicate that pectin based in situ gels can be successfully used to prolong the duration of action of azithromycin. PMID:23112394

  19. Comparison effect of azithromycin gel 2% with clindamycin gel 1% in patients with acne

    PubMed Central

    Mokhtari, Fatemeh; Faghihi, Gita; Basiri, Akram; Farhadi, Sadaf; Nilforoushzadeh, Mohammadali; Behfar, Shadi

    2016-01-01

    Background: Acne vulgaris is the most common skin disease. Local and systemic antimicrobial drugs are used for its treatment. But increasing resistance of Propionibacterium acnes to antibiotics has been reported. Materials and Methods: In a double-blind clinical trial, 40 patients with mild to moderate acne vulgaris were recruited. one side of the face was treated with Clindamycin Gel 1% and the other side with Azithromycin Topical Gel 2% BID for 8 weeks and then they were assessed. Results: Average age was 21. 8 ± 7 years. 82.5% of them were female. Average number of papules, pustules and comedones was similarly reduced in both groups and, no significant difference was observed between the two groups (P > 0.05, repeated measurs ANOVA). The mean indexes of ASI and TLC also significantly decreased during treatment in both groups, no significant difference was observed between the two groups. (P > 0.05, repeated measurs ANOVA). Also, impact of both drugs on papules and pustules was 2-3 times greater than the effect on comedones. Average satisfaction score was not significant between the two groups (P = 0.6, repeated measurs ANOVA). finally, frequency distribution of complications was not significant between the two groups (P > 0.05, Fisher Exact test). Conclusion: Azithromycin gel has medical impact at least similar to Clindamycin Gel in treatment of mild to moderate acne vulgaris, and it may be consider as suitable drug for resistant acne to conventional topical therapy. PMID:27169103

  20. Attenuation of Pseudomonas aeruginosa biofilm formation by Vitexin: A combinatorial study with azithromycin and gentamicin

    PubMed Central

    Das, Manash C.; Sandhu, Padmani; Gupta, Priya; Rudrapaul, Prasenjit; De, Utpal C.; Tribedi, Prosun; Akhter, Yusuf; Bhattacharjee, Surajit

    2016-01-01

    Microbial biofilm are communities of surface-adhered cells enclosed in a matrix of extracellular polymeric substances. Extensive use of antibiotics to treat biofilm associated infections has led to the emergence of multiple drug resistant strains. Pseudomonas aeruginosa is recognised as a model biofilm forming pathogenic bacterium. Vitexin, a polyphenolic group of phytochemical with antimicrobial property, has been studied for its antibiofilm potential against Pseudomonas aeruginosa in combination with azithromycin and gentamicin. Vitexin shows minimum inhibitory concentration (MIC) at 260 μg/ml. It’s antibiofilm activity was evaluated by safranin staining, protein extraction, microscopy methods, quantification of EPS and in vivo models using several sub-MIC doses. Various quorum sensing (QS) mediated phenomenon such as swarming motility, azocasein degrading protease activity, pyoverdin and pyocyanin production, LasA and LasB activity of the bacteria were also evaluated. Results showed marked attenuation in biofilm formation and QS mediated phenotype of Pseudomonas aeruginosa in presence of 110 μg/ml vitexin in combination with azithromycin and gentamicin separately. Molecular docking of vitexin with QS associated LuxR, LasA, LasI and motility related proteins showed high and reasonable binding affinity respectively. The study explores the antibiofilm potential of vitexin against P. aeruginosa which can be used as a new antibiofilm agent against microbial biofilm associated pathogenesis. PMID:27000525

  1. Attenuation of Pseudomonas aeruginosa biofilm formation by Vitexin: A combinatorial study with azithromycin and gentamicin

    NASA Astrophysics Data System (ADS)

    Das, Manash C.; Sandhu, Padmani; Gupta, Priya; Rudrapaul, Prasenjit; de, Utpal C.; Tribedi, Prosun; Akhter, Yusuf; Bhattacharjee, Surajit

    2016-03-01

    Microbial biofilm are communities of surface-adhered cells enclosed in a matrix of extracellular polymeric substances. Extensive use of antibiotics to treat biofilm associated infections has led to the emergence of multiple drug resistant strains. Pseudomonas aeruginosa is recognised as a model biofilm forming pathogenic bacterium. Vitexin, a polyphenolic group of phytochemical with antimicrobial property, has been studied for its antibiofilm potential against Pseudomonas aeruginosa in combination with azithromycin and gentamicin. Vitexin shows minimum inhibitory concentration (MIC) at 260 μg/ml. It’s antibiofilm activity was evaluated by safranin staining, protein extraction, microscopy methods, quantification of EPS and in vivo models using several sub-MIC doses. Various quorum sensing (QS) mediated phenomenon such as swarming motility, azocasein degrading protease activity, pyoverdin and pyocyanin production, LasA and LasB activity of the bacteria were also evaluated. Results showed marked attenuation in biofilm formation and QS mediated phenotype of Pseudomonas aeruginosa in presence of 110 μg/ml vitexin in combination with azithromycin and gentamicin separately. Molecular docking of vitexin with QS associated LuxR, LasA, LasI and motility related proteins showed high and reasonable binding affinity respectively. The study explores the antibiofilm potential of vitexin against P. aeruginosa which can be used as a new antibiofilm agent against microbial biofilm associated pathogenesis.

  2. Determination of benzalkonium chloride in viscous ophthalmic drops of azithromycin by high-performance liquid chromatography.

    PubMed

    Shen, Yan; Xu, Sheng-jie; Wang, Shi-chun; Tu, Jia-sheng

    2009-12-01

    A high-performance liquid chromatography (HPLC) system was used in the reversed phase mode for the determination of benzalkonium chloride (BKC) in azithromycin viscous ophthalmic drops. A Venusil-XBP(L)-C(18) (150 mmx4.6 mm, 5 microm) column was used at 50 degrees C. The mobile phase consisted of a mixture of methanol-potassium phosphate (16:5, v/v). Two sample preparation methods were compared. The results suggested that, compared with an extraction procedure, a deproteinization procedure was much quicker and more convenient. Using the deproteinization procedure for sample preparation, calibration curves were linear in the range 5.0 to approximately 50 microg/ml. The within-day and inter-day coefficients of variation were less than 10%. The average recoveries were determined as 96.70%, 98.52%, and 97.96% at concentrations of 10.0, 30.0, and 50.0 microg/ml, respectively. Variability in precision did not exceed 5%. In conclusion, this HPLC method using a simple sample treatment procedure appears suitable for monitoring BKC content in azithromycin viscous ophthalmic drops. PMID:19946951

  3. From Erythromycin to Azithromycin and New Potential Ribosome-Binding Antimicrobials.

    PubMed

    Jelić, Dubravko; Antolović, Roberto

    2016-01-01

    Macrolides, as a class of natural or semisynthetic products, express their antibacterial activity primarily by reversible binding to the bacterial 50S ribosomal subunits and by blocking nascent proteins' progression through their exit tunnel in bacterial protein biosynthesis. Generally considered to be bacteriostatic, they may also be bactericidal at higher doses. The discovery of azithromycin from the class of macrolides, as one of the most important new drugs of the 20th century, is presented as an example of a rational medicinal chemistry approach to drug design, applying classical structure-activity relationship that will illustrate an impressive drug discovery success story. However, the microorganisms have developed several mechanisms to acquire resistance to antibiotics, including macrolide antibiotics. The primary mechanism for acquiring bacterial resistance to macrolides is a mutation of one or more nucleotides from the binding site. Although azithromycin is reported to show different, two-step process of the inhibition of ribosome function of some species, more detailed elaboration of that specific mode of action is needed. New macrocyclic derivatives, which could be more potent and less prone to escape bacterial resistance mechanisms, are also continuously evaluated. A novel class of antibiotic compounds-macrolones, which are derived from macrolides and comprise macrocyclic moiety, linker, and either free or esterified quinolone 3-carboxylic group, show excellent antibacterial potency towards key erythromycin-resistant Gram-positive and Gram-negative bacterial strains, with possibly decreased potential of bacterial resistance to macrolides. PMID:27598215

  4. Attenuation of Pseudomonas aeruginosa biofilm formation by Vitexin: A combinatorial study with azithromycin and gentamicin.

    PubMed

    Das, Manash C; Sandhu, Padmani; Gupta, Priya; Rudrapaul, Prasenjit; De, Utpal C; Tribedi, Prosun; Akhter, Yusuf; Bhattacharjee, Surajit

    2016-01-01

    Microbial biofilm are communities of surface-adhered cells enclosed in a matrix of extracellular polymeric substances. Extensive use of antibiotics to treat biofilm associated infections has led to the emergence of multiple drug resistant strains. Pseudomonas aeruginosa is recognised as a model biofilm forming pathogenic bacterium. Vitexin, a polyphenolic group of phytochemical with antimicrobial property, has been studied for its antibiofilm potential against Pseudomonas aeruginosa in combination with azithromycin and gentamicin. Vitexin shows minimum inhibitory concentration (MIC) at 260 μg/ml. It's antibiofilm activity was evaluated by safranin staining, protein extraction, microscopy methods, quantification of EPS and in vivo models using several sub-MIC doses. Various quorum sensing (QS) mediated phenomenon such as swarming motility, azocasein degrading protease activity, pyoverdin and pyocyanin production, LasA and LasB activity of the bacteria were also evaluated. Results showed marked attenuation in biofilm formation and QS mediated phenotype of Pseudomonas aeruginosa in presence of 110 μg/ml vitexin in combination with azithromycin and gentamicin separately. Molecular docking of vitexin with QS associated LuxR, LasA, LasI and motility related proteins showed high and reasonable binding affinity respectively. The study explores the antibiofilm potential of vitexin against P. aeruginosa which can be used as a new antibiofilm agent against microbial biofilm associated pathogenesis. PMID:27000525

  5. Efficacy and safety of azithromycin for uncomplicated typhoid fever: an open label non-comparative study.

    PubMed

    Aggarwal, Anju; Ghosh, Apurba; Gomber, Sunil; Mitra, Monjori; Parikh, A O

    2011-07-01

    An open-labelled, non-comparative study was conducted in 117 children aged 2-12 years to evaluate the efficacy and safety of azithromycin (20mg/ kg/day for 6 days) for the treatment of uncomplicated typhoid fever. Of the patients enrolled based on a clinical definition of typhoid fever, 109 (93.1%) completed the study.Mean (SD) of duration of fever at presentation was 9.1(4.5) days. Clinical cure was seen in 102 (93.5%) subjects, while 7 were withdrawn from the study because of clinical deterioration. Mean day of response was 3.45±1.97. BACTEC blood culture was positive for Salmonella typhi in 17/109 (15.5%) and all achieved bacteriological cure. No serious adverse event was observed. Global well being assessed by the investigator and subjects was good in 95% cases which was done at the end of the treatment. Azithromycin was found to be safe and efficacious for the management of uncomplicated typhoid fever. PMID:21555791

  6. Susceptibility of Ureaplasma urealyticum to tetracycline, doxycycline, erythromycin, roxithromycin, clarithromycin, azithromycin, levofloxacin and moxifloxacin.

    PubMed

    Samra, Z; Rosenberg, S; Dan, M

    2011-04-01

    The in vitro activity of tetracycline, doxycycline, erythromycin, roxithromycin, clarithromycin, azithromycin, levofloxacin and moxifloxacin was tested against 63 clinical isolates of Ureaplasma urealyticum. The minimal inhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs) were determined by the broth microdilution method in A7 medium. The MIC(50) and MIC(90) of the tested agents after 24 h of incubation were as follows: tetracycline, 0.5 and 2.0 μg/ml; doxycycline, 0.125 and 0.25 μg/ml; erythromycin, 2.0 and 8.0 μg/ml; roxithromycin, 2.0 and 4.0 μg/ml; clarithromycin, 0.25 and 1.0 μg/ml; azithromycin, 2.0 and 4.0 μg/ml; levofloxacin, 1.0 and 2.0 μg/ml; and moxifloxacin, 0.5 and 0.5 μg/ml, respectively. The MIC values after 24 h and 48 h incubation differed by no more than one dilution for all the agents with the exception of doxycycline (two dilution difference for MIC(90)). Overall, moxifloxacin was the most active agent in vitro against U. urealyticum, with the narrowest difference between MIC and MBC values, followed closely by levofloxacin. Clarithromycin was the most active macrolide. PMID:21571622

  7. Comparison of E-test with agar dilution methods in testing susceptibility of N. gonorrhoeae to azithromycin.

    PubMed

    Yasin, R M; Suan, K A; Meng, C Y

    1997-05-01

    A single dose of a new antibiotic, azithromycin, has been shown to be effective in the treatment of uncomplicated Neisseria gonorrhoeae. A clinical study was conducted to assess the in vitro susceptibility of N gonorrhoeae to azithromycin and compare the reliability of results obtained using the new E-test methodology for determination of the minimum inhibitory concentration (MIC) of antibiotic with those obtained through the standard agar dilution method. 135 clinical isolates of N gonorrhoeae were obtained from patients attending hospital-based sexually transmitted disease clinics in five geographic locations in Malaysia. 76 of the isolates were penicillinase-producing N gonorrhoeae and 69 were high-level tetracycline-resistant N gonorrhoeae. All isolates were susceptible to azithromycin based on the susceptible MIC breakpoint of 2.0 mcg/ml. The MICs ranged from 0.0078-0.25 mcg/ml by agar dilution method and from 0.016-0.50 mcg/ml by E-test. Agreement between these two methods was 97.8%. The single-dose regime and good antigonococcal and antichlamydial activity of azithromycin make this antibiotic a suitable treatment choice. Moreover, the findings of this study suggest that the simpler, faster E-test is as reliable as the agar dilution method. Given the tendency of the antimicrobial susceptibility pattern of N gonorrhoeae to change rapidly, it is important to monitor MICs to detect the emergence of resistance. PMID:9153733

  8. A CASE STUDY: CROP (LETTUCE, SPINACH, AND CARROTS) UPTAKE OF THREE MACROLIDE ANTIBIOTICS (AZITHROMYCIN, CLINDAMYCIN AND ROXITHROMYCIN) AND OTHER DRUGS

    EPA Science Inventory

    It has been shown that human-use macrolide antibiotics (azithromycin, clindamycin, and roxithromycin) are environmentally available in wastewaters, source waters, and biosolids. In order to better understand the fate of these compounds into food crops via root migration, we condu...

  9. A Comparative Study of Efficacy and Safety of Azithromycin and Ofloxacin in Uncomplicated Typhoid Fever: A Randomised, Open Labelled Study

    PubMed Central

    Chandey, Manish; Multani, A.S.

    2012-01-01

    Objective To compare the efficacy and safety of azithromycin with ofloxacin in patients with uncomplicated typhoid fever. Material and Methods Forty adult patients with bacteriologically or serologically diagnosed, uncomplicated typhoid fever were included from Medicine out-patient department at Government medical college, Amritsar, India. They were randomized into 2 groups of 20 patients each. Group I: patients received ofloxacin 200mg orally twice daily for 7 days. Group II: Patients received Azithromycin orally 1 gm on day 1 and then 500 mg daily from day 2 to day 6. The following parameters were noted a) fever clearance time b) cure rate c) adverse drug reaction d) recurrence of symptoms, if any, during 4 weeks follow up. Results Nineteen out of 20 patients from group I were cured with mean fever clearance time of 3.68 days while all 20 patients from group II were cured with mean fever clearance time of 3.65 days. No significant side effects were noted in any of the patients. No relapse was recorded in the present study in a follow up period of 4 weeks in both study groups. Conclusion Both ofloxacin and Azithromycin are almost equally efficacious and safe in treatment of typhoid fever with no major adverse effect. Azithromycin is an effective alternative in conditions where ofloxacin is contraindicated i.e., children, pregnant women and quinolone resistant cases of typhoid fever. PMID:23373040

  10. Microbiological effects of periodontal therapy plus azithromycin in patients with diabetes: results from a randomized clinical trial.

    PubMed

    Hincapié, Juan P; Castrillón, Cesar A; Yepes, Fanny L; Roldan, Natalia; Becerra, María A; Moreno, Sandra M; Consuegra, Jessika; Contreras, Adolfo; Botero, Javier E

    2014-01-01

    Current evidence suggests that periodontal infection may aggravate diabetes control. The aim of this study was to determine the changes in the frequency with which Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola and Aggregatibacter actinomycetemcomitans were detected in patients with diabetes with the use of non-surgical therapy plus azithromycin in a randomized clinical trial. One hundred and five (105) patients with diabetes and chronic periodontitis were randomly assigned to three treatment groups: subgingival mechanical therapy with azithromycin, subgingival mechanical therapy with placebo and supragingival prophylaxis with azithromycin. Complete periodontal clinical examinations and detection of periodontal pathogens using polymerase chain reaction were carried out at baseline, 3, 6 and 9 months after periodontal therapy. The frequency with which Porphyromonas gingivalis, Treponemadenticola and Aggregatibacter actinomycetemcomitans were detected decreased at 3 months in all groups. Tannerella forsythia increased after3 months in all groups. All organisms had similar frequencies at 9 months in all groups. Subgingival mechanical therapy with adjunctive azithromycin had no additional effect on the frequency with which the periodontal pathogens investigated were detected in patients with diabetes. PMID:25523961

  11. Short-term triple therapy with azithromycin for Helicobacter pylori eradication: Low cost, high compliance, but low efficacy

    PubMed Central

    Silva, Fernando M; Eisig, Jaime N; Teixeira, Ana Cristina S; Barbuti, Ricardo C; Navarro-Rodriguez, Tomás; Mattar, Rejane

    2008-01-01

    Background The Brazilian consensus recommends a short-term treatment course with clarithromycin, amoxicillin and proton-pump inhibitor for the eradication of Helicobacter pylori (H. pylori). This treatment course has good efficacy, but cannot be afforded by a large part of the population. Azithromycin, amoxicillin and omeprazole are subsidized, for several aims, by the Brazilian federal government. Therefore, a short-term treatment course that uses these drugs is a low-cost one, but its efficacy regarding the bacterium eradication is yet to be demonstrated. The study's purpose was to verify the efficacy of H. pylori eradication in infected patients who presented peptic ulcer disease, using the association of azithromycin, amoxicillin and omeprazole. Methods Sixty patients with peptic ulcer diagnosed by upper digestive endoscopy and H. pylori infection documented by rapid urease test, histological analysis and urea breath test were treated for six days with a combination of azithromycin 500 mg and omeprazole 20 mg, in a single daily dose, associated with amoxicillin 500 mg 3 times a day. The eradication control was carried out 12 weeks after the treatment by means of the same diagnostic tests. The eradication rates were calculated with 95% confidence interval. Results The eradication rate was 38% per intention to treat and 41% per protocol. Few adverse effects were observed and treatment compliance was high. Conclusion Despite its low cost and high compliance, the low eradication rate does not allow the recommendation of the triple therapy with azithromycin as an adequate treatment for H. pylori infection. PMID:18510773

  12. Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy

    PubMed Central

    Tsai, Mao-Song; Yang, Chia-Jui; Lee, Nan-Yao; Hsieh, Szu-Min; Lin, Yu-Hui; Sun, Hsin-Yun; Sheng, Wang-Huei; Lee, Kuan-Yeh; Yang, Shan-Ping; Liu, Wen-Chun; Wu, Pei-Ying; Ko, Wen-Chien; Hung, Chien-Ching

    2014-01-01

    Introduction The Jarisch-Herxheimer reaction, a febrile inflammatory reaction that often occurs after the first dose of chemotherapy in spirochetal diseases, may result in deleterious effects to patients with neurosyphilis and to pregnant women. A single 2-g oral dose of azithromycin is an alternative treatment to benzathine penicillin G for early syphilis in areas with low macrolide resistance. With its potential anti-inflammatory activity, the impact of azithromycin on the incidence of the Jarisch-Herxheimer reaction in HIV-positive patients with early syphilis has rarely been investigated. Methods In HIV-positive patients with early syphilis, the Jarisch-Herxheimer reaction was prospectively investigated using the same data collection form in 119 patients who received benzathine penicillin G between 2007 and 2009 and 198 who received azithromycin between 2012 and 2013, when shortage of benzathine penicillin G occurred in Taiwan. Between 2012 and 2013, polymerase chain reaction (PCR) assay was performed to detect Treponema pallidum DNA in clinical specimens, and PCR restriction fragment length polymorphism of the 23S ribosomal RNA was performed to detect point mutations (2058G or A2059G) that are associated with macrolide resistance. Results The overall incidence of the Jarisch-Herxheimer reaction was significantly lower in patients receiving azithromycin than those receiving benzathine penicillin G (14.1% vs. 56.3%, p<0.001). The risk increased with higher rapid plasma reagin (RPR) titres (adjusted odds ratio [AOR] per 1-log2 increase, 1.21; confidence interval [CI], 1.04–1.41), but decreased with prior penicillin therapy for syphilis (AOR, 0.37; 95% CI, 0.19–0.71) and azithromycin treatment (AOR, 0.15; 95% CI, 0.08–0.29). During the study period, 310 specimens were obtained from 198 patients with syphilis for PCR assays, from whom T. pallidum was identified in 76 patients, one of whom (1.3%) was found to be infected with T. pallidum harbouring the

  13. Efficacy and safety of azithromycin 1.5% eye drops in paediatric population with purulent bacterial conjunctivitis

    PubMed Central

    Bremond-Gignac, Dominique; Nezzar, Hachemi; Bianchi, Paolo Emilio; Messaoud, Riadh; Lazreg, Sihem; Voinea, Liliana; Speeg-Schatz, Claude; Hartani, Dahbia; Kaercher, Thomas; Kocyla-Karczmarewicz, Beata; Murta, Joaquim; Delval, Laurent; Renault, Didier; Chiambaretta, Frédéric

    2014-01-01

    Objective To determine the efficacy and safety of azithromycin 1.5% eye drops in a paediatric population with purulent bacterial conjunctivitis. Patients and methods This was a multicentre, international, randomised, investigator-masked study in 286 children with purulent discharge and bulbar conjunctival injection. Patients received either azithromycin 1.5% eye drops (twice daily for 3 days) or tobramycin 0.3% eye drops (every 2 h for 2 days, then four times daily for 5 days). Clinical signs were evaluated on day (D) 0, 3 and 7, and cultures on D0 and D7. The primary variable was the clinical cure (absence of bulbar conjunctival injection and discharge) on D3 in the worse eye for patients with positive cultures on D0. Results 286 patients (mean age 3.2 years; range 1 day–17 years) were included; 203 had positive cultures on D0. Azithromycin was superior to tobramycin in clinical cure rate on D3 (47.1% vs 28.7%, p=0.013) and was non-inferior to tobramycin on D7 (89.2% vs 78.2%, respectively). Azithromycin treatment eradicated causative pathogens, including resistant species, with a similar resolution rate to tobramycin (89.8% vs 87.2%, respectively). These results were confirmed in a subgroup of patients younger than 24 months old. Conclusions Azithromycin 1.5% eye drops provided a more rapid clinical cure than tobramycin 0.3% eye drops in the treatment of purulent bacterial conjunctivitis in children, with a more convenient twice-a-day dosing regimen. PMID:24526744

  14. Azithromycin for Indigenous children with bronchiectasis: study protocol for a multi-centre randomized controlled trial

    PubMed Central

    2012-01-01

    Background The prevalence of chronic suppurative lung disease (CSLD) and bronchiectasis unrelated to cystic fibrosis (CF) among Indigenous children in Australia, New Zealand and Alaska is very high. Antibiotics are a major component of treatment and are used both on a short or long-term basis. One aim of long-term or maintenance antibiotics is to reduce the frequency of acute pulmonary exacerbations and symptoms. However, there are few studies investigating the efficacy of long-term antibiotic use for CSLD and non-CF bronchiectasis among children. This study tests the hypothesis that azithromycin administered once a week as maintenance antibiotic treatment will reduce the rate of pulmonary exacerbations in Indigenous children with bronchiectasis. Methods/design We are conducting a multicentre, randomised, double-blind, placebo controlled clinical trial in Australia and New Zealand. Inclusion criteria are: Aboriginal, Torres Strait Islander, Maori or Pacific Island children aged 1 to 8 years, diagnosed with bronchiectasis (or probable bronchiectasis) with no underlying disease identified (such as CF or primary immunodeficiency), and having had at least one episode of pulmonary exacerbation in the last 12 months. After informed consent, children are randomised to receive either azithromycin (30 mg/kg once a week) or placebo (once a week) for 12–24 months from study entry. Primary outcomes are the rate of pulmonary exacerbations and time to pulmonary exacerbation determined by review of patient medical records. Secondary outcomes include length and severity of pulmonary exacerbation episodes, changes in growth, school loss, respiratory symptoms, forced expiratory volume in 1-second (FEV1; for children ≥6 years), and sputum characteristics. Safety endpoints include serious adverse events. Antibiotic resistance in respiratory bacterial pathogens colonising the nasopharynx is monitored. Data derived from medical records and clinical assessments every 3 to 4

  15. Diagnostic Characteristics of Tests for Ocular Chlamydia after Mass Azithromycin Distributions

    PubMed Central

    See, Craig W.; Moncada, Jeanne; Ayele, Berhan; Gebre, Teshome; Stoller, Nicole E.; McCulloch, Charles E.; Porco, Travis C.; Gaynor, Bruce D.; Emerson, Paul M.; Schachter, Julius; Lietman, Thomas M.

    2012-01-01

    Purpose. Although trachoma control programs frequently use the World Health Organization (WHO) simplified grading system for trachoma to monitor the clinical response after repeated mass azithromycin treatments, the programmatic relevance of this evaluation after multiple rounds of antibiotic treatments is unclear. Methods. Three rounds of annual mass azithromycin were distributed to 12 villages in Ethiopia. Twelve months after the third treatment, children were assessed for follicular trachomatous inflammation (TF) and intense trachomatous inflammation (TI) using the WHO simplified grading system and for ocular chlamydial infection using DNA-based and RNA-based tests. Test characteristics for predicting chlamydial infection were computed assuming a chlamydial RNA-based gold standard. As a secondary analysis, test characteristics were also assessed using a latent class analysis. Results. The prevalence of RNA evidence of ocular chlamydia was 7.1% (95% confidence interval [CI], 2.7–17.4). A DNA-based test and TF had sensitivities of 61.0% (95% CI, 47.1–73.3) and 65.9% (95% CI, 41.6–83.9), specificities of 100% (95% CI, 99.3–100) and 67.5% (95% CI, 61.0–73.5), and positive predictive values of 100% (95% CI, 86.3–100) and 13.4% (95% CI, 5.5–29.3) compared with an RNA-based gold standard. The latent class analysis confirmed that the RNA-based test was a reasonable choice for a gold standard, with a sensitivity of 100% (95% CI, 67.1–100) and specificity of 99.6% (95% CI, 98.1–100). Conclusions. Basing treatment decisions after mass azithromycin distributions on the WHO simplified grading system will maximize the treatment of infected persons compared with a DNA-based test but will also result in more uninfected persons being treated. The RNA-based test was considerably more sensitive, and almost equivalently specific, compared with a DNA-based test. (ClinicalTrials.gov number, NCT00322972.) PMID:22159017

  16. Update and critical appraisal of the use of topical azithromycin ophthalmic 1% (AzaSite®) solution in the treatment of ocular infections

    PubMed Central

    Utine, Canan Asli

    2011-01-01

    Azithromycin is an azalide that acts by binding to the 50S ribosomal subunit of susceptible microorganisms and interfering with microbial protein synthesis. Azithromycin is also noted by anti-inflammatory and immunomodulatory activity. AzaSite® (Inspire Pharmaceuticals, Inc, Durham, NC) is azithromycin ophthalmic solution, 1% formulated in polycarbophil (the aqueous mucoadhesive polymer contained in DuraSite®) that delivers high and prolonged azithromycin concentrations in a variety of ocular tissues, including the conjunctiva, cornea and particularly the eyelid. AzaSite was approved by the Food and Drug Administration (FDA) in the US in 2007, for the treatment of bacterial conjunctivitis caused by susceptible isolates. This article aims to evaluate the peer-reviewed published scientific literature and to define well-established uses of AzaSite eye drops in the field of ocular infections. PMID:21750614

  17. Pharmacokinetics of azithromycin in serum and sinus fluid after administration of extended-release and immediate-release formulations in patients with acute bacterial sinusitis.

    PubMed

    Ehnhage, A; Rautiainen, M; Fang, A F; Sanchez, S P

    2008-06-01

    As high drug levels at the infection site are desirable for optimal activity, this study explored whether one dose of azithromycin extended release (AZ-ER) achieved higher azithromycin exposure in sinus fluid than azithromycin immediate release (AZ-IR) in adults with acute bacterial sinusitis. Subjects received AZ-ER (2g single dose; n=5) or AZ-IR (500mg daily for 3 days; n=4) and blood and sinus aspirates were collected until 120 h after initial dosing. Within 24 h, exposure was four- and three-fold higher with AZ-ER than with AZ-IR in serum and sinus fluid, respectively. Sinus fluid exposure was five- and three-fold higher than serum for AZ-IR and AZ-ER, respectively. Azithromycin concentrations in sinus fluid were maintained up to 120 h. PMID:18456465

  18. Pulsed azithromycin treatment is as effective and safe as 2-week-longer daily doxycycline treatment of acne vulgaris: a randomized, double-blind, noninferiority study.

    PubMed

    Maleszka, Romuald; Turek-Urasinska, Katarzyna; Oremus, Marijana; Vukovic, Jacinta; Barsic, Bruno

    2011-01-01

    Efficacy and safety of azithromycin and doxycycline for the treatment of moderate acne vulgaris were evaluated (240 patients) in both intention-to-treat and per-protocol populations. The evaluation of clinical efficacy was based on the change in the number of facial inflammatory lesions from baseline to the end of treatment, and noninferiority was defined by the upper 95% confidence limit of the difference between two treatments being less than 9. Reduction in the number of lesions was similar with both azithromycin and doxycycline treatments (27 +/- 12 and 30 +/- 12, respectively) in both groups. Also, the upper 95% confidence limit of 5 inflammatory lesions has satisfied the noninferiority criterion. The incidence of adverse events did not differ between the two treatment groups. The shorter and simpler treatment schedule of azithromycin had similar efficacy and safety as doxycycline in the treatment of moderate acne vulgaris, confirming noninferiority of azithromycin as compared with doxycycline. PMID:21548512

  19. A comparison of ciprofloxacin, norfloxacin, ofloxacin, azithromycin and cefixime examined by observational cohort studies.

    PubMed

    Wilton, L V; Pearce, G L; Mann, R D

    1996-04-01

    1. The safety in everyday clinical usage of three 4-quinolone antibiotics, (ciprofloxacin, norfloxacin and ofloxacin), was compared with similar data for azithromycin and cefixime, each agent being examined by Prescription-Event Monitoring (PEM) during the early post-marketing period. 2. In PEM the exposure data are derived from general practitioner prescriptions confidentially provided by the Prescription Pricing Authority. Outcome data are provided by questionnaires (green forms) on which the prescribing medical practitioner records event data. When necessary, further information is obtained from a number of sources which include follow-up of all pregnancies and the patients' life-time medical record. 3. The main outcome measures were demographic information, including the patient's date of birth and sex; the indication for prescribing the drug being monitored; the reason for stopping treatment; the start and stop dates of treatment and the events recorded during and after treatment. 4. The final cohort for each of the five antibiotics exceeded 11000 patients. The only event significantly related to the use of all five antibiotics was nausea/vomiting. This was also the most frequent adverse event causing treatment to be discontinued with norfloxacin, ofloxacin and azithromycin (relevant information was not requested in the studies of ciprofloxacin and cefixime). Vaginal candidiasis was significantly more frequently associated with the use of the three 4-quinolones than with azithromycin and cefixime but it was frequently delayed until the week or two after the cessation of therapy. Within each event, as recorded in these studies, the highest event rates (the number of events per 1000 patients) in the week following the start of therapy were: 9.2 for diarrhoea with cefixime; 4.9 for nausea/vomiting with ofloxacin; 2.4 for rash with azithromycin; 2.2 for abdominal pain with norfloxacin; 1.5 for headache/migraine with ofloxacin; 1.4 for malaise/lassitude with

  20. Azithromycin and Ciprofloxacin Resistance in Salmonella Bloodstream Infections in Cambodian Adults

    PubMed Central

    Vlieghe, Erika R.; Phe, Thong; De Smet, Birgit; Veng, Chhun H.; Kham, Chun; Bertrand, Sophie; Vanhoof, Raymond; Lynen, Lut; Peetermans, Willy E.; Jacobs, Jan A.

    2012-01-01

    Background Salmonella enterica is a frequent cause of bloodstream infection (BSI) in Asia but few data are available from Cambodia. We describe Salmonella BSI isolates recovered from patients presenting at Sihanouk Hospital Centre of Hope, Phnom Penh, Cambodia (July 2007–December 2010). Methodology Blood was cultured as part of a microbiological prospective surveillance study. Identification of Salmonella isolates was performed by conventional methods and serotyping. Antibiotic susceptibilities were assessed using disk diffusion, MicroScan and E-test macromethod. Clonal relationships were assessed by Pulsed Field Gel Electrophoresis; PCR and sequencing for detection of mutations in Gyrase and Topoisomerase IV and presence of qnr genes. Principal Findings Seventy-two Salmonella isolates grew from 58 patients (mean age 34.2 years, range 8–71). Twenty isolates were identified as Salmonella Typhi, 2 as Salmonella Paratyphi A, 37 as Salmonella Choleraesuis and 13 as other non-typhoid Salmonella spp. Infection with human immunodeficiency virus (HIV) was present in 21 of 24 (87.5%) patients with S. Choleraesuis BSI. Five patients (8.7%) had at least one recurrent infection, all with S. Choleraesuis; five patients died. Overall, multi drug resistance (i.e., co-resistance to ampicillin, sulphamethoxazole-trimethoprim and chloramphenicol) was high (42/59 isolates, 71.2%). S. Typhi displayed high rates of decreased ciprofloxacin susceptibility (18/20 isolates, 90.0%), while azithromycin resistance was very common in S. Choleraesuis (17/24 isolates, 70.8%). Two S. Choleraesuis isolates were extended spectrum beta-lactamase producer. Conclusions and Significance Resistance rates in Salmonella spp. in Cambodia are alarming, in particular for azithromycin and ciprofloxacin. This warrants nationwide surveillance and revision of treatment guidelines. PMID:23272255

  1. Comparative efficacy and safety of 3-day azithromycin and 10-day penicillin V treatment of group A beta-hemolytic streptococcal pharyngitis in children.

    PubMed Central

    Pacifico, L; Scopetti, F; Ranucci, A; Pataracchia, M; Savignoni, F; Chiesa, C

    1996-01-01

    The efficacy and safety of a 3-day course of azithromycin oral suspension (10 mg/kg of body weight once daily) were compared with those of penicillin V (50,000 U/kg/day in two divided doses) in children aged 3 to 12 years for the treatment of symptomatic pharyngitis caused by the group A beta-hemolytic streptococcus (GABHS). For the 154 evaluable patients, the original infecting strain of GABHS was eliminated at the end of follow-up (34 to 36 days after treatment started) from 67 (85.8%) of 78 penicillin-treated patients and 41 (53.9%) of 76 azithromycin-treated patients (P < 0.0001). Overall clinical success was achieved in 71 (91.0%) of 78 penicillin V-treated patients and 57 (75.0%) of 76 azithromycin-treated patients (P < 0.05). Potential drug-related adverse events were reported for 5.5 and 8.6% of the penicillin V- and azithromycin-treated patients, respectively (P = 0.6). In the present study, a once-daily (10 mg/kg), 3-day oral regimen of azithromycin was as safe as a 10-day course of penicillin but did not represent an effective alternative to penicillin for the treatment of GABHS pharyngitis, even for those children with azithromycin-susceptible strains. PMID:8849215

  2. In Vivo Efficacy and Tolerability of Artesunate-Azithromycin for the Treatment of Falciparum Malaria in Vietnam.

    PubMed

    Phong, Nguyen Chinh; Quang, Huynh Hong; Thanh, Nguyen Xuan; Trung, Trieu Nguyen; Dai, Bui; Shanks, G Dennis; Chavchich, Marina; Edstein, Michael D

    2016-07-01

    Safe and effective antimalarial drugs are required for the treatment of pregnant women. We report a 3-day regimen of artesunate (4 mg/kg/day)-azithromycin (25 mg/kg/day) (ASAZ) to be efficacious (polymerase chain reaction-corrected cure rate of 96.7%) and well tolerated in the treatment of Plasmodium falciparum malaria in children (N = 11) and adults (N = 19), in Vietnam in 2010. In comparison, the cure rate for artesunate (4 mg/kg on day 0, 2 mg/kg on days 1-6) was 90.0% in children (N = 7) and adults (N = 23). Because azithromycin is considered safe in pregnancy, our findings provide further evidence that ASAZ should be evaluated for the treatment of pregnant women with malaria. PMID:27215294

  3. Protective Effects of Carvedilol and Vitamin C against Azithromycin-Induced Cardiotoxicity in Rats via Decreasing ROS, IL1-β, and TNF-α Production and Inhibiting NF-κB and Caspase-3 Expression

    PubMed Central

    El-Shitany, Nagla A.; El-Desoky, Karema

    2016-01-01

    The Food and Drug Administration recently warned of the fatal cardiovascular risks of azithromycin in humans. In addition, a recently published study documented azithromycin-induced cardiotoxicity in rats. This study aimed to justify the exact cardiovascular events accompanying azithromycin administration in rats, focusing on electrocardiographic, biochemical, and histopathological changes. In addition, the underlying mechanisms were studied regarding reactive oxygen species production, cytokine release, and apoptotic cell-death. Finally, the supposed protective effects of both carvedilol and vitamin C were assessed. Four groups of rats were used: (1) control, (2) azithromycin, (3) azithromycin + carvedilol, and (4) azithromycin + vitamin C. Azithromycin resulted in marked atrophy of cardiac muscle fibers and electrocardiographic segment alteration. It increased the heart rate, lactate dehydrogenase, creatine phosphokinase, malondialdehyde, nitric oxide, interleukin-1 beta (IL1-β), tumor necrosis factor alpha (TNF-α), nuclear factor kappa beta (NF-κB), and caspase-3. It decreased reduced glutathione, glutathione peroxidase, and superoxide dismutase. Carvedilol and vitamin C prevented most of the azithromycin-induced electrocardiographic and histopathological changes. Carvedilol and vitamin C decreased lactate dehydrogenase, malondialdehyde, IL1-β, TNF-α, NF-κB, and caspase-3. Both agents increased glutathione peroxidase. This study shows that both carvedilol and vitamin C protect against azithromycin-induced cardiotoxicity through antioxidant, immunomodulatory, and antiapoptotic mechanisms. PMID:27274777

  4. Protective Effects of Carvedilol and Vitamin C against Azithromycin-Induced Cardiotoxicity in Rats via Decreasing ROS, IL1-β, and TNF-α Production and Inhibiting NF-κB and Caspase-3 Expression.

    PubMed

    El-Shitany, Nagla A; El-Desoky, Karema

    2016-01-01

    The Food and Drug Administration recently warned of the fatal cardiovascular risks of azithromycin in humans. In addition, a recently published study documented azithromycin-induced cardiotoxicity in rats. This study aimed to justify the exact cardiovascular events accompanying azithromycin administration in rats, focusing on electrocardiographic, biochemical, and histopathological changes. In addition, the underlying mechanisms were studied regarding reactive oxygen species production, cytokine release, and apoptotic cell-death. Finally, the supposed protective effects of both carvedilol and vitamin C were assessed. Four groups of rats were used: (1) control, (2) azithromycin, (3) azithromycin + carvedilol, and (4) azithromycin + vitamin C. Azithromycin resulted in marked atrophy of cardiac muscle fibers and electrocardiographic segment alteration. It increased the heart rate, lactate dehydrogenase, creatine phosphokinase, malondialdehyde, nitric oxide, interleukin-1 beta (IL1-β), tumor necrosis factor alpha (TNF-α), nuclear factor kappa beta (NF-κB), and caspase-3. It decreased reduced glutathione, glutathione peroxidase, and superoxide dismutase. Carvedilol and vitamin C prevented most of the azithromycin-induced electrocardiographic and histopathological changes. Carvedilol and vitamin C decreased lactate dehydrogenase, malondialdehyde, IL1-β, TNF-α, NF-κB, and caspase-3. Both agents increased glutathione peroxidase. This study shows that both carvedilol and vitamin C protect against azithromycin-induced cardiotoxicity through antioxidant, immunomodulatory, and antiapoptotic mechanisms. PMID:27274777

  5. In Vitro Synergism Observed with Azithromycin, Clarithromycin, Minocycline, or Tigecycline in Association with Antifungal Agents against Pythium insidiosum

    PubMed Central

    Jesus, Francielli P. K.; Ferreiro, Laerte; Loreto, Érico S.; Pilotto, Maiara B.; Ludwig, Aline; Bizzi, Karine; Tondolo, Juliana S. M.; Zanette, Régis A.; Alves, Sydney H.

    2014-01-01

    We describe here the in vitro activities of azithromycin, clarithromycin, minocycline, or tigecycline alone and in combination with amphotericin B, itraconazole, terbinafine, voriconazole, anidulafungin, caspofungin, or micafungin against 30 isolates of the oomycete Pythium insidiosum. The assays were based on the CLSI M38-A2 technique and the checkerboard microdilution method. The main synergisms observed were through the combination of minocycline with amphotericin B (73.33%), itraconazole (70%), and micafungin (70%) and of clarithromycin with micafungin (73.33%). PMID:25001300

  6. In vitro synergism observed with azithromycin, clarithromycin, minocycline, or tigecycline in association with antifungal agents against Pythium insidiosum.

    PubMed

    Jesus, Francielli P K; Ferreiro, Laerte; Loreto, Érico S; Pilotto, Maiara B; Ludwig, Aline; Bizzi, Karine; Tondolo, Juliana S M; Zanette, Régis A; Alves, Sydney H; Santurio, Janio M

    2014-09-01

    We describe here the in vitro activities of azithromycin, clarithromycin, minocycline, or tigecycline alone and in combination with amphotericin B, itraconazole, terbinafine, voriconazole, anidulafungin, caspofungin, or micafungin against 30 isolates of the oomycete Pythium insidiosum. The assays were based on the CLSI M38-A2 technique and the checkerboard microdilution method. The main synergisms observed were through the combination of minocycline with amphotericin B (73.33%), itraconazole (70%), and micafungin (70%) and of clarithromycin with micafungin (73.33%). PMID:25001300

  7. Mass drug administration of azithromycin for trachoma reduces the prevalence of genital Chlamydia trachomatis infection in the Solomon Islands

    PubMed Central

    Bottomley, C; Tome, H; Pitakaka, R; Butcher, R; Sokana, O; Kako, H; Solomon, A W; Mabey, D C

    2016-01-01

    Objectives Chlamydia trachomatis is the most common bacterial sexually transmitted infection and is frequently asymptomatic; ocular C. trachomatis strains cause trachoma. Mass drug administration (MDA) of azithromycin for trachoma might also reduce the prevalence of genital C. trachomatis. In a survey conducted in the Solomon Islands in 2014, prior to MDA, the prevalence of genital C. trachomatis was 20.3% (95% CI 15.9% to 25.4%). We conducted a survey to establish the impact of MDA with azithromycin on genital C. trachomatis. Methods Women attending three community outpatient clinics, predominantly for antenatal care, 10 months after MDA with azithromycin given for trachoma elimination, were enrolled in this survey. Self-taken high vaginal swabs were for C. trachomatis and Neisseria gonorrhoeae using the BD Probetec strand displacement assay. Results 298 women were enrolled. C. trachomatis infection was diagnosed in 43 women (14.4%, 95% CI 10.6% to 18.9%) and N. gonorrhoeae in 9 (3%, 95% CI 1.4% to 5.7%). The age-adjusted OR for C. trachomatis infection was consistent with a significant decrease in the prevalence of C. trachomatis following MDA (OR 0.58, 95% CI 0.37 to 0.94, p=0.027). There was no change in the prevalence of N. gonorrhoeae between following MDA (OR 0.51, 95% CI 0.22 to 1.22, p=0.13). Conclusions This study demonstrated a 40% reduction in the age-adjusted prevalence of genital C. trachomatis infection following azithromycin MDA for trachoma elimination. PMID:26888658

  8. Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) syndrome associated with azithromycin presenting like septic shock: a case report

    PubMed Central

    2014-01-01

    Introduction Drug reaction with eosinophilia and systemic symptoms syndrome is a potentially life-threatening cutaneous hypersensitivity reaction characterized by extensive mucocutaneous eruption, fever, hematologic abnormalities including eosinophilia and/or atypical lymphocytosis, and extensive organ involvement. The drugs most often responsible for causing drug reaction with eosinophilia and systemic symptoms syndrome are anticonvulsants, antimicrobial agents and antipyretic or anti-inflammatory analgesics. Although azithromycin is widely prescribed in clinical practice, serious cutaneous reactions from this agent have been rarely described. We report the first adult case of drug reaction with eosinophilia and systemic symptoms syndrome associated with azithromycin. Case presentation A 44-year-old previously healthy Caucasian man with history of tobacco use presented to his primary care physician with fever and productive cough. He was prescribed azithromycin, promethazine hydrochloride and dextromethorphan hydrobromide syrup. One week later, he developed a blistering erythematous rash over both hands, which over the next two weeks spread to involve nearly his entire body surface, sparing only his face. He was admitted to an outside hospital with signs of systemic inflammatory response syndrome and severe sepsis, presumably from a skin infection. Despite aggressive therapy he deteriorated, with worsening diffuse erythema, and was transferred to our institution. He developed multiple organ failure requiring ventilatory and hemodynamic support. Pertinent laboratory studies included a leukocytosis with a white blood cell count of 17.6×109/L and 47% eosinophils. A skin biopsy showed evidence of spongiotic lichenoid dermatitis with eosinophils and neutrophils, compatible with a systemic drug-induced hypersensitivity reaction. Our patient was started on high-dose steroids and showed dramatic improvement within 48 hours. Conclusions We report the first adult case of

  9. Increased carriage of macrolide-resistant fecal E. coli following mass distribution of azithromycin for trachoma control

    PubMed Central

    Seidman, Jessica C; Coles, Christian L; Silbergeld, Ellen K; Levens, Joshua; Mkocha, Harran; Johnson, Lashaunda B; Muñoz, Beatriz; West, Sheila K

    2014-01-01

    Background: Mass drug treatment with azithromycin (MDA) is part of the WHO-endorsed ‘SAFE’ strategy for trachoma control in endemic communities. MDA has been associated with reduced trachoma prevalence and short-term reductions in other bacterial infections, but can also lead to increased circulation of macrolide-resistant bacteria. Methods: We prospectively monitored macrolide resistance in fecal E. coli collected from young children participating in the PRET+ Study in rural Tanzania. MDA was administered in four villages with >10% trachoma prevalence. Four nearby communities with lower trachoma prevalence served as controls. Rectal swabs were collected during cross-sectional surveys performed at baseline, 1, 3 and 6 months after MDA. Fecal E. coli isolates were screened for macrolide susceptibility using disc diffusion and minimum inhibitory concentration methods. Cross-sectional and longitudinal differences in resistance prevalence by MDA exposure were compared using t-tests and logistic regression. Results: There was no difference in the proportion of individuals carrying azithromycin-resistant E. coli at baseline (0.21 vs 0.16, P > 0.05). Azithromycin resistance carriage prevalence remained stable over follow-up in non-MDA villages but increased sharply in MDA villages (0.61 at 1 month, 0.42 at 3 months and 0.31 at 6 months). MDA exposure was highly associated with azithromycin resistance carriage at 1 month post-MDA (OR 15.27, P < 0.001) and subsequent surveys. Younger age and recent diarrhoea were also associated with increased odds of resistance (P < 0.01). Conclusions: MDA resulted in significantly increased prevalence of macrolide resistance in E. coli. Although MDA is effective for trachoma elimination, it has costs; it is essential to monitor antimicrobial resistance following MDA. PMID:24659584

  10. Surface plasmon resonance based selective and sensitive colorimetric determination of azithromycin using unmodified silver nanoparticles in pharmaceuticals and human plasma.

    PubMed

    Chavada, Vijay D; Bhatt, Nejal M; Sanyal, Mallika; Shrivastav, Pranav S

    2017-01-01

    In this article we report a novel method for colorimetric sensing and selective determination of a non-chromophoric drug-azithromycin, which lacks native absorbance in the UV-Visible region using unmodified silver nanoparticles (AgNPs). The citrate-capped AgNps dispersed in water afforded a bright yellow colour owing to the electrostatic repulsion between the particles due to the presence of negatively charged surface and showed surface plasmon resonance (SPR) band at 394nm. Addition of positively charged azithromycin at a concentration as low as 0.2μM induced rapid aggregation of AgNPs by neutralizing the negative charge on the particle surface. This phenomenon resulted in the colour change from bright yellow to purple which could be easily observed by the naked eye. This provided a simple platform for rapid determination of azithromycin based on colorimetric measurements. The factors affecting the colorimetric response like pH, volume of AgNPs suspension and incubation time were suitably optimized. The validated method was found to work efficiently in the established concentration range of 0.2-100.0μM using two different calibration models. The selectivity of the method was also evaluated by analysis of nanoparticles-aggregation response upon addition of several anions, cations and some commonly prescribed antibiotics. The method was successfully applied for the analysis of azithromycin in pharmaceuticals and spiked human plasma samples with good accuracy and precision. The simplicity, efficiency and cost-effectiveness of the method hold tremendous potential for the analysis of such non-chromophoric pharmaceuticals. PMID:27419643

  11. Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses

    PubMed Central

    Mauger, David T.; Boehmer, Susan; Beigelman, Avraham; Fitzpatrick, Anne M.; Jackson, Daniel J.; Baxi, Sachin N.; Benson, Mindy; Burnham, Carey-Ann D.; Cabana, Michael; Castro, Mario; Chmiel, James F.; Covar, Ronina; Daines, Michael; Gaffin, Jonathan M.; Gentile, Deborah Ann; Holguin, Fernando; Israel, Elliot; Kelly, H. William; Lazarus, Stephen C.; Lemanske, Robert F.; Ly, Ngoc; Meade, Kelley; Morgan, Wayne; Moy, James; Olin, Tod; Peters, Stephen P.; Phipatanakul, Wanda; Pongracic, Jacqueline A.; Raissy, Hengameh H.; Ross, Kristie; Sheehan, William J.; Sorkness, Christine; Szefler, Stanley J.; Teague, W. Gerald; Thyne, Shannon; Martinez, Fernando D.

    2016-01-01

    IMPORTANCE Many preschool children develop recurrent, severe episodes of lower respiratory tract illness (LRTI). Although viral infections are often present, bacteria may also contribute to illness pathogenesis. Strategies that effectively attenuate such episodes are needed. OBJECTIVE To evaluate if early administration of azithromycin, started prior to the onset of severe LRTI symptoms, in preschool children with recurrent severe LRTIs can prevent the progression of these episodes. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, placebo-controlled, parallel-group trial conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute’s AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by December 2014. Participants were 607 children aged 12 through 71 months with histories of recurrent, severe LRTIs and minimal day-to-day impairment. INTERVENTION Participants were randomly assigned to receive azithromycin (12 mg/kg/d for 5 days; n = 307) or matching placebo (n = 300), started early during each predefined RTI (child’s signs or symptoms prior to development of LRTI), based on individualized action plans, over a 12-through 18-month period. MAIN OUTCOMES AND MEASURES The primary outcome measure was the number of RTIs not progressing to a severe LRTI, measured at the level of the RTI, that would in clinical practice trigger the prescription of oral corticosteroids. Presence of azithromycin-resistant organisms in oropharyngeal samples, along with adverse events, were among the secondary outcome measures. RESULTS A total of 937 treated RTIs (azithromycin group, 473; placebo group, 464) were experienced by 443 children (azithromycin group, 223; placebo group, 220), including 92 severe LRTIs (azithromycin group, 35; placebo group, 57). Azithromycin significantly reduced the risk of progressing to severe LRTI relative to placebo (hazard ratio, 0.64 [95% CI, 0.41-0.98], P = .04; absolute risk for

  12. Differential Effects of Azithromycin, Doxycycline, and Cotrimoxazole in Ingested Blood on the Vectorial Capacity of Malaria Mosquitoes

    PubMed Central

    Gendrin, Mathilde; Yerbanga, Rakiswendé Serge; Ouedraogo, Jean Bosco; Lefèvre, Thierry; Cohuet, Anna; Christophides, George K.

    2016-01-01

    Background. The gut microbiota of malaria vector mosquitoes grows after a blood meal and limits Plasmodium infection. We previously showed that penicillin and streptomycin in the ingested blood affect bacterial growth and positively impact mosquito survival and permissiveness to Plasmodium. In this study, we examine the effects of doxycycline, azithromycin, and co-trimoxazole. All 3 antibiotics are used in mass drug administration programs and have antimicrobial activities against bacteria and various stages of malaria parasites. Methods. The effects of blood meal supplementation with antibiotics on the mosquito microbiota, lifespan, and permissiveness to Plasmodium falciparum were assessed. Results. Ingestion of any of the 3 antibiotics significantly affected the mosquito microbiota. Azithromycin decreased P falciparum infection load and mosquito lifespan, whereas at high concentrations, doxycycline increased P falciparum infection load. Co-trimoxazole negatively impacted infection intensity but had no reproducible effect on mosquito lifespan. Conclusions. Our data suggest that the overall effect of antibiotic treatment on parameters critical for mosquito vectorial capacity is drug specific. The negative effect of azithromycin on malaria transmission is consistent with current efforts for disease elimination, whereas additional, larger scale investigations are required before conclusions can be drawn about doxycycline. PMID:27419152

  13. Differential Effects of Azithromycin, Doxycycline, and Cotrimoxazole in Ingested Blood on the Vectorial Capacity of Malaria Mosquitoes.

    PubMed

    Gendrin, Mathilde; Yerbanga, Rakiswendé Serge; Ouedraogo, Jean Bosco; Lefèvre, Thierry; Cohuet, Anna; Christophides, George K

    2016-04-01

    Background.  The gut microbiota of malaria vector mosquitoes grows after a blood meal and limits Plasmodium infection. We previously showed that penicillin and streptomycin in the ingested blood affect bacterial growth and positively impact mosquito survival and permissiveness to Plasmodium. In this study, we examine the effects of doxycycline, azithromycin, and co-trimoxazole. All 3 antibiotics are used in mass drug administration programs and have antimicrobial activities against bacteria and various stages of malaria parasites. Methods.  The effects of blood meal supplementation with antibiotics on the mosquito microbiota, lifespan, and permissiveness to Plasmodium falciparum were assessed. Results.  Ingestion of any of the 3 antibiotics significantly affected the mosquito microbiota. Azithromycin decreased P falciparum infection load and mosquito lifespan, whereas at high concentrations, doxycycline increased P falciparum infection load. Co-trimoxazole negatively impacted infection intensity but had no reproducible effect on mosquito lifespan. Conclusions.  Our data suggest that the overall effect of antibiotic treatment on parameters critical for mosquito vectorial capacity is drug specific. The negative effect of azithromycin on malaria transmission is consistent with current efforts for disease elimination, whereas additional, larger scale investigations are required before conclusions can be drawn about doxycycline. PMID:27419152

  14. Determination of azithromycin residue in pork using a molecularly imprinted monolithic microcolumn coupled to liquid chromatography with tandem mass spectrometry.

    PubMed

    Zhou, Tong; Yang, Haicui; Jin, Zhen; Liu, Qingying; Song, Xuqin; He, Limin; Fang, Binghu; Meng, Chenying

    2016-04-01

    Using spiramycin as a dummy template, a molecularly imprinted polymer monolithic micro-column with high selection to azithromycin was prepared in a micropipette tip. The imprinting factor of the monolithic micro-column prepared was approximately 2.67 and the morphological structure of the polymers was characterized by scanning electron microscopy. A simple, sensitive, and reproducible method based on the imprinted monolithic micro-column coupled to liquid chromatography with tandem mass spectrometry was developed for determining the residues of azithromycin in pork. Pork samples were extracted with acetonitrile, cleaned up under the optimal monolithic micro-column conditions, and analyzed using liquid chromatography with tandem mass spectrometry in the multiple reaction monitoring mode. The assay exhibited a linear dynamic range of 0.50-50 μg/L with the correlation coefficient (r(2) ) above 0.99. In the three spiking levels of 0.50, 1.0, and 10 μg/kg, the average recoveries of azithromycin from pork samples were between 85.8 and 96.5% with a relative standard deviation below 10%. The limit of detection and limit of quantitation were 0.03 and 0.1 μg/kg, respectively. PMID:26854282

  15. Accumulation and clearance of orally administered erythromycin and its derivative, azithromycin, in juvenile fall chinook salmon Oncorhynchus tshawytscha.

    PubMed

    Fairgrieve, William T; Masada, Cyndy L; McAuley, W Carlin; Peterson, Mark E; Myers, Mark S; Strom, Mark S

    2005-04-18

    Fall Chinook salmon Oncorhynchus tshawytscha were fed practical diets medicated with azithromycin (30 mg kg(-1) fish for 14 d) or erythromycin (100 mg kg(-1) fish for 28 d) either 1, 2, or 3 times beginning 14 d after initiation of exogenous feeding (February) and ending at smoltification (June). Average tissue concentrations of azithromycin increased from 19.0 microg g(-1) in fry to 44.9 microg g(-1) in smolts, and persisted in the tissues > 76 d after treatment ceased. Tissue concentrations of erythromycin were comparatively low, ranging from 0.2 microg g(-1) in fry to 10.4 microg g(-1) in smolts. Erythromycin was not detectable 21 d post-treatment. Neither antibiotic caused histopathologically significant lesions in the trunk kidney or other organ tissues. The high tissue concentrations and prolonged retention of azithromycin in Chinook may be factors that increase the efficacy of the antibiotic against Renibacterium salmoninarum, compared with erythromycin, particularly in early life history stages before covertly infected fish show clinical signs of disease. PMID:15918472

  16. Pharmacokinetics, microbial response, and pulmonary outcomes of multidose intravenous azithromycin in preterm infants at risk for Ureaplasma respiratory colonization.

    PubMed

    Merchan, L Marcela; Hassan, Hazem E; Terrin, Michael L; Waites, Ken B; Kaufman, David A; Ambalavanan, Namasivayam; Donohue, Pamela; Dulkerian, Susan J; Schelonka, Robert; Magder, Laurence S; Shukla, Sagar; Eddington, Natalie D; Viscardi, Rose M

    2015-01-01

    The study objectives were to refine the population pharmacokinetics (PK) model, determine microbial clearance, and assess short-term pulmonary outcomes of multiple-dose azithromycin treatment in preterm infants at risk for Ureaplasma respiratory colonization. Fifteen subjects (7 of whom were Ureaplasma positive) received intravenous azithromycin at 20 mg/kg of body weight every 24 h for 3 doses. Azithromycin concentrations were determined in plasma samples obtained up to 168 h post-first dose by using a validated liquid chromatography-tandem mass spectrometry method. Respiratory samples were obtained predose and at three time points post-last dose for Ureaplasma culture, PCR, antibiotic susceptibility testing, and cytokine concentration determinations. Pharmacokinetic data from these 15 subjects as well as 25 additional subjects (who received either a single 10-mg/kg dose [n = 12] or a single 20-mg/kg dose [n = 13]) were analyzed by using a nonlinear mixed-effect population modeling (NONMEM) approach. Pulmonary outcomes were assessed at 36 weeks post-menstrual age and 6 months adjusted age. A 2-compartment model with all PK parameters allometrically scaled on body weight best described the azithromycin pharmacokinetics in preterm neonates. The population pharmacokinetics parameter estimates for clearance, central volume of distribution, intercompartmental clearance, and peripheral volume of distribution were 0.15 liters/h · kg(0.75), 1.88 liters · kg, 1.79 liters/h · kg(0.75), and 13 liters · kg, respectively. The estimated area under the concentration-time curve over 24 h (AUC24)/MIC90 value was ∼ 4 h. All posttreatment cultures were negative, and there were no drug-related adverse events. One Ureaplasma-positive infant died at 4 months of age, but no survivors were hospitalized for respiratory etiologies during the first 6 months (adjusted age). Thus, a 3-day course of 20 mg/kg/day intravenous azithromycin shows preliminary efficacy in eradicating

  17. Pharmacokinetics, Microbial Response, and Pulmonary Outcomes of Multidose Intravenous Azithromycin in Preterm Infants at Risk for Ureaplasma Respiratory Colonization

    PubMed Central

    Merchan, L. Marcela; Hassan, Hazem E.; Terrin, Michael L.; Waites, Ken B.; Kaufman, David A.; Ambalavanan, Namasivayam; Donohue, Pamela; Dulkerian, Susan J.; Schelonka, Robert; Magder, Laurence S.; Shukla, Sagar; Eddington, Natalie D.

    2014-01-01

    The study objectives were to refine the population pharmacokinetics (PK) model, determine microbial clearance, and assess short-term pulmonary outcomes of multiple-dose azithromycin treatment in preterm infants at risk for Ureaplasma respiratory colonization. Fifteen subjects (7 of whom were Ureaplasma positive) received intravenous azithromycin at 20 mg/kg of body weight every 24 h for 3 doses. Azithromycin concentrations were determined in plasma samples obtained up to 168 h post-first dose by using a validated liquid chromatography-tandem mass spectrometry method. Respiratory samples were obtained predose and at three time points post-last dose for Ureaplasma culture, PCR, antibiotic susceptibility testing, and cytokine concentration determinations. Pharmacokinetic data from these 15 subjects as well as 25 additional subjects (who received either a single 10-mg/kg dose [n = 12] or a single 20-mg/kg dose [n = 13]) were analyzed by using a nonlinear mixed-effect population modeling (NONMEM) approach. Pulmonary outcomes were assessed at 36 weeks post-menstrual age and 6 months adjusted age. A 2-compartment model with all PK parameters allometrically scaled on body weight best described the azithromycin pharmacokinetics in preterm neonates. The population pharmacokinetics parameter estimates for clearance, central volume of distribution, intercompartmental clearance, and peripheral volume of distribution were 0.15 liters/h · kg0.75, 1.88 liters · kg, 1.79 liters/h · kg0.75, and 13 liters · kg, respectively. The estimated area under the concentration-time curve over 24 h (AUC24)/MIC90 value was ∼4 h. All posttreatment cultures were negative, and there were no drug-related adverse events. One Ureaplasma-positive infant died at 4 months of age, but no survivors were hospitalized for respiratory etiologies during the first 6 months (adjusted age). Thus, a 3-day course of 20 mg/kg/day intravenous azithromycin shows preliminary efficacy in eradicating Ureaplasma spp

  18. Emergence of clinical Salmonella enterica serovar Typhimurium isolates with concurrent resistance to ciprofloxacin, ceftriaxone, and azithromycin.

    PubMed

    Wong, Marcus Ho Yin; Yan, Meiying; Chan, Edward Wai Chi; Biao, Kan; Chen, Sheng

    2014-07-01

    Salmonella infection is an important public health issue for which the needs of antimicrobial treatment are increasing. A total of 546 human clinical S. enterica serovar Typhimurium isolates were recovered from patients in hospitals in China during the period of 2005 to ∼ 2011. Twenty percent of the isolates exhibited resistance to ciprofloxacin, and 4% were resistant to ceftriaxone. Importantly, for the first time, 12 (2%) S. Typhimurium isolates resistant to both ciprofloxacin and ceftriaxone were recovered; among these 12 isolates, two were also resistant to azithromycin, and one was resistant to all other drugs tested. The combined effects of various transferrable extended-spectrum β-lactamase determinants and a novel efflux-based ciprofloxacin resistance mechanism encoded by the mobile efflux gene oqxAB were responsible for the emergence of these extremely (highly) drug-resistant (XDR) S. Typhimurium isolates. The dissemination of resistance genes, such as those encoding ESBLs and the OqxAB pump, among Salmonella organisms will speed up the selection of XDR Salmonella, posing a huge threat to public health and Salmonella infection control. PMID:24752251

  19. Cellular uptake and efflux of azithromycin, erythromycin, clarithromycin, telithromycin, and cethromycin.

    PubMed

    Bosnar, Martina; Kelnerić, Zeljko; Munić, Vesna; Eraković, Vesna; Parnham, Michael J

    2005-06-01

    Macrolide antibiotics have an outstanding ability to concentrate within host cells, particularly phagocytes. In the study described in this paper five different macrolide antibiotics were compared regarding the uptake and release kinetics in human peripheral blood polymorphonuclear neutrophils (PMNs) and three different cell lines, two phagocytic cell lines (RAW 264.7 and THP-1) and an epithelial cell line (MDCK). Based on the results obtained, the substances tested could be clustered into different groups. Azithromycin constituted the first group, characterized by rapid and nonsaturable uptake into phagocytic cells and a high degree of retention in the preloaded cells. The second group included erythromycin and clarithromycin. These two substances do not exhibit cell specificity; consequently, they are taken up to a similar extent and are released by all cell types studied. Ketolides constituted the last group. Their uptake was saturable in cells of monocytic lineage as well as in nondifferentiated cells of myeloid lineage, and they were rapidly released from all the cell lines studied. However, in PMNs, ketolide uptake was not saturable; and unlike telithromycin, cethromycin rapidly egressed from the loaded cells. PMID:15917536

  20. Pharmacokinetics of Transfer of Azithromycin into the Breast Milk of African Mothers.

    PubMed

    Salman, Sam; Davis, Timothy M E; Page-Sharp, Madhu; Camara, Bully; Oluwalana, Claire; Bojang, Abdoulie; D'Alessandro, Umberto; Roca, Anna

    2016-03-01

    Azithromycin (AZI) is used for its antibiotic and antimalarial properties in pregnancy. Reported estimates of AZI breast milk transfer, based on concentrations in mostly single samples from small numbers of women, have suggested that infant intake is safe. To better characterize infant intake and the associated potential benefits and risks, AZI was measured by liquid chromatography-mass spectrometry in four breast milk samples taken over 28 days postpartum from each of 20 Gambian women given 2 g AZI during labor. A population pharmacokinetic model utilizing published parameters for AZI disposition in pregnancy, the present breast milk concentrations, and increasing/decreasing sigmoid maximum-effect (Emax) functions adequately described temporal changes in the milk/plasma ratio. The median estimated absolute and relative cumulative infant doses were 4.5 mg/kg of body weight (95% prediction interval, 0.6 to 7.0 mg/kg) and 15.7% (95% prediction interval, 2.0 to 27.8%) of the maternal dose, respectively; the latter exceeded the recommended 10% safety limit. Although some infants with bacterial infections may benefit from AZI in breast milk, there is a risk of hypertrophic pyloric stenosis with a worst-case number needed to harm of 60 based on the present and available epidemiologic data. (This study has been registered at ClinicalTrials.gov under registration no. NCT01800942.). PMID:26711756

  1. Pharmacokinetics of Transfer of Azithromycin into the Breast Milk of African Mothers

    PubMed Central

    Page-Sharp, Madhu; Camara, Bully; Oluwalana, Claire; Bojang, Abdoulie; D'Alessandro, Umberto; Roca, Anna

    2015-01-01

    Azithromycin (AZI) is used for its antibiotic and antimalarial properties in pregnancy. Reported estimates of AZI breast milk transfer, based on concentrations in mostly single samples from small numbers of women, have suggested that infant intake is safe. To better characterize infant intake and the associated potential benefits and risks, AZI was measured by liquid chromatography-mass spectrometry in four breast milk samples taken over 28 days postpartum from each of 20 Gambian women given 2 g AZI during labor. A population pharmacokinetic model utilizing published parameters for AZI disposition in pregnancy, the present breast milk concentrations, and increasing/decreasing sigmoid maximum-effect (Emax) functions adequately described temporal changes in the milk/plasma ratio. The median estimated absolute and relative cumulative infant doses were 4.5 mg/kg of body weight (95% prediction interval, 0.6 to 7.0 mg/kg) and 15.7% (95% prediction interval, 2.0 to 27.8%) of the maternal dose, respectively; the latter exceeded the recommended 10% safety limit. Although some infants with bacterial infections may benefit from AZI in breast milk, there is a risk of hypertrophic pyloric stenosis with a worst-case number needed to harm of 60 based on the present and available epidemiologic data. (This study has been registered at ClinicalTrials.gov under registration no. NCT01800942.) PMID:26711756

  2. Intermittent azithromycin for treatment of Mycobacterium avium infection in beige mice.

    PubMed Central

    Klemens, S P; Cynamon, M H

    1994-01-01

    The activity of azithromycin (AZI) was evaluated in the beige mouse model of disseminated Mycobacterium avium infection. Mice were infected intravenously with approximately 10(7) viable avium ATCC 49601. AZI at 50, 100, or 200 mg/kg of body weight or clarithromycin (CLA) at 200 mg/kg was given by gavage 5 days per week for 4 weeks. Groups of treated mice were compared with untreated control animals. A dose-related reduction in cell counts in organs was observed with AZI treatment. AZI at 200 mg/kg was more active than CLA at 200 mg/kg against organisms in spleens. The activities of these two agents at 200 mg/kg were comparable against organisms in lungs. In a second study, AZI at 200 mg/kg was given daily for 5 days; this was followed by intermittent AZI treatment for the next 3 weeks. The activities of AZI given on a three-times- and five-times-per-week basis in the continuation phase were comparable. AZI given on a once-weekly basis was less active. The regimen of AZI given in combination with rifapentine on a once-weekly basis for 8 weeks showed promising activity. Clinical evaluation of AZI and rifapentine will help to define the roles of these agents in the treatment of disseminated M. avium complex infection. PMID:7986001

  3. Development and validation of a reversed-phase HPLC method for simultaneous estimation of ambroxol hydrochloride and azithromycin in tablet dosage form.

    PubMed

    Shaikh, K A; Patil, S D; Devkhile, A B

    2008-12-15

    A simple, precise and accurate reversed-phase liquid chromatographic method has been developed for the simultaneous estimation of ambroxol hydrochloride and azithromycin in tablet formulations. The chromatographic separation was achieved on a Xterra RP18 (250 mm x 4.6 mm, 5 microm) analytical column. A Mixture of acetonitrile-dipotassium phosphate (30 mM) (50:50, v/v) (pH 9.0) was used as the mobile phase, at a flow rate of 1.7 ml/min and detector wavelength at 215 nm. The retention time of ambroxol and azithromycin was found to be 5.0 and 11.5 min, respectively. The validation of the proposed method was carried out for specificity, linearity, accuracy, precision, limit of detection, limit of quantitation and robustness. The linear dynamic ranges were from 30-180 to 250-1500 microg/ml for ambroxol hydrochloride and azithromycin, respectively. The percentage recovery obtained for ambroxol hydrochloride and azithromycin were 99.40 and 99.90%, respectively. Limit of detection and quantification for azithromycin were 0.8 and 2.3 microg/ml, for ambroxol hydrochloride 0.004 and 0.01 microg/ml, respectively. The developed method can be used for routine quality control analysis of titled drugs in combination in tablet formulation. PMID:18993009

  4. Notes from the field: Shigella with decreased susceptibility to azithromycin among men who have sex with men - United States, 2002-2013.

    PubMed

    Heiman, Katherine E; Karlsson, Maria; Grass, Julian; Howie, Becca; Kirkcaldy, Robert D; Mahon, Barbara; Brooks, John T; Bowen, Anna

    2014-02-14

    Bacteria of the genus Shigella cause approximately 500,000 illnesses each year in the United States. Diarrhea (sometimes bloody), fever, and stomach cramps typically start 1-2 days after exposure and usually resolve in 5-7 days. For patients with severe disease, bloody diarrhea, or compromised immune systems, antibiotic treatment is recommended, but resistance to traditional first-line antibiotics (e.g., ampicillin and trimethoprim-sulfamethoxazole) is common. For multidrugresistant cases, azithromycin, the most frequently prescribed antibiotic in the United States, is recommended for both children and adults. However, not all Shigellae are susceptible to azithromycin. Nonsusceptible isolates exist but are not usually identified because there are no clinical laboratory guidelines for azithromycin susceptibility testing. However, to monitor susceptibility of Shigellae in the United States, CDC's National Antimicrobial Resistance Monitoring System (NARMS) has, since 2011, routinely measured the azithromycin minimum inhibitory concentration (MIC) for every 20th Shigella isolate submitted from public health laboratories to CDC, as well as outbreak-associated isolates. All known U.S. Shigella isolates with decreased susceptibility to azithromycin (DSA-Shigella), and the illnesses caused by them, are described in this report. PMID:24522098

  5. A Randomized Controlled Pilot Trial of Azithromycin or Artesunate Added to Sulfadoxine-Pyrimethamine as Treatment for Malaria in Pregnant Women

    PubMed Central

    Kalilani, Linda; Mofolo, Innocent; Chaponda, Marjorie; Rogerson, Stephen J.; Alker, Alisa P.; Kwiek, Jesse J.; Meshnick, Steven R.

    2007-01-01

    Objective New anti-malarial regimens are urgently needed in sub-Saharan Africa because of the increase in drug resistance. We investigated the safety and efficacy of azithromycin or artesunate combined with sulfadoxine-pyrimethamine used for treatment of malaria in pregnant women in Blantyre, Malawi. Methods/Findings This was a randomized open-label clinical trial, conducted at two rural health centers in Blantyre district, Malawi. A total of 141 pregnant women with uncomplicated Plasmodium falciparum malaria were recruited and randomly allocated to 3 treatment groups: sulfadoxine-pyrimethamine (SP; 3 tablets, 500 mg sulfadoxine and 25 mg pyrimethamine per tablet); SP plus azithromycin (1 g/day×2 days); or SP plus artesunate (200 mg/day×3 days). Women received two doses administered at least 4 weeks apart. Heteroduplex tracking assays were performed to distinguish recrudescence from new infections. Main outcome measures were incidence of adverse outcomes, parasite and fever clearance times and recrudescence rates. All treatment regimens were well tolerated. Two women vomited soon after ingesting azithromycin. The parasite clearance time was significantly faster in the SP-artesunate group. Recrudescent episodes of malaria were less frequent with SP-azithromycin [Hazard Ratio 0.19 (95% confidence interval 0.06 to 0.63)] and SP-artesunate [Hazard Ratio 0.25 (95% confidence interval 0.10 to 0.65)] compared with SP monotherapy. With one exception (an abortion in the SP-azithromycin group), all adverse pregnancy outcomes could be attributed to known infectious or obstetrical causes. Because of the small sample size, the effect on birth outcomes, maternal malaria or maternal anemia could not be evaluated. Conclusions Both SP-artesunate and SP-azithromycin appeared to be safe, well tolerated and efficacious for the treatment of malaria during pregnancy. A larger study is needed to determine their safety and efficacy in preventing poor birth outcomes. Trial Registration

  6. Oral azithromycin given during labour decreases bacterial carriage in the mothers and their offspring: a double-blind randomized trial.

    PubMed

    Roca, A; Oluwalana, C; Bojang, A; Camara, B; Kampmann, B; Bailey, R; Demba, A; Bottomley, C; D'Alessandro, U

    2016-06-01

    Bacterial sepsis remains a leading cause of death among neonates with Staphylococcus aureus, group B streptococcus (GBS) and Streptococcus pneumoniae identified as the most common causative pathogens in Africa. Asymptomatic bacterial colonization is an intermediate step towards sepsis. We conducted a phase III, double-blind, placebo-controlled randomized trial to determine the impact of giving one oral dose of azithromycin to Gambian women in labour on the nasopharyngeal carriage of S. aureus, GBS or S. pneumoniae in the newborn at day 6 postpartum. Study participants were recruited in a health facility in western Gambia. They were followed for 8 weeks and samples were collected during the first 4 weeks. Between April 2013 and April 2014 we recruited 829 women who delivered 843 babies, including 13 stillbirths. Sixteen babies died during the follow-up period. No maternal deaths were observed. No serious adverse events related to the intervention were reported. According to the intent-to-treat analysis, prevalence of nasopharyngeal carriage of the bacteria of interest in the newborns at day 6 was lower in the intervention arm (28.3% versus 65.1% prevalence ratio 0.43; 95% CI 0.36-0.52, p <0.001). At the same time-point, prevalence of any bacteria in the mother was also lower in the azithromycin group (nasopharynx, 9.3% versus 40.0%, p <0.001; breast milk, 7.9% versus 21.6%, p <0.001; and the vaginal tract, 13.2% versus 24.2%, p <0.001). Differences between arms lasted for at least 4 weeks. Oral azithromycin given to women in labour decreased the carriage of bacteria of interest in mothers and newborns and may lower the risk of neonatal sepsis. Trial registrationClinicalTrials.gov Identifier NCT01800942. PMID:27026482

  7. Comparative evaluation of 2 g single dose versus conventional dose azithromycin in uncomplicated skin and skin structure infections

    PubMed Central

    Dey, Sudipta Kumar; Das, Amal Kanti; Sen, Sumit; Hazra, Avijit

    2015-01-01

    Objectives: Uncomplicated skin and skin structure infections (uSSSIs) are a common clinical problem. Majority are caused by staphylococci and streptococci. Different oral antibiotics are used for uSSSI, with comparable efficacy but varying treatment duration, cost, and adverse event profile. Azithromycin is used in uSSSI in adults conventionally in a dose of 500 mg once for 5 days. The extensive tissue distribution of the drug and its long elimination half-life prompted us to explore whether a single 2 g dose of the drug would produce a response in uSSSI comparable to conventional dosing. Materials and Methods: We conducted a parallel group, open-label, randomized, controlled trial (CTRI/2015/07/005969) with subjects of either sex, ≥12 years of age, presenting with uSSSI to the dermatology outpatient department. One group (n = 146) received 2 g single supervised dose while the other (n = 146) received conventional dose of 500 mg once daily for 5 days. Subjects were followed up on day 4 and day 8. Complete clinical cure implied complete healing of lesions, without residual signs or symptoms, within 7 days. Results: High cure rate was observed in both arms (97.97% and 98.63%, respectively) along with noticeable improvement in symptom profile from baseline but without statistically significant difference between groups. However, excellent adherence (defined as no tablets missed) was better in single dosing arm (98.65% vs. 86.30%). Tolerability was also comparable between groups with the majority of adverse events encountered being gastrointestinal in nature and mild. Conclusions: Single 2 g azithromycin dose achieved the same result as conventional azithromycin dosing in uSSSI with comparable tolerability but with the advantage of assured adherence. This dose can, therefore, be recommended as an alternative and administration supervised if feasible. PMID:26288467

  8. Eradication of Helicobacter pylori in Children by Triple Therapy Regimens of Amoxicillin, Omeprazole, and Clarithromycin or Azithromycin

    PubMed Central

    Esmaeili-Dooki, Mohammad Reza; Shirdel, Hossein; Hajiahmadi, Mahmood

    2015-01-01

    Background and Objectives: The present study aimed to evaluate the effect of classical and azithromycin-containing triple therapy eradication regimen against H. Pylori in children, and to determine the level of patients’ tolerance. Patients and Methods: This single clinical trial was performed in 2014 on 2 to 15 years old children. All children, in whom H. Pylori infection was confirmed through multiple biopsies of the stomach and required treatment, were enrolled in the study. H. Pylori-positive patients were treated alternately with two different drug regimens; Group OCA received clarithromycin 7.5 mg/kg/day every 12 hours for 10 days, amoxicillin 50 mg/kg/day every 12 hours for 10 days, and omeprazole 1 mg/kg/day every 12 hours for two weeks, and Group OAA received azithromycin 10 mg/kg/day once a day (before meal) for 6 days along with amoxicillin and omeprazole. Four to six weeks after completion of treatment, patients’ stool was tested for H. Pylori through the monoclonal method using the Helicobacter antigen quick kit. Results: There were no significant differences between the two groups regarding gender and age of patients. Based on ITT analysis, the therapeutic response in the OAA and OCA groups were 56.2% and 62.5%, respectively (P = 0.40). Drug adverse effects were 15.6% in the OCA and 3.1% in the OAA group (P = 0.19). Conclusions: The therapeutic response was seen in more than half of the patients treated with triple therapy of H. Pylori eradication regimen including azithromycin or clarithromycin, and there was no significant difference between the two treatment groups. PMID:26635936

  9. Replacement of clarithromycin with azithromycin in triple therapy regimens for the eradication of helicobacter pylori: A randomized clinical trial

    PubMed Central

    Khoshnood, A; Hakimi, P; Salman-Roghani, H; Reza Mirjalili, M

    2014-01-01

    Abstract Background: Eradication of helicobacter pylori is important for treatment of GU but an ideal regimen is not available. HP is resistant to metronidazole and clarithromycin. Clarithromycin is expensive and is not available in under developing countries. This study aimed to compare two regimens containing clarithromycin or azithromycin. Methods: Totally, seventy-eight patients with GU (confirmed with endoscopy) and infection of HP (Confirmed by Rapid Urease Test (RUT)) were allocated to one of the groups of study (35 participants in each group). Two weeks regimen of Clarithromycin (2×500 mg) + Amoxicillin (2×1 gr) + omeprazole (2×20 mg) was administered for group A of patients while group B got a 10 days regimen of Azithromycin (1×250 mg) + 14 days Amoxicillin (2×1 gr) + omeprazole (2×20 mg). At the end of the treatment course, the patients were evaluated according to the side effects of the drugs. In addition, two months after the end of therapy, patients underwent endoscopy and biopsy to evaluate HP eradication. Results: After two weeks, the side effects of the drug were: Nausea 8 patients in group A and 7 patients in group B, Diarrhea 2 patients in group A, 3 patients in group B and vomiting 2 patients in group A, 3 patients in group B. There were no serious side effects in any group. Eradication rate in group A was 82.9% (based on per protocol analysis (PPA)) and 84.6 % (intention to treat (ITT)). In group B, eradication rate was 77.1 % (PPA) and 79.5 % (ITT) (P=0.55). Conclusion: Based on our study results, azithromycin can be used in HP eradication regimen because of its similar efficacy to clarithromycin but also have lower cost, side effects and resistance. PMID:25408735

  10. No proarrhythmic properties of the antibiotics Moxifloxacin or Azithromycin in anaesthetized dogs with chronic-AV block

    PubMed Central

    Thomsen, M B; Beekman, J D M; Attevelt, N J M; Takahara, A; Sugiyama, A; Chiba, K; Vos, M A

    2006-01-01

    Background & purpose: The therapeutically available quinolone antibiotic moxifloxacin has been used as a positive control for prolonging the QT interval in both clinical and non-clinical studies designed to assess the potential of new drugs to delay cardiac repolarization. Despite moxifloxacin prolonging QT, it has not been shown to cause torsades de pointes arrhythmias (TdP). Azithromycin is a macrolide antibiotic that has rarely been associated, clinically, with cases of proarrhythmia. As there is a lack of clinical data available, the cardiac safety of these drugs was assessed in a TdP-susceptible animal model by evaluating their repolarization and proarrhythmia effects. Experimental approach & Key results: In transfected HEK cells, the IC50s for I hERG were 45±6 and 856±259 μg ml-1 for moxifloxacin and azithromycin, respectively. Intravenous administration of 2 and 8 mg kg-1 moxifloxacin (total peak-plasma concentrations 4.6±1.5 and 22.9±6.8 μg ml-1) prolonged the QTc in 6 anaesthetized dogs with chronic AV block by 7±3 and 21±19%, respectively. Similar intravenous doses of azithromycin (total peak-plasma concentrations 5.4±1.3 and 20.8±4.9 μg ml-1) had no electrophysiological effects in the same dogs. The reference compound, dofetilide (25 μg kg-1 i.v.) caused QTc prolongation (29±15%) and TdP in all dogs. Beat-to-beat variability of repolarization (BVR), quantified as short-term variability of the left ventricular monophasic action potential duration, was only increased after dofetilide (1.8±0.7 to 3.8±1.5 ms; P<0.05). Conclusion & implications: As neither moxifloxacin nor azithromycin caused TdP or an increase in the BVR, we conclude that both drugs can be used safely in clinical situations. PMID:17088870

  11. Effect of Azithromycin plus Rifampin versus Amoxicillin Alone on Eradication and Inflammation in the Chronic Course of Chlamydia pneumoniae Pneumonitis in Mice

    PubMed Central

    Bin, Xie Xiao; Wolf, Katerina; Schaffner, Thomas; Malinverni, Raffaele

    2000-01-01

    The effects of treatment with azithromycin plus rifampin (A+R), amoxicillin (A), or placebo (P) on the chronic course of experimental Chlamydia pneumoniae pneumonitis in mice were assessed by culture, PCR, and immunocytochemistry as well as by degree of inflammation in lung tissue. Eradication of the pathogen was significantly more frequent and inflammation in tissue was significantly reduced after treatment with A+R compared to after treatment with A or P. Combination therapy with azithromycin plus rifampin showed favorable effects in the chronic course of C. pneumoniae pneumonitis. PMID:10817751

  12. Clinical effect of azithromycin as an adjunct to non-surgical treatment of chronic periodontitis: a meta-analysis of randomized controlled clinical trials.

    PubMed

    Zhang, Z; Zheng, Y; Bian, X

    2016-06-01

    The results of recent published studies focusing on the effect of azithromycin as an adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis are inconsistent. We conducted a meta-analysis of randomized controlled clinical trials to examine the effect of azithromycin combined with SRP on periodontal clinical parameters as compared to SRP alone. An electronic search was carried out on Pubmed, Embase and the Cochrane Central Register of Controlled Trials from their earliest records through December 28, 2014 to identify studies that met pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. Data were extracted independently by two authors. Either a fixed- or random-effects model was used to calculate the overall effect sizes of azithromycin on probing depth, attachment level (AL) and bleeding on probing (BOP). Heterogeneity was evaluated using the Q test and I(2) statistic. Publication bias was evaluated by Begg's test and Egger's test. A total of 14 trials were included in the meta-analysis. Compared with SRP alone, locally delivered azithromycin plus SRP statistically significantly reduced probing depth by 0.99 mm (95% CI 0.42-1.57) and increased AL by 1.12 mm (95% CI 0.31-1.92). In addition, systemically administered azithromycin plus SRP statistically significantly reduced probing depth by 0.21 mm (95% CI 0.12-0.29), BOP by 4.50% (95% CI 1.45-7.56) and increased AL by 0.23 mm (95% CI 0.07-0.39). Sensitivity analysis yielded similar results. No evidence of publication bias was observed. The additional benefit of systemic azithromycin was shown at the initially deep probing depth sites, but not at shallow or moderate sites. The overall effect sizes of systemic azithromycin showed a tendency to decrease with time, and meta-regression analysis suggested a negative relation between the length of follow-up and net change in probing depth (r = -0.05, p = 0.02). This meta-analysis provides further

  13. Azithromycin resistance and its mechanism in Neisseria gonorrhoeae strains in Hyogo, Japan.

    PubMed

    Shigemura, Katsumi; Osawa, Kayo; Miura, Makiko; Tanaka, Kazushi; Arakawa, Soichi; Shirakawa, Toshiro; Fujisawa, Masato

    2015-05-01

    Therapeutic options are limited for Neisseria gonorrhoeae infection, especially for oral drugs. The purpose of this study was to investigate the susceptibility of N. gonorrhoeae to oral azithromycin (AZM) and the correlation between AZM resistance-related gene mutations and MIC. We examined the AZM MICs of clinical strains of N. gonorrhoeae, sequenced the peptidyltransferase loop in domain V of 23S rRNA, and investigated the statistical correlation between AZM MIC and the presence and number of the mutations. Among 59 N. gonorrhoeae strains, our statistical data showed that a deletion mutation was seen significantly more often in the higher-MIC group (0.5 μg/ml or higher) (35/37; 94.6%) than in the lower-MIC group (0.25 μg/ml or less) (4/22; 18.2%) (P < 0.0001). However, a mutation of codon 40 (Ala → Asp) in the mtrR gene (helix-turn-helix) was seen significantly more often in the lower-MIC group (12/22; 54.5%) (P < 0.0001). In N. gonorrhoeae multiantigen sequence typing (NG-MAST) analyses, ST4777 was representative of the lower-MIC group and ST1407, ST6798, and ST6800 were representative of the higher-MIC group. NG-MAST type 1407 was detected as the most prevalent type in AZM-resistant or -intermediate strains, as previously described. In conclusion, a deletion mutation in the mtrR promoter region may be a significant indicator for higher MIC (0.5 μg/ml or higher). ST4777 was often seen in the lower-MIC group, and ST1407, ST6798, and ST6800 were characteristic of the higher-MIC group. Further research with a greater number of strains would help elucidate the mechanism of AZM resistance in N. gonorrhoeae infection. PMID:25712352

  14. Involvement of intestinal uptake transporters in the absorption of azithromycin and clarithromycin in the rat.

    PubMed

    Garver, Eric; Hugger, Erin D; Shearn, Shawn P; Rao, Anuradha; Dawson, Paul A; Davis, Charles B; Han, Chao

    2008-12-01

    Macrolide antibiotics azithromycin (AZI) and clarithromycin (CLARI) are large molecular weight compounds and are substrates for apically polarized efflux transporters such as P-glycoprotein, which can potentially restrict intestinal absorption. However, despite these undesired physicochemical and biopharmaceutical properties, AZI and CLARI exhibit moderate to excellent p.o. bioavailability in preclinical species and humans. Intestinal uptake transporters, such as organic anion transporting polypeptides (OATPs), can facilitate the uptake of drugs that are substrates and hence increase p.o. absorption. The present study was designed to determine whether the intestinal Oatps are involved in absorption of these macrolides. AZI or CLARI was dosed p.o. to Sprague-Dawley rats after p.o. administration with vehicle or rifamycin SV (RIF), an OATP inhibitor. The p.o. exposures of AZI and CLARI were reduced 65 and 45%, respectively, when coadministered with an optimized RIF regimen. The p.o. RIF had no affect on the total blood clearance of these macrolides and most likely did not cause induction of metabolizing enzymes and/or transporters. Therefore, the results suggest that inhibition of an RIF-sensitive uptake transporter such as Oatp along the rat gastrointestinal tract was responsible for reduced p.o. exposure of AZI and CLARI. In addition, AZI and CLARI caused inhibition of taurocholate uptake in rat Oatp1a5-transfected Madin-Darby canine kidney cell monolayers. The in vitro and in vivo results suggest that the intestinal Oatps are involved in the p.o. absorption of AZI and CLARI in the rat. PMID:18755851

  15. Impact of Azithromycin on the Quorum Sensing-Controlled Proteome of Pseudomonas aeruginosa

    PubMed Central

    Swatton, J. E.; Davenport, P. W.; Maunders, E. A.; Griffin, J. L.; Lilley, K. S.; Welch, M.

    2016-01-01

    The macrolide antibiotic, azithromycin (AZM), has been reported to improve the clinical outcome of cystic fibrosis patients, many of whom are chronically-infected with Pseudomonas aeruginosa. However, the highest clinically-achievable concentrations of this drug are well-below the minimum inhibitory concentration for P. aeruginosa, raising the question of why AZM exhibits therapeutic activity. One possibility that has been raised by earlier studies is that AZM inhibits quorum sensing (QS) by P. aeruginosa. To explicitly test this hypothesis the changes brought about by AZM treatment need to be compared with those associated with specific QS mutants grown alongside in the same growth medium, but this has not been done. In this work, we used quantitative 2D-difference gel electrophoresis and 1H-NMR spectroscopy footprint analysis to examine whether a range of clinically-relevant AZM concentrations elicited proteomic and metabolomic changes in wild-type cultures that were similar to those seen in cultures of defined QS mutants. Consistent with earlier reports, over half of the AZM-induced spot changes on the 2D gels were found to affect QS-regulated proteins. However, AZM modulated very few protein spots overall (compared with QS) and collectively, these modulated proteins comprised only a small fraction (12–13%) of the global QS regulon. We conclude that AZM perturbs a sub-regulon of the QS system but does not block QS per se. Reinforcing this notion, we further show that AZM is capable of attenuating virulence factor production in another Gram-negative species that secretes copious quantities of exoenzymes (Serratia marcescens), even in the absence of a functional QS system. PMID:26808156

  16. Impact of Azithromycin on the Quorum Sensing-Controlled Proteome of Pseudomonas aeruginosa.

    PubMed

    Swatton, J E; Davenport, P W; Maunders, E A; Griffin, J L; Lilley, K S; Welch, M

    2016-01-01

    The macrolide antibiotic, azithromycin (AZM), has been reported to improve the clinical outcome of cystic fibrosis patients, many of whom are chronically-infected with Pseudomonas aeruginosa. However, the highest clinically-achievable concentrations of this drug are well-below the minimum inhibitory concentration for P. aeruginosa, raising the question of why AZM exhibits therapeutic activity. One possibility that has been raised by earlier studies is that AZM inhibits quorum sensing (QS) by P. aeruginosa. To explicitly test this hypothesis the changes brought about by AZM treatment need to be compared with those associated with specific QS mutants grown alongside in the same growth medium, but this has not been done. In this work, we used quantitative 2D-difference gel electrophoresis and 1H-NMR spectroscopy footprint analysis to examine whether a range of clinically-relevant AZM concentrations elicited proteomic and metabolomic changes in wild-type cultures that were similar to those seen in cultures of defined QS mutants. Consistent with earlier reports, over half of the AZM-induced spot changes on the 2D gels were found to affect QS-regulated proteins. However, AZM modulated very few protein spots overall (compared with QS) and collectively, these modulated proteins comprised only a small fraction (12-13%) of the global QS regulon. We conclude that AZM perturbs a sub-regulon of the QS system but does not block QS per se. Reinforcing this notion, we further show that AZM is capable of attenuating virulence factor production in another Gram-negative species that secretes copious quantities of exoenzymes (Serratia marcescens), even in the absence of a functional QS system. PMID:26808156

  17. Geospatial Distribution and Clustering of Chlamydia trachomatis in Communities Undergoing Mass Azithromycin Treatment

    PubMed Central

    Yohannan, Jithin; He, Bing; Wang, Jiangxia; Greene, Gregory; Schein, Yvette; Mkocha, Harran; Munoz, Beatriz; Quinn, Thomas C.; Gaydos, Charlotte; West, Sheila K.

    2014-01-01

    Purpose. We detected spatial clustering of households with Chlamydia trachomatis infection (CI) and active trachoma (AT) in villages undergoing mass treatment with azithromycin (MDA) over time. Methods. We obtained global positioning system (GPS) coordinates for all households in four villages in Kongwa District, Tanzania. Every 6 months for a period of 42 months, our team examined all children under 10 for AT, and tested for CI with ocular swabbing and Amplicor. Villages underwent four rounds of annual MDA. We classified households as having ≥1 child with CI (or AT) or having 0 children with CI (or AT). We calculated the difference in the K function between households with and without CI or AT to detect clustering at each time point. Results. Between 918 and 991 households were included over the 42 months of this analysis. At baseline, 306 households (32.59%) had ≥1 child with CI, which declined to 73 households (7.50%) at 42 months. We observed borderline clustering of households with CI at 12 months after one round of MDA and statistically significant clustering with growing cluster sizes between 18 and 24 months after two rounds of MDA. Clusters diminished in size at 30 months after 3 rounds of MDA. Active trachoma did not cluster at any time point. Conclusions. This study demonstrates that CI clusters after multiple rounds of MDA. Clusters of infection may increase in size if the annual antibiotic pressure is removed. The absence of growth after the three rounds suggests the start of control of transmission. PMID:24906862

  18. Relationship between Azithromycin Susceptibility and Administration Efficacy for Nontypeable Haemophilus influenzae Respiratory Infection

    PubMed Central

    Euba, Begoña; Moleres, Javier; Viadas, Cristina; Barberán, Montserrat; Caballero, Lucía; Grilló, María-Jesús; Bengoechea, José Antonio; de-Torres, Juan Pablo; Liñares, Josefina; Leiva, José

    2015-01-01

    Nontypeable Haemophilus influenzae (NTHI) is an opportunistic pathogen that is an important cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). COPD is an inflammatory disease of the airways, and exacerbations are acute inflammatory events superimposed on this background of chronic inflammation. Azithromycin (AZM) is a macrolide antibiotic with antibacterial and anti-inflammatory properties and a clinically proven potential for AECOPD prevention and management. Relationships between AZM efficacy and resistance by NTHI and between bactericidal and immunomodulatory effects on NTHI respiratory infection have not been addressed. In this study, we employed two pathogenic NTHI strains with different AZM susceptibilities (NTHI 375 [AZM susceptible] and NTHI 353 [AZM resistant]) to evaluate the prophylactic and therapeutic effects of AZM on the NTHI-host interplay. At the cellular level, AZM was bactericidal toward intracellular NTHI inside alveolar and bronchial epithelia and alveolar macrophages, and it enhanced NTHI phagocytosis by the latter cell type. These effects correlated with the strain MIC of AZM and the antibiotic dose. Additionally, the effect of AZM on NTHI infection was assessed in a mouse model of pulmonary infection. AZM showed both preventive and therapeutic efficacies by lowering NTHI 375 bacterial counts in lungs and bronchoalveolar lavage fluid (BALF) and by reducing histopathological inflammatory lesions in the upper and lower airways of mice. Conversely, AZM did not reduce bacterial loads in animals infected with NTHI 353, in which case a milder anti-inflammatory effect was also observed. Together, the results of this work link the bactericidal and anti-inflammatory effects of AZM and frame the efficacy of this antibiotic against NTHI respiratory infection. PMID:25712355

  19. Expression comparison of azithromycin and clarithromycin in triple-therapy regimens for eradication of Helicobacter pylori in hemodialysis patients.

    PubMed

    Vafaeimanesh, Jamshid; Jalalzadeh, Mojgan; Nazarian, Morteza

    2014-01-01

    To compare a triple-therapy regimen based on change of antibiotic (azithromycin and clarithromycin) for the eradication of Helicobacter pylori in hemodialysis (HD) patients, we studied in a prospective, randomized, double-blinded clinical trial 39 patients who had dyspepsia and showed two positive results from the diagnostic tests of H. pylori infection including anti-H. pylori serology and stool antigen (HpSAg) and urease breath test (UBT). The patients were divided into two groups: Group-A received omeprazol 20 mg, amoxycilin 500 mg and clarithromycin 500 mg twice a day and Group-B received omeprazol 20 mg, amoxicillin 500 mg and azithromycin 250 mg twice a day. The adverse events and compliance with triple therapy were reviewed at one visit per week. Both groups were prescribed their medications for 14 days. Of the 39 patients, only 37 patients completed the treatment schedule (20 men and 19 women, with the mean being 59 years). Two patients died due to myocardial infarction before the start of treatment and were out of the study. The eradication rate of H. pylori, evaluated by negative results of UBT, was 82.4% in Group-A and 80% in Group-B (P-value = 1.0). The results of our study showed no significant difference of azitromycin versus claritromycin in the eradication of H. pylori infection in HD patients. PMID:24434382

  20. Clinical efficacy and safety of a short regimen of azithromycin sequential therapy vs standard cefuroxime sequential therapy in the treatment of community-acquired pneumonia: an international, randomized, open-label study.

    PubMed

    Kuzman, I; Daković-Rode, O; Oremus, M; Banaszak, A M

    2005-12-01

    An international, randomized, open-label, comparative study was undertaken in order to assess the efficacy and safety of azithromycin and cefuroxime, short sequential vs standard sequential therapy, respectively, in the treatment of patients with community-acquired pneumonia (CAP). 180 adult patients were included in the study. 89 patients received azithromycin 500 mg intravenously (i.v.) once daily for 1-4 days followed by azithromycin 500 mg orally once daily for 3 days. 91 patients received cefuroxime 1.5 g i.v. three times daily for 1-4 days followed by cefuroxime axetil 500 mg orally twice daily for 7 days. Clinical efficacy was achieved in 67/82 (81.7%) patients treated with azithromycin, and in 73/89 (82.0%) patients treated with cefuroxime. The mean duration of total (i.v. and oral) therapy was significantly shorter for the azithromycin group than for the cefuroxime group (6.2 days vs 10.1 days). Adverse events were recorded in 38.2% of patients treated with azithromycin, and in 29.7% of patients treated with cefuroxime (p = 0.20). Shorter sequential i.v.-to-oral azithromycin therapy of patients with CAP was as effective as standard sequential i.v.-to-oral cefuroxime therapy. PMID:16433194

  1. Prevalence of Active and Latent Yaws in the Solomon Islands 18 Months after Azithromycin Mass Drug Administration for Trachoma

    PubMed Central

    Sokana, Oliver; Nachamkin, Eli; Puiahi, Elliot; Kilua, Georgina; Pillay, Allan; Bottomley, Christian; Solomon, Anthony W.; Mabey, David C.

    2016-01-01

    Introduction Both yaws and trachoma are endemic in the Pacific. Mass treatment with azithromycin is the mainstay of the WHO strategy for both the eradication of yaws and the elimination of trachoma as a public health problem, but the dose recommended for trachoma is lower than that for yaws. In countries where both diseases are endemic, there is a potential for synergy between yaws and trachoma control programs if mass treatment with the lower dose of azithromycin was shown to be effective for the treatment of yaws. In an earlier study, we demonstrated a profound reduction in the clinical and serological prevalence of yaws following a single round of mass treatment with azithromycin 20 mg/kg undertaken for the purposes of trachoma elimination. Methods This survey was conducted 18 months following a single round of azithromycin mass treatment in the same communities in which we had conducted our previous six-month follow-up survey. We examined children aged 1–14 years and took blood and lesion samples for yaws diagnosis using the Treponema pallidum particle agglutination assay (TPPA) and the non-treponemal Rapid Plasma Reagin (RPR) test. Results A total of 1,284 children were enrolled in the study. Amongst children aged 5–14 years, 223 had a positive TPPA (27.5%, 95% CI 13.6–47.7%). The TPPA seroprevalence amongst this age group did not differ significantly from either our pre-mass treatment survey or our initial follow-up survey. Thirty-five children had positive TPPA and positive RPR (4.3%, 95% CI 2.1–8.7%), and this did not differ significantly from our initial post-mass drug administration (MDA) follow-up survey (4.3% versus 3.5%, p = 0.43) but remained significantly lower than our initial pre-MDA survey (4.3% vs 21.7%, p <0.0001). Village-level MDA coverage was strongly associated with dual-seropositivity (p = 0.005). Amongst children aged 1–4 years, 16 had a positive TPPA (3.5%, 95% CI 1.6–7.1%). This did not differ significantly from the

  2. 3‐day treatment with azithromycin 1.5% eye drops versus 7‐day treatment with tobramycin 0.3% for purulent bacterial conjunctivitis: multicentre, randomised and controlled trial in adults and children

    PubMed Central

    Cochereau, Isabelle; Meddeb‐Ouertani, Amel; Khairallah, Moncef; Amraoui, Abdelouahed; Zaghloul, Khalid; Pop, Mihai; Delval, Laurent; Pouliquen, Pascale; Tandon, Radhika; Garg, Prashant; Goldschmidt, Pablo; Bourcier, Tristan

    2007-01-01

    Aim To compare the efficacy and safety of Azyter, azithromycin 1.5% eye drops, for 3 days with tobramycin 0.3% for 7 days to treat purulent bacterial conjunctivitis. Methods This was a multicentre, randomised, investigator‐masked study including 1043 children and adults with purulent bacterial conjunctivitis. Patients received either azithromycin 1.5% twice‐daily for 3 days or tobramycin 0.3%, 1 drop every two hours for 2 days, then four times daily for 5 days. Clinical signs were evaluated and cultures obtained at D0, D3 and D9 (where D refers to “day”). Primary variable was the clinical cure at the Test‐of‐Cure (TOC)‐visit (D9±1), for patients with D0‐positive cultures. The cure was defined as: bulbar conjunctival injection and discharge scores of 0. Results Among 471 patients with D0‐positivity in the per protocol set, 87.8% of the azithromycin 1.5% group and 89.4% of the tobramycin group were clinically cured at the TOC‐visit. Azithromycin was non‐inferior to tobramycin for clinical and bacteriological cure. Clinical cure was significantly higher with azithromycin 1.5% at D3. The safety profile of azithromycin was satisfactory with a good patient and investigator's acceptability. Conclusions Azithromycin 1.5% for 3 days was as effective and as safe as tobramycin for 7 days. Furthermore, more azithromycin than tobramycin patients presented an early clinical cure at Day 3. Due to its twice daily dosing regimen for 3 days, azithromycin represents a step forward in the management of purulent bacterial conjunctivitis, especially in children. PMID:17050578

  3. Outcome of Intravenous Azithromycin Therapy in Patients with Complicated Scrub Typhus Compared with That of Doxycycline Therapy Using Propensity-Matched Analysis

    PubMed Central

    Jang, Mi-Ok; Jang, Hee-Chang; Kim, Uh Jin; Ahn, Joon Hwan; Kang, Seung-Ji; Jung, Sook-In; Shin, Hee-Young

    2014-01-01

    There are no well-matched, controlled studies comparing azithromycin with doxycycline for the treatment of complicated scrub typhus. A retrospective propensity score-matched case-control study was performed for patients who presented with complicated scrub typhus and were treated with doxycycline or azithromycin between 2001 and 2011. Data on comorbidities, clinical manifestations, laboratory studies, treatments, and outcomes were extracted for analysis. The clinical characteristics and outcomes of the azithromycin-treated group (n = 73) were compared to those of the doxycycline-treated group (n = 108). Of 181 patients, 73 from each group were matched by propensity scores. There were no significant differences in baseline characteristics between the matched groups. The treatment success and survival rates were not significantly different (89% [65/73 patients] versus 96% [70/73 patients] and 96% [70/73 patients] versus 96% [70/73 patients], respectively [P > 0.05]). No difference was observed in the time to defervescence or length of hospital stay between the two groups (P > 0.05). In complicated scrub typhus patients (n = 181), multivariate analysis showed that only APACHE II score was an independent risk factor for mortality (95% confidence interval, 1.11 to 1.56; P < 0.001). Our data suggest that outcomes of azithromycin therapy are comparable to those of doxycycline therapy in patients with complicated scrub typhus. PMID:24366734

  4. Azithromycin resistance is coevolving with reduced susceptibility to cephalosporins in Neisseria gonorrhoeae in Ontario, Canada.

    PubMed

    Allen, Vanessa G; Seah, Christine; Martin, Irene; Melano, Roberto G

    2014-05-01

    Azithromycin (AZM) is routinely recommended as a component of dual therapy for gonorrhea in combination with third-generation cephalosporins (3GC). In this study, we examined the prevalence of AZM-resistant (AZM(r)) Neisseria gonorrhoeae from July 2010 to February 2013, assessed the rate of concurrent cephalosporin resistance under the current treatment recommendations, and analyzed the clonal distribution of AZM(r) isolates in Ontario, Canada. Nineteen AZM(r) clinical isolates (one per patient; MIC, ≥2 μg/ml) were included in the study. Susceptibility profiles of these isolates to 11 antibiotics, molecular typing, characterization of macrolide resistance mechanisms, and penicillin-binding protein 2 (PBP2) patterns were determined for all the isolates. Two groups were defined based on AZM(r) level; group A isolates displayed high-level resistance (MIC, ≥2,048 μg/ml) due to mutations (A2143G) in the four copies of the 23S rRNA rrl gene, and group B isolates had moderate resistance to AZM (MICs, 2 to 8 μg/ml, C2599T mutation in the rrl gene), with a subgroup belonging to sequence type 3158 (ST3158) (n = 8), which also showed reduced susceptibility to 3GC (MICs, 0.12 to 0.25 μg/ml, PBP2 pattern XXXIV). This AZM(r) phenotype was not observed in previous provincial surveillance in 2008 (the ST3158 clone was found, with AZM MICs of 0.25 to 0.5 μg/ml associated with mtrR mutations). We hypothesized that the AZM mutant prevention concentration (MPC) in the ST3158 subpopulation we found in 2008 was higher than the MPC in wild-type isolates (AZM MIC, ≤0.031 μg/ml), increasing the chances of additional selection of AZM(r) mutations. Full AZM resistance is now emerging in this clone together with reduced susceptibility to 3GC, threatening the future efficacy of these antibiotics as therapeutic options for treatment of gonorrhea. PMID:24514092

  5. How Much Surface Coating of Hydrophobic Azithromycin Is Sufficient to Prevent Moisture-Induced Decrease in Aerosolisation of Hygroscopic Amorphous Colistin Powder?

    PubMed

    Zhou, Qi Tony; Loh, Zhi Hui; Yu, Jiaqi; Sun, Si-Ping; Gengenbach, Thomas; Denman, John A; Li, Jian; Chan, Hak-Kim

    2016-09-01

    Aerosolisation performance of hygroscopic particles of colistin could be compromised at elevated humidity due to increased capillary forces. Co-spray drying colistin with a hydrophobic drug is known to provide a protective coating on the composite particle surfaces against moisture-induced reduction in aerosolisation performance; however, the effects of component ratio on surface coating quality and powder aerosolisation at elevated relative humidities are unknown. In this study, we have systematically examined the effects of mass ratio of hydrophobic azithromycin on surface coating quality and aerosolisation performance of the co-spray dried composite particles. Four combination formulations with varying drug ratios were prepared by co-spray drying drug solutions. Both of the drugs in each combination formulation had similar in vitro deposition profiles, suggesting that each composite particle comprises two drugs in the designed mass ratio, which is supported by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) data. XPS and ToF-SIMS measurements also revealed that 50% by weight (or 35% by molecular fraction) of azithromycin in the formulation provided a near complete coating of 96.5% (molar fraction) on the composite particle surface, which is sufficient to prevent moisture-induced reduction in fine particle fraction (FPF)recovered and FPFemitted. Higher azithromycin content did not increase coating coverage, while contents of azithromycin lower than 20% w/w did not totally prevent the negative effects of humidity on aerosolisation performance. This study has highlighted that a critical amount of azithromycin is required to sufficiently coat the colistin particles for short-term protection against moisture. PMID:27255350

  6. In vitro susceptibilities of Rhodococcus equi and other common equine pathogens to azithromycin, clarithromycin, and 20 other antimicrobials.

    PubMed

    Jacks, Stephanie S; Giguère, Steeve; Nguyen, An

    2003-05-01

    The objective of this study was to determine in vitro activities of azithromycin (AZM), clarithromycin (CLR), and 20 other antimicrobial agents against Rhodococcus equi and other common equine bacterial pathogens. A total of 201 bacterial isolates from various equine clinical samples were examined. CLR was more active than AZM against R. equi, with MICs at which 90% of the isolates were inhibited of 0.12 and 1.0 micro g/ml, respectively. Other antimicrobial agents highly active against at least 90% of R. equi isolates in vitro included rifampin, gentamicin, and imipenem. Both AZM and CLR showed good activity against beta-hemolytic streptococci and Staphylococcus spp. AZM was more active than other macrolides against Pasteurella spp. and Salmonella enterica. PMID:12709351

  7. Development of NIRS method for quality control of drug combination artesunate–azithromycin for the treatment of severe malaria

    PubMed Central

    Boyer, Chantal; Gaudin, Karen; Kauss, Tina; Gaubert, Alexandra; Boudis, Abdelhakim; Verschelden, Justine; Franc, Mickaël; Roussille, Julie; Boucher, Jacques; Olliaro, Piero; White, Nicholas J.; Millet, Pascal; Dubost, Jean-Pierre

    2012-01-01

    Near infrared spectroscopy (NIRS) methods were developed for the determination of analytical content of an antimalarial-antibiotic (artesunate and azithromycin) co-formulation in hard gelatin capsule (HGC). The NIRS consists of pre-processing treatment of spectra (raw spectra and first-derivation of two spectral zones), a unique principal component analysis model to ensure the specificity and then two partial least-squares regression models for the determination content of each active pharmaceutical ingredient. The NIRS methods were developed and validated with no reference method, since the manufacturing process of HGC is basically mixed excipients with active pharmaceutical ingredients. The accuracy profiles showed β-expectation tolerance limits within the acceptance limits (±5%). The analytical control approach performed by reversed phase (HPLC) required two different methods involving two different preparation and chromatographic methods. NIRS offers advantages in terms of lower costs of equipment and procedures, time saving, environmentally friendly. PMID:22579599

  8. Comparison of Azithromycin and Metronidazole in a Quadruple-Therapy Regimen for Helicobacter pylori Eradication in Dyspepsia

    PubMed Central

    Agah, Shahram; Shazad, Babak; Abbaszadeh, Babak

    2009-01-01

    Background/Aim: Helicobacter pylori (H pylori) plays an important role in the pathogenesis of chronic gastritis, peptic ulcer disease, and gastric neoplasms. Therefore, it is necessary to select an effective regimen for H pylori eradication. The aim of this study was to compare the efficacy of two quadruple-therapy regimens—one with azithromycin and the other with metronidazole—for H pylori eradication in patients with dyspepsia. Materials and Methods: In this double-blind randomized clinical trial conducted in Rasoule-Akram Hospital in 2006, we included 60 patients (aged 15–70 years) who had dyspepsia and H pylori infection as diagnosed by upper gastrointestinal endoscopy and rapid urease test. Patients were randomly assigned to receive a quadruple-therapy regimen for 2 weeks: 1) the MAO-B group (n= 30) received metronidazole 500 mg b.i.d, amoxicillin 1g b.i.d, omeprazole 20 mg b.i.d, and bismuth 240 mg b.i.d and 2) the AAO-B group (n = 30) received azithromycin 500 mg once daily for 1 week and amoxicillin 1g b.i.d, omeprazole 20 mg b.i.d, and bismuth 240 mg b.i.d for 2 weeks). H pylori eradication was assessed by the rapid urease test (RUT) 2 months after the cessation of treatment. Results: H pylori was eradicated in 68% and 69% of patients in the MAO-B and AAO-B groups, respectively. There was no significant difference in H pylori eradication rates between the two groups (P = 0.939). Conclusion: No significant difference exists between the two quadruple-therapy regimens that were tested. PMID:19794266

  9. Prevalence of Trachoma in Car-Nicobar Island, India after Three Annual Rounds of Mass Drug Administration with Azithromycin

    PubMed Central

    Malhotra, Sumit; Vashist, Praveen; Gupta, Noopur; Kalaivani, Mani; Satpathy, Gita; Shah, Anita; Krishnan, Sujaya; Azad, Rajvardhan

    2016-01-01

    Background A high proportion of active trachoma infection in children of Car-Nicobar Island was reported through the Trachoma Rapid Assessment survey conducted in year 2010 by the same researchers. Annual mass drug treatment with azithromycin was administered from years 2010–12 to all individuals residing in this island for reducing the burden of active trachoma infection. A cross-sectional prevalence survey was conducted in the year 2013 to assess the post-treatment burden of trachoma in this population. Methods In the 15 randomly selected compact segments from each village of the island, children aged 1–9 years were examined for evidence of active trachoma infection and participants aged ten years and above were examined for trachomatous trichiasis and corneal opacity. Results A total of 809 children (1–9 years) and 2735 adults were examined. Coverage with azithromycin for all the three rounds was more than 80%. The prevalence of active trachoma infection in children aged 1–9 years old was 6.8% (95% CI 5.1, 8.5) and Trachomatous Trichiasis (TT) was 3.9% (95% CI 3.2, 4.6). The risk factors associated with active trachoma infection were older age and unclean faces. The risk factors associated with TT were older age and lower literacy level. Conclusion Trachoma has not been eliminated from Car-Nicobar Island in accordance to ‘Global Elimination of Trachoma, 2020’ guidelines. Sustained efforts and continuous surveillance admixed with adequate programmatic response is imperative for elimination of trachoma in the island. PMID:27391274

  10. Increasing Spectrum in Antimicrobial Resistance of Shigella Isolates in Bangladesh: Resistance to Azithromycin and Ceftriaxone and Decreased Susceptibility to Ciprofloxacin

    PubMed Central

    Mahbubur, Rahman; Shoma, Shereen; Rashid, Harunur; Arifeen, Shams El; Baqui, A.H.; Siddique, A.K.; Nair, G.B.; Sack, D.A.

    2007-01-01

    Antimicrobial resistance of Shigella isolates in Bangladesh, during 2001-2002, was studied and compared with that of 1991-1992 to identify the changes in resistance patterns and trends. A significant increase in resistance to trimethoprim-sulphamethoxazole (from 52% to 72%, p<0.01) and nalidixic acid (from 19% to 51%, p<0.01) was detected. High, but unchanged, resistance to tetracycline, ampicillin, and chloramphenicol, low resistance to mecillinam (resistance 3%, intermediate 3%), and to emergence of resistance to azithromycin (resistance 16%, intermediate 62%) and ceftriaxone/cefixime (2%) were detected in 2001-2002. Of 266 recent isolates, 63% were resistant to ≥3 anti-Shigella drugs (multidrug-resistant [MDR]) compared to 52% of 369 strains (p<0.007) in 1991-1992. Of 154 isolates tested by E-test in 2001-2002, 71% were nalidixic acid-resistant (minimum inhibitory concentration [MIC] ≥32 μg/mL) and had 10-fold higher MIC90 (0.25 μg/mL) to ciprofloxacin than that of nalidixic acid-susceptible strains exhibiting decreased ciprofloxacin susceptibility, which were detected as ciprofloxacin-susceptible and nalidixic acid-resistant by the disc-diffusion method. These strains were frequently associated with MDR traits. High modal MICs were observed to azithromycin (MIC 6 μg/mL) and nalidixic acid (MIC 128 μg/mL) and low to ceftriaxone (MIC 0.023 μg/mL). Conjugative R-plasmids-encoded extended-spectrum ß-lactamase was responsible for resistance to ceftriaxone/cefixime. The growing antimicrobial resistance of Shigella is worrying and mandates monitoring of resistance. Pivmecillinam or ciprofloxacin might be considered for treating shigellosis with caution. PMID:17985817

  11. Increasing spectrum in antimicrobial resistance of Shigella isolates in Bangladesh: resistance to azithromycin and ceftriaxone and decreased susceptibility to ciprofloxacin.

    PubMed

    Rahman, Mahbubur; Shoma, Shereen; Rashid, Harunur; El Arifeen, Shams; Baqui, A H; Siddique, A K; Nair, G B; Sack, D A

    2007-06-01

    Antimicrobial resistance of Shigella isolates in Bangladesh, during 2001-2002, was studied and compared with that of 1991-1992 to identify the changes in resistance patterns and trends. A significant increase in resistance to trimethoprim-sulphamethoxazole (from 52% to 72%, p < 0.01) and nalidixic acid (from 19% to 51%, p < 0.01) was detected. High, but unchanged, resistance to tetracycline, ampicillin, and chloramphenicol, low resistance to mecillinam (resistance 3%, intermediate 3%), and to emergence of resistance to azithromycin (resistance 16%, intermediate 62%) and ceftriaxone/cefixime (2%) were detected in 2001-2002. Of 266 recent isolates, 63% were resistant to > or =3 anti-Shigella drugs (multidrug-resistant [MDR]) compared to 52% of 369 strains (p < 0.007) in 1991-1992. Of 154 isolates tested by E-test in 2001-2002, 71% were nalidixic acid-resistant (minimum inhibitory concentration [MIC] > or =32 microg/mL) and had 10-fold higher MIC90 (0.25 microg/mL) to ciprofloxacin than that of nalidixic acid-susceptible strains exhibiting decreased ciprofloxacin susceptibility, which were detected as ciprofloxacin-susceptible and nalidixic acid-resistant by the disc-diffusion method. These strains were frequently associated with MDR traits. High modal MICs were observed to azithromycin (MIC 6 microg/mL) and nalidixic acid (MIC 128 micdrog/mL) and low to ceftriaxone (MIC 0.023 microg/mL). Conjugative R-plasmids-encoded extended-spectrum beta-lactamase was responsible for resistance to ceftriaxone/cefixime. The growing antimicrobial resistance of Shigella is worrying and mandates monitoring of resistance. Pivmecillinam or ciprofloxacin might be considered for treating shigellosis with caution. PMID:17985817

  12. In vitro effects of four macrolides (roxithromycin, spiramycin, azithromycin (CP-62,993), and A-56268) on Toxoplasma gondii

    SciTech Connect

    Chang, H.R.; Pechere, J.C.

    1988-04-01

    The effect of four macrolides against intracellular Toxoplasma gondii was determined in three different in vitro systems. Unactivated murine peritoneal macrophages were infected with the virulent RH strain of T. gondii. The activity of the macrolides was first measured with (/sup 3/H)uracil, which is incorporated by the parasite but not the host cell. The 50% inhibitory concentrations (IC50s) and 95% confidence limits were calculated at 54 (38 to 73), 140 (98 to 201), 147 (101 to 214), and 246 (187 to 325) micron for roxithromycin, azithromycin (CP-62,993), A-56268, and spiramycin, respectively. Inhibition of Toxoplasma growth was confirmed by microscopic examination of the infected macrophages after treatment with roxithromycin. Compared with untreated controls, roxithromycin concentrations near the IC50s decreased the number of infected cells, the number of tachyzoites per vacuole, and the number of cells containing rosettes (i.e., clusters of more than eight tachyzoites). After treatment with the four macrolides, tachyzoites were released from the macrophages and subcultured in HeLa cells, which are nonprofessional phagocytes, to assess the viability of the remaining parasites. This showed that the macrolides at concentrations corresponding to four times their 90% inhibitory concentrations (IC90s) had no significant killing effect. At 8 times the IC90, roxithromycin showed an incomplete killing effect, similar to that of the combination of pyrimethamine (0.41 microM)-sulfadiazine (99.42 microM). All macrolides tested showed inhibitory effects against intracellular T. gondii, but amounts of azithromycin and A-56268 corresponding to the IC90 appeared to be toxic against the host macrophages, which might have had nonspecific activity against Toxoplasma metabolism.

  13. Bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (BEST-2): study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Bronchiectasis unrelated to cystic fibrosis (CF) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. Methods This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed) to receive: 1) azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2) amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and bacteriological data

  14. Azithromycin to prevent bronchopulmonary dysplasia in ureaplasma-infected preterm infants: pharmacokinetics, safety, microbial response, and clinical outcomes with a 20-milligram-per-kilogram single intravenous dose.

    PubMed

    Viscardi, Rose M; Othman, Ahmed A; Hassan, Hazem E; Eddington, Natalie D; Abebe, Elias; Terrin, Michael L; Kaufman, David A; Waites, Ken B

    2013-05-01

    Ureaplasma respiratory tract colonization is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Previously, we demonstrated that a single intravenous (i.v.) dose of azithromycin (10 mg/kg of body weight) is safe but inadequate to eradicate Ureaplasma spp. in preterm infants. We performed a nonrandomized, single-arm open-label study of the pharmacokinetics (PK) and safety of intravenous 20-mg/kg single-dose azithromycin in 13 mechanically ventilated neonates with a gestational age between 24 weeks 0 days and 28 weeks 6 days. Pharmacokinetic data from 25 neonates (12 dosed with 10 mg/kg i.v. and 13 dosed with 20 mg/kg i.v.) were analyzed using a population modeling approach. Using a two-compartment model with allometric scaling of parameters on body weight (WT), the population PK parameter estimates were as follows: clearance, 0.21 liter/h × WT(kg)(0.75) [WT(kg)(0.75) indicates that clearance was allometrically scaled on body weight (in kilograms) with a fixed exponent of 0.75]; intercompartmental clearance, 2.1 liters/h × WT(kg)(0.75); central volume of distribution (V), 1.97 liters × WT (kg); and peripheral V, 17.9 liters × WT (kg). There was no evidence of departure from dose proportionality in azithromycin exposure over the tested dose range. The calculated area under the concentration-time curve over 24 h in the steady state divided by the MIC90 (AUC24/MIC90) for the single dose of azithromycin (20 mg/kg) was 7.5 h. Simulations suggest that 20 mg/kg for 3 days will maintain azithromycin concentrations of >MIC50 of 1 μg/ml for this group of Ureaplasma isolates for ≥ 96 h after the first dose. Azithromycin was well tolerated with no drug-related adverse events. One of seven (14%) Ureaplasma-positive subjects and three of six (50%) Ureaplasma-negative subjects developed physiologic BPD. Ureaplasma was eradicated in all treated Ureaplasma-positive subjects. Simulations suggest that a multiple-dose regimen may be efficacious for microbial

  15. A 3-day regimen with azithromycin 1.5% eyedrops for the treatment of purulent bacterial conjunctivitis in children: efficacy on clinical signs and impact on the burden of illness

    PubMed Central

    Bremond-Gignac, Dominique; Messaoud, Riadh; Lazreg, Sihem; Speeg-Schatz, Claude; Renault, Didier; Chiambaretta, Frédéric

    2015-01-01

    Purpose To compare the efficacy of azithromycin 1.5% versus tobramycin 0.3% eyedrops on clinical ocular signs and symptoms of bacterial conjunctivitis in children and to assess the parents’ satisfaction regarding the dosing regimen. Patients and methods An international, multicenter, randomized, investigator-masked, controlled clinical trial conducted in children (1 day to 18 years old) with bulbar conjunctival hyperemia and purulent discharge. Azithromycin 1.5% was administered as 1 drop twice daily for 3 days, and tobramycin 0.3% as 1 drop every 2 hours for 2 days, then 4 times daily for 5 days. Results A total of 286 patients (mean age: 3.2 years) were enrolled. In children with bacteriologically positive cultures (N=203), azithromycin produced a significantly greater improvement in conjunctival discharge (P<0.01) and a trend (P=0.054) toward improvement in conjunctival hyperemia at day 7 than did tobramycin. Complete resolution of conjunctival discharge was significantly more frequent at day 3 on azithromycin than tobramycin (P=0.005). More parents found azithromycin easier to use (in terms of treatment duration, total number of instillations, instilling drops during the day, and difficulty in performing daily activities) than tobramycin. Conclusion The azithromycin 1.5% regimen produced a rapid resolution of cardinal signs of purulent bacterial conjunctivitis with a more convenient dosage regimen. Such improved convenience is likely to improve compliance and lessen the burden of illness for patients and carers. PMID:25945033

  16. Determination of the etiological organism during acute exacerbations of COPD and efficacy of azithromycin, ampicillin-sulbactam, ciprofloxacin and cefaclor. Turkish Thoracic Society COPD Working Group.

    PubMed

    Umut, S; Tutluoglu, B; Aydin Tosun, G; Müsellim, B; Erk, M; Yildirim, N; Vahapoglu, H; Yilmaz, N; Arseven, O; Türker, H; Erelel, M; Ilvan, A; Göylüsün, V; Yilmaz Kuyucu, T; Koşar, F; Soysal, F; Gür, A; Unutmaz, S; Oztürk, S; Akman, M

    1999-06-01

    Acute exacerbations, most of which are due to lower respiratory tract infections, cause great morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD) and most of these are due to lower respiratory tract infections. The aim of this study was to determine the causative organism and the effects of azithromycin, ampicillin sulbactam (sultamicillin), ciprofloxacin and cefaclor monohydrate therapy in COPD. One hundred and six patients with COPD in acute exacerbation were randomized into four groups for empiric antibiotic treatment following lung function tests and sputum examination. The most common strains isolated from sputum were Haemophilus influenzae (30.8%), Streptoccocus pneumoniae (12%) and Moraxella catarrhalis (7.7%). Azithromycin, sultamicillin, ciprofloxacin and cefaclor monohydrate were found to be effective in treating COPD exacerbations. PMID:10435684

  17. Poor response to azithromycin in cutaneous leishmaniasis leading to a premature interruption of a multicentric phase III clinical trial in Brazil.

    PubMed

    Toledo Junior, Antonio; Daher, André Bastos; Amaral, Thaís Alves; Carvalho, Sílvio Fernando Guimarães; Romero, Gustavo Adolfo Sierra; Rabello, Ana

    2014-01-01

    Introduction Parenteral antimony-based compounds are still the standard of care for cutaneous leishmaniasis (CL) treatment in many countries, despite their high toxicity. Previous studies showed that oral azithromycin could be an option for CL treatment. The aim of this study was to evaluate efficacy and safety of oral azithromycin (AZ) for CL treatment compared with injectable meglumine antimoniate (MA). Methods This was a randomized, open-label, 2-arm, non-inferiority clinical trial. Treatment-naïve patients with localized CL were treated with MA (15mg/kg/day up to 1,215mg) or AZ (500mg/day) during 20 consecutive days. The primary efficacy end point was a CL cure 90 days after treatment completion. The analysis was performed with intention-to-treat (ITT) and per protocol (PP) analyses. After an anticipated interim analysis, the study was interrupted due to the high failure rate in the azithromycin group. Results Twenty-four volunteers were included in each group. The MA group had a higher cure rate than the AZ group with the ITT and PP analyses, which were 54.2% versus 20.8% [relative risk (RR) 1.97; 95% confidence intervals (95%CI) 1.13-3.42] and 72.2% versus 23.8% (RR 3.03; 95%CI 1.34-6.87), respectively. No unexpected adverse events were observed. Conclusions Azithromycin is ineffective for CL treatment and does not seem to have a role in the therapeutic arsenal for CL. PMID:25626655

  18. Both combined oral azithromycin plus allopurinol and intramuscular Glucantime yield low efficacy in the treatment of Old World cutaneous leishmaniasis: a randomized controlled clinical trial.

    PubMed

    Dastgheib, Ladan; Naseri, Mahsa; Mirashe, Zahra

    2012-12-01

    Old World cutaneous leishmaniasis (OWCL) is an endemic and major health problem in Iran. The optimal treatment of OWCL is unknown, and current treatments are not ideally effective and have many adverse effects. To compare the efficacy and tolerability of combined oral azithromycin and allopurinol with intramuscular Glucantime in the treatment of OWCL, we conducted a prospective randomized clinical trial. A total of 86 patients with OWCL were assigned and divided randomly into two groups; they received a combination of azithromycin capsule 10 mg/kg/d and allopurinol tablet 10 mg/kg/d for two months or IM injection of Glucantime 20 mg/kg of antimony daily for 20 days. All patients were followed for two months after termination of treatment. Although immediately at the end of the treatment period, complete response was seen in 27.8% of patients on combination therapy vs. 0% in the Glucantime group. The combination of azithromycin and allopurinol had a better outcome; two months after the end of the treatment period, complete, partial, and no responses were seen in 38.9%, 22.2%, and 38.9% in combination therapy and 40%, 31.4%, and 28.6% in the Glucantime group. There was no significant difference between the response rate in both groups after two months (P = 0.5). No severe adverse effect occurred. This study demonstrated that the efficacy of combined oral azithromycin and allopurinol at the above doses and duration was similar to that of IM Glucantime in the treatment of OWCL. PMID:23171020

  19. Azithromycin and cough-specific health status in patients with chronic obstructive pulmonary disease and chronic cough: a randomised controlled trial

    PubMed Central

    2013-01-01

    Background Macrolides reduce exacerbations in patients with COPD. Their effects on health status has not been assessed as primary outcome and is less clear. This study assessed the effects of prophylactic azithromycin on cough-specific health status in COPD-patients with chronic productive cough. Methods In this randomised controlled trial 84 patients met the eligibility criteria: age of ≥40 years, COPD GOLD stage ≥2 and chronic productive cough. The intervention-group (n = 42) received azithromycin 250 mg 3 times a week and the control-group (n = 42) received a placebo. Primary outcome was cough-specific health status at 12 weeks, measured with the Leicester Cough Questionnaire (LCQ). Secondary outcomes included generic and COPD-specific health status and exacerbations. Changes in adverse events and microbiology were monitored. Results Mean age of participants was 68 ± 10 years and mean FEV1 was 1.36 ± 0.47 L. The improvement in LCQ total score at 12 weeks was significantly greater with azithromycin (difference 1.3 ± 0.5, 95% CI 0.3;2.3, p = 0.01) and met the minimal clinically important difference. Similar results were found for the domain scores, and COPD-specific and generic health status questionnaires. Other secondary endpoints were non-significant. No imbalances in adverse events were found. Conclusions Prophylactic azithromycin improved cough-specific health status in COPD-patients with chronic productive cough to a clinically relevant degree. Trial registration ClinicalTrials.gov NCT01071161 PMID:24229360

  20. Reduced persistence of the macrolide antibiotics erythromycin, clarithromycin and azithromycin in agricultural soil following several years of exposure in the field.

    PubMed

    Topp, Edward; Renaud, Justin; Sumarah, Mark; Sabourin, Lyne

    2016-08-15

    The macrolide antibiotics erythromycin, clarithromycin and azithromycin are very important in human and animal medicine, and can be entrained onto agricultural ground through application of sewage sludge or manures. In the present study, a series of replicated field plots were left untreated or received up to five annual spring applications of a mixture of three drugs to achieve a nominal concentration for each of 10 or 0.1mgkg(-1) soil; the latter an environmentally relevant concentration. Soil samples were incubated in the laboratory, and supplemented with antibiotics to establish the dissipation kinetics of erythromycin and clarithromycin using radioisotope methods, and azithromycin using HPLC-MS/MS. All three drugs were dissipated significantly more rapidly in soils with a history of field exposure to 10mgkg(-1) macrolides, and erythromycin and clarithromycin were also degraded more rapidly in field soil exposed to 0.1mgkg(-1) macrolides. Rapid mineralization of (14)C-labelled erythromycin and clarithromycin are consistent with biodegradation. Analysis of field soils revealed no carryover of parent compound from year to year. Azithromycin transformation products were detected consistent with removal of the desosamine and cladinose moieties. Overall, these results have revealed that following several years of exposure to macrolide antibiotics these are amenable to accelerated degradation. The potential accelerated degradation of these drugs in soils amended with manure and sewage sludge should be investigated as this phenomenon would attenuate environmental exposure and selection pressure for clinically relevant resistance. PMID:27096634

  1. Development of a Simple RP-HPLC-UV Method for Determination of Azithromycin in Bulk and Pharmaceutical Dosage forms as an Alternative to the USP Method

    PubMed Central

    Ghari, Tayebeh; Kobarfard, Farzad; Mortazavi, Seyed Alireza

    2013-01-01

    The present study was designed to develop a simple, validated liquid chromatographic method for the analysis of azithromycin in bulk and pharmaceutical dosage forms using ultraviolet detector. The best stationary phase was determined as C18 column, 5 μm, 250 mm × 4.6 mm. Mobile phase was optimized to obtain a fast and selective separation of the drug. Flow rate was 1.5 mL/min, Wavelength was set at 210 nm and the volume of each injection was 500 μL. An isocratic methanol/buffer mobile phase at the ratio of 90:10 v/v gave the best separation and resolution. The proposed method was accurate, precise, sensitive, and linear over a wide range of concentration of azithromycin. The developed method has the advantage of using UV detector compared to the USP method in which electrochemical detector has been used. The validated method was successfully applied to the determination of azithromycin in bulk and pharmaceutical dosage forms. PMID:24250672

  2. Genomic Epidemiology and Molecular Resistance Mechanisms of Azithromycin-Resistant Neisseria gonorrhoeae in Canada from 1997 to 2014.

    PubMed

    Demczuk, Walter; Martin, Irene; Peterson, Shelley; Bharat, Amrita; Van Domselaar, Gary; Graham, Morag; Lefebvre, Brigitte; Allen, Vanessa; Hoang, Linda; Tyrrell, Greg; Horsman, Greg; Wylie, John; Haldane, David; Archibald, Chris; Wong, Tom; Unemo, Magnus; Mulvey, Michael R

    2016-05-01

    The emergence of Neisseria gonorrhoeae strains with decreased susceptibility to cephalosporins and azithromycin (AZM) resistance (AZM(r)) represents a public health threat of untreatable gonorrhea infections. Genomic epidemiology through whole-genome sequencing was used to describe the emergence, dissemination, and spread of AZM(r) strains. The genomes of 213 AZM(r) and 23 AZM-susceptible N. gonorrhoeae isolates collected in Canada from 1989 to 2014 were sequenced. Core single nucleotide polymorphism (SNP) phylogenomic analysis resolved 246 isolates into 13 lineages. High-level AZM(r) (MICs ≥ 256 μg/ml) was found in 5 phylogenetically diverse isolates, all of which possessed the A2059G mutation (Escherichia coli numbering) in all four 23S rRNA alleles. One isolate with high-level AZM(r) collected in 2009 concurrently had decreased susceptibility to ceftriaxone (MIC = 0.125 μg/ml). An increase in the number of 23S rRNA alleles with the C2611T mutations (E. coli numbering) conferred low to moderate levels of AZM(r) (MICs = 2 to 4 and 8 to 32 μg/ml, respectively). Low-level AZM(r) was also associated with mtrR promoter mutations, including the -35A deletion and the presence of Neisseria meningitidis-like sequences. Geographic and temporal phylogenetic clustering indicates that emergent AZM(r) strains arise independently and can then rapidly expand clonally in a region through local sexual networks. PMID:26935729

  3. Comparative Plasma Exposure and Lung Distribution of Two Human Use Commercial Azithromycin Formulations Assessed in Murine Model: A Preclinical Study

    PubMed Central

    Rivulgo, Virginia; Sparo, Mónica; Ceci, Mónica; Fumuso, Elida; Confalonieri, Alejandra; Sánchez Bruni, Sergio F.

    2013-01-01

    Azithromycin (AZM) therapeutic failure and relapses of patients treated with generic formulations have been observed in clinical practice. The main goal of this research was to compare in a preclinical study the serum exposure and lung tissue concentration of two commercial formulations AZM-based in murine model. The current study involved 264 healthy Balb-C. Mice were divided into two groups (n = 44): animals of Group A (reference formulation -R-) were orally treated with AZM suspension at 10 mg/kg of b.w. Experimental animals of Group B (generic formulation -G-) received identical treatment than Group A with a generic formulation AZM-based. The study was repeated twice as Phase II and III. Serum and lung tissue samples were taken 24 h post treatment. Validated microbiological assay was used to determine the serum pharmacokinetic and lung distribution of AZM. After the pharmacokinetic analysis was observed, a similar serum exposure for both formulations of AZM assayed. In contrast, statistical differences (P < 0.001) were obtained after comparing the concentrations of both formulations in lung tissue, being the values obtained for AUC and Cmax (AZM-R-) +1586 and 122%, respectively, than those obtained for AZM-G- in lung. These differences may indicate large differences on the distribution process of both formulations, which may explain the lack of efficacy/therapeutic failure observed on clinical practice. PMID:24073402

  4. Growth hormone suppression test

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003376.htm Growth hormone suppression test To use the sharing features on this page, please enable JavaScript. The growth hormone suppression test determines whether growth hormone production is ...

  5. Dexamethasone suppression test

    MedlinePlus

    Dexamethasone suppression test measures whether adrenocorticotrophic hormone ( ACTH ) secretion by the pituitary can be suppressed. ... During this test, you will receive dexamethasone. This is a strong ... your blood is drawn so that the cortisol level in your blood ...

  6. Dexamethasone suppression test

    MedlinePlus

    DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medication. Afterward, your blood is drawn ...

  7. Growth hormone suppression test

    MedlinePlus

    The growth hormone suppression test determines whether growth hormone production is being suppressed by high blood sugar. ... away. The lab measures the glucose and growth hormone (GH) levels in each sample.

  8. The Belgian trial with azithromycin for acute COPD exacerbations requiring hospitalization: an investigator-initiated study protocol for a multicenter, randomized, double-blind, placebo-controlled trial

    PubMed Central

    Vermeersch, Kristina; Gabrovska, Maria; Deslypere, Griet; Demedts, Ingel K; Slabbynck, Hans; Aumann, Joseph; Ninane, Vincent; Verleden, Geert M; Troosters, Thierry; Bogaerts, Kris; Brusselle, Guy G; Janssens, Wim

    2016-01-01

    Background Long-term use of macrolide antibiotics is effective to prevent exacerbations in chronic obstructive pulmonary disease (COPD). As risks and side effects of long-term intervention outweigh the benefits in the general COPD population, the optimal dose, duration of treatment, and target population are yet to be defined. Hospitalization for an acute exacerbation (AE) of COPD may offer a targeted risk group and an obvious risk period for studying macrolide interventions. Methods/design Patients with COPD, hospitalized for an AE, who have a smoking history of ≥10 pack-years and had ≥1 exacerbation in the previous year will be enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (NCT02135354). On top of a standardized treatment of systemic corticosteroids and antibiotics, subjects will be randomized to receive either azithromycin or placebo during 3 months, at an uploading dose of 500 mg once a day for 3 days, followed by a maintenance dose of 250 mg once every 2 days. The primary endpoint is the time-to-treatment failure during the treatment phase (ie, from the moment of randomization until the end of intervention). Treatment failure is a novel composite endpoint defined as either death, the admission to intensive care or the requirement of additional systemic steroids or new antibiotics for respiratory reasons, or the diagnosis of a new AE after discharge. Discussion We investigate whether azithromycin initiated at the onset of a severe exacerbation, with a limited duration and at a low dose, might be effective and safe in the highest risk period during and immediately after the acute event. If proven effective and safe, this targeted approach may improve the treatment of severe AEs and redirect the preventive use of azithromycin in COPD to a temporary intervention in the subgroup with the highest unmet needs. PMID:27099485

  9. An Italian experience of sequential intravenous and oral azithromycin plus intravenous ampicillin/sulbactam in hospitalized patients with community-acquired pneumonia.

    PubMed

    Todisco, T; Dal Farra, F; Ciliberti, G; Pirina, P; Pirica, P; Guelfi, R; Ghelfi, R; Serra, G; Paris, R; Mancuso, I; Cepparulo, M

    2008-04-01

    The efficacy and safety of intravenous (i.v.) azithromycin followed by the oral form, given in addition to i.v. ampicillin-sulbactam, were evaluated in 151 patients hospitalized due to community-acquired pneumonia (CAP). Azithromycin 500 mg i.v. once daily plus ampicillin/sulbactam 3 g i.v. twice daily were administered for 2-5 days, then followed by oral azithromycin 500 mg once daily plus the same i.v. ampicillin/sulbactam regimen for a total of 7-10 days of treatment. The clinical response at day 14 was defined as cure, improvement or failure (with the addition of relapse at follow-up at day 30). The other efficacy measures included microbiological (eradication, presumed eradication, persistence, relapse, superinfection) and radiological (resolution, improvement, failure) findings, and outcome of signs and symptoms. Adverse events, vital signs and routine laboratory tests were the safety variables. The number and rate of patients with a positive clinical outcome at day 14 (cured + improved) in the intention-to-treat (ITT) analysis (n = 138) were 119 (86.2%), while 118 (87.4%) were cured or improved in the per-protocol population (PP) subset (n = 135). The rate of success at day 14 was slightly lower in the treated population (78.8%), which included all patients discontinued due to any cause. Clinical failures in the ITT population were 19 (13.8%) at day 14 and 1 (0.9%) at day 30, while 4 patients (3.6%) relapsed at day 30. Signs and symptoms of CAP improved from baseline to endpoint. The results in patients with a pathogen isolated at baseline in the cultures of respiratory tract secretions showed that 17 patients (77.3%) had eradication and 5 (22.7%) had presumed eradication (i.e. absence of adequate sputum for culture) at day 14, with no cases of persistence or superinfection. In the X-ray exam at day 30, 96 patients (85.0%) had resolution, 11 (9.7%) had improvement and 4 (3.5%) had failure. Treatment-related adverse events were reported in 10 patients (6

  10. Postantibiotic Effect and Postantibiotic Sub-MIC Effect of Levofloxacin Compared to Those of Ofloxacin, Ciprofloxacin, Erythromycin, Azithromycin, and Clarithromycin against 20 Pneumococci

    PubMed Central

    Spangler, Sheila K.; Lin, Gengrong; Jacobs, Michael R.; Appelbaum, Peter C.

    1998-01-01

    The postantibiotic effect (PAE) (10 times the MIC of quinolones, 5 times the MIC of macrolides) and postantibiotic sub-MIC effect (PAE-SME) at 0.125, 0.25, and 0.5 times the MIC were determined for levofloxacin, ciprofloxacin, ofloxacin, erythromycin, azithromycin, and clarithromycin against 20 pneumococci. Quinolone PAEs ranged between 0.5 and 6.5 h, and macrolide PAEs ranged between 1 and 6 h. Measurable PAE-SMEs (in hours) at the three concentrations were 1 to 5, 1 to 8, and 1 to 8, respectively, for quinolones and 1 to 8, 1 to 8, and 1 to 6, respectively, for macrolides. PMID:9593160

  11. Postantibiotic effect and postantibiotic sub-MIC effect of levofloxacin compared to those of ofloxacin, ciprofloxacin, erythromycin, azithromycin, and clarithromycin against 20 pneumococci.

    PubMed

    Spangler, S K; Lin, G; Jacobs, M R; Appelbaum, P C

    1998-05-01

    The postantibiotic effect (PAE) (10 times the MIC of quinolones, 5 times the MIC of macrolides) and postantibiotic sub-MIC effect (PAE-SME) at 0.125, 0.25, and 0.5 times the MIC were determined for levofloxacin, ciprofloxacin, ofloxacin, erythromycin, azithromycin, and clarithromycin against 20 pneumococci. Quinolone PAEs ranged between 0.5 and 6.5 h, and macrolide PAEs ranged between 1 and 6 h. Measurable PAE-SMEs (in hours) at the three concentrations were 1 to 5, 1 to 8, and 1 to 8, respectively, for quinolones and 1 to 8, 1 to 8, and 1 to 6, respectively, for macrolides. PMID:9593160

  12. Killing of Staphylococcus aureus in murine macrophages by chloroquine used alone and in combination with ciprofloxacin or azithromycin

    PubMed Central

    Dey, Somrita; Bishayi, Biswadev

    2015-01-01

    This study aimed to determine any alteration in the killing of Staphylococcus aureus in murine peritoneal macrophages when chloroquine (CQ) is used alone compared with when it is used in combination with ciprofloxacin (CIP) or azithromycin (AZM). The study also aimed to find out the implication of reactive oxygen species (ROS) production and cytokine release in the intracellular killing of S. aureus in macrophages. We present here data obtained with a model of S. aureus-infected mouse peritoneal macrophages in which the intracellular growth of the bacteria and the influence of antibiotics was monitored for 30, 60, and 90 minutes in the presence or absence of CQ along with the production of ROS and alteration in levels of antioxidant enzymes and cytokines. It was observed that S. aureus-triggered cytokine response was regulated when macrophages were co-cultured with CQ and AZM as compared with CQ stimulation only. It can be suggested that action of AZM in mediating bacterial killing is enhanced by the presence of CQ, indicating enhanced uptake of AZM during early infection that may be essential for bacteria killing by AZM. Reduction of oxidative stress burden on the S. aureus-infected macrophages may pave the way for better killing of internalized S. aureus by CQ plus ciprofloxacin (CIP) or CQ plus AZM. Based on these observations, one may speculate that in an inflammatory milieu, CQ loaded with AZM elicits a stronger proinflammatory response by increasing the intracellular uptake of AZM or CIP, thus enabling the immune system to mount a more robust and prolonged response against intracellular pathogens. PMID:25653549

  13. Azithromycin pharmacokinetics in the serum and its distribution to the skin in healthy dogs and dogs with pyoderma.

    PubMed

    Zur, Gila; Soback, Stefan; Weiss, Yfat; Perry, Elad; Lavy, Eran; Britzi, Malka

    2014-04-01

    Serum and skin tissue azithromycin (AZM) concentrations were analysed in healthy and pyoderma affected dogs to determine AZM pharmacokinetics and to establish the effect of disease on AZM skin disposition. AZM was administered orally to two groups of healthy dogs: (1) at 7.02 mg/kg (n=7) and (2) at 11.2mg/kg (n=9). A crossover design was used on five of them. Seven dogs with pyoderma were treated with AZM at 10.7 mg/kg. The two groups of healthy dogs received AZM once daily over three consecutive days and dogs with pyoderma received the same treatment repeated twice with an interval of 1 week. AZM concentrations were determined by liquid chromatography-tandem mass spectrometry. AZM was rapidly absorbed and slowly excreted. In healthy dogs, maximum serum concentrations appeared 2h after administration and were (mean ± standard deviation) 0.60 ± 0.25 μg/mL and 1.03 ± 0.43 μg/mL, and the half-lives were 49.9 ± 5.10 and 51.9 ± 6.69 h for doses of 7.02 and 11.2mg/kg, respectively. Clearance (CL0-24/F) was similar in both dosing groups (1.24 ± 0.24 and 1.29 ± 0.24 L/h/kg) and the respective mean residence time (MRT0-24) was 11.1 ± 0.8 and 8.4 ± 2.2h. The skin concentration in healthy dogs was 3.5-6.5 and 5.0-12.0 times higher than the corresponding serum concentration after the two doses and increased after the cessation of AZM administration. The ratio increased significantly in inflamed tissue (9.5-26.2). PMID:24472431

  14. Maternal Intravenous Administration of Azithromycin Results in Significant Fetal Uptake in a Sheep Model of Second Trimester Pregnancy

    PubMed Central

    Miura, Yuichiro; Payne, Matthew S.; Jobe, Alan H.; Kallapur, Suhas G.; Saito, Masatoshi; Stock, Sarah J.; Spiller, O. Brad; Ireland, Demelza J.; Yaegashi, Nobuo; Clarke, Michael; Hahne, Dorothee; Rodger, Jennifer; Keelan, Jeffrey A.; Newnham, John P.

    2014-01-01

    Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks of gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation age-approriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intra-amniotic AZ dose or repeated maternal intravenous (i.v.) AZ doses would safely yield therapeutic levels of AZ in an 80-day-gestation (term is 150 days) ovine fetus. Fifty sheep carrying single pregnancies at 80 days gestation were randomized to receive either: (i) a single intra-amniotic AZ administration or (ii) maternal intravenous AZ administration every 12 h. Amniotic fluid, maternal plasma, and fetal AZ concentrations were determined over a 5-day treatment regimen. Markers of liver injury and amniotic fluid inflammation were measured to assess fetal injury in response to drug exposure. A single intra-amniotic administration yielded significant AZ accumulation in the amniotic fluid and fetal lung. In contrast, repeated maternal intravenous administrations achieved high levels of AZ accumulation in the fetal lung and liver and a statistically significant increase in the fetal plasma drug concentration at 120 h. There was no evidence of fetal injury in response to drug exposure. These data suggest that (i) repeated maternal i.v. AZ dosing yields substantial fetal tissue uptake, although fetal plasma drug levels remain low; (ii) transfer of AZ from the amniotic fluid is less than transplacental transfer; and (iii) exposure to high concentrations of AZ did not elicit overt changes in fetal white blood cell counts, amniotic fluid monocyte chemoattractant protein 1 concentrations, or hepatotoxicity, all consistent with an absence of fetal injury. PMID:25155606

  15. Maternal intravenous administration of azithromycin results in significant fetal uptake in a sheep model of second trimester pregnancy.

    PubMed

    Kemp, Matthew W; Miura, Yuichiro; Payne, Matthew S; Jobe, Alan H; Kallapur, Suhas G; Saito, Masatoshi; Stock, Sarah J; Spiller, O Brad; Ireland, Demelza J; Yaegashi, Nobuo; Clarke, Michael; Hahne, Dorothee; Rodger, Jennifer; Keelan, Jeffrey A; Newnham, John P

    2014-11-01

    Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks of gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation age-approriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intra-amniotic AZ dose or repeated maternal intravenous (i.v.) AZ doses would safely yield therapeutic levels of AZ in an 80-day-gestation (term is 150 days) ovine fetus. Fifty sheep carrying single pregnancies at 80 days gestation were randomized to receive either: (i) a single intra-amniotic AZ administration or (ii) maternal intravenous AZ administration every 12 h. Amniotic fluid, maternal plasma, and fetal AZ concentrations were determined over a 5-day treatment regimen. Markers of liver injury and amniotic fluid inflammation were measured to assess fetal injury in response to drug exposure. A single intra-amniotic administration yielded significant AZ accumulation in the amniotic fluid and fetal lung. In contrast, repeated maternal intravenous administrations achieved high levels of AZ accumulation in the fetal lung and liver and a statistically significant increase in the fetal plasma drug concentration at 120 h. There was no evidence of fetal injury in response to drug exposure. These data suggest that (i) repeated maternal i.v. AZ dosing yields substantial fetal tissue uptake, although fetal plasma drug levels remain low; (ii) transfer of AZ from the amniotic fluid is less than transplacental transfer; and (iii) exposure to high concentrations of AZ did not elicit overt changes in fetal white blood cell counts, amniotic fluid monocyte chemoattractant protein 1 concentrations, or hepatotoxicity, all consistent with an absence of fetal injury. PMID:25155606

  16. Effects of Azithromycin, Metronidazole, Amoxicillin, and Metronidazole plus Amoxicillin on an In Vitro Polymicrobial Subgingival Biofilm Model

    PubMed Central

    Teles, Flavia; Starr, Jacqueline R.; Feres, Magda; Patel, Michele; Martin, Lynn

    2015-01-01

    Chronic periodontitis is one of the most prevalent human diseases and is caused by dysbiosis of the subgingival microbiota. Treatment involves primarily mechanical disruption of subgingival biofilms and, in certain cases, adjunctive use of systemic antibiotic therapy. In vitro biofilm models have been developed to study antimicrobial agents targeting subgingival species. However, these models accommodate a limited number of taxa, lack reproducibility, and have low throughput. We aimed to develop an in vitro multispecies biofilm model that mimics subgingival plaque, to test antimicrobial agents. Biofilms were cultivated using the Calgary Biofilm Device and were exposed to amoxicillin (AMX), metronidazole (MTZ), azithromycin (AZM), and AMX-MTZ at four different concentrations for 12, 24, or 36 h. Chlorhexidine (CHX) (0.12%) was used as the positive control. The compositions of the biofilms were analyzed by checkerboard DNA-DNA hybridization, and the percent reduction in biofilm metabolic activity was determined using 2,3,5-triphenyltetrazolium chloride and spectrophotometry. Thirty-five of the 40 species used in the inoculum were consistently recovered from the resulting in vitro biofilms. After 36 h of exposure at the 1:27 dilution, AMX-MTZ reduced metabolic activity 11% less than CHX (q = 0.0207) but 54% more than AMX (q = 0.0031), 72% more than MTZ (q = 0.0031), and 67% more than AZM (q = 0.0008). Preliminary evidence of a synergistic interaction between AMX and MTZ was also observed. In summary, we developed reproducible biofilms with 35 subgingival bacterial species, and our results suggested that the combination of AMX and MTZ had greater antimicrobial effects on these in vitro multispecies biofilms than expected on the basis of the independent effects of the drugs. PMID:25733510

  17. Fluticasone, Azithromycin, and Montelukast Treatment for New-Onset Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation.

    PubMed

    Williams, Kirsten M; Cheng, Guang-Shing; Pusic, Iskra; Jagasia, Madan; Burns, Linda; Ho, Vincent T; Pidala, Joseph; Palmer, Jeanne; Johnston, Laura; Mayer, Sebastian; Chien, Jason W; Jacobsohn, David A; Pavletic, Steven Z; Martin, Paul J; Storer, Barry E; Inamoto, Yoshihiro; Chai, Xiaoyu; Flowers, Mary E D; Lee, Stephanie J

    2016-04-01

    Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT) is associated with high mortality. We hypothesized that inhaled fluticasone, azithromycin, and montelukast (FAM) with a brief steroid pulse could avert progression of new-onset BOS. We tested this in a phase II, single-arm, open-label, multicenter study (NCT01307462). Thirty-six patients were enrolled within 6 months of BOS diagnosis. The primary endpoint was treatment failure, defined as 10% or greater forced expiratory volume in 1 second decline at 3 months. At 3 months, 6% (2 of 36, 95% confidence interval, 1% to 19%) had treatment failure (versus 40% in historical controls, P < .001). FAM was well tolerated. Steroid dose was reduced by 50% or more at 3 months in 48% of patients who could be evaluated (n = 27). Patient-reported outcomes at 3 months were statistically significantly improved for Short-Form 36 social functioning score and mental component score, Functional Assessment of Cancer Therapies emotional well-being, and Lee symptom scores in lung, skin, mouth, and the overall summary score compared to enrollment (n = 24). At 6 months, 36% had treatment failure (95% confidence interval, 21% to 54%, n = 13 of 36, with 6 documented failures, 7 missing pulmonary function tests). Overall survival was 97% (95% confidence interval, 84% to 100%) at 6 months. These data suggest that FAM was well tolerated and that treatment with FAM and steroid pulse may halt pulmonary decline in new-onset BOS in the majority of patients and permit reductions in systemic steroid exposure, which collectively may improve quality of life. However, additional treatments are needed for progressive BOS despite FAM. PMID:26475726

  18. Studies on ocular and parenteral application potentials of azithromycin- loaded anionic, cationic and neutral-charged emulsions.

    PubMed

    Tamilvanan, Shunmugaperumal; Khanum, Ramona; Senthilkumar, Sudalimuthu Ramachandran; Muthuraman, Marimuthu; Rajasekharan, Thenrajan

    2013-10-01

    Ocular and parenteral application potentials of azithromycin-containing, non-phospholipid-based cationic nanosized emulsion in comparison to the phospholipid-based anionic and neutral-charged nanosized emulsions were investigated. Various physical, chemical, nonclinical toxicity and antimicrobial activity studies (mean droplet diameter, surface charge, creaming index, entrapment efficiency, accelerated, long-term and freeze-thaw cycling stabilities, TLC study, modified hen's egg chorioallantoic membrane (HET-CAM) test, in vitro hemolysis test, in vitro and in vivo myotoxicity, and in vitro antimicrobial activity) were conducted for assessing the potentials of these three types of emulsions. Following autoclave sterilization, all of these emulsions exhibited a nanometer range mean particle diameter (200 ± 29 to 434 ± 13 nm). While the anionic and cationic emulsions did show high negative (-34.2 ± 1.23 mV) and positive zeta potential (42.6 ± 1.45 mV) values, the neutral-charged emulsion did not. Even with 5 freeze-thaw cycles, the cationic emulsion remained stable whereas other two emulsions underwent phase-separation. The hen's egg chorioallantoic membrane test revealed an irritation score value that was higher for the anionic emulsion than for cationic or neutral-charged emulsion. A significantly higher % hemolysis value was also noticed for the anionic emulsion when compared to the % hemolysis value of cationic emulsion (ANOVA, P ‹ 0.05). However, all of the emulsions showed a lesser intracellular creatine kinase (CK) release/plasma CK level in comparison to the positive control (phenytoin) indicating their lesser myotoxicity at the injection site . When compared to anionic and neutral-charged emulsions, the possible controlled drug release from cationic emulsion delayed the in vitro antimicrobial action against H.influenzae and S.pneumoniae. PMID:23721117

  19. Recycling of peptidyl-tRNAs by peptidyl-tRNA hydrolase counteracts azithromycin-mediated effects on Pseudomonas aeruginosa.

    PubMed

    Gödeke, Julia; Pustelny, Christian; Häussler, Susanne

    2013-04-01

    Acute and chronic infections caused by the opportunistic pathogen Pseudomonas aeruginosa pose a serious threat to human health worldwide, and its increasing resistance to antibiotics requires alternative treatments that are more effective than available strategies. Clinical studies have clearly demonstrated that cystic fibrosis (CF) patients with chronic P. aeruginosa infections benefit from long-term low-dose azithromycin (AZM) treatment. Immunomodulating activity, the impact of AZM on the expression of quorum-sensing-dependent virulence factors, type three secretion, and motility in P. aeruginosa seem to contribute to the therapeutic response. However, to date, the molecular mechanisms underlying these AZM effects have remained elusive. Our data indicate that the AZM-mediated phenotype is caused by a depletion of the intracellular pools of tRNAs available for protein synthesis. Overexpression of the P. aeruginosa peptidyl-tRNA hydrolase, which recycles the tRNA from peptidyl-tRNA drop-off during translation, counteracted the effects of AZM on stationary-phase cell killing, cytotoxicity, and the production of rhamnolipids and partially restored swarming motility. Intriguingly, the exchange of a rare for a frequent codon in rhlR also explicitly diminished the AZM-mediated decreased production of rhamnolipids. These results indicate that depletion of the tRNA pools by AZM seems to affect the translation of genes that use rare aminoacyl-tRNA isoacceptors to a great extent and might explain the selective activity of AZM on the P. aeruginosa proteome and possibly also on the protein expression profiles of other bacterial pathogens. PMID:23318806

  20. Transplacental Transfer of Azithromycin and Its Use for Eradicating Intra-amniotic Ureaplasma Infection in a Primate Model

    PubMed Central

    Acosta, Edward P.; Grigsby, Peta L.; Larson, Kajal B.; James, Amanda M.; Long, Mary C.; Duffy, Lynn B.; Waites, Ken B.; Novy, Miles J.

    2014-01-01

    Background. Our goals were to describe azithromycin (AZI) pharmacokinetics in maternal plasma (MP), fetal plasma (FP), and amniotic fluid (AF) following intra-amniotic infection (IAI) with Ureaplasma in pregnant rhesus monkeys and to explore concentration-response relationships. Methods. Following intra-amniotic inoculation of Ureaplasma parvum, rhesus monkeys received AZI (12.5 mg/kg every 12 hours intravenously for 10 days; n = 10). Intensive pharmacokinetic sampling of MP, FP, and AF was scheduled following the first (ie, single) dose and the last (ie, multiple) dose. Noncompartmental and pharmacokinetic modeling methods were used. Results. The AF area under the concentration-time curve at 12 hours was 0.22 µg×h/mL following a single dose and 6.3 µg×h/mL at day 10. MP and AF accumulation indices were 8.4 and 19, respectively. AZI AF half-life following the single dose and multiple dose were 156 and 129 hours, respectively. The median MP:FP ratio in concomitantly drawn samples was 3.2 (range, 1.3–9.6; n = 9). Eradication of U. parvum occurred at 6.6 days, with a 95% effective concentration (EC95) of 39 ng/mL for the maximum AZI AF concentration. Conclusions. Our study demonstrates that a maternal multiple-dose AZI regimen is effective in eradicating U. parvum IAI by virtue of intra-amniotic accumulation and suggests that antenatal therapy has the potential to mitigate complications associated with U. parvum infection in pregnancy, such as preterm labor and fetal sequelae. PMID:24179112

  1. Development of a Population Pharmacokinetic Model To Describe Azithromycin Whole-Blood and Plasma Concentrations over Time in Healthy Subjects

    PubMed Central

    Anic-Milic, T.; Oreskovic, K.; Padovan, J.; Brouwer, K. L. R.; Zuo, P.; Schmith, V. D.

    2013-01-01

    Azithromycin (AZI), a broad-spectrum antibiotic, accumulates in polymorphonuclear cells and peripheral blood mononuclear cells. The distribution of AZI in proinflammatory cells may be important to the anti-inflammatory properties. Previous studies have described plasma AZI pharmacokinetics. The objective of this study was to describe the pharmacokinetics of AZI in whole blood (concentration in whole blood [Cb]) and plasma (concentration in plasma [Cp]) of healthy subjects. In this study, 12 subjects received AZI (500 mg once a day for 3 days). AZI Cb and Cp were quantified in serial samples collected up to 3 weeks after the last dose and analyzed using noncompartmental and compartmental methods. After the last dose, Cb was greater than Cp. Importantly, Cb, but not Cp, was quantifiable in all but one subject at 3 weeks. The blood area under the curve during a 24-h dosing interval (AUC24) was ∼2-fold greater than the plasma AUC24, but simulations suggested that Cb was not at steady state by day 3. Upon exploration of numerous models, an empirical 3-compartment model adequately described Cp and Cb, but Cp was somewhat underestimated. Intercompartmental clearance (CL; likely representing cells) was lower than apparent oral CL (18 versus 118 liters/h). Plasma, peripheral, and cell compartmental volumes were 439 liters, 2,980 liters, and 3,084 liters, respectively. Interindividual variability in CL was low (26.2%), while the volume of distribution variability was high (107%). This is the first report to describe AZI Cb in healthy subjects, the distribution parameters between Cp and Cb, and AZI retention in blood for up to 3 weeks following 3 daily doses. The model can be used to predict Cb from Cp for AZI under various dosing regimens. (This study has been registered at ClinicalTrials.gov under registration no. NCT01026064.) PMID:23629714

  2. Fire Suppression and Response

    NASA Technical Reports Server (NTRS)

    Ruff, Gary A.

    2004-01-01

    This report is concerned with the following topics regarding fire suppression:What is the relative effectiveness of candidate suppressants to extinguish a representative fire in reduced gravity, including high-O2 mole fraction, low -pressure environments? What are the relative advantages and disadvantages of physically acting and chemically-acting agents in spacecraft fire suppression? What are the O2 mole fraction and absolute pressure below which a fire cannot exist? What effect does gas-phase radiation play in the overall fire and post-fire environments? Are the candidate suppressants effective to extinguish fires on practical solid fuels? What is required to suppress non-flaming fires (smoldering and deep seated fires) in reduced gravity? How can idealized space experiment results be applied to a practical fire scenario? What is the optimal agent deployment strategy for space fire suppression?

  3. Combination therapy with ampicillin and azithromycin in an experimental pneumococcal pneumonia is bactericidal and effective in down regulating inflammation in mice

    PubMed Central

    2014-01-01

    Objectives Emergence of multidrug resistance among Streptococcus pneumoniae (SP), has limited the available options used to treat infections caused by this organism. The objective of this study was to compare the role of monotherapy and combination therapy with ampicillin (AMP) and azithromycin (AZM) in eradicating bacterial burden and down regulating lung inflammation in a murine experimental pneumococcal infection model. Methods Balb/C mice were infected with 106 CFU of SP. Treatments with intravenous ampicillin (200 mg/kg) and azithromycin (50 mg/kg) either alone or in combination was initiated 18 h post infection, animals were sacrificed from 0 – 6 h after initiation of treatment. AMP and AZM were quantified in serum by microbiological assay. Levels of TNF-α, IFN-γ IL-6, and IL-10 in serum and in lungs, along with myeloperoxidase, inflammatory cell count in broncho alveolar lavage fluid, COX-2 and histopathological changes in lungs were estimated. Results Combination therapy down regulated lung inflammation and accelerated bacterial clearance. This approach also significantly decreased TNF-α, IFN-γ, IL-6 and increased IL-10 level in serum and lungs along with decreased myeloperoxidase, pulmonary vascular permeability, inflammatory cell numbers and COX-2 levels in lungs. Conclusions Combinatorial therapy resulted in comparable bactericidal activity against the multi-drug resistant isolate and may represent an alternative dosing strategy, which may help to alleviate problems with pneumococcal pneumonia. PMID:24565171

  4. Effect of Repeated Treatment of Pregnant Women with Sulfadoxine-Pyrimethamine and Azithromycin on Preterm Delivery in Malawi: A Randomized Controlled Trial

    PubMed Central

    Luntamo, Mari; Kulmala, Teija; Mbewe, Bernard; Cheung, Yin Bun; Maleta, Kenneth; Ashorn, Per

    2010-01-01

    Preterm delivery, which is associated with infections during pregnancy, is common in sub-Saharan Africa. We enrolled 1,320 pregnant women into a randomized, controlled trial in Malawi to study whether preterm delivery and low birth weight (LBW) incidence can be reduced by intermittent preventive treatment of maternal malaria and reproductive tract infections. The participants received either sulfadoxine-pyrimethamine (SP) twice (controls), monthly SP, or monthly SP and two doses of azithromycin (AZI-SP). The incidence of preterm delivery was 17.9% in controls, 15.4% in the monthly SP group (P = 0.32), and 11.8% in AZI-SP group (risk ratio = 0.66, P = 0.01). Compared with controls, those in AZI-SP group had a risk ratio of 0.61 (P = 0.02) for LBW. Incidence of serious adverse events was low in all groups. In conclusion, the incidence of preterm delivery and LBW can in some conditions be reduced by treating pregnant women with monthly SP and two azithromycin doses. PMID:21118924

  5. A Cross-Sectional Study of ‘Yaws’ in Districts of Ghana Which Have Previously Undertaken Azithromycin Mass Drug Administration for Trachoma Control

    PubMed Central

    Ghinai, Rosanna; El-Duah, Philip; Chi, Kai-Hua; Pillay, Allan; Solomon, Anthony W.; Bailey, Robin L.; Agana, Nsiire; Mabey, David C. W.; Chen, Cheng-Yen

    2015-01-01

    Yaws, caused by Treponema pallidum ssp. pertenue, is reportedly endemic in Ghana. Mass distribution of azithromycin is now the cornerstone of the WHO yaws eradication campaign. Mass distribution of azithromycin at a lower target dose was previously undertaken in two regions of Ghana for the control of trachoma. Ongoing reporting of yaws raises the possibility that resistance may have emerged in T. pallidum pertenue, or that alternative infections may be responsible for some of the reported cases. We conducted a cross-sectional survey in thirty communities in two districts of Ghana where MDA for trachoma had previously been conducted. Children aged 5–17 years with ulcerative lesions compatible with yaws were enrolled. Samples for treponemal serology and lesion PCR were collected from all children. 90 children with 98 lesions were enrolled. Syphilis serology was negative in all of them. PCR for T. pallidum ssp pertenue was negative in all children, but Haemophilus ducreyi DNA was detected in 9 lesions. In these communities, previously treated for trachoma, we found no evidence of ongoing transmission of yaws. H. ducreyi was associated with a proportion of skin lesions, but the majority of lesions remain unexplained. Integration of diagnostic testing into both pre and post-MDA surveillance systems is required to better inform yaws control programmes. PMID:25632942

  6. A cross-sectional study of 'yaws' in districts of Ghana which have previously undertaken azithromycin mass drug administration for trachoma control.

    PubMed

    Ghinai, Rosanna; El-Duah, Philip; Chi, Kai-Hua; Pillay, Allan; Solomon, Anthony W; Bailey, Robin L; Agana, Nsiire; Mabey, David C W; Chen, Cheng-Yen; Adu-Sarkodie, Yaw; Marks, Michael

    2015-01-01

    Yaws, caused by Treponema pallidum ssp. pertenue, is reportedly endemic in Ghana. Mass distribution of azithromycin is now the cornerstone of the WHO yaws eradication campaign. Mass distribution of azithromycin at a lower target dose was previously undertaken in two regions of Ghana for the control of trachoma. Ongoing reporting of yaws raises the possibility that resistance may have emerged in T. pallidum pertenue, or that alternative infections may be responsible for some of the reported cases. We conducted a cross-sectional survey in thirty communities in two districts of Ghana where MDA for trachoma had previously been conducted. Children aged 5-17 years with ulcerative lesions compatible with yaws were enrolled. Samples for treponemal serology and lesion PCR were collected from all children. 90 children with 98 lesions were enrolled. Syphilis serology was negative in all of them. PCR for T. pallidum ssp pertenue was negative in all children, but Haemophilus ducreyi DNA was detected in 9 lesions. In these communities, previously treated for trachoma, we found no evidence of ongoing transmission of yaws. H. ducreyi was associated with a proportion of skin lesions, but the majority of lesions remain unexplained. Integration of diagnostic testing into both pre and post-MDA surveillance systems is required to better inform yaws control programmes. PMID:25632942

  7. Effects of Azithromycin in Combination with Vancomycin, Daptomycin, Fosfomycin, Tigecycline, and Ceftriaxone on Staphylococcus epidermidis Biofilms ▿

    PubMed Central

    Presterl, Elisabeth; Hajdu, Stefan; Lassnigg, Andrea M.; Hirschl, Alexander M.; Holinka, Johannes; Graninger, Wolfgang

    2009-01-01

    Staphylococcal biofilms on surgical implants are the underlying cause of a lack of response to antimicrobial treatment. We investigated the effects of vancomycin (VAN), daptomycin (DAP), fosfomycin (FOS), tigecycline (TGC), and ceftriaxone (CRX), alone and in combination with azithromycin (AZI), on established biofilms of Staphylococcus epidermidis. Biofilms were studied using the static microtiter plate model with established S. epidermidis biofilms, with an initial inoculum of 106/ml in 96-well polystyrene flat-bottom microtiter plates. Biofilms were inoculated with VAN, DAP, FOS, TGC, or CRX at two concentrations, alone or in combination with AZI (2, 512, or 1,024 mg/liter). To assess the reduction in biomass, the optical density ratio (ODr), calculated as (optical density [OD] of the treated biofilm)/(OD of the untreated biofilm, taken as 1), was used. For antibacterial efficacy, the viable bacterial count was used. Reductions in the biofilm ODr were observed for VAN (15 and 40 mg/liter) and FOS (200 mg/liter) only (ODr [mean ± standard deviation] for VAN at 15 and 40 mg/liter, 0.77 ± 0.32 and 0.8 ± 0.35, respectively; ODr for FOS at 200 mg/liter, 0.78 ± 0.26; P < 0.05), but not for DAP (2 and 5 mg/liter), TGC (0.2 and 2 mg/liter), or CRX (600 and 2,400 mg/liter). The addition of AZI had no further effect on the ODr, but a significant reduction of bacterial growth was achieved with high doses of AZI plus TGC or AZI plus CRX (a 3-log count reduction for AZI at 1,024 mg/liter plus CRX at 600 mg/liter and for AZI at 512 or 1,024 mg/liter plus CRX at 2,400 mg/liter; a 2-log count reduction for AZI at 512 or 1,024 mg/liter plus TGC at 2 mg/liter [P < 0.05]). No significant reduction in bacterial growth was observed for FOS (50 and 200 mg/liter), DAP (2 and 5 mg/liter), or TGC (0.2 mg/liter) in combination with AZI. None of the antibiotics at either concentration reduced the bacterial count of the biofilms when used alone. Thus, the use of a combination of AZI

  8. In vitro activity of fosfomycin alone and in combination with ceftriaxone or azithromycin against clinical Neisseria gonorrhoeae isolates.

    PubMed

    Hauser, Christoph; Hirzberger, Lea; Unemo, Magnus; Furrer, Hansjakob; Endimiani, Andrea

    2015-03-01

    New therapeutic strategies are needed to combat the emergence of infections due to multidrug-resistant Neisseria gonorrhoeae. In this study, fosfomycin (FOS) was tested against 89 N. gonorrhoeae isolates using the Etest method, showing MIC50/MIC90s of only 8/16 μg/ml (range, ≤1 to 32 μg/ml). FOS in combination with ceftriaxone (CRO) or azithromycin (AZT) was then evaluated using the checkerboard method for eight strains, including N. gonorrhoeae F89 (CRO-resistant) and AZT-HLR (high-level AZT-resistant). All combinations that included FOS gave indifferent effects (fractional inhibitory concentration [FIC] index values, 1.2 to 2.3 for FOS plus CRO, 1.8 to 3.2 for FOS plus AZT). Time-kill experiments for FOS, CRO, AZT, and their combinations (at 0.5×, 1×, 2×, and 4× the MIC) were performed against N. gonorrhoeae strain ATCC 49226, one N. gonorrhoeae multiantigen sequence typing (NG-MAST) sequence type 1407 (ST1407) strain, F89, and AZT-HLR. For all strains, at 24 h, the results indicated that (i) FOS was bactericidal at 2× the MIC, but after >24 h, there was regrowth of bacteria; (ii) CRO was bactericidal at 0.5× the MIC; (iii) AZT was bactericidal at 4× the MIC; (iv) CRO plus AZT was less bactericidal than was CRO alone; (v) FOS plus AZT was bactericidal at 2× the MIC; and (vi) CRO plus AZT and FOS plus CRO were both bactericidal at 0.5× the MIC, but FOS plus CRO had more rapid effects. FOS is appealing for use in the management of N. gonorrhoeae infections because of its single and oral formulation. However, our results suggest it be used in combination with CRO. After the appropriate clinical trials are conducted, this strategy could be implemented for the treatment of infections due to isolates possessing resistance to CRO and/or AZT. PMID:25547354

  9. In Vitro Activity of Fosfomycin Alone and in Combination with Ceftriaxone or Azithromycin against Clinical Neisseria gonorrhoeae Isolates

    PubMed Central

    Hauser, Christoph; Hirzberger, Lea; Unemo, Magnus; Furrer, Hansjakob

    2014-01-01

    New therapeutic strategies are needed to combat the emergence of infections due to multidrug-resistant Neisseria gonorrhoeae. In this study, fosfomycin (FOS) was tested against 89 N. gonorrhoeae isolates using the Etest method, showing MIC50/MIC90s of only 8/16 μg/ml (range, ≤1 to 32 μg/ml). FOS in combination with ceftriaxone (CRO) or azithromycin (AZT) was then evaluated using the checkerboard method for eight strains, including N. gonorrhoeae F89 (CRO-resistant) and AZT-HLR (high-level AZT-resistant). All combinations that included FOS gave indifferent effects (fractional inhibitory concentration [FIC] index values, 1.2 to 2.3 for FOS plus CRO, 1.8 to 3.2 for FOS plus AZT). Time-kill experiments for FOS, CRO, AZT, and their combinations (at 0.5×, 1×, 2×, and 4× the MIC) were performed against N. gonorrhoeae strain ATCC 49226, one N. gonorrhoeae multiantigen sequence typing (NG-MAST) sequence type 1407 (ST1407) strain, F89, and AZT-HLR. For all strains, at 24 h, the results indicated that (i) FOS was bactericidal at 2× the MIC, but after >24 h, there was regrowth of bacteria; (ii) CRO was bactericidal at 0.5× the MIC; (iii) AZT was bactericidal at 4× the MIC; (iv) CRO plus AZT was less bactericidal than was CRO alone; (v) FOS plus AZT was bactericidal at 2× the MIC; and (vi) CRO plus AZT and FOS plus CRO were both bactericidal at 0.5× the MIC, but FOS plus CRO had more rapid effects. FOS is appealing for use in the management of N. gonorrhoeae infections because of its single and oral formulation. However, our results suggest it be used in combination with CRO. After the appropriate clinical trials are conducted, this strategy could be implemented for the treatment of infections due to isolates possessing resistance to CRO and/or AZT. PMID:25547354

  10. Cough suppression disorders spectrum.

    PubMed

    Reich, Jerome M

    2014-02-01

    Volitional cough suppression, identified exclusively in females, is an unusual causal mechanism for instances of lobar atalectasis and bronchiectasis. It is a postulated mechanism for the genesis of Lady Windermere Syndrome. PMID:24462261